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Sample records for prolonged release pr

  1. A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR.

    Science.gov (United States)

    Dupoiron, D; Stachowiak, A; Loewenstein, O; Ellery, A; Kremers, W; Bosse, B; Hopp, M

    2017-10-01

    Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study. Measured were: opioid-induced constipation [bowel function index score (BFI)]; analgesic efficacy (NRS 0-10); daily laxative rescue medication use; rescue medication use, and the number of complete spontaneous bowel movements (CSBMs) per week. A subanalysis was conducted in cancer patients. Greater reductions in mean BFI scores were reported for the OXN PR group compared with OxyPR from Week 1 onwards; at Week 5 the mean change from baseline was -32.5 versus -14.2. Average 24-h pain scores were low and remained stable in the range 3-4 in both treatment groups. Analgesic rescue medication use was similar between the groups. Patients receiving OXN PR used significantly lower mean daily doses of laxative rescue medication than those receiving OxyPR (P = 0.006). The number of CSBM in the OXN PR group approximately doubled compared with a 25% decrease in the OxyPR group. Comparable results to the total study population were reported in the cancer patient subgroup. OXN PR in daily doses of up to 160/80 mg significantly improves bowel function compared with equivalent doses of OxyPR while still providing comparable analgesic efficacy. Effective analgesia can be achieved using oxycodone/naloxone PR up to 160/80 mg daily without compromising bowel function. A similar outcome was reported in cancer and non-cancer patients. © 2017 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  2. PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study.

    Science.gov (United States)

    Montalvo, Mayra; Tadi, Prasanna; Merkler, Alexander; Gialdini, Gino; Martin-Schild, Sheryl; Navalkele, Digvijaya; Samai, Alyana; Nouh, Amre; Hussain, Mohammad; Goldblatt, Steven; Hemendinger, Morgan; Chu, Antony; Song, Christopher; Kamel, Hooman; Furie, Karen L; Yaghi, Shadi

    2017-10-01

    Atrial dysfunction or "cardiopathy" has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared with known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes. We used prospective ischemic stroke databases of 3 comprehensive stroke centers to identify patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke between December 1, 2013 and August 31, 2015. The main outcome was ischemic stroke subtype (CS versus NCNCS). We compared PR intervals as a continuous and categorical variable (PR interval prolongation and CS. We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). Patients with CS were more likely to have a PR of 200 milliseconds or greater when compared with those with NCNCS (23.2% versus 13.8%, P = .009). After adjusting for factors that were significant in univariate analyses, a PR of 200 milliseconds or greater was independently associated with CS (odds ratio [OR] 1.70, 95% CI 1.08-2.70). The association was more pronounced when excluding patients on atrioventricular nodal blocking agents (OR 2.64, 95% CI 1.44-4.83). A PR of 200 milliseconds or greater is associated with CS and may be a biomarker of atrial cardiopathy in the absence of atrial fibrillation. Prospective studies are needed to confirm this association. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Electrocardiographic PR prolongation and atrial fibrillation risk: a meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Cheng, Min; Lu, Xiangfeng; Huang, Jianfeng; Zhang, Shu; Gu, Dongfeng

    2015-01-01

    Electrocardiographic PR interval prolongation is considered a benign condition, but recent studies have challenged the notion by demonstrating that prolonged PR interval is associated with an increased risk of atrial fibrillation (AF). The purpose of this study was to perform a meta-analysis of prospective cohort studies to evaluate the evidence supporting an association of prolonged PR interval with AF incidence. We searched the MEDLINE and EMBASE database (from inception to May 2014) supplemented by manual searches of references of relevant retrieved articles. Prospective cohort studies were included with hazard ratio (HR) of prolonged PR interval for incident AF. The search strategy yielded 6 cohort studies meeting eligibility criteria. A total of 328,932 participants were included, with 14,191 participants suffering from AF during follow-up. Pooled HRs of prolonged PR interval for incident AF was 1.30 (95% CI: 1.13 to 1.49) using random-effect model (I(2) = 30%). There was a significant difference of combined HRs between studies with and without adjustment for taking of AV nodal blocking agents in subgroup analysis. Sensitivity analysis supported the robustness of the results. Prolonged PR interval is not a totally benign condition but an independent risk factor for AF incidence. The mechanisms underlying the association of prolonged PR interval with AF incidence need further research. © 2014 Wiley Periodicals, Inc.

  4. Interleukin-6 release from the human brain during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund

    2002-01-01

    Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 m...... influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response....... in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 +/- 0.03 ng min(-1)). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 +/- 0.08 ng min(-1); P

  5. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    International Nuclear Information System (INIS)

    Dakhel, Yaman; Jamali, Fakhreddin

    2006-01-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists

  6. Predicting QRS and PR interval prolongations in humans using nonclinical data.

    Science.gov (United States)

    Bergenholm, L; Parkinson, J; Mettetal, J; Evans, N D; Chappell, M J; Collins, T

    2017-10-01

    Risk of cardiac conduction slowing (QRS/PR prolongations) is assessed prior to clinical trials using in vitro and in vivo studies. Understanding the quantitative translation of these studies to the clinical situation enables improved risk assessment in the nonclinical phase. Four compounds that prolong QRS and/or PR (AZD1305, flecainide, quinidine and verapamil) were characterized using in vitro (sodium/calcium channels), in vivo (guinea pigs/dogs) and clinical data. Concentration-matched translational relationships were developed based on in vitro and in vivo modelling, and the in vitro to clinical translation of AZD1305 was quantified using an in vitro model. Meaningful (10%) human QRS/PR effects correlated with low levels of in vitro Na v 1.5 block (3-7%) and Ca v 1.2 binding (13-21%) for all compounds. The in vitro model developed using AZD1305 successfully predicted QRS/PR effects for the remaining drugs. Meaningful QRS/PR changes in humans correlated with small effects in guinea pigs and dogs (QRS 2.3-4.6% and PR 2.3-10%), suggesting that worst-case human effects can be predicted by assuming four times greater effects at the same concentration from dog/guinea pig data. Small changes in vitro and in vivo consistently translated to meaningful PR/QRS changes in humans across compounds. Assuming broad applicability of these approaches to assess cardiovascular safety risk for non-arrhythmic drugs, this study provides a means of predicting human QRS/PR effects of new drugs from effects observed in nonclinical studies. © 2017 The British Pharmacological Society.

  7. Prolonged PR interval predicts clinical recurrence of atrial fibrillation after catheter ablation.

    Science.gov (United States)

    Park, Junbeom; Kim, Tae-Hoon; Lee, Jihei Sara; Park, Jin Kyu; Uhm, Jae Sun; Joung, Boyoung; Lee, Moon Hyoung; Pak, Hui-Nam

    2014-10-07

    A prolonged PR interval is known to be a poor prognostic factor in cardiovascular disease. The aim of this study was to investigate the association between PR interval and clinical outcome in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We prospectively included 576 patients with AF (75.5% male, 57.8±11.6 years old, 68.8% paroxysmal AF) who underwent RFCA. We analyzed preprocedural sinus rhythm ECGs obtained in the absence of antiarrhythmic drug, and all enrolled patients were categorized into 4 groups based on the quartile values of the PR interval (166, 182, and 202 ms), and were analyzed according to the left atrium (LA) volume (CT; Computed tomography), LA voltage (NavX), and clinical outcome of AF ablation. Based on quartile value of PR interval, the highest quartile of PR interval (Q4; PR ≥202 ms) was oldest (PPR interval was a significant predictor of AF recurrence after RFCA of AF (HR=1.969, 95% CI 1.343 to 2.886, P=0.001). The PR interval was closely associated with advanced LA remodeling due to AF, and had a noninvasive significant predictive value of clinical recurrence of AF after RFCA. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  8. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    Science.gov (United States)

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350.

    Science.gov (United States)

    Poulsen, Jakob L; Mark, Esben B; Brock, Christina; Frøkjær, Jens B; Krogh, Klaus; Drewes, Asbjørn M

    2018-01-30

    Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350. In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency. Total colorectal volume did not change after 5 days' treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035). PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment.

  10. Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

    NARCIS (Netherlands)

    Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

    2007-01-01

    Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

  11. The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

    Science.gov (United States)

    Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

    2015-01-23

    To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain.

    Science.gov (United States)

    Kress, H G; Koch, E D; Kosturski, H; Steup, A; Karcher, K; Dogan, C; Etropolski, M; Eerdekens, M

    2016-10-01

    A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329-343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100-250 mg bid) or morphine sulphate-controlled release (40-100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). Responder rates (responders: completed titration, mean pain intensity pain could safely switch from prior treatment with the weak centrally acting analgesic tramadol directly to the strong centrally acting analgesic tapentadol PR, for an improved analgesic therapy for severe pain. WHAT DOES THIS STUDY ADD?: Results of this post hoc analysis show that patients who had received prior tramadol therapy could switch directly to tapentadol PR, with the majority (˜70%) experiencing improved efficacy. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  13. PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights.

    Science.gov (United States)

    Chan, Yap-Hang; Hai, Jo Jo; Lau, Kui-Kai; Li, Sheung-Wai; Lau, Chu-Pak; Siu, Chung-Wah; Yiu, Kai-Hang; Tse, Hung-Fat

    2017-08-24

    Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

  14. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

    Directory of Open Access Journals (Sweden)

    Hui Ming Chua

    2016-01-01

    Full Text Available Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58, whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

  15. Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

    Science.gov (United States)

    McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

    1990-01-01

    Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

  16. Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

    Science.gov (United States)

    Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

    2012-07-01

    The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

  17. A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis.

    Science.gov (United States)

    Ramió-Torrentà, L; Álvarez-Cermeño, J C; Arroyo, R; Casanova-Estruch, B; Fernández, O; García-Merino, J A; Hernández, M A; Izquierdo, G; Martínez-Yélamos, S; Meca, J; Moral, E; Olascoaga, J; Prieto, J M; Saiz, A

    2018-06-01

    Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

    DEFF Research Database (Denmark)

    Baandrup, Lone; Lindschou, Jane; Winkel, Per

    2016-01-01

    OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

  19. Prolonged local anesthetic action through slow release from poly (lactic acid co castor oil).

    Science.gov (United States)

    Sokolsky-Papkov, Marina; Golovanevski, Ludmila; Domb, Abraham J; Weiniger, Carolyn F

    2009-01-01

    To evaluate a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(lactic acid co castor oil) in prolonging motor and sensory block when injected locally. The polyesters were synthesized from DL: -lactic acid and castor oil with feed ratio of 4:6 and 3:7 w/w. Bupivacaine was dispersed in poly(fatty ester) liquid and tested for drug release in vitro. The polymer p(DLLA:CO) 3:7 loaded with 10% bupivacaine was injected through a 22G needle close to the sciatic nerve of ICR mice and the duration of sensory and motor nerve blockade was measured. The DL: -lactic acid co castor oil p(DLLA:CO) 3:7 released 65% of the incorporated bupivacaine during 1 week in vitro. Single injection of 10% bupivacaine loaded into this polymer caused motor block that lasted 24 h and sensory block that lasted 48 h. Previously we developed a ricinoleic acid based polymer with incorporated bupivacaine which prolonged anesthesia to 30 h. The new polymer poly(lactic acid co castor oil) 3:7 provides slow release of effective doses of the incorporated local anesthetic agent and prolongs anesthesia to 48 h.

  20. Inorganically modified diatomite as a potential prolonged-release drug carrier.

    Science.gov (United States)

    Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

    2014-09-01

    Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Polymer based microspheres of aceclofenac as sustained release parenterals for prolonged anti-inflammatory effect

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Manpreet; Sharma, Sumit; Sinha, VR, E-mail: sinha_vr@rediffmail.com

    2017-03-01

    Poly(lactic-co-glycolic acid) (PLGA) (75:25) and polycaprolactone (PCL) microspheres were fabricated for prolonged release of aceclofenac by parenteral administration. Microspheres encapsulating aceclofenac were designed to release the drug at controlled rate for around one month. Biodegradable microspheres were prepared by solvent emulsification evaporation method in different polymer:drug ratios (1:1, 2:1 and 3:1). After drug loading, PLGA and PCL microspheres showed a controlled size distribution with an average size of 11.75 μm and 3.81 μm respectively and entrapment efficiency in the range of 90 ± 0.72% to 91.06 ± 4.01% with PLGA and 83.01 ± 2.13% to 90.4 ± 2.11% with PCL. Scanning electron microscopy has confirmed good spherical structures of microspheres. The percent yield of biodegradable polymeric microspheres ranged between 30.95 ± 10.14% to 92.84 ± 3.15% and 47.33 ± 4.72% to 80 ± 3.60% for PLGA and PCL microspheres respectively. PLGA microspheres followed Higuchi release pattern while Korsmeyer-Peppas explained the release pattern of PCL microspheres. Stability studies of microspheres were also carried out by storing the preparations at 2-8 °C for 30, 60 and 90 days and evaluating them for entrapment efficiency, residual drug content and polymer drug compatability. In-vivo studies showed significant anti-inflammatory activity of microspheres upto 48 hours using the carrageenan induced rat paw oedema model. - Highlights: • PLGA and PCL polymeric microspheres for parenteral prolonged drug delivery system were formulated. • Polymeric microspheres were characterized physically and drug excipient incompatability. • Three months accelerated stability studies were carried for drug loaded polymeric microspheres. • Pharmacodynamic studies prove the rationality of sustained therapeutic effect of designed drug delivery system.

  2. Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Buitelaar, J.K.; Ramos-Quiroga, J.A.; Casas, M.; Kooij, J.J.; Niemela, A.; Konofal, E.; Dejonckheere, J.; Challis, B.H.; Medori, R.

    2009-01-01

    The osmotic release oral system (OROS) methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety

  3. Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

    Science.gov (United States)

    Gasperini, Claudio; Hupperts, Raymond; Lycke, Jan; Short, Christine; McNeill, Manjit; Zhong, John; Mehta, Lahar R

    2016-11-15

    Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Evaluation of adherence and tolerability of prolonged-release tacrolimus (Advagraf™) in kidney transplant patients in Germany: A multicenter, noninterventional study.

    Science.gov (United States)

    Lehner, Lukas J; Reinke, Petra; Hörstrup, Jan H; Rath, Thomas; Suwelack, Barbara; Krämer, Bernhard K; Budde, Klemens; Banas, Bernhard

    2018-01-01

    This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4) months. Composite primary endpoint: nonadherence at V4, defined as self-reported nonadherence on the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS © ), investigator-rated nonadherence, and/or V4 tacrolimus trough level outside a predefined range. Secondary endpoints: individual BAASIS items, incidence of rejection, kidney function, and safety. Overall, 153 adult kidney recipients (mean [standard deviation] time post-transplant 5.8 [4.6] years) were included. Nonadherence was high at V4 (67.7% [95% confidence interval 58.9%, 75.6%]). Medication-taking adherence was 86.9% and 91.3% at V1 and V4, respectively; adherence to timing of medication intake was 58.2% and 58.3%, with little evidence of missed doses/drug holidays. Investigators rated adherence "good" in 85.6% of patients (V4). Two (1.3%) patients had acute rejection episodes. Kidney function remained stable (mean creatinine clearance, V1: 62.1 mL/min; V4: 65.3 mL/min). Investigators rated effectiveness of PR-T as "very good"/"good" in 91.5% of patients. Most patients (94.7%) found PR-T dosing more convenient than immediate-release tacrolimus. PR-T was well tolerated with high medication persistence. © 2017 The Authors. Clinical Transplantation Published by John Wiley & Sons Ltd.

  5. In Situ Loading of Basic Fibroblast Growth Factor Within Porous Silica Nanoparticles for a Prolonged Release

    Directory of Open Access Journals (Sweden)

    Postovit Lynne-Marie

    2009-01-01

    Full Text Available Abstract Basic fibroblast growth factor (bFGF, a protein, plays a key role in wound healing and blood vessel regeneration. However, bFGF is easily degraded in biologic systems. Mesoporous silica nanoparticles (MSNs with well-tailored porous structure have been used for hosting guest molecules for drug delivery. Here, we report an in situ route to load bFGF in MSNs for a prolonged release. The average diameter (d of bFGF-loaded MSNs is 57 ± 8 nm produced by a water-in-oil microemulsion method. The in vitro releasing profile of bFGF from MSNs in phosphate buffer saline has been monitored for 20 days through a colorimetric enzyme linked immunosorbent assay. The loading efficiency of bFGF in MSNs is estimated at 72.5 ± 3%. In addition, the cytotoxicity test indicates that the MSNs are not toxic, even at a concentration of 50 μg/mL. It is expected that the in situ loading method makes the MSNs a new delivery system to deliver protein drugs, e.g. growth factors, to help blood vessel regeneration and potentiate greater angiogenesis.

  6. Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries.

    Science.gov (United States)

    Clay, Emilie; Falissard, Bruno; Moore, Nicholas; Toumi, Mondher

    2013-04-01

    Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with major adverse events including, but not limited to, falls and fractures, domestic and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and cancer. The prolonged use of these drugs is thought to be related to severe withdrawal symptoms and potential dependency. The chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR) melatonin is the first of a new class of melatonin receptor agonist drugs that has demonstrated clinically relevant efficacy on improving quality of sleep and morning alertness, with a good safety profile. This study aimed to analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the availability of alternative pharmacotherapy (PR-melatonin) on the consumption of BZD and Z-drugs in several European countries. Annual sales data from nine European countries were extracted from the IMS sales database and analyzed to determine whether trends in use of these treatment options were attributed to campaigns and/or availability and affordability of safer alternatives on the market. Campaigns aiming to reduce the use of BZD/Z-drugs failed when they were not associated with the availability and market uptake of PR-melatonin. The reimbursement of PR-melatonin supports better penetration rates and a higher reduction in sales for BZD/Z-drugs.

  7. Comparison of the cardiovascular effects of tamsulosin oral controlled absorption system (OCAS) and alfuzosin prolonged release (XL)

    NARCIS (Netherlands)

    Michel, Martin C.; Chapple, Christopher R.

    2006-01-01

    OBJECTIVE: The cardiovascular (CV) effects of tamsulosin oral controlled absorption system (OCAS) 0.4 mg were compared with those of alfuzosin prolonged release (XL) 10 mg. METHODS: Two single-dose, crossover studies were performed. In study 1, CV alpha1-adrenoceptor antagonism was assessed by

  8. New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

    Directory of Open Access Journals (Sweden)

    Vigo DE

    2012-10-01

    Full Text Available Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is attributed to the MT1 and MT2 melatonin receptors present in the hypothalamic suprachiasmatic nucleus and other brain areas. The sleep-promoting actions of melatonin, which are demonstrable in healthy humans, have been found to be useful in subjects suffering from circadian rhythm sleep disorders and in elderly patients, who had low nocturnal melatonin production and secretion. The effectiveness of melatonin in treating sleep disturbances in these patients is relevant because the sleep-promoting compounds that are usually prescribed, such as benzodiazepines and related drugs, have many adverse effects, such as next-day hangover, dependence, and impairment of memory. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause any hangover or show any addictive potential. However, there is a lack of consistency concerning its therapeutic value (partly because of its short half-life and the small quantities of melatonin used. Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow-release melatonin preparations. A prolonged-release preparation of melatonin 2 mg (Circadin® has been approved for the treatment of primary insomnia in patients aged ≥55 years in the European Union. This prolonged-release preparation of melatonin had no effect on psychomotor functions, memory recall, or driving skills during the night or the next morning relative to placebo

  9. Effect of polymer degradation on prolonged release of paclitaxel from filomicelles of polylactide/poly(ethylene glycol) block copolymers.

    Science.gov (United States)

    Jelonek, Katarzyna; Li, Suming; Kasperczyk, Janusz; Wu, Xiaohan; Orchel, Arkadiusz

    2017-06-01

    Paclitaxel is one of the most efficient anticancer agents, but the conventional dosage formulations cause many side effects. PLA-PEG filomicelles are promising carriers of paclitaxel because high loading capacity and long term release can be achieved. Slow release of cytostatic drugs is very advantageous due to prolonged exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for prolonged delivery of paclitaxel. Paclitaxel is encapsulated in PLLA-PEG filomicelles and PDLLA-PEG spherical micelles. Drug release was studied in PBS at 37°C at various pH values to elucidate the influence of polymer degradation on drug release. NMR, GPC and HPLC were used to follow polymer degradation and drug release. The release of paclitaxel is strongly dependent on the degradation of micelles. A biphasic drug release profile is observed for both PLLA-PEG and PDLLA-PEG micelles: slow release in the first phase and faster release in the second phase. Degradation is faster at acidic pH than at pH7.4, and PLLA-PEG filomicelles degrade less rapidly than PDLLA-PEG spherical micelles, leading to various rates of drug release. The correlation between degradation and drug release is very helpful for the development of novel drug carriers with tailored properties. Importantly, the cytotoxic activity of PLLA-PEG filomicelles was evidenced, thus showing their potential as carrier of antitumor drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Randomized controlled trial of a protein substitute with prolonged release on the protein status of children with phenylketonuria.

    Science.gov (United States)

    Giovannini, Marcello; Riva, Enrica; Salvatici, Elisabetta; Cefalo, Graziella; Radaelli, Giovanni

    2014-01-01

    To examine whether a phenylalanine-free protein substitute with prolonged release may be beneficial to the protein status of children with phenylketonuria (PKU) compared to conventional substitutes. Sixty children with PKU, 7 to 16 years of age, were randomly allocated to receive either a prolonged-release (test) or the current conventional protein substitute for 30 days. Subjects were additionally sex and age matched with 60 subjects with mild hyperphenylalaninemia and 60 unaffected subjects. The protein status in children with PKU was assessed by albumin, transthyretin, and retinol-binding protein (RBP), and changes throughout the trial period were the primary outcome measures. Children with PKU did not differ in anthropometry from children with mild hyperphenylalaninemia or unaffected children but they ingested lower amounts of proteins (p phenylketonuria.

  11. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets

    OpenAIRE

    Devjak Novak, Sabina; Šporar, Elena; Vrečer, Franc; Baumgartner, Saša

    2015-01-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by differentb manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of act...

  12. Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective.

    Science.gov (United States)

    Roze, S; Ferrières, J; Bruckert, E; Van Ganse, E; Chapman, M J; Liens, D; Renaudin, C

    2007-11-01

    To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

  13. Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study.

    Science.gov (United States)

    Abedini, Sadollah; Gøransson, Lasse; Cockburn, Elinor; Kilany, Suzanne; Holdaas, Hallvard

    2018-02-01

    This study investigated medication adherence in kidney transplant patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T)-based immunosuppression in routine practice. Noninterventional, observational, multicenter study in Norway. Included adult KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1 mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and 12 postconversion. Primary endpoint: adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale. Secondary assessments: tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal Disease]), and adverse events. Ninety-one KTPs (mean ± SD age 47.7 ± 14.3 years) were analyzed. Mean ± SD change in PR-T dose from baseline (4.4 ± 2.4 mg/d) to month 12 was -0.1 ± 0.9 mg/d; mean tacrolimus trough levels remained within target. Overall medication adherence increased from 45.6% at baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and timing adherence followed a similar pattern. Odds ratio (OR) for adherence at month 1 (but not at other time points) was greater versus baseline for overall (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P = 0.0252) dimensions. Mean ± SD Basel Assessment of Adherence to Immunosuppressive Medication Scale visual analogue scale score at baseline was 96.4 ± 5.5%, and increased postconversion. Estimated glomerular filtration rate remained stable (month 12, 61.6 ± 17.7 mL/min per 1.73 m 2 ), as did other laboratory parameters. Two (2.2%) patients had adverse events considered probably/possibly treatment-related. There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal

  14. Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350

    DEFF Research Database (Denmark)

    Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie

    2017-01-01

    /naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool...

  15. An open-label extension study to evaluate the safety of ropinirole prolonged release in Chinese patients with advanced Parkinson's disease.

    Science.gov (United States)

    Zhang, Zhenxin; Wang, Jian; Zhang, Xiaoying; Chen, Shengdi; Wang, Zhenfu; Zhang, Baorong; Liu, Chunfeng; Qu, Qiumin; Cheng, Yan; Zhu, Rongxuan; Li, Jie; Hu, Jingqiu; Cai, Meng

    2015-04-01

    This open-label extension (OLE) study evaluated the safety profile of ropinirole prolonged release (PR) administered for 24 weeks as adjunctive to levodopa in Chinese patients with advanced Parkinson's disease (PD). This was a 24 week, flexible-dose, OLE study in Chinese patients with advanced PD who received 24 week treatment with ropinirole PR in the preceding double-blind (DB), phase III study (NCT01154166) and had no break in receiving study treatment while switching from the DB study to the OLE study. In the OLE study, patients received ropinirole PR once daily, starting with 2 mg/d and increasing up to 8 mg/d at week 4 (2 mg increment/week); if tolerable, the dose could be further increased in 4 mg increments up to 24 mg/d according to clinical judgment. There were no efficacy assessments. Safety assessments included monitoring adverse events (AEs), neurological examination, Gambling Symptom Assessment Scale questionnaire, liver chemistry, and laboratory tests. Of the 295 enrolled patients, 282 completed the study. The most common reason for withdrawal was AEs (n = 9, 3.1%). The mean duration to ropinirole PR treatment was 173.1 days and an overall median daily dose of ropinirole was 8 mg (range: 2-24 mg). Overall, 114 (38.6%) patients experienced on-treatment AEs; the most frequent reported AEs ( ≥ 2%) were dyskinesia (6.1%), dizziness (4.1%), nausea (3.4%), hallucinations (3.4%), somnolence (2.7%) and decreased weight (2.4%). Sixty-eight patients (23.1%) experienced treatment-related AEs. Six patients experienced serious AEs (SAEs), of which hallucination was determined to be a treatment-related SAE. There were no other significant safety findings. No new safety signals for ropinirole were identified. The safety profile of ropinirole was consistent with the preceding DB study and also with the established safety profile for ropinirole. Results support the long-term use of ropinirole PR as an adjunctive to levodopa in Chinese patients

  16. Development and evaluation of a biocide release system for prolonged antifungal activity in finishing materials

    NARCIS (Netherlands)

    Eversdijk, J.; Erich, S.J.F.; Hermanns, S.P.M.; Adan, O.C.G.; Bolle, de M.; Meyer, de K.; Bylemans, D.; Bekker, M.; Cate, ten A.T.

    2012-01-01

    This paper focuses on the use of modified nano-clay particles as a controlled release system for biocides from building materials. Different (model) biocides were incorporated in a biocide/nano-clay composite and subsequently the release of the biocides was monitored under different environmental

  17. Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone.

    Science.gov (United States)

    Iurian, Sonia; Turdean, Luana; Tomuta, Ioan

    2017-01-01

    This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon ® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio ( X 1 ), the type of hydrophilic polymer ( X 2 ), and the percentage of hydrophilic polymer ( X 3 ) on the percentages of dissolved Pal over 24 h ( Y 1 - Y 9 ). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring.

  18. Local delivery of nimodipine by prolonged-release microparticles-feasibility, effectiveness and dose-finding in experimental subarachnoid hemorrhage.

    Directory of Open Access Journals (Sweden)

    Daniel Hänggi

    Full Text Available BACKGROUND AND PURPOSE: To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH. METHODS: 70 male Wistar rats were categorized into three groups: 1 sham operated animals (control, 2 animals with SAH only (control and the 3 treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40% of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA. Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry. RESULTS: DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only, as compared to the sham operated group (p<0.001. Only animals within group 3 and the highest nimodipine microparticles concentration (40% as well as group 1 (sham demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury. CONCLUSIONS: Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.

  19. New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists

    Directory of Open Access Journals (Sweden)

    Rüdiger Hardeland

    2009-06-01

    Full Text Available Rüdiger HardelandJohann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, GermanyAbstract: Hypnotic effects of melatonin and melatoninergic drugs are mediated via MT1 and MT2 receptors, especially those in the circadian pacemaker, the suprachiasmatic nucleus, which acts on the hypothalamic sleep switch. Therefore, they differ fundamentally from GABAergic hypnotics. Melatoninergic agonists primarily favor sleep initiation and reset the circadian clock to phases allowing persistent sleep, as required in circadian rhythm sleep disorders. A major obstacle for the use of melatonin to support sleep maintenance in primary insomnia results from its short half-life in the circulation. Solutions to this problem have been sought by developing prolonged-release formulations of the natural hormone, or melatoninergic drugs of longer half-life, such as ramelteon, tasimelteon and agomelatine. With all these drugs, improvements of sleep are statistically demonstrable, but remain limited, especially in primary chronic insomnia, so that GABAergic drugs may be indicated. Melatoninergic agonists do not cause next-day hangover and withdrawal effects, or dependence. They do not induce behavioral changes, as sometimes observed with z-drugs. Despite otherwise good tolerability, the use of melatoninergic drugs in children, adolescents, and during pregnancy has been a matter of concern, and should be avoided in autoimmune diseases and Parkinsonism. Problems and limits of melatoninergic hypnotics are compared.Keywords: agomelatine, hypnotics, melatonin, prolonged-release, ramelteon, tasimelteon

  20. A New Environmentally Safe Formulation and of Low Cost for Prolonged Release System of Atrazine and Diuron

    Directory of Open Access Journals (Sweden)

    Gracy karla da Rocha Cortes

    2017-07-01

    Full Text Available Diuron and atrazine were incorporated in new formulations developed with the purpose to improve herbicides action through release systems, as well as to reduce the environmental toxicity. A low cost formulation (ALG/ESC was obtained by combining sodium alginate (ALG with fish scales of the Piau fish (ESC from the Leporinus elongatus species. From the crosslinking of ALG/ESC with CaCl2, the formulation ALG/ESC-CaCl2 was obtained. For ALG/ESC-CaCl2, the results are successful, showing a prolonged release of 3.5 and 4.5 days for atrazine and diuron, respectively. Based on parameters of an empirical equation used to fit the herbicide release data, it appears that the release systems of diuron and atrazine from ALG/ESC-CaCl2 are by diffusion processes due to anomalous transport, which did not follow Fick’s laws of diffusion. DOI: http://dx.doi.org/10.17807/orbital.v9i3.994

  1. Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Garcia-Leal, C; Del-Ben, C M; Leal, F M; Graeff, F G; Guimarães, F S

    2010-05-01

    Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

  2. Microspheres prepared with biodegradable PHBV and PLA polymers as prolonged-release system for ibuprofen: in vitro drug release and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Giovana Carolina Bazzo

    2012-12-01

    Full Text Available In this study, poly(hydroxybutyrate-co-hydroxyvalerate (PHBV and poly(l-lactide (PLA microspheres containing ibuprofen were prepared with the aim of prolonging the drug release. The oil-in-water (O/W emulsion solvent evaporation technique was used, varying the polymer ratio. All formulations provided spherical particles with drug crystals on the surface and a porous and rough polymeric matrix when PHBV was used and smooth external surface when prepared with PLA. The in vitro dissolution profiles show that the formulation containing PHBV/PLA at the proportion of 30/70 presented the best results in terms of prolonging the ibuprofen release. The analysis of the concentration of ibuprofen in the blood of rats showed that maximum levels were achieved at between one and two hours after administration of the immediate-release form (pure drug, while the prolonged microspheres led to a small amount of the drug being released within the first two hours and reached the maximum level after six hours of administration. It was concluded that it is possible to prolong the release of ibuprofen through its incorporation into PHBV/PLA microspheres.No presente estudo foram preparadas microesferas de poli(hidroxibutirato-co-hidroxivalerato (PHBV e poli(ácido láctico (PLA com o objetivo de prolongar a liberação do ibuprofeno, utilizado como fármaco modelo. Empregou-se o método de emulsificação e evaporação do solvente óleo em água (O/A, variando-se a proporção entre os polímeros. Todas as formulações originaram partículas esféricas com cristais de fármaco aderidos à superfície externa. As microesferas apresentaram superfície rugosa e porosa, quando o PHBV foi utilizado, e superfície externa lisa, quando preparadas com o PLA. Os perfis de dissolução in vitro evidenciaram que a formulação que continha PHBV/PLA na proporção de 30/70 apresentou melhores resultados para prolongar a liberação do ibuprofeno. Através da análise da concentra

  3. Fast-Dissolving, Prolonged Release, and Antibacterial Cyclodextrin/Limonene-Inclusion Complex Nanofibrous Webs via Polymer-Free Electrospinning.

    Science.gov (United States)

    Aytac, Zeynep; Yildiz, Zehra Irem; Kayaci-Senirmak, Fatma; San Keskin, Nalan Oya; Kusku, Semran Ipek; Durgun, Engin; Tekinay, Turgay; Uyar, Tamer

    2016-10-05

    We have proposed a new strategy for preparing free-standing nanofibrous webs from an inclusion complex (IC) of a well-known flavor/fragrance compound (limonene) with three modified cyclodextrins (HPβCD, MβCD, and HPγCD) via electrospinning (CD/limonene-IC-NFs) without using a polymeric matrix. The experimental and computational modeling studies proved that the stoichiometry of the complexes was 1:1 for CD/limonene systems. MβCD/limonene-IC-NF released much more limonene at 37, 50, and 75 °C than HPβCD/limonene-IC-NF and HPγCD/limonene-IC-NF because of the greater amount of preserved limonene. Moreover, MβCD/limonene-IC-NF has released only 25% (w/w) of its limonene, whereas HPβCD/limonene-IC-NF and HPγCD/limonene-IC-NF released 51 and 88% (w/w) of their limonene in 100 days, respectively. CD/limonene-IC-NFs exhibited high antibacterial activity against E. coli and S. aureus. The water solubility of limonene increased significantly and CD/limonene-IC-NFs were dissolved in water in a few seconds. In brief, CD/limonene-IC-NFs with fast-dissolving character enhanced the thermal stability and prolonged the shelf life along with antibacterial properties could be quite applicable in food and oral care applications.

  4. A comparison between the administration of oral prolonged-release oxycodone-naloxone and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis

    Directory of Open Access Journals (Sweden)

    Roberto A

    2017-09-01

    Full Text Available A Roberto,1 MT Greco,2 L Legramandi,3 F Galli,3 M Galli,4 O Corli1 1Pain and Palliative Care Research Unit, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 2Department of Clinical Sciences and Community, University of Milan, Milan, Italy, 3Methodology for Clinical Research Laboratory, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 4Scientific Medical Communication srl, Novara, Italy Background: Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF and oral prolonged-release oxycodone-naloxone (OXN-PR are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared.Patients and methods: Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline. Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups.Results: Three hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR were included in the comparative analysis. The amount of responders was comparable after TDF (75.3% and OXN-PR administration (82.9%, not significant [NS]. The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p<0.0001. A daily opioid dose escalation >5% was less common after

  5. Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone

    Directory of Open Access Journals (Sweden)

    Iurian S

    2017-03-01

    Full Text Available Sonia Iurian, Luana Turdean, Ioan Tomuta Department of Pharmaceutical Technology and Biopharmacy, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania Abstract: This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal delivery, containing Kollidon® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC, or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio (X1, the type of hydrophilic polymer (X2, and the percentage of hydrophilic polymer (X3 on the percentages of dissolved Pal over 24 h (Y1–Y9. Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring. Keywords: pharmaceutical development, quality by design, failure mode effects analysis, Ishikawa diagram, fish-bone diagram, hydrophilic matrix

  6. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    Science.gov (United States)

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

  7. Prolonged amelioration of experimental postoperative pain by bupivacaine released from microsphere-coated hernia mesh.

    Science.gov (United States)

    Ohri, Rachit; Wang, Jeffery Chi-Fei; Pham, Lan; Blaskovich, Phillip D; Costa, Daniel; Nichols, Gary; Hildebrand, William; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary R

    2014-01-01

    Postoperative pain alters physiological functions and delays discharge. Perioperative local anesthetics are effective analgesics in the immediate 1- to 2-day postoperative period, but acute pain often lasts longer. The goal of this work was to develop a local anesthetic formulation adhering to an intraoperative implanted device that reduces pain for at least 3 days after surgery. Six groups, each with 8 rats, were studied. In a control group (group I), one 1.2-cm-long incision of the skin was followed by blunt dissection to separate the skin away from the underlying tissues and closing with 2 sutures. In 3 of the treatment groups, the same surgical procedure was used, with the subcutaneous space formed by the blunt dissection lined with a 1-cm square patch of hernia mesh coated with poly lactide co-glycolic acid microspheres containing approximately 17 mg of bupivacaine (group II), no drug (placebo; group III), or bupivacaine free-base powder (group IV). Uncoated mesh implants (group V) served as a secondary control. A standard bupivacaine solution (0.4 mL, 0.5%; 2-mg dose) was infiltrated subcutaneously 30 minutes before the surgery and served as a standard control (group VI). Mechanosensitivity of the skin was tested by the local subcutaneous muscle responses to cutaneous tactile stimulation by von Frey hairs with forces of 4 g (for allodynia) and 15 g (for hyperalgesia) preoperatively and for 7 postoperative days. Control rats (group I) showed mechanohypersensitivity, indicative of postoperative allodynia and hyperalgesia, for all 7 postoperative days. Mechanohyperalgesia in rats that received mesh coated with bupivacaine-releasing microspheres (group II) was reduced during this period to 13% of control postoperative values (P < 0.001); mesh coated with bupivacaine base (group IV) reduced it by 50% (P = 0.034). The placebo mesh (group III) and uncoated mesh (group V) caused no significant reduction of mechanohypersensitivity, and bupivacaine solution infiltrated

  8. Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jan K Buitelaar

    2009-08-01

    Full Text Available Jan K Buitelaar1, J Antoni Ramos-Quiroga2, Miguel Casas2, J J Sandra Kooij3, Asko Niemelä4, Eric Konofal5, Joachim Dejonckheere6, Bradford H Challis7, Rossella Medori81Department of Psychiatry, University Medical Center, St. Radboud and Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands; 2Department of Psychiatry, Hospital Universitari Vall d’Hebron and Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 3PsyQ, Psycho-Medical Programs, Program Adult ADHD, Den Haag, The Netherlands; 4Oulu University Hospital, Department of Psychiatry, Oulu, Finland; 5Groupe Hospitalier Pitie-Salpetriere, Paris, France; 6SGS Life Sciences, Mechelen, Belgium; 7Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ, USA; 8Janssen-Cilag EMEA, Neuss, GermanyAbstract: The osmotic release oral system (OROS methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety and tolerability of OROS methylphenidate in a flexible dose regimen (18–90 mg daily for the treatment of adults diagnosed with ADHD (N = 370. Medication was adjusted to optimize efficacy and tolerability for each patient. Adverse events, vital signs, and laboratory parameters were assessed. Most patients (337; 91% completed the seven-week treatment and the final dispensed dose was 18 mg (8%, 36 mg (29%, 54 mg (34%, 72 mg (20%, or 90 mg (9%. Adverse events were reported in 253 (68% patients and most were mild or moderate in severity; most frequently reported included headache (17%, decreased appetite (13%, and insomnia (11%. Adverse events were rarely serious (<1%; 2/370. Small mean increases in systolic and diastolic blood pressure (both 2.4 mmHg and pulse (3.2 bpm were observed. Body weight decreased

  9. Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres.

    Science.gov (United States)

    Liao, Yu-Te; Liu, Chia-Hung; Yu, Jiashing; Wu, Kevin C-W

    2014-01-01

    A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS.

  10. Effectiveness of prolonged-release melatonin in Improving Quality of Sleep in Patients Aged 55 or Over

    Directory of Open Access Journals (Sweden)

    G. V. Kovrov

    2016-01-01

    Full Text Available Objective: to evaluate the efficacy of prolonged-release melatonin used in routine practice to improve sleep quality in Russian patients over 55 years of age.Patients and methods. The results of the multicenter open-label observational study of Circadin (prolonged-release melatonin efficiency for treatment of insomnia in 36 patients older than 55 yeare presented. The drug was administered at a dose of 2 mg one-two hours before bedtime for 3 weeks.Results. Treatment with Circadin resulted in statistically significant (p<0.0001 according to pared t-test (95% CI: 4.8; 7.3 improvement of the sleep quality: the mean value of the modified subjective sleep characteristics scale increased from 11.8±2.6 points at baseline to 17.8±2.3 points after 3 weeks of treatment. The modified Questionnaire Scoring Subjective Characteristics of Sleep was grade from 0 (very bad to 20 (very good taking into account: the amount of time required to fall asleep, the sleep duration, the number of night awakenings and the general well-being in the morning. An increase of 6 points on a scale from 0 to 20 was considered as clinically relevant. A greater effect was observed in patients with severely impaired sleep quality as well as with low level of depression and anxiety and absence of cognitive impairment. Upon completion of Circadin treatment there were statistically significant improvement (p<0.0001 of attention (the mean value of the symbol-digit coding test increased from 34.2±9.7 to 37.3±10.6 points and memory (the median value of the short-term verbal memory test increased from 4 points at baseline to 5 points at the study end, p=0.0069.The drug had a good safety profile; only one adverse event related to study medication (allergic rush was registered in the study. The absolute majority (91.7% of the study patients considered Circadin treatment as either effective or very effective.Conclusion. Taking into consideration the good safety profile of this drug

  11. Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres

    Directory of Open Access Journals (Sweden)

    Liao YT

    2014-06-01

    Full Text Available Yu-Te Liao,1 Chia-Hung Liu,2 Jiashing Yu,1 Kevin C-W Wu1,3 1Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan; 2Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; 3Division of Medical Engineering Research, National Health Research Institutes, Zhunan Township, Miaoli County, Taiwan Abstract: A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs and organic alginate (denoted as MSN@Alg was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine4-tyrosine-arginine-glycine-aspartic acid (K4YRGD peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2. The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold for the arginine-glycine-aspartic acid (RGD-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS. Keywords

  12. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets.

    Science.gov (United States)

    Devjak Novak, S; Šporar, E; Baumgartner, S; Vrečer, F

    2012-07-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by different manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of active pharmaceutical ingredients (API). This study investigates whether HPMC manufactured by two manufacturers using different chemical procedures differs in particle-size distribution, particle shape, particle morphology, chemical composition, and dissolution of diclofenac sodium as a model drug. NIR spectroscopy was introduced and calibration models were developed to detect physical differences among HPMC batches from two different origins. The physical differences between HPMC samples were additionally confirmed with scanning electron microscopy (SEM), gas chromatography (GC) measurements, and dissolution testing of hydrophilic matrix tablets. Our results prove that, even if HPMC polymers manufactured from two different sources comply with the pharmacopeial specification, they significantly differ in physicochemical properties and thus influence the properties of the formulated dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

    Directory of Open Access Journals (Sweden)

    Cai Y

    2014-07-01

    Full Text Available Yunpeng Cai,1,2 Mingxin Xu,2 Minglu Yuan,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, School of Medicine, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: Since the availability of recombinant human growth hormone (rhGH enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot® microsphere and injectors (Zomajet®, Serojet®, and NordiFlex®. Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product. Keywords: intranasal, pulmonary, transdermal, microsphere, microneedle, hydrogel

  14. Restless legs syndrome: a new entity of neuropathic pain? Treatment with prolonged release oxycodone/naloxone combination

    Directory of Open Access Journals (Sweden)

    Gemignani F

    2016-04-01

    Full Text Available Franco Gemignani,1 Andrea Melpignano,1,2 Giulia Milioli,1,2 Silvia Riccardi,1,2 Liborio Parrino1,2 1Neurology Unit, Department of Neurosciences, University of Parma, Parma, Italy; 2Sleep Disorders Center, Department of Neurosciences, University of Parma, Parma, Italy Abstract: Restless legs syndrome (RLS is a disorder of sensorimotor integration characterized by an urge to move the legs when at rest, especially at night or in the evening, which is relieved by movement. Sensory symptoms may be prominent, often exhibiting features consistent with neuropathic pain. Iron deficiency and genetic factors are implicated in RLS causation in most patients. The pathogenetic model of impaired circadian dopaminergic modulation of sensorimotor integration circuitry at the spinal level is fitting with the co-occurrence of movement disorders, sensory symptoms, and sleep disruption in RLS. Accordingly, levodopa and dopamine agonists are effective for RLS symptoms, which compensate for the impaired descending control by diencephalo-spinal dopa(minergic pathway. Dopamine agonists are usually indicated as the first-line therapy, but their use in long-term treatment is often complicated by augmentation and impulse control disorder, thus alpha-2-delta ligands also are now considered the first line of treatment. It has been recognized that endogenous opioid system is also involved in the mechanisms generating RLS, possibly through an impaired modulation of pain pathways. Opioids can be considered as an alternative therapy, particularly in patients with augmentation and/or refractory to other treatments. Recently introduced prolonged-release oxycodone–naloxone was efficacious for short-term treatment of patients with severe RLS inadequately controlled with previous treatment. It will be important to assess whether opioids, as well as other drugs, are especially effective in definite RLS subtypes such as the painful phenotype. Keywords: small fiber neuropathy

  15. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2011-07-01

    Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

  16. Applicability of near-infrared spectroscopy in the monitoring of film coating and curing process of the prolonged release coated pellets.

    Science.gov (United States)

    Korasa, Klemen; Hudovornik, Grega; Vrečer, Franc

    2016-10-10

    Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit® RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at-line NIR was capable to predict the thickness of Eudragit® RS/RL film coating in a wide range (up to 40μm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

    Science.gov (United States)

    Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

    2015-01-01

    Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

  18. Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

    Directory of Open Access Journals (Sweden)

    Theodora Nikolaidou

    Full Text Available Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ. Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT. Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

  19. Amine bridges grafted mesoporous silica, as a prolonged/controlled drug release system for the enhanced therapeutic effect of short life drugs

    International Nuclear Information System (INIS)

    Rehman, Fozia; Ahmed, Khalid; Airoldi, Claudio; Gaisford, Simon; Buanz, Asma; Rahim, Abdur; Muhammad, Nawshad; Volpe, Pedro L.O.

    2017-01-01

    Hybrid mesoporous silica SBA-15, with surface incorporated cross-linked long hydrophobic organic bridges was synthesized using stepwise synthesis. The synthesized materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-rays diffraction, thermogravimetry and scanning and transmission electron microscopy. The functionalized material showed highly ordered mesoporous network with a surface area of 629.0 m 2 g −1 . The incorporation of long hydrophobic amine chains on silica surface resulted in high drug loading capacity (21% Mass/Mass) and prolonged release of ibuprofen up till 75.5 h. The preliminary investigations suggests that the synthesized materials could be proposed as controlled release devices to prolong the therapeutic effect of short life drugs such as ibuprofen to increase its efficacy and to reduce frequent dosage. - Highlights: • Silica SBA-15 was synthesized and modified with long hydrophobic amine linkers. • These materials were characterized using different techniques. • The modified material showed high drug loading capacity and control ibuprofen release in biological fluids.

  20. Amine bridges grafted mesoporous silica, as a prolonged/controlled drug release system for the enhanced therapeutic effect of short life drugs

    Energy Technology Data Exchange (ETDEWEB)

    Rehman, Fozia, E-mail: foziaics@yahoo.com [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084–971 Campinas, SP (Brazil); Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore (Pakistan); Ahmed, Khalid; Airoldi, Claudio [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084–971 Campinas, SP (Brazil); Gaisford, Simon; Buanz, Asma [UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX (United Kingdom); Rahim, Abdur; Muhammad, Nawshad [Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS Institute of Information Technology, Lahore (Pakistan); Volpe, Pedro L.O. [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084–971 Campinas, SP (Brazil)

    2017-03-01

    Hybrid mesoporous silica SBA-15, with surface incorporated cross-linked long hydrophobic organic bridges was synthesized using stepwise synthesis. The synthesized materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-rays diffraction, thermogravimetry and scanning and transmission electron microscopy. The functionalized material showed highly ordered mesoporous network with a surface area of 629.0 m{sup 2} g{sup −1}. The incorporation of long hydrophobic amine chains on silica surface resulted in high drug loading capacity (21% Mass/Mass) and prolonged release of ibuprofen up till 75.5 h. The preliminary investigations suggests that the synthesized materials could be proposed as controlled release devices to prolong the therapeutic effect of short life drugs such as ibuprofen to increase its efficacy and to reduce frequent dosage. - Highlights: • Silica SBA-15 was synthesized and modified with long hydrophobic amine linkers. • These materials were characterized using different techniques. • The modified material showed high drug loading capacity and control ibuprofen release in biological fluids.

  1. mTOR inhibition in macrophages of asymptomatic HIV+ persons reverses the decrease in TLR4-mediated TNFα release through prolongation of MAPK pathway activation1

    Science.gov (United States)

    Li, Xin; Han, Xinbing; Llano, Juliana; Bole, Medhavi; Zhou, Xiuqin; Swan, Katharine; Anandaiah, Asha; Nelson, Benjamin; Patel, Naimish R.; Reinach, Peter S.; Koziel, Henry; Tachado, Souvenir D.

    2011-01-01

    Toll-like receptor 4 (TLR4) mediated signaling is significantly impaired in macrophages from HIV+ persons predominantly due to altered MyD88-dependent pathway signaling caused in part by constitutive activation of PI3K. Here we assessed in these macrophages if the blunted increase in TLR4-mediated TNFα release induced by lipid A are associated with PI3K-induced upregulation of mammalian target of rapamycin (mTOR) activity. mTOR inhibition with rapamycin enhanced TLR4-mediated TNFα release, but instead suppressed anti-inflammatory IL-10 release. Targeted gene silencing of mTOR in macrophages resulted in lipid A-induced TNFα and IL-10 release patterns similar to those induced by rapamycin. Rapamycin restored MyD88-IRAK interaction in a dose-dependent manner. Targeted gene silencing of MyD88 (shRNA) and mTOR (RNAi) inhibition resulted in TLR4-mediated p70s6K activation and enhanced TNFα release, whereas IL-10 release was inhibited in both silenced and non-silenced HIV+ macrophages. Furthermore, mTOR inhibition augmented lipid A-induced TNFα release through enhanced and prolonged phosphorylation of ERK1/2 and JNK1/2 MAP kinases, which was associated with time-dependent MKP-1 destabilization. Taken together, impaired TLR4-mediated TNFα release in HIV+ macrophages is attributable in part to mTOR activation by constitutive PI3K expression in a MyD88-dependent signaling pathway. These changes result in MKP-1 stabilization, which shortens and blunts MAP kinase activation. mTOR inhibition may serve as a potential therapeutic target to upregulate macrophage innate immune host defense responsiveness in HIV+ persons. PMID:22025552

  2. Preparation and in vitro evaluation of carboxymethylated κ-carrageenan aluminum hydrogel microbeads for prolonged release of mefenamic acid

    International Nuclear Information System (INIS)

    Beron, Pia Maria G.; Cruzado, Shervin T.; Dela Cruz, Sharmaine F.; Estanislao, Fides Mae L.; Evangelista, Charina Joy; Mandocdoc, Larra Minnellie W.; Salas, Sharlaine B.; Tiu, Mark Brian C.; Carigma, Andrea Q.; Bayquen, Aristea V.

    2012-01-01

    Polymers that swell in an aqueous medium have been widely used to formulate controlled-release dosage forms. This study aims to prepare carboxymethyl κ-carrageenan (CMKC) microbeads and evaluate its potential for controlled release of mefenamic acid in comparison to the positive control, carboxymethylcellulose (CMC) microbeads. The powdered κ-carrageenan was carboxymethylated and Fourier-Transform Infrared Spectroscopy confirmed the carboxy methylation. Aqueous solutions of CMC (3% w/v) and CMKC (3%, 4%, 5% w/v) were prepared as microbeads using ionotropic gelation technique. Microbeads were loaded with mefenamic acid by suspending it in the aqueous solution (0.5% w/v) of the drug for 72 hours. Particle size and surface morphology were characterized using scanning electron microscopy. One-way ANOVA was used to determine a significant difference between the release activity of the drug-loaded CMKC and CMC microbeads. Differential Scanning Calorimetry was performed on the drug, drug- free, and drug-loaded microbeads of CMC and CMKC. Two-way ANOVARM showed significant interaction in % drug release of the three groups being analyzed in respect to time effect (p≤0.001) and group effect (p≤0.001). Post Hoc Duncan Multiple Range Test showed that 3% CMC and 4% CMKC has equal average % drug release values and is significantly higher compared to the commercial mefenamic acid. Also, one way ANOVA showed that 3% CMC was able to release the drug with no significant difference in time (p = 0.159), while 4% CMKC (p < 0.001) and the commercial mefenamic acid (p≤0.001) were able to release the drug with significant difference in time (author)

  3. Novel polymeric bioerodable microparticles for prolonged-release intrathecal delivery of analgesic agents for relief of intractable cancer-related pain.

    Science.gov (United States)

    Han, Felicity Y; Thurecht, Kristofer J; Lam, Ai-Leen; Whittaker, Andrew K; Smith, Maree T

    2015-07-01

    Intractable cancer-related pain complicated by a neuropathic component due to nerve impingement is poorly alleviated even by escalating doses of a strong opioid analgesic. To address this unmet medical need, we developed sustained-release, bioerodable, hydromorphone (potent strong opioid)- and ketamine (analgesic adjuvant)-loaded microparticles for intrathecal (i.t.) coadministration. Drug-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared using a water-in-oil-in-water method with evaporation. Encapsulation efficiency of hydromorphone and ketamine in PLGA (50:50) microparticles was 26% and 56%, respectively. Microparticles had the desired size range (20-60 μm) and in vitro release was prolonged at ≥28 days. Microparticles were stable for ≥6 months when stored refrigerated protected from light in a desiccator. Desirably, i.t. injected fluorescent dye-labeled PLGA microparticles in rats remained in the lumbar region for ≥7 days. In a rat model of neuropathic pain, i.t. coinjection of hydromorphone- and ketamine-loaded microparticles (each 1 mg) produced analgesia for 8 h only. Possible explanations include inadequate release of ketamine and/or hydromorphone into the spinal fluid, and/or insufficient ketamine loading to prevent development of analgesic tolerance to the released hydromorphone. As sub-analgesic doses of i.t. ketamine at 24-48 h intervals restored analgesia on each occasion, insufficient ketamine loading appears problematic. We will investigate these issues in future work. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Hyaluronate nanoparticles included in polymer films for the prolonged release of vitamin E for the management of skin wounds.

    Science.gov (United States)

    Pereira, Gabriela Garrastazu; Detoni, Cassia Britto; Balducci, Anna Giulia; Rondelli, Valeria; Colombo, Paolo; Guterres, Silvia Stanisçuaski; Sonvico, Fabio

    2016-02-15

    Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    Directory of Open Access Journals (Sweden)

    Oranje Bob

    2011-10-01

    Full Text Available Abstract Background Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life. Methods/Design Randomized, blinded, two-armed, parallel superiority trial. We plan to include 80 consenting outpatients diagnosed with schizophrenia or schizoaffective disorder, 18-55 years of age, treated with antipsychotic drug(s and at least one benzodiazepine derivative for the last three months before inclusion. Exclusion criteria: currently under treatment for alcohol or drug abuse, aggressive or violent behavior, known mental retardation, pervasive developmental disorder, dementia, epilepsy, terminal illness, severe co morbidity, inability to understand Danish, allergy to melatonin, lactose, starch, gelatin, or talc, hepatic impairment, pregnancy or nursing, or lack of informed consent. After being randomized to prolonged-release melatonin (Circadin® 2 mg daily or matching placebo, participants are required to slowly taper off their benzodiazepine dose. The primary outcome measure is benzodiazepine dose at 6 months follow-up. Secondary outcome measures include sleep, psychophysiological, and neurocognitive measures. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, psychophysiology, adverse events, social function, and quality of life are also collected at 2 and 4

  6. A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Liu

    Full Text Available Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA-loaded poly (d,l-lactide-co-ε-caprolactone (PLC microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK using a rat model. The drug release profiles of the microfilms were characterized (group 1. Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2, allogeneic control grafts (group 3, allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4, and allogeneic grafts with PA eye drops (group 5; n = 12 in each. PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006-0.009 mg/day, with a consistent aqueous drug concentration of 207-209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3. Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001. There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  7. Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction.

    Science.gov (United States)

    Adeyeye, M C; Mwangi, E; Katondo, B; Jain, A; Ichikawa, H; Fukumori, Y

    2005-06-01

    The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions--Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60 degrees C for 48 h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48 h (T50 = microcapsules (T50 = 6 h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287 degrees C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2theta of 12 degrees and 18 degrees , suggestive of interaction. Some changes in drug peak characteristics at 18 degrees and 23 degrees were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of drug and powdered forms of

  8. Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

    Science.gov (United States)

    Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

    2017-10-01

    Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

  9. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    DEFF Research Database (Denmark)

    Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

    2011-01-01

    Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...

  10. Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

    Science.gov (United States)

    Undre, Nasrullah; Dickinson, James

    2017-04-04

    Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10

  11. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol

    DEFF Research Database (Denmark)

    Baandrup, Lone; Fagerlund, Birgitte; Jennum, Poul

    2011-01-01

    Treatment of schizophrenia frequently includes prolonged benzodiazepine administration despite a lack of evidence of its use. It is often difficult to discontinue benzodiazepines because of the development of dependence. We aim to assess if melatonin can facilitate the withdrawal of prolonged...... benzodiazepine administration in patients with schizophrenia. Furthermore, we aim to investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life....

  12. Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study

    Directory of Open Access Journals (Sweden)

    Sadollah Abedini, MD, PhD

    2018-02-01

    Conclusions. There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal function remained stable.

  13. Budget impact of switching from an immediate-release to a prolonged-release formulation of tacrolimus in renal transplant recipients in the UK based on differences in adherence

    Directory of Open Access Journals (Sweden)

    Muduma G

    2014-03-01

    Full Text Available Gorden Muduma,1 Isaac Odeyemi,1 Jayne Smith-Palmer,2 Richard F Pollock21Astellas Pharma Europe, Chertsey, UK; 2Ossian Health Economics and Communications, Basel, SwitzerlandBackground and aims: Advagraf is a once-daily prolonged-release formulation of tacrolimus with proven noninferiority to Prograf, a twice-daily immediate-release formulation of tacrolimus, in biopsy-proven acute rejection, graft survival and patient survival in renal transplant recipients. Advagraf is associated with improved adherence compared with Prograf, which may ultimately improve long-term outcomes. The present study assessed the budget impact of switching patients from Prograf to Advagraf in the UK.Materials and methods: A budget-impact model was constructed based on published data on acute rejection, graft failure, and mortality in the UK setting. Patients were assumed to convert from Prograf to Advagraf on a 1:1 milligram:milligram basis. In a study comparing the adherence rates between once-daily versus twice-daily formulations of tacrolimus, the proportion of patients taking the prescribed number of daily doses was 88.2% in Advagraf patients and 78.8% in Prograf patients. The model applied a relative risk of graft failure of 3.47 to nonadherent patients based on data from a 2004 meta-analysis (based on graft-failure rates of 1.3%–40.0% in adherent patients, compared with 6.1%–100% in nonadherent patients. Cost data were taken from the March 2013 British National Formulary and 2012–2013 National Health Service tariff information. The analysis was performed over a 5-year time horizon and future costs were not discounted, in line with International Society for Pharmacoeconomics and Outcomes Research guidelines.Results: Over a 5-year time horizon, the mean cost per patient (including tacrolimus, concomitant immunosuppressive medications, dialysis after graft failure, and treatment for acute rejection was £29,328 (standard deviation [SD] £2,844 for Advagraf

  14. Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

    Science.gov (United States)

    Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H L; Brown, Malcolm W; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R J

    2017-08-01

    ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10

  15. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

    Czech Academy of Sciences Publication Activity Database

    Maletínská, L.; Nagelová, V.; Tichá, A.; Zemenová, J.; Pirník, Z.; Holubová, M.; Špolcová, A.; Mikulášková, Barbora; Blechová, M.; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, B.; Kuneš, Jaroslav

    2015-01-01

    Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA TA ČR(CZ) TE01020028 Institutional support: RVO:67985823 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

  16. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Nagelová, Veronika; Tichá, Anežka; Zemenová, Jana; Pirník, Zdenko; Holubová, Martina; Špolcová, Andrea; Mikulášková, Barbora; Blechová, Miroslava; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, Blanka; Kuneš, Jaroslav

    2015-01-01

    Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

  17. Technology of stable, prolonged-release eye-drops containing Cyclosporine A, distributed between lipid matrix and surface of the solid lipid microspheres (SLM).

    Science.gov (United States)

    Wolska, Eliza; Sznitowska, Małgorzata

    2013-01-30

    The aim of this study was to prepare solid lipid microspheres (SLM) with incorporated Cyclosporine A (Cs), suitable for ocular application. For this purpose, SLM were formulated by using different lipids and three different nonionic surfactants. The SLM were produced using a hot emulsification method. The SLM dispersions contained 10, 20 or 30% of lipid (w/w) and up to 2% (w/w) of Cs. The size of the microspheres with Cs ranged from 1 to 15 μm. Physically stable SLM with Cs were prepared using Compritol, as a lipid matrix, and Tween 80, as a surfactant. In contrast, dispersion with Precirol alone, formed semi-solid gels during storage, while in formulations with Precirol and Miglyol, crystals of Cs were observed. In vitro release profile of Compritol formulations showed that 40% of Cs is released within 1h, while the release of the following 40% takes more time, depending on lipid content in the formulations. The large part of Cs, added to SLM formulations (from 45 to 80%), was found on the surface of microparticles, but no drug crystallization occurred during a long-term storage. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Differential effects of 18- and 24-Gy cranial irradiation on growth rate and growth hormone release in children with prolonged survival after acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Cicognani, A.; Cacciari, E.; Vecchi, V.; Cau, M.; Balsamo, A.; Pirazzoli, P.; Tosi, M.T.; Rosito, P.; Paolucci, G.

    1988-01-01

    To evaluate the effects of two different doses of cranial irradiation on growth and growth hormone (GH) release, we studied 61 children with acute lymphocytic leukemia who had survived at least five years in continuous complete remission. Forty-three children received 24 Gy (group 1) and 18 children received 18 Gy (group 2). Height was evaluated at diagnosis, at the end of treatment, and 6, 12, and 24 months later. Growth hormone release was evaluated by arginine and levodopa tests after the end of treatment. After diagnosis, the height SD score decreased significantly in both groups; two years after the end of treatment, only group 1 showed an SD score for height that was still significantly lower than at diagnosis. Group 1 showed impaired GH responses to the tests and, compared with controls, group 1 in fact included a percentage of subjects with a normal response to levodopa (ie, greater than 8 micrograms/L) that was significantly lower (56.4% vs 83.3%) and a percentage of nonresponders to both tests that was significantly higher (21.6% vs 0%). These data indicate that only patients treated with lower cranial irradiation dosage (18 Gy) had complete growth recovery and normal GH responses to pharmacologic tests

  19. Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75.

    Science.gov (United States)

    Bokser, L; Bajusz, S; Groot, K; Schally, A V

    1990-09-01

    Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl)-D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB-75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng/ml was observed, corresponding to the "burst" effect. Levels of the analog decreased to 19.6 ng/ml on day 2, gradually reached a concentration of 4.7 ng/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum

  20. Risk of atrial fibrillation as a function of the electrocardiographic PR interval

    DEFF Research Database (Denmark)

    Nielsen, Jonas Bille; Pietersen, Adrian; Graff, Claus

    2013-01-01

    Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF).......Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF)....

  1. Recovery of pituitary-gonadal function in male and female rats after prolonged administration of a potent antagonist of luteinizing hormone-releasing hormone (SB-75).

    Science.gov (United States)

    Bokser, L; Srkalovic, G; Szepeshazi, K; Schally, A V

    1991-08-01

    The reversibility of the antifertility effects induced by long-term administration of the LH-RH antagonistic analog [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]-LH-RH (SB-75) was investigated in male and female rats. Male rats were implanted with osmotic minipumps releasing 50 micrograms of SB-75/day for 60 days. The control rats were implanted with minipumps containing only vehicle. The treatment with the antagonist caused a significant decrease in the weights of the testes, seminal vesicles and ventral prostates (p less than 0.01) and reduced serum LH and testosterone levels (p less than 0.01). The histology of the testes from the treated rats showed that spermatogenesis was totally depressed. No mature elongated or round spermatids were found in the seminiferous tubules, spermatocytes being the most advanced germ cell form in 100% of the testicular tubules. These changes indicate that a total spermatogenetic arrest occurred in the treated animals. Ninety days after cessation of treatment with the LH-RH antagonist, there was a complete recovery of the weights of the testes, seminal vesicles and ventral prostates and LH and testosterone returned to control levels. Histological studies revealed a complete recovery of spermatogenesis, with 99.2% of seminiferous tubules containing mature elongated spermatids. Immediately after the discontinuation of treatment with SB-75, a significant down-regulation of the pituitary LH-RH receptors was found, but 90 days later, this phenomenon was completely reversed. Female rats were injected every 3 weeks for 6 weeks with SB-75 microcapsules, at a dose calculated to release 27 micrograms/day of the antagonist. The treatment with SB-75 disrupted the normal estrous cycle. Body weights were not affected, but ovarian and uterine weights were significantly decreased (p less than 0.01 and p less than 0.05, respectively) in the animals treated with the antagonist. Treated rats had significantly lower LH (p less than 0.05) and

  2. Exhaustion from prolonged gambling

    Directory of Open Access Journals (Sweden)

    Fatimah Lateef

    2013-01-01

    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  3. [Pathophysiology of prolonged hypokinesia].

    Science.gov (United States)

    Kovalenko, E A

    1976-01-01

    Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

  4. Characteristics of PR interval as predictor for atrial fibrillation: association with biomarkers and outcomes.

    Science.gov (United States)

    Schumacher, Katja; Dagres, Nikolaos; Hindricks, Gerhard; Husser, Daniela; Bollmann, Andreas; Kornej, Jelena

    2017-10-01

    The PR interval may be considered as a simple and easily obtainable predictor for adverse events, including atrial fibrillation (AF), pacemaker implantation, and mortality. Interestingly, both high and low extremes of the PR duration are associated with AF risk. However, the results regarding PR prolongation as a risk factor for AF are inconsistent. Some studies have analyzed the impact of P duration (as a part of the PR interval) and demonstrated that the P-duration contributes to the length of PR interval and adverse outcomes. The PR prolongation could be considered as a marker for cardiovascular degenerative aging caused by myocardial fibrosis and vascular inflammation. Furthermore, due to PR prolongation chronically raised intra-atrial pressure and consequential neuro-hormonal activation predispose systemic vascular endothelial dysfunction and explain the associations with adverse vascular events. In this review, we discuss the association between biomarkers with PR interval in AF.

  5. Management of prolonged pregnancy

    International Nuclear Information System (INIS)

    Iqbal, S.

    2004-01-01

    Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

  6. PR Crisis Melalui Media Sosial

    Directory of Open Access Journals (Sweden)

    Gladys Carlina

    2017-07-01

    Full Text Available The background of this research is communication, new media, PR and PR Crisis. Fourth of this background has a close relationship, starting from communication, human in everyday life would require communication to receive and convey information, human can not be released from human life. The advancement of the times and the development of technology, causing people to communicate easily and the development of this era caused a new challenge for the PR and PR Crisis of a company, they should be able to maintain a positive image of the company in the minds of people. In this study using descriptive qualitative methodology, it contains many writings and drawings compared to the numbers. The purpose of this research is to know the strategy used by Pizza Hut in dealing with the issue of expired food. Penelitin results, social media is very positive impact on Pizza Hut in the recovery of food issues expired. The strategy used by the Pizza Hut Crisis PR is to utilize social media. Visible from the issue of expired food that disappeared in public and Pizza Hut restaurant until now crowded visited. Latar belakang dari penelitian ini yaitu komunikasi, media baru, PR dan PR Krisis. Keempat dari latar belakang ini mempunyai hubungan yang erat, dimulai dari komunikasi, manusia di dalam kehidupan sehari-hari tentunya memerlukan komunikasi untuk menerima dan menyampaikan informasi, manusia tidak bisa dilepaskan dari kehidupan manusia. Majunya perkembangan zaman dan perkembangan teknologi, menyebabkan manusia melakukan komunikasi dengan mudah dan perkembangan zaman ini menyebabkan adanya tantangan baru bagi para PR dan PR Krisis sebuah perusahaan, mereka harus bisa mempertahankan citra positif perusahaan di benak masyarakat. Dalam penelitian ini menggunakan metodologi kualitatif deksriptif, memuat banyak tulisan dan gambar dibandingkan angka-angka. Tujuan dari penelitian ini untuk mengetahui strategi yang digunakan oleh Pizza Hut dalam menangani isu makanan

  7. Understanding the Press Kit and Its Use by the Media: When PR Material Becomes News

    Science.gov (United States)

    Weisgerber, Corinne

    2006-01-01

    This activity helps students understand the relationship between public relations (PR) writing and news writing by demonstrating how PR material gets used in the production of news stories. Considering that "more than 70 percent of daily newspaper copy emanates from PR-generated releases," it is important for students to learn how PR professionals…

  8. Prolongation of islet allograft survival

    International Nuclear Information System (INIS)

    Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

    1979-01-01

    Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

  9. Genetic influence on prolonged gestation

    DEFF Research Database (Denmark)

    Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

    2004-01-01

    OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

  10. ESO PR Highlights in 2000

    Science.gov (United States)

    2001-01-01

    At the beginning of the new millennium, ESO and its staff are facing the future with confidence. The four 8.2-m Unit Telescopes of the Very Large Telescope (VLT) are in great shape and the VLT Interferometer (VLTI) will soon have "first fringes". The intercontinental ALMA project is progressing well and concepts for extremely large optical/infrared telescopes are being studied. They can also look back at a fruitful and rewarding past year. Perhaps the most important, single development has been the rapid transition of the Very Large Telescope (VLT). From being a "high-tech project under construction" it has now become a highly proficient, world-class astronomical observatory. This trend is clearly reflected in ESO's Press Releases , as more and more front-line scientific results emerge from rich data obtained at this very efficient facility. There were also exciting news from several of the instruments at La Silla. At the same time, the ESO community may soon grow, as steps towards membership are being taken by various European countries. Throughout 2000, a total of 54 PR communications were made, with a large number of Press Photos and Video Clips, cf. the 2000 PR Index. Some of the ESO PR highlights may be accessed directly via the clickable image on the present page. ESO PR Photo 01/01 is also available in a larger (non-clickable) version [ JPEG: 566 x 566 pix - 112k]. It may be reproduced, if credit is given to the European Southern Observatory.

  11. [Conversion to tapentadol PR improves analgesia and quality of life in patients with severe and chronic pain despite using tramadol > 300 mg/d].

    Science.gov (United States)

    Richter, Uwe; Waldmann-Rex, Susanne; Lehmann, Ute

    2015-06-01

    This subgroup analysis of a non-interventional study involving general practitioners and internists investigated the administration of tapentadol PR (prolonged release) in patients with widely-utilized tramadol pretreatment in routine clinical practice in Germany. Data of all patients in the study cohort who had tramadol as the only opioid in their previous therapy were included in the analysis (n = 685); among them especially the 99 patients with tramadol dosages exceeding 300 mg/d were focused. Data collection during the 3-month observation period included previous and concomitant analgesic treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. Back pain was the most common cause of pain (n = 86/99), other pain diagnoses were (partly additionally) recorded in 68 cases. A mixed type of pain dominated. The previous tramadol therapy was usually combined with non-opioids (n = 74), co-analgesics (n = 44) and analgesic rescue medication (n = 35). Tapentadol PR therapy reduced the mean initial pain intensity of 7.3 ± 1.5 to 3.1 ± 1.8 points (NRS-11, 11-point pain scale, n = 96) at the end of observation, using an average dosage of 218.7 mg/d. Tapentadol PR was finally applied as the sole analgesic in 32/95 patients. 69/96 patients achieved a clinically meaningful pain relief of at least 50 %, while 63 patients gained a pain reduction of ≥ 4 NRS-points. 89/95 patients reached or exceeded their additional individual treatment goal. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. Data analysis shows a clinically relevant benefit in patients unsuccessfully pretreated with tramadol by consecutive conversion to the potent analgesic tapentadol PR.

  12. Prolonged unexplained fatigue in paediatrics

    NARCIS (Netherlands)

    Bakker, R.J.

    2010-01-01

    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

  13. Physiology Of Prolonged Bed Rest

    Science.gov (United States)

    Greenleaf, John E.

    1991-01-01

    Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

  14. Dissection of a Quantitative Trait Locus for PR Interval Duration Identifies Tnni3k as a Novel Modulator of Cardiac Conduction

    NARCIS (Netherlands)

    Lodder, Elisabeth M.; Scicluna, Brendon P.; Milano, Annalisa; Sun, Albert Y.; Tang, Hao; Remme, Carol Ann; Moerland, Perry D.; Tanck, Michael W. T.; Pitt, Geoffrey S.; Marchuk, Douglas A.; Bezzina, Connie R.

    2012-01-01

    Atrio-ventricular conduction disease is a common feature in Mendelian rhythm disorders associated with sudden cardiac death and is characterized by prolongation of the PR interval on the surface electrocardiogram (ECG). Prolongation of the PR interval is also a strong predictor of atrial

  15. RD50 Prolongation Request 2018

    CERN Document Server

    Casse, Gianluigi

    2018-01-01

    With this document, we request the prolongation of the CERN RD50 research program for 5 years. A very brief historical review of the RD50 research program since the RD50 project approval by the Research Board in the year 2002 is presented and the biggest RD50 achievements are highlighted. The present composition of the collaboration, its organizational structure, and the research methodology are described. The role of RD50 in the present various upgrade and research programs of the LHC Experiments community is given and the overall work plan explained. Finally, a detailed 5-years work program with precise milestones and deliverables for the various research activities is presented. We conclude with our prolongation request towards the LHCC.

  16. Conditions promoting and restraining agronomic effectiveness of water-insoluble phosphate sources, in particular phosphate rock (PR): III. 32P-aided soil-PR interaction studies aimed at enhancing P bioavailability from PR

    International Nuclear Information System (INIS)

    Borlan, Z.; Soare, M.; Gavriluta, I.; Alexandrescu, A.; Stefanescu, D.

    2002-01-01

    Mobilization of PR and bioavailability of PR-P for plants takes place through complex chemical and biochemical processes that occurs during prolonged soil interaction with PR. There is a high probability that certain processes of a biochemical nature are also involved through proteinaceous ion carriers whose concentration and physiological activity in plant roots may be influenced by means of specially formulated foliar fertilizer compositions. 32 P-aided studies have contributed to identify possibilities of enhancing PR-P bioavailability through foliar fertilizer application. (author)

  17. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. PR-PR: cross-platform laboratory automation system.

    Science.gov (United States)

    Linshiz, Gregory; Stawski, Nina; Goyal, Garima; Bi, Changhao; Poust, Sean; Sharma, Monica; Mutalik, Vivek; Keasling, Jay D; Hillson, Nathan J

    2014-08-15

    To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.

  19. Prolonged pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1......) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... the risk of recurrence of prolonged pregnancy as a function of change in male partner and social conditions (IV). The National Birth Cohort provided data for the study on prenatal risk indicators of prolonged pregnancy in a follow-up design (V). The self-reported gestational ages from this database...

  20. Safety information on QT-interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

    2014-01-01

    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve...

  1. Risk factors for QTc interval prolongation

    NARCIS (Netherlands)

    Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

    2018-01-01

    Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

  2. Prenatal risk indicators of a prolonged pregnancy

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn

    2006-01-01

    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from...

  3. Neutron Scattering from fcc Pr and Pr3Tl

    DEFF Research Database (Denmark)

    Birgeneau, R. J.; Als-Nielsen, Jens Aage; Bucher, E.

    1972-01-01

    Elastic-neutron-scattering measurements on the singlet-ground-state ferromagnets fcc Pr and Pr3 Tl are reported. Both exhibit magnetic phase transitions, possibly to a simple ferromagnetic state at 20 and 11.6 °K, respectively. The transitions appear to be of second order although that in fcc Pr...

  4. [Brain function recovery after prolonged posttraumatic coma].

    Science.gov (United States)

    Klimash, A V; Zhanaidarov, Z S

    2016-01-01

    To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

  5. 9. Nuclear power plant service life prolongation

    International Nuclear Information System (INIS)

    Evropin, S.V.

    1998-01-01

    The problem of prolongation of nuclear power plant service life duration is discussed. A schematic diagram of the program developed in the course of activities dealing with NPP service time prolongation is shown and analyzed in details. It is shown that the basic moment when determining the strategy for NPP service time prolongation is the positive confirmation of the agreement between the NPP safety provisions and modern safety requirements. The other very important aspect of the problem is engineering substantiation of the measures assuring the reactor operation prolongation. The conclusion is made that available methods of recovering reactor materials properties, main components repair and replacement, the modern techniques for nondestructive testing of metals and NPP pipelines, as well as the developed approaches to reactor facility safety improvements make the prolongation of the Russian NPP service lifetimes possible from engineering viewpoint and economically desirable

  6. Sialic Acid on the Glycosylphosphatidylinositol Anchor Regulates PrP-mediated Cell Signaling and Prion Formation.

    Science.gov (United States)

    Bate, Clive; Nolan, William; Williams, Alun

    2016-01-01

    The prion diseases occur following the conversion of the cellular prion protein (PrP(C)) into disease-related isoforms (PrP(Sc)). In this study, the role of the glycosylphosphatidylinositol (GPI) anchor attached to PrP(C) in prion formation was examined using a cell painting technique. PrP(Sc) formation in two prion-infected neuronal cell lines (ScGT1 and ScN2a cells) and in scrapie-infected primary cortical neurons was increased following the introduction of PrP(C). In contrast, PrP(C) containing a GPI anchor from which the sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc). Furthermore, the presence of desialylated PrP(C) inhibited the production of PrP(Sc) within prion-infected cortical neurons and ScGT1 and ScN2a cells. The membrane rafts surrounding desialylated PrP(C) contained greater amounts of sialylated gangliosides and cholesterol than membrane rafts surrounding PrP(C). Desialylated PrP(C) was less sensitive to cholesterol depletion than PrP(C) and was not released from cells by treatment with glimepiride. The presence of desialylated PrP(C) in neurons caused the dissociation of cytoplasmic phospholipase A2 from PrP-containing membrane rafts and reduced the activation of cytoplasmic phospholipase A2. These findings show that the sialic acid moiety of the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation. These results suggest that pharmacological modification of GPI glycosylation might constitute a novel therapeutic approach to prion diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. PR, Lobbyism and Democracy

    DEFF Research Database (Denmark)

    Ørsten, Mark; Willig, Ida; Pedersen, Leif Hemming

    2017-01-01

    The growth of PR in Scandinavia is linked both to the mediatization of politics and to the decline of corporatism. Studies in Sweden and Norway suggest that one consequence of these changes is the increasing number of politicians who find new careers as lobbyists in the private sector. In this st......The growth of PR in Scandinavia is linked both to the mediatization of politics and to the decline of corporatism. Studies in Sweden and Norway suggest that one consequence of these changes is the increasing number of politicians who find new careers as lobbyists in the private sector....... Still, 89 percent of all the registered job positions fall outside of lobbyism. 11 percent of the job positions fall within the wider field associated with the emerging field of policy professionals (including lobbyism), while lobbyism on its own accounts for 2 percent of the job positions....

  8. [Properties of live antibiotics-resistant anthrax vaccine STI-PR after long-term storage].

    Science.gov (United States)

    Aksenova, L Iu; Buravtseva, N P; Kogotkova, O I; Eremenko, E I; Tsygankova, O I

    2007-01-01

    Study showed that cultural, morphologic, genetic, immunologic characteristics, and resistance to antibiotics of STI-PR anthrax vaccine did not change after storage during 20 years in lyophilized condition. It has been shown that medium for lyophilization plays important role in preservation of vitality of anthrax spores. Optimal preservative properties have been observed for thioureal and sucrose-gelatinous media for lyophilization. Obtained results give reasons for prolongation of shelf live of STI-PR vaccine from 2 - 3 to 5 - 8 years.

  9. Electrical PR Interval Variation Predicts New Occurrence of Atrial Fibrillation in Patients With Frequent Premature Atrial Contractions.

    Science.gov (United States)

    Chun, Kwang Jin; Hwang, Jin Kyung; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    Atrial fibrillation (AF) is associated with the autonomic nervous system (ANS), and fluctuation of autonomic tone is more prominent in patients with AF. As autonomic tone affects the heart rate (HR), and there is an inverse relationship between HR and PR interval, PR interval variation could be greater in patients with AF than in those without AF. The purpose of this study was to investigate the correlation between PR interval variation and new-onset AF in patients with frequent PACs.We retrospectively enrolled 207 patients with frequent PACs who underwent electrocardiographs at least 4 times during the follow-up period. The PR variation was calculated by subtracting the minimum PR interval from the maximum PR interval. The outcomes were new occurrence of AF and all-cause mortality during the follow-up period.During a median follow-up of 8.3 years, 24 patients (11.6%) developed new-onset AF. Univariate analysis showed that prolonged PR interval (PR interval > 200 ms, P = 0.021), long PR variation (PR variation > 36.5 ms, P = 0.018), and PR variation (P = 0.004) as a continuous variable were associated with an increased risk of AF. Cox regression analysis showed that prolonged PR interval (hazard ratio = 3.321, 95% CI 1.064-10.362, P = 0.039) and PR variation (hazard ratio = 1.013, 95% CI 1.002-1.024, P = 0.022) were independent predictors for new-onset AF. However, PR variation and prolonged PR interval were not associated with all-cause mortality (P = 0.465 and 0.774, respectively).PR interval variation and prolonged PR interval are independent risk factors for new-onset AF in patients with frequent PACs. However we were unable to determine a cut-off value of PR interval variation for new-onset AF.

  10. À jamais, à présent

    OpenAIRE

    Pierrepont, Alexandre

    2007-01-01

    L’objet de cet article serait de rendre compte de quelques-unes des lignes de vie de cette expérience musicale nommée « jazz », telles qu’elles se sont prolongées au cours des trois dernières décennies, particulièrement aux États-Unis. Interroger la manière avec laquelle la transmission (de parole, de présences, de jeux et d’intelligences) se fait alors et aujourd’hui, dans quelles conditions, sous quelles pressions peut-être, à partir de quels constats ou de quelles intuitions, comment en dé...

  11. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. ... therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ..... is simple to adopt and cost-effective. In this ...

  12. Prolonged CT urography in duplex kidney.

    Science.gov (United States)

    Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

    2016-05-13

    Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

  13. Licence prolongations of US nuclear power plants

    International Nuclear Information System (INIS)

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  14. Effectiveness of a prolonged incarceration and rehabilitation measure for high-frequency offenders

    NARCIS (Netherlands)

    Tollenaar, N.; van der Laan, A. M.; van der Heijden, P. G M

    2014-01-01

    Objectives: To estimate the incapacitation effect and the impact on post-release recidivism of a measure combining prolonged incarceration and rehabilitation, the ISD measure for high frequency offenders (HFOs) was compared to the standard practice of short-term imprisonment. Methods: We applied a

  15. Préface

    Science.gov (United States)

    Chardonnet, Christian; Millot, Guy

    2006-10-01

    COLOQ, réunion nationale biennale initiée en 1988 par la communauté française des lasers, de l'optique non linéaire et de l'optique quantique atteint sa neuvième édition. Depuis sa création, les objectifs poursuivis sont les suivants : - réunir la communauté française des lasers, de l'optique non linéaire et de l'optique quantique, en dépassant les clivages fondamental/appliqué, recherche publique/industrielle, - faire le point sur les avancées récentes, - permettre aux jeunes chercheurs de se rencontrer, de s'exprimer et de s'aguerrir au plan national. Le but est que tout thésard du domaine de l'optique puisse participer à COLOQ une fois durant sa thèse, présenter son travail et de se confronter à la communauté de l'optique. COLOQ9 s'est tenu, pour sa 9e édition, sur le campus universitaire de Dijon, du 7 au 9 septembre 2005. Il a été une grande réussite : nombre de participants (255) et de présentations scientifiques record (148 affiches), forte représentation des industriels (15) et participation d'environ 200 lycéens aux conférences grand public. Le nombre plus élevé que prévu d'affiches a rendu un peu serrée leur présentation : une attention particulière sera portée à cet aspect lors des prochaines éditions. Ces journées ont été consacrées à des conférences invitées données par des scientifiques de haut niveau et à des présentations sous forme d'affiches. Une plage de temps importante a été réservée pour des discussions autour des affiches. À proximité immédiate de la salle de conférence, l'exposition de matériels spécialisés pour les lasers, l'optique et l'optoélectronique a été une occasion pour les jeunes participants de découvrir et contacter les industriels et les autres grands acteurs de l'optique. L'année 2005 ayant été l'année mondiale de la physique, COLOQ9 a retenu comme thème central ”1905-2005 : à propos d'Einstein". Plusieurs grandes conférences ont été dédiées à ce th

  16. Présentation

    Directory of Open Access Journals (Sweden)

    Stéphane Haber

    2010-08-01

    Full Text Available Les articles réunis dans ce dossier de la revue Astérion portent sur la première génération de la Théorie critique (dont Max Horkheimer, Walter Benjamin, Theodor W. Adorno, Herbert Marcuse et Erich Fromm constituent sans doute les figures principales. Ils se concentrent plus précisément sur les contributions philosophiques qui marquèrent la période ouverte par l’accession de Horkheimer à la direction de l’Institut de recherches sociales (1931 et close par la publication en 1944 de Dialektik...

  17. Prolonged delirium misdiagnosed as a mood disorder.

    Science.gov (United States)

    Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

    2017-01-01

    Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

  18. QT Prolongation due to Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Zain Kulairi

    2017-01-01

    Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

  19. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    DEFF Research Database (Denmark)

    Estmann, Anne; Qvist, Niels; Husby, Steffen

    2002-01-01

    to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  20. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    ) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... an ultrasound scan in the first or second trimester, or menstrual history was best at predicting the day of delivery; 5) to study the risk of recurrence of prolonged pregnancy as a function of change in male partner, social status and municipality; and 6) to detect prenatal risk indicators of prolonged...... of perinatal and obstetrical complications was high in post-term delivery compared to term delivery (OR between 1.2 and 3.1). The risk of perinatal death (OR=1.36 (1.08-1.72)) was also higher in the post-term group (I). The self-reported gestational ages in the National Birth Cohort correlated well with data...

  1. QT interval prolongation associated with sibutramine treatment

    Science.gov (United States)

    Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

    2006-01-01

    Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

  2. On PR group classes and PR algebra membership

    International Nuclear Information System (INIS)

    Lebedenko, V.M.

    1978-01-01

    The necessary and sufficient conditions are found for the membership of Lee algebras to PR algebra class, to algebras with commutation relations of [Hsub(i), Hsub(j)]=rsub(ij)Hsub(i) (i< j) type. Due to this, a criterion is obtained for the membership of the Lee froups to PR group classes, connected and simply connected Lee groups, which Lee algebras are PR algebras

  3. Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

    Directory of Open Access Journals (Sweden)

    Hui Qun Fu

    Full Text Available Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001 and up to 6 hours (p<0.001 following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG, IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.

  4. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.

    Science.gov (United States)

    Chun, Kwang Jin; Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs.

  5. Quality of drug label information on QT interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

    2014-01-01

    BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  6. Nickel may be released from laptop computers

    DEFF Research Database (Denmark)

    Jensen, Peter; Jellesen, Morten Stendahl; Møller, Per

    2012-01-01

    Consumer nickel sensitization and dermatitis is caused by prolonged or repeated skin exposure to items that release nickel, for example jewellery, belts, buttons, watches, and mobile phones (1–3). We recently described a patient in whom primary nickel contact sensitization and dermatitis develope...

  7. Role of PR-Interval In Predicting the Occurrence of Atrial Fibrillation

    DEFF Research Database (Denmark)

    Bidstrup, Signe Brøker; Salling Olesen, Morten; Hastrup Svendsen, Jesper

    2013-01-01

    The identification of individuals at high risk of developing atrial fibrillation (AF) is important to prevent potentially lethal and invalidating complications of this arrhythmia. Recently, several studies have investigated the association between PR-interval and the risk of AF and have tested...... the value of PR-interval in personalized risk scores for AF. However, the results of these studies are generally conflicting. When looking for an association between a prolonged PR-interval (first-degree atrioventricular [AV] block vs. normal PR-interval) and an increased risk of AF, not all studies were...... able to find a consistent and statistically significant association. In two recent studies, however, the investigators were able to show an increased risk of AF for individuals with PR-intervals in the short range compared with individuals in the middle range. The existence of a true U...

  8. STRATEGIJSKA ULOGA PR U SPORTU

    Directory of Open Access Journals (Sweden)

    Duško Tomić

    2005-05-01

    Full Text Available PR in the modern world are developed with rapid speed and become important aspect of strategic management. Modern menagers are very interesting in PR and they observe that there is not successful strategy without experiance theory and practice in PR. The goals must be defined, basic phylosophy to, and managers must take responsability and describe everithing what they have to do. It must be financial fond and evaluation must be done

  9. Préface

    Directory of Open Access Journals (Sweden)

    Sylvie Duvillard

    2010-09-01

    Full Text Available Le moment est opportun, la question foncière est de retour, légitimée par presque une décennie (2001-2008 d’augmentation continue des prix de l’immobilier. De « sommets » , en articles de presse, la montagne et les Alpes en particulier font l’objet, dans ce domaine, d’une attention toute particulière. Le contexte est ici délicat. Les sociétés alpines sont partagées entre désir de préservation d’une forte identité montagnarde et crainte d’une « déprise » économique (agricole, touristique et/...

  10. Présentation

    Directory of Open Access Journals (Sweden)

    Frédéric Hitzel

    2009-05-01

    Full Text Available « À ma connaissance, il n'est pas de compagnon plus fidèle à ses engagements, plus prompt à honorer les faveurs reçues, plus empressé à offrir ses services, et ce à moindre frais, que le livre. Je ne connais aucun arbre qui ait un fruit plus succulent, plus précoce, plus aisé à cueillir, plus disponible à tout moment, comme le livre. Je ne sais pas de produit qui, malgré son jeune âge et la proximité de sa naissance, la facilité avec laquelle on peut se le procurer, la modicité de son prix, a...

  11. Présentation

    Directory of Open Access Journals (Sweden)

    Agnès Bouvier

    2012-02-01

    Full Text Available Le 7 juin 1844, Flaubert écrit à Louis de Cormenin : « J’ai lu Candide vingt fois, je l’ai traduit en anglais et je l’ai encore relu de temps à autre. » Quel que soit le degré de sérieux de cette affirmation, elle témoigne d’un intérêt précoce de Flaubert pour l’acte de traduire. De même, l’écrivain attachait de l’importance aux traductions qu’il lisait : « Je relis maintenant Don Quichotte dans la nouvelle traduction de Damas Hinard » écrit-il à Louise Colet en novembre 1847. Il lui arrivait...

  12. Présentation

    Directory of Open Access Journals (Sweden)

    Aurore Monod Becquelin

    2010-09-01

    Full Text Available Les recherches présentées dans ce volume sont issues des travaux de chercheurs qui se réunissent régulièrement depuis 2005 sur le thème de l’« Agentivité ». Ce groupe rassemble des ethnologues et des linguistes du Laboratoire d’ethnologie et de sociologie comparative (umr 7186, cnrs/université Paris Ouest Nanterre La Défense, du Laboratoire d’anthropologie sociale (umr 7130, Collège de France/ehess Paris/cnrs, de l’École des hautes études en sciences sociales, de l’Institut des hautes étude...

  13. State diagram of Pr-Bi system

    International Nuclear Information System (INIS)

    Abulkhaev, V.L.; Ganiev, I.N.

    1994-01-01

    By means of thermal differential analysis, X-ray and microstructural analysis the state diagram of Pr-Bi system was studied. Following intermetallic compounds were defined in the system: Pr 2 Bi, Pr 5 Bi 3 , Pr 4 Bi 3 , Pr Bi, PrBi 2 , Pr 2 Bi, Pr 5 Bi 3 , Pr 4 Bi 3 and PrBi 2 . The data analysis on Ln-Bi diagram allowed to determine the regularity of change of properties of intermetallic compounds in the line of rare earth elements of cerium subgroup.

  14. The PR Officer's Survival Kit.

    Science.gov (United States)

    Woodrum, Robert L.

    1996-01-01

    A former corporate public relations (PR) professional shares strategies for communicating and cooperating with the chief executive officer, and particularly for coping with differences in perceptions of the public relations officer's role. Basic attributes of a successful PR professional are outlined: good communication skills, an analytical…

  15. PR's involvement in International Cooperation

    NARCIS (Netherlands)

    Anonymous,

    1995-01-01

    In The Netherlands, the Research Station for Cattle, Sheep and Horse Husbandry (in Dutch abbreviated as PR) bridges the gap between more basic and disciplinary research done at universities and research institutes on the one hand and the extension service and the farmers on the other hand. The PR

  16. Prólogo

    Directory of Open Access Journals (Sweden)

    Alta Hooker

    2013-02-01

    Full Text Available Este volumen No. 11 presenta una compilación estructurada en 6 secciones temáticas las cuales comprenden 9 artículos. La primera sección en Educación, presenta los artículos: Métodos de enseñanza de Física en la modalidad a distancia en el instituto sabatino “Esperanza”,en el municipio de Siuna; y, Comportamiento disciplinario en la escuela “Niño Jesús”, Siuna, Región Autónoma Atlántico Norte, 2011. La segunda sección, titulada Educación Superior en la Costa Caribe Nicaragüense presenta los artículos: Formación de los docentes de la URACCAN en el Área de Recursos Naturales; asimismo, Pertinencia de los programas para el aprendizaje del inglés en Administración de Empresas, Recinto Nueva Guinea y Prácticas de campo en la formación de estudiantes de Ingeniería en Zootecnia, URACCAN Nueva Guinea. La tercera sección denominada Revitalización Lingüística y Cultural comprende dos artículos: Etno-matemática en indígenas ulwas, comunidad de Karawala, Región Autónoma Atlántico Sur, Nicaragua y Ma-Kuagro: Elementos de la cultura de San Basilio Palenque, Colombia, y su incidencia en las prácticas pedagógicas. La cuarta sección Cultura Indígena y Afrodescendiente comprende un artículo: Economía indígena en la comunidad de Wasakín, municipio de Rosita, RAAN. Clausura la quinta sección denominada Ciencias Sociales, el artículo La república Bolivariana de Venezuela y Nicaragua, en el marco del acuerdo energético.

  17. Deletion of Pr130 Interrupts Cardiac Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Jie Yang

    2016-11-01

    Full Text Available Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A, a regulatory subunit of protein phosphatase 2A (PP2A, is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR, plays an important role in the excitation-contraction (EC coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated proteins (Cas system. Pr130-knockout zebrafish exhibited cardiac looping defects and decreased cardiac function (decreased fractional area and fractional shortening. Hematoxylin and eosin (H&E staining demonstrated reduced cardiomyocytes. Subsequent transmission electron microscopy revealed that the bright and dark bands were narrowed and blurred, the Z- and M-lines were fogged, and the gaps between longitudinal myocardial fibers were increased. Additionally, increased apoptosis was observed in cardiomyocyte in pr130-knockout zebrafish compared to wild-type (WT. Taken together, our results suggest that pr130 is required for normal myocardium formation and efficient cardiac contractile function.

  18. Préface

    Science.gov (United States)

    Aspect, Alain

    2004-11-01

    COLOQ est une conférence regroupant, tous les deux ans, la communauté scientifique et industrielle nationale travaillant dans les domaines des lasers, de l'optique non-linéaire et de l'optique quantique. Elle s'est tenue pour sa huitième édition à Toulouse, du 3 au 5 septembre 2004, sur le campus de I'INSA. Comme il est de tradition tous les quatre ans, COLOQ était couplé avec Horizons de l'optique, avec en particulier une journée commune dont le programme avait été préparé en concertation par les deux comités scientifiques. Depuis sa création, COLOQ a pour but de favoriser les rencontres entre les chercheurs des différents laboratoires nationaux publics ou privés travaillant sur les lasers et l'optique quantique au sens large. C'est un moyen privilégié de resserrer les liens de cette communauté et d'y intégrer les jeunes chercheurs. Ces derniers y trouvent l'occasion de se connaître, de se faire connaître, de découvrir la communauté à laquelle ils appartiennent et d'élargir leurs connaissances des thèmes qui la structurent. La participation de 230 chercheurs et d'une vingtaine d'exposants de matériels spécialisés dans les lasers et l'optoélectronique témoigne de la vitalité de COLOQ et de son audience dans les laboratoires et chez les industriels de l'optique. Le programme de COLOQ 8 comportait d'une vingtaine de conférences générales données par des chercheurs de renom international, et des séances de communications par affiches, occasions privilégiées de rencontres et d'échanges. Les exposés ont porté sur des sujets particulièrement actifs au niveau national et international, avec un accent sur des thèmes importants pour la région toulousaine : contrôle cohérent, optique et nanosciences, optique et astronomie, sans oublier la traditionnelle rubrique phénomènes fondamentaux, éclectique pour ne pas dire hétéroclite, mais si représentative d'une des ambitions de COLOQ qui est d'offrir à ses participants une

  19. SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

    Directory of Open Access Journals (Sweden)

    Suzanne Schneider

    2013-01-01

    Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

  20. Prolonged displacement may compromise resilience in Eritrean ...

    African Journals Online (AJOL)

    Objective: to assess the impact of prolonged displacement on the resilience of Eritrean mothers. Methods: an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Results: Displaced ...

  1. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. © The Author(s) 2013.

  2. Hippocampal Abnormalities after Prolonged Febrile Convulsions

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

  3. Acute Right Ventricular Dysfunction Complicating Prolonged ...

    African Journals Online (AJOL)

    We report a case of transient right ventricular dysfunction associated with prolonged cardiac tamponade, an unusual complication of uncertain etiology. We believe that in this case dynamic coronary flow restriction resulted in ischemic injury and stunning of the right ventricle. Other possible causes are briefly reviewed. Right ...

  4. Préface

    Science.gov (United States)

    Ouerdane, Youcef; Laporte, Pierre

    2005-06-01

    L'objectif de la série de colloques UVX est de réunir, au rythme d'une fois tous les deux ans, les scientifiques et industriels travaillant dans le domaine du développement des sources de photon de grande énergie (UV, VUV, et X) et de leurs applications. En particulier cette manifestation est l'occasion de faire se rencontrer une communauté très pluridisciplinaire (physique, chimie, biologie, sciences de l'univers) liée à des domaines en forte évolution technologique (lasers et rayonnement synchrotron notamment). Le colloque UVX 2004 s'est tenu au Palais des Congrès de Saint-Étienne (42000) du 7 au 11 juin 2004. La période écoulée depuis l'édition précédente (Oléron 2002) a été particulièrement active dans tous les domaines concernés : grands projets de sources, méthodes de diagnostic au sens large. Une nouvelle fois on constate que le bref et l'ultra-bref ont une place privilégiée, qu'il s'agisse du travail sur les accélérateurs ou sur les lasers qui, bien sûr, dans la course aux temps courts remportent la palme avec la présence de spécialistes du domaine attoseconde. La communauté représentée a la chance d'être en prise directe avec de très grands projets en phase active de réalisation comme le Laser Megajoule (LMJ), la source SOLEIL, et un projet d'ampleur plus modeste mais remarquable dans son domaine : la source LASERIX d'Orsay/Palaiseau. On pourra citer aussi le projet Arc en Ciel qui, lui, est encore au stade de sa définition. - SOLEIL, source de nouvelle génération de rayonnement synchrotron (plateau de Saclay) est dans une phase active de réalisation : achèvement de l'infrastructure en 2005 et injection du 1o faisceau dans l'anneau de stockage prévu également en 2005. Cette source devrait être la meilleure au monde dans le domaine VUV/X mous, tout en restant très polyvalente (brillance, accordabilité, structure temporelle, polarisation) et complémentaire de l'ESRF. Au final on disposera de 21 lignes de lumi

  5. PKPD modelling of PR and QRS intervals in conscious dogs using standard safety pharmacology data.

    Science.gov (United States)

    Bergenholm, Linnéa; Collins, Teresa; Evans, Neil D; Chappell, Michael J; Parkinson, Joanna

    2016-01-01

    Pharmacokinetic-pharmacodynamic (PKPD) modelling can improve safety assessment, but few PKPD models describing drug-induced QRS and PR prolongations have been published. This investigation aims to develop and evaluate PKPD models for describing QRS and PR effects in routine safety studies. Exposure and telemetry data from safety pharmacology studies in conscious beagle dogs were acquired. Mixed effects baseline and PK-QRS/PR models were developed for the anti-arrhythmic compounds AZD1305, flecainide, quinidine and verapamil and the anti-muscarinic compounds AZD8683 and AZD9164. RR interval correction and circadian rhythms were investigated for predicting baseline variability. Individual PK predictions were used to drive the pharmacological effects evaluating linear and non-linear direct and effect compartment models. Conduction slowing induced by the tested anti-arrhythmics was direct and proportional at low exposures, whilst time delays and non-linear effects were evident for the tested anti-muscarinics. AZD1305, flecainide and quinidine induced QRS widening with 4.2, 10 and 5.6% μM(-1) unbound drug. AZD1305 and flecainide also prolonged PR with 13.5 and 11.5% μM(-1). PR prolongations induced by the anti-muscarinics and verapamil were best described by Emax models with maximal effects ranging from 55 to 95%. RR interval correction and circadian rhythm improved PR but not QRS modelling. However, circadian rhythm had minor impact on estimated drug effects. Baseline and drug-induced effects on QRS and PR intervals can be effectively described with PKPD models using routine data, providing quantitative safety information to support drug discovery and development. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Prolonged QRS Widening After Aripiprazole Overdose.

    Science.gov (United States)

    Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

    2018-05-05

    Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

  7. ESO PR Highlights in 2006

    Science.gov (United States)

    2007-01-01

    Last year proved to be another exceptional year for the European organisation for ground-based astronomy. ESO should begin the New Year with two new member states: Spain (PR 05/06) and the Czech Republic (PR 52/06). ESO PR Highlights 2006 2006 was a year of renovation and revolution in the world of planets. A new Earth-like exoplanet has been discovered (PR 03/06) using a network of telescopes from all over the world (including the Danish 1.54-m one at ESO La Silla). It is not the only child of this fruitful year: thanks to the combined use of ESO's Very Large Telescope (VLT) and La Silla instruments, a surprising system of twin giant exoplanets was found (PR 29/06), and a trio of Neptune-like planets hosted by a nearby star were identified (PR 18/06). These results open new perspectives on the search for habitable zones and on the understanding of the mechanism of planet formation. The VISIR instrument on the VLT has been providing unique information to answer this last question, by supplying a high resolution view of a planet-forming disc (PR 36/06). There are not only new members in the planets' register: during the General Assembly of the International Astronomical Union held in Prague (Czech Republic), it was decided that Pluto is not a planet anymore but a 'dwarf planet'. Whatever its status, Pluto still has a satellite, Charon, whose radius and density have been measured more accurately by observing a rare occultation from different sites, including Cerro Paranal (PR 02/06). The scientific community dedicated 2006 to the great physicist James Clerk Maxwell (it was the 175th anniversary of the birth): without his electromagnetic theory of light, none of the astonishing discoveries of modern physics could have been achieved. Nowadays we can look at distant galaxies in great detail: the GIRAFFE spectrograph on the VLT revealed that galaxies 6 billion years ago had the same amount of dark matter relative to stars than nowadays (PR 10/06), while SINFONI gave an

  8. Préface

    Science.gov (United States)

    Hamieh, Tayssir

    2005-05-01

    Né simultanément à Mulhouse et à Beyrouth en 1996 dans le cadre d'une collaboraiion franco-libanaise sur une initiative personnelle de Monsieur Tayssir HAMIEH. le Colloque Franco-Libanais sur la Science des Matériaux (CSM), qui s'inscrit dans le cadre des relations étroites entre la France et le Liban, est très vite devenu une occasion très importante de rencontre entre scientifiques de haut niveau, non seulement, du contour méditerranéen mais également des pays européens, américains et arabes. La quatrieme édition CSM4 est une véritable réussite grâce à la participation des chercheurs confirmés dans tous les domaines des sciences de matériaux et venant de plusieurs pays tels que la France, I'Algérie, Le Liban, la Syrie, le Maroc, la Tunisie, l'Italie, l'Espagne, le Portugal, le Royaume Uni, les États-Unis, la Russie, l'Allemagne, le Japon et I'Inde ; pour présenter plus de 350 communications orales et par affiche et couvrant presque toutes les disciplines des systèmes des matériaux. Le choix des diffèrents thèmes du colloque sur la science des matériaux a été dicté par l'importance capitale de cette discipline dans notre civilisation moderne. En fait, les matériaux utilisés pour la fabrication artisanale ou industrielle d'objets, de produits et de systèmes ainsi que pour la réalisation de constructions et d'équipements ont de tout temps défini le niveau de notre civilisation technique. La réalisation des objectifs communs de notre monde en plein développement, pour ne pas dire en pleine mutation, est en grande partie tributaire de la mise au point de nouveaux matériaux et de procédés de transformation et d'assemblages nouveaux, présentant des performances et des qualités améliorées. Le colloque a illustré et traduit, de manière remarquables, l'excellente collaboration entre chercheurs libanais et français. Le partenariat est exemplaire par la qualité des laboratoires impliqués et par le niveau scientifique des r

  9. Características da sucção nutritiva na liberação da via oral em recém-nascidos pré-termo de diferentes idades gestacionais Characteristics of nutritive sucking in the release for oral feeding in preterm newborns of different gestational ages

    Directory of Open Access Journals (Sweden)

    Raquel Coube de Carvalho Yamamoto

    2009-01-01

    Full Text Available OBJETIVO: Analisar as características da sucção nutritiva na liberação da via oral em recém-nascidos pré-termo (RNPT de diferentes idades gestacionais. MÉTODOS: A amostra constou de 32 RNPT, avaliados no momento da liberação para alimentação por via oral, dividida em dois grupos: Grupo 1 (G1 com idade gestacional inferior a 34 semanas; e Grupo 2 (G2 com idade gestacional igual ou superior a 34 semanas. O desempenho da sucção nutritiva foi avaliado observando-se presença ou ausência de blocos de sucção, número e tempo das sucções nos três primeiros blocos apresentados, e presença ou ausência de coordenação entre sucção/deglutição/respiração (S/D/R. Nenhum RNPT recebeu estimulação fonoaudiológica prévia. RESULTADOS: O G2 apresentou, na maioria dos RNPT, presença de coordenação entre S/D/R, além de melhor desempenho em relação ao número e ao tempo de sucção nos blocos de sucção quando comparado ao G1. Na correlação do número versus tempo de sucção por bloco, o G1 apresentou resultados aproximados aos do G2. Considerando-se a classificação quanto ao desenvolvimento intra-útero adequado para a idade gestacional, os RNPT do G1 apresentaram desempenho semelhante aos do G2, no primeiro e segundo blocos, observando-se queda, no G1, apenas no terceiro bloco. CONCLUSÃO: O melhor desempenho no padrão de sucção nutritiva foi apresentado pelo G2, sugerindo que a idade gestacional corrigida dos RNPT interfere diretamente nos resultados obtidos na avaliação da sucção nutritiva. Assim sendo, esta também é uma variável a ser considerada para liberação da alimentação por via oral.PURPOSE: To analyze the characteristics of nutritive sucking in preterm infants of different gestational ages after the medical prescription for oral feeding. METHODS: The sample comprised 32 preterm infants who were evaluated at the time they were released for oral feeding. The subjects were divided into two groups

  10. Licence prolongations of US nuclear power plants; Les prolongations de licence des centrales nucleaires americaines

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  11. Political PR is dying. Long live business PR! / Ilyn Oleg

    Index Scriptorium Estoniae

    Oleg, Ilyn

    2005-01-01

    Vene suurima suhtekorraldusagentuuri Imageland Public Relations rahvusvaheliste suhete juhi hinnangul on Venemaal peamisteks probleemideks PR professionaalide vähesus, nende kehv haritus oma erialal, samuti vähene teadlikkus suhtekorralduse tähtsusest äris

  12. Erfolgsfaktoren unternehmerischer Krisen-PR

    OpenAIRE

    Scharr, Florian

    2006-01-01

    Ob "Peanuts", "Elchtest" oder "Hoechst-Störfall" - bei diesen bekannten Öffentlichkeitskrisen der letzten Jahre rief die mangelhafte Krisen-PR der betroffenen Unternehmen bei Medien und Bevölkerung mehr Empörung hervor als die originären Auslöser und potenzierte so den entstandenen Vertrauensverlust. Auch die sich gerade erst entwickelnde PR-Forschung bietet noch keine konkrete Hilfestellung zur Gestaltung von Krisen-PR. Mit dem bedeutenden Diskurs- und dadurch Realitätsgestaltungsmittel Pres...

  13. Brain mapping after prolonged cycling and during recovery in the heat.

    Science.gov (United States)

    De Pauw, Kevin; Roelands, Bart; Marusic, Uros; Tellez, Helio Fernandez; Knaepen, Kristel; Meeusen, Romain

    2013-11-01

    The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

  14. Mechanoluminescence and photoluminescence of Pr3+ activated KMgF3 phosphor

    International Nuclear Information System (INIS)

    Dhoble, S.J.; Kher, R.S.; Furetta, C.

    2003-01-01

    A Czochralski method for the preparation of crystalline KMgF 3 : Pr phosphors are reported. Photoluminescence (PL) and mechanoluminescence (ML) characteristics are studied. Photoluminescence of Pr 3+ activated KMgF 3 shows the strong emission of Pr 3+ ions were observed at 498 and 650 nm by excitation of 213 mn. ML of KMgF 3 : Pr 3+ shows two peaks, which have been observed in ML intensity versus time curve. The ML peak shows the recombination of electrons with free radical (anion radical produced by γ-irradiation) released from two type traps during the mechanical pressure applied on KMgF 3 : Pr 3+ phosphor. It has a supra linear ML response with γ-ray exposure and a negligible fading. These properties of phosphor should be suitable in dosimetry of ionization relation using ML technique. Therefore the KMgF 3 : Pr 3+ phosphor proposed for ML dosimetry of ionization radiations. (Author)

  15. Methane release

    International Nuclear Information System (INIS)

    Seifert, M.

    1999-01-01

    The Swiss Gas Industry has carried out a systematic, technical estimate of methane release from the complete supply chain from production to consumption for the years 1992/1993. The result of this survey provided a conservative value, amounting to 0.9% of the Swiss domestic output. A continuation of the study taking into account new findings with regard to emission factors and the effect of the climate is now available, which provides a value of 0.8% for the target year of 1996. These results show that the renovation of the network has brought about lower losses in the local gas supplies, particularly for the grey cast iron pipelines. (author)

  16. Présentation

    Directory of Open Access Journals (Sweden)

    Gregor Perko

    2011-12-01

    Full Text Available Au cours des dernières décennies où l’on assiste à une refondation de la morphologie, la discipline s’intéresse de plus en plus à des phénomènes « périphériques », « marginaux », « irréguliers » ou « extragrammaticaux », à des phénomènes n’appartenant pas aux « régions nodales » de la morphologie. Le présent numéro de Linguistica, premier numéro thématique de notre revue, réunit des études qui s’intéres- sent aux frontières internes et externes de la morphologie. La diversité et la richesse des thèmes abordés et des approches proposées témoignent d’un intérêt croissant que les linguistes, non pas uniquement les morphologues, portent à cette thématique. Les articles proposés s’articulent autour de cinq axes majeurs. Un premier axe rassemble les articles qui étudient les frontières entre différentes composantes de la morphologie. L’étude de Michel Roché examine les contraintes lexicales et morphophonologiques sur le paradigme des dérivés en –aie. Les résultats de son analyse remettent en question la notion de « règle de construction des lexèmes ». Irena Stramljič Breznik et Ines Voršič se penchent sur les néologismes de sport en slovène et essaient d’évaluer la productivité ou la créativité des procédés morphologiques en jeu. Dans une étude d’inspiration cognitiviste, Alexandra Bagasheva aborde l’hétérogénéité des verbes composés en anglais. En s’appuyant sur les données fournies par les para- digmes verbaux du maltais, Maris Camilleri examine la complexité du phénomène de classes flexionnelles basées sur les radicaux. Trois travaux concernent des procédés typiquement « extragrammaticaux » servant à former le plus souvent des occasionnalismes: Arnaud Léturgie tente de dégager des propriétés prototypiques de l’amalgamation lexicale en français, notamment celles de la création des mots-valises; Silvia Cacchiani analyse, à l

  17. Phase diagram of Pr-P system

    International Nuclear Information System (INIS)

    Mironov, K.E.

    1981-01-01

    An area of the Pr-P system, adjoining to the Pr ordinate, is plotted up by the DTA method. Presence of P solid solution in Pr is established. Data on thermal stability of PrP, PrP 2 , PrP 5 and PrP 7 are generalized. The diagram of phase transformations in Pr-P system is plotted up proceeding from the whole complex of the data, presented. A supposition is made on a possible formation of solid solutions between the highest polyphosphide and phosphorus [ru

  18. On the PR-algebras

    International Nuclear Information System (INIS)

    Lebedenko, V.M.

    1978-01-01

    The PR-algebras, i.e. the Lie algebras with commutation relations of [Hsub(i),Hsub(j)]=rsub(ij)Hsub(i)(i< j) type are investigated. On the basis of former results a criterion for the membership of 2-solvable Lie algebras to the PR-algebra class is given. The conditions imposed by the criterion are formulated in the linear algebra language

  19. Prácticas curriculares

    OpenAIRE

    García-Gordillo, Mar; Checa Godoy, Antonio; Gómez Mompart, Josep Lluis (Coordinador); Herrero Subías, Mónica (Coordinador)

    2015-01-01

    Esta ponencia pretende analizar, sucintamente, la situacion presente de las prácticas externas en las facultades de Comunicacion españolas. En una coyuntura sumamente peculiar, no solo para las prácticas de los titulos de Comunicacion, sino para todas las practicas universitarias, por los numerosos y a veces contradictorios cambios acaecidos en la legislacion reciente y los vaivenes normativos de las universidades; por la profunda crisis que viene atravesando el sector de la...

  20. The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV.

    Directory of Open Access Journals (Sweden)

    Hanumant S Tanwar

    2017-02-01

    Full Text Available The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0 that is further enhanced by the oligomerization of Pr55Gag. The change in enthalpy (ΔH widens sequentially from: (1 Pr55Gag-Psi RNA binding during HIV genome selection; to (2 Pr55Gag-Guanosine Uridine (GU-containing RNA binding in cytoplasm/plasma membrane; and then to (3 Pr55Gag-Adenosine(A-containing RNA binding in immature HIV. These data imply the stepwise increments of heat being released during HIV biogenesis may help to facilitate the process of viral assembly. By mimicking the interactions between A-containing RNA and oligomeric Pr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficient than full-length Pr55Gag in this thermodynamic process. These data suggest a potential unknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction during HIV assembly. Our data provide direct evidence on how nucleic acid sequences and the oligomeric state of Pr55Gag regulate HIV assembly.

  1. Severe bradycardia and prolonged hypotension in ciguatera.

    Science.gov (United States)

    Chan, Thomas Yan Keung

    2013-06-01

    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  2. Internet innovation in PR management

    Directory of Open Access Journals (Sweden)

    Ćalasan Veljko B.

    2014-01-01

    Full Text Available PR Management in the last decade has evolved to unimaginable limits . Its rapid 'evolution ' is directly linked to the development and innovation, above all, of internet communications - Cyber 'world'. Although the genesis of PR management was announced in a way, the changes of the modern PR management have led to a change in the general attitude towards this particular activity. It has become an indispensable factor for the success of every business or social enterprise. In the general run for internet contents with better quality, as an indispensable tool of PR management , for better use of cyberspace , a new generation of PR manager is created, who has almost no resemblance to the earlier managers before two decades. For these reasons, we believe that Internet innovation through the implementation of PR management, changed the world economy and society. Adjusting speed to this, virtual , yet very real world , is proportional to the speed of development of an economic system as a whole, or any company at the micro level , and society in general .Internet is not an important innovation itself to be sufficient to meet the form and define the essence of economic relations. Only its proper exploitation with the constant use of tested and more intense innovation is the only way to the overall success . The absence of the above, in our opinion, is a sure path to failure.

  3. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

    OpenAIRE

    Allam, Ayat; Fetih, Gihan

    2016-01-01

    Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to...

  4. Variation in Definition of Prolonged Mechanical Ventilation.

    Science.gov (United States)

    Rose, Louise; McGinlay, Michael; Amin, Reshma; Burns, Karen Ea; Connolly, Bronwen; Hart, Nicholas; Jouvet, Philippe; Katz, Sherri; Leasa, David; Mawdsley, Cathy; McAuley, Danny F; Schultz, Marcus J; Blackwood, Bronagh

    2017-10-01

    Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of

  5. Prolonged Exposure: a Rapid Treatment for Phobias

    Science.gov (United States)

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  6. Design of a new type of coating for the controlled release of heparin

    NARCIS (Netherlands)

    Hinrichs, W.L.J.; Hinrichs, W.L.J.; ten Hoopen, Hermina W.M.; Wissink, M.J.B.; Engbers, G.H.M.; Feijen, Jan

    1997-01-01

    Thrombus formation at the surface of blood contacting devices can be prevented by local release of heparin. Preferably, the release rate should be constant for prolonged periods of time. The minimum heparin release rate to achieve thromboresistance will be different for various applications and

  7. Functions of two distinct prolactin-releasing peptides evolved from a common ancestral gene

    Directory of Open Access Journals (Sweden)

    Tetsuya eTachibana

    2014-11-01

    Full Text Available Prolactin-releasing peptide (PrRP is one of the RF-amide peptides and was originally identified in the bovine hypothalamus as a stimulator of prolactin (PRL release. Independently, another RF-amide peptide was found in Japanese crucian carp and named Carassius RFa (C-RFa, which shows high homology to PrRP and stimulates PRL secretion in teleost fish. Therefore, C-RFa has been recognized as fish PrRP. However, recent work has revealed that PrRP and C-RFa in non-mammalian vertebrates are encoded by separate genes originated through duplication of an ancestral gene. Indeed, both PrRP and C-RFa are suggested to exist in teleost, amphibian, reptile, and avian species. Therefore, we propose that non-mammalian PrRP (C-RFa be renamed PrRP2. Despite a common evolutionary origin, PrRP2 appears to be a physiological regulator of PRL, whereas this is not a consistent role for PrRP itself. Further work revealed that the biological functions of PrRP and PrRP2 are not limited solely to PRL release, because they are also neuromodulators of several hypothalamus-pituitary axes and are involved in some brain circuits related to the regulation of food intake, stress, and cardiovascular functions. However, these actions appear to be different among vertebrates. For example, central injection of PrRP inhibits feeding behavior in rodents and teleosts while it stimulates it in chicks. Therefore, both PrRP and PrRP2 have acquired diverse actions through evolution. In this review, we integrate the burgeoning information of structures, expression profiles, and multiple biological actions of PrRP in higher vertebrates, as well as those of PrRP2 in non-mammals.

  8. A rare sign of ischemia during exercise ECG: PR interval lengthening in the recovery period.

    Science.gov (United States)

    Durakoğlugil, Murtaza Emre; Kocaman, Sinan Altan; Ciçek, Yüksel; Cetin, Mustafa

    2012-12-01

    Exercise electrocardiography (ECG) is one of the most commonly utilized tests in cardiology. Despite the drawbacks, exercise ECG is widely preferred due to low cost, standardization, and strong prognostic information. A prolonged PR interval during recovery has recently been proposed as an indicator of mortality. Herein, we report an interesting case of a patient who presented with the complaint of exertional dyspnea and exhibited PR lengthening during the recovery period on the exercise ECG. The patient had a PR interval of 240 ms before exercise, which decreased to 160 ms at peak stress. However, during recovery, the PR interval prolonged gradually, reaching 320 ms at the second minute and persisting at that length until the end of the recovery period. The patient achieved 87% of the age predicted maximum heart rate, and experienced non-disabling shortness of breath and a pressure sensation in the chest, with no apparent ST segment depression. Recovery parameters, including heart rate recovery and systolic blood pressure recovery, were also within normal limits. The patient underwent coronary angiography with the suspicion of CAD which revealed severe multi-vessel disease. This rare case emphasizes the importance of PR lengthening in the recovery period as a sign of severe ischemia, in addition to other signs, such as prominent ST-segment changes, chronotropic incompetence, impaired hemodynamic response, and poor exercise capacity during stress ECG evaluation.

  9. Prolonged labour as indication for emergency caesarean section

    DEFF Research Database (Denmark)

    Maaløe, Nanna; Sorensen, B L; Onesmo, R

    2012-01-01

    To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

  10. In vitro and in vivo studies identify important features of dengue virus pr-E protein interactions.

    Directory of Open Access Journals (Sweden)

    Aihua Zheng

    2010-10-01

    Full Text Available Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors.

  11. Laryngotracheal Injury following Prolonged Endotracheal Intubation

    Directory of Open Access Journals (Sweden)

    J. Mehdizadeh

    2006-07-01

    Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

  12. Ten years experience of PR

    International Nuclear Information System (INIS)

    Dobak, Dobroslav

    2002-01-01

    This paper is an effort to summarize the way Slovak Bohunice NPP has gone through since the historical change in the Middle and Eastern European countries. Milestones on the way were: 1989 - change of political system; increasing interest of the public appearance; creation of work capacities - personnel and technical; education/exchange with Western countries; 1994 - establishment of Foreign Affairs and PR Department reporting directly to the NPP manager; application of various approaches, some observed from other countries; creation of utility policy - place of PR in the company; establishment of QA system - description of PR activities, goals, interlinks etc.; annual planning process including activities, finance, education (training). Lessons learned are: the NPP managers were not prepared; the public was not (and still is not) prepared to obtain specific information; education is crucial in opinion winning; simple overtake of methods from others is not always applicable; strategy and feedback are necessary. Special case was the early closure Bohunice V1 NPP

  13. Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

    Science.gov (United States)

    van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

    2012-12-10

    Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

  14. Topical Drug Formulations for Prolonged Corneal Anesthesia

    Science.gov (United States)

    Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

    2013-01-01

    Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

  15. Risk factors for prolonged length of stay after colorectal surgery

    Directory of Open Access Journals (Sweden)

    Luiz Felipe de Campos Lobato

    2013-01-01

    Full Text Available Objective: Colorectal surgeons often struggle to explain to administrators/payers reasons for prolonged length of stay (LOS. This study aim was to identify factors associated with increased LOS after colorectal surgery. Design: The study population included patients from the 2007 American-College-of-Sur- geons-National-Surgical-Quality-Improvement-Program (ACS-NSQIP database undergoing ileocolic resection, segmental colectomy, or anterior resection. The study population was divided into normal (below 75th percentile and prolonged LOS (above the 75th percentile. A multivariate analysis was performed using prolonged LOS as dependent variable and ACS- NSQIP variables as predictive variables. P-value < 0.01 was considered significant. Results: 12,269 patients with a median LOS of 6 (inter-quartile range 4-9 days were includ- ed. There were 2,617 (21.3% patients with prolonged LOS (median 15 days, inter-quartile range 13-22. 1,308 (50% were female, and the median age was 69 (inter-quartile range 57-79 years. Risk factors for prolonged LOS were male gender, congestive heart failure, weight loss, Crohn's disease, preoperative albumin < 3.5 g/dL and hematocrit < 47%, base- line sepsis, ASA class ≥ 3, open surgery, surgical time ≥ 190 min, postoperative pneumonia, failure to wean from mechanical ventilation, deep venous thrombosis, urinary-tract in- fection, systemic sepsis, surgical site infection and reoperation within 30-days from the primary surgery. Conclusion: Multiple factors are associated with increased LOS after colorectal surgery. Our results are useful for surgeons to explain prolonged LOS to administrators/payers who are critical of this metric. Resumo: Objetivo: Os cirurgiões proctologistas muitas vezes enfrentam dificuldades para explicar aos administradores/contribuintes as razões para o prolongamento do tempo de interna- ção hospitalar (TIH. O objetivo deste estudo foi identificar os fatores associados ao aumen- to do TIH ap

  16. PERAN DAN STRATEGI KONSULTAN PR DALAM KAMPANYE POLITIK INDONESIA (STUDI KASUS DI TANGERANG SELATAN)

    OpenAIRE

    Novi Erlita

    2015-01-01

    His study used a case study that describes circumstances or events that occur in the South Tangerang election as a public relations consultant efforts in Indonesia's political campaign. Various strategies and activities of PR Consultants in South Tangerang first round of elections by political parties to attract the votes and sympathy of the masses. Many things done, starting with the media utilizing PR (Press Release print and website mediated political party), take direct action against the...

  17. Nickel on the market: a baseline survey of articles in 'prolonged contact' with skin.

    Science.gov (United States)

    Ringborg, Evelina; Lidén, Carola; Julander, Anneli

    2016-08-01

    In April 2014, the European Chemicals Agency defined the concept of 'prolonged contact with skin' as used in the EU nickel restriction. To establish a baseline of nickel-releasing items on the Swedish market conforming with the EU nickel restriction according to the definition of 'prolonged contact' with the skin. We performed a limited market survey in Stockholm, Sweden. Items with metallic parts that come into contact with the skin, except those explicitly mentioned in the legal text, were chosen. The dimethylglyoxime (DMG) test was used to evaluate nickel release. One hundred and forty-one items belonging to one of three categories - accessories, utensils for needlework, painting and writing (called utensils), and electronic devices - were tested in the study. Forty-four percent of all items were DMG test-positive (releasing nickel), and 9% gave a doubtful DMG test result. The large proportion of nickel-releasing items in the present study shows clearly that broader parts of industry need to take action to prevent nickel allergy. The high proportion of DMG test-positive items indicates that there is still much work to be done to reduce the nickel exposure of the population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. QT prolongation and sudden cardiac death risk in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Patel, Salma I; Ackerman, Michael J; Shamoun, Fadi E; Geske, Jeffrey B; Ommen, Steve R; Love, William T; Cha, Stephen S; Bos, Johan M; Lester, Steven J

    2018-03-07

    Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p  450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

  19. Comparison between TRMM PR and

    Indian Academy of Sciences (India)

    A comparison between TRMM PR rainfall estimates and rain gauge data from ANEEL and com- bined gauge/satellite ..... correctly the of the south Atlantic convergence ..... vapor, snow cover, and sea ice derived from SSM/I mea- surements ...

  20. Credibility Discourse of PR Agencies

    DEFF Research Database (Denmark)

    Isaksson, Maria; Jørgensen, Poul Erik Flyvholm

    2008-01-01

    to giving assurance of their expertise, trustworthiness and empathy, thus confirming our overall expectation that corporate credibility discourse is relatively uniform from a European perspective. However, contrary to our assumptions, the results of our study show that PR credibility discourse demonstrates...

  1. Profesi PR Identik dengan Perempuan ?

    Directory of Open Access Journals (Sweden)

    Neni Yulianita

    2004-09-01

    Full Text Available Profesi Public Relations (PR atau di Indonesia lebih dikenal dengan Humas, seringkali diidentikkan dengan profesi yang pantas dijabat oleh kaum perempuan. Adanya sebagian kalangan masyarakat yang menjudge bahwa profesi ini lebih tepat dijabat oleh kaum perempuan, dengan alasan profesi ini menuntut keterampilan, daya tarik, dan keluwesan. Dengan adanya anggapan tersebut,  tentu saja telah memberikan implikasi pada kaum laki-laki  sehingga menimbulkan keraguan pada mereka untuk menekuni bidang kajian PR/Humas di berbagai Perguruan Tinggi yang memiliki bidang ini. Ironisnya, user masih menganggap kaum laki-lakilah yang lebih tepat menjabat profesi PR, dengan anggapan antara lain bahwa laki-laki lebih energik, aktif, rasional, agresif, memiliki stamina atau fisik yang lebih kuat, dan memiliki kemampuan dalam penguasaan hardware atau teknologi komunikasi mutakhir yang lebih baik dibanding wanita yang dianggap lebih emosional, pasif, dan submisif. Anggapan ini tentu saja sangat merugikan perempuan,  walaupun hasil penelitian Robins dinyatakan bahwa,  “Tidak ada beda  laki-laki dan perempuan yang konsisten dalam kemampuan memecahkan masalah, keterampilan analitis, dorongan kompetitif, motivasi, sosiobilitas, atau kemampuan belajar”.  Untuk itu, dalam tulisan ini, penulis menyajikan jawaban apakah benar Profesi PR lebih tepat dijabat oleh Perempuan?

  2. PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers

    Science.gov (United States)

    Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

    2016-01-01

    Introduction HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Discussion Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Conclusions Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes. PMID:27760688

  3. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Michael Gysel

    2014-01-01

    Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

  4. Prolonged toxicity from Kambo cleansing ritual.

    Science.gov (United States)

    Li, Kai; Horng, Howard; Lynch, Kara; Smollin, Craig G

    2018-04-02

    Kambo cleanse is a purification, cleansing ritual traditionally performed by South American shaman to confer luck and health to hunters. We report a patient who presented to the emergency department with prolonged symptoms of vomiting, flushing, facial swelling, altered mental status, and agitation requiring chemical restraints, 22 h after a Kambo cleanse. The patient was found with four small, circular, superficial burns to the ankle at the site where the resin was introduced. The cleanse consists of rubbing resin obtained from the secretions of the giant leaf frog (Phyllomedusa bicolor) into superficial wounds to produce intense gastrointestinal symptoms followed by a sensation of increased stamina and strength. The cleanse is now being increasingly performed in Europe and USA.

  5. Bywalled plasma formation in vacuum prolonged channels

    International Nuclear Information System (INIS)

    Korenev, S.A.; Rubin, N.B.

    1982-01-01

    To produce homogeneous along the channel length plasma the application of incomplete rate-in surface dielectric discharge for generating the bywalled plasma in prolonged cylindrical channels at a pressure of the residual gas of P approximately 10 -5 Torr is proposed. Experimental set-up consisted of a pulse voltage generator and a plasma channel. The plasma channel was a coaxial system of three tubes inserted into each other. The first outer tube is made of a stainless steel, the second - of a dielectric material, the third - of smallsized stainless steel greed. It is demonstrated that the plasma being formed in the process is sufficiently homogeneous by concentration of the components, by the channel length and azimuth. The length of the experimental channel under investigation was 1.6 m, its diameter amounted 0.05 m. The maximum concentration of electron component was 10 17 m -3

  6. Neurohumoral responses during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Blomstrand, Eva

    2003-01-01

    This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine......, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 +/- 0.1 degrees C (mean +/- SE) in the control trial, whereas it increased to 39.7 +/- 0.2 degrees C...... in the hyperthermic trial, with a concomitant increase in perceived exertion (P exercise trials. Both the arterial and jugular venous dopamine levels...

  7. Prolonged grieving after abortion: a descriptive study.

    Science.gov (United States)

    Brown, D; Elkins, T E; Larson, D B

    1993-01-01

    Although flawed by methodological problems, the research literature tends to provide support for the assumption that induced abortion in the 1st trimester is not accompanied by enduring negative psychological sequelae. In cases where such sequelae are reported, the morbidity is attributed to a pre-existing psychiatric condition or circumstances precipitating the choice of abortion. However, detailed descriptive letters from 45 women prepared in response to a request by a pastor of an upper-middle-class Protestant congregation in Florida indicate that prolonged grieving after abortion may be more widespread phenomenon than previously believed. Letter writers ranged in age from 25-60 years; 75% were unmarried at the time of the procedure and 29% aborted before the legalization of abortion in the US. The most frequently cited long-term sequela, especially among those who felt coerced to abort, was a continued feeling of guilt. Fantasies about the aborted fetus was the next most frequently mentioned experience. Half of the letter writers referred to their abortions, as "murder" and 44% voiced regret about their decision to abort. Other long-term effects included depression (44%), feelings of loss (31%), shame (27%), and phobic responses to infants (13%). For 42% of these women, the adverse psychological effects of abortion endured over 10 years. Since letter-writers came from a self-selected population group with a known bias against abortion and only negative experiences were solicited, these experiences must be regarded as subjectives and anecdotal. However, they draw attention to the need for methodologically sound studies of a possible prolonged grief syndrome among a small percentage of women who have abortions, especially when coercion is involved.

  8. Prolonged pain and disability are common after rib fractures.

    Science.gov (United States)

    Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

    2013-05-01

    The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.

    Science.gov (United States)

    Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg; Kretzschmar, Hans; Westaway, David

    2017-01-01

    Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.

  10. Prion infections and anti-PrP antibodies trigger converging neurotoxic pathways.

    Directory of Open Access Journals (Sweden)

    Uli S Herrmann

    2015-02-01

    Full Text Available Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS induced the production of reactive oxygen species (ROS. Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifespan of prion-infected mice and protected prion-infected COCS from neurodegeneration. Instead, neither glutamate receptor antagonists nor inhibitors of endoplasmic reticulum calcium channels abolished neurotoxicity in either model. Secondly, antibodies against the flexible tail (FT of PrPC reduced neurotoxicity in both GDL-exposed and prion-infected COCS, suggesting that the FT executes toxicity in both paradigms. Thirdly, the PERK pathway of the unfolded protein response was activated in both models. Finally, 80% of transcriptionally downregulated genes overlapped between prion-infected and GDL-treated COCS. We conclude that GDL mimic the interaction of PrPSc with PrPC, thereby triggering the downstream events characteristic of prion infection.

  11. Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Werner, Mads U; Lacouture, Peter G

    2002-01-01

    BACKGROUND: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available. METHODS: In a double-blinded study, 12 healthy male volunteers were...... randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection...... curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection. RESULTS: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence...

  12. Pathogenesis of PR3-ANCA associated vasculitis

    NARCIS (Netherlands)

    Kallenberg, C. G. M.

    2008-01-01

    Wegener's Granulomatosis (WG) is closely associated with antineutrophil cytoplasmic autoantibodies (ANCA), particularly those directed to proteinase 3 (PR3). ANCA directed to myeloperoxidase (MPO) are associated with microscopic polyangiitis (MPA) and the Churg Strauss syndrome. PR3-ANCA associated

  13. Cancer de la próstata

    OpenAIRE

    Mendoza, Lupi Alejandro; Fundación Valle de Lili; Gutierrez, María Carolina; López Cardona, Arturo

    1997-01-01

    ¿Qué es la próstata?/¿Qué es la hiperplasia benigna de próstata?/El cáncer de próstata/¿Se hereda el cáncer de próstata?/¿Cómo se presenta y hacia donde se disemina el cáncer de próstata?/¿Cómo de descubre el cáncer de próstata?/¿Qué estudia la ultrasonografía transrectal o ecografía a través de recto?/¿Cómo se analizan los niveles de PSA?/¿Cómo se clasifica el cáncer de próstata?¿Cómo se determina la terapia más adecuada para un cáncer de próstata?/¿Cuáles son las opciones de tratamiento par...

  14. Competency profile of PR professional in sport

    OpenAIRE

    Gazdíková, Lenka

    2013-01-01

    Title: Competency profile of PR professional in sport Objective: The objective is to identify competencies required to a position of PR professional in sport. The aim of a survey is to verify the level of competencies which follows compiling competency profile and comparison with existing profile of PR specialist. Methods: The objective is achieved using survey, interview and analysis of competency models database. Results: The result of this paper is competency profile of PR professional in ...

  15. Does UTI cause prolonged jaundice in otherwise well infants?

    Science.gov (United States)

    Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

    2015-07-01

    The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

  16. Bruken av nasjonale prøver

    DEFF Research Database (Denmark)

    Skov, Poul

    2010-01-01

    Artiklen beskriver resultater fra en omfattende evaluering af brugen af de nationale prøver i norsk grundskole. De nationale prøver er blevet modtaget positivt af mange kommuner og skoleledere og i mindre grad af lærerne. Resultaterne viser også, at prøverne er styrende for undervisningen, at bru...

  17. Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

    Science.gov (United States)

    Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

    2010-01-01

    Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

  18. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  19. Fermionic covariant prolongation structure theory for supernonlinear evolution equation

    International Nuclear Information System (INIS)

    Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

    2010-01-01

    We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

  20. Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice.

    Science.gov (United States)

    Moda, Fabio; Vimercati, Chiara; Campagnani, Ilaria; Ruggerone, Margherita; Giaccone, Giorgio; Morbin, Michela; Zentilin, Lorena; Giacca, Mauro; Zucca, Ileana; Legname, Giuseppe; Tagliavini, Fabrizio

    2012-01-01

    Prion diseases are caused by a conformational modification of the cellular prion protein (PrP (C)) into disease-specific forms, termed PrP (Sc), that have the ability to interact with PrP (C) promoting its conversion to PrP (Sc). In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrP (C) region involved in the interaction with PrP (Sc) thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrP (Sc) in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding.

  1. Carbohydrate Dependence During Prolonged, Intense Endurance Exercise.

    Science.gov (United States)

    Hawley, John A; Leckey, Jill J

    2015-11-01

    A major goal of training to improve the performance of prolonged, continuous, endurance events lasting up to 3 h is to promote a range of physiological and metabolic adaptations that permit an athlete to work at both higher absolute and relative power outputs/speeds and delay the onset of fatigue (i.e., a decline in exercise intensity). To meet these goals, competitive endurance athletes undertake a prodigious volume of training, with a large proportion performed at intensities that are close to or faster than race pace and highly dependent on carbohydrate (CHO)-based fuels to sustain rates of muscle energy production [i.e., match rates of adenosine triphosphate (ATP) hydrolysis with rates of resynthesis]. Consequently, to sustain muscle energy reserves and meet the daily demands of training sessions, competitive athletes freely select CHO-rich diets. Despite renewed interest in high-fat, low-CHO diets for endurance sport, fat-rich diets do not improve training capacity or performance, but directly impair rates of muscle glycogenolysis and energy flux, limiting high-intensity ATP production. When highly trained athletes compete in endurance events lasting up to 3 h, CHO-, not fat-based fuels are the predominant fuel for the working muscles and CHO, not fat, availability becomes rate limiting for performance.

  2. Prolonged disengagement from distractors near the hands

    Directory of Open Access Journals (Sweden)

    Daniel B Vatterott

    2013-08-01

    Full Text Available Because items near our hands are often more important than items far from our hands, the brain processes visual items near our hands differently than items far from our hands. Multiple experiments have attributed this processing difference to spatial attention, but the exact mechanism behind how spatial attention near our hands changes is still under investigation. The current experiments sought to differentiate between two of the proposed mechanisms: a prioritization of the space near the hands and a prolonged disengagement of spatial attention near the hands. To differentiate between these two accounts, we used the additional singleton paradigm in which observers searched for a shape singleton among homogenously shaped distractors. On half the trials, one of the distractors was a different color. Both the prioritization and disengagement accounts predict differently colored distractors near the hands will slow target responses more than differently colored distractors far from the hands, but the prioritization account also predicts faster responses to targets near the hands than far from the hands. The disengagement account does not make this prediction, because attention does not need to be disengaged when the target appears near the hand. We found support for the disengagement account: Salient distractors near the hands slowed responses more than those far from the hands, yet observers did not respond faster to targets near the hands.

  3. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Allam A

    2016-08-01

    Full Text Available Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes, while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration following sublingual administration was found to be significantly higher (91.06%±13.28%, as compared with that after oral tablet administration (39.37%±11.4%. These results indicate that the fast dissolving niosomal film could be a promising delivery system to

  4. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate.

    Science.gov (United States)

    Allam, Ayat; Fetih, Gihan

    2016-01-01

    The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug's bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate.

  5. Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

    DEFF Research Database (Denmark)

    Mourtzakis, Marina; Saltin, B.; Graham, T.

    2006-01-01

    During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline...... amino acid taken up during exercise and recovery. Alanine and glutamine were also associated...... with pyruvate metabolism, and they comprised 68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism...

  6. Isothermal sections of the state diagram for the Pr-Ni-Ge system at 870 (0-0,5Pr) and 670 K (0,5-1Pr)

    International Nuclear Information System (INIS)

    Fedyna, M.F.; Pecharskij, V.K.; Bodak, O.I.

    1987-01-01

    Method of X-ray phase and microstructural analyses were used to study Pr-Ni-Ge ternary system at 870K (0-0.50 at.fractions of Pr) and 670K (0.50-1.00 at.fractions of Pr). 11 ternary compounds exist in the system: Pr 1-x (NiGe) 13 (x=0.24), PrNi 2 Ge 2 , Pr 2 Ni 3 Ge 5 , PrNiGe 3 , Pr 2 NiGe 6 , Pr 3 Ni 4 Ge 4 , PrNi (1-x) Ge 2 (x=0.33), PrNiGe, Pr(NiGe) 2-x (x=0.14), Pr 3 NiGe 2 , ∼Pr 5 NiGe 4 . Crystal structure was determined for seven ternary compounds

  7. Microencapsulation of aspartame by double emulsion followed by complex coacervation to provide protection and prolong sweetness.

    Science.gov (United States)

    Rocha-Selmi, Glaucia A; Bozza, Fernanda T; Thomazini, Marcelo; Bolini, Helena M A; Fávaro-Trindade, Carmen S

    2013-08-15

    The objective of this work was to microencapsulate aspartame by double emulsion followed by complex coacervation, aiming to protect it and control its release. Six treatments were prepared using sunflower oil to prepare the primary emulsion and gelatin and gum Arabic as the wall materials. The microcapsules were evaluated structurally with respect to their sorption isotherms and release into water (36°C and 80°C). The microcapsules were multinucleated, not very water-soluble or hygroscopic and showed reduced rates of equilibrium moisture content and release at both temperatures. FTIR confirmed complexation between the wall materials and the intact nature of aspartame. The results indicated it was possible to encapsulate aspartame with the techniques employed and that these protected the sweetener even at 80°C. The reduced solubility and low release rates indicated the enormous potential of the vehicle developed in controlling the release of the aspartame into the food, thus prolonging its sweetness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Photoemission of heavy fermion superconductor PrOs4Sb12 and other Pr compounds

    International Nuclear Information System (INIS)

    Imada, S.; Yamasaki, A.; Sekiyama, A.; Settai, R.; Onuki, Y.; Suga, S.; Sugawara, H.; Sato, H.; Ochiai, A.

    2004-01-01

    Full text: Strongly correlated electronic states due to Pr 4f electrons found in several Pr compounds have recently been attracting much attention. The Pr 4f electrons are much more localized than in Ce due to the lanthanoid contraction. Therefore, the number of the Pr systems that show strong electron correlation is much smaller than Ce systems. We will present a comparative study of Pr 4f electronic states in such systems as the heavy fermion superconductor PrOs 4 Sb 12 , the Kondo system PrSn 3 and the localized 4f systems Pr 4 X 3 (X = Sb and Bi). The Pr 4f electronic state was probed by means of the Pr 3d → 4f resonant photoemission (RPES). Because the kinetic energy (E K ) of the photoelectrons is as high as ∼ 900 eV, this method is much more bulk sensitive than the 4d → 4f RPES with E K ∼ 100 eV. The energy resolution could be set to about 100 meV by utilizing the soft X-rays from BL25SU in SPring-8 and the SCIENTA SES-200 analyzer. The Pr 4f excitation spectrum of PrSn 3 was found to show a very strong intensity at the Fermi level (E F ). This can be interpreted as the Kondo resonance which has been observed in the Kondo Ce and Yb compounds. In the Pr 4f spectrum of the heavy fermion superconductor PrOs 4 Sb 12 , the intensity at E F was smaller than in PrSn 3 . This clearly shows that the Kondo temperature (T K ) is much lower in PrOs 4 Sb 12 than in PrSn 3 . We have further found a strong excitation energy dependence in the RPES line shape. In the case of Pr 4 X 3 (X = Sb and Bi), the intensity at E B was much smaller than PrSn 3 and PrOs 4 Sb 12 , which is consistent with the localized character of Pr 4f electrons in Pr 4 X 3 . The Pr 4f spectra of these localized systems are qualitatively well reproduced by a cluster model calculation that takes into account the hybridization between the Pr 4f orbital and the conduction and valence bands made up by the X p and Pr 5d states

  9. Detection of fast light-activated H+ release and M intermediate formation from proteorhodopsin.

    Directory of Open Access Journals (Sweden)

    DeVita Anne

    2002-04-01

    Full Text Available Abstract Background Proteorhodopsin (pR is a light-activated proton pump homologous to bacteriorhodopsin and recently discovered in oceanic γ-proteobacteria. One perplexing difference between these two proteins is the absence in pR of homologues of bR residues Glu-194 and Glu-204. These two residues, along with Arg-82, have been implicated in light-activated fast H+ release to the extracellular medium in bR. It is therefore uncertain that pR carries out its physiological activity using a mechanism that is completely homologous to that of bR. Results A pR purification procedure is described that utilizes Phenylsepharose™ and hydroxylapatite columns and yields 85% (w/w purity. Through SDS-PAGE of the pure protein, the molecular weight of E.-coli-produced pR was determined to be 36,000, approximately 9,000 more than the 27,000 predicted by the DNA sequence. Post-translational modification of one or more of the cysteine residues accounts for 5 kDa of the weight difference as measured on a cys-less pR mutant. At pH 9.5 and in the presence of octylglucoside and diheptanoylphosphotidylcholine, flash photolysis results in fast H+ release and a 400-nm absorbing (M-like photoproduct. Both of these occur with a similar rise time (4–10 μs as reported for monomeric bR in detergent. Conclusions The presence of fast H+ release in pR indicates that either different groups are responsible for fast H+ release in pR and bR (i.e. that the H+ release group is not highly conserved; or, that the H+ release group is conserved and is therefore likely Arg-94 itself in pR (and Arg-82 in bR, correspondingly.

  10. Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation

    Science.gov (United States)

    Sobieski, Courtney; Shu, Hong-Jin

    2018-01-01

    Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. PMID:29617444

  11. Parameters affecting the tidal volume during expiratory abdominal compression in patients with prolonged tracheostomy mechanical ventilation.

    Science.gov (United States)

    Morino, Akira; Shida, Masahiro; Tanaka, Masashi; Sato, Kimihiro; Seko, Toshiaki; Ito, Shunsuke; Ogawa, Shunichi; Takahashi, Naoaki

    2015-07-01

    [Purpose] The aim of this study was to clarify physical parameters affecting the tidal volume during expiratory abdominal compression in patients with prolonged tracheostomy mechanical ventilation. [Methods] Eighteen patients with prolonged mechanical ventilation were included in this study. Expiratory abdominal compression was performed on patients lying in a supine position. The abdomen above the navel was vertically compressed in synchronization with expiration and released with inspiration. We measured the tidal volume during expiratory abdominal compression. [Results] The mean tidal volume during expiratory abdominal compression was higher than that at rest (430.6 ± 127.1 mL vs. 344.0 ± 94.3 mL). The tidal volume during expiratory abdominal compression was correlated with weight, days of ventilator support, dynamic compliance and abdominal expansion. Stepwise multiple regression analysis revealed that weight (β = 0.499), dynamic compliance (β = 0.387), and abdominal expansion (β = 0.365) were factors contributing to the tidal volume during expiratory abdominal compression. [Conclusion] Expiratory abdominal compression increased the tidal volume in patients with prolonged tracheostomy mechanical ventilation. The tidal volume during expiratory abdominal compression was influenced by each of the pulmonary conditions and the physical characteristics.

  12. Identification and expression analysis of a pathogenresponsive PR ...

    African Journals Online (AJOL)

    related (PR) proteins. PR-1 genes represent the first identified PR gene family. Most members of PR-1 gene family are not inducible by pathogen attacks. In this study, we identified a pathogen-responsive PR-1 gene designated as VqPR-1 ...

  13. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

    Directory of Open Access Journals (Sweden)

    Wang Wen-Quan

    2012-11-01

    Full Text Available Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR of hepatocellular carcinoma (HCC. Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR upregulation. Although the microvessel density (MVD of residual tumor tissue increased after PR, the microvessel integrity (MVI was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical

  14. Sustained release nimesulide microparticles: evaluation of release modifying property of ethy

    International Nuclear Information System (INIS)

    Khan, S.A.; Ahmed, M.; Nisar-ur-Rehman; Madni, A.U.; Aamir, M.N.; Murtaza, G.

    2011-01-01

    Microencapsulated controlled-release preparations of nimesulide were formulated. Microparticles were prepared by modified phase separation (non-solvent addition) technique using different ratios of ethylcellulose. The microparticles (M/sub 1/, M/sub 2/, and M/sub 3/) were yellow, free flowing and spherical in shape with the particle size varying from 93.62 +- 14.15 to 104.19 +- 18.15 mu m. The t/sub 60%/of nimesulide release from microparticles was found to be 3 +- 0.6, 5 +- 0.6 and 8 +- 0.8 h for formulations M/sub 1/, M/sub 2/, and M/sub 3/, respectively. FT-IR, XRD, and thermal analysis were done which showed that there is no interaction between the polymer and drug. The mechanism of drug release from nimesulide microparticles was studied by using Higuchi and Korsmeyer-Peppas models. The value of coefficient of determination (R/sup 2/) for M/sub 1/, M/sub 2/, and M/sub 3/ indicates anomalous and case-II transport release mechanism. The dissolution data of designed system verified its ability to maintain plasma concentration without the need of frequent dosing. The Nimesulide microparticles prolonged drug release for 12 hours or longer. Based on the results of release studies, M/sub 3/ was opted as a suitable microparticulate formulation allowing the controlled release of nimesulide over a prolonged period of time. Moreover, its encapsulation efficiency was also comparable to the other two formulations (M/sub 1/ and M/sub 2/). In conclusion, the influence of polymer concentration should be considered during formulation development. (author)

  15. Nanosilver-Silica Composite: Prolonged Antibacterial Effects and Bacterial Interaction Mechanisms for Wound Dressings.

    Science.gov (United States)

    Mosselhy, Dina A; Granbohm, Henrika; Hynönen, Ulla; Ge, Yanling; Palva, Airi; Nordström, Katrina; Hannula, Simo-Pekka

    2017-09-06

    Infected superficial wounds were traditionally controlled by topical antibiotics until the emergence of antibiotic-resistant bacteria. Silver (Ag) is a kernel for alternative antibacterial agents to fight this resistance quandary. The present study demonstrates a method for immobilizing small-sized (~5 nm) silver nanoparticles on silica matrix to form a nanosilver-silica (Ag-SiO₂) composite and shows the prolonged antibacterial effects of the composite in vitro. The composite exhibited a rapid initial Ag release after 24 h and a slower leaching after 48 and 72 h and was effective against both methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli ( E . coli ). Ultraviolet (UV)-irradiation was superior to filter-sterilization in retaining the antibacterial effects of the composite, through the higher remaining Ag concentration. A gauze, impregnated with the Ag-SiO₂ composite, showed higher antibacterial effects against MRSA and E . coli than a commercial Ag-containing dressing, indicating a potential for the management and infection control of superficial wounds. Transmission and scanning transmission electron microscope analyses of the composite-treated MRSA revealed an interaction of the released silver ions with the bacterial cytoplasmic constituents, causing ultimately the loss of bacterial membranes. The present results indicate that the Ag-SiO₂ composite, with prolonged antibacterial effects, is a promising candidate for wound dressing applications.

  16. Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

    Science.gov (United States)

    Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

    2011-01-01

    Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

  17. Quelle préposition ?

    CERN Document Server

    Grevisse, Maurice

    1996-01-01

    Pour bien parler ou bien écrire, il faut avant tout posséder un bon vocabulaire, puis savoir bien remuer les mots, leur faire exprimer quelque chose et agencer adroitement les propositions. Il faut aussi - et cela n'est pas négligeable - amener congrûment les divers compléments des noms, des adjectifs ou des verbes ; quand ces compléments sont de construction indirecte, c'est-à-dire quand ils doivent être introduits par une préposition, on hésite parfois sur la bonne manière de les accrocher. Ne pas négliger le bon choix! Cela ne crée pas le style, sans doute, mais peut, pour une part, témoigner de sa bonne qualité.

  18. Parimad suhtekorraldusteod konkursil Baltic PR Awards

    Index Scriptorium Estoniae

    2012-01-01

    Balti riikide suhtekorraldusliidud koostöös Rahvusvahelise Avalike Suhete Assotsiatsiooniga (IPRA) korraldavad 2001. aastast iga aasta kommunikatsioonijuhtimisalast auhinnakonkurssi Baltic PR Awards

  19. Plasma cell-free mitochondrial DNA declines in response to prolonged moderate aerobic exercise.

    Science.gov (United States)

    Shockett, Penny E; Khanal, Januka; Sitaula, Alina; Oglesby, Christopher; Meachum, William A; Castracane, V Daniel; Kraemer, Robert R

    2016-01-01

    Increased plasma cell-free mitochondrial DNA (cf-mDNA), a damage-associated molecular pattern (DAMP) produced by cellular injury, contributes to neutrophil activation/inflammation in trauma patients and arises in cancer and autoimmunity. To further understand relationships between cf-mDNA released by tissue injury, inflammation, and health benefits of exercise, we examined cf-mDNA response to prolonged moderate aerobic exercise. Seven healthy moderately trained young men (age = 22.4 ± 1.2) completed a treadmill exercise trial for 90 min at 60% VO2 max and a resting control trial. Blood was sampled immediately prior to exercise (0 min = baseline), during (+18, +54 min), immediately after (+90 min), and after recovery (R40). Plasma was analyzed for cf-mDNA, IL-6, and lactate. A significant difference in cf-mDNA response was observed between exercise and control trials, with cf-mDNA levels reduced during exercise at +54 and +90 (with or without plasma volume shift correction). Declines in cf-mDNA were accompanied by increased lactate and followed by an increase in IL-6, suggesting a temporal association with muscle stress and inflammatory processes. Our novel finding of cf-mDNA decline with prolonged moderate treadmill exercise provides evidence for increased clearance from or reduced release of cf-mDNA into the blood with prolonged exercise. These studies contrast with previous investigations involving exhaustive short-term treadmill exercise, in which no change in cf-mDNA levels were reported, and contribute to our understanding of differences between exercise- and trauma-induced inflammation. We propose that transient declines in cf-mDNA may induce health benefits, by reducing systemic inflammation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  20. Thermodynamic assessment of the Pr-Zn binary system

    International Nuclear Information System (INIS)

    Huang, X.M.; Liu, L.B.; Zhang, L.G.; Jia, B.R.; Jin, Z.P.; Zheng, F.

    2008-01-01

    On the basis of available experimental data of phase diagram and thermodynamic properties, the Pr-Zn binary system has been optimized using the CALPHAD approach. The phases, including liquid and bcc A 2(βPr) were treated as substitutional solutions, while the intermetallic compounds, including PrZn, PrZn 2 , PrZn 3 , Pr 3 Zn 11 , Pr 13 Zn 58 , Pr 3 Zn 22 , Pr 2 Zn 17 and PrZn 11 were modeled as stoichiometric compounds. As the result of optimization, a set of self-consistent thermodynamic parameters has been obtained, which can be used to reproduce the reported experimental data

  1. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  2. Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis.

    Science.gov (United States)

    Oh, Eun Jo; Oh, Se Heang; Lee, In Soo; Kwon, Oh Soo; Lee, Jin Ho

    2016-05-01

    Osteomyelitis is still considered to be one of the major challenges for orthopedic surgeons despite advanced antiseptic surgical procedures and pharmaceutical therapeutics. In this study, hydrophilized poly(methyl methacrylate) (PMMA) bone cements containing Pluronic F68 (EG79PG28EG79) as a hydrophilic additive and vancomycin (F68-VAcements) were prepared to allow the sustained release of the antibiotic for adequate periods of time without any significant loss of mechanical properties. The compressive strengths of the bone cements with Pluronic F68 compositions less than 7 wt% were not significantly different compared with the control vancomycin-loaded bone cement (VAcement). TheF68 (7 wt%)-VAcement showed sustained release of the antibiotic for up to 11 weeks and almost 100% release from the bone cement. It also prohibited the growth ofS. aureus(zone of inhibition) over six weeks (the required period to treat osteomyelitis), and it did not show any notable cytotoxicity. From an animal study using a femoral osteomyelitis rat model, it was observed that theF68 (7 wt%)-VAcement was effective for the treatment of osteomyelitis, probably as a result of the prolonged release of antibiotic from the PMMA bone cement. On the basis of these findings, it can be suggested that the use of Pluronic F68 as a hydrophilic additive for antibiotic-eluting PMMA bone cement can be a promising strategy for the treatment of osteomyelitis. © The Author(s) 2016.

  3. Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.

    Science.gov (United States)

    Zilony, Neta; Rosenberg, Michal; Holtzman, Liran; Schori, Hadas; Shefi, Orit; Segal, Ester

    2017-07-10

    Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge, due to the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect.

    Science.gov (United States)

    Sonvico, Fabio; Conti, Chiara; Colombo, Gaia; Buttini, Francesca; Colombo, Paolo; Bettini, Ruggero; Barchielli, Marco; Leoni, Barbara; Loprete, Luca; Rossi, Alessandra

    2017-09-28

    In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats

    NARCIS (Netherlands)

    Meng, Li; Rijntjes, Eddy; Swarts, Hans J.M.; Keijer, Jaap; Teerds, Katja J.

    2017-01-01

    Background: There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The

  6. Predictive factors associated with prolonged chest drain production after esophagectomy

    NARCIS (Netherlands)

    Lagarde, S. M.; Omloo, J. M. T.; Ubbink, D. T.; Busch, O. R. C.; Obertop, H.; van Lanschot, J. J. B.

    2007-01-01

    After esophagectomy, pleural drainage is performed to ensure complete drainage of the pleural cavities. The aim of this study was to detect predisposing factors for prolonged drainage. Patients who underwent transhiatal or extended transthoracic esophagectomy for adenocarcinoma of the distal

  7. Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

    Science.gov (United States)

    Sloan, Paul A; Rasul, Mazhar

    2002-01-01

    We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

  8. PrP Conformational Transitions Alter Species Preference of a PrP-specific antibody

    NARCIS (Netherlands)

    Zou, W.Q.; Langeveld, J.P.M.; Xiao, X.; Chen, S.; McGeer, P.L.; Yuan, J.; Payne, M.C.; Kang, H.E.; McGeehan, J.M.; Sy, M.S.; Greenspan, N.S.; Kaplan, D.; Wang, G.X.; Parchi, P.; Hoover, E.A.; Kneale, G.; Telling, G.; Surewicz, W.; Kong, Q.; Guo, J.

    2010-01-01

    The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist of residues Met-Lys-His-Met (MKHM) corresponding to human PrP-(109–112). This assumption is based mainly on the observation that 3F4 reacts with human and hamster PrP but not with PrP from

  9. Suured prügifirmad valmistuvad prügipuuduseks / Mirko Ojakivi

    Index Scriptorium Estoniae

    Ojakivi, Mirko

    2010-01-01

    Ragn-Sells ja Adelan Prügiveod soovivad luba jäätmete pikaajaliseks vaheladestamiseks Tallinna piiril. Ragn-Sells saaks jäätmekütusetehase planeerimise ja ehitamise ajal endale koguda ligi 35 000 t segaolmejäätmeid aastas, Adelan Prügiveod sooviks ladestada ligi 50 000 t prügi aastas

  10. Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2015-09-01

    Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

  11. Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival

    International Nuclear Information System (INIS)

    Kenyon, N.S.; Strasser, S.; Alejandro, R.

    1990-01-01

    Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100

  12. Growth hormone-releasing peptides.

    Science.gov (United States)

    Ghigo, E; Arvat, E; Muccioli, G; Camanni, F

    1997-05-01

    Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration: in fact, prolonged administration of GHRPs increases IGF-1 levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and

  13. PrEP (Pre-Exposure Prophylaxis) 101

    Science.gov (United States)

    ... than 70%. Your risk of getting HIV from sex can be even lower if you combine PrEP with condoms and other prevention methods. Download PrEP 101 Consumer Info Sheet Vital Signs Fact Sheet on Daily Pill Can Prevent HIV (PrEP) Expand All Collapse All Video Introductions to PrEP What is PrEP? A Brief ...

  14. CD36 participates in PrP(106-126-induced activation of microglia.

    Directory of Open Access Journals (Sweden)

    Mohammed Kouadir

    Full Text Available Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP fragment 106-126 (PrP(106-126. We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb. The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126. The results showed that PrP(106-126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α, increased iNOS expression and nitric oxide (NO production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126. Together, these results suggest that CD36 is involved in PrP(106-126-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides

  15. Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Jeonghyeon Park

    Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

  16. Aspects of Pr3+ luminescence in solids

    International Nuclear Information System (INIS)

    Srivastava, A.M.

    2016-01-01

    A brief perspective on the influence of “host lattice-Pr 3+ ” interactions on the optical properties of the Pr 3+ ion in solids is presented. How the energy position of the Pr 3+ 4f 1 5d 1 configuration relative to the 1 S 0 , 3 P J and host lattice conduction band levels influences the Pr 3+ optical properties is highlighted by considering solids in which the 4f 1 5d 1 configuration (1) is energetically above the 1 S 0 level, (2) is energetically below the 1 S 0 level, (3) is energetically close to the 1 S 0 level, and (4) overlaps with the host lattice conduction band. - Highlights: • Spectroscopic properties of Pr 3+ in solids is examined. • The influence of Pr 3+ 4f 1 5d 1 energy position relative to the 4f 2 levels is discussed. • The effect of interaction between Pr 3+ 4f 1 5d 1 and host conduction level is illustrated. • The paper identifies potential commercial applications.

  17. Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release

    International Nuclear Information System (INIS)

    Yuan Peng; Southon, Peter D; Kepert, Cameron J; Liu Zongwen

    2012-01-01

    The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release. (paper)

  18. Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release.

    Science.gov (United States)

    Yuan, Peng; Southon, Peter D; Liu, Zongwen; Kepert, Cameron J

    2012-09-21

    The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release.

  19. Studies in the Crystalline Electric Field in Pr2 Al and Pr Al by the Inelastic Neutron Scattering Method

    International Nuclear Information System (INIS)

    Slisenko, V.I.; Ivanitskij, P.G.; Vasil'kevich, A.A.; Krotenko, V.T.; Majstrenko, A.N.

    1993-01-01

    Results of inelastic neutron scattering in polycrystalline Pr 2 Al and Pr Al are reported. The parameters of the crystal field Hamiltonian for the orthorhombic point symmetry of the Pr 3+ ions in Pr 2 Al and Pr Al are derived from neutron spectra. Using These parameters the magnetic contribution to the specific heat is calculated

  20. Diclofenac sodium entrapment and release from halloysite nanotubules.

    Science.gov (United States)

    Krejčová, Kateřina; Deasy, Patrick B; Rabišková, Miloslava

    2013-02-01

    Halloysite was found to have interesting nanotubular geometry viable for the entrapment of various active agents. In this experiment, the ability of hollow halloysite cylinders to entrap the anionic model drug diclofenac sodium and to retard drug dissolution rate was investigated. Drugs could be incorporated into layered tubules via three different mechanisms: adsorption, intercalation and tubular entrapment. Based on the adsorption studies, some diclofenac sodium was shown to be adsorbed to the polyionic mineral surface despite its permanent negative charge. The X-ray powder diffraction analysis (XRPD) results did not prove any intercalation reaction to occur. The most important drug-loading mechanism involved the tubular entrapment with encapsulation efficiency 48.1%. The drug release from halloysite was prolonged in comparison with the dissolution of pure drug. Halloysite itself as well as halloysite loaded with the drug proved to be appropriate material to form pellets by extrusion /spheronization method. halloysite diclofenac sodium drug entrapment pellets prolonged drug release.

  1. Crystal structure of PrOHSO4

    International Nuclear Information System (INIS)

    Fahey, J.A.; Williams, G.J.B.; Haschke, J.M.

    1979-01-01

    PrOHSO 4 was prepared by hydrothermal reaction of Pr(OH) 3 with Pr 2 (SO 4 ) 3 x H 2 O at 450 to 500 0 C and 1,200 +- 200 atm water pressure. The space group is P2 1 /c; the cell parameters are a = 4.488, b = 12.495, c = 7.091 A, β = 111.08, Z = 4, d/sub x/ = 4.49 g/cm 3 . Atomic coordinates and anisotropic thermal parameters are tabulated. A stereoscopic protection of the cation coordination sphere is shown and discussed. 2 figures, 3 tables

  2. Women's experiences of becoming a mother after prolonged labour.

    Science.gov (United States)

    Nystedt, Astrid; Högberg, Ulf; Lundman, Berit

    2008-08-01

    This paper is a report of a study to explore women's experiences of becoming a mother after prolonged labour. The negativity associated with a complicated labour such as prolonged labour can lead to a struggle to become a healthy mother and could restrict the process of becoming a mother. Interviews were conducted in 2004 with 10 mothers who had been through a prolonged labour with assisted vaginal or caesarean delivery 1-3 months previously. Thematic content analysis was used. Three themes were formulated, describing women's experiences as fumbling in the dark, struggling for motherhood and achieving confidence in being a mother. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like 'fumbling in the dark'. Women experienced bodily fatigue, accompanied by feelings of illness and detachment from the child. Having the child when in this condition entailed a struggle to become a mother. In spite of these experiences and the desire to achieve confidence in being a mother, the reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged interaction and relationship with the child, and contributed to their adaptation to motherhood. Women experiencing prolonged labour may be comparable with the experience of and recovery from illness, which could contribute to difficulties transitioning to motherhood and limit a woman's ability to be emotionally available for the child.

  3. PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection.

    Science.gov (United States)

    Marshall, Karen E; Hughson, Andrew; Vascellari, Sarah; Priola, Suzette A; Sakudo, Akikazu; Onodera, Takashi; Baron, Gerald S

    2017-01-15

    Glycosylphosphatidylinositol (GPI) anchoring of the prion protein (PrP C ) influences PrP C misfolding into the disease-associated isoform, PrP res , as well as prion propagation and infectivity. GPI proteins are found in cholesterol- and sphingolipid-rich membrane regions called rafts. Exchanging the GPI anchor for a nonraft transmembrane sequence redirects PrP C away from rafts. Previous studies showed that nonraft transmembrane PrP C variants resist conversion to PrP res when transfected into scrapie-infected N2a neuroblastoma cells, likely due to segregation of transmembrane PrP C and GPI-anchored PrP res in distinct membrane environments. Thus, it remained unclear whether transmembrane PrP C might convert to PrP res if seeded by an exogenous source of PrP res not associated with host cell rafts and without the potential influence of endogenous expression of GPI-anchored PrP C To further explore these questions, constructs containing either a C-terminal wild-type GPI anchor signal sequence or a nonraft transmembrane sequence containing a flexible linker were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2. NpL2 cells have physiological similarities to primary neurons, representing a novel and advantageous model for studying transmissible spongiform encephalopathy (TSE) infection. Cells were infected with inocula from multiple prion strains and in different biochemical states (i.e., membrane bound as in brain microsomes from wild-type mice or purified GPI-anchorless amyloid fibrils). Only GPI-anchored PrP C supported persistent PrP res propagation. Our data provide strong evidence that in cell culture GPI anchor-directed membrane association of PrP C is required for persistent PrP res propagation, implicating raft microdomains as a location for conversion. Mechanisms of prion propagation, and what makes them transmissible, are poorly understood. Glycosylphosphatidylinositol (GPI) membrane anchoring of the prion protein (PrP C

  4. Percutaneous release of the plantar fascia. New surgical procedure.

    Science.gov (United States)

    Oliva, Francesco; Piccirilli, Eleonora; Tarantino, Umberto; Maffulli, Nicola

    2017-01-01

    Plantar fasciopathy presents with pain at the plantar and medial aspect of the heel. If chronic, it can negatively impact on quality of life. Plantar fasciopathy is not always self-limiting, and can be debilitating. Surgical management involves different procedures. We describe a percutaneous plantar fascia release. A minimally invasive access to the plantar tuberosity of the calcaneus is performed, and a small scalpel blade is used to release the fascia. With this procedure, skin healing problems, nerve injuries, infection and prolonged recovery time are minimised, allowing early return to normal activities. V.

  5. Prolonged social withdrawal disorder: a hikikomori case in Spain.

    Science.gov (United States)

    Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

    2014-09-01

    The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

  6. Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

    DEFF Research Database (Denmark)

    Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.

    2016-01-01

    Doppler imaging, and two-dimensional speckle tracking. Correlation between echocardiographic variables and cardiac troponin I was evaluated. Results: Early diastolic myocardial velocities decreased significantly in longitudinal (baseline: −17.4 ± 2.4cm/s; end of ride: −15.8 ± 3.2cm/s (P = .013); morning......Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...... and diastolic function in horses. Animals: Twenty-six horses competing in 120–160 km endurance rides. Methods: Cross-sectional field study. Echocardiography was performed before and after rides, and the following morning, and included two-dimensional echocardiography, anatomical M-mode, pulsed-wave tissue...

  7. Thermoelectric power of PrMg3

    Science.gov (United States)

    Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

    2010-01-01

    PrMg3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg3.

  8. Thermoelectric power of PrMg3

    International Nuclear Information System (INIS)

    Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

    2010-01-01

    PrMg 3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg 3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg 3 .

  9. Crystal Field Levels of Pr3+ in PrFeO3 and PrGaO3 Determined by Inelastic Neutron Scattering

    DEFF Research Database (Denmark)

    Feldmann, K.; Henning, K.; Kaun, L.

    1975-01-01

    The crystal field splitting of the 3H4 ground state of the Pr ion in PrFeO3 and PrGaO3 has been investigated by inelastic scattering of thermal neutrons. At several temperatures the transitions have been measured by TAS and TOF methods for polycrystalline PrFeO3 and by the TOF method...... for polycrystalline PrGaO3. Energy level schemes which are different for these materials are given....

  10. Ultrasound-assisted endoscopic partial plantar fascia release.

    Science.gov (United States)

    Ohuchi, Hiroshi; Ichikawa, Ken; Shinga, Kotaro; Hattori, Soichi; Yamada, Shin; Takahashi, Kazuhisa

    2013-01-01

    Various surgical treatment procedures for plantar fasciitis, such as open surgery, percutaneous release, and endoscopic surgery, exist. Skin trouble, nerve disturbance, infection, and persistent pain associated with prolonged recovery time are complications of open surgery. Endoscopic partial plantar fascia release offers the surgeon clear visualization of the anatomy at the surgical site. However, the primary medial portal and portal tract used for this technique have been shown to be in close proximity to the posterior tibial nerves and their branches, and there is always the risk of nerve damage by introducing the endoscope deep to the plantar fascia. By performing endoscopic partial plantar fascia release under ultrasound assistance, we could dynamically visualize the direction of the endoscope and instrument introduction, thus preventing nerve damage from inadvertent insertion deep to the fascia. Full-thickness release of the plantar fascia at the ideal position could also be confirmed under ultrasound imaging. We discuss the technique for this new procedure.

  11. Phase diagrams of Pr-C system

    International Nuclear Information System (INIS)

    Eremenko, V.N.; Velikanova, T.Ya.; Gordijchuk, O.V.

    1988-01-01

    Results of the X-ray phase, metallographic and high-temperature differential thermal analysis are used for the first time to plot a diagram of the Pr-C system state. Carbides are formed in the system: Pr 2 C 3 with the bcc-structure of the Pu 2 C 3 type and with the period a 0 = 0.85722+-0.00026 within the phase region + 2 C 3 >, a 0 0.86078+-0.00016 nm - within the region 2 C 3 >+α-PrC 2 ; dimorphous PrC 2 : α-PrC 2 with the bct-structure of the CaC 2 type and periods a 0.38517+-0.00011, c 0 = 0.64337+-0.00019 nm; β-PrC 2 with the fcc-structure, probably, of KCN type. Dicarbide melts congruently at 2320 grad. C, forming eutectics with graphite at 2254+-6 grad. C and composition of 71.5% (at.)C. It is polymorphously transformed in the phase region 2 C 3 > + 2 > at 1145+-4 grad. C, and in the region 2 >+C at 1134+-4 grad. C. Sesquicarbide melts incongruently at 1545+-4 grad. C. The eutectic reaction L ↔ + 2 C 3 > occurs at 800+-4 grad. C, the eutectic composition ∼ 15% (at.)C. The temperature of the eutectoid reaction ↔ + 2 C 3 > is 675+-6 grad C. The limiting carbon solubility in β-Pr is about 8 and in α-Pr it is about 5% (at.)

  12. On the subgroups of PR groups

    International Nuclear Information System (INIS)

    Lebedenko, V.M.

    1979-01-01

    The subgroups of PR-groups are being studied, i.e., the subgroups of connected and simply connected nonabelian Lie groups, their Lie algebras being defined by the commuting relations of the type [Hsub(i), Hsub(j)] = rsub(ij)Hsub(i) (i 1 of PR-group G there exists such complementary subgroup G 2 and that group G is expanded in semidirect product G = G 1 xG 2 [ru

  13. Cerebral ammonia uptake and accumulation during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam

    2005-01-01

    We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebral...... blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise...... exercise with glucose, and further to 16.1 ± 3.3 µM after the placebo trial (P

  14. Revisiting progesterone receptor (PR) actions in breast cancer: Insights into PR repressive functions.

    Science.gov (United States)

    Proietti, Cecilia J; Cenciarini, Mauro E; Elizalde, Patricia V

    2018-05-01

    Progesterone receptor (PR) is a master regulator in female reproductive tissues that controls developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy. PR also plays a role in progression of endocrine-dependent breast cancer. As a member of the nuclear receptor family of ligand-dependent transcription factors, the main action of PR is to regulate networks of target gene expression in response to binding its cognate steroid hormone, progesterone. Liganded-PR transcriptional activation has been thoroughly studied and associated mechanisms have been described while progesterone-mediated repression has remained less explored. The present work summarizes recent advances in the understanding of how PR-mediated repression is accomplished in breast cancer cells and highlights the significance of fully understanding the determinants of context-dependent PR action. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Katie A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Woodley, Christa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seaburg, Adam [Univ. of Washington, Seattle, WA (United States); Skalski, John R. [Univ. of Washington, Seattle, WA (United States); Eppard, Matthew B. [U.S. Army Corps of Engineers, Portland, OR (United States)

    2014-07-17

    While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na+, K+, Ca2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were no mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na+, Ca2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na+, Ca2+, K+, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.

  16. Prolonged submaximal eccentric exercise is associated with increased levels of plasma IL-6

    DEFF Research Database (Denmark)

    Rohde, Thomas; MacLean, D A; Richter, Erik

    1997-01-01

    To study the relationship between exercise-related muscle proteolysis and the cytokine response, a prolonged eccentric exercise model of one leg was used. Subjects performed two trials [a branched-chain amino acid (BCAA) supplementation and a control trial]. The release of amino acids from muscle...... during and after the eccentric exercise was decreased in the BCAA trial, suggesting a suppression of net muscle protein degradation. The plasma concentrations of interleukin (IL)-6 increased from 0.75 +/- 0.19 (preexercise) to 5.02 +/- 0.96 pg/ml (2 h postexercise) in the control trial and in the BCAA...... supplementation trial from 1.07 +/- 0.41 to 4.15 +/- 1.21 pg/ml. Eccentric exercise had no effect on the concentrations of neutrophils, lymphocytes, CD16+/CD56+, CD4+, CD8+, CD14+/CD38+, lymphocyte proliferative response, or cytotoxic activities. BCAA supplementation reduced the concentration of CD14+/CD38+ cells...

  17. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xin Hua

    Full Text Available Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF. An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  18. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Science.gov (United States)

    Hua, Xin; Tan, Shengnan; Bandara, H M H N; Fu, Yujie; Liu, Siguo; Smyth, Hugh D C

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  19. Large scientific releases

    International Nuclear Information System (INIS)

    Pongratz, M.B.

    1981-01-01

    The motivation for active experiments in space is considered, taking into account the use of active techniques to obtain a better understanding of the natural space environment, the utilization of the advantages of space as a laboratory to study fundamental plasma physics, and the employment of active techniques to determine the magnitude, degree, and consequences of artificial modification of the space environment. It is pointed out that mass-injection experiments in space plasmas began about twenty years ago with the Project Firefly releases. Attention is given to mass-release techniques and diagnostics, operational aspects of mass release active experiments, the active observation of mass release experiments, active perturbation mass release experiments, simulating an artificial modification of the space environment, and active experiments to study fundamental plasma physics

  20. Photon cascade luminescence from Pr3+ ions in LiPrP4O12 polyphosphate

    International Nuclear Information System (INIS)

    Shalapska, T; Stryganyuk, G; Romanyshyn, Yu; Demchenko, P; Voloshinovskii, A; Trots, D; Gektin, A; Dorenbos, P

    2010-01-01

    The spectral-kinetic properties of luminescence from LiY 1-x Pr x P 4 O 12 (x = 1, 0.1) phosphors are studied in the 10-300 K temperature range upon excitation within the UV-VUV spectral range. The luminescence observed for LiPrP 4 O 12 at low temperatures is attributed to both intra-configurational 4f 2 → 4f 2 and inter-configurational 4f5d → 4f 2 radiative transitions of Pr 3+ . The temperature dependence of emission and the decay kinetics of Pr 3+ luminescence from LiY 1-x Pr x P 4 O 12 (x = 1, 0.1) phosphors are explained by temperature stimulated transitions from the 1 S 0 to the Pr 3+ 4f5d state. At low temperatures, the energy potential barrier between the 1 S 0 and 4f5d states is 0.014 eV for LiPrP 4 O 12 . The spectral overlap of the 1 S 0 and 4f5d states of Pr 3+ in LiY 0.9 Pr 0.1 P 4 O 12 determines the luminescence properties in the entire temperature range studied.

  1. A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

    Science.gov (United States)

    Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

    2016-07-01

    Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

  2. Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise.

    Science.gov (United States)

    Baggish, Aaron L; Park, Joseph; Min, Pil-Ki; Isaacs, Stephanie; Parker, Beth A; Thompson, Paul D; Troyanos, Chris; D'Hemecourt, Pierre; Dyer, Sophia; Thiel, Marissa; Hale, Andrew; Chan, Stephen Y

    2014-03-01

    Short nonprotein coding RNA molecules, known as microRNAs (miRNAs), are intracellular mediators of adaptive processes, including muscle hypertrophy, contractile force generation, and inflammation. During basal conditions and tissue injury, miRNAs are released into the bloodstream as "circulating" miRNAs (c-miRNAs). To date, the impact of extended-duration, submaximal aerobic exercise on plasma concentrations of c-miRNAs remains incompletely characterized. We hypothesized that specific c-miRNAs are differentially upregulated following prolonged aerobic exercise. To test this hypothesis, we measured concentrations of c-miRNAs enriched in muscle (miR-1, miR-133a, miR-499-5p), cardiac tissue (miR-208a), and the vascular endothelium (miR-126), as well as those important in inflammation (miR-146a) in healthy male marathon runners (N = 21) at rest, immediately after a marathon (42-km foot race), and 24 h after the race. In addition, we compared c-miRNA profiles to those of conventional protein biomarkers reflective of skeletal muscle damage, cardiac stress and necrosis, and systemic inflammation. Candidate c-miRNAs increased immediately after the marathon and declined to prerace levels or lower after 24 h of race completion. However, the magnitude of change for each c-miRNA differed, even when originating from the same tissue type. In contrast, traditional biomarkers increased after exercise but remained elevated 24 h postexercise. Thus c-miRNAs respond differentially to prolonged exercise, suggesting the existence of specific mechanisms of c-miRNA release and clearance not fully explained by generalized cellular injury. Furthermore, c-miRNA expression patterns differ in a temporal fashion from corollary conventional tissue-specific biomarkers, emphasizing the potential of c-miRNAs as unique, real-time markers of exercise-induced tissue adaptation.

  3. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    International Nuclear Information System (INIS)

    Hamlekhan, Azhang; Shokuhfar, Tolou; Sinha-Ray, Suman; Yarin, Alexander L; Takoudis, Christos; Mathew, Mathew T; Sukotjo, Cortino

    2015-01-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT. (paper)

  4. The application of povidone in the preparation of modified release tablets

    Directory of Open Access Journals (Sweden)

    Kasperek Regina

    2016-06-01

    Full Text Available The aim of the study was to investigate the modified release of a model substance, of tablets containing different types of Kollidon and particular additives. Additionally, the release kinetics and mechanism of prolonged release of certain tablet preparations were investigated. In this work, tablets containing different types of povidone (Kollidon CL, Kollidon 30, Kollidon SR and other excipients were prepared by the direct compression technique. The results showed that tablets with fast disintegration and release should contain in their composition, Kollidon CL, lactose and Avicel, however, the use of β-CD instead of lactose or Avicel brings about a slight prolongation in the disintegration time of tablets and the release of an active substance. Furthermore, while other tablet compositions generated within this study must be considered as being prolonged release types, only two of these showed the best fitted mathematical models. The in vitro dissolution data reveal that the dissolution profiles of the two formulations, one containing Kollidon SR with the addition of Kollidon 30, and the second with HPMC K15M, Kollidon 30, Kollidon CL and lactose, best fitted the Higuchi model. Moreover, the release mechanism of these two formulations plotted well into Korsmeyer-Peppas, indicating a coupling of drug diffusion in the hydrated matrix, as well as polymer relaxation – the so-called anomalous transport (non-Fickian.

  5. Performance, Economics and Potential Impact of Perennial Rice PR23 Relative to Annual Rice Cultivars at Multiple Locations in Yunnan Province of China

    Directory of Open Access Journals (Sweden)

    Guangfu Huang

    2018-04-01

    Full Text Available Perennial grain crops hold the promise of stabilizing fragile lands, while contributing grain and grazing in mixed farming systems. Recently, perennial rice was reported to successfully survive, regrow, and yield across a diverse range of environments in Southern China and Laos, with perennial rice PR23 being identified as a prime candidate for release to farmers. This paper reports the evaluation of PR23 for release, by (1 comparing its survival, regrowth, performance, and adaptation with preferred annual rices across nine ecological regions in southern Yunnan Province of China; (2 examining the economic costs and benefits of perennial versus annual rice there; and (3 discussing the evidence for the release of PR23 as a broadly adapted and acceptable cultivar for farmers. Overall, the grain yield of PR23 was similar to those of the preferred annual rice cultivars RD23 and HXR7, but the economic analysis indicated substantial labour savings for farmers by growing the perennial instead of the annual. PR23 was comparable to the annuals in phenology, plant height, grain yield, and grain size, and was acceptable in grain and cooking quality. Farmers were keen to grow it because of reduced costs and especially savings in labour. PR23 is proposed for release to farmers because of its comparable grain yields to annual rices, its acceptable grain and milling quality, its cost and labour savings, and the likely benefits to soil stability and ecological sustainability, along with more flexible farming systems.

  6. Public stigma of prolonged grief disorder : An experimental study

    NARCIS (Netherlands)

    Eisma, Maarten C.

    Prolonged grief disorder (PGD), characterized by severe, persistent and disabling grief, is being considered for inclusion in the International Classification of Diseases’ 11 (ICD-11) and a related disorder, Persistent Complex Bereavement Disorder (PCBD), is included for further investigation in the

  7. Prolonged use of indwelling urinary catheter following acute urinary ...

    African Journals Online (AJOL)

    J.O. Bello

    prolonged use of urinary catheters following acute urinary retention secondary to benign prostate enlarge- ment (BPE) and urethral ... indwelling urinary catheter for >3 months following acute urinary retention due to BPE or USD. The study .... the major health-care financing strategy in Nigeria and accounts for more than ...

  8. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.

    2011-01-01

    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  9. MRI findings of prolonged post-traumatic sternal pain

    International Nuclear Information System (INIS)

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne; Steinbach, Lynne

    2007-01-01

    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  10. Diet-consumer nitrogen isotope fractionation for prolonged fasting arthropods.

    Science.gov (United States)

    Mizota, Chitoshi; Yamanaka, Toshiro

    2011-12-01

    Nitrogen acquisition for cellular metabolism during diapause is a primary concern for herbivorous arthropods. Analyses of naturally occurring stable isotopes of nitrogen help elucidate the mechanism. Relevant articles have cited (58 times up to mid-June 2011) anomalously elevated δ(15)N (per mil deviation of (15)N/(14)N, relative to atmospheric nitrogen=0 ‰) values (diet-consumer nitrogen isotope fractionation; up to 12 ‰) for a prolonged fasting raspberry beetle (Byturus tomentosus Degeer (Coleoptera: Byturidae)), which feeds on red raspberries (Rubus idaeus: δ(15)N= ~ +2 ‰). Biologists have hypothesised that extensive recycling of amino acid nitrogen is responsible for the prolonged fasting. Since this hypothesis was proposed in 1995, scientists have integrated biochemical and molecular knowledge to support the mechanism of prolonged diapausing of animals. To test the validity of the recycling hypothesis, we analysed tissue nitrogen isotope ratios for four Japanese arthropods: the shield bug Parastrachia japonensis Scott (Hemiptera: Cydnidae), the burrower bug Canthophorus niveimarginatus Scott (Hemiptera: Cydnidae), leaf beetle Gastrophysa atrocyanea Motschulsky (Coleoptera: Chrysomelidae) and the Japanese oak silkworm Antheraea yamamai (Lepidoptera: Saturniidae), all of which fast for more than 6 months as part of their life-history strategy. Resulting diet-consumer nitrogen isotope discrimination during fasting ranged from 0 to 7‰, as in many commonly known terrestrial arthropods. We conclude that prolonged fasting of arthropods does not always result in anomalous diet-consumer nitrogen isotope fractionation, since the recycling process is closed or nearly closed with respect to nitrogen isotopes.

  11. Prolonged Intrauterine Retention of Foetal Bones after Midtrimester ...

    African Journals Online (AJOL)

    Prolonged retention of foetal bones in the uterus is a rare complication of induced abortion. We present the case of a 37 year old nullipara with retained foetal bones following a second trimester induced abortion. Accurate diagnosis and removal of the bony fragments led to restoration of fertility and subsequent delivery of a ...

  12. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    NARCIS (Netherlands)

    De Bruin, ML; Hoes, AW; Leufkens, HGM

    2003-01-01

    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and

  13. The Prolonged Neonatal Admission: Implications for our National Children's Hospital

    LENUS (Irish Health Repository)

    McGlacken-Byrne, SM

    2016-06-01

    A significant number of neonates are admitted to tertiary paediatric units for prolonged stays annually, despite limited availability of neonatal beds. As the three Dublin paediatric hospitals merge, this pressure will be transferred to our new National Children’s Hospital.\\r\

  14. The Importance of Prolonged Provocation in Drug Allergy

    DEFF Research Database (Denmark)

    Fransson, Sara; Mosbech, Holger; Kappel, Mogens

    2017-01-01

    BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. OBJECTIVE: To evaluate drug allergy investigations on the basis of drug...

  15. Influence of prolonged cold ischemia in renal transplantation.

    NARCIS (Netherlands)

    Vliet, J.A. van der; Warle, M.C.; Cheung, C.L.; Teerenstra, S.; Hoitsma, A.J.

    2011-01-01

    van der Vliet JA, Warle MC, Cheung CLS, Teerenstra S, Hoitsma AJ. Influence of prolonged cold ischemia in renal transplantation. Clin Transplant 2011: 25: E612-E616. (c) 2011 John Wiley & Sons A/S. Abstract: Aim: To determine to what extent current cold ischemia times (CITs) affect the results of

  16. The impact of obesity on physiological responses during prolonged exercise

    NARCIS (Netherlands)

    Eijsvogels, T.M.H.; Veltmeijer, M.T.; Schreuder, T.H.A.; Poelkens, F.; Thijssen, D.H.J.; Hopman, M.T.E.

    2011-01-01

    Background:Prolonged, moderate-intensity exercise training is routinely prescribed to subjects with obesity. In the general population, this type of exercise can lead to fluid and sodium imbalance. However, little is known whether obesity alters the risk of fluid and sodium imbalances.Objective:This

  17. Physiological response of rabbit bucks to prolonged feeding of ...

    African Journals Online (AJOL)

    Sixty-four (64) weanling rabbit bucks, 5 to 6 weeks old, were involved in a 2 x 4 factorial experiment to evaluate the effects of prolonged feeding of cottonseed cake (CSC) – based diets with or without vitamin E supplementation on the physiological response of the bucks. There were eight treatment combinations comprising ...

  18. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    Science.gov (United States)

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  19. Internalized stigma in adults with early phase versus prolonged psychosis.

    Science.gov (United States)

    Firmin, Ruth L; Lysaker, Paul H; Luther, Lauren; Yanos, Philip T; Leonhardt, Bethany; Breier, Alan; Vohs, Jenifer L

    2018-03-30

    Although internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one's illness stigma is internalized and the impact of internalization on symptoms or social functioning over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with social functioning or symptoms among those with prolonged compared to early phase psychosis. Individuals with early phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and social functioning. Controlling for education, race and sex differences, internalized stigma was significantly greater among those with prolonged psychosis compared to early phase. Internalized stigma was negatively related to social functioning and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early phase. Stereotype endorsement, discrimination experiences and social withdrawal also differentially related to symptoms and social functioning across the 2 samples. Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Furthermore, internalized stigma may be a possible treatment target among those with early phase psychosis. © 2018 John Wiley & Sons Australia, Ltd.

  20. Brain activity and fatigue during prolonged exercise in the heat

    DEFF Research Database (Denmark)

    Nielsen, Bodil; Hyldig, Tino; Bidstrup, F.

    2001-01-01

    We hypothesized that fatigue due to hyperthermia during prolonged exercise in the heat is in part related to alterations in frontal cortical brain activity. The electroencephalographic activity (EEG) of the frontal cortex of the brain was measured in seven cyclists [maximal O2 uptake (VO2max) 4...... min of exercise; P

  1. Streptococcus suis meningitis can require a prolonged treatment course

    Directory of Open Access Journals (Sweden)

    Jean Dejace

    2017-12-01

    Full Text Available We report a case of recrudescent Streptococcus suis meningitis requiring a prolonged treatment course. A few similar cases can be found in the burgeoning literature on what remains a relatively uncommon disease in humans, and these patients should be monitored carefully upon completion of therapy. Keywords: Meningitis, Relapse, Duration, Streptococcus suis

  2. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    Science.gov (United States)

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  3. Intrinsic motivation and amotivation in first episode and prolonged psychosis.

    Science.gov (United States)

    Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L

    2015-12-01

    The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Prognostic Significance Of QT Interval Prolongation In Adult ...

    African Journals Online (AJOL)

    Prognostic survival studies for heart-rate corrected QT interval in patients with chronic heart failure are few; although these patients are known to have a high risk of sudden cardiac death. This study was aimed at determining the mortality risk associated with prolonged QTc in Nigerians with heart failure. Ninety-six ...

  5. Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

    Science.gov (United States)

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate…

  6. Prolonged multifocal electroretinographic implicit times in the ocular ischemic syndrome

    DEFF Research Database (Denmark)

    Kofoed, Peter Kristian; Munch, Inger Christine; Sander, Birgit

    2010-01-01

    .4 +/- 1.7 mm Hg, respectively. Summed mfERG implicit times (N1, P1, N2) were prolonged in eyes with OIS, by 7.6%, 6.2%, and 7.5%, respectively, compared with fellow eyes (P macula, whereas the assessment of responses from...

  7. Prolongation Structure of Semi-discrete Nonlinear Evolution Equations

    International Nuclear Information System (INIS)

    Bai Yongqiang; Wu Ke; Zhao Weizhong; Guo Hanying

    2007-01-01

    Based on noncommutative differential calculus, we present a theory of prolongation structure for semi-discrete nonlinear evolution equations. As an illustrative example, a semi-discrete model of the nonlinear Schroedinger equation is discussed in terms of this theory and the corresponding Lax pairs are also given.

  8. Inclusion rate and physiological effects of prolonged feeding of ...

    African Journals Online (AJOL)

    The effect of incluusion of cocoa bean cake (CBC) on productive performance and physiological response of Isa Brown pullets to prolonged feeding of CBC were investigated. Dietary Inclusions or CBC (0, 50, 100 and 200g/ kg-1 diet) were monitored in typical poultry diets from day old to 51 weeks of age. Sexual maturity ...

  9. Preferences for Prolonging Life: A Prospect Theory Approach

    Science.gov (United States)

    Winter, Laraine; Lawton, M. Powell; Ruckdeschel, Katy

    2003-01-01

    Kahneman and Tversky's (1979) Prospect theory was tested as a model of preferences for prolonging life under various hypothetical health statuses. A sample of 384 elderly people living in congregate housing (263 healthy, 131 frail) indicated how long (if at all) they would want to live under each of nine hypothetical health conditions (e.g.,…

  10. Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress

    Science.gov (United States)

    2014-10-01

    Post - traumatic stress disorder ( PTSD ) is a chronic, debilitating psychiatric disorder that can...SPS animals. Post - traumatic stress disorder ( PTSD ) is associated with neurocognitive impairments that have been attributed to functional deficits...and resilience. 2. KEYWORDS Post - traumatic stress disorder , Single Prolonged Stress , Neurobiological Mechanisms 5 3. ACCOMPLISHMENTS

  11. Effect Of Prolonged Monocular Occlusion On Latent Nystagms

    NARCIS (Netherlands)

    H.J. Simonsz (Huib); G. Kommerell (Guntram)

    1992-01-01

    textabstractThe authors recorded nystagmus during seeing with one eye in eight patients with latent nystagmus (LN) before and after two or three days of prolonged occlusion of the better eye (POBE). Before POBE, the slow-phase speed of the nystagmus (SPS) was usually higher when the better eye was

  12. Effects of strict prolonged bed rest on cardiorespiratory fitness

    DEFF Research Database (Denmark)

    Ried-Larsen, Mathias; Aarts, Hugo M; Joyner, Michael J

    2017-01-01

    The aim of this systematic review and meta-analysis [International Prospective Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the effects of strict prolonged bed rest (without countermeasures) on maximal oxygen uptake (V̇o2max) and to explore sources of variation therein....

  13. The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking.

    Science.gov (United States)

    Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M; Baehr, Wolfgang

    2012-12-15

    Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d(-/-) mouse. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

    Science.gov (United States)

    Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

    2014-12-01

    Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

    Directory of Open Access Journals (Sweden)

    M. V. Grigoreva

    2013-10-01

    Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

  16. Nuclear refugees after large radioactive releases

    International Nuclear Information System (INIS)

    Pascucci-Cahen, Ludivine; Groell, Jérôme

    2016-01-01

    However improbable, large radioactive releases from a nuclear power plant would entail major consequences for the surrounding population. In Fukushima, 80,000 people had to evacuate the most contaminated areas around the NPP for a prolonged period of time. These people have been called “nuclear refugees”. The paper first argues that the number of nuclear refugees is a better measure of the severity of radiological consequences than the number of fatalities, although the latter is widely used to assess other catastrophic events such as earthquakes or tsunami. It is a valuable partial indicator in the context of comprehensive studies of overall consequences. Section 2 makes a clear distinction between long-term relocation and emergency evacuation and proposes a method to estimate the number of refugees. Section 3 examines the distribution of nuclear refugees with respect to weather and release site. The distribution is asymmetric and fat-tailed: unfavorable weather can lead to the contamination of large areas of land; large cities have in turn a higher probability of being contaminated. - Highlights: • Number of refugees is a good indicator of the severity of radiological consequences. • It is a better measure of the long-term consequences than the number of fatalities. • A representative meteorological sample should be sufficiently large. • The number of refugees highly depends on the release site in a country like France.

  17. PR Interval Associated Genes, Atrial Remodeling and Rhythm Outcome of Catheter Ablation of Atrial Fibrillation—A Gene-Based Analysis of GWAS Data

    Directory of Open Access Journals (Sweden)

    Daniela Husser

    2017-12-01

    Full Text Available Background: PR interval prolongation has recently been shown to associate with advanced left atrial remodeling and atrial fibrillation (AF recurrence after catheter ablation. While different genome-wide association studies (GWAS have implicated 13 loci to associate with the PR interval as an AF endophenotype their subsequent associations with AF remodeling and response to catheter ablation are unknown. Here, we perform a gene-based analysis of GWAS data to test the hypothesis that PR interval candidate genes also associate with left atrial remodeling and arrhythmia recurrence following AF catheter ablation.Methods and Results: Samples from 660 patients with paroxysmal (n = 370 or persistent AF (n = 290 undergoing AF catheter ablation were genotyped for ~1,000,000 SNPs. Gene-based association was investigated using VEGAS (versatile gene-based association study. Among the 13 candidate genes, SLC8A1, MEIS1, ITGA9, SCN5A, and SOX5 associated with the PR interval. Of those, ITGA9 and SOX5 were significantly associated with left atrial low voltage areas and left atrial diameter and subsequently with AF recurrence after radiofrequency catheter ablation.Conclusion: This study suggests contributions of ITGA9 and SOX5 to AF remodeling expressed as PR interval prolongation, low voltage areas and left atrial dilatation and subsequently to response to catheter ablation. Future and larger studies are necessary to replicate and apply these findings with the aim of designing AF pathophysiology-based multi-locus risk scores.

  18. The efficacy of antipsychotics for prolonged delirium with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Asano S

    2017-11-01

    Full Text Available Satoko Asano, Yasuto Kunii, Hiroshi Hoshino, Yusuke Osakabe, Tetsuya Shiga, Shuntaro Itagaki, Itaru Miura, Hirooki Yabe Department of Neuropsychiatry, School of Medicine Fukushima Medical University, Fukushima, Japan Aim: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization.Methods: We extracted all new inpatients (n=523 consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an “early improvement group” in which delirium resolved in ≤3 days after starting psychiatric medication, and a “prolonged group” with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2, we defined an “early improvement group with renal dysfunction” in which delirium resolved in ≤3 days after starting psychiatric medication and a “prolonged group with renal dysfunction” with delirium lasting for >3 days. We then examined differences between groups for different categorical variables.Results: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction.Conclusion: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction. Keywords: antipsychotic, prolonged delirium, chronic kidney disease, pharmacokinetics 

  19. Bremsstrahlung parameters of praseodymium-142 in different human tissues. A dosimetric perspective for 142Pr radionuclide therapy

    International Nuclear Information System (INIS)

    Bakht, M.K.; Jabal-Ameli, H.; Ahmadi, S.J.; Sadeghi, M.; Sadjadi, S.; Tenreiro, Claudio

    2012-01-01

    Praseodymium-142 [T 1/2 =19.12 h, E β -=2.162 MeV (96.3%), E γ =1575 keV (3.7%)] is one of the 141 Pr radioisotopes. Many studies have been attempted to assess the significance of usage 142 Pr in radionuclide therapy. In many studies, the dosimetric parameters of 142 Pr sources were calculated by modeling 142 Pr sources in the water phantom and scoring the energy deposited around it. However, the medical dosimetry calculations in water phantom consider Bremsstrahlung production, raising the question: ''How important is to simulate human tissues instead of using water phantom?'' This study answers these questions by estimation of 142 Pr Bremsstrahlung parameters. The Bremsstrahlung parameters of 142 Pr as therapeutic beta nuclides in different human tissues (adipose, blood, brain, breast, cell nucleus, eye lens, gastrointestinal tract, heart, kidney, liver, lung deflated, lymph, muscle, ovary, pancreas, cartilage, red marrow, spongiosa, yellow marrow, skin, spleen, testis, thyroid and different skeleton bones) were calculated by extending the national council for radiation protection model. The specific Bremsstrahlung constant (Γ Br ), probability of energy loss by beta during Bremsstrahlung emission (P Br ) and Bremsstrahlung activity (A release ) Br were estimated. It should be mentioned that Monte Carlo simulation was used for estimation of 142 Pr Bremsstrahlung activity based on the element compositions of different human tissues and the calculated exposures from the anthropomorphic phantoms. Γ Br for yellow marrow was smallest amount (1.1962 x 10 -3 C/kg-cm 2 /MBq-h) compared to the other tissues and highest for cortical bone (2.4764 x 10 -3 C/kg-cm 2 /MBq-h), and, overall, Γ Br for skeletal tissues were greater than other tissues. In addition, Γ Br breast was 1.8261 x 10 -3 C/kg-cm 2 /MBq-h which was greater than sacrum and spongiosa bones. Moreover, according to (A release ) Br of 142 Pr, the patients receiving 142 Pr do not have to be hospitalized for

  20. E-PR technologies in political party activities

    OpenAIRE

    Tereshchuk Vitaliy Ivanovych

    2016-01-01

    The article discusses the role of the Internet as an important communicative tool in the field of political PR. The article reviews the characteristics of PR-activities on the Internet and the features of e-PR in the political sphere. Particular attention is paid to the system of political party’s e-PR tools.

  1. New insights into flavivirus biology: the influence of pH over interactions between prM and E proteins

    Science.gov (United States)

    Oliveira, Edson R. A.; de Alencastro, Ricardo B.; Horta, Bruno A. C.

    2017-11-01

    Diseases caused by flaviviruses, such as dengue and zika, are globally recognized as major threats. During infection, a critical point in their replicative cycle is the maturation step, which occurs throughout the cellular exocytic pathway. This step is a pH-dependent process that involves the modification of the viral envelope by converting prM (pre-membrane) into M (membrane) proteins with the release of a "pr peptide". After this reaction, the pr peptides remain bound to the viral envelope while the virions cross the acidic trans-Golgi network, and are released only at neutral pH after secretion of the virus particles. Despite this current knowledge, the molecular basis of the flavivirus maturation step is largely unknown. Here, based on the crystal structure of the dengue pr-E complex ("pr peptide" bound to virus envelope protein) and using molecular dynamics simulations, we found that the pH shift from acidic to neutral yields considerable structural changes in the system. Dynamic cross correlation maps and root mean square deviation analyses revealed that the pr-E junction is clearly unstable under neutral pH. Secondary structure analysis also revealed that the fusion loop region, present in the E protein, is sensitive to pH and tends to unstructure at a neutral environment. Moreover, we found that five residues present in the E protein, Gly102, His244, Thr70, Thr68 and Asn67 are critical to confer stability to the pr-E complex while inside the Golgi apparatus. This work brings details about the dynamical behavior of the pr-E system, helps to better understand the flavivirus biology and may also be of use in the development of novel antiviral strategies.

  2. PrP N-terminal domain triggers PrPSc-like aggregation of Dpl

    International Nuclear Information System (INIS)

    Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurelie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

    2008-01-01

    Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP C , for 'cellular prion protein') into an abnormal state (PrP Sc , for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP C . In contrast to its homologue PrP C , Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP Sc -like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP C (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the α-helical monomer forms soluble β-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy

  3. Tips for the PR Chairman for Education Associations. PR Bookshelf No. 2.

    Science.gov (United States)

    National Education Association, Washington, DC.

    This booklet is intended to aid leaders of local education associations in developing a continuing public relations (PR) program aimed at establishing and maintaining a favorable public image for teachers. Although it offers useful guidelines for developing a PR program, the booklet does not contain lists of specific things to do. Instead, it…

  4. La préservation, atout essentiel pour contrer la précarité des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La préservation, atout essentiel pour contrer la précarité des moyens de subsistance en ... Union mondiale pour la conservation de la nature et des ressources ... la recherche menée dans les domaines des sciences sociales, des sciences ...

  5. The 2017 Release Cloudy

    Science.gov (United States)

    Ferland, G. J.; Chatzikos, M.; Guzmán, F.; Lykins, M. L.; van Hoof, P. A. M.; Williams, R. J. R.; Abel, N. P.; Badnell, N. R.; Keenan, F. P.; Porter, R. L.; Stancil, P. C.

    2017-10-01

    We describe the 2017 release of the spectral synthesis code Cloudy, summarizing the many improvements to the scope and accuracy of the physics which have been made since the previous release. Exporting the atomic data into external data files has enabled many new large datasets to be incorporated into the code. The use of the complete datasets is not realistic for most calculations, so we describe the limited subset of data used by default, which predicts significantly more lines than the previous release of Cloudy. This version is nevertheless faster than the previous release, as a result of code optimizations. We give examples of the accuracy limits using small models, and the performance requirements of large complete models. We summarize several advances in the H- and He-like iso-electronic sequences and use our complete collisional-radiative models to establish the densities where the coronal and local thermodynamic equilibrium approximations work.

  6. EIA new releases

    International Nuclear Information System (INIS)

    1994-09-01

    This report is a compliation of news releases from the Energy Information Administration. The september-october report includes articles on energy conservation, energy consumption in commercial buildings, and a short term energy model for a personal computer

  7. Sellafield (release of radioactivity)

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, J; Goodlad, A; Morris, M

    1986-02-06

    A government statement is reported, about the release of plutonium nitrate at the Sellafield site of British Nuclear Fuels plc on 5 February 1986. Matters raised included: details of accident; personnel monitoring; whether radioactive material was released from the site; need for public acceptance of BNFL activities; whether plant should be closed; need to reduce level of radioactive effluent; number of incidents at the plant.

  8. Pr-magnetism in the quasi-skutterudite compound PrFe2Al8.

    Science.gov (United States)

    Nair, Harikrishnan S; Ogunbunmi, Michael O; Kumar, C M N; Adroja, D T; Manuel, P; Fortes, D; Taylor, J; Strydom, A M

    2017-08-31

    The intermetallic compound PrFe 2 Al 8 that possesses a three-dimensional network structure of Al polyhedra centered at the transition metal element Fe and the rare earth Pr is investigated through neutron powder diffraction and inelastic neutron scattering in order to elucidate the magnetic ground state of Pr and Fe and the crystal field effects of Pr. Our neutron diffraction study confirms long-range magnetic order of Pr below [Formula: see text] K in this compound. Subsequent magnetic structure estimation reveals a magnetic propagation vector [Formula: see text] with a magnetic moment value of [Formula: see text]/Pr along the orthorhombic c-axis and evidence the lack of ordering in the Fe sublattice. The inelastic neutron scattering study reveals one crystalline electric field excitation near 19 meV at 5 K in PrFe 2 Al 8 . The energy-integrated intensity of the 19 meV excitation as a function of [Formula: see text] follows the square of the magnetic form factor of [Formula: see text] thereby confirming that the inelastic excitation belongs to the Pr sublattice. The second sum rule applied to the dynamic structure factor indicates only 1.6(2) [Formula: see text] evolving at the 19 meV peak compared to the 3.58 [Formula: see text] for free [Formula: see text], indicating that the crystal field ground state is magnetic and the missing moment is associated with the resolution limited quasi-elastic line. The magnetic order occurring in Pr in PrFe 2 Al 8 is counter-intuitive to the symmetry-allowed crystal field level scheme, hence, is suggestive of exchange-mediated mechanisms of ordering stemming from the magnetic ground state of the crystal field levels.

  9. In-situ phase transition from microemulsion to liquid crystal with the potential of prolonged parenteral drug delivery.

    Science.gov (United States)

    Ren, Xiazhong; Svirskis, Darren; Alany, Raid G; Zargar-Shoshtari, Sara; Wu, Zimei

    2012-07-15

    This study is the first to investigate and demonstrate the potential of microemulsions (MEs) for sustained release parenteral drug delivery, due to phase transition behavior in aqueous environments. Phase diagrams were constructed with Miglyol 812N oil and a blend of (co)surfactants Solutol HS 15 and Span 80 with ethanol. Liquid crystal (LC) and coarse emulsion (CE) regions were found adjacent to the ME region in the water-rich corner of the phase diagram. Two formulations were selected, a LC-forming ME and a CE-forming ME and each were investigated with respect to their rheology, particle size, drug release profiles and particularly, the phase transition behavior. The spreadability in an aqueous environment was determined and release profiles from MEs were generated with gamma-scintigraphy. The CE-forming ME dispersed readily in an aqueous environment, whereas the LC-forming ME remained in a contracted region possibly due to the transition of ME to LC at the water/ME interface. Gamma-scintigraphy showed that the LC-forming ME had minimal spreadability and a slow release of (99m)Tc in the first-order manner, suggesting phase conversion at the interface. In conclusion, owing to the potential of phase transition, LC-forming MEs could be used as extravascular injectable drug delivery vehicles for prolonged drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Alginate-polyvinyl alcohol based interpenetrating polymer network for prolonged drug therapy, Optimization and in-vitro characterization.

    Science.gov (United States)

    Anwar, Hina; Ahmad, Mahmood; Minhas, Muhammad Usman; Rehmani, Sahrish

    2017-06-15

    A new natural and synthetic polymeric blend to form interpenetrating polymer network (IPN) hydrogels was synthesized utilizing sodium alginate and PVA as polymers by free radical polymerization employing 2-Acylamido-2-methylpropane-sulfonic acid as monomer (AMPS) and tramadol HCl as model drug through 3 2 level full factorial design to evaluate the impact of selected independent factors i.e. polymer (sodium alginate) and monomer (AMPS) contents on swelling index at 18th hour, percent drug release at 18th hour, time required for 80% drug release and drug entrapment efficiency as dependent variables. FTIR, SEM, sol-gel analysis, equilibrium swelling studies and in-vitro release kinetics were performedfor in-vitro characterization of formulated IPN hydrogels. In-vitro studies carried out at pH 1.2 and pH 7.4 revealed pH independent swelling and drug release from polymeric IPN, providing controlled drug release for an extended period of time with improved entrapment efficiency, thereby concluding that this polymeric blend may be a promising system for the prolonged drug delivery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients with post-stroke seizure.

    Science.gov (United States)

    Siniscalchi, Antonio; Scaglione, Francesco; Sanzaro, Enzo; Iemolo, Francesco; Albertini, Giorgio; Quirino, Gianluca; Manes, Maria Teresa; Gratteri, Santo; Mercuri, Nicola Biagio; De Sarro, Giovambattista; Gallelli, Luca

    2014-12-01

    Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic drugs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke seizures. We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls. Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p phenobarbital prolonged QTc interval more so than levetiracetam.

  12. 75 FR 44847 - Proposed Collection; Comment Request for Forms 943, 943-PR, 943-A, and 943A-PR

    Science.gov (United States)

    2010-07-29

    ... 943, 943-PR, 943- A, and 943A-PR AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and... comments concerning Forms 943, Employer's Annual Tax Return for Agricultural Employees, 943-PR, Planilla..., Agricultural Employer's Record of Federal Tax Liability, and 943A-PR, Registro De La Obligacion Contributiva...

  13. 78 FR 47051 - Proposed Collection; Comment Request for Forms 943, 943-PR, 943-A, and 943A-PR

    Science.gov (United States)

    2013-08-02

    ... 943, 943-PR, 943- A, and 943A-PR AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and..., 943-PR, Planilla Para La Declarcion Anual De La Contribucion Federal Del Patrono De Empleados Agricolas, 943-A, Agricultural Employer's Record of Federal Tax Liability, and 943A-PR, Registro De La...

  14. Multivesicular release underlies short term synaptic potentiation independent of release probability change in the supraoptic nucleus.

    Directory of Open Access Journals (Sweden)

    Michelle E Quinlan

    Full Text Available Magnocellular neurons of the supraoptic nucleus receive glutamatergic excitatory inputs that regulate the firing activity and hormone release from these neurons. A strong, brief activation of these excitatory inputs induces a lingering barrage of tetrodotoxin-resistant miniature EPSCs (mEPSCs that lasts for tens of minutes. This is known to accompany an immediate increase in large amplitude mEPSCs. However, it remains unknown how long this amplitude increase can last and whether it is simply a byproduct of greater release probability. Using in vitro patch clamp recording on acute rat brain slices, we found that a brief, high frequency stimulation (HFS of afferents induced a potentiation of mEPSC amplitude lasting up to 20 min. This amplitude potentiation did not correlate with changes in mEPSC frequency, suggesting that it does not reflect changes in presynaptic release probability. Nonetheless, neither postsynaptic calcium chelator nor the NMDA receptor antagonist blocked the potentiation. Together with the known calcium dependency of HFS-induced potentiation of mEPSCs, our results imply that mEPSC amplitude increase requires presynaptic calcium. Further analysis showed multimodal distribution of mEPSC amplitude, suggesting that large mEPSCs were due to multivesicular glutamate release, even at late post-HFS when the frequency is no longer elevated. In conclusion, high frequency activation of excitatory synapses induces lasting multivesicular release in the SON, which is independent of changes in release probability. This represents a novel form of synaptic plasticity that may contribute to prolonged excitatory tone necessary for generation of burst firing of magnocellular neurons.

  15. HIV providers' likelihood to prescribe pre-exposure prophylaxis (PrEP) for HIV prevention differs by patient type: a short report.

    Science.gov (United States)

    Adams, Leah M; Balderson, Benjamin H

    2016-09-01

    Pre-exposure prophylaxis (PrEP), the antiretroviral treatment regimen for HIV-negative people at high risk of acquiring HIV, has demonstrated efficacy across clinical trials in several patient populations. The Centers for Disease Control (CDC) have released detailed guidelines to aid providers in prescribing PrEP for their high-risk patients, including men who have sex with men (MSM), high-risk heterosexuals, and injection drug users (IDUs). Given that much attention in PrEP has focused on MSM patients, the present study used an online survey to assess factors involved in HIV care providers' (n = 363) decisions about prescribing PrEP, along with their willingness to prescribe PrEP to patients from various risk populations (e.g., MSM, heterosexuals, IDUs). The efficacy of PrEP was an important factor in providers' decisions about prescribing PrEP, as were considerations about patients' adherence to the regimen, regular follow-up for care, and medication costs. This survey's findings also suggest that providers' willingness to prescribe PrEP varies by patient group, with providers most willing to initiate the regimen with MSM who have an HIV-positive partner, and least willing to prescribe to high-risk heterosexuals or IDUs. In the context of the current CDC recommendations for PrEP that include MSM, heterosexuals, and IDUs, examining providers' rationales for and barriers against supporting this HIV prevention strategy across patient groups merits further attention.

  16. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

    2003-01-01

    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

  17. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    Science.gov (United States)

    Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

    2015-09-01

    Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

  18. Prolonged radioprotective activity of WR-2721 linked to dextran

    International Nuclear Information System (INIS)

    Moenig, H.; Konermann, G.; Oehlert, W.

    1990-01-01

    The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14±0.04 and 1.10±0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugats. (orig.) [de

  19. Smoking prolongs the infectivity of patients with tuberculosis.

    LENUS (Irish Health Repository)

    Siddiqui, U A

    2010-10-01

    We sought to establish if smokers on anti-tuberculosis treatment are more likely to have a prolonged period of infectivity, compared to non-smoking tuberculosis patients, in a low tuberculosis prevalence country. We conducted a cross-sectional, retrospective study in Ireland that recruited 53 microbiologically confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios (AOR) suggest that the infectivity status of PTB on treatment was four times more likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR: 4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear conversion in PTB patients on treatment.

  20. Atraumatic femoral neck fracture secondary to prolonged lactation induced osteomalacia

    Directory of Open Access Journals (Sweden)

    Dhammapal Sahebrao Bhamare

    2013-01-01

    Full Text Available Presenting a case of atraumatic fracture neck femur secondary to 2 years of prolonged lactation. A 26-year-old lactating mother presented with pain in left hip from last 12 months. She was apparently alright before and during pregnancy. Plain radiograph showed a complete undisplaced fracture of femoral neck. Osteomalacia was diagnosed by radiological and serological investigations. The fracture was fixed using AO type cannulated cancellous screws. The fracture showed good clinical and radiological union at 3 months. Literature review shows that this is a first case of atraumatic fracture of neck femur due to prolonged lactational osteomalacia. It showed that even apparently healthy Indians are susceptible to osteomalacia, more so during pregnancy and lactation and can be presented as atraumatic fracture. Although considered relatively stable, a compression type incomplete fracture neck femur may progress to a complete fracture if not treated in time.

  1. Cu4Pr6(MoO4)11-Pr2(MoO4)3 system

    International Nuclear Information System (INIS)

    Arzumanyan, G.A.

    1982-01-01

    Existence boundaries and Dalton compositions (CuPr(MoO 4 ) 2 , CuPr 3 (MoO 4 ) 5 ) of solid solutions that in the mojority are of shcheelite dsitored structure have been determined in the Cu 4 Pr 6 (MoO 4 ) 11 -Pr 2 (MoO 4 ) 3 system. It has been revealed that regions of homogeneity near the CuPr(MoO 4 ) 2 composition have a horseshoeshaped profile

  2. Validation of PR interval length as a criterion for development of atrial fibrillation in non-Hispanic whites, African Americans and Hispanics.

    Science.gov (United States)

    Shulman, Eric; Aagaard, Philip; Kargoli, Faraj; Hoch, Ethan; Zheng, Laura; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Ferrick, Kevin; Krumerman, Andrew

    2015-01-01

    PR interval prolongation on electrocardiogram (ECG) increases the risk of atrial fibrillation (AF). Non-Hispanic Whites are at higher risk of AF compared to African Americans and Hispanics. However, it remains unknown if prolongation of the PR interval for the development of AF varies by race/ethnicity. Therefore, we determined whether race affects the PR interval length's ability to predict AF and if the commonly used criterion of 200 ms in AF prediction models can continue to be used for non-White cohorts. This is a retrospective epidemiological study of consecutive inpatient and outpatients. An ECG database was initially interrogated. Patients were included if their initial ECG demonstrated sinus rhythm and had two or more electrocardiograms and declared a race and/or ethnicity as non-Hispanic White, African American or Hispanic. Development of AF was stratified by race/ethnicity along varying PR intervals. Cox models controlled for age, gender, race/ethnicity, systolic blood pressure, BMI, QRS, QTc, heart rate, murmur, treatment for hypertension, heart failure and use of AV nodal blocking agents to assess PR interval's predictive ability for development of AF. 50,870 patients met inclusion criteria of which 5,199 developed AF over 3.72 mean years of follow-up. When the PR interval was separated by quantile, prolongation of the PR interval to predict AF first became significant in Hispanic and African Americans at the 92.5th quantile of 196-201 ms (HR: 1.42, 95% CI: 1.09-1.86, p=0.01; HR: 1.32, 95% CI: 1.07-1.64, p=0.01, respectively) then in non-Hispanic Whites at the 95th quantile at 203-212 ms (HR: 1.24, 95% CI: 1.24-1.53, p=0.04). For those with a PR interval above 200 ms, African Americans had a lower risk than non-Hispanic Whites to develop AF (HR: 0.80, 95% CI: 0.64-0.95, p=0.012), however, no significant difference was demonstrated in Hispanics. This is the first study to validate a PR interval value of 200 ms as a criterion in African Americans and

  3. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

    Directory of Open Access Journals (Sweden)

    Christina Bognet

    2011-12-01

    Full Text Available Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL solutions, with or without epinephrine 5 µg/mL (1:200,000 in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001 or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001. Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

  4. A Case of QT Prolongation Associated with Panhypopituitarism

    Directory of Open Access Journals (Sweden)

    Dilek Arpaci

    2013-01-01

    Full Text Available We describe a 37-year-old patient with panhypopituitarism who experienced symptoms and signs of hormonal insufficiency and QT prolongation on electrocardiogram without electrolyte disturbances. After hormonal (steroidal and thyroid replacement therapy electrocardiographic findings were normalized. Hormonal disorders should be considered as a cause of long QT intervals which may lead to torsade de pointes, even if plasma electrolyte levels are normal, because life-threatening arrhythmia is treatable by supplementation of the hormone that is lacking.

  5. MRI findings of prolonged post-traumatic sternal pain

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne [University Hospital of Berne, Department of Diagnostic, Pediatric and Interventional Radiology, Berne (Switzerland); Steinbach, Lynne [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)

    2007-05-15

    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  6. Hormone supply of the organism in prolonged emotional stress

    Science.gov (United States)

    Amiragova, M. G.; Stulnikov, B. V.; Svirskaya, R. I.

    1980-01-01

    The effect of prolonged emotional stress of varying genesis on the hormonal function of the pancreas, thyroid gland, and adrenal cortex was studied. The amount of the hormonal secretion was found to depend on the type of adaptation activity and its duration. High secretion of the hormones observed outside the adaptation activity was examined as an index of the phase transition of defense reactions to the phase of overstress.

  7. The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation.

    Science.gov (United States)

    Weng, Yi-Ming; Wu, Shih-Hao; Li, Wen-Cheng; Kuo, Chan-Wei; Chen, Shou-Yen; Chen, Jih-Chang

    2013-03-01

    This study was performed to determine the effects of sodium bicarbonate injection during prolonged cardiopulmonary resuscitation (for >15 minutes). The retrospective cohort study consisted of adult patients who presented to the emergency department (ED) with the diagnosis of cardiac arrest in 2009. Data were retrieved from the institutional database. A total of 92 patients were enrolled in the study. Patients were divided into 2 groups based on whether they were treated (group1, n = 30) or not treated (group 2, n = 62) with sodium bicarbonate. There were no significant differences in demographic characteristics between groups. The median time interval between the administration of CPR and sodium bicarbonate injection was 36.0 minutes (IQR: 30.5-41.8 minutes). The median amount of bicarbonate injection was 100.2 mEq (IQR: 66.8-104.4). Patients who received a sodium bicarbonate injection during prolonged CPR had a higher percentage of return of spontaneous circulation, but not statistical significant (ROSC, 40.0% vs. 32.3%; P = .465). Sustained ROSC was achieved by 2 (6.7%) patients in the sodium bicarbonate treatment group, with no survival to discharge. No significant differences in vital signs after ROSC were detected between the 2 groups (heart rate, P = .124; systolic blood pressure, P = .094). Sodium bicarbonate injection during prolonged CPR was not associated with ROSC after adjust for variables by regression analysis (Table 3; P = .615; odds ratio, 1.270; 95% confidence interval: 0.501-3.219) The administration of sodium bicarbonate during prolonged CPR did not significantly improve the rate of ROSC in out-of-hospital cardiac arrest. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

    Directory of Open Access Journals (Sweden)

    Attila Kristóf

    Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

  9. Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

    Science.gov (United States)

    Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

    2012-01-01

    Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

  10. Prolonged fever in peritoneal tuberculosis: A case report

    Science.gov (United States)

    Zein, U.; Irwandi, S.; Habib, H.; Lim, H.; Pasha, M.; Janis, I.; Saragih, R. H.; Ginting, Y.; Effendy-Y S, R.

    2018-03-01

    Peritoneal tuberculosis may lead to delayed diagnosis because of the nonspecific features such as fever, abdominal distension, abdominal tenderness, ascites, and weight loss. Here, wereported a case of prolonged fever and abdominal pain which was due to peritoneal tuberculosis. Initial examinations including acomplete blood test and serologic tests did not lead to the diagnosis. A final diagnosis was made by abdominal CT-scan and laparoscopy combined with histopathological studies. Antituberculous medications provided a good clinical response in this patient.

  11. The incidence of hyponatremia during prolonged ultraendurance exercise.

    Science.gov (United States)

    Noakes, T D; Norman, R J; Buck, R H; Godlonton, J; Stevenson, K; Pittaway, D

    1990-04-01

    Recent studies have shown that potentially fatal hyponatremia can develop during prolonged exercise. To determine the incidence of hyponatremia in athletes competing in ultradistance events, we measured serum sodium levels in 315 of 626 (50%) runners who were treated for collapse after two 90 km ultramarathon footraces (total starters 20,335; total finishers 18,031) and in 101 of 147 (69%) finishers in a 186 km ultratriathlon. In both races the athletes drank fluids with low sodium chloride content (less than 6.8 mmol.l-1). Hyponatremia (serum sodium level less than 130 mmol.l-1) was identified in 27 of 315 (9%) collapsed runners in the 90 km races and in none of the triathletes. In response to diuretic therapy, the runner with the most severe hyponatremia (serum sodium level = 112 mmol.l-1) excreted in excess of 7.5 l dilute urine during the first 17 h of hospitalization. These data suggest that, although symptomatic hyponatremia occurs in less than 0.3% of competitors during prolonged exercise even when they ingest little sodium chloride, it is found in a significant proportion (9%) of collapsed runners. A regulated contraction of the extracellular fluid volume would explain why the majority of athletes maintain normal serum sodium levels even though they develop a significant sodium chloride deficit during prolonged exercise. Alternatively, sodium chloride losses during prolonged exercise may be substantially less than are currently believed. Physicians treating collapsed ultradistance athletes need to be aware that as many as 10% or more of such patients may be hyponatremic.

  12. Risk Factors of Prolonged Hospitalization in Patients with Hyperemesis Gravidarum

    Directory of Open Access Journals (Sweden)

    Hasan Onur Topcu

    2015-03-01

    Conclusion: Number of vomiting per day and maternal serum TSH levels could help physicians to estimate the risk of prolonged hospitalization; however further investigations are needed in large population studies. Identifying the high risk patients is important both for prevention of HEG and beginning appropriate antiemetic treatment to avoid complications to reduce the economic costs. [Cukurova Med J 2015; 40(1.000: 113-118

  13. Translating QT interval prolongation from conscious dogs to humans.

    Science.gov (United States)

    Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

    2017-02-01

    In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

  14. Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

    Science.gov (United States)

    Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

    2014-01-01

    Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

  15. Secondary bacteraemia in adult patients with prolonged dengue fever.

    Science.gov (United States)

    Premaratna, R; Dissanayake, D; Silva, F H D S; Dassanayake, M; de Silva, H J

    2015-03-01

    Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.

  16. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇÝGÝL

    2012-08-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

  17. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇİGİL

    2012-07-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

  18. Dynamics of heterogeneous liners with prolonged plasma creation

    International Nuclear Information System (INIS)

    Aleksandrov, V.V.; Branitskii, A.V.; Volkov, G.S.; Grabovskii, E.V.; Zurin, M.V.; Nedoseev, S.L.; Oleinik, G.M.; Samokhin, A.A.; Smirnov, V.P.; Fedulov, M.V.; Frolov, I.N.; Sasorov, P.V.

    2001-01-01

    Prolonged plasma creation in heterogeneous liners, in which the liner substance is separated into two phase states (a hot plasma and a cold skeleton), is investigated both experimentally and theoretically. This situation is typical of multiwire, foam, and even gas liners in high-current high-voltage facilities. The main mechanisms governing the rate at which the plasma is created are investigated, and the simplest estimates of the creation rate are presented. It is found that, during prolonged plasma creation, the electric current flows through the entire cross section of the produced plasma shell, whose thickness is comparable with the liner radius; in other words, a current skin layer does not form. During compression, such a shell is fairly stable because of its relatively high resilience. It is shown that, under certain conditions, even a thick plasma shell can be highly compressed toward the discharge axis. A simplified numerical simulation of the compression of a plasma shell in a liner with prolonged plasma creation is employed in order to determine the conditions for achieving regimes of fairly compact and relatively stable radial compression of the shell

  19. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    Science.gov (United States)

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  20. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  1. La prolongation de la vie humaine selon Francis Bacon. Ou : quel Tithon voulons-nous être ?

    Directory of Open Access Journals (Sweden)

    Dominique Weber

    2011-07-01

    Full Text Available Afin de comprendre avec exactitude la manière dont Francis Bacon envisage la question de la prolongation de la vie humaine, il faut impérativement examiner l’assise théologique de la réflexion du philosophe à ce sujet. Il convient aussi de restituer l’intégration de cette réflexion dans les objectifs plus amples de la philosophie naturelle nouvelle. Enfin, il est nécessaire de comprendre les dimensions proprement morales de la question. Car la prolongation de la vie humaine n’est pas seulement, au sein de la philosophie naturelle nouvelle, un cas parmi d’autres des recherches qu’il faut désormais effectuer : en réalité, c’est elle qui lui donne et qui lui fixe son sens ; avec elle se joue l’effectivité de l’identité espérée entre science et puissance. Mais il faut encore préciser qu’il ne s’agit aucunement pour l’homme de vieillir pour vieillir : il s’agit pour lui de pouvoir vieillir bien. Les leçons que Bacon tire de la fable de Tithon sont ici véritablement décisives.

  2. Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

    Science.gov (United States)

    Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

    2017-12-01

    Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

  3. Optimization of Pr3+:ZBLAN fiber amplifiers

    DEFF Research Database (Denmark)

    Pedersen, B.; Miniscalco, J. W.; Quimby, R. S.

    1992-01-01

    Experimental parameters have been measured and used in a quantitative model of Pr3+-doped fluorozirconate fiber amplifiers. The optimum cutoff wavelength was determined to be 800 nm and the gain for 400 mW of pump was found to increase from 12 to 34 dB if the NA was increased from 0.15 to 0...

  4. Prøvetagning af grundvand

    DEFF Research Database (Denmark)

    Sørensen, Inga

    Bogen fokuserer på prøveatgning af grundvand og drikkevand til forskellige formål såsom undersøgelse af forurenede grunde, grundvandsmonitering samt produktion af drikkevand. Da grundvand i sagens natur findes under jordoverfladen, beskriver bogen også væsentlige forhold om hydrogeologi og...

  5. Mechanistic prospective for human PrPC conversion to PrPSc: Molecular dynamic insights

    OpenAIRE

    Nooshin Azari; Mohammad Reza Dayer; Nematollah Razmi; Mohammad Saaid Dayer

    2013-01-01

    PrPC conversion to PrPSc isoform is the main known cause for prion diseases including Crutzfeldt-Jakob, Gerstmann-Sträussler-Sheinker syndrome and fatal familial insomnia in human. The precise mechanism underling this conversion is yet to be well understood. In the present work, using the coordinate file of PrPC (available on the Protein Data Bank) as a starting structure, separate molecular dynamic simulations were carried out at neutral and acidic pH in an explicit water box at 37°C and 1 ...

  6. RAVEN Beta Release

    International Nuclear Information System (INIS)

    Rabiti, Cristian; Alfonsi, Andrea; Cogliati, Joshua Joseph; Mandelli, Diego; Kinoshita, Robert Arthur; Wang, Congjian; Maljovec, Daniel Patrick; Talbot, Paul William

    2016-01-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  7. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  8. Quantification of the PR-39 cathelicidin compound in porcine blood by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Smolira, Anna; Hałas, Stanisław; Wessely-Szponder, Joanna

    2015-10-15

    The PR-39 porcine cathelicidin occurs naturally in animal neutrophils. Its main function is antimicrobial activity, which potentially can be used in antibiotic treatments in veterinary medicine. Investigations concerning such a use require the detection and quantification of PR-39 in a given sample. The aim of this work is to determine the concentration of PR-39 contained in porcine blood. Prior to matrix-assisted laser desorption/ionization (MALDI) analysis, the porcine blood sample was subjected to crude extraction in order to release the active form of PR-39 from the neutrophil granules. Next, gel filtration chromatography was performed to separate PR-39 from other cathelicidins present in porcine blood. Positive ion MALDI time-of-flight (TOF) mass spectra of the resulting portion of lyophilisate with unknown PR-39 content were acquired in linear mode. To quantify PR-39 in the lyophilisate sample, the standard addition method was applied. The PR-39 concentration obtained in the lyophilisate sample was then converted into the peptide concentration in porcine blood. The linear fit function of the constructed calibration curve indicates an excellent correlation between the PR-39 peak intensity and the added quantity of synthetic PR-39 (R(2) = 0.994) and a low relative standard deviation of the slope = 1.98%. From the x-intercept of the straight line, we estimated the PR-39 concentration in porcine blood to be 20.5 ± 4.6 ng/mL. The MALDI method was successfully applied for the quantitative analysis of PR-39 found in porcine blood. Compared with other available methods, it is relatively easy, inexpensive and not time-consuming. Despite the method having lower accuracy than the enzyme-linked immunosorbent assay (ELISA), the results obtained here, by a much simpler method, are in good agreement with the literature data. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Prolonged storage of packed red blood cells for blood transfusion.

    Science.gov (United States)

    Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Peña-González, Barbra S

    2015-07-14

    A blood transfusion is an acute intervention, used to address life- and health-threatening conditions on a short-term basis. Packed red blood cells are most often used for blood transfusion. Sometimes blood is transfused after prolonged storage but there is continuing debate as to whether transfusion of 'older' blood is as beneficial as transfusion of 'fresher' blood. To assess the clinical benefits and harms of prolonged storage of packed red blood cells, in comparison with fresh, on recipients of blood transfusion. We ran the search on 1st May 2014. We searched the Cochrane Injuries Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO Host) and two other databases. We also searched clinical trials registers and screened reference lists of the retrieved publications and reviews. We updated this search in June 2015 but these results have not yet been incorporated. Randomised clinical trials including participants assessed as requiring red blood cell transfusion were eligible for inclusion. Prolonged storage was defined as red blood cells stored for ≥ 21 days in a blood bank. We did not apply limits regarding the duration of follow-up, or country where the study took place. We excluded trials where patients received a combination of short- and long-stored blood products, and also trials without a clear definition of prolonged storage. We independently performed study selection, risk of bias assessment and data extraction by at least two review authors. The major outcomes were death from any cause, transfusion-related acute lung injury, and adverse events. We estimated relative risk for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. We identified three randomised clinical trials, involving a total of 120 participants, comparing packed red blood cells with ≥ 21 days storage

  10. Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells.

    Science.gov (United States)

    Renteria, Lissette S; Raj, J Usha; Ibe, Basil O

    2010-12-01

    Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6) cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis.

    Science.gov (United States)

    Stampanoni Bassi, Mario; Iezzi, Ennio; Marfia, Girolama A; Simonelli, Ilaria; Musella, Alessandra; Mandolesi, Georgia; Fresegna, Diego; Pasqualetti, Patrizio; Furlan, Roberto; Finardi, Annamaria; Mataluni, Giorgia; Landi, Doriana; Gilio, Luana; Centonze, Diego; Buttari, Fabio

    2018-04-14

    In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a

  13. Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.

    Science.gov (United States)

    Ciric, Danica; Richard, Charles-Adrien; Moudjou, Mohammed; Chapuis, Jérôme; Sibille, Pierre; Daude, Nathalie; Westaway, David; Adrover, Miguel; Béringue, Vincent; Martin, Davy; Rezaei, Human

    2015-06-01

    Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into a β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment. Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase. Copyright © 2015, American Society for Microbiology. All Rights

  14. Release and Degradation of Microencapsulated Spinosad and Emamectin Benzoate.

    Science.gov (United States)

    Huang, Bin Bin; Zhang, Shao Fei; Chen, Peng Hao; Wu, Gang

    2017-09-07

    The dynamics of release and degradation of the microencapsulation formulation containing spinosad (SP) and emamectin benzoate (EM) were evaluated in the present study. SP and EM were microencapsulated using biodegradable poly-lactic acid (PLA) as the wall material. Their release from and degradation within the prepared SP and EM microspheres (SP-EM-microspheres) were studied. It was found that the encapsulation significantly prolonged the insecticide release. The release could be further extended if the external aqueous phase was pre-saturated with the insecticides and the microspheres were additionally coated with gelatin. On the other hand, increasing the water content of the emulsion or the hydrophilic polycaprolactone (PCL) content in the PLA/PCL mixture accelerated the release. Due to the photolysis and hydrolysis of SP and EM by sunlight, the toxicity of the non-encapsulated insecticides in water declined continuously from 0 through the 9 th day (d), and dissipated in 13 d. In contrast, an aqueous suspension containing 5% SP-EM-microspheres maintained a mostly constant toxicity to Plutella xylostella for 17 d. The biodegradable SP-EM-microspheres showed significantly higher long-term toxicity to P. xylostella due to lower release, reduced photolysis and hydrolysis of the encapsulated insecticides, which were affected by the varied preparation conditions.

  15. Induction of Maltose Release by Light in the Endosymbiont Chlorella variabilis of Paramecium bursaria.

    Science.gov (United States)

    Shibata, Aika; Takahashi, Fumio; Kasahara, Masahiro; Imamura, Nobutaka

    2016-11-01

    The endosymbiotic green algae of Paramecium bursaria are known to release a photosynthate to the host cells. The endosymbiont Chlorella variabilis F36-ZK isolated in Japan releases maltose under acidic conditions, and such release requires both light and low pH. However, whether photosynthate release is due to light sensing by photoreceptors or is merely a consequence of active photosynthesis is unclear. Herein, we studied the effect of light on maltose release from C. variabilis F36-ZK; we measured maltose release using a combination of 1-phenyl-3-methyl-5-pyrazolone derivative and 14 C-tracer methods. Blue (450nm) or red (around 600nm) light was most effective to stimulate maltose release. This suggests that the photosynthetic pathway probably participates in maltose release, because the effective wavelength corresponds to the absorption spectrum of chlorophyll. Furthermore, maltose release was slightly affected by addition of a photosynthetic inhibitor, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, but was abolished by another inhibitor of photosynthesis, 2,5-dibromo-6-isopropyl-3-methyl-1,4-benzoquinone, suggesting that electron flow through photosystem I may be more involved in maltose release. Interestingly, starving F36-ZK cells cultured under prolonged dark conditions did not release maltose but retained their photosynthetic capacity. Our results thus show that maltose release is regulated by light and cellular conditions in endosymbiotic Chlorella. Copyright © 2016. Published by Elsevier GmbH.

  16. Hydraulic release oil tool

    International Nuclear Information System (INIS)

    Mims, M.G.; Mueller, M.D.; Ehlinger, J.C.

    1992-01-01

    This patent describes a hydraulic release tool. It comprises a setting assembly; a coupling member for coupling to drill string or petroleum production components, the coupling member being a plurality of sockets for receiving the dogs in the extended position and attaching the coupling member the setting assembly; whereby the setting assembly couples to the coupling member by engagement of the dogs in the sockets of releases from and disengages the coupling member in movement of the piston from its setting to its reposition in response to a pressure in the body in exceeding the predetermined pressure; and a relief port from outside the body into its bore and means to prevent communication between the relief port and the bore of the body axially of the piston when the piston is in the setting position and to establish such communication upon movement of the piston from the setting position to the release position and reduce the pressure in the body bore axially of the piston, whereby the reduction of the pressure signals that the tool has released the coupling member

  17. APASS Data Release 10

    Science.gov (United States)

    Henden, Arne A.; Levine, Stephen; Terrell, Dirk; Welch, Douglas L.; Munari, Ulisse; Kloppenborg, Brian K.

    2018-06-01

    The AAVSO Photometric All-Sky Survey (APASS) has been underway since 2010. This survey covers the entire sky from 7.5 knowledge of the optical train distortions. With these changes, DR10 includes many more stars than prior releases. We describe the survey, its remaining limitations, and prospects for the future, including a very-bright-star extension.

  18. Release the Prisoners Game

    Science.gov (United States)

    Van Hecke, Tanja

    2011-01-01

    This article presents the mathematical approach of the optimal strategy to win the "Release the prisoners" game and the integration of this analysis in a math class. Outline lesson plans at three different levels are given, where simulations are suggested as well as theoretical findings about the probability distribution function and its mean…

  19. Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor signaling crosstalk in breast cancer models.

    Science.gov (United States)

    Leehy, Katherine A; Truong, Thu H; Mauro, Laura J; Lange, Carol A

    2018-02-01

    Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Prévalence, facteurs associés et prédisposant au syndrome ...

    African Journals Online (AJOL)

    Introduction: Le syndrome métabolique est associé aux maladies cardiovasculaires. L'infection au VIH est devenue aujourd'hui une maladie chronique. L'objectif de cette étude est de déterminer la prévalence, les facteurs associés et prédisposant au syndrome métabolique chez les patients infectés par le VIH sous ...

  1. Der Effekt von Akupunktur in der Prävention von Prüfungsangst

    OpenAIRE

    Krüger, Peter

    2017-01-01

    Prüfungsangst ist ein weit verbreitetes gesellschaftliches Phänomen, das bisher in nur wenigen wissenschaftlichen Ansätzen untersucht wurde. Die Zahl der Studenten, die Gehirn - Doping zur Leistungssteigerung und zur Minimierung von Prüfungsangst nutzen, steigt stetig an. In bisherigen Studien wurde Akupunktur an Herz 7 als vielversprechende Behandlungsalternative dargestellt. Basierend auf diesen Ergebnissen, wurde in dieser Arbeit untersucht, ob eine Einzelpunktakupunktur an Herz 7 die ...

  2. Nitric Oxide-Releasing Silica Nanoparticle-Doped Polyurethane Electrospun Fibers

    Science.gov (United States)

    Koh, Ahyeon; Carpenter, Alexis W.; Slomberg, Danielle L.; Schoenfisch, Mark H.

    2013-01-01

    Electrospun polyurethane fibers doped with nitric oxide (NO)-releasing silica particles are presented as novel macromolecular scaffolds with prolonged NO-release and high porosity. Fiber diameter (119–614 nm) and mechanical strength (1.7–34.5 MPa of modulus) were varied by altering polyurethane type and concentration, as well as the NO-releasing particle composition, size, and concentration. The resulting NO-releasing electrospun nanofibers exhibited ~83% porosity with flexible plastic or elastomeric behavior. The use of N-diazeniumdiolate- or S-nitrosothiol-modified particles yielded scaffolds exhibiting a wide range of NO release totals and durations (7.5 nmol mg−1–0.12 μmol mg−1 and 7 h to 2 weeks, respectively). The application of NO-releasing porous materials as coating for subcutaneous implants may improve tissue biocompatibility by mitigating the foreign body response and promoting cell integration. PMID:23915047

  3. Extended release formulations for local anaesthetic agents.

    Science.gov (United States)

    Weiniger, C F; Golovanevski, L; Domb, A J; Ickowicz, D

    2012-08-01

    Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  4. Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs.

    Science.gov (United States)

    Burka, J F; Eyre, P

    1975-01-01

    Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the formation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and aspirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A release at low concentrations. The possible modes of actions of these drugs are discussed.

  5. Magnetic properties of Pr ions in perovskite-type oxides

    International Nuclear Information System (INIS)

    Sekizawa, K.; Kitagawa, M.; Takano, Y.

    1998-01-01

    Magnetic properties of Pr ions with the controlled valence on the A and B sites of perovskite-type oxides (ABO 3 ) were investigated for two systems. PrSc 1-x Mg x O 3 and BaPr 1-x Bi x O 3 . From the magnetic susceptibility χ versus temperature T curves of PrSc 1-x Mg x O 3 , the χ-T curve for molar Pr 3+ ions on the A site and that of Pr 4+ ions were obtained. The 1/χ-T curves for both ions exhibit the crystalline electric field (CEF) effect and the effective magneticmoment μ eff above 100 K is 3.41 μ B for Pr 3- and 2.58 μ B for Pr 4+ , respectively. The χ-T curve of PrSc 0.8 Mg 0.2 O 3 is similar to that of PrBa 2 Cu 3 O y . In the BaPr 1-x Bi x O 3 system, only one intermediate phase BaPr 0.5 Bi 0.5 O 3 exists, in which Pr and Bi take an ordered arrangement on the B site. The magnetic susceptibility χ for Pr 4+ and that of Pr 3+ in the ordered arrangement with Bi 5- on the B site are much smaller than those for the A site, reflecting the strong CEF effect on the B site. Experimental χ-T curves can be well reproducedby the numerical calculation for Pr 3+ or Pr 4+ ions in the molecular field and the CEF with proper respective parameters. (orig.)

  6. Piperazine derivatives inhibit PrP/PrP(res) propagation in vitro and in vivo.

    Science.gov (United States)

    Leidel, Fabienne; Eiden, Martin; Geissen, Markus; Hirschberger, Thomas; Tavan, Paul; Giese, Armin; Kretzschmar, Hans A; Schätzl, Hermann; Groschup, Martin H

    2014-02-28

    Prion diseases are fatal neurodegenerative disorders, which are not curable and no effective treatment exists so far. The major neuropathological change in diseased brains is the conversion of the normal cellular form of the prion protein PrPc(C) into a disease-associated isoform PrP(Sc). PrP(Sc) accumulates into multimeres and fibrillar aggregates, which leads to the formation of amyloid plaques. Increasing evidence indicates a fundamental role of PrP(Sc) species and its aggregation in the pathogenesis of prion diseases, which initiates the pathological cascade and leads to neurodegeneration accompanied by spongiform changes. In search of compounds that have the potential to interfere with PrP(Sc) formation and propagation, we used a cell based assay for the screening of potential aggregation inhibitors. The assay deals with a permanently prion infected cell line that was adapted for a high-throughput screening of a compound library composed of 10,000 compounds (DIVERset 2, ChemBridge). We could detect six different classes of highly potent inhibitors of PrP(Sc) propagation in vitro and identified piperazine derivatives as a new inhibitory lead structure, which increased incubation time of scrapie infected mice. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

    OpenAIRE

    Sakudo, Akikazu; Onodera, Takashi

    2015-01-01

    Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp ?/?) mice. So far, six types of Prnp ?/? mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not ...

  8. Prion protein with Y145STOP mutation induces mitochondria-mediated apoptosis and PrP-containing deposits in vitro

    International Nuclear Information System (INIS)

    Hachiya, Naomi S.; Watanabe, Kota; Kawabata, Makiko Y.; Jozuka, Akiko; Kozuka, Yoshimichi; Sakasegawa, Yuji; Kaneko, Kiyotoshi

    2005-01-01

    A pathogenic truncation of an amber mutation at codon 145 (Y145STOP) in Gerstmann-Straussler-Scheinker disease (GSS) was investigated through the real-time imaging in living cells, by utilizing GFP-PrP constructs. GFP-PrP(1-144) exhibited an aberrant localization to mitochondria in mouse neuroblastoma neuro2a (N2a) and HpL3-4 cells, a hippocampal cell line established from prnp gene-ablated mice, whereas full-length GFP-PrP did not. The aberrant mitochondrial localization was also confirmed by Western blot analysis. Since GFP-PrP(1-121), as previously reported, and full-length GFP-PrP do not exhibit such mitochondrial localization, the mitochondrial localization of GFP-PrP(1-144) requires not only PrP residues 121-144 (in human sequence) but also COOH-terminal truncation in the current experimental condition. Subsequently, the GFP-PrP(1-144) induced a change in the mitochondrial innermembrane potential (ΔΨ m ), release of cytochrome c from the intermembrane space into the cytosol, and DNA fragmentation in these cells. Non-fluorescent PrP(1-144) also induced the DNA fragmentation in N2a and HpL3-4 cells after the proteasomal inhibition. These data may provide clues as to the molecular mechanism of the neurotoxic property of Y145STOP mutation. Furthermore, immunoelectron microscopy revealed numerous electron-dense deposits in mitochondria clusters of GFP-PrP(1-144)-transfected N2a cells, whereas no deposit was detected in the cells transfected with full-length GFP-PrP. Co-localization of GFP/PrP-immunogold particles with porin-immunogold particles as a mitochondrial marker was observed in such electron-dense vesicular foci, resembling those found in autophagic vacuoles forming secondary lysosomes. Whether such electron-dense deposits may serve as a seed for the growth of amyloid plaques, a characteristic feature of GSS with Y145STOP, awaits further investigations

  9. Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

    Science.gov (United States)

    Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

    2014-07-01

    The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  10. BCR-crosslinking induces a transcription of protein phosphatase component G5PR that is required for mature B-cell survival

    International Nuclear Information System (INIS)

    Huq Ronny, Faisal Mahmudul; Igarashi, Hideya; Sakaguchi, Nobuo

    2006-01-01

    BCR-crosslinking triggers activation-induced cell death (AICD) selectively in the restricted stage of B-cell differentiation. We examined the transcription of a protein phosphatase subunit G5PR in immature and mature B-cells, because absence of this factor augmented cell sensitivity to AICD, associated with increased activation of JNK and Bim. BCR-crosslinking-induced G5pr transcription in AICD-resistant mature splenic IgM lo IgD hi B-cells but not in AICD susceptible immature IgM hi IgD lo B-cells. Thus, G5pr induction correlated with the prevention of AICD; High in mature splenic CD23 hi B-cells but low in immature B-cells of neonatal mice, sub-lethally irradiated mice, or xid mice. Lack of G5pr upregulation was associated with the prolonged activation of JNK. The G5pr cDNA transfection protected an immature B-cell line WEHI-231 from BCR-mediated AICD. The differential expression of G5PR might be responsible for the antigen-dependent selection of B-cells

  11. Predictive factors for oropharyngeal dysphagia after prolonged orotracheal intubation.

    Science.gov (United States)

    Oliveira, Ana Carolina Martins de; Friche, Amélia Augusta de Lima; Salomão, Marina Silva; Bougo, Graziela Chamarelli; Vicente, Laélia Cristina Caseiro

    2017-09-13

    Lesions in the oral cavity, pharynx and larynx due to endotracheal intubation can cause reduction in the local motility and sensitivity, impairing the swallowing process, resulting in oropharyngeal dysphagia. To verify the predictive factors for the development of oropharyngeal dysphagia and the risk of aspiration in patients with prolonged orotracheal intubation admitted to an intensive care unit. This is an observational, analytical, cross-sectional and retrospective data collection study of 181 electronic medical records of patients submitted to prolonged orotracheal intubation. Data on age; gender; underlying disease; associated comorbidities; time and reason for orotracheal intubation; Glasgow scale on the day of the Speech Therapist assessment; comprehension; vocal quality; presence and severity of dysphagia; risk of bronchoaspiration; and the suggested oral route were collected. The data were analyzed through logistic regression. The level of significance was set at 5%, with a 95% Confidence Interval. The prevalence of dysphagia in this study was 35.9% and the risk of aspiration was 24.9%. As the age increased, the altered vocal quality and the degree of voice impairment increased the risk of the presence of dysphagia by 5-; 45.4- and 6.7-fold, respectively, and of aspiration by 6-; 36.4- and 4.8-fold. The increase in the time of orotracheal intubation increased the risk of aspiration by 5.5-fold. Patients submitted to prolonged intubation who have risk factors associated with dysphagia and aspiration should be submitted to an early speech-language/audiology assessment and receive appropriate and timely treatment. The recognition of these predictive factors by the entire multidisciplinary team can minimize the possibility of clinical complications inherent to the risk of dysphagia and aspiration in extubated patients. Copyright © 2017. Published by Elsevier Editora Ltda.

  12. Depressive disorders during weaning from prolonged mechanical ventilation.

    Science.gov (United States)

    Jubran, Amal; Lawm, Gerald; Kelly, Joanne; Duffner, Lisa A; Gungor, Gokay; Collins, Eileen G; Lanuza, Dorothy M; Hoffman, Leslie A; Tobin, Martin J

    2010-05-01

    Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival. A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders. Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score [odds ratio (OR), 1.23; P = 0.007], functional dependence before the acute illness (OR, 1.70, P = 0.03) and history of psychiatric disorders (OR, 3.04, P = 0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61 vs. 33%, P = 0.0001), as was mortality (24 vs. 10%, P = 0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; P = 0.0002); age (OR, 1.06; P = 0.001) and co-morbidity score (OR, 1.24; P = 0.02) also predicted mortality. Depressive disorders were diagnosed in 42% of patients who were being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death.

  13. Spontaneous development of hepatocellular carcinoma with cancer stem cell properties in PR-SET7-deficient livers

    Science.gov (United States)

    Nikolaou, Kostas C; Moulos, Panagiotis; Chalepakis, George; Hatzis, Pantelis; Oda, Hisanobu; Reinberg, Danny; Talianidis, Iannis

    2015-01-01

    PR-SET7-mediated histone 4 lysine 20 methylation has been implicated in mitotic condensation, DNA damage response and replication licensing. Here, we show that PR-SET7 function in the liver is pivotal for maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 phase arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis, accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic regenerative cycles coupled with oncogenic STAT3 activation led to the spontaneous development of hepatic tumors composed of cells with cancer stem cell characteristics. These include a capacity to self-renew in culture or in xenografts and the ability to differentiate to phenotypically distinct hepatic cells. Hepatocellular carcinoma in PR-SET7-deficient mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes. PMID:25515659

  14. Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

    DEFF Research Database (Denmark)

    Hvid, L G; Gejl, Kasper Degn; Bech, R D

    2013-01-01

    Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...... recovery on the contractile function of single muscle fibres obtained from elite athletes....

  15. Hemiplegic Migraine Presenting with Prolonged Somnolence: A Case Report

    Directory of Open Access Journals (Sweden)

    Christian Saleh

    2016-10-01

    Full Text Available Hemiplegic migraine is a rare and complex disease, characterized by migraine with a reversible motor aura. Hemiplegic migraine can be easily misdiagnosed at its first presentation with an atypical severe form of migraine, a stroke, multiple sclerosis, metabolic disorders, conversion disorder or an epilepsy. We present the case of a young 24-year-old male patient, who since the age of 4 years had been having multiple episodes of migraine associated with hemiparesis, paraesthesia, prolonged somnolence, aphasia and confusion. We review the literature and discuss important diagnostic findings in hemiplegic migraine to help establishing a prompt diagnosis.

  16. Intestinal ultrastructure after prolonged use of an elemental diet

    International Nuclear Information System (INIS)

    Hugon, J.S.

    1976-01-01

    The role of 3 diets (Purina, whole casein and hydrolyzed casein) on the morphological aspect of the intestinal mucosa has been studied in adult mice, irradiated with a single dose of 950 R or with 4 doses of 600 R. The experimental group receiving the hydrolyzed casein exhibited always the fastest recovery. 45 days after a single irradiation, some alterations of columnar cells were still noted in the other groups. The prolonged use of an hydrolyzed casein (6 months) did not alter the structure of the mucosal cells. (orig.) [de

  17. Complete maternal and fetal recovery after prolonged cardiac arrest.

    Science.gov (United States)

    Selden, B S; Burke, T J

    1988-04-01

    A case of complete maternal and fetal recovery after prolonged cardiac arrest from massive lidocaine overdose is presented. A 27-year-old woman at 15 weeks gestation had a complete neurologic recovery after 22 minutes of CPR, including 19 minutes of electromechanical dissociation and asystole, with normal fetal heart function and fetal motion confirmed by ultrasound immediately after resuscitation. The patient delivered a healthy and neurologically normal infant at 40 weeks gestation. This is the longest cardiac arrest in early pregnancy reported in the medical literature with normal maternal and fetal outcome.

  18. How long would SDH/SONET be prolonged?

    Science.gov (United States)

    Tao, Zhiyong; Mao, Qian

    2004-04-01

    As we all know, the increasing speed of data traffic is exceeding gradually from voice in today"s communication network. The main reason is the explosive of Internet. The controversy with IP over ATM/SDH/Optical becomes hotter and hotter, Many people in the telecommunication field are doubt: HOW LONG WOULD SDH/SONET BE PROLONGED? WHAT KIND OF SDH EQUIPMENTS COULD BE USED IN THE NETWORK? With the analysis from several aspects: services in the network, new development with SDH technology, market in transport equipment, This paper is considered that the SDH with some new features would be predominant transport technology in the recent years.

  19. Disseminated Mycobacterium celatum disease with prolonged pulmonary involvement

    DEFF Research Database (Denmark)

    Patsche, Cecilie Blenstrup; Svensson, Erik; Wejse, Christian

    2014-01-01

    Mycobacterium celatum is a rare cause of human infection, causing disseminated disease in immunosuppressed individuals. Infections localized to the lungs and the lymph nodes have also been reported in immunocompetent individuals. The existing literature on the subject is limited as are experiences...... with treatment regimens and durations. In the case presented herein, two different treatment regimens were applied to an immunocompromised HIV-negative patient with primary skin involvement and extensive pulmonary involvement due to suspected relapse on isoniazid, ethambutol, and clarithromycin treatment....... The treatment regimen was changed to azithromycin, ciprofloxacin, and pyrazinamide and the treatment duration was prolonged to a total of 24 months, with good effect....

  20. New developments in the treatment of primary insomnia in elderly patients: focus on prolonged-release melatonin

    OpenAIRE

    Vigo DE; Vidal MF; Cardinali DP

    2012-01-01

    Daniel P Cardinali, María F Vidal, Daniel E VigoDepartment of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, ArgentinaAbstract: A temporal relationship between the nocturnal rise in melatonin secretion and the increase in sleep propensity at the beginning of the night, coupled with the sleep-promoting effects of exogenous melatonin, indicate that melatonin is involved in the regulation of sleep. This action is...

  1. Microstructure and martensitic transformation of Ni-Ti-Pr alloys

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Chunwang [Inner Mongolia University of Technology, College of Science, Hohhot (China); Shanghai Maritime University, College of Arts and Sciences, Shanghai (China); Zhao, Shilei; Jin, Yongjun; Hou, Qingyu [Inner Mongolia University of Technology, College of Science, Hohhot (China); Guo, Shaoqiang [Beihang University, Key Laboratory of Micro-nano Measurement, Manipulation and Physics (Ministry of Education), Department of Physics, Beijing (China)

    2017-09-15

    The effect of Pr addition on the microstructure and martensitic transformation behavior of Ni{sub 50}Ti{sub 50-x}Pr{sub x} (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9) alloys were investigated experimentally. Results show that the microstructures of Ni-Ti-Pr alloys consist of the NiTi matrix and the NiPr precipitate with the Ti solute. The martensitic transformation start temperature decreases gradually with the increase in Pr fraction. The stress around NiPr precipitates is responsible for the decrease in martensitic transformation temperature with the increase in Pr fraction in Ni-Ti-Pr alloys. (orig.)

  2. Bi3+–Pr3+ energy transfer processes and luminescent properties of LuAG:Bi,Pr and YAG:Bi,Pr single crystalline films

    International Nuclear Information System (INIS)

    Zorenko, Y.; Gorbenko, V.; Savchyn, V.; Zorenko, T.; Nikl, M.; Mares, J.A.; Beitlerova, A.; Jary, V.

    2013-01-01

    Absorption, cathodoluminescence, excitation spectra of photoluminescence (PL) and PL decay kinetics were studied at 300 K for the double doped with Bi 3+ –Pr 3+ and separately doped with Bi 3+ and Pr 3+ Lu 3 Al 5 O 12 (LuAG) and Y 3 Al 5 O 12 (YAG) single crystalline film (SCF) phosphors grown by the liquid phase epitaxy method. The emission bands in the UV range arising from the intrinsic radiative transitions of Bi 3+ based centers, and emission bands in the visible range, related to the luminescence of excitons localized around Bi 3+ based centers, were identified both in Bi–Pr and Bi-doped LuAG and YAG SCFs. The energy transfer processes from the host lattice simultaneously to Bi 3+ and Pr 3+ ions and from Bi 3+ to Pr 3+ ions were investigated. Competition between Pr 3+ and Bi 3+ ions in the energy transfer processes from the LuAG and YAG hosts was evidenced. The strong decrease of the intensity of Pr 3+ luminescence both in LuAG:Pr and YAG:Pr SCFs phosphors, grown from Bi 2 O 3 flux, is observed due to the quenching influence of Bi 3+ flux related impurity. Due to overlap of the UV emission band of Bi 3+ centers with the f–d absorption bands of Pr 3+ ions in the UV range and the luminescence of excitons localized around Bi ions with the f–f absorption bands of Pr 3+ ions in the visible range, an effective energy transfer from Bi 3+ ions to Pr 3+ ions takes place in LuAG:Bi,Pr and YAG:Bi,Pr SCFs, resulting in the appearance of slower component in the decay kinetics of the Pr 3+ d–f luminescence. -- Highlights: • Bi and Pr doped film phosphor grown by liquid phase epitaxy method. • Energy transfer from Bi 3+ to Pr 3+ ions. • Strong quenching of the Pr 3+ luminescence by Bi 3+ co-dopant

  3. Præverbalitet i Musikterapi

    Directory of Open Access Journals (Sweden)

    Niels Hannibal

    2003-03-01

    Full Text Available Denne artikel er en oversættelse af mit foredrag på verdenskongressen i musikterapi i Oxford 2002. Den er baseret på min ph.d. afhandling »Præverbal Overføring i Musikterapi«, der blev forsvaret juni 2001. Formålet med artiklen er at validere min forskning om præverbal overføring i musikterapi i den musikalske interaktion gennem formidling af den pragmatiske anvendelse. I artiklen argumenterer jeg for anvendelse af Sterns psykologiske udviklingsteori og Sotolorow & Atwoodes teori om psykoterapi som fortolkningskontekst for musikalsk interaktion, når fokus er interaktion, relation og overføring. Det illustreres gennem en case analyse hvorledes begreberne kan anvendes på kliniske data. Det konkluderes at psykologisk teori og tænkning er nødvendig for at kunne forstå og beskrive musikalsk interaktion i et psykologisk perspektiv.

  4. Favoriser la prévention

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les limites de ces axes d'in- tervention ... Le principal intérêt d'une stratégie nationale de prévention réside .... ricain pour le Développement Intégré (RADI,) le Comité de. Lutte contre ... logistiques et humains suffisants pour prendre en charge les cas. ... niveaux, participent à une dispersion des initiatives, des stratégies et ...

  5. Insight into Eu redox and Pr

    NARCIS (Netherlands)

    Zhou, Rongfu; Lin, Litian; Liu, Chunmeng; Dorenbos, P.; Tao, Ye; Huang, Yan; Liang, Hongbin

    2018-01-01

    A series of Ln-doped KSrPO4 (Ln = Ce3+, Eu3+, Eu2+, Pr3+) phosphors are prepared through a high-temperature solid-state method. The KSrPO4 compound is confirmed to possess a β-K2SO4 structure with the Pnma

  6. Advancing tendencies? PR leadership, general leadership, and leadership pedagogy

    OpenAIRE

    McKie, D; Willis, P

    2014-01-01

    What are the best ways to advance PR leadership? In exploring answers, we consider the last two decades of PR literature and identify two main tendencies. We link those two with general leadership literature and practices, as well as with literature on leadership pedagogy. We conclude that, rather than recent moves to look within the field, without self-reflection, to existing PR perspectives and figures for solutions, looking outwards has greater potential to transform not only the PR leader...

  7. In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release

    DEFF Research Database (Denmark)

    Larsen, Dorrit Bjerg; Joergensen, Stig; Olsen, Niels Vidiendal

    2002-01-01

    A non-randomized cross-over study was performed with bupivacaine HCl (5 mg x ml(-1)) aqueous solution and bupivacaine free base (4.44 mg x ml(-1)) in Viscoleo/castor oil 2:1 (v/v) administered s.c. to male Wistar rats. Plasma levels were analyzed by LC-MS. Plasma profiles obtained after...... administration of oily solution showed a prolonged bupivacaine release with lower peak plasma levels as compared to administration of an aqueous formulation applied in the same compartment. t(1/2), t(max), C(max) and AUC(0-infinity) for the aqueous solution were 63+/-8 min, 19+/-16 min, 194+/-46 ng x ml(-1......) and 25,000+/-3000 ng min x ml(-1), respectively, while the corresponding data for the oil solution were 368+/-89 min, 334+/-186 min, 36+/-25 ng x ml(-1) and 25,000+/-6000 ng x min x ml(-1). The present data indicate the potential of designing an oil formulation of bupivacaine with a prolonged local...

  8. Decontamination for free release

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, K A; Elder, G R [Bradtec Ltd., Bristol (United Kingdom)

    1997-02-01

    Many countries are seeking to treat radioactive waste in ways which meet the local regulatory requirements, but yet are cost effective when all contributing factors are assessed. In some countries there are increasing amounts of waste, arising from nuclear plant decommissioning, which are categorized as low level waste: however with suitable treatment a large part of such wastes might become beyond regulatory control and be able to be released as non-radioactive. The benefits and disadvantages of additional treatment before disposal need to be considered. Several processes falling within the overall description of decontamination for free release have been developed and applied, and these are outlined. In one instance the process seeks to take advantage of techniques and equipment used for decontaminating water reactor circuits intermittently through reactor life. (author). 9 refs, 1 fig., 3 tabs.

  9. Atmospheric Release Advisory Capability

    International Nuclear Information System (INIS)

    Dickerson, M.H.; Gudiksen, P.H.; Sullivan, T.J.

    1983-02-01

    The Atmospheric Release Advisory Capability (ARAC) project is a Department of Energy (DOE) sponsored real-time emergency response service available for use by both federal and state agencies in case of a potential or actual atmospheric release of nuclear material. The project, initiated in 1972, is currently evolving from the research and development phase to full operation. Plans are underway to expand the existing capability to continuous operation by 1984 and to establish a National ARAC Center (NARAC) by 1988. This report describes the ARAC system, its utilization during the past two years, and plans for its expansion during the next five to six years. An integral part of this expansion is due to a very important and crucial effort sponsored by the Defense Nuclear Agency to extend the ARAC service to approximately 45 Department of Defense (DOD) sites throughout the continental US over the next three years

  10. Border cell release

    DEFF Research Database (Denmark)

    Mravec, Jozef

    2017-01-01

    Plant border cells are specialised cells derived from the root cap with roles in the biomechanics of root growth and in forming a barrier against pathogens. The mechanism of highly localised cell separation which is essential for their release to the environment is little understood. Here I present...... in situ analysis of Brachypodium distachyon, a model organism for grasses which possess type II primary cell walls poor in pectin content. Results suggest similarity in spatial dynamics of pectic homogalacturonan during dicot and monocot border cell release. Integration of observations from different...... species leads to the hypothesis that this process most likely does not involve degradation of cell wall material but rather employs unique cell wall structural and compositional means enabling both the rigidity of the root cap as well as detachability of given cells on its surface....

  11. Energy released in fission

    International Nuclear Information System (INIS)

    James, M.F.

    1969-05-01

    The effective energy released in and following the fission of U-235, Pu-239 and Pu-241 by thermal neutrons, and of U-238 by fission spectrum neutrons, is discussed. The recommended values are: U-235 ... 192.9 ± 0.5 MeV/fission; U-238 ... 193.9 ± 0.8 MeV/fission; Pu-239 ... 198.5 ± 0.8 MeV/fission; Pu-241 ... 200.3 ± 0.8 MeV/fission. These values include all contributions except from antineutrinos and very long-lived fission products. The detailed contributions are discussed, and inconsistencies in the experimental data are pointed out. In Appendix A, the contribution to the total useful energy release in a reactor from reactions other than fission are discussed briefly, and in Appendix B there is a discussion of the variations in effective energy from fission with incident neutron energy. (author)

  12. Genetic determinants of P wave duration and PR segment

    NARCIS (Netherlands)

    Verweij, Niek; Mateo Leach, Irene; van den Boogaard, Malou; van Veldhuisen, Dirk J.; Christoffels, Vincent M.; Hillege, Hans L.; van Gilst, Wiek H.; Barnett, Phil; de Boer, Rudolf A.; van der Harst, Pim

    2014-01-01

    The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic loci for PR interval, but it remains to be determined

  13. Genetic Determinants of P Wave Duration and PR Segment

    NARCIS (Netherlands)

    Verweij, Niek; Mateo Leach, Irene; van den Boogaard, Malou; van Veldhuisen, Dirk J.; Christoffels, Vincent M.; Hillege, Hans L.; van Gilst, Wiek H.; Barnett, Phil; de Boer, Rudolf A.; van der Harst, Pim

    Background-The PR interval on the ECG reflects atrial depolarization and atrioventricular nodal delay which can be partially differentiated by P wave duration and PR segment, respectively. Genome-wide association studies have identified several genetic loci for PR interval, but it remains to be

  14. On orbits and admissible subalgebras for the PR groups

    International Nuclear Information System (INIS)

    Lebedenko, V.M.

    1977-01-01

    The PR-groups (Lie groups with commutation relations of [Hsub(i),Hsub(0)] = rsub(ij)Hsub(i) (i< j)-type) are investigated within the Kirillov orbit method. Orbits for all the PR-groups are constructed in a general form. For some classes of PR-groups orbits and admissible subalgebras are obtained in an explicit form

  15. Slow-release fertilizer

    Science.gov (United States)

    Ming, Douglas W.; Golden, D. C.

    1992-10-01

    A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

  16. EIA new releases

    International Nuclear Information System (INIS)

    1994-12-01

    This report was prepared by the Energy Information Administration. It contains news releases on items of interest to the petroleum, coal, nuclear, electric and alternate fuels industries ranging from economic outlooks to environmental concerns. There is also a listing of reports by industry and an energy education resource listing containing sources for free or low-cost energy-related educational materials for educators and primary and secondary students

  17. Atmospheric release advisory capability

    International Nuclear Information System (INIS)

    Sullivan, T.J.

    1981-01-01

    The ARAC system (Atmospheric Release Advisory Capability) is described. The system is a collection of people, computers, computer models, topographic data and meteorological input data that together permits a calculation of, in a quasi-predictive sense, where effluent from an accident will migrate through the atmosphere, where it will be deposited on the ground, and what instantaneous and integrated dose an exposed individual would receive

  18. Slow-release fertilizer

    Science.gov (United States)

    Ming, Douglas W. (Inventor); Golden, Dadigamuwage C. (Inventor)

    1995-01-01

    A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

  19. Contact: Releasing the news

    Science.gov (United States)

    Pinotti, Roberto

    The problem of mass behavior after man's future contacts with other intelligences in the universe is not only a challenge for social scientists and political leaders all over the world, but also a cultural time bomb as well. In fact, since the impact of CETI (Contact with Extraterrestrial Intelligence) on human civilization, with its different cultures, might cause a serious socio-anthropological shock, a common and predetermined worldwide strategy is necessary in releasing the news after the contact, in order to keep possible manifestations of fear, panic and hysteria under control. An analysis of past studies in this field and of parallel historical situations as analogs suggests a definite "authority crisis" in the public as a direct consequence of an unexpected release of the news, involving a devastating "chain reaction" process (from both the psychological and sociological viewpoints) of anomie and maybe the collapse of today's society. The only way to prevent all this is to prepare the world's public opinion concerning contact before releasing the news, and to develop a long-term strategy through the combined efforts of scientists, political leaders, intelligence agencies and the mass media, in order to create the cultural conditions in which a confrontation with ETI won't affect mankind in a traumatic way. Definite roles and tasks in this multi-level model are suggested.

  20. ERYTHEMA NODOSUM AND PROLONGED FEVER ASSOCIATED TO SECONDARY HYPERPARATHYROIDISM

    Directory of Open Access Journals (Sweden)

    Galimberti R

    2005-08-01

    Full Text Available SUMMARYSecondary hyperparathyroidism is one of the main deragements caused by chronic renal failure, and parathyroid hormone is considered one of the toxins of the uremic syndrome. Prolonged fever due to primary hyperparathyroidism have already been described in the literature but not yet as induced by secondary hyperparathyroidism. In this case report a patient suffering from an erythema nodosum and prolonged fever associated to secondary hyperparathyroidism that disappeared through subtotal parathyroidectomy is presented.RESUMENEl hiperparatiroidismo secundario es uno de los principales disturbios causados por la insuficiencia renal crónica, y la paratohormona es considerada una de las toxinas del sindrome urémico. El sindrome febril prolongado secundario a hiperparatiroidismo primario ya ha sido descripto en la literatura, aunque no lo ha sido aun el inducido por hiperparatiroidismo secundario. En el presente reporte se presenta un caso de eritema nodoso y sindrome febril prolongado asociado a hiperparatiroidismo secundario y que resolvió luego de efectuada una paratiroidectomía subtotal.

  1. Risk Factors for Prolonged Treatment of Whiplash-Associated Disorders.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Oka

    Full Text Available Whiplash-associated disorders (WAD are the most common injuries that are associated with car collisions in Japan and many Western countries. However, there is no clear evidence regarding the potential risk factors for poor recovery from WAD. Therefore, we used an online survey of the Japanese population to examine the association between potential risk factors and the persistence of symptoms in individuals with WAD.An online survey was completed by 127,956 participants, including 4,164 participants who had been involved in a traffic collision. A random sample of the collision participants (n = 1,698 were provided with a secondary questionnaire. From among the 974 (57.4% respondents to the secondary questionnaire, we selected 183 cases (intractable neck pain that was treated over a period of 6 months and 333 controls (minor neck pain that was treated within 3 months. Multivariable logistic regression analysis was used to evaluate the potential risk factors for prolonged treatment of WAD.Female sex, the severity of the collision, poor expectations of recovery, victim mentality, dizziness, numbness or pain in the arms, and lower back pain were associated with a poor recovery from WAD.In the present study, the baseline symptoms (dizziness, numbness or pain in the arms, and lower back pain had the strongest associations with prolonged treatment for WAD, although the psychological and behavioral factors were also important. These risk factors should be considered when evaluating patients who may have the potential for poor outcomes.

  2. Prolonged preconditioning with natural honey against myocardial infarction injuries.

    Science.gov (United States)

    Eteraf-Oskouei, Tahereh; Shaseb, Elnaz; Ghaffary, Saba; Najafi, Moslem

    2013-07-01

    Potential protective effects of prolonged preconditioning with natural honey against myocardial infarction were investigated. Male Wistar rats were pre-treated with honey (1%, 2% and 4%) for 45 days then their hearts were isolated and mounted on a Langendorff apparatus and perfused with a modified Krebs-Henseleit solution during 30 min regional ischemia fallowed by 120 min reperfusion. Two important indexes of ischemia-induced damage (infarction size and arrhythmias) were determined by computerized planimetry and ECG analysis, respectively. Honey (1% and 2%) reduced infarct size from 23±3.1% (control) to 9.7±2.4 and 9.5±2.3%, respectively (Phoney (1%) significantly reduced (PHoney (1% and 2%) also significantly decreased number of ventricular ectopic beats (VEBs). In addition, incidence and duration of reversible ventricular fibrillation (Rev VF) were lowered by honey 2% (Phoney produced significant reduction in the incidences of VT, total and Rev VF, duration and number of VT. The results showed cardioprotective effects of prolonged pre-treatment of rats with honey following myocardial infarction. Maybe, the existence of antioxidants and energy sources (glucose and fructose) in honey composition and improvement of hemodynamic functions may involve in those protective effects.

  3. Prolonged fasting impairs neural reactivity to visual stimulation.

    Science.gov (United States)

    Kohn, N; Wassenberg, A; Toygar, T; Kellermann, T; Weidenfeld, C; Berthold-Losleben, M; Chechko, N; Orfanos, S; Vocke, S; Laoutidis, Z G; Schneider, F; Karges, W; Habel, U

    2016-01-01

    Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

  4. Effect of prolonged exposure to low antigen concentration for sensitization

    International Nuclear Information System (INIS)

    Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

    2003-01-01

    The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

  5. Survival without sequelae after prolonged cardiopulmonary resuscitation after electric shock.

    Science.gov (United States)

    Motawea, Mohamad; Al-Kenany, Al-Sayed; Hosny, Mostafa; Aglan, Omar; Samy, Mohamad; Al-Abd, Mohamed

    2016-03-01

    "Electrical shock is the physiological reaction or injury caused by electric current passing through the human body. It occurs upon contact of a human body part with any source of electricity that causes a sufficient current through the skin, muscles, or hair causing undesirable effects ranging from simple burns to death." Ventricular fibrillation is believed to be the most common cause of death after electrical shock. "The ideal duration of cardiac resuscitation is unknown. Typically prolonged cardiopulmonary resuscitation is associated with poor neurologic outcomes and reduced long term survival. No consensus statement has been made and traditionally efforts are usually terminated after 15-30 minutes." The case under discussion seems worthy of the somewhat detailed description given. It is for a young man who survived after 65 minutes after electrical shock (ES) after prolonged high-quality cardiopulmonary resuscitation (CPR), multiple defibrillations, and artificial ventilation without any sequelae. Early start of adequate chest compressions and close adherence to advanced cardiac life support protocols played a vital role in successful CPR.

  6. Paternal work stress and prolonged time to pregnancy.

    Science.gov (United States)

    Lee, Mi-Sun; Paek, Domyung; Eum, Ki-Do; Siegrist, Johannes; Li, Jian; Lee, Hye-Eun; Cho, Sung-Il

    2009-01-01

    The aim of this study was to explore an association between psychosocial stress at work in married men and their spouses' prolonged time to pregnancy (TTP). All married male workers of a large Korean petrochemical enterprise and their wives fulfilling the selection criteria were included. Main selection criteria were lack of use of contraceptives and experienced pregnancy in recent past. Data were available from 322 couples. Psychosocial stress at work was measured by the effort-reward imbalance questionnaire. Prolonged TTP was measured by the "TTP questionnaire". After adjustment for confounding effects of demographic and life-style characteristics and benzene exposure, delayed TTP, defined by frequency of first-cycle pregnancy, was associated with one standard deviation (SD) increase of the effort-reward ratio in the chronically stressed group of married men (OR = 0.47; 95% CI = 0.22-0.99) in logistic regression analysis. A similar, but somewhat weaker effect, was found for the overall group (OR = 0.67; 95% CI = 0.47-0.94). Paternal stress at work, as measured by effort-reward imbalance, seemed to be associated with a decreased number of conceptions in the first menstrual cycle.

  7. Lumbosacral Plexus Injury and Brachial Plexus Injury Following Prolonged Compression

    Directory of Open Access Journals (Sweden)

    Chung-Lan Kao

    2006-11-01

    Full Text Available We report the case of a 36-year-old woman who developed right upper and lower limb paralysis with sensory deficit after sedative drug overdose with prolonged immobilization. Due to the initial motor and sensory deficit pattern, brachial plexus injury or C8/T1 radiculopathy was suspected. Subsequent nerve conduction study/electromyography proved the lesion level to be brachial plexus. Painful swelling of the right buttock was suggestive of gluteal compartment syndrome. Elevation of serum creatine phosphokinase and urinary occult blood indicated rhabdomyolysis. The patient received medical treatment and rehabilitation; 2 years after the injury, her right upper and lower limb function had recovered nearly completely. As it is easy to develop complications such as muscle atrophy and joint contracture during the paralytic period of brachial plexopathy and lumbosacral plexopathy, early intervention with rehabilitation is necessary to ensure that the future limb function of the patient can be recovered. Our patient had suspected gluteal compartment syndrome that developed after prolonged compression, with the complication of concomitant lumbosacral plexus injury and brachial plexus injury, which is rarely reported in the literature. A satisfactory outcome was achieved with nonsurgical management.

  8. Influence of a Prolonged Tennis Match Play on Serve Biomechanics.

    Directory of Open Access Journals (Sweden)

    Caroline Martin

    Full Text Available The aim of this study was to quantify kinematic, kinetic and performance changes that occur in the serve throughout a prolonged tennis match play. Serves of eight male advanced tennis players were recorded with a motion capture system before, at mid-match, and after a 3-hour tennis match. Before and after each match, electromyographic data of 8 upper limb muscles obtained during isometric maximal voluntary contraction were compared to determine the presence of muscular fatigue. Vertical ground reaction forces, rating of perceived exertion, ball speed, and ball impact height were measured. Kinematic and upper limb kinetic variables were computed. The results show decrease in mean power frequency values for several upper limb muscles that is an indicator of local muscular fatigue. Decreases in serve ball speed, ball impact height, maximal angular velocities and an increase in rating of perceived exertion were also observed between the beginning and the end of the match. With fatigue, the majority of the upper limb joint kinetics decreases at the end of the match. No change in timing of maximal angular velocities was observed between the beginning and the end of the match. A prolonged tennis match play may induce fatigue in upper limb muscles, which decrease performance and cause changes in serve maximal angular velocities and joint kinetics. The consistency in timing of maximal angular velocities suggests that advanced tennis players are able to maintain the temporal pattern of their serve technique, in spite of the muscular fatigue development.

  9. Evolution of perceived footwear comfort over a prolonged running session.

    Science.gov (United States)

    Hintzy, F; Cavagna, J; Horvais, N

    2015-12-01

    The purpose of this study was to investigate the subjective perception of overall footwear comfort over a prolonged running session. Ten runners performed two similar sessions consisting of a 13-km trail run (5 laps of 2.6 km) as fast as possible. The overall footwear comfort was evaluated before running and at the end of each lap with a 150-mm visual analogic scale, as well as speed, heart rate and rate of perceived exertion. The results showed that both overall footwear comfort and speed decreased consistently during the run session, and significantly after 44 min of running (i.e. the 3rd lap). It could be hypothesized that the deterioration of overall footwear comfort was explained by mechanical and energetical parameter changes with time and/or fatigue occurring at the whole body, foot and footwear levels. These results justify the use of a prolonged running test for running footwear comfort evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Muscular soreness following prolonged intermittent high-intensity shuttle running.

    Science.gov (United States)

    Thompson, D; Nicholas, C W; Williams, C

    1999-05-01

    The aim of this study was to examine the impact of prolonged intermittent high-intensity shuttle running on soreness and markers of muscle damage. Sixteen males took part in the study, half of whom were assigned to a running group and half to a resting control group. The exercise protocol involved 90 min of intermittent shuttle running and walking (Loughborough Intermittent Shuttle Test: LIST), reflecting the activity pattern found in multiple-sprint sports such as soccer. Immediately after exercise, there was a significant increase (P < 0.05) in serum activities of creatine kinase and aspartate aminotransferase, and values remained above baseline for 48 h (P < 0.05). Median peak activities of creatine kinase and aspartate aminotransferase occurred 24 h post-exercise and were 774 and 43 U x l(-1), respectively. The intensity of general muscle soreness, and in the specific muscles investigated, was greater than baseline for 72 h after the shuttle test (P < 0.05), peaking 24-48 h post-exercise (P < 0.05). Muscle soreness was not correlated with either creatine kinase or aspartate aminotransferase activity. Soreness was most frequently reported in the hamstrings. Neither soreness nor serum enzyme activity changed in the controls over the 4 day observation period. It appears that unaccustomed performance of prolonged intermittent shuttle running produces a significant increase in both soreness and markers of muscle damage.

  11. AVS-1357 inhibits melanogenesis via prolonged ERK activation.

    Science.gov (United States)

    Kim, Dong-Seok; Lee, Hyun-Kyung; Park, Seo-Hyoung; Chae, Chong Hak; Park, Kyoung-Chan

    2009-08-01

    In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a novel skin-whitening compound. AVS-1357 was found to significantly inhibit melanin production in a dose-dependent manner; however, it did not directly inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged activation of extracellular signal-regulated kinase (ERK) and Akt, while it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase. It has been reported that the activation of ERK and/or Akt is involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059 dramatically increased melanogenesis, whereas LY294002 had no effect. Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the downregulation of MITF and tyrosinase. These findings suggest that the effects of AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS-1357-induced prolonged ERK activation. Taken together, our results indicate that AVS-1357 has the potential as a new skin whitening agent.

  12. PERAN DAN STRATEGI KONSULTAN PR DALAM KAMPANYE POLITIK INDONESIA (STUDI KASUS DI TANGERANG SELATAN

    Directory of Open Access Journals (Sweden)

    Novi Erlita

    2015-11-01

    Full Text Available His study used a case study that describes circumstances or events that occur in the South Tangerang election as a public relations consultant efforts in Indonesia's political campaign. Various strategies and activities of PR Consultants in South Tangerang first round of elections by political parties to attract the votes and sympathy of the masses. Many things done, starting with the media utilizing PR (Press Release print and website mediated political party, take direct action against the villages of the people distributing food, providing support to mothers during informal gatherings, open campaigning, as well as campaigns involving voters directly. While the lure voters to vote is the responsibility of a political party's election campaign team. How that is done is also quite diverse, ranging from positive campaign, negative campaign / black campaign, even to the black propaganda. Negative campaigning is done to bring down opponents by distributing leaflets whose content contains weaknesses and ugliness opponent.   Dalam penelitian ini digunakan studi kasus yang memaparkan situasi atau peristiwa yang terjadi dalam proses Pilkada Tangerang Selatan sebagai upaya konsultan PR dalam kampanye politik Indonesia. Berbagai strategi dan aktivitas Konsultan PR pada Pilkada Tangerang Selatan putaran pertama dilakukan oleh partai politik demi menarik perolehan suara dan simpati massa. Banyak hal dilakukan, mulai dengan memanfaatkan media humas (Press Release dimedia cetak maupun website parpol, melakukan aksi langsung ke kampung-kampung rakyat membagikan sembako, memberikan bantuan pada ibu-ibu majelis ta’lim, melakukan kampanye terbuka, serta kampanye yang melibatkan pemilih langsung. Sedangkan untuk menarik simpati pemilih suara yang menjadi tanggung jawab tim pemenangan pemilu partai politik. Cara yang dilakukanpun cukup beragam, mulai dari kampanye positif, kampanye negatif/black campaign, bahkan sampai pada black propaganda. Kampanye negatif

  13. Drug delivery systems with modified release for systemic and biophase bioavailability.

    Science.gov (United States)

    Leucuta, Sorin E

    2012-11-01

    This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

  14. Synthesis and characterization of emamectin-benzoate slow-release microspheres with different surfactants.

    Science.gov (United States)

    Wang, Yan; Wang, Anqi; Wang, Chunxin; Cui, Bo; Sun, Changjiao; Zhao, Xiang; Zeng, Zhanghua; Shen, Yue; Gao, Fei; Liu, Guoqiang; Cui, Haixin

    2017-10-06

    Pesticide slow-release formulations provide a way to increase the efficiency of active components by reducing the amount of pesticide that needs to be applied. Slow-release formulations also increase the stability and prolong the control effect of photosensitive pesticides. Surfactants are an indispensable part of pesticide formulations, and the choice of surfactant can strongly affect formulation performance. In this study, emamectin-benzoate (EMB) slow-release microspheres were prepared by the microemulsion polymerization method. We explored the effect of different surfactants on the particle size and dispersity of EMB in slow-release microspheres. The results indicated that the samples had uniform spherical shapes with an average diameter of 320.5 ±5.24 nm and good dispersity in the optimal formulation with the polymeric stabilizer polyvinyl alcohol (PVA) and composite non-ionic surfactant polyoxyethylene castor oil (EL-40). The optimal EMB pesticide slow-release microspheres had excellent anti-photolysis performance, stability, controlled release properties, and good leaf distribution. These results demonstrated that EMB slow-release microspheres are an attractive candidate for improving pesticide efficacy and prolonging the control effect of EMB in the environment.

  15. Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

    Science.gov (United States)

    Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

    2018-01-01

    Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

  16. Sol-gel encapsulation for controlled drug release and biosensing

    Science.gov (United States)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  17. Die prädikatsergänzung (das prädikatsattribut in der Slovenischen Syntax

    Directory of Open Access Journals (Sweden)

    Breda Pogorelec

    1972-12-01

    Full Text Available In der vorliegenden Abhandlung wird die erwähnte Problematik in der slovenischen grammatischen -Überlieferung behandelt und mit interessanten Ergebnissen vor allem der tschechischen Sprachtheorie ergänzt, es wird der Terminus Prädikatsergänzung gegenüber dem Terminus Prädikatsattribut begründet; auf dieser Grundlage werden auch die bisher behandelten Arten von Prädikatsergänzungen mit neuen ergänzt. Dabei findet wenn nur möglich das einfache Transformationsverfahren Verwendung, das die Veranschaulichung der stufenweisen Determinierung durch das Prädikatsattribut ermöglicht. Das Material entstammt vorwiegend der Sprache der Kunst, der Grund dafür ist vor allem in der Tatsache zu suchen, daß in dieser Sprache dieser Form die Rolle eines natürlichen Kondensators zufällt, weshalb sie verhältnismäßig häufig vorkommt. Die Abhandlung befaßt sich eingehender auch mit dem Problem der Wortfolge und berührt auch die graphische Darstellung der bei der Prädikatsergänzung üblichen Pausen.

  18. Protecting privacy in data release

    CERN Document Server

    Livraga, Giovanni

    2015-01-01

    This book presents a comprehensive approach to protecting sensitive information when large data collections are released by their owners. It addresses three key requirements of data privacy: the protection of data explicitly released, the protection of information not explicitly released but potentially vulnerable due to a release of other data, and the enforcement of owner-defined access restrictions to the released data. It is also the first book with a complete examination of how to enforce dynamic read and write access authorizations on released data, applicable to the emerging data outsou

  19. Triggered Release from Polymer Capsules

    Energy Technology Data Exchange (ETDEWEB)

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry

    2011-07-06

    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  20. Liposomal Fasudil, a Rho-Kinase Inhibitor, for Prolonged Pulmonary Preferential Vasodilation in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Gupta, Vivek; Gupta, Nilesh; Shaik, Imam H.; Mehvar, Reza; McMurtry, Ivan F.; Oka, Masahiko; Nozik-Grayck, Eva; Komatsu, Masanobu; Ahsan, Fakhrul

    2013-01-01

    Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were then characterized for various physicochemical properties. Optimized formulations were tested for pulmonary absorption and their pharmacological efficacy in a monocrotaline (MCT) induced rat model of PAH. The entrapment efficiency of optimized liposomal fasudil formulations was between 68.1±0.8% and 73.6±2.3%, and the cumulative release at 37°C was 98–99% over a period of 5 days. Compared to intravenous (IV) fasudil, a ~10 fold increase in the terminal plasma half-life was observed when liposomal fasudil was administered as aerosols. The t1/2 of IV fasudil was 0.39±0.12 h. and when given as liposomes via pulmonary route, the t1/2 extended to 4.71±0.72 h. One h after intratracheal instillation of liposomal fasudil, mean pulmonary arterial pressure (MPAP) was reduced by 37.6±5.7% and continued to decrease for about 3 h, suggesting that liposomal formulations produced pulmonary preferential vasodilation in MCT induced PAH rats. Overall, this study established the proof-of-principle that aerosolized liposomal fasudil is a feasible option for a non-invasive, controlled release and pulmonary preferential treatment of PAH. PMID:23353807

  1. Bolonia y la buena práctica de las prácticas

    OpenAIRE

    García Delgado, Javier

    2016-01-01

    A propósito de la implantación del controvertido “plan Bolonia” se están difundiendo algunas ideas negativas en relación con una supuesta “mercantilización” de la universidad, algunas relacionadas con la explotación de los estudiantes a través de las prácticas en empresas, o prácticas externas, sobre las cuales se reflexiona en este artículo. ¿Qué hemos aprendido tras las ya casi tres décadas transcurridas desde la promulgación del decreto del año 81 que autorizaba este tipo de prácticas? Ese...

  2. Magnetic and thermodynamic properties of the Pr-based ferromagnet PrGe2-δ

    Science.gov (United States)

    Matsumoto, Keisuke T.; Morioka, Naoya; Hiraoka, Koichi

    2018-03-01

    We investigated the magnetization, M, and specific heat, C, of ThSi2-type PrGe2-δ. A polycrystalline sample of PrGe2-δ was prepared by arc-melting. Magnetization divided by magnetic field, M / B, increased sharply and C showed a clear jump at the Curie temperature, TC, of 14.6 K; these results indicate that PrGe2-δ ordered ferromagnetically. The magnetic entropy at TC reached R ln 3, indicating a quasi-triplet crystalline electric field (CEF) ground state. The maximum value of magnetic entropy change was 11.5 J/K kg with a field change of 7 T, which is comparable to those of other right rare-earth based magnetocaloric materials. This large magnetic entropy change was attributed to the quasi-triplet ground state of the CEF.

  3. Growth and scintillation properties of Pr doped YAP with different Pr concentrations

    International Nuclear Information System (INIS)

    Yanagida, Takayuki; Kamada, Kei; Fujimoto, Yutaka; Sugiyama, Makoto; Furuya, Yuki; Yamaji, Akihiro; Yokota, Yuui; Yoshikawa, Akira

    2010-01-01

    Pr 3+ 0.2, 0.75, and 3 mol% doped YAP single crystalline scintillators were grown by using the micro-pulling down (μ-PD) method. Pr 3+ 0.05 mol% doped YAP was also prepared by using the Czochralski method. In transmittance spectra, 4f-5d absorption line appeared at 230 nm. The μ-PD grown crystals showed intense emission at 290 nm while the Czochralski grown one showed an emission peak at 245 nm in radio luminescence spectra under X-ray excitation. Among them, the Czochralski grown one exhibited the highest light yield under 137 Cs 662 keV excitation and the absolute light yield of this sample was estimated to be 20400±2000 ph/MeV. The decay time constants of these scintillators were around 10 ns due to Pr 3+ 5d-4f transition.

  4. Growth and scintillation properties of Pr doped YAP with different Pr concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Yanagida, Takayuki, E-mail: t_yanagi@tagen.tohoku.ac.j [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Kamada, Kei; Fujimoto, Yutaka; Sugiyama, Makoto; Furuya, Yuki [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Yamaji, Akihiro [New Industry Creation Hatchery Center (NICHe), Tohoku University, 6-6-10 Aoba, Aramaki, Aoba-ku, Sendai 980-8579 (Japan); Yokota, Yuui [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Yoshikawa, Akira [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); New Industry Creation Hatchery Center (NICHe), Tohoku University, 6-6-10 Aoba, Aramaki, Aoba-ku, Sendai 980-8579 (Japan)

    2010-11-21

    Pr{sup 3+} 0.2, 0.75, and 3 mol% doped YAP single crystalline scintillators were grown by using the micro-pulling down ({mu}-PD) method. Pr{sup 3+} 0.05 mol% doped YAP was also prepared by using the Czochralski method. In transmittance spectra, 4f-5d absorption line appeared at 230 nm. The {mu}-PD grown crystals showed intense emission at 290 nm while the Czochralski grown one showed an emission peak at 245 nm in radio luminescence spectra under X-ray excitation. Among them, the Czochralski grown one exhibited the highest light yield under {sup 137}Cs 662 keV excitation and the absolute light yield of this sample was estimated to be 20400{+-}2000 ph/MeV. The decay time constants of these scintillators were around 10 ns due to Pr{sup 3+} 5d-4f transition.

  5. PrPC from stem cells to cancer

    Directory of Open Access Journals (Sweden)

    Séverine eMartin-Lannerée

    2014-09-01

    Full Text Available The cellular prion protein PrPC was initially discovered as the normal counterpart of the pathological scrapie prion protein PrPSc, the main component of the infectious agent of Transmissible Spongiform Encephalopathies. While clues as to the physiological function of this ubiquitous protein were greatly anticipated from the development of knock-out animals, PrP-null mice turned out to be viable and to develop without major phenotypic abnormalities. Notwithstanding, the discovery that hematopoietic stem cells from PrP-null mice have impaired long-term repopulating potential has set the stage for investigating into the role of PrPC in stem cell biology. A wealth of data have now exemplified that PrPC is expressed in distinct types of stem cells and regulates their self-renewal as well as their differentiation potential. A role for PrPC in the fate restriction of embryonic stem cells has further been proposed. Paralleling these observations, an overexpression of PrPC has been documented in various types of tumours. In line with the contribution of PrPC to stemness and to the proliferation of cancer cells, PrPC was recently found to be enriched in subpopulations of tumour-initiating cells. In the present review, we summarize the current knowledge of the role played by PrPC in stem cell biology and discuss how the subversion of its function may contribute to cancer progression.

  6. Exotic behaviours in the Pr-based filled skutterudites

    International Nuclear Information System (INIS)

    Sato, H; Sugawara, H; Namiki, T; Saha, S R; Osaki, S; Matsuda, T D; Aoki, Y; Inada, Y; Shishido, H; Settai, R; Onuki, Y

    2003-01-01

    The exotic features of the Pr-based filled skutterudites are reviewed based on the electronic transport properties, specific heat and de Haas-van Alphen experiments, putting the emphasis on PrFe 4 P 12 and PrOs 4 Sb 12 . As references, the experiments on the related La- and Ce-filled skutterudites are also examined and discussed. Compared to their La reference compounds, the Fermi surface is very similar in PrOs 4 Sb 12 , suggesting the well localized character of 4f electrons, while it looks largely different in PrFe 4 P 12 . For the cyclotron effective mass, both PrFe 4 P 12 and PrOs 4 Sb 12 exhibit a strong enhancement, in reasonable agreement with the large specific heat coefficient

  7. A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast.

    Science.gov (United States)

    Wang, Kai; Melki, Ronald; Kabani, Mehdi

    2017-01-01

    Self-replicating 'proteinaceous infectious particles' or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

  8. A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    Full Text Available Self-replicating 'proteinaceous infectious particles' or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

  9. Identification of cardiac repercussions after intense and prolonged concentric isokinetic exercise in young sedentary people.

    Science.gov (United States)

    Le Goff, Caroline; Kaux, Jean-François; Couffignal, Vincent; Coubard, Romain; Mélon, Pierre; Cavalier, Etienne; Croisier, Jean-Louis

    2015-09-01

    Cardiopathies are the world's leading cause of mortality and morbidity. Although rare, cardiovascular accidents can occur during intense and infrequent sporting activity, particularly among those who are unaware of their heart condition. The development of cardiospecific biochemical markers has led to a reconsideration of the role of biology in the diagnosis of cardiovascular illnesses. The aim of this study therefore was, through the use of cardiac biomarker assays, to highlight the impact of sustained physical effort in the form of intense and prolonged concentric isokinetic exercise and to research potential cardiovascular risks. Eighteen subjects participated in a maximal concentric isokinetic exercise involving 30 knee flexion-extensions for each leg. Five blood tests were taken to study the kinetics of the cardiac biomarkers. Haemodynamic parameters were measured continuously using a Portapres, and respiratory parameters were measured using a Sensormedics Vmax 29C. The results showed significant increases in the creatine kinase, myoglobin, homocysteine and haemoglobin cardiac markers. Evolutionary trends were also observed for the following biomarkers: NT-proBNP, myeloperoxydase and C-reactive protein. All the physiological parameters measured presented statistically significant changes. Isokinetic effort leads to the release of cardiac markers in the blood, but these do not exceed the reference values in healthy subjects. Maximal concentric isokinetic exercise does not, therefore, lead to an increased risk of cardiovascular pathologies. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  10. Suppression of endothelial t-PA expression by prolonged high laminar shear stress

    International Nuclear Information System (INIS)

    Ulfhammer, Erik; Carlstroem, Maria; Bergh, Niklas; Larsson, Pia; Karlsson, Lena; Jern, Sverker

    2009-01-01

    Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low (≤1.5 dyn/cm 2 ) or high (25 dyn/cm 2 ) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30% of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.

  11. Riola release report

    Energy Technology Data Exchange (ETDEWEB)

    Woodward, E.C.

    1983-08-04

    Eleven hours after execution of the Riola Event (at 0826 PDT on 25 September 1980) in hole U2eq of the Nevada Test Site (NTS), a release of radioactivity began. When the seepage stopped at about noon the following day, up to some 3200 Ci of activity had been dispersed by light variable winds. On 26 September, examination of the geophone records showed six hours of low-level, but fairly continuous, activity before the release. Electrical measurements indicated that most cables were still intact to a depth below the stemming platform. A survey of the ground zero area showed that the seepage came through cracks between the surface conductor and the pad, through cracks in the pad, and through a crack adjacent to the pad around the mousehole (a small hole adjacent to the emplacement hole). To preclude undue radiation exposure or injury from a surprise subsidence, safety measures were instituted. Tritium seepage was suffucient to postpone site activities until a box and pipeline were emplaced to contain and remove the gas. Radiation release modeling and calculations were generally consistent with observations. Plug-hole interaction calculations showed that the alluvium near the bottom of the plug may have been overstressed and that improvements in the design of the plug-medium interface can be made. Experimental studies verified that the surface appearance of the plug core was caused by erosion, but, assuming a normal strength for the plug material, that erosion alone could not account for the disappearance of such a large portion of the stemming platform. Samples from downhole plug experiments show that the plug may have been considerably weaker than had been indicted by quality assurance (QA) samples. 19 references, 32 figures, 10 tables.

  12. Riola release report

    International Nuclear Information System (INIS)

    Woodward, E.C.

    1983-01-01

    Eleven hours after execution of the Riola Event (at 0826 PDT on 25 September 1980) in hole U2eq of the Nevada Test Site (NTS), a release of radioactivity began. When the seepage stopped at about noon the following day, up to some 3200 Ci of activity had been dispersed by light variable winds. On 26 September, examination of the geophone records showed six hours of low-level, but fairly continuous, activity before the release. Electrical measurements indicated that most cables were still intact to a depth below the stemming platform. A survey of the ground zero area showed that the seepage came through cracks between the surface conductor and the pad, through cracks in the pad, and through a crack adjacent to the pad around the mousehole (a small hole adjacent to the emplacement hole). To preclude undue radiation exposure or injury from a surprise subsidence, safety measures were instituted. Tritium seepage was suffucient to postpone site activities until a box and pipeline were emplaced to contain and remove the gas. Radiation release modeling and calculations were generally consistent with observations. Plug-hole interaction calculations showed that the alluvium near the bottom of the plug may have been overstressed and that improvements in the design of the plug-medium interface can be made. Experimental studies verified that the surface appearance of the plug core was caused by erosion, but, assuming a normal strength for the plug material, that erosion alone could not account for the disappearance of such a large portion of the stemming platform. Samples from downhole plug experiments show that the plug may have been considerably weaker than had been indicted by quality assurance (QA) samples. 19 references, 32 figures, 10 tables

  13. PrP expression, PrPSc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie.

    Directory of Open Access Journals (Sweden)

    Randi Sørby

    Full Text Available BACKGROUND: In prion disease, the peripheral expression of PrP(C is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc accumulation, localisation of nerve fibres and PrP(C expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C and PrP(Sc in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc-laden germinal centres. However, the close association between nerves and PrP(Sc was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc accumulation does not depend on the expression level of PrP(C. Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc.

  14. Allegheny County Toxics Release Inventory

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  15. Radio- and VUV - Excited Luminescence of YAP:Ce, YAP:Pr and YAG:Pr

    Science.gov (United States)

    2001-01-01

    Pr 3+ ions.", Acta Physica Polonica A, 90 pp.407-10, 1996. 6. C. Pedrini, D. Bouttet, C. Dujardin, B. Moine, I. Dafinei, P. Lecoq, M. Koselja, K...34Spectroscopy and thermoluminescence of LuAIO 3:Ce" Acta Physica Polonica A,.90, pp.377-383, 1996 17. A.J. Wojtowicz, J. Glodo, W. Drozdowski, K.R. Przegietka...Malinowski, M.F. Joubert, B. Jacquier. "Simultaneous laser action at blue and orange wavelengths in YAG:Pr 3+ Physica Status Solidi A, 140, pp.K49-52, 1993 5

  16. Media Impacts on Women's Fertility Desires: A Prolonged Exposure Experiment.

    Science.gov (United States)

    Knobloch-Westerwick, Silvia; Willis, Laura E; Kennard, Ashley R

    2016-06-01

    Media exposure may have implications for family planning, a public health issue of key importance. Drawing on social comparison theory and social identity theory, a prolonged exposure experiment examined whether media portrayals of women's social roles affect fertility desires among 166 American, nonstudent, never married, childless women ages 21-35 years old. After sign-up and baseline sessions, participants viewed magazine pages five days in a row. Stimuli presented women in either mother/homemaker roles, beauty ideal roles, or professional roles. Three days later, participants again indicated their number of desired children and time planned until first birth. Exposure to mother/homemaker and beauty ideal portrayals increased the number of desired children across time. Exposure to professional portrayals increased the time planned until 1st birth compared to beauty ideal portrayals-this impact was partially mediated by a shift toward more progressive gender norms (per social identity theory) and assimilation (per social comparison theory).

  17. Naloxone fails to prolong seizure length in ECT.

    Science.gov (United States)

    Rasmussen, K G; Pandurangi, A K

    1999-12-01

    Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

  18. Sex differences in cardiac function after prolonged strenuous exercise.

    Science.gov (United States)

    Cote, Anita T; Phillips, Aaron A; Foulds, Heather J; Charlesworth, Sarah A; Bredin, Shannon S D; Burr, Jamie F; Koehle, Michael S; Warburton, Darren E R

    2015-05-01

    To evaluate sex differences in left ventricular (LV) function after an ultramarathon, and the association of vascular and training indices with the magnitude of exercise-induced cardiac fatigue. Descriptive field study. Fat Dog 100 Ultramarathon Trail Race, Canada. Thirty-four (13 women) recreational runners (aged 28-56 years). A 100-km or 160-km mountain marathon. Baseline baroreceptor sensitivity, heart rate variability, and arterial compliance; Pre-exercise and postexercise echocardiographic evaluations of LV dimensions, volumes, Doppler flow velocities, tissue velocities, strain, and strain rate. Finishers represented 17 men (44.8 ± 6.6 years) and 8 women (45.9 ± 10.2 years; P = 0.758). After ultraendurance exercise, significant reductions (P training status/experience. These findings suggest that vascular health is an important contributor to the degree of cardiovascular strain incurred as the result of an acute bout of prolonged strenuous exercise.

  19. Fractures and Fanconi syndrome due to prolonged sodium valproate use.

    Science.gov (United States)

    Dhillon, N; Högler, W

    2011-06-01

    Sodium valproate (VPA) is commonly used to treat epilepsy in children. Renal dysfunction is a rare side eff ect but can present as tubulopathy such as Fanconi syndrome. We report on an 8-year-old disabled girl with myoclonic epilepsy who was referred for investigation of recurrent low impact fractures of the distal femur which were initially thought to be caused by her severe immobility. However, she was subsequently found to have hypophosphataemia secondary to Fanconi syndrome due to prolonged VPA use. After VPA withdrawal renal function and serum phosphate levels normalised and X-rays improved dramatically. The possibility of drug-induced osteoporosis and fractures should always be considered in disabled children, even in the presence of severe immobility.

  20. Prolonged reorganization of thiol-capped Au nanoparticles layered structures

    Directory of Open Access Journals (Sweden)

    Sarathi Kundu

    2013-09-01

    Full Text Available Prolonged reorganization behaviour of mono-, di-, tri- and multi-layer films of Au nanoparticles prepared by Langmuir-Blodgett method on hydrophobic Si(001 substrates have been studied by using X-ray scattering techniques. Out-of-plane study shows that although at the initial stage the reorganization occurs through the compaction of the films keeping the layered structure unchanged but finally all layered structures modify to monolayer structure. Due to this reorganization the Au density increases within the nanometer thick films. In-plane study shows that inside the reorganized films Au nanoparticles are distributed randomly and the particle size modifies as the metallic core of Au nanoparticles coalesces.

  1. New Heterogeneous Clustering Protocol for Prolonging Wireless Sensor Networks Lifetime

    Directory of Open Access Journals (Sweden)

    Md. Golam Rashed

    2014-06-01

    Full Text Available Clustering in wireless sensor networks is one of the crucial methods for increasing of network lifetime. The network characteristics of existing classical clustering protocols for wireless sensor network are homogeneous. Clustering protocols fail to maintain the stability of the system, especially when nodes are heterogeneous. We have seen that the behavior of Heterogeneous-Hierarchical Energy Aware Routing Protocol (H-HEARP becomes very unstable once the first node dies, especially in the presence of node heterogeneity. In this paper we assume a new clustering protocol whose network characteristics is heterogeneous for prolonging of network lifetime. The computer simulation results demonstrate that the proposed clustering algorithm outperforms than other clustering algorithms in terms of the time interval before the death of the first node (we refer to as stability period. The simulation results also show the high performance of the proposed clustering algorithm for higher values of extra energy brought by more powerful nodes.

  2. CNS fatigue provoked by prolonged exercise in the heat

    DEFF Research Database (Denmark)

    Nybo, Lars

    2010-01-01

    to the brain. However, exercise with superimposed hyperthermia is not only a challenge to the brain it also provides an excellent model for studying factors of importance for central fatigue. Excessive heat storage within the brain appears to be the primary cause for the central fatigue during exercise......Exercise-induced hyperthermia is associated with central fatigue as indicated by an impaired ability to sustain maximal motor activation during prolonged voluntary efforts. Therefore, exercise in hot environments challenges not only to the cardiorespiratory and locomotive systems but also...... to aggravate central fatigue and degrade exercise performance. Hyperthermia mediated central fatigue may include other cerebral perturbations such as reduced perfusion of the brain, accumulation of ammonia or depletion of neuronal energy stores, but further research is needed to elucidate their possible...

  3. Prolonged intensive dominance behavior between gray wolves, Canis lupus

    Science.gov (United States)

    Mech, L. David; Cluff, H. Dean

    2010-01-01

    Dominance is one of the most pervasive and important behaviors among wolves in a pack, yet its significance in free-ranging packs has been little studied. Insights into a behavior can often be gained by examining unusual examples of it. In the High Arctic near Eureka, Nunavut, Canada, we videotaped and described an unusually prolonged and intensive behavioral bout between an adult male Gray Wolf (Canis lupus) and a male member of his pack, thought to be a maturing son. With tail raised, the adult approached a male pack mate about 50 m from us and pinned and straddled this packmate repeatedly over 6.5 minutes, longer than we had ever seen in over 50 years of studying wolves. We interpreted this behavior as an extreme example of an adult wolf harassing a maturing offspring, perhaps in prelude to the offspring?s dispersal.

  4. Effect of prolonged continuous irradiation of humoral immunity of mice

    International Nuclear Information System (INIS)

    Kirillova, E.N.; Muksinova, K.N.; Skukovskaya, T.L.

    1988-01-01

    Changes in the content and function of cell populations and subpopulations involved in the humoral response of mice to the thymus-dependent antigen were investigated. The effect was followed during a prolonged continuous exposure to 137 C gamma-emitter (total dose - 5 Gy and daily dose - 12 cGy for 22 hours) and after its termination. The data obtained give evidence for a decrease of the pool of polypotent lymphocyte precursors (CFUs), stable moderate hypoplasia of central and peripheral organs of the immune system, distinct inhibition of antibody production at the expense of reduced activity of precursors of lymphocytes, B-lymphocytes and T-helpers. In the remote post-irradiation period residual radiation damage was seen in polypotent and committed precursors of lymphocytes and T-helpers, which was responsible for the trend towards the decline of antibody production, hypoplasia in the spleen and lymph nodes being persistent

  5. Gas hydrate dissociation prolongs acidification of the Anthropocene oceans

    NARCIS (Netherlands)

    Boudreau, B.P.; Luo, Yiming; Meysman, Filip J R; Middelburg, J.J.; Dickens, G.R.

    2015-01-01

    Anthropogenic warming of the oceans can release methane (CH4) currently stored in sediments as gas hydrates. This CH4 will be oxidized to CO2, thus increasing the acidification of the oceans. We employ a biogeochemical model of the multimillennial carbon cycle to determine the evolution of the

  6. Présentation des auteurs

    OpenAIRE

    2016-01-01

    Jean-Pierre Cléro, université de Haute-Normandie, Rouen Andrea Emiliani, président de l’academia Clementina de Bologna (Italie) Pascal Griener, université de Neuchâtel (Suisse) Yves Hersant, École des hautes études en sciences sociales, Paris Philippe Junod, université de Lausane (Suisse) Françoise Knopper, université de Toulouse 2-Le Mirail Centre de Recherches et d’Études germaniques (CREG) Didier Laroque, École supérieure d’architecture, Paris Val de Seine Alain Michel, de l’Institut Jacki...

  7. Efficacy of prolonged antimicrobial chemotherapy for brucellar spondylodiscitis.

    Science.gov (United States)

    Ioannou, S; Karadima, D; Pneumaticos, S; Athanasiou, H; Pontikis, J; Zormpala, A; Sipsas, N V

    2011-05-01

    The standard treatment of brucellar spondylitis with a combination of two antibiotics for 6-12 weeks is associated with high rates of treatment failure and relapse. The present study aimed to assess the safety and efficacy of a treatment strategy based on the prolonged administration of a triple combination of suitable antibiotics. Eighteen patients with brucellar spondylitis were treated with a combination of at least three suitable antibiotics (doxycycline, rifampin, plus intramuscular streptomycin or cotrimoxazole or ciprofloxacin) until the completion of at least 6 months of treatment, when clinical, radiological and serology re-evaluation was performed. If necessary, the treatment was continued with additional 6-month cycles, until resolution or significant improvement of clinical and radiological findings, or for a maximum of 18 months. At presentation, the median age was 66 years (range, 42-85 years) with male predominance. The median duration of therapy was 48 weeks (range 24-72 weeks). Treatment was discontinued early because of side-effects in only one patient. Surgical intervention was required for three patients. At the end of treatment all patients had a complete response. After completion of treatment, all patients were followed up with regular visits. During the follow-up period (duration 1-96 months, median 36.5 months), no relapses were observed. In conclusion, prolonged (at least 6 months) administration of a triple combination of suitable antibiotics appears to be an effective treatment for brucellar spondylitis. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

  8. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Forman, Henry Jay; Crocker, Daniel E.; Ortiz, Rudy M.

    2011-01-01

    SUMMARY Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin–angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40–50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma γ-glutamyl glutamine, γ-glutamyl isoleucine and γ-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals. PMID:21430206

  9. Survival in Patients Receiving Prolonged Ventilation: Factors that Influence Outcome

    Directory of Open Access Journals (Sweden)

    A. James Mamary

    2011-01-01

    Full Text Available Background Prolonged mechanical ventilation is increasingly common. It is expensive and associated with significant morbidity and mortality. Our objective is to comprehensively characterize patients admitted to a Ventilator Rehabilitation Unit (VRU for weaning and identify characteristics associated with survival. Methods 182 consecutive patients over 3.5 years admitted to Temple University Hospital (TUH VRU were characterized. Data were derived from comprehensive chart review and a prospectively collected computerized database. Survival was determined by hospital records and social security death index and mailed questionnaires. Results Upon admission to the VRU, patients were hypoalbuminemic (albumin 2.3 ± 0.6 g/dL, anemic (hemoglobin 9.6 ± 1.4 g/dL, with moderate severity of illness (APACHE II score 10.7 + 4.1, and multiple comorbidities (Charlson index 4.3 + 2.3. In-hospital mortality (19% was related to a higher Charlson Index score ( P = 0.006; OR 1.08-1.6, and APACHE II score ( P = 0.016; OR 1.03-1.29. In-hospital mortality was inversely related to admission albumin levels ( P = 0.023; OR 0.17-0.9. The presence of COPD as a comorbid illness or primary determinant of respiratory failure and higher VRU admission APACHE II score predicted higher long-term mortality. Conversely, higher VRU admission hemoglobin was associated with better long term survival (OR 0.57-0.90; P = 0.0006. Conclusion Patients receiving prolonged ventilation are hypoalbuminemic, anemic, have moderate severity of illness, and multiple comorbidities. Survival relates to these factors and the underlying illness precipitating respiratory failure, especially COPD.

  10. Prolonged operative time increases infection rate in tibial plateau fractures.

    Science.gov (United States)

    Colman, Matthew; Wright, Adam; Gruen, Gary; Siska, Peter; Pape, Hans-Christoph; Tarkin, Ivan

    2013-02-01

    Fractures of the tibial plateau present a treatment challenge and are susceptible to both prolonged operative times and high postoperative infection rates. For those fractures treated with open plating, we sought to identify the relationship between surgical site infection and prolonged operative time as well as to identify other surgical risk factors. We performed a retrospective controlled analysis of 309 consecutive unicondylar and bicondylar tibial plateau fractures treated with open plate osteosynthesis at our institution's level I trauma centre during a recent 5-year period. We recorded operative times, injury characteristics, surgical treatment, and need for operative debridement due to infection. Operative times of infected cases were compared to uncomplicated surgical cases. Multivariable logistic regression analysis was performed to identify independent risk factors for postoperative infection. Mean operative time in the infection group was 2.8h vs. 2.2h in the non-infected group (p=0.005). 15 fractures (4.9%) underwent four compartment fasciotomies as part of their treatment, with a significantly higher infection rate than those not undergoing fasciotomy (26.7% vs. 6.8%, p=0.01). Open fracture grade was also significantly related to infection rate (closed fractures: 5.3%, grade 1: 14.3%, grade 2: 40%, grade 3: 50%, pinfection rates (13.9% vs. 8.7%, p=0.36). Multivariable logistic regression analysis of the entire study group identified longer operative times (OR 1.78, p=0.013) and open fractures (OR 7.02, psite infection. Operative times approaching 3h and open fractures are related to an increased overall risk for surgical site infection after open plating of the tibial plateau. Dual incision approaches with bicolumnar plating do not appear to expose the patient to increased risk compared to single incision approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Ibuprofen-loaded poly(lactic-co-glycolic acid films for controlled drug release

    Directory of Open Access Journals (Sweden)

    Pang JM

    2011-04-01

    Full Text Available Jianmei Pang1, Yuxia Luan1, Feifei Li1, Xiaoqing Cai1, Jimin Du2, Zhonghao Li31School of Pharmaceutical Science, Shandong University, Jinan, Shandong Province, PR China; 2School of Chemistry and Chemical Engineering, Anyang Normal University, Henan Province, PR China; 3School of Materials Science and Engineering, Shandong University, Jinan, Shandong Province, PR ChinaAbstract: Ibuprofen- (IBU loaded biocompatible poly(lactic-co-glycolic acid (PLGA films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.Keywords: ibuprofen, controlled release, poly(lactic-co-glycolic acid, films

  12. Formulation and Evaluation of a Sustained-Release Tablets of Metformin Hydrochloride Using Hydrophilic Synthetic and Hydrophobic Natural Polymers

    OpenAIRE

    Wadher, K. J.; Kakde, R. B.; Umekar, M. J.

    2011-01-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study ...

  13. CRISPR/Cas9-based knockouts reveal that CpRLP1 is a negative regulator of the sex pheromone PR-IP in the Closterium peracerosum-strigosum-littorale complex.

    Science.gov (United States)

    Kanda, Naho; Ichikawa, Machiko; Ono, Ayaka; Toyoda, Atsushi; Fujiyama, Asao; Abe, Jun; Tsuchikane, Yuki; Nishiyama, Tomoaki; Sekimoto, Hiroyuki

    2017-12-19

    Heterothallic strains of the Closterium peracerosum-strigosum-littorale (C. psl.) complex have two sexes, mating-type plus (mt + ) and mating-type minus (mt - ). Conjugation between these two sexes is regulated by two sex pheromones, protoplast-release-inducing protein (PR-IP) and PR-IP Inducer, which are produced by mt + and mt - cells, respectively. PR-IP mediates the release of protoplasts from mt - cells during mating. In this study, we examined the mechanism of action of CpRLP1 (receptor-like protein 1), which was previously identified in a cDNA microarray analysis as one of the PR-IP-inducible genes. Using CRISPR/Cas9 technology, we generated CpRLP1 knockout mutants in mt - cells of the C. psl. complex. When the knockout mt - cells were mixed with wild-type mt + cells, conjugation was severely reduced. Many cells released protoplasts without pairing, suggesting a loss of synchronization between the two mating partners. Furthermore, the knockout mutants were hypersensitive to PR-IP. We conclude that CpRLP1 is a negative regulator of PR-IP that regulates the timing of protoplast release in conjugating C. psl. cells. As the first report of successful gene knockout in the class Charophyceae, this study provides a basis for research aimed at understanding the ancestral roles of genes that are indispensable for the development of land plants.

  14. Values and Preferences on the Use of Oral Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A Systematic Review of the Literature.

    Science.gov (United States)

    Koechlin, Florence M; Fonner, Virginia A; Dalglish, Sarah L; O'Reilly, Kevin R; Baggaley, Rachel; Grant, Robert M; Rodolph, Michelle; Hodges-Mameletzis, Ioannis; Kennedy, Caitlin E

    2017-05-01

    Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection. WHO released new guidelines in 2015 recommending PrEP for all populations at substantial risk of HIV infection. To prepare these guidelines, we conducted a systematic review of values and preferences among populations that might benefit from PrEP, women, heterosexual men, young women and adolescent girls, female sex workers, serodiscordant couples, transgender people and people who inject drugs, and among healthcare providers who may prescribe PrEP. A comprehensive search strategy reviewed three electronic databases of articles and HIV-related conference abstracts (January 1990-April 2015). Data abstraction used standardised forms to categorise by population groups and relevant themes. Of 3068 citations screened, 76 peer-reviewed articles and 28 conference abstracts were included. Geographic coverage was global. Most studies (N = 78) evaluated hypothetical use of PrEP, while 26 studies included individuals who actually took PrEP or placebo. Awareness of PrEP was low, but once participants were presented with information about PrEP, the majority said they would consider using it. Concerns about safety, side effects, cost and effectiveness were the most frequently cited barriers to use. There was little indication of risk compensation. Healthcare providers would consider prescribing PrEP, but need more information before doing so. Findings from a rapidly expanding evidence base suggest that the majority of populations most likely to benefit from PrEP feel positively towards it. These same populations would benefit from overcoming current implementation challenges with the shortest possible delay.

  15. Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

    Science.gov (United States)

    Admon, Roee; Treadway, Michael T; Valeri, Linda; Mehta, Malavika; Douglas, Samuel; Pizzagalli, Diego A

    2017-08-16

    The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response ( n = 10), moderate-response ( n = 21), and mild-response ( n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability. SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how

  16. Thermal reorientation of hydrogenic Pr3+ centers

    International Nuclear Information System (INIS)

    Jones, G. D.

    1996-01-01

    Sets of five multi-hydrogenic centers of both CaF 2 :Pr 3+ and SrF 2 :Pr 3 + show bleaching under selective polarized-light irradiation. Two forms of bleaching behaviour are observed. In reversible polarized bleaching, irradiation creates re-oriented equivalent centers, which can be restored to the original orientation by switching the laser polarization by 90 deg. Indefinite sequences of bleaching and recovery can be established. In photoproduct bleaching, inequivalent centers are produced, which can be reverted by subsequently selectively exciting their absorption lines. Thermal recovery of the bleached centers on warming the crystals occurs abruptly over a 5 K range around 100 K and is noteworthy in occurring at essentially identical temperatures for H - , D - and T - centers. The simplest model for this thermal recovery is thermal activation of the mobile hydrogenic ions over a double well potential barrier. An alternative model proposed by Universitaet Regensburg requires the involvement of high frequency excitations in scattering processes for surmounting the barrier

  17. Cobalt release from inexpensive jewellery

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Jellesen, Morten Stendahl; Menné, Torkil

    2010-01-01

    . Conclusions: This study showed that only a minority of inexpensive jewellery purchased in Denmark released cobalt when analysed with the cobalt spot test. As fashion trends fluctuate and we found cobalt release from dark appearing jewellery, cobalt release from consumer items should be monitored in the future......Objectives: The aim was to study 354 consumer items using the cobalt spot test. Cobalt release was assessed to obtain a risk estimate of cobalt allergy and dermatitis in consumers who would wear the jewellery. Methods: The cobalt spot test was used to assess cobalt release from all items...

  18. Determination of the differences in oxidation potentials for the Pr3+/Pr2+ and Ce3+/Ce2+ pairs in halide melts

    International Nuclear Information System (INIS)

    Mikheev, N.B.; Auerman, L.N.; Rumer, I.A.; D'yachkova, R.A.

    1983-01-01

    Cocrystallization has been used with the (PrOCl)/sub s. ph/ - (PrCl 2 , PrCl 3 , SrCl 2 ) melt system to examine the dependence of the cerium(III) cocrystallization coefficient on the X/sub Pr 2+ /X/sub Pr 3+ / ratio in the melt. Measurement has been made in this way of the difference in oxidation potentials for the pairs Pr 3+ /Pr 2+ and Ce 3+ /Ce 2+ : ΔE/sub Pr 3+ /Pr 2+0 -E/sub Ce 3+ /Ce 2+ / 0 , which is 0.08 +/- 0.04 V for chloride

  19. The PR in PN for Education Associations. PR Bookshelf, No. 3.

    Science.gov (United States)

    National Education Association, Washington, DC.

    This booklet presents suggestions and guidelines for the effective use of public relations (PR) techniques during professional negotiations (PN) among teachers, administrators, and boards of education. Introductory sections present the National Education Association (NEA) position regarding professional negotiation and grievance procedures and…

  20. Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study.

    Science.gov (United States)

    de Jong, Jan; Hellemans, Peter; Jiao, James Juhui; Huang, Yuhan; Mesens, Sofie; Sukbuntherng, Juthamas; Ouellet, Daniele

    2017-12-01

    Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval. 64 healthy subjects were planned to be enrolled. Baseline-adjusted QT (QTc) intervals for ibrutinib and moxifloxacin (assay sensitivity) were compared to placebo using linear mixed-effect model. A concentration-QTc analysis was also conducted. No clinically relevant safety observations were noted in Part 1. During Part 2, one subject experienced Grade 4 ALT/AST elevations with ibrutinib 1680 mg, leading to study termination and limiting the enrollment to 20 subjects. Ibrutinib demonstrated dose-dependent increases in exposure. The upper bounds of the 90% CIs for the mean difference in change from baseline in QTc between ibrutinib and placebo were Ibrutinib caused a concentration-dependent mild shortening of QTc and mild PR prolongation, but these effects were not considered clinically meaningful. Therapeutic and supratherapeutic concentrations of ibrutinib do not prolong the QTc interval. CLINICALTRIALS.GOV: NCT02271438.

  1. alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and follicle-stimulating hormone secretion in the immature female rat.

    Science.gov (United States)

    Thyssen, S M; Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1997-06-01

    Polyamines play an essential role in tissue growth and differentiation, in body weight increment, in brain organization, and in the molecular mechanisms of hormonal action, intracellular signaling, and cell-to-cell communication. In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rats, was followed by prolonged high follicle-stimulating hormone (FSH) serum level and a delayed puberty onset. Those changes were relatively independent of body mass and did not impair posterior fertility. The present work studies the mechanisms and site of action of polyamine participation in FSH secretion during development. DFMO was injected in female rats between Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin-releasing hormone (GnRH) release were measured. The response to membrane depolarization was altered in DFMO hypothalami. Increased GnRH release in response to a low K+ concentration was evidenced. Adenohypophyses of the same treated prepubertal rats were perifused in vitro and the response to GnRH pulses was checked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in adenohypophyseal membranes from treated and control groups was quantified. A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the control group. In summary, DFMO treatment in a critical developmental period in the female rat impacts the immature GnRH neuronal network and immature gonadotropes. A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic explants. These events could explain the prolonged high FSH serum levels and delayed puberty onset seen in

  2. The re-establishment of the normal blood lactate response to exercise in humans after prolonged acclimatization to altitude

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Calbet, J A; Søndergaard, H

    2001-01-01

    1. One to five weeks of chronic exposure to hypoxia has been shown to reduce peak blood lactate concentration compared to acute exposure to hypoxia during exercise, the high altitude 'lactate paradox'. However, we hypothesize that a sufficiently long exposure to hypoxia would result in a blood......, in lowlanders acclimatized for 9 weeks to an altitude of 5260 m, the arterial lactate concentration was similar at 0 m acute hypoxia and 5260 m chronic hypoxia. The net lactate release from the active leg was higher at 5260 m chronic hypoxia compared to 0 m acute hypoxia, implying an enhanced lactate...... utilization with prolonged acclimatization to altitude. The present study clearly shows the absence of a lactate paradox in lowlanders sufficiently acclimatized to altitude....

  3. Molecular machines regulating the release probability of synaptic vesicles at the active zone.

    Directory of Open Access Journals (Sweden)

    Christoph eKoerber

    2016-03-01

    Full Text Available The fusion of synaptic vesicles (SVs with the plasma membrane of the active zone (AZ upon arrival of an action potential (AP at the presynaptic compartment is a tightly regulated probabil-istic process crucial for information transfer. The probability of a SV to release its transmitter content in response to an AP, termed release probability (Pr, is highly diverse both at the level of entire synapses and individual SVs at a given synapse. Differences in Pr exist between different types of synapses, between synapses of the same type, synapses originating from the same axon and even between different SV subpopulations within the same presynaptic terminal. The Pr of SVs at the AZ is set by a complex interplay of different presynaptic properties including the availability of release-ready SVs, the location of the SVs relative to the voltage-gated calcium channels (VGCCs at the AZ, the magnitude of calcium influx upon arrival of the AP, the buffer-ing of calcium ions as well as the identity and sensitivity of the calcium sensor. These properties are not only interconnected, but can also be regulated dynamically to match the requirements of activity patterns mediated by the synapse. Here, we review recent advances in identifying mole-cules and molecular machines taking part in the determination of vesicular Pr at the AZ.

  4. Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

    Science.gov (United States)

    Sakudo, Akikazu; Onodera, Takashi

    2015-01-01

    Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp−/−) mice. So far, six types of Prnp−/− mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not fully reveal PrP functions. Recently, varieties of Prnp−/− cell lines established from Prnp−/− mice have contributed to the analysis of PrP functions. In this mini-review, we focus on Prnp−/− cell lines and summarize currently available Prnp−/− cell lines and their characterizations. In addition, we introduce the recent advances in the methodology of cell line generation with knockout or knockdown of the PrP gene. We also discuss how these cell lines have provided valuable insights into PrP functions and show future perspectives. PMID:25642423

  5. Salvinorin A analogues PR-37 and PR-38 attenuate compound 48/80-induced itch responses in mice.

    Science.gov (United States)

    Salaga, M; Polepally, P R; Zielinska, M; Marynowski, M; Fabisiak, A; Murawska, N; Sobczak, K; Sacharczuk, M; Do Rego, J C; Roth, B L; Zjawiony, J K; Fichna, J

    2015-09-01

    The opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR-37 and PR-38, exhibit antipruritic properties in mice. To examine the antiscratch effect of PR-37 and PR-38 we used a mouse model of compound 48/80-induced pruritus. In order to elucidate the mechanism of action of tested compounds, specific antagonists of opioid and cannabinoid receptors were used. The effect of PR-37 on the CNS was assessed by measuring motor parameters and exploratory behaviours in mice. PR-37 and PR-38, jnjected s.c., significantly reduced the number of compound 48/80-induced scratching behaviours in mice in a dose- and time-dependent manner. PR-38 was also active when orally administered. The antiscratch activity of PR-37 was blocked by the selective κ opioid receptor antagonist, nor-binaltorphimine, and that of PR-38 by the selective μ opioid receptor antagonist, β-funaltrexamine. In conclusion, a novel framework for the development of new antipruritic drugs derived from salvinorin A has been validated. © 2015 The British Pharmacological Society.

  6. Diverse definitions of prolonged labour and its consequences with sometimes subsequent inappropriate treatment

    OpenAIRE

    Nystedt, Astrid; Hildingsson, Ingegerd

    2014-01-01

    Background: Prolonged labour very often causes suffering from difficulties that may have lifelong implications. This study aimed to explore the prevalence and treatment of prolonged labour and to compare birth outcome and women's experiences of prolonged and normal labour. Method: Women with spontaneous onset of labour, living in a Swedish county, were recruited two months after birth, to a cross-sectional study. Women (n = 829) completed a questionnaire that investigated socio-demographic an...

  7. AORN Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings.

    Science.gov (United States)

    Hughes, Nancy L; Nelson, Audrey; Matz, Mary W; Lloyd, John

    2011-06-01

    Prolonged standing during surgical procedures poses a high risk of causing musculoskeletal disorders, including back, leg, and foot pain, which can be chronic or acute in nature. Ergonomic Tool 4: Solutions for Prolonged Standing in Perioperative Settings provides recommendations for relieving the strain of prolonged standing, including the use of antifatigue mats, supportive footwear, and sit/stand stools, that are based on well-accepted ergonomic safety concepts, current research, and access to new and emerging technology. Published by Elsevier Inc.

  8. Experimental Models of Inherited PrP Prion Diseases.

    Science.gov (United States)

    Watts, Joel C; Prusiner, Stanley B

    2017-11-01

    The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. Histone Deacetylase Inhibitors Prolong Cardiac Repolarization through Transcriptional Mechanisms.

    Science.gov (United States)

    Spence, Stan; Deurinck, Mark; Ju, Haisong; Traebert, Martin; McLean, LeeAnne; Marlowe, Jennifer; Emotte, Corinne; Tritto, Elaine; Tseng, Min; Shultz, Michael; Friedrichs, Gregory S

    2016-09-01

    Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown. We demonstrate that administration of structurally diverse HDAC inhibitors to dogs causes delayed but persistent increases in the heart rate corrected QT interval (QTc), an in vivo measure of cardiac repolarization, at timepoints far removed from the Tmax for parent drug and metabolites. Transcriptional profiling of ventricular myocardium from dogs treated with various HDAC inhibitors demonstrated effects on genes involved in protein trafficking, scaffolding and insertion of various ion channels into the cell membrane as well as genes for specific ion channel subunits involved in cardiac repolarization. Extensive in vitro ion channel profiling of various structural classes of HDAC inhibitors (and their major metabolites) by binding and acute patch clamp assays failed to show any consistent correlations with direct ion channel blockade. Drug-induced rescue of an intracellular trafficking-deficient mutant potassium ion channel, hERG (G601S), and decreased maturation (glycosylation) of wild-type hERG expressed by CHO cells in vitro correlated with prolongation of QTc intervals observed in vivo The results suggest that HDAC inhibitor-induced prolongation of cardiac repolarization may be mediated in part by transcriptional changes of genes required for ion channel trafficking and localization to the sarcolemma. These data have broad implications for the development of these drug classes and

  10. Parto inducido por embarazo prolongado Induced delivery in prolonged gestation

    Directory of Open Access Journals (Sweden)

    Mercedes Peña Abraham

    2006-12-01

    Full Text Available Se realizó un estudio retrospectivo, descriptivo, explicativo y longitudinal sobre el comportamiento de la inducción del parto por embarazo prolongado en el Hospital Gineco-Obstétrico "Justo Legón Padilla", en el período comprendido entre enero del 2004 y diciembre del 2005.El universo estuvo constituido por la totalidad de los nacimientos por embarazo prolongado que se produjeron en el período, donde el grupo estudio estaba exclusivamente formado por las gestantes con trabajo de parto inducido (n=104; se estudiaron variables de la madre, del nacimiento y del producto de la concepción y a los datos obtenidos se les aplicó porcentaje. La edad materna más frecuente fue la del grupo de 20 - 35 años (65,5%; predominaron las nulíparas (40,4%, la vía del parto que predominó fue la transpelviana (42,3%; todos con un índice de Bishop >7 puntos La causa más frecuente de cesárea fue el sufrimiento fetal agudo (23%; el embarazo prolongado no constituyó una causa importante de Apgar Bajo, en el parto distócico fue donde ocurrió el mayor número de morbilidad materna y neonatal (9,5%, no se encontró valor significativo en la macrosomía fetal y predominó el sexo femenino en los recién nacidos (65,3%.A retrospective, descriptive, explicative and longitudinal study about the behavior of the induction of labor in prolonged pregnancy was conducted at "Justo Legón Padilla" Gyneco-Obstetric Hospital during the period of January 2004 to December 2005. The whole sample was constituted by the totality of births in prolongad pregnancy during the period where the study group was exclusively formed by pregnants who underwent induced labor (n = 104.Variables of mother, birth and conception product were taken, and percentage method was applied to data collected. The group of most frequent maternal age was 20 - 35 (65,5%, prevailing nulliparous (40,4% and transpelvic labor (42,3%, having a Bishop index = 7. The most frequent cause of cesarean section

  11. Features of History, Anthropometric Data and Individual Functions of the Liver in Children with Prolonged Jaundice

    Directory of Open Access Journals (Sweden)

    O.V. Tyajka

    2016-11-01

    Full Text Available Background. Neonatal jaundice is one of the urgent problems in neonatology. There is a tendency to increase the incidence of prolonged jaundice. The aim of our study was to explore the features of history, anthropometric data and some liver functions in children with prolonged jaundice. Materials and methods. The study involved 111 children with prolonged jaundice aged from 3 weeks to 3 months. In all children with prolonged jaundice, we have examined complete blood count, urinalysis, blood chemistry (determination of total bilirubin and fractions, total protein, albumin, glucose and used instrumental methods of examination — ultrasound of the abdominal cavity and cranial ultrasonography, electrocardiography. Most children with prolonged jaundice were breastfed and were term infants. Results. Indicators of physical development at birth (body weight, body length, head circumference, chest circumference in children with prolonged jaundice and in healthy children had not statistically significant differences. Neonatal jaundice was prolonged in children, who were born from the first pregnancy, — 60 children (54.1 %. A high level of total and indirect bilirubin was accompanied by a low level of albumin in the blood serum of children with prolonged jaundice. Protein-synthesis function of the liver was reduced in children with prolonged jaundice.

  12. Are shame and self-esteem risk factors in prolonged grief after death of a spouse?

    Science.gov (United States)

    Dellmann, Thomas

    2018-07-01

    Although many single factors of prolonged grief have been identified in the literature, a comprehensive understanding of predictors is still lacking. This article argues that shame and low self-esteem, present risk factors in prolonged grief after spousal loss, based on a review of correlational studies. Using a practitioner-scientist approach, a developmental model of shame as a core factor in prolonged grief is proposed, outlining the progression from childhood relational trauma, to insecure attachment, shame, self-esteem contingent on spousal approval to eventual prolonged grief.

  13. Study of PrP - I heterogeneous equilibrium

    International Nuclear Information System (INIS)

    Vasil'eva, I.G.; Mironov, K.E.; Tarasenko, A.D.

    1976-01-01

    Using static methods the authors have measured the equilibrium vapor pressure in the system PrP+I 2 at different temperatures and different initial iodine concentrations. The equilibrium reactions in the system have been determined. The reaction of PrP with iodine is irreversible. The content of PrI 3 and I 2 in the gas phase is negligible. The pressure in the system is determined by the partial pressure of phosphorus

  14. Features of the advertising and PR in tourism

    OpenAIRE

    M. A. Zubarieva

    2015-01-01

    The article discusses the use of topical issues of important tools of social communication of applied tactical direction (advertising) and strategic (PR). The main types of advertising in tourism and types of PR ­ activities are characterized.The main difference between advertising and PR in the tourism sector is defined, the main attention is given to correct choice of optimal (most efficient) advertising channel (means). Specific nature, advertising issues as the main tool for the promotion...

  15. Prion propagation in cells expressing PrP glycosylation mutants.

    Science.gov (United States)

    Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-04-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

  16. Controlled release systems containing solid dispersions: strategies and mechanisms.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

    2011-10-01

    In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

  17. Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

    Science.gov (United States)

    Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

    2017-10-01

    Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. La práctica del paisajismo

    Directory of Open Access Journals (Sweden)

    Medina Muro, María

    2010-12-01

    Full Text Available The practice of landscaping is best understood by looking at who the contemporary designers are what work they do and in what professional realm they operate. If we take into account the range of possibilities a landscape architect has —from work on projects that take place in the wilderness to rural and urban environments— one can go from designing a small interior patio to projects that hace major environmental impact. Based on my knowledge and professional experience I am going to focus mainly on the types of landscapes I have been able to develop; the restoration of historic gardens, urban landscapes and private gardens, making reference to and showing examples of the works of other professionals in the field. In conclusion I will underline the importance of gardens and the relationship between ecology and the traditions of landscape design.

    La práctica del paisajismo se entiende mejor si se aclara quién es hoy un paisajista, en que ámbito profesional puede trabajar, y cuáles son sus obras. Si tenemos en cuenta la posibilidad que tiene un paisajista de actuar o participar en trabajos que abarcan tanto el paisaje natural, el rural como el urbano, su ámbito de trabajo puede ser muy amplio: desde diseñar un pequeño patio a realizar un estudio de impacto medioambiental. Me voy a referir preferentemente, y basándome en mis conocimientos y experiencia profesional, a aquellos paisajes que en la práctica he podido desarrollar: restauración de jardines y paisajes históricos; paisajes urbanos; y jardines privados, citando y mostrando algunos ejemplos de trabajos realizados por profesionales del paisaje. Por último, destacaré la importancia de los jardines y la relación entre ecología y tradición en la práctica del paisajismo. [fr] La pratique du l’aménagement paysager est mieux comprise en précisant qui est aujourd’hui un paysagiste, dans lequel cadre professionnel peut travailler, et quelles sont ses oeuvres. Si

  19. (Prérif central, Maroc septentrional

    Directory of Open Access Journals (Sweden)

    Abdelghani Gartet

    2005-01-01

    Full Text Available El artículo tiene por objeto evaluar la degradación específi ca, y especialmente cuantifi car la carga de transporte sólido, en la cuenca del oued Lebène (Prérif central, caracterizada por altas tasas de erosión hídrica. La fuerte erosionabilidad de las rocas, la agresividad climática y las frecuentes variaciones de caudal hacen que el volumen de los materiales transportados por el Lebène alcancen una magnitud considerable. La irregularidad espacio-temporal de las precipitaciones y caudales condicionan el volumen de los transportes sólidos, de ahí las estrechas correlaciones existentes entre las tres variables. Los análisis relativos a la turbidez de las aguas y a la naturaleza granulométrica de los sedimentos refuerzan dicha relación.

  20. Computerbasiert prüfen [Computer-based Assessment

    Directory of Open Access Journals (Sweden)

    Frey, Peter

    2006-08-01

    Full Text Available [english] Computer-based testing in medical education offers new perspectives. Advantages are sequential or adaptive testing, integration of movies or sound, rapid feedback to candidates and management of web-based question banks. Computer-based testing can also be implemented in an OSCE examination. In e-learning environments formative self-assessment are often implemented and gives helpful feedbacks to learners. Disadvantages in high-stake exams are the high requirements as well for the quality of testing (e.g. standard setting as additionally for the information technology and especially for security. [german] Computerbasierte Prüfungen im Medizinstudium eröffnen neue Möglichkeiten. Vorteile solcher Prüfungen liegen im sequentiellen oder adaptiven Prüfen, in der Integration von Bewegtbildern oder Ton, der raschen Auswertung und zentraler Verwaltung der Prüfungsfragen via Internet. Ein Einsatzgebiet mit vertretbarem Aufwand sind Prüfungen mit mehreren Stationen wie beispielsweise die OSCE-Prüfung. Computerbasierte formative Selbsttests werden im Bereiche e-learning häufig angeboten. Das hilft den Lernenden ihren Wissensstand besser einzuschätzen oder sich mit den Leistungen anderer zu vergleichen. Grenzen zeigen sich bei den summativen Prüfungen beim Prüfungsort, da zuhause Betrug möglich ist. Höhere ärztliche Kompetenzen wie Untersuchungstechnik oder Kommunikation eigenen sich kaum für rechnergestützte Prüfungen.

  1. Thermodynamic database for the Co-Pr system

    Directory of Open Access Journals (Sweden)

    S.H. Zhou

    2016-03-01

    Full Text Available In this article, we describe data on (1 compositions for both as-cast and heat treated specimens were summarized in Table 1; (2 the determined enthalpy of mixing of liquid phase is listed in Table 2; (3 thermodynamic database of the Co-Pr system in TDB format for the research articled entitle Chemical partitioning for the Co-Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase W. Keywords: Thermodynamic database of Co-Pr, Solution calorimeter measurement, Phase diagram Co-Pr

  2. Triinu rukkileib nimetati Baltimaade parimaks PR-projektiks

    Index Scriptorium Estoniae

    2014-01-01

    Leiburi leivatehase ja kommunikatsioonibüroo Hamburg ja Partnerid ühisprojekt "Leiburi Leivategu" nimetati üleeuroopalisel pr-spetsialistide konkursil 2013. a. parimaks kommunikatsiooniprojektiks Baltimaades

  3. Electrocardiographic PR-interval duration and cardiovascular risk

    DEFF Research Database (Denmark)

    Rasmussen, Peter Vibe; Nielsen, Jonas Bille; Skov, Morten Wagner

    2017-01-01

    Background Because of ambiguous reports in the literature, we aimed to investigate the association between PR interval and the risk of all-cause and cardiovascular death, heart failure, and pacemaker implantation, allowing for a nonlinear relationship. MethodsWe included 293,111 individuals...... into 7 groups based on the population PR interval distribution. Cox models were used, with reference to a PR interval between 152 and 161 ms (40th to heart failure...... adjustment. A long PR interval conferred an increased risk of heart failure ( > 200 ms; HR, 1.31; 95% CI, 1.22-1.42; P 200 ms (HR, 3...

  4. Israel: a crise próxima

    Directory of Open Access Journals (Sweden)

    Peter DEMANT

    2014-12-01

    Full Text Available Apesar de êxitos indisputáveis, o Estado de Israel enfrenta problemas estruturais decorrentes do conflito com o mundo árabe. O texto analisa cinco vulnerabilidades subestimadas: (1 demografia: o crescimento dos ultraortodoxos e dos árabes israelenses, ambos antissionistas, que arrisca tornar minoria os judeus sionistas; (2 estratégia: novas formas de resistência usadas pelos árabes, tanto militares, como os mísseis, quanto pacíficas, como a resistência não violenta, estão progressivamente se tornando contraproducentes à ocupação israelense de territórios inimigos; (3 regional: a Primavera Árabe, apesar dos fracassos, é uma etapa na democratização e modernização das sociedades árabes que acabará erodindo a vantagem qualitativa-educacional israelense; (4 internacional: Israel depende, militar e economicamente, do apoio ocidental, mas, movidos por seus próprios desenvolvimentos demográficos e culturais, os europeus se mostram cada vez mais indiferentes ou hostis a Israel; e até nos EUA, último reduto de simpatia pró-israelense, a identificação com o Estado judaico pode se tornar mais frágil; (5 mundo judaico: devido à orientação cada vez mais particularista de Israel, há, em vez de legitimação recíproca, ameaça de alienação entre as diásporas judaicas e Israel. O artigo conclui que, a termo, as custas políticas, militares e socioculturais que a beligerância permanente impõe a Israel podem constituir um risco existencial para este país. Eventualmente, os dilemas podem se tornar perigosos para sua sobrevivência como Estado judaico.

  5. Mean arterial pressure following prolonged exercise in the heat

    DEFF Research Database (Denmark)

    Gagnon, D; Lynn, A G; Binder, K

    2012-01-01

    benefit to its regulation. We examined MAP (Finometer) in eight trained (T) and eight untrained (UT) individuals prior to, and following, 120 min of cycling at 42 °C with (HYD) and without (DEHY) fluid replacement. Exercise during DEHY induced significant hyperthermia (T: 39.20 ± 0.52 °C vs UT: 38.70 ± 0......Prolonged exercise in the heat without fluid replacement represents a significant challenge to the regulation of mean arterial pressure (MAP). It is unknown, however, if MAP is equally challenged during the post-exercise period, and whether regular endurance exercise training can provide any.......36 °C, P = 0.941) and body weight losses (T: 3.4 ± 1.2% vs UT: 2.7 ± 0.9%, P = 0.332), which did not differ between groups. Although MAP was equally reduced 5 min into the post-exercise period of DEHY (T: -20 ± 11 mmHg vs UT: -22 ± 13 mmHg, P = 0.800), its subsequent recovery was significantly different...

  6. Response of Escherichia coli to Prolonged Berberine Exposure.

    Science.gov (United States)

    Budeyri Gokgoz, Nilay; Avci, Fatma Gizem; Yoneten, Kubra Karaosmanoglu; Alaybeyoglu, Begum; Ozkirimli, Elif; Sayar, Nihat Alpagu; Kazan, Dilek; Sariyar Akbulut, Berna

    2017-07-01

    Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.

  7. Color stability and staining of silorane after prolonged chemical challenges

    DEFF Research Database (Denmark)

    de Jesus, Vivian CBR; Martinelli, Nata Luiz; Poli-Frederico, Regina Célia

    Objectives: The purpose of this study was to investigate the effect of prolonged chemical challenges on color stability and staining susceptibility of a silorane-based composite material when compared to methacrylate-based composites. Methods: Cylindrical specimens (n=24) were fabricated from...... methacrylate (Filtek Z250, 3M ESPE; Filtek Z350XT, 3M ESPE; Master Fill, Biodinâmica) or silorane-based (Filtek P90, 3M ESPE) composite materials. Initial color was registered in a spectrophotometer. Specimens were divided in four groups and individually stored at 37°C in 0.02N citric acid, 0.02N phosphoric...... acid, 75% ethanol or distilled water (control) for 7, 14, 21, and 180 days, when new measurements were performed. A staining test was performed (n=12) after 21 days of chemical challenge by immersion in coffee during 3 weeks at 37°C. Color changes (¿E) were characterized using the CIEL*a*b* color...

  8. Burst stimulation improves hemodynamics during resuscitation after prolonged ventricular fibrillation.

    Science.gov (United States)

    Walcott, Gregory; Melnick, Sharon; Killingsworth, Cheryl; Ideker, Raymond

    2009-02-01

    Although return of spontaneous circulation (ROSC) is frequently achieved during resuscitation for sudden cardiac arrest, systolic blood pressure can then decrease, requiring additional myocardial support. Previous studies have shown that a series of 1-ms electrical pulses delivered through the defibrillation patches during ventricular fibrillation (VF) can stimulate the autonomic nervous system to increase myocardial function following defibrillation. We hypothesized that a similar series of electrical pulses could increase myocardial function and blood pressure during the early post-resuscitation period. Six swine were studied that underwent 6-7 min. Each animal received 5, 10, 15, or 20 pulse packets consisting of 6 10 A, 1-ms pulses every 3-4 s in random order whenever systolic blood pressure became less than 50 mmHg. All four sets of pulse packets were delivered to each animal. Systolic blood pressure and cardiac function (left ventricular +dP/dt) were increased to pre-stimulation levels or above by all four sets of pulse packets. The increases were significantly greater for the longer than the shorter number of pulse packets. The mean+/-SD duration of the time that the systolic pressure remained above 50 mmHg following pulse delivery was 4.2+/-2.5 min. Electrical stimulation during regular rhythm following prolonged VF and resuscitation can increase blood pressure and cardiac function to above prestimulation levels.

  9. Prolonged displacement may compromise resilience in Eritrean mothers.

    Science.gov (United States)

    Almedom, Astier; Tesfamichael, Berhe; Mohammed, Zein; Mascie-Taylor, Nick; Muller, Jocelyn; Alemu, Zemui

    2005-12-01

    to assess the impact of prolonged displacement on the resilience of Eritrean mothers. an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Displaced women's SOC scores were significantly less than those of the non-displaced: Mean = 54.84; SD = 6.48 in internally displaced person (IDP) camps, compared to non-displaced urban and rural/pastoralist: Mean = 48. 94, SD = 11.99; t = 3.831, p urban (non-displaced). Rural but traditionally mobile (pastoralist or transhumant) communities scored more or less the same as the urban non-displaced--i.e., significantly higher than those in IDP camps (p urban and pastoralist/transhumant groups were similar, while women in IDP camps were lower scoring--RR = .268, p < .001. The implications of these findings for health policy are critical. It is incumbent on the international health institutions including the World Health Organization and regional as well as local players to address the plight of internally displaced women, their families and communities in Eritrea and other places of dire conditions such as, for example Darfur in the Sudan.

  10. Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

    Science.gov (United States)

    Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

    2018-05-01

    Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

  11. Predictors of successful weaning from prolonged mechanical ventilation in Taiwan.

    Science.gov (United States)

    Wu, Yao-Kuang; Kao, Kuo-Chin; Hsu, Kuang-Hung; Hsieh, Meng-Jer; Tsai, Ying-Huang

    2009-08-01

    For adult patients on prolonged mechanical ventilation (PMV, >/=21 days), successful weaning has been attributed to various factors. The purpose of this study was to describe patient outcomes, weaning rates and factors in successful weaning at a hospital-based respiratory care center (RCC) in Taiwan. This was a retrospective observational study performed in a 24-bed RCC over six years. A total of 1307 patients on PMV were included in the study. The overall survival rate was 62%. Fifty-six percent of patients were successfully weaned. Unsuccessfully weaned patients had higher MICU transfer rates, higher Acute Physiology and Chronic Health Evaluation II scores, longer duration of RCC stay, higher rates of being bed-ridden prior to admission, increased hemodialysis rates, higher modified Glasgow Coma Scale scores, higher rapid shallow breathing index, lower inspiratory pressure at residual volume (PImax) and lower blood urea nitrogen (BUN) and creatinine levels. Factors found to be associated with unsuccessful weaning were length of RCC stay (OR=1.04, Pventilator independence can be achieved in an RCC setting as an alternative to ICU care. Factors associated with unsuccessful weaning included longer duration of RCC stay, elevated BUN levels and lower modified GCS scores, serum albumin and PImax levels.

  12. Significant prolongation of segmental pancreatic allograft survival in two species

    Energy Technology Data Exchange (ETDEWEB)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  13. Significant prolongation of segmental pancreatic allograft survival in two species

    International Nuclear Information System (INIS)

    Du Toit, D.F.; Heydenrych, J.J.

    1988-01-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival

  14. Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report

    Directory of Open Access Journals (Sweden)

    Laura Pratchett

    2010-12-01

    Full Text Available Rationale: Prolonged exposure (PE therapy has been found to reduce symptoms of posttraumatic stress disorder (PTSD; however, it is difficult for many patients to engage fully in the obligatory retelling of their traumatic experiences. This problem is compounded by the fact that habituation and cognitive restructuring – the main mechanisms through which PE is hypothesized to work – are not instantaneous processes, and often require several weeks before the distress associated with imaginal exposure abates. Case reports: Two cases are described that respectively illustrate the use of hydrocortisone and placebo, in combination with PE, for the treatment of combat-related PTSD. Based on known effects of glucocorticoids on learning and memory performance, we hypothesized that augmentation with hydrocortisone would improve the therapeutic effects of PE by hastening “new” learning and facilitating decreases in the emotional impact of fear memories during the course of treatment. The veteran receiving hydrocortisone augmentation of PE displayed an accelerated and ultimately greater decline in PTSD symptoms than the veteran receiving placebo. Conclusions: While no general conclusion can be derived from comparison of two patients, the findings are consistent with the rationale for augmentation. These case reports support the potential for an appropriately designed and powered clinical trial to examine the efficacy of glucocorticoids in augmenting the effects of psychotherapy for PTSD.

  15. Physiological Responses and Hedonics During Prolonged Physically Interactive Videogame Play.

    Science.gov (United States)

    Santo, Antonio S; Barkley, Jacob E; Hafen, Paul S; Navalta, James

    2016-04-01

    This study was designed to assess physiologic responses and hedonics (i.e., liking) during prolonged physically interactive videogame play. Participants (n = 24) completed three 30-minute videogame conditions on separate days in a random order. During two of the conditions participants played physically interactive videogames (Nintendo of America, Inc. [Redmond, WA] "Wii™ Fit" "Basic Run" and "Basic Step"). During the third condition participants played a traditional/sedentary game ("Tanks!"), which required minimal physical movement for gameplay. Oxygen consumption (VO2) was assessed using indirect calorimetry throughout each condition and averaged every 5 minutes. Liking was assessed via visual analog scale at the 15- and 30-minute time points during each condition. Mean VO2 was significantly (P videogame (5.39 ± 1.0 mL/kg/minute, 1.5 ± 0.1 METs). "Basic Step" was also greater (P videogame conditions. Furthermore, because liking was similar across all gaming conditions, participants may be willing to substitute the physically interactive videogames in place of the traditional/sedentary game.

  16. Effect of prolonged space flight on cardiac function and dimensions

    Science.gov (United States)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1974-01-01

    Echocardiographic studies were performed preflight 5 days before launch and on recovery day and 1, 2, 4, 11, 31 and 68 days postflight. From these echocardiograms measurements were made. From these primary measurements, left ventricular end-diastolic volume, end-systolic volume, stroke volume, and mass were derived using the accepted assumptions. Findings in the Scientist Pilot and Pilot resemble those seen in trained distance runners. Wall thickness measurements were normal in all three crewmembers preflight. Postflight basal studies were unchanged in the Commander on recovery day through 68 days postflight in both the Scientist Pilot and Pilot, however, the left ventricular end-diastolic volume, stroke volume, and mass were decreased slightly. Left ventricular function curves were constructed for the Commander and Pilot by plotting stroke volume versus end-diastolic volume. In both astronauts, preflight and postflight data fell on the same straight line demonstrating that no deterioration in cardiac function had occurred. These data indicate that the cardiovascular system adapts well to prolonged weightlessness and suggest that alterations in cardiac dimensions and function are unlikely to limit man's future in space.

  17. Thermoregulatory responses to skin wetting during prolonged treadmill running.

    Science.gov (United States)

    Bassett, D R; Nagle, F J; Mookerjee, S; Darr, K C; Ng, A V; Voss, S G; Napp, J P

    1987-02-01

    We examined the physiological responses to skin wetting during a 120-min level treadmill run to assess whether skin wetting would reduce the dehydration and the increase in core temperature associated with prolonged exercise. Testing was conducted in an environmental chamber (T = 29.5 degrees C, wind velocity = 3 m X sec-1) under two different humidity conditions (33 or 66% relative humidity). Ten male subjects performed two runs in each humidity condition; one served as a control run. The other included spraying the body with 50 ml of water (T = 29.5 degrees C) every 10 min. Spraying had no effect on rectal temperature (Tre), heart rate, oxygen consumption, perceived exertion, sweat loss, or percent change in plasma volume in both the humid and the dry conditions. Spraying produced a significant reduction in mean skin temperature (Tsk), which increased the (Tre - Tsk) gradient. At the same time, overall skin conductance (K) was decreased, presumably as a result of cutaneous vasoconstriction due to the low Tsk. Since heat transfer from the body's core to the skin is expressed by the equation: heat transfer = K X (Tre - Tsk) the spraying had no effect on heat transfer away from the core, and Tre remained unchanged.

  18. Drained coastal peatlands: A potential nitrogen source to marine ecosystems under prolonged drought and heavy storm events-A microcosm experiment.

    Science.gov (United States)

    Wang, Hongjun; Richardson, Curtis J; Ho, Mengchi; Flanagan, Neal

    2016-10-01

    Over the past several decades there has been a massive increase in coastal eutrophication, which is often caused by increased runoff input of nitrogen from landscape alterations. Peatlands, covering 3% of land area, have stored about 12-21% of global soil organic nitrogen (12-20Pg N) around rivers, lakes and coasts over millennia and are now often drained and farmed. Their huge nitrogen pools may be released by intensified climate driven hydrologic events-prolonged droughts followed by heavy storms-and later transported to marine ecosystems. In this study, we collected peat monoliths from drained, natural, and restored coastal peatlands in the Southeastern U.S., and conducted a microcosm experiment simulating coupled prolonged-drought and storm events to (1) test whether storms could trigger a pulse of nitrogen export from drought-stressed peatlands and (2) assess how differentially hydrologic managements through shifting plant communities affect nitrogen export by combining an experiment of nitrogen release from litter. During the drought phase, we observed a significant temporal variation in net nitrogen mineralization rate (NMR). NMR spiked in the third month and then decreased rapidly. This pattern indicates that drought duration significantly affects nitrogen mineralization in peat. NMR in the drained site reached up to 490±110kgha(-1)year(-1), about 5 times higher than in the restored site. After the 14-month drought phase, we simulated a heavy storm by bringing peat monoliths to saturation. In the discharge waters, concentrations of total dissolved nitrogen in the monoliths from the drained site (72.7±16.3mgL(-1)) was about ten times as high as from the restored site. Our results indicate that previously drained peatlands under prolonged drought are a potent source of nitrogen export. Moreover, drought-induced plant community shifts to herbaceous plants substantially raise nitrogen release with lasting effects by altering litter quality in peatlands

  19. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits

    International Nuclear Information System (INIS)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-01-01

    Purpose: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Materials and methods: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. Results: The renal parenchymal platinum concentrations (μg/ml) with 4.51 ± 2.25 (day 0), 1.59 ± 0.70 (day 1), 0.72 ± 0.10 (day 3) and 0.20 ± 0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99 ± 0.55, 0.08 ± 0.03, 0.18 ± 0.01 and 0.10 ± 0.07, respectively. Relative tumor growth rates resulted in 84.5% ± 26.4 (group I); 241.4% ± 145.1 (II); 331.9% ± 72.2 (III), and 413.6% ± 103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. Conclusions: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an

  20. Released radioactivity reducing facility

    International Nuclear Information System (INIS)

    Tanaka, Takeaki.

    1992-01-01

    Upon occurrence of a reactor accident, penetration portions of a reactor container, as a main leakage source from a reactor container, are surrounded by a plurality of gas-tight chambers, the outside of which is surrounded by highly gas-tightly buildings. Branched pipelines of an emergency gas processing system are introduced to each of the gas-tight chambers and they are joined and in communication with an emergency gas processing device. With such a constitution, radioactive materials are prevented from leaking directly from the buildings. Further, pipeline openings of the emergency gas processing facility are disposed in the plurality highly gas-tight penetration chambers. If the radioactive materials are leaked from the reactor to elevate the pressure in the penetration chambers, the radioactive materials are introduced to a filter device in the emergency gas processing facility by way of the branched pipelines, filtered and then released to the atmosphere. Accordingly, the reliability and safety of the system can be improved. (T.M.)