WorldWideScience

Sample records for releasers potential treatment

  1. Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization.

    Science.gov (United States)

    Moreno, Miguel; Pow, Poh Yih; Tabitha, Tan Su Teng; Nirmal, Sonali; Larsson, Andreas; Radhakrishnan, Krishna; Nirmal, Jayabalan; Quah, Soo Tng; Geifman Shochat, Susana; Agrawal, Rupesh; Venkatraman, Subbu

    2017-08-01

    This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface. Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology. The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability. The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization.

  2. Assessment of potential climate change impacts on peatland dissolved organic carbon release and drinking water treatment from laboratory experiments

    International Nuclear Information System (INIS)

    Tang, R.; Clark, J.M.; Bond, T.; Graham, N.; Hughes, D.; Freeman, C.

    2013-01-01

    Catchments draining peat soils provide the majority of drinking water in the UK. Over the past decades, concentrations of dissolved organic carbon (DOC) have increased in surface waters. Residual DOC can cause harmful carcinogenic disinfection by-products to form during water treatment processes. Increased frequency and severity of droughts combined with and increased temperatures expected as the climate changes, have potentials to change water quality. We used a novel approach to investigate links between climate change, DOC release and subsequent effects on drinking water treatment. We designed a climate manipulation experiment to simulate projected climate changes and monitored releases from peat soil and litter, then simulated coagulation used in water treatment. We showed that the ‘drought’ simulation was the dominant factor altering DOC release and affected the ability to remove DOC. Our results imply that future short-term drought events could have a greater impact than increased temperature on DOC treatability. - Highlights: ► We model realistic temperature and moisture changes on peat and surface vegetation. ► Quantity, quality and treatability changes of dissolved organic carbon were examined. ► Moisture has significantly greater influence than temperature on DOC production. ► Dry conditions alter treatability of DOC released from surface litter. ► Droughts have greater impact on water treatment than short-term heat waves alone. - Future drought events are likely to alter soil moisture, which predominately controls production of peat-derived dissolved organic carbon and subsequently drinking water quality.

  3. Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Martinez-Raga J

    2015-05-01

    Full Text Available Jose Martinez-Raga,1,2 Carlos Knecht,3 Raquel de Alvaro4 1Teaching Unit of Psychiatry and Psychological Medicine, University Hospital Doctor Peset, University of Valencia, 2CEU Cardenal Herrera University, 3Área de Salud Mental, Hospital Padre Jofré, Valencia, 4Hospital General, Consorcio Hospitalario Provincial, Castellon, Spain Abstract: The α2-adrenergic receptor agonist guanfacine, in its extended-release formulation (GXR, is the most recent nonstimulant medication approved in several countries for the treatment of attention-deficit hyperactivity disorder (ADHD as monotherapy and as adjunctive pharmacotherapy to stimulants in children and adolescents. The present paper aims to review comprehensively and critically the pharmacodynamic and pharmacokinetic characteristics and the published evidence on the efficacy and safety profile of GXR in the treatment of ADHD. A comprehensive search of relevant databases (PubMed, Embase, and PsycInfo was conducted to identify studies published in peer-reviewed journals until January 15, 2015. Though the precise mechanism of action of guanfacine in the treatment of ADHD is not fully understood, it is thought to act directly by enhancing noradrenaline functioning via α2A-adrenoceptors in the prefrontal cortex. Weight-adjusted doses should be used, with a dosing regime on a milligram per kilogram basis, starting at doses in the range 0.05–0.08 mg/kg/day, up to 0.12 mg/kg/day. As evidenced in short-term randomized controlled trials and in long-term open-label extension studies, GXR has been shown to be effective as monotherapy in the treatment of ADHD. Furthermore, GXR has also been found to be effective as adjunctive therapy to stimulant medications in patients with suboptimal responses to stimulants. Many of the adverse reactions associated with GXR, particularly sedation-related effects, were dose-related, transient, mild to moderate in severity, and did not interfere with attention or overall

  4. The estrogen myth: potential use of gonadotropin-releasing hormone agonists for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Casadesus, Gemma; Garrett, Matthew R; Webber, Kate M; Hartzler, Anthony W; Atwood, Craig S; Perry, George; Bowen, Richard L; Smith, Mark A

    2006-01-01

    Estrogen and other sex hormones have received a great deal of attention for their speculative role in Alzheimer's disease (AD), but at present a direct connection between estrogen and the pathogenesis of AD remains elusive and somewhat contradictory. For example, on one hand there is a large body of evidence suggesting that estrogen is neuroprotective and improves cognition, and that hormone replacement therapy (HRT) at the onset of menopause reduces the risk of developing AD decades later. However, on the other hand, studies such as the Women's Health Initiative demonstrate that HRT initiated in elderly women increases the risk of dementia. While estrogen continues to be investigated, the disparity of findings involving HRT has led many researchers to examine other hormones of the hypothalamic-pituitary-gonadal axis such as luteinising hormone (LH) and follicle-stimulating hormone. In this review, we propose that LH, rather than estrogen, is the paramount player in the pathogenesis of AD. Notably, both men and women experience a 3- to 4-fold increase in LH with aging, and LH receptors are found throughout the brain following a regional pattern remarkably similar to those neuron populations affected in AD. With respect to disease, serum LH level is increased in women with AD relative to non-diseased controls, and levels of LH in the brain are also elevated in AD. Mechanistically, we propose that elevated levels of LH may be a fundamental instigator responsible for the aberrant reactivation of the cell cycle that is seen in AD. Based on these aforementioned aspects, clinical trials underway with leuprolide acetate, a gonadotropin-releasing hormone agonist that ablates serum LH levels, hold great promise as a ready means of treatment in individuals afflicted with AD.

  5. Progesterone treatment inhibits and dihydrotestosterone (DHT) treatment potentiates voltage-gated calcium currents in gonadotropin-releasing hormone (GnRH) neurons.

    Science.gov (United States)

    Sun, Jianli; Moenter, Suzanne M

    2010-11-01

    GnRH neurons are central regulators of fertility, and their activity is modulated by steroid feedback. In normal females, GnRH secretion is regulated by estradiol and progesterone (P). Excess androgens present in hyperandrogenemic fertility disorders may disrupt communication of negative feedback signals from P and/or independently stimulate GnRH release. Voltage-gated calcium channels (VGCCs) are important in regulating excitability and hormone release. Estradiol alters VGCCs in a time-of-day-dependent manner. To further elucidate ovarian steroid modulation of GnRH neuron VGCCs, we studied the effects of dihydrotestosterone (DHT) and P. Adult mice were ovariectomized (OVX) or OVX and treated with implants containing DHT (OVXD), estradiol (OVXE), estradiol and DHT (OVXED), estradiol and P (OVXEP), or estradiol, DHT, and P (OVXEDP). Macroscopic calcium current (I(Ca)) was recorded in the morning or afternoon 8-12 d after surgery using whole-cell voltage-clamp. I(Ca) was increased in afternoon vs. morning in GnRH neurons from OVXE mice but this increase was abolished in cells from OVXEP mice. I(Ca) in cells from OVXD mice was increased regardless of time of day; there was no additional effect in OVXED mice. P reduced N-type and DHT potentiated N- and R-type VGCCs; P blocked the DHT potentiation of N-type-mediated current. These data suggest P and DHT have opposing actions on VGCCs in GnRH neurons, but in the presence of both steroids, P dominates. VGCCs are targets of ovarian steroid feedback modulation of GnRH neuron activity and, more specifically, a potential mechanism whereby androgens could activate GnRH neuronal function.

  6. Ecotoxicological screen of Potential Release Site 50-006(d) of Operable Unit 1147 of Mortandad Canyon and relationship to the Radioactive Liquid Waste Treatment Facilities project

    International Nuclear Information System (INIS)

    Gonzales, G.J.; Newell, P.G.

    1996-04-01

    Potential ecological risk associated with soil contaminants in Potential Release Site (PRS) 50-006(d) of Mortandad Canyon at the Los Alamos National Laboratory was assessed by performing an ecotoxicological risk screen. The PRS surrounds Outfall 051, which discharges treated effluent from the Radioactive Liquid Waste Treatment Facility. Discharge at the outfall is permitted under the Clean Water Act National Pollution Discharge Elimination System. Radionuclide discharge is regulated by US Department of Energy (DOE) Order 5400.5. Ecotoxicological Screening Action Levels (ESALSs) were computed for nonradionuclide constituents in the soil, and human risk SALs for radionuclides were used as ESALs. Within the PRS and beginning at Outfall 051, soil was sampled at three points along each of nine linear transects at 100-ft intervals. Soil samples from 3 depths for each sampling point were analyzed for the concentration of a total of 121 constituents. Only the results of the surface sampling are reported in this report

  7. Antibiotic-Releasing Silk Biomaterials for Infection Prevention and Treatment

    OpenAIRE

    Pritchard, Eleanor M.; Valentin, Thomas; Panilaitis, Bruce; Omenetto, Fiorenzo; Kaplan, David L.

    2012-01-01

    Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled release polymer implants have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery including biocompatibility, tunable biodegradation, stabilizing effects, water-based processing and diverse material f...

  8. Releases of radioactivity from uranium mills and effluent treatment costs

    International Nuclear Information System (INIS)

    Witherspoon, J.P.; Sears, M.B.; Blanco, R.E.

    1977-01-01

    Airborne releases of radioactive materials from uranium milling to the environment consist of ore dust, yellowcake dust, tailings dust, and radon gas while the mill is active. After a mill has ceased operations, tailings may be stabilized to minimize or prevent airborne releases of radioactive particulates. However, radon gas will continue to be released in amounts inversely proportional to the degree of stabilization treatment (and expense). Liquid waste disposal is by evaporation and natural seepage to the ground beneath the tailings impoundment area. The release of radioactive materials (and potential radiation exposures) determines the majority of costs associated with minimizing the environmental impact of uranium milling. Radwaste treatments to reduce estimated radiation doses to individuals to 3 to 5% of those received with current milling practices are equivalent to $0.66 per pounds of U 3 O 8 and 0.032 mill per kWhr of electricity. This cost would cover a high efficiency reverse jet bag filter and high energy venturi scrubbers for dusts, neutralization of liquids, and an asphalt-lined tailings basin with a clay core dam to reduce seepage. In addition, this increased cost would cover stabilization of tailings, after mill closure, with a 1-in. asphalt membrane topped by 2 ft of earth and 0.5 ft of crushed rock to provide protection against future leaching and wind erosion. The cost of reducing the radiological hazards associated with uranium milling to this degree would contribute about 0.4% to the current total cost of nuclear power

  9. Calculations in support of a potential definition of large release

    International Nuclear Information System (INIS)

    Hanson, A.L.; Davis, R.E.; Mubayi, V.

    1994-05-01

    The Nuclear Regulatory Commission has stated a hierarchy of safety goals with the qualitative safety goals as Level I of the hierarchy, backed up by the quantitative health objectives as Level II and the large release guideline as Level III. The large release guideline has been stated in qualitative terms as a magnitude of release of the core inventory whose frequency should not exceed 10 -6 per reactor year. However, the Commission did not provide a quantitative specification of a large release. This report describes various specifications of a large release and focuses, in particular, on an examination of releases which have a potential to lead to one prompt fatality in the mean. The basic information required to set up the calculations was derived from the simplified source terms which were obtained from approximations of the NUREG-1150 source terms. Since the calculation of consequences is affected by a large number of assumptions, a generic site with a (conservatively determined) population density and meteorology was specified. At this site, various emergency responses (including no response) were assumed based on information derived from earlier studies. For each of the emergency response assumptions, a set of calculations were performed with the simplified source terms; these included adjustments to the source terms, such as the timing of the release, the core inventory, and the release fractions of different radionuclides, to arrive at a result of one mean prompt fatality in each case. Each of the source terms, so defined, has the potential to be a candidate for a large release. The calculations show that there are many possible candidate source terms for a large release depending on the characteristics which are felt to be important

  10. 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.

  11. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment

    Science.gov (United States)

    Gordon, Michael S.; Vocci, Frank J.; Fitzgerald, Terrence T.; O'Grady, Kevin E.; O'Brien, Charles P.

    2017-01-01

    Background Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases have been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Methods Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. PMID:28011389

  12. Surgical Treatment of Trigger Finger: Open Release

    Directory of Open Access Journals (Sweden)

    Firat Ozan

    2016-01-01

    Full Text Available In this study, open A1 pulley release results were evaluated in patients with a trigger finger diagnosis. 45 patients (29 females, 16 males, mean age 50.7 ± 11.9; range (24-79, 45 trigger fingers were released via open surgical technique. On the 25 of 45 cases were involved in the right hand and 16 of them were at the thumb, 2 at index, 6 at the middle and 1 at ring finger. Similarly, at the left hand, 15 of 20 cases were at the thumb, 1 at the index finger, 2 at middle finger and 2 at ring finger. Average follow-up time was 10.2 ± 2.7 (range, 6-15 months. Comorbidities in patients were; diabetes mellitus at 6 cases (13.3%, hypertension at 11 cases (24.4%, hyperthyroidism at 2 cases (4.4%, dyslipidemia at 2 cases (4.4% and lastly 2 cases had carpal tunnel syndrome operation. The mean time between the onset of symptoms to surgery was 6.9 ± 4.8 (range, 2-24 months. Patient satisfaction was very good in 34 cases (75.4% and good in 11 (24.6% patients. The distance between the pulpa of the operated finger and the palm was normal in every case postoperatively. We have not encountered any postoperative complications. We can recommend that; A1 pulley release via open incision is an effective and reliable method in trigger finger surgery.

  13. Punishment, Pharmacological Treatment, and Early Release

    DEFF Research Database (Denmark)

    Ryberg, Jesper

    2013-01-01

    Recent studies have shown that pharmacological treatment may have an impact on aggressive and impulsive behavior. Assuming that these results are correct, would it be morally acceptable to instigate violent criminals to accept pharmacological rehabilitation by offering this treatment in return fo...... relates to the acceptability of the fact that those criminals who accepted the treatment would be exempted from the punishment they rightly deserved. It is argued that none of these reasons succeeds in rejecting this sort of offer....

  14. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment.

    Science.gov (United States)

    Gordon, Michael S; Vocci, Frank J; Fitzgerald, Terrence T; O'Grady, Kevin E; O'Brien, Charles P

    2017-02-01

    Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. We describe the background and rationale for the study, its aims, hypotheses, and study design. The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Wolfram Eisenreich

    2010-01-01

    Full Text Available Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.

  16. Potential detection systems for monitoring UF6 releases

    International Nuclear Information System (INIS)

    Beck, D.E.; Bostick, W.D.; Armstrong, D.P.; McNeely, J.R.; Stockdale, J.A.D.

    1994-09-01

    In the near future, the Nuclear Regulatory Commission (NRC) will begin to regulate the gaseous diffusion plants. Them is a concern that the smoke detectors currently used for uranium hexafluoride (UF 6 ) release detection will not meet NRC safety system requirements such as high reliability and rapid response. The NRC's position is that licensees should utilize state-of-the-art equipment such as hydrogen fluoride (HF) detectors that would provide more dependable detection of a UF 6 release. A survey of the literature and current vendor information was undertaken to define the state-of-the-art and commercial availability of HF (or other appropriate) detection systems. For the purpose of this report, classification of the available HF detection systems is made on the basis of detection principle (e.g., calorimetric, electrochemical, separational, or optical). Emphasis is also placed on whether the device is primarily sensitive to response from a point source (e.g., outleakage in the immediate vicinity of a specific set of components), or whether the device is potentially applicable to remote sensing over a larger area. Traditional HF point source monitoring typically uses gas sampling tubes or coated paper tapes with color developing indicator, portable and small area HF monitors are often based upon electrochemical or extractive/separational systems; and remote sensing by optical systems holds promise for indoor and outdoor large area monitoring (including plant boundary/ambient air monitoring)

  17. Uncertainty about the release and postpenal treatment for convict women

    OpenAIRE

    Marussig, Špela

    2017-01-01

    Postpenal treatment is, as of yet, a poorly researched concept in Slovenia. It deals with aiding and supporting convicts during their sentence and after their release from prison. This entails assis-tance in arranging accommodation, finding employment, psychological counselling for the convict as well as support for his family. Using qualitative research, I intend to explore how the postpenal treatment process takes place in practice. The research relates exclusively to the female populati...

  18. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

    International Nuclear Information System (INIS)

    Menon, M.; Peegel, H.; Katta, V.

    1985-01-01

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

  19. Potential release scenarios for carbon nanotubes used in composites

    Science.gov (United States)

    The expected widespread use of carbon nanotube (CNT)-composites in consumer products calls for an assessment of the possible release and exposure to workers, consumers and the environment. Release of CNTs may occur at all steps in the life cycle of products, but to date only limi...

  20. Potential release scenarios for carbon nanotubes used in composites

    NARCIS (Netherlands)

    Nowack, B.; David, R.M.; Fissan, H.; Morris, H.; Shatkin, J.A.; Stintz, M.; Zepp, R.; Brouwer, D.

    2013-01-01

    The expected widespread use of carbon nanotube (CNT)-composites in consumer products calls for an assessment of the possible release and exposure to workers, consumers and the environment. Release of CNTs may occur at all steps in the life cycle of products, but to date only limited information is

  1. Bacterial inclusion bodies as potential synthetic devices for pathogen recognition and a therapeutic substance release.

    Science.gov (United States)

    Talafová, Klaudia; Hrabárová, Eva; Chorvát, Dušan; Nahálka, Jozef

    2013-02-07

    Adhesins of pathogens recognise the glycans on the host cell and mediate adherence. They are also crucial for determining the tissue preferences of pathogens. Currently, glyco-nanomaterials provide potential tool for antimicrobial therapy. We demonstrate that properly glyco-tailored inclusion bodies can specifically bind pathogen adhesins and release therapeutic substances. In this paper, we describe the preparation of tailored inclusion bodies via the conjugation of indicator protein aggregated to form inclusion bodies with soluble proteins. Whereas the indicator protein represents a remedy, the soluble proteins play a role in pathogen recognition. For conjugation, glutaraldehyde was used as linker. The treatment of conjugates with polar lysine, which was used to inactivate the residual glutaraldehyde, inhibited unwanted hydrophobic interactions between inclusion bodies. The tailored inclusion bodies specifically interacted with the SabA adhesin from Helicobacter pylori aggregated to form inclusion bodies that were bound to the sialic acids decorating the surface of human erythrocytes. We also tested the release of indicator proteins from the inclusion bodies using sortase A and Ssp DNAB intein self-cleaving modules, respectively. Sortase A released proteins in a relatively short period of time, whereas the intein cleavage took several weeks. The tailored inclusion bodies are promising "nanopills" for biomedical applications. They are able to specifically target the pathogen, while a self-cleaving module releases a soluble remedy. Various self-cleaving modules can be enabled to achieve the diverse pace of remedy release.

  2. Colloid electrochemistry of conducting polymer: towards potential-induced in-situ drug release

    International Nuclear Information System (INIS)

    Sankoh, Supannee; Vagin, Mikhail Yu.; Sekretaryova, Alina N.; Thavarungkul, Panote; Kanatharana, Proespichaya; Mak, Wing Cheung

    2017-01-01

    Highlights: • Pulsed electrode potential induced an in-situ drug release from dispersion of conducting polymer microcapsules. • Fast detection of the released drug within the colloid microenvironment. • Improved the efficiency of localized drug release at the electrode interface. - Abstract: Over the past decades, controlled drug delivery system remains as one of the most important area in medicine for various diseases. We have developed a new electrochemically controlled drug release system by combining colloid electrochemistry and electro-responsive microcapsules. The pulsed electrode potential modulation led to the appearance of two processes available for the time-resolved registration in colloid microenvironment: change of the electronic charge of microparticles (from 0.5 ms to 0.1 s) followed by the drug release associated with ionic equilibration (1–10 s). The dynamic electrochemical measurements allow the distinction of drug release associated with ionic relaxation and the change of electronic charge of conducting polymer colloid microparticles. The amount of released drug (methylene blue) could be controlled by modulating the applied potential. Our study demonstrated a surface-potential driven controlled drug release of dispersion of conducting polymer carrier at the electrode interfaces, while the bulk colloids dispersion away from the electrode remains as a reservoir to improve the efficiency of localized drug release. The developed new methodology creates a model platform for the investigations of surface potential-induced in-situ electrochemical drug release mechanism.

  3. Near-infrared remotely triggered drug-release strategies for cancer treatment

    Science.gov (United States)

    Goodman, Amanda M.; Neumann, Oara; Nørregaard, Kamilla; Henderson, Luke; Choi, Mi-Ran; Clare, Susan E.; Halas, Naomi J.

    2017-11-01

    Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

  4. The Human Exposure Potential from Propylene Releases to the Environment

    Directory of Open Access Journals (Sweden)

    David A. Morgott

    2018-01-01

    Full Text Available A detailed literature search was performed to assess the sources, magnitudes and extent of human inhalation exposure to propylene. Exposure evaluations were performed at both the community and occupational levels for those living or working in different environments. The results revealed a multitude of pyrogenic, biogenic and anthropogenic emission sources. Pyrogenic sources, including biomass burning and fossil fuel combustion, appear to be the primary contributors to atmospheric propylene. Despite a very short atmospheric lifetime, measurable levels could be detected in highly remote locations as a result of biogenic release. The indoor/outdoor ratio for propylene has been shown to range from about 2 to 3 in non-smoking homes, which indicates that residential sources may be the largest contributor to the overall exposure for those not occupationally exposed. In homes where smoking takes place, the levels may be up to thirty times higher than non-smoking residences. Atmospheric levels in most rural regions are typically below 2 ppbv, whereas the values in urban levels are much more variable ranging as high as 10 ppbv. Somewhat elevated propylene exposures may also occur in the workplace; especially for firefighters or refinery plant operators who may encounter levels up to about 10 ppmv.

  5. The levonorgestrel-releasing intrauterine device potentiates stress reactivity.

    Science.gov (United States)

    Aleknaviciute, Jurate; Tulen, Joke H M; De Rijke, Yolanda B; Bouwkamp, Christian G; van der Kroeg, Mark; Timmermans, Mirjam; Wester, Vincent L; Bergink, Veerle; Hoogendijk, Witte J G; Tiemeier, Henning; van Rossum, Elisabeth F C; Kooiman, Cornelis G; Kushner, Steven A

    2017-06-01

    The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability. We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure. Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (Pcontraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Treatment-Continuity of ADHD Compared Using Immediate-Release and Extended-Release MPH

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-07-01

    Full Text Available The continuity of methylphenidate (MPH therapy for ADHD in young Medicaid beneficiaries (ages 6 to 17 years treated with immediate-release (IR or extended-release (ER MPH formulations was compared in an analysis of statewide California Medicaid claims (2000-2003 conducted at Columbia University, New York; University of Pennsylvania, Philadelphia; and McNeil Pharmaceuticals, Fort Washington, PA.

  7. Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

    Science.gov (United States)

    Rivier, Jean E; Rivier, Catherine L

    2014-04-01

    Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations.

    Science.gov (United States)

    McLatchie, L M; Young, J S; Fry, C H

    2014-07-01

    The aim of this study was to quantify and characterize the mechanism of non-neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti-muscarinic drugs. A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release. Minimal mechanical stimulus achieved full ACh release, indicating a small dynamic range and possible all-or-none signal. ACh release involved a mechanism dependent on the anion channel CFTR and intracellular calcium concentration, but was independent of extracellular calcium, vesicular trafficking, connexins or pannexins, organic cation transporters and was not affected by botulinum-A toxin. Stimulating ACh receptors increased ATP production and antagonizing them reduced ATP release, suggesting a link between ACh and ATP release. These results suggest that release of non-neuronal ACh from the urothelium is large enough and well located to act as a modulator of ATP release. It is hypothesized that this pathway may contribute to the actions of anti-muscarinic drugs in reducing the symptoms of lower urinary tract syndromes. Additionally the involvement of CFTR in ACh release suggests an exciting new direction for the treatment of these conditions. © 2014 The British Pharmacological Society.

  9. Potential risks of TiO{sub 2} and ZnO nanoparticles released from sunscreens into outdoor swimming pools

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Soo-kyung [Center for Water Resource Cycle, Green City Technology Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791 (Korea, Republic of); Energy Environment Policy and Technology, Green School, Korea University (KU)-Korea Institute of Science and Technology (KIST), Seoul 136-701 (Korea, Republic of); Kim, Eun-ju [Center for Water Resource Cycle, Green City Technology Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791 (Korea, Republic of); Lee, Jaesang [Energy Environment Policy and Technology, Green School, Korea University (KU)-Korea Institute of Science and Technology (KIST), Seoul 136-701 (Korea, Republic of); Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Lee, Seunghak, E-mail: seunglee@kist.re.kr [Center for Water Resource Cycle, Green City Technology Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791 (Korea, Republic of); Energy Environment Policy and Technology, Green School, Korea University (KU)-Korea Institute of Science and Technology (KIST), Seoul 136-701 (Korea, Republic of)

    2016-11-05

    Highlights: • Nanoparticles from sunscreen products can be released into public pools. • Nanoparticles and organic ingredients can generate reactive oxygen species (ROS). • A negative impact of ROS should not be significant in swimming pool. - Abstract: The potential risks of nanoparticles (NPs) in sunscreens being released into swimming water were evaluated by a series of laboratory experiments simulating the fate and transport of NPs in outdoor swimming pools. NPs released from sunscreen-applied skin were estimated using pig skins covered with five different commercial sunscreens containing TiO{sub 2}, ZnO, or both at various concentrations. Assuming that the swimming water treatment processes consisted of filtration, UV irradiation, heating, and chlorination, possible removal of the released NPs by each process was estimated. Generation of hydrogen peroxide (H{sub 2}O{sub 2}) by the NPs under sunlight and after UV photochemical treatment were measured, and the H{sub 2}O{sub 2} concentration possibly present in the swimming pool was calculated based on some specific scenarios of operating an outdoor swimming pool. It was found that a significant amount of the NPs in sunscreens could be released into the swimming water, and accumulate during circulation through the treatment system. However, the concentration of H{sub 2}O{sub 2} possibly present in the swimming pool should be below the level at which an adverse effect to bathers is concerned.

  10. Potential risks of TiO_2 and ZnO nanoparticles released from sunscreens into outdoor swimming pools

    International Nuclear Information System (INIS)

    Jeon, Soo-kyung; Kim, Eun-ju; Lee, Jaesang; Lee, Seunghak

    2016-01-01

    Highlights: • Nanoparticles from sunscreen products can be released into public pools. • Nanoparticles and organic ingredients can generate reactive oxygen species (ROS). • A negative impact of ROS should not be significant in swimming pool. - Abstract: The potential risks of nanoparticles (NPs) in sunscreens being released into swimming water were evaluated by a series of laboratory experiments simulating the fate and transport of NPs in outdoor swimming pools. NPs released from sunscreen-applied skin were estimated using pig skins covered with five different commercial sunscreens containing TiO_2, ZnO, or both at various concentrations. Assuming that the swimming water treatment processes consisted of filtration, UV irradiation, heating, and chlorination, possible removal of the released NPs by each process was estimated. Generation of hydrogen peroxide (H_2O_2) by the NPs under sunlight and after UV photochemical treatment were measured, and the H_2O_2 concentration possibly present in the swimming pool was calculated based on some specific scenarios of operating an outdoor swimming pool. It was found that a significant amount of the NPs in sunscreens could be released into the swimming water, and accumulate during circulation through the treatment system. However, the concentration of H_2O_2 possibly present in the swimming pool should be below the level at which an adverse effect to bathers is concerned.

  11. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    Science.gov (United States)

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  12. Controlled release gelatin hydrogels and lyophilisates with potential application as ocular inserts

    Energy Technology Data Exchange (ETDEWEB)

    Natu, Madalina V [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Sardinha, Jose P [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Correia, IlIdio J [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal)

    2007-12-15

    Hydrogels and lyophilisates were obtained by chemical crosslinking of gelatin using N-hydroxysuccinimide and N, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride. The systems were characterized with respect to the degree of crosslinking, morphology, water uptake, in vitro drug release and biocompatibility studies. Pilocarpine hydrochloride, a drug for the treatment of glaucoma, was loaded by soaking in an aqueous solution containing the drug. In vitro, the released drug percentage varied between 29.2% and 99.2% in 8 h of study. The release data were fitted to the Korsmeyer-Peppas equation to calculate the release exponent, which indicated anomalous transport for the release of pilocarpine. The corneal endothelial cell culture tests indicated that the prepared biomaterials are not cytotoxic.

  13. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

    Directory of Open Access Journals (Sweden)

    Rocío Herrero-Vanrell, Jose Augusto Cardillo

    2011-02-01

    Full Text Available Rocío Herrero-Vanrell1, Jose Augusto Cardillo2, Baruch D Kuppermann31Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain; 2Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil; 3Gavin Herbert Eye Institute, University of California, Irvine, CA, USAAbstract: Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex® has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome.Keywords: diabetic retinopathy, macular edema, Ozurdex®, posterior-segment inflammatory disease, retinal vein occlusion, sustained-release dexamethasone implant

  14. Feasibility and preliminary safety of nitric oxide releasing solution as a treatment for bovine mastitis.

    Science.gov (United States)

    Regev, Gilly; Martins, James; Sheridan, Michael P; Leemhuis, Jonathan; Thompson, James; Miller, Christopher

    2018-06-01

    Nitric oxide-releasing solution (NORS) is a liquid formulation that releases nitric oxide, a broad spectrum antimicrobial, single electron nitroxide radical. This solution was investigated as a potential antimicrobial treatment for bovine mastitis (BM). Three experiments were performed: a) NORS' effect on Staphylococcus aureus and Escherichia coli in an in vitro model; b) NORS' effect on milk obtained from dairy cows showing symptoms of clinical mastitis; and c) the consequences of administering NORS to healthy milking cattle using a dose-escalating in vivo study. Metabolite concentrations were estimated in their blood for methaemoglobin and nitrite; also, milk nitrite concentration and somatic cell count (SCC) were measured to study possible mammary gland inflammation following treatment. NORS lowered the bacterial concentration in all infected samples, in a time- and milk-diluted dependant fashion. Blood methemoglobin concentrations following treatment were all within the normal range for cattle. However, blood and milk nitrite concentrations increased initially but, during the next 24 h, returned to normal range, as did SCC, without any clinical signs of mammary gland inflammation. NORS, if shown to be effective, could be an alternative treatment for mastitis with a shorter clearance time. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Application of Emergency Action Levels from Potential Release at Research Reactor HANARO

    International Nuclear Information System (INIS)

    Kim, Jongsoo; Lee, Goan Yub; Lee, Hae Choi; Kim, Bong Suk

    2014-01-01

    Execution of the protective action promptly is possible that Emergency Action Levels (EALs) must be established for a radiological release from nuclear facility. The EALs for electric power reactor are already developed and applied to recognize an emergency situation rapidly. Recently the IAEA published the safety report including the EALs for research reactor. This paper describes the EALs to apply for a potential release pathway at the research reactor HANARO. The results of table 1 and 2 will be higher than actual because the weather condition in real situation is difference. However, the EALs applying the potential stack release, ground release and site can be useful for research reactor HANARO making the emergency declaration. The EALs at the site boundary of the table 3 can be applied to protect the off-site public

  16. Prolactin-releasing peptide: a new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Pražienková, V.; Popelová, A.; Mikulášková, Barbora; Zemenová, J.; Maletínská, L.

    2016-01-01

    Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

  17. Prolactin-releasing peptide: a new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Pražienková, Veronika; Popelová, Andrea; Mikulášková, Barbora; Zemenová, Jana; Maletínská, Lenka

    2016-01-01

    Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

  18. HPLC analysis of potentially harmful substances released from dental filing aterials available on the EU market

    Directory of Open Access Journals (Sweden)

    Konrad Małkiewicz

    2014-03-01

    Full Text Available Introduction. Incomplete cross-linking of composite dental materials leads to their susceptibility to degradation in the environment of non-organic and organic solvents, contributing to the release of chemical compounds which are potentially harmful to living organisms. Objective. The aim of the study was an evaluation in in vitro conditions of releasing of potentially toxic substances from six dental composite materials available in EU countries. Materials and methods. The following compounds released from the samples stored in water were analyzed: bisphenol A (BPA, triethylene glycol-dimethacrylate (TEGDMA, urethane dimethacrylate (UDMA and ethylene glycol dimethacrylate (EDGMA. Analysis of the substances was performed with the use of high performance liquid chromatography, after the following incubation periods: 1 hour, 24 hours, 7 days and 30 days. Results. Among the analyzed substances, after 1 hour of incubation, the highest average concentration was found for TEGDMA – 2045 μg cm-3 (in Herculite XRV material, after 24 hours – for UDMA 4.402 μg cm-3 (in Gradia Direct Anterior material and after 7 and 30 days for TEGDMA: 8.112 and 6.458 μg•cm-3 respectively (in Charisma material. Conclusions. The examined composites used for reconstruction of hard tissues of teeth remain chemically unstable after polymerization, and release potentially harmful substances in conditions of the present study. The dynamics of the releasing of potentially harmful substances is correlated with the period of sample storage in water.

  19. Conductive polymers for controlled release and treatment of central nervous system injury

    Science.gov (United States)

    Saigal, Rajiv

    As one of the most devastating forms of neurotrauma, spinal cord injury remains a challenging clinical problem. The difficulties in treatment could potentially be resolved by better technologies for therapeutic delivery. In order to develop new approaches to treating central nervous system injury, this dissertation focused on using electrically-conductive polymers, controlled drug release, and stem cell transplantation. We first sought to enhance the therapeutic potential of neural stem cells by electrically increasing their production of neurotrophic factors (NTFs), important molecules for neuronal cell survival, differentiation, synaptic development, plasticity, and growth. We fabricated a new cell culture device for growing neural stem cells on a biocompatible, conductive polymer. Electrical stimulation via the polymer led to upregulation of NTF production by neural stem cells. This approach has the potential to enhance stem cell function while avoiding the pitfalls of genetic manipulation, possibly making stem cells more viable as a clinical therapy. Seeing the therapeutic potential of conductive polymers, we extended our studies to an in vivo model of spinal cord injury (SCI). Using a novel fabrication and extraction technique, a conductive polymer was fabricated to fit to the characteristic pathology that follows contusive SCI. Assessed via quantitative analysis of MR images, the conductive polymer significantly reduced compression of the injured spinal cord. Further characterizing astroglial and neuronal response of injured host tissue, we found significant neuronal sparing as a result of this treatment. The in vivo studies also demonstrated improved locomotor recovery mediated by a conductive polymer scaffold over a non-conductive control. We next sought to take advantage of conductive polymers for local, electronically-controlled release of drugs. Seeking to overcome reported limitations in drug delivery via polypyrrole, we first embedded drugs in poly

  20. Exposure to potentially toxic hydrocarbons and halocarbons released from the dialyzer and tubing set during hemodialysis.

    Science.gov (United States)

    Lee, Hyun Ji Julie; Meinardi, Simone; Pahl, Madeleine V; Vaziri, Nostratola D; Blake, Donald R

    2012-10-01

    Although much is known about the effect of chronic kidney failure and dialysis on the composition of solutes in plasma, little is known about their impact on the composition of gaseous compounds in exhaled breath. This study was designed to explore the effect of uremia and the hemodialysis (HD) procedure on the composition of exhaled breath. Breath samples were collected from 10 dialysis patients immediately before, during, and after a dialysis session. To determine the potential introduction of gaseous compounds from dialysis components, gasses emitted from dialyzers, tubing set, dialysate, and water supplies were collected. Prospective cohort study. 10 HD patients and 10 age-matched healthy individuals. Predictors include the dialyzers, tubing set, dialysate, and water supplies before, during, and after dialysis. Changes in the composition of exhaled breath. A 5-column/detector gas chromatography system was used to measure hydrocarbon, halocarbon, oxygenate, and alkyl nitrate compounds. Concentrations of 14 hydrocarbons and halocarbons in patients' breath rapidly increased after the onset of the HD treatment. All 14 compounds and 5 others not found in patients' breath were emitted from the dialyzers and tubing sets. Contrary to earlier reports, exhaled breath ethane concentrations in our dialysis patients were virtually unchanged during the HD treatment. Single-center study with a small sample size may limit the generalizability of the findings. The study documented the release of several potentially toxic hydrocarbons and halocarbons to patients from the dialyzer and tubing sets during the HD procedure. Because long-term exposure to these compounds may contribute to the morbidity and mortality in dialysis population, this issue should be considered in the manufacturing of the new generation of dialyzers and dialysis tubing sets. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. Selective release of phosphorus and nitrogen from waste activated sludge with combined thermal and alkali treatment.

    Science.gov (United States)

    Kim, Minwook; Han, Dong-Woo; Kim, Dong-Jin

    2015-08-01

    Selective release characteristics of phosphorus and nitrogen from waste activated sludge (WAS) were investigated during combined thermal and alkali treatment. Alkali (0.001-1.0N NaOH) treatment and combined thermal-alkali treatment were applied to WAS for releasing total P(T-P) and total nitrogen(T-N). Combined thermal-alkali treatment released 94%, 76%, and 49% of T-P, T-N, and COD, respectively. Release rate was positively associated with NaOH concentration, while temperature gave insignificant effect. The ratio of T-N and COD to T-P that released with alkali treatment ranged 0.74-0.80 and 0.39-0.50, respectively, while combined thermal-alkali treatment gave 0.60-0.90 and 0.20-0.60, respectively. Selective release of T-P and T-N was negatively associated with NaOH. High NaOH concentration created cavities on the surface of WAS, and these cavities accelerated the release rate, but reduced selectivity. Selective release of P and N from sludge has a beneficial effect on nutrient recovery with crystallization processes and it can also enhance methane production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Assessment of the Potential Release of Radioactivity from Installations at AERE, Harwell. Implications for Emergency Planning

    Energy Technology Data Exchange (ETDEWEB)

    Flew, Elizabeth M.; Lister, B. A.J. [Atomic Energy Research Establishment, Harwell, Didcot, Berks. (United Kingdom)

    1969-10-15

    As part of a review of the site emergency organization at AERE, a realistic reappraisal has been made of the potential hazard to the establishment and district of all the buildings containing significant amounts of radioactive materials. To assess the amount of radioactive material which might be released under specified accident conditions, four factors have been applied to the total building stock: (a) the fraction of the stock involved, (b) the percentage conversion to an aerosol form, (c) release from primary containment and (d) release from the building. These potential release figures have been compared with ''site hazardous release'' figures for relevant radionuclides i.e., amounts which could give rise to exposure above defined reference levels. Those buildings with more than one tenth of the potential for causing; a site or district hazard have been designated ''risk buildings''. Such a quantitative assessment, although necessarily very approximate, has been of considerable value in determining the type and complexity of the central emergency organization required and in producing the right emphasis on exercises, training, liaison with outside bodies, etc. (author)

  3. Modulation of the effect of acetylcholine on insulin release by the membrane potential of B cells

    International Nuclear Information System (INIS)

    Hermans, M.P.; Schmeer, W.; Henquin, J.C.

    1987-01-01

    Mouse islets were used to test the hypothesis that the B cell membrane must be depolarized for acetylcholine to increase insulin release. The resting membrane potential of B cells (at 3 mM glucose) was slightly decreased (5 mV) by acetylcholine, but no electrical activity appeared. This depolarization was accompanied by a Ca-independent acceleration of 86 Rb and 45 Ca efflux but no insulin release. When the B cell membrane was depolarized by a stimulatory concentration of glucose (10 mM), acetylcholine potentiated electrical activity, accelerated 86 Rb and 45 Ca efflux, and increased insulin release. This latter effect, but not the acceleration of 45 Ca efflux, was totally dependent on extracellular Ca. If glucose-induced depolarization of the B cell membrane was prevented by diazoxide, acetylcholine lost all effects but those produced at low glucose. In contrast, when the B cell membrane was depolarized by leucine or tolbutamide (at 3 mM glucose), acetylcholine triggered a further depolarization with appearance of electrical activity, accelerated 86 Rb and 45 Ca efflux, and stimulated insulin release. Acetylcholine produced similar effects (except for electrical activity) in the presence of high K or arginine which, unlike the above test agents, depolarize the B cell membrane by a mechanism other than a decrease in K+ permeability. Omission of extracellular Ca abolished the releasing effect of acetylcholine under all conditions but only partially decreased the stimulation of 45 Ca efflux. The results show thus that acetylcholine stimulation of insulin release does not result from mobilization of cellular Ca but requires that the B cell membrane be sufficiently depolarized to reach the threshold potential where Ca channels are activated. This may explain why acetylcholine alone does not initiate release but becomes active in the presence of a variety of agents

  4. Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

    Science.gov (United States)

    Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

    2013-09-01

    Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

  5. Exploring the Nutrient Release Potential of Organic Materials as Integrated Soil Fertility Management Components Using SAFERNAC

    NARCIS (Netherlands)

    Maro, G.P.; Mrema, J.P.; Msanya, B.M.; Janssen, B.H.; Teri, J.M.

    2014-01-01

    The aim of this study was to establish the nutrient release potential of different organic materials and assess their role in integrated soil fertility management for coffee using the new coffee yield model SAFERNAC. It involved an incubation experiment conducted at TaCRI Lyamungu Screenhouse for

  6. Recidivism of Offenders with Mental Illness Released from Prison to an Intensive Community Treatment Program

    Science.gov (United States)

    Theurer, Gregory; Lovell, David

    2008-01-01

    An intensive case management treatment program for mentally ill offenders (MIOs) is outlined, and subsequent recidivism of participants is evaluated. Features of the program and its development are discussed. Sixty-four (64) participants released from state prison between 1998 and 2003 were matched with a group of MIOs released earlier on eight…

  7. Lateral Cricoarytenoid Release: Development of a Novel Surgical Treatment Option for Adductor Spasmodic Dysphonia in a Canine Laryngeal Model.

    Science.gov (United States)

    Park, Andrea M; Paniello, Randal C

    2016-09-01

    To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease the force of vocal fold adduction, as a potential surgical therapy for patients with adductor spasmodic dysphonia (ADSD). Experimental animal study. A canine laryngeal model was used to assess the acute and sustained efficacy of a lateral cricoarytenoid (LCA) muscle release. A total of 34 canine hemilaryngeal preparations were divided among 7 experimental groups. The LCA muscle was separated from its cricoid cartilage origin via an open, anterior, submucosal approach. The laryngeal adductory pressures (LAP) were assessed pre- and post-muscle release via direct recurrent laryngeal nerve stimulation. Measurements were repeated at 1.5, 3, or 6 months postoperatively. Another study evaluated release of the thyroarytenoid (TA) muscle from its thyroid cartilage origin. Releasing the LCA muscle demonstrated a significant decrease in LAP acutely and was maintained at all 3 time points with the aid of a barrier (P < .05). Without the barrier, the LCA muscle reattached to the cricoid. Acute release of the TA muscle did not significantly decrease the LAP. The proposed LCA release procedure may provide patients with a permanent treatment option for ADSD. However, longer-term studies and human trials are needed. © The Author(s) 2016.

  8. Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

    Science.gov (United States)

    Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

    2016-01-01

    Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin

  9. Calcium-Induced calcium release during action potential firing in developing inner hair cells.

    Science.gov (United States)

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

    2015-03-10

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  10. A review of ''The potential effects of release of krypton-85''

    International Nuclear Information System (INIS)

    Saunders, C.P.R.

    1993-06-01

    A Report into the potential effects of the release of Krypton-85 from the Thermal Oxide Reprocessing Plant (THORP) at Sellafield, was commissioned by British Nuclear Fuels Ltd. The report dealt with the atmospheric impact of the release of Krypton-85 and considered specifically the areas of atmospheric electricity, ionisation, aerosols and conductivity, in terms of the releases of Krypton-85 from THORP. This present review has three objectives: to consider the atmospheric effects of the proposed discharges from THORP, to comment upon the magnitude of the postulated effects from Krypton-85 discharges compared with those from other sources of radioactivity in the atmosphere, and, to comment on the conclusions drawn by the authors of the report. This review was conducted under the aegis of the United Kingdom Inspectorate of Pollution. (author)

  11. Characteristics of Polybrominated Diphenyl Ethers Released from Thermal Treatment and Open Burning of E-Waste.

    Science.gov (United States)

    Li, Ting-Yu; Zhou, Jun-Feng; Wu, Chen-Chou; Bao, Lian-Jun; Shi, Lei; Zeng, Eddy Y

    2018-04-17

    Primitive processing of e-waste potentially releases abundant organic contaminants to the environment, but the magnitudes and mechanisms remain to be adequately addressed. We conducted thermal treatment and open burning of typical e-wastes, that is, plastics and printed circuit boards. Emission factors of the sum of 39 polybrominated diphenyl ethers (∑ 39 PBDE) were 817-1.60 × 10 5 ng g -1 in thermal treatment and nondetected-9.14 × 10 4 ng g -1 , in open burning. Airborne particles (87%) were the main carriers of PBDEs, followed by residual ashes (13%) and gaseous constituents (0.3%), in thermal treatment, while they were 30%, 43% and 27% in open burning. The output-input mass ratios of ∑ 39 PBDE were 0.12-3.76 in thermal treatment and 0-0.16 in open burning. All PBDEs were largely affiliated with fine particles, with geometric mean diameters at 0.61-0.83 μm in thermal degradation and 0.57-1.16 μm in open burning from plastic casings, and 0.44-0.56 and nondetected- 0.55 μm, from printed circuit boards. Evaporation and reabsorption may be the main emission mechanisms for lightly brominated BDEs, but heavily brominated BDEs tend to affiliate with particles from heating or combustion. The different size distributions of particulate PBDEs in emission sources and adjacent air implicated a noteworthy redisposition process during atmospheric dispersal.

  12. Selenium release from coal mines in the Elk Valley, and treatment R and D plans

    International Nuclear Information System (INIS)

    Jones, R.G.; Briennes, S.H.; Jensen, S.E.; Tompkins, A.N.

    2009-01-01

    This paper reported on methods to address the increase in mean selenium (Se) concentration in the Elk River in southeastern British Columbia, where Teck Coal Limited operates 5 coal mines. The primary sources of Se are the large rock spoils in the drainage area. Research into the removal of Se by water treatment is underway. The 3 management approaches to control Se include release prevention; control of Se in the environment; and water treatment. Although all 3 approaches are being investigated by Teck, this paper focused on water treatment alternatives and mobilization of Se from settling pond settlements. Bench-scale testing of active, passive and hybrid bioreactors at Teck's Applied Research and Technology (ART) centre showed that up to 98 per cent Se can be removed. Mobilization experiments in humidity cells showed the potential for Se to leach from sediment samples. It was concluded that biological treatment involving reduction and volatilization methods is effective for Se removal in high flow, multiple discharge and low concentration scenarios typical at the study sites. 9 refs., 2 tabs., 7 figs.

  13. Automated identification of potential snow avalanche release areas based on digital elevation models

    Science.gov (United States)

    Bühler, Y.; Kumar, S.; Veitinger, J.; Christen, M.; Stoffel, A.; Snehmani

    2013-05-01

    The identification of snow avalanche release areas is a very difficult task. The release mechanism of snow avalanches depends on many different terrain, meteorological, snowpack and triggering parameters and their interactions, which are very difficult to assess. In many alpine regions such as the Indian Himalaya, nearly no information on avalanche release areas exists mainly due to the very rough and poorly accessible terrain, the vast size of the region and the lack of avalanche records. However avalanche release information is urgently required for numerical simulation of avalanche events to plan mitigation measures, for hazard mapping and to secure important roads. The Rohtang tunnel access road near Manali, Himachal Pradesh, India, is such an example. By far the most reliable way to identify avalanche release areas is using historic avalanche records and field investigations accomplished by avalanche experts in the formation zones. But both methods are not feasible for this area due to the rough terrain, its vast extent and lack of time. Therefore, we develop an operational, easy-to-use automated potential release area (PRA) detection tool in Python/ArcGIS which uses high spatial resolution digital elevation models (DEMs) and forest cover information derived from airborne remote sensing instruments as input. Such instruments can acquire spatially continuous data even over inaccessible terrain and cover large areas. We validate our tool using a database of historic avalanches acquired over 56 yr in the neighborhood of Davos, Switzerland, and apply this method for the avalanche tracks along the Rohtang tunnel access road. This tool, used by avalanche experts, delivers valuable input to identify focus areas for more-detailed investigations on avalanche release areas in remote regions such as the Indian Himalaya and is a precondition for large-scale avalanche hazard mapping.

  14. Automated identification of potential snow avalanche release areas based on digital elevation models

    Directory of Open Access Journals (Sweden)

    Y. Bühler

    2013-05-01

    Full Text Available The identification of snow avalanche release areas is a very difficult task. The release mechanism of snow avalanches depends on many different terrain, meteorological, snowpack and triggering parameters and their interactions, which are very difficult to assess. In many alpine regions such as the Indian Himalaya, nearly no information on avalanche release areas exists mainly due to the very rough and poorly accessible terrain, the vast size of the region and the lack of avalanche records. However avalanche release information is urgently required for numerical simulation of avalanche events to plan mitigation measures, for hazard mapping and to secure important roads. The Rohtang tunnel access road near Manali, Himachal Pradesh, India, is such an example. By far the most reliable way to identify avalanche release areas is using historic avalanche records and field investigations accomplished by avalanche experts in the formation zones. But both methods are not feasible for this area due to the rough terrain, its vast extent and lack of time. Therefore, we develop an operational, easy-to-use automated potential release area (PRA detection tool in Python/ArcGIS which uses high spatial resolution digital elevation models (DEMs and forest cover information derived from airborne remote sensing instruments as input. Such instruments can acquire spatially continuous data even over inaccessible terrain and cover large areas. We validate our tool using a database of historic avalanches acquired over 56 yr in the neighborhood of Davos, Switzerland, and apply this method for the avalanche tracks along the Rohtang tunnel access road. This tool, used by avalanche experts, delivers valuable input to identify focus areas for more-detailed investigations on avalanche release areas in remote regions such as the Indian Himalaya and is a precondition for large-scale avalanche hazard mapping.

  15. Layered double hydroxide using hydrothermal treatment: morphology evolution, intercalation and release kinetics of diclofenac sodium

    Institute of Scientific and Technical Information of China (English)

    Mathew JOY; Srividhya J.IYENGAR; Jui CHAKRABORTY; Swapankumar GHOSH

    2017-01-01

    The present work demonstrates the possibilities of hydrothermal transformation of Zn-AI layered double hydroxide (LDH) nanostructure by varying the synthetic conditions.The manipulation in washing step before hydrothermal treatment allows control over crystal morphologies,size and stability of their aqueous solutions.We examined the crystal growth process in the presence and the absence of extra ions during hydrothermal treatment and its dependence on the drug (diclofenac sodium (DicNa)) loading and release processes.Hexagonal plate-like crystals show sustained release with ~90% of the drug from the matrix in a week,suggesting the applicability of LDH nanohybrids in sustained drug delivery systems.The fits to the release kinetics data indicated the drug release as a diffusion-controlled release process.LDH with rod-like morphology shows excellent colloidal stability in aqueous suspension,as studied by photon correlation spectroscopy.

  16. Layered double hydroxide using hydrothermal treatment: morphology evolution, intercalation and release kinetics of diclofenac sodium

    Science.gov (United States)

    Joy, Mathew; Iyengar, Srividhya J.; Chakraborty, Jui; Ghosh, Swapankumar

    2017-12-01

    The present work demonstrates the possibilities of hydrothermal transformation of Zn-Al layered double hydroxide (LDH) nanostructure by varying the synthetic conditions. The manipulation in washing step before hydrothermal treatment allows control over crystal morphologies, size and stability of their aqueous solutions. We examined the crystal growth process in the presence and the absence of extra ions during hydrothermal treatment and its dependence on the drug (diclofenac sodium (Dic-Na)) loading and release processes. Hexagonal plate-like crystals show sustained release with ˜90% of the drug from the matrix in a week, suggesting the applicability of LDH nanohybrids in sustained drug delivery systems. The fits to the release kinetics data indicated the drug release as a diffusion-controlled release process. LDH with rod-like morphology shows excellent colloidal stability in aqueous suspension, as studied by photon correlation spectroscopy.

  17. Atmospheric Dispersion Assessment for Potential Accidental Releases at Yonggwang Nuclear Power Plants

    International Nuclear Information System (INIS)

    Na, Man Gyun; Sim, Young Rok; Jung, Chul Kee; Lee, Goung Jin; Kim, Soong Pyung; Chung, Sung Tai

    2000-01-01

    XOQ DW code is currently used to assess the atmospheric dispersion for the routine releases of radioactive gaseous effluents at Yonggwang nuclear power plants. This code was developed based on XOQDOQ code and an additional code is required to assess the atmospheric dispersion for potential accidental releases. In order to assess the atmospheric dispersion for the accidental releases, XOQAR code has been developed by using PAVAN code that is based on Reg. Guide 1.145. The terrain data of XOQ DW code inputs and the relative concentrations (X/Q) of XOQ DW code outputs are used as the inputs of the XOQAR code through the interface with XOQ DW code. By using this code, the maximum values of X/Q at exclusion area and low population zone boundaries except for sea areas were assessed as 1.33 x 10 -4 and 7.66 x 10 -6 sec/m 3 , respectively. Through the development of this code, a code system is prepared for assessing the atmospheric dispersion for the accidental releases as well as the routine releases. This developed code can be used for other domestic nuclear power plants by modifying the terrain input data

  18. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  19. 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.

  20. Potential of Phytase-Mediated Iron Release from Cereal-Based Foods: A Quantitative View

    Science.gov (United States)

    Nielsen, Anne V. F.; Tetens, Inge; Meyer, Anne S.

    2013-01-01

    The major part of iron present in plant foods such as cereals is largely unavailable for direct absorption in humans due to complexation with the negatively charged phosphate groups of phytate (myo-inositol (1,2,3,4,5,6)-hexakisphosphate). Human biology has not evolved an efficient mechanism to naturally release iron from iron phytate complexes. This narrative review will evaluate the quantitative significance of phytase-catalysed iron release from cereal foods. In vivo studies have shown how addition of microbially derived phytases to cereal-based foods has produced increased iron absorption via enzyme-catalysed dephosphorylation of phytate, indicating the potential of this strategy for preventing and treating iron deficiency anaemia. Despite the immense promise of this strategy and the prevalence of iron deficiency worldwide, the number of human studies elucidating the significance of phytase-mediated improvements in iron absorption and ultimately in iron status in particularly vulnerable groups is still low. A more detailed understanding of (1) the uptake mechanism for iron released from partially dephosphorylated phytate chelates, (2) the affinity of microbially derived phytases towards insoluble iron phytate complexes, and (3) the extent of phytate dephosphorylation required for iron release from inositol phosphates is warranted. Phytase-mediated iron release can improve iron absorption from plant foods. There is a need for development of innovative strategies to obtain better effects. PMID:23917170

  1. The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels.

    Science.gov (United States)

    Riquelme, Manuel A; Cea, Luis A; Vega, José L; Boric, Mauricio P; Monyer, Hannah; Bennett, Michael V L; Frank, Marina; Willecke, Klaus; Sáez, Juan C

    2013-12-01

    During repetitive stimulation of skeletal muscle, extracellular ATP levels raise, activating purinergic receptors, increasing Ca2+ influx, and enhancing contractile force, a response called potentiation. We found that ATP appears to be released through pannexin1 hemichannels (Panx1 HCs). Immunocytochemical analyses and function were consistent with pannexin1 localization to T-tubules intercalated with dihydropyridine and ryanodine receptors in slow (soleus) and fast (extensor digitorum longus, EDL) muscles. Isolated myofibers took up ethidium (Etd+) and released small molecules (as ATP) during electrical stimulation. Consistent with two glucose uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter (GLUT4), and blocked by dual blockade. Adult skeletal muscles apparently do not express connexins, making it unlikely that connexin hemichannels contribute to the uptake and release of small molecules. ATP release, Etd+ uptake, and potentiation induced by repetitive electrical stimulation were blocked by HC blockers and did not occur in muscles of pannexin1 knockout mice. MRS2179, a P2Y1R blocker, prevented potentiation in EDL, but not soleus muscles, suggesting that in fast muscles ATP activates P2Y1 but not P2X receptors. Phosphorylation on Ser and Thr residues of pannexin1 was increased during potentiation, possibly mediating HC opening. Opening of Panx1 HCs during repetitive activation allows efflux of ATP, influx of glucose and possibly Ca2+ too, which are required for potentiation of contraction. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Pharmacokinetic drug evaluation of extended release lorcaserin for the treatment of obesity.

    Science.gov (United States)

    Hurren, Kathryn M; Dunham, Marissa W

    2017-08-01

    Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3 and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

  3. Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

    Directory of Open Access Journals (Sweden)

    Chendi Ding

    2016-12-01

    Full Text Available Benefiting from the development of nanotechnology, drug delivery systems (DDSs with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs, quantum dots (QDs and carbon nanotubes (CNTs. The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules and extrinsic (temperature, light irradiation, magnetic field and ultrasound ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

  4. Oxytocin and potential benefits for obesity treatment.

    Science.gov (United States)

    Olszewski, Pawel K; Klockars, Anica; Levine, Allen S

    2017-10-01

    Laboratory animal experiments have consistently shown that oxytocin causes early termination of food intake, thereby promoting a decrease in body weight in a long term. Recent studies have also assessed some of oxytocin's effects on appetite and energy balance in humans. The present study examines the findings of the key basic research and of the few clinical studies published thus far in the context of potential benefits and challenges stemming from the use of oxytocin in obese patients. Basic research indicates the involvement of oxytocin in satiety, processing, in reducing a drive to eat for pleasure and because of psychosocial factors. Although the results of clinical studies are very scarce, they suggest that oxytocin administered intranasally in humans decreases energy-induced and reward-induced eating, supports cognitive control of food choices, and improves glucose homeostasis, and its effectiveness may be BMI dependent. Despite the wealth of basic research showing broad anorexigenic effects of oxytocin, clinical studies on oxytocin's therapeutic potential in obesity, are still in their infancy. Future implementation of oxytocin-based pharmacological strategies in controlling energy balance will likely depend on our ability to integrate diverse behavioral and metabolic effects of oxytocin in obesity treatment regimens.

  5. The Impact of Employee Satisfaction on the Release of Human Creative Potential

    OpenAIRE

    Damjana Dragman

    2014-01-01

    Research Question (RQ): Does employee satisfaction in the workplace affect the release of human creative potential? Purpose: Based on interviews conducted in the context of a particular department, the purpose was to determine whether employee satisfaction affects creativity and efficiency of employees. Method: A qualitative method was used as the research method, where interviews were used to obtain data. Results: The results showed that employee satisfaction in the workplace str...

  6. Preliminary evaluation of the potential for plutonium release from burial grounds at Los Alamos Scientific Laboratory

    International Nuclear Information System (INIS)

    Wheeler, M.L.; Smith, W.J.; Gallegos, A.F.

    1977-02-01

    An analysis was made of a number of natural phenomena which could result in the release of plutonium from radioactive wastes buried at the Los Alamos Scientific Laboratory (LASL). Background information concerning the history and practice of radioactive waste disposal at LASL is provided. The potential impact of buried radioactive wastes on the environment is addressed through the mechanisms and rates by which the radionuclides can enter the environment. Only mechanisms independent of human activity are considered. They are divided into two classes, acute and chronic. The acute release mechanisms considered are earthquakes, meteorite impacts, and tornadoes. These have been typified by low occurrence probabilities (10 -6 to 10 -7 /yr). The chronic mechanisms that have been considered are release through uptake by plant roots, exposure by soil erosion, and transport by soil water. The rates of these processes are low, but may result in radionuclide release over long time periods. The analysis of uptake by plant roots was made using an environmental model currently under development; the model is discussed in some detail

  7. Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release

    Science.gov (United States)

    Wang, Juan; Yin, Zhuping; Xue, Xiang; Kundu, Subhas C.; Mo, Xiumei; Lu, Shenzhou

    2016-01-01

    Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications. PMID:27916946

  8. Current and potential treatment options for hyperphosphatemia.

    Science.gov (United States)

    Carfagna, Fabio; Del Vecchio, Lucia; Pontoriero, Giuseppe; Locatelli, Francesco

    2018-05-21

    Hyperphosphatemia is common in late stages of chronic kidney disease and is often associated with elevated parathormone levels, abnormal bone mineralization, extra-osseous calcification, and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control plasma phosphorus levels. Although effective at lowering serum phosphorus, they all have safety, tolerability, and compliance issues that need to be considered when selecting which one to use. Areas covered: This paper reviews the most established treatment options for hyperphosphatemia, in patients with chronic kidney disease, focusing on the new inhibitors of active phosphate absorption. Expert opinion: The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Nonetheless, an extending range of phosphate binders are now available. Aluminum has potentially serious toxic risks. Calcium-based binders are very effective but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, and long-term effects of tissue deposition seem clinically irrelevant. Sevelamer, appear to have profiles that would lead to pleiotropic effects and reduced progression of vascular calcification, and the main adverse events seen with these agents are gastrointestinal. Iron has a powerful capability of binding phosphate, thus numerous preparations are available, both with and without significant systemic absorption of the iron component. The inhibitors of active intestinal phosphate transport, with their very selective mechanism of action and low pill burden seem the most interesting approach; however, do not seem at present to be effective alone, in reducing serum phosphorus levels.

  9. Delignification and Enhanced Gas Release from Soil Containing Lignocellulose by Treatment with Bacterial Lignin Degraders.

    Science.gov (United States)

    Rashid, Goran M M; Duran-Pena, Maria Jesus; Rahmanpour, Rahman; Sapsford, Devin; Bugg, Timothy D H

    2017-04-10

    The aim of the study was to isolate bacterial lignin-degrading bacteria from municipal solid waste soil, and to investigate whether they could be used to delignify lignocellulose-containing soil, and enhance methane release. A set of 20 bacterial lignin degraders, including 11 new isolates from municipal solid waste soil, were tested for delignification and phenol release in soil containing 1% pine lignocellulose. A group of 7 strains were then tested for enhancement of gas release from soil containing 1% lignocellulose in small-scale column tests. Using an aerobic pre-treatment, aerobic strains such as Pseudomonas putida showed enhanced gas release from the treated sample, but four bacterial isolates showed 5-10 fold enhancement in gas release in an in situ experiment under microanaerobic conditions: Agrobacterium sp., Lysinibacillus sphaericus, Comamonas testosteroni, and Enterobacter sp.. The results show that facultative anaerobic bacterial lignin degraders found in landfill soil can be used for in situ delignification and enhanced gas release in soil containing lignocellulose. The study demonstrates the feasibility of using an in situ bacterial treatment to enhance gas release and resource recovery from landfill soil containing lignocellulosic waste. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Electrolytic treatment of liquid effluents: decontamination by electro coagulation of release water of a petroleum platform

    International Nuclear Information System (INIS)

    Nanseu-Njiki, Ch.P.; Ngameni, E.; Poumiba, S.; Darchen, A.

    2005-01-01

    The water releases of petroleum platforms present lots of pollutants; Usually, these waters are reinjected in ground water when it is possible. In the other cases they are released at the surface and need then a treatment. The electro-coagulation is a suitable method often used. The authors propose to study the optimum conditions of decontamination by this method, by a parametric evaluation (water flow, charge density, ph). Experiments used iron and aluminium electrodes. (A.L.B.)

  11. Evaluating Potential for Large Releases from CO2 Storage Reservoirs: Analogs, Scenarios, and Modeling Needs

    International Nuclear Information System (INIS)

    Birkholzer, Jens; Pruess, Karsten; Lewicki, Jennifer; Tsang, Chin-Fu; Karimjee, Anhar

    2005-01-01

    While the purpose of geologic storage of CO 2 in deep saline formations is to trap greenhouse gases underground, the potential exists for CO 2 to escape from the target reservoir, migrate upward along permeable pathways, and discharge at the land surface. Such discharge is not necessarily a serious concern, as CO 2 is a naturally abundant and relatively benign gas in low concentrations. However, there is a potential risk to health, safety and environment (HSE) in the event that large localized fluxes of CO 2 were to occur at the land surface, especially where CO 2 could accumulate. In this paper, we develop possible scenarios for large CO 2 fluxes based on the analysis of natural analogues, where large releases of gas have been observed. We are particularly interested in scenarios which could generate sudden, possibly self-enhancing, or even eruptive release events. The probability for such events may be low, but the circumstances under which they might occur and potential consequences need to be evaluated in order to design appropriate site selection and risk management strategies. Numerical modeling of hypothetical test cases is needed to determine critical conditions for such events, to evaluate whether such conditions may be possible at designated storage sites, and, if applicable, to evaluate the potential HSE impacts of such events and design appropriate mitigation strategies

  12. The potential role of HMGB1 release in peritoneal dialysis-related peritonitis.

    Directory of Open Access Journals (Sweden)

    Shirong Cao

    Full Text Available High mobility group box 1 (HMGB1, a DNA-binding nuclear protein, has been implicated as an endogenous danger signal in the pathogenesis of infection diseases. However, the potential role and source of HMGB1 in the peritoneal dialysis (PD effluence of patients with peritonitis are unknown. First, to evaluate HMDB1 levels in peritoneal dialysis effluence (PDE, a total of 61 PD patients were enrolled in this study, including 42 patients with peritonitis and 19 without peritonitis. Demographic characteristics, symptoms, physical examination findings and laboratory parameters were recorded. HMGB1 levels in PDE were determined by Western blot and ELISA. The concentrations of TNF-α and IL-6 in PDE were quantified by ELISA. By animal model, inhibition of HMGB1 with glycyrrhizin was performed to determine the effects of HMGB1 in LPS-induced mice peritonitis. In vitro, a human peritoneal mesothelial cell line (HMrSV5 was stimulated with lipopolysaccharide (LPS, HMGB1 extracellular content in the culture media and intracellular distribution in various cellular fractions were analyzed by Western blot or immunofluorescence. The results showed that the levels of HMGB1 in PDE were higher in patients with peritonitis than those in controls, and gradually declined during the period of effective antibiotic treatments. Furthermore, the levels of HMGB1 in PDE were positively correlated with white blood cells (WBCs count, TNF-α and IL-6 levels. However, pretreatment with glycyrrhizin attenuated LPS-induced acute peritoneal inflammation and dysfunction in mice. In cultured HMrSV5 cells, LPS actively induced HMGB1 nuclear-cytoplasmic translocation and release in a time and dose-dependent fashion. Moreover, cytosolic HMGB1 was located in lysosomes and secreted via a lysosome-mediated secretory pathway following LPS stimulation. Our study demonstrates that elevated HMGB1 levels in PDE during PD-related peritonitis, at least partially, from peritoneal mesothelial cells

  13. Microstructure, mechanical property and metal release of As-SLM CoCrW alloy under different solution treatment conditions.

    Science.gov (United States)

    Lu, Yanjin; Wu, Songquan; Gan, Yiliang; Zhang, Shuyuan; Guo, Sai; Lin, Junjie; Lin, Jinxin

    2015-03-01

    In the study, the microstructure, mechanical property and metal release behavior of selective laser melted CoCrW alloys under different solution treatment conditions were systemically investigated to assess their potential use in orthopedic implants. The effects of the solution treatment on the microstructure, mechanical properties and metal release were systematically studied by OM, SEM, XRD, tensile test, and ICP-AES, respectively. The XRD indicated that during the solution treatment the alloy underwent the transformation of γ-fcc to ε-hcp phase; the ε-hcp phase nearly dominated in the alloy when treated at 1200°C following the water quenching; the results from OM, SEM showed that the microstructural change was occurred under different solution treatments; solution at 1150°C with furnace cooling contributed to the formation of larger precipitates at the grain boundary regions, while the size and number of the precipitates was decreased as heated above 1100°C with the water quenching; moreover, the diamond-like structure was invisible at higher solution temperature over 1150°C following water quenching; compared with the furnace cooling, the alloy quenched by water showed excellent mechanical properties and low amount of metal release; as the alloy heated at 1200°C, the mechanical properties of the alloy reached their optimum combination at UTS=1113.6MPa, 0.2%YS=639.5MPa, and E%=20.1%, whilst showed the lower total quantity of metal release. It is suggested that a proper solution treatment is an efficient strategy for improving the mechanical properties and corrosion resistance of As-SLM CoCrW alloy that show acceptable tensile ductility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents

    Directory of Open Access Journals (Sweden)

    Bello NT

    2015-06-01

    Full Text Available Nicholas T Bello Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Abstract: Attention deficit hyperactivity disorder (ADHD is the most common psychiatric illness in children and adolescents. Several stimulant medications, such as methylphenidate and amphetamine derivatives, are available to treat ADHD in pediatric patients. Nonstimulant medications are more preferred by some parents, other caregivers, and patients because they lack the abuse potential of stimulant medications. In the US, one available nonstimulant option is guanfacine extended release (XR. As a selective α2A adrenergic receptor, guanfacine acts on the central noradrenergic pathways and cortical noradrenergic targets to improve working memory and attention. The XR formulation of guanfacine, compared with the immediate-release formulation, is more effective for the long-term management of ADHD and is associated with fewer adverse effects. Available data also indicate that guanfacine XR is superior to atomoxetine and is as effective as the nonselective α2 adrenergic receptor agonist, clonidine XR. The most common adverse effects associated with guanfacine XR are somnolence, fatigue, bradycardia, and hypotension. Somnolence is the most often cited reason for discontinuation. Guanfacine XR is also labeled for use as an adjuvant to stimulant treatment for ADHD. A similar profile of adverse effects as reported with monotherapy is reported when guanfacine XR is “added on” to stimulant therapy with somnolence as the most commonly reported adverse event. This review discusses the clinical efficacy and patient preference of guanfacine XR based on available published data on the safety, relative effectiveness, and tolerance of this medication to treat ADHD. Keywords: Intuniv, norepinephrine, prefrontal cortex, locus coeruleus, impulsivity, inattentive

  15. Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

    Science.gov (United States)

    Belz, Jodi E; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S; Royce, Darlene B; Zhang, Di; van de Ven, Anne L; Liby, Karen T; Sridhar, Srinivas

    2017-01-01

    Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1 -deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1 -deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1 Co/Co ;MMTV-Cre;p53 +/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro . Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

  16. Study about the integrated treatment of chemical and radioactive effluents, introducing the zero release concept

    International Nuclear Information System (INIS)

    Mierzwa, Jose Carlos

    1996-01-01

    An Integrated System to the treatment of Chemical and Radioactive Effluents to the Centro Experimental Aramar is proposed and evaluated, introducing the Effluent Zero Release concept, where factors related to the environmental regulation in vigor in the country, as well as the availability of hydrological resources in the place where CEA have been implanted, are considered. Through a literature analysis of the main effluents treatment techniques available nowadays and after a case of study selection, take into account two industrial installations that will be implanted at CEA, it was defined an arrangement to compose the Integrated System to the Treatment of Chemicals and Radioactive Effluents, focusing the Zero Release concept consolidation. A defined arrangement uses a combination among three treatment processes, it means chemical precipitation, reverse osmosis and evaporation, that were experimentally evaluated. The proposed arrangement was evaluated using synthetic effluents, that were prepared based on data from literature and conception documents of the installation considered in this work. Three kinds of effluents were simulated, one arising from a nuclear reactor laundry, one arising from the water refrigeration system and demineralized water production to the nuclear reactor and the other one arising from a nuclear material production laboratory. Each effluent were individually submitted to the selected treatment processes, to get the best operational conditions for each treatment process. The results got during the laboratory assays show that the proposed Integrated System to the Treatment of Chemicals and Radioactive Effluents is feasible, consolidating the Effluent Zero Release concept, which is the proposition of this work. (author)

  17. The Impact of Employee Satisfaction on the Release of Human Creative Potential

    Directory of Open Access Journals (Sweden)

    Damjana Dragman

    2014-09-01

    Full Text Available Research Question (RQ: Does employee satisfaction in the workplace affect the release of human creative potential? Purpose: Based on interviews conducted in the context of a particular department, the purpose was to determine whether employee satisfaction affects creativity and efficiency of employees. Method: A qualitative method was used as the research method, where interviews were used to obtain data. Results: The results showed that employee satisfaction in the workplace strongly affects their motivation at work and their effectiveness. Also personal praise from leaders influences employee satisfaction, which in turn also affect the release of human creative potential. Organization: Several factors affect employee satisfaction that is typical for the entire company. A special role is played by those who are responsible for creating a positive atmosphere within their working environment and encouraging employees towards increased creativity and efficiency. Society: Research shows that employee satisfaction significantly affects their performance. For this reason employees should create a pleasant working environment within the entire company and for good relationships with co-workers. Originality: The first such study conducted in the context of a particular department. Limitations/further research: The research study was carried out in only one department of one organization.

  18. Releases of UF6 to the atmosphere after a potential fire in a cylinder storage yard

    International Nuclear Information System (INIS)

    Lombardi, D.A.; Williams, W.R.; Anderson, J.C.

    1997-01-01

    Uranium hexafluoride (UF 6 ), a toxic material, is stored in just over 6200 cylinders at the K-25 site in Oak Ridge, Tennessee. The safety analysis report (SAR) for cylinder yard storage operations at the plant required the development of accident scenarios for the potential release of UF 6 to the atmosphere. In accordance with DOE standards and guidance, the general approach taken in this SAR was to examine the functions and contents of the cylinder storage yards to determine whether safety-significant hazards were present for workers in the immediate vicinity, workers on-site, the general public off-site, or the environment. and to evaluate the significance of any hazards that were found. A detailed accident analysis was performed to determine a set of limiting accidents that have potential for off-site consequences. One of the limiting accidents identified in the SAR was the rupture of a cylinder engulfed in a fire

  19. Potential role of aromatase inhibitors in the treatment of endometriosis

    Directory of Open Access Journals (Sweden)

    Abu Hashim H

    2014-07-01

    Full Text Available Hatem Abu HashimDepartment of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, EgyptAbstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%–10% of reproductive-age women, with a prevalence of 5%–50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis

  20. Dual-release hydrocortisone treatment: glycometabolic profile and health-related quality of life

    Directory of Open Access Journals (Sweden)

    L M Mongioì

    2018-01-01

    Full Text Available Objective: Adrenal insufficiency (AI is a chronic condition associated with increased mortality and morbidity. The treatment of AI in the last years has been object of important changes due to the development of a dual-release preparation of hydrocortisone. It differs from previous therapeutic strategy as it contemplates a once-daily tablet that allows more closely mimicking the physiological circadian cortisol rhythm. The aim of the study was to evaluate the effects of dual-release hydrocortisone treatment on the glycometabolic profile and health-related quality of life of patients with AI. Design and Methods: In this clinical open trial, we enrolled ten patients with primary AI (41 ± 2.67 years and nine patients with AI secondary to hypopituitarism (53.2 ± 17.7 years. We evaluated the glycometabolic profile before and 3, 6, 9 and 12 months after dual-release hydrocortisone administration. We also evaluated health-related quality of life, estimated by the AddiQol questionnaire. The mean dose administered of dual-release hydrocortisone was 28.33 ± 6.68 mg/day. Results: One female hypopituitary patient dropped out from the study. After 12 months of treatment, the mean dosage administered of dual-release hydrocortisone was significantly lower (P < 0.05 and all patients reported improved quality of life and well-being. The glycometabolic profile improved and the glycosylated hemoglobin decreased significantly in patients with primary AI (6.25 ± 0.2 vs 5.35 ± 0.17, P < 0.05. In contrast, hypopituitary patients had worse glycometabolic profile and a trend toward hypertriglyceridemia. Conclusions: Dual-release hydrocortisone treatment improved the quality of life of patients with AI, and it allowed a decrease of cortisol dosage administered in the absence of side effects. The glycometabolic profile worsened in hypopituitary patients.

  1. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

    2014-07-01

    The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  2. Sustained release of estrogens from PEGylated nanoparticles for treatment of secondary spinal cord injury

    Science.gov (United States)

    Barry, John

    Spinal Cord Injury (SCI) is a debilitating condition which causes neurological damage and can result in paralysis. SCI results in immediate mechanical damage to the spinal cord, but secondary injuries due to inflammation, oxidative damage, and activated biochemical pathways leading to apoptosis exacerbate the injury. The only currently available treatment, methylprednisolone, is controversial because there is no convincing data to support its therapeutic efficacy for SCI treatment. In the absence of an effective SCI treatment option, 17beta-estradiol has gained significant attention for its anti-oxidant, anti-inflammatory, and anti-apoptotic abilities, all events associated with secondary. Sadly, 17beta-estradiol is associated with systemic adverse effects preclude the use of free estrogen even for local administration due to short drug half-life in the body. Biodegradable nanoparticles can be used to increase half-life after local administration and to bestow sustained release. Sustained release using PEGylated biodegradable polymeric nanoparticles constructed from poly(lactic-co-glycolic acid) (PLGA) will endow a consistent, low, but effective dose to be delivered locally. This will limit systemic effects due to local administration and low dose, sustained release. PLGA was chosen because it has been used extensively for sustained release, and has a record of safety in humans. Here, we show the in vitro efficacy of PEGylated nanoparticles loaded with 17beta-estradiol for treatment of secondary SCI. We achieved a high loading efficiency and controlled release from the particles over a several day therapeutic window. The particles also show neuroprotection in two in vitro cell culture models. Both the dose and pretreatment time with nanoparticles was evaluated in an effort to translate the treatment into an animal model for further study.

  3. Phosphorus fractions and its potential release in the sediments of Koycegiz Lake, Turkey

    Directory of Open Access Journals (Sweden)

    Yalçın Şahin

    2012-12-01

    Full Text Available This study was conducted to find out the seasonal and spatial patterns of the phosphorus in the littoral sediment and its potential release into the Koycegiz Lake, south west Turkey, between November 2011 and March 2012 at two months intervals. The scanning electron microscopy was used for elemental compositions of the sediment. The amounts and forms of phosphorus (P in surface sediments of Koycegiz Lake were examined using a not sequential chemical extraction procedure. Four fractions of sedimentary P, including organic bound phosphorus fraction (Org≈P, calcium bound phosphorus fraction (Ca≈P, iron+aluminium bound phosphorus fraction (Fe+Al≈P and carbonate bound phosphorus fraction (CO3≈P were separately quantified. The results indicated that the contents of different phosphorus fractions in the sediments varied greatly. The proportion of phosphorus fractions was estimated as Org≈P (90.20 %, this fraction was followed by Ca≈P (9.06 %, Fe+Al≈P (0.47 % and CO3≈P (0.27 % in this study. The level of phosphorus release from the sediment to the lake is calculated as low. The sediment phosphorus release fluctuated between -6.647–75.883 μg/m2.d-1 and the total phosphorus (TP concentrations of the sediment samples were changed between 980.39 μg/gDW (Dry Weight - 1990.81 μg/gDW. The results show that it can be evaluation as eutrophic for Koycegiz Lake.

  4. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

    OpenAIRE

    White, John R.; Belmont, Marco A.; Metcalfe, Chris D.

    2006-01-01

    Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the ...

  5. Oak regeneration potential increased by shelterwood treatments

    Science.gov (United States)

    Richard C. Schlesinger; Ivan L. Sander; Kenneth R. Davidson

    1993-01-01

    In much of the Central Hardwood Forest Region, oak species are not regenerating well, even though large oak trees are common within the existing forests. The shelterwood method has been suggested as a potential tool for establishing and developing advanced regeneration where it is lacking. The 10-yr results from a study of several variants of the shelterwood method...

  6. Methane emission estimates using chamber and tracer release experiments for a municipal waste water treatment plant

    Science.gov (United States)

    Yver Kwok, C. E.; Müller, D.; Caldow, C.; Lebègue, B.; Mønster, J. G.; Rella, C. W.; Scheutz, C.; Schmidt, M.; Ramonet, M.; Warneke, T.; Broquet, G.; Ciais, P.

    2015-07-01

    This study presents two methods for estimating methane emissions from a waste water treatment plant (WWTP) along with results from a measurement campaign at a WWTP in Valence, France. These methods, chamber measurements and tracer release, rely on Fourier transform infrared spectroscopy and cavity ring-down spectroscopy instruments. We show that the tracer release method is suitable for quantifying facility- and some process-scale emissions, while the chamber measurements provide insight into individual process emissions. Uncertainties for the two methods are described and discussed. Applying the methods to CH4 emissions of the WWTP, we confirm that the open basins are not a major source of CH4 on the WWTP (about 10 % of the total emissions), but that the pretreatment and sludge treatment are the main emitters. Overall, the waste water treatment plant is representative of an average French WWTP.

  7. Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

    Directory of Open Access Journals (Sweden)

    Abimael González-Hernández

    2016-01-01

    Full Text Available Calcitonin gene-related peptide (CGRP is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP, the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor. This receptor is an atypical G-protein coupled receptor (GPCR composed of three functional proteins: (i the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein, (ii the activity-modifying protein type 1 (RAMP1, and (iii a receptor component protein (RCP. Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia. The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

  8. Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges.

    Science.gov (United States)

    Gulati, Karan; Ivanovski, Sašo

    2017-08-01

    The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO 2 nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization. Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity. Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.

  9. Scenarios for potential radionuclide release from marine reactors dumped in the Kara Sea

    International Nuclear Information System (INIS)

    Lynn, N.; Mount, M.; Gussgard, K.

    1995-01-01

    The largest inventory of radioactive materials dumped in the Kara Sea by the former Soviet Union comes from the spent nuclear fuel (SNF) of seven marine reactors, the current (1994) inventory of which makes a total of approximately 4.7x10 15 Bq. In progressing its work for the International Arctic Seas Assessment Project, under the auspices of the International Atomic Energy Agency, the Source Term Working Group has analysed the Source Term and subsequently developed a number of model scenarios for the potential release patterns of radionuclides into the Kara Sea from the SNF and activated components dumped within the marine reactors.These models are based on the present and future conditions of the barrier materials and their configuration within the dumped objects. They account for progressive corrosion of the outer and inner steel barriers, breakdown of the organic fillers, and degradation and leaching from the SNFs. Annual release rates are predicted to four thousand years into the future. 5 refs., 1 fig., 1 tab

  10. Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.

    Science.gov (United States)

    Cherkasova, Mariya V; Faridi, Nazlie; Casey, Kevin F; O'Driscoll, Gillian A; Hechtman, Lily; Joober, Ridha; Baker, Glen B; Palmer, Jennifer; Dagher, Alain; Leyton, Marco; Benkelfat, Chawki

    2014-05-01

    Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

  11. Bromelain: A potential strategy for the adjuvant treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Felipe Rodolfo Pereira da Silva

    2016-01-01

    Full Text Available Introduction: Bromelain, a mixture of proteases derived from different parts of pineapple, has been described to have therapeutic benefits in a diversity of inflammatory diseases. Such effects are associated to its proteolytic activity. As one of the most common and multifactorial diseases, periodontitis is a bacterial infection that results from the damage to the integrity of the tissues around the tooth, which includes gingiva, periodontal ligament, and alveolar bone. In periodontitis, the recruitment of defense cells occurs, which releases several pro-inflammatory cytokines. At elevated levels, they can potentiate the alveolar bone loss. Studies have been conducted trying to alleviate the damage to the periodontium, however, the regeneration of the periodontal tissues is still limited. The Hypotheses: Based on previous studies showing that bromelain can act by decreasing the periodontal microorganism growth by proteolytically cleaving important cell surface molecules in leucocytes, by reducing neutrophils migration to periodontal sites, by downregulating the inflammation mediator levels, and by decreasing alveolar bone loss in the periodontitis. Evaluation of the Hypothesis: In a first moment, to evaluate this hypothesis, could be used two animal models: the ligature or bacteria inoculation induced periodontitis. If studies using animal models show encouraging results, appropriate clinical trials should be designed to evaluate the effect of bromelain as a complementary treatment for periodontal disease in humans, during the active phase or after the healing phase of mechanical therapy could be tested; to conduct a placebo-controlled study where health and periodontitis patients could be used.

  12. The production of volvox spheres and their potential application in multi-drugs encapsulation and release

    Energy Technology Data Exchange (ETDEWEB)

    Teong, Benjamin; Chang, Shwu Jen [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China); Chuang, Chin Wen [Department of Electrical Engineering, I-Shou University, No. 1, Sec. 1, Syuecheng Rd., Dashu District, Kaohsiung City 84001, Taiwan (China); Kuo, Shyh Ming, E-mail: smkuo@isu.edu.tw [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China); Manousakas, Ioannis, E-mail: i.manousakas@ieee.org [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China)

    2013-12-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (∼ 4 °C) and warm (∼ 50 °C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. - Highlights: • Volvox spheres contain smaller microspheres which can encapsulate drugs and/or cells. • Alginate is the primary material for the inner and outer spheres. • Encapsulation is affected by the crosslinking, temperature and the selection of drugs.

  13. The production of volvox spheres and their potential application in multi-drugs encapsulation and release

    International Nuclear Information System (INIS)

    Teong, Benjamin; Chang, Shwu Jen; Chuang, Chin Wen; Kuo, Shyh Ming; Manousakas, Ioannis

    2013-01-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (∼ 4 °C) and warm (∼ 50 °C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. - Highlights: • Volvox spheres contain smaller microspheres which can encapsulate drugs and/or cells. • Alginate is the primary material for the inner and outer spheres. • Encapsulation is affected by the crosslinking, temperature and the selection of drugs.

  14. Emergency patients receiving anaesthesiologist-based pre-hospital treatment and subsequently released at the scene

    DEFF Research Database (Denmark)

    Højfeldt, S G; Sørensen, L P; Mikkelsen, Søren

    2014-01-01

    BACKGROUND: The Mobile Emergency Care Unit in Odense, Denmark consists of a rapid response car, manned with an anaesthesiologist and an emergency medical technician. Eleven per cent of the patients are released at the scene following treatment. The aim of the study was to investigate which...... investigated. In each patient, diagnosis as well as any renewed contact with the Mobile Emergency Care Unit or the hospital within 24 h was registered. RESULTS: ONE THOUSAND SIX HUNDRED NINE: patients were released at the scene. Diagnoses within the category 'examination and investigation' [International...... with the Mobile Emergency Care Unit within 24 h. Of the 143 victims of traffic accidents, 19 (13%) required renewed contact with the emergency department and one required admission to hospital (0.7%). Of all 1609 patients, four died within 24 h of contact (0.2%). CONCLUSION: Patients treated and released...

  15. Investigation of hypereosinophilia and potential treatments.

    Science.gov (United States)

    Lilliehöök, Inger; Tvedten, Harold

    2003-11-01

    Hypereosinophilia is excessive eosinophilia and has been defined in dogs and cats as eosinophils greater than 5 x 10(9)/L (> 5000/microL). Canine breeds with a predisposition to higher eosinophil counts or certain eosinophilic diseases include the Rottweiler, German Shepard, Siberian Husky, Alaskan Malamute, and Cavalier King Charles Spaniel. Two of the more common causes of canine hypereosinophilia are pulmonary infiltrates with eosinophils (PIE) and gastrointestinal disease. The highest eosinophil counts are expected in dogs with pneumonia or PIE. The most common cause of eosinophilia in cats is flea allergy. The greatest eosinophilia occurs in cats with flea allergy, feline asthma, and eosinophilic granuloma. Innovative recent treatments for human patients with asthma have been successful in reducing eosinophil numbers but have had a confusing and disappointing lack of reducing symptoms. The role of eosinophils in many eosinophilic diseases remains a mystery.

  16. Potential new treatments for diabetic kidney disease.

    Science.gov (United States)

    Kania, Deanna S; Smith, Cory T; Nash, Christy L; Gonzalvo, Jasmine D; Bittner, Andrea; Shepler, Brian M

    2013-01-01

    Antifibrotic agents, antioxidant agents, ET-a receptor antagonists, and a few other agents with nonspecific or multifaceted mechanisms of action have been evaluated and progressed to small clinical studies in human subjects. Although there are limited data at the present time, these early evaluations have produced some favorable results that at least warrant further investigation. There is certainly not enough compelling evidence to justify the routine use of any of these products specifically for DKD at the moment; however, more well-controlled and adequately powered studies in several hundred patients will help determine which of these may have a place in the DKD treatment armamentarium of the future. Published by Elsevier Inc.

  17. 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

  18. Osteopetroses, emphasizing potential approaches to treatment.

    Science.gov (United States)

    Teti, Anna; Econs, Michael J

    2017-09-01

    interfering RNA approach and novel pharmacologic treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Rapid release of tissue enzymes into blood after blast exposure: potential use as biological dosimeters.

    Directory of Open Access Journals (Sweden)

    Peethambaran Arun

    Full Text Available Explosive blast results in multiple organ injury and polytrauma, the intensity of which varies with the nature of the exposure, orientation, environment and individual resilience. Blast overpressure alone may not precisely indicate the level of body or brain injury after blast exposure. Assessment of the extent of body injury after blast exposure is important, since polytrauma and systemic factors significantly contribute to blast-induced traumatic brain injury. We evaluated the activity of plasma enzymes including aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH and creatine kinase (CK at different time points after blast exposure using a mouse model of single and repeated blast exposures to assess the severity of injury. Our data show that activities of all the enzymes in the plasma were significantly increased as early as 1 h after blast exposure. The elevated enzyme activity remained up to 6 h in an overpressure dose-dependent manner and returned close to normal levels at 24 h. Head-only blast exposure with body protection showed no increase in the enzyme activities suggesting that brain injury alone does not contribute to the systemic increase. In contrast to plasma increase, AST, ALT and LDH activity in the liver and CK in the skeletal muscle showed drastic decrease at 6 h after blast exposures. Histopathology showed mild necrosis at 6 h and severe necrosis at 24 h after blast exposures in liver and no changes in the skeletal muscle suggesting that the enzyme release from the tissue to plasma is probably triggered by transient cell membrane disruption from shockwave and not due to necrosis. Overpressure dependent transient release of tissue enzymes and elevation in the plasma after blast exposure suggest that elevated enzyme activities in the blood can be potentially used as a biological dosimeter to assess the severity of blast injury.

  20. Progress report on evaluation of potential impact of 14C releases from an HTGR reprocessing facility

    International Nuclear Information System (INIS)

    Killough, G.G.; Dixon, K.R.; Edwards, N.T.; Murphy, B.D.; Rohwer, P.S.; Harris, W.F.; Kaye, S.V.

    1976-07-01

    The potential radiological impacts of atmospheric releases of 14 CO 2 are assessed for a model HTGR reprocessing facility. Two off-gas systems were considered: (1) a 300-ft stack with no thermal output, and (2) a 1000-ft stack with a stack gas temperature of 80 0 C and heat output of 4.2 x 10 7 Btu/hr. Meteorological data for the Oak Ridge area were used with an assumed annual release rate of 5000 Ci as input to an atmospheric transport model, which in turn was used to predict air concentrations of 14 C at points of habitation and food production in the local area (within 50 miles) of the facility. The total-body dose rates estimated for the average resident living in the local area were 0.107 mrem/yr for the 300-ft stack and 0.063 mrem/yr for the 1000-ft stack. Population doses were computed for a population of 10 6 individuals uniformly distributed within the 50-mile local area of the facility; these were 110 man-rem for the 300-ft stack and 63 man-rem for the 1000-ft stack. The results of these dose calculations suggest that a 1000-ft stack would be very effective in reducing the estimated doses. Plant growth carbon assimilation model was derived in order to investigate the adequacy of the assumption of tissue equilibration with time-averaged ambient specific activity as a basis for dose estimates. Simulation runs with these models suggest that in the presence of frequent fluctuations of large amplitude in the ambient air 14 CO 2 concentrations, specific activity in plant tissue can exceed conventionally calculated time-averaged specific activity

  1. Limited capsular release and controlled manipulation under anaesthesia for the treatment of frozen shoulder.

    Science.gov (United States)

    Bidwai, Amit S; Mayne, Alistair Iw; Nielsen, Maryke; Brownson, Peter

    2016-01-01

    In light of recent interest in the cost-effectiveness of the treatment options available for frozen shoulder, we aimed to determine the results of limited anterior capsular release and controlled manipulation under anaesthesia (MUA) in the treatment of primary frozen shoulder in terms of patient-related outcomes measure, range of motion and re-intervention rates. This single-surgeon series included prospectively collected data on all patients undergoing capsular release with MUA from March 2011 until June 2013, with a minimum follow-up of 6 months from the index procedure. Outcome measures included pre- and postoperative Oxford Shoulder Score (OSS), range of motion and need for re-intervention. Fifty-four procedures were performed in 52 patients. Mean age 50 years (range 42 years to 59 years); male: female ratio = 11: 41. There was a highly statistically significant improvement in both pain and function modules of the OSS (p patients were diabetics. There was no significant difference in pre-operative and postoperative OSS or range of motion between the diabetic group and the non-diabetic groups. No patients required surgical re-intervention. A combination of limited capsular release and MUA for the treatment of primary frozen shoulder is a safe and effective procedure resulting in marked improvement in pain, function and range of motion.

  2. Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment.

    Science.gov (United States)

    Torner, Luz; Plotsky, Paul M; Neumann, Inga D; de Jong, Trynke R

    2017-03-01

    The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail. In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175μg/kg i.v.) 5min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range. Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175μg/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion. In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN. Copyright © 2016 Elsevier Ltd. All rights

  3. Controlled release of phenytoin for epilepsy treatment from titania and silica based materials

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Tessy, E-mail: tessy3@prodigy.net.mx [Universidad Autonoma Metropolitana-Xochimilco. Departamento de Microbiologia. Calzada del Hueso 1100, Col. Villa Quietud, Coyoacan, C.P. 04960, Mexico D.F. Mexico (Mexico); Instituto Nacional de Neurologia y Neurocirugia ' MVS' . Laboratorio de Nanotecnologia. Av. Insurgentes Sur 3877, Col. La Fama, Tlalpan, 14269, Mexico, D.F. Mexico (Mexico); Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA 70118 (United States); Ortiz, Emma [Instituto Nacional de Neurologia y Neurocirugia ' MVS' . Laboratorio de Nanotecnologia. Av. Insurgentes Sur 3877, Col. La Fama, Tlalpan, 14269, Mexico, D.F. Mexico (Mexico); Meza, Doraliz [Universidad Autonoma Metropolitana-Iztapalapa, Departamento de Quimica, Av. San Rafael Atlixco 186, A.P. 55-534, Mexico D.F., C.P. 09340 (Mexico); Basaldella, Elena [CIC-CINDECA - Universidad Nacional de La Plata - Calle 47 No 257 - La Plata (Argentina); Bokhimi, Xim; Magana, Carlos [Instituto de fisica, UNAM. Circuito de la Investigacion s/n. C.U. Mexico D.F. 01000 (Mexico); Sepulveda, Antonio; Rodriguez, Francisco; Ruiz, Javier [Departamento de Quimica Inorganica, Universidad de Alicante. Apartado 99, E-03080 Alicante, Espana Spain (Spain)

    2011-04-15

    Research highlights: {yields} Template technique was used to obtain well ordered nanostructured materials: SBA-15 and titania tubes. {yields} Phenytoin (PH), a drug used in epilepsy treatment, was loaded in these materials to used como PH release. {yields} Loaded PH showed a good stability inside the used materials as observed by spectroscopy analysis. {yields} The load-release PH are faster in nanostructured TiO2 tubes than in mesoporous silica matrix. {yields} There is an inverse effect of the surface area of the structured materials on the amount of released PH. - Abstract: Template technique was used to obtain well ordered nanostructured materials: mesoporous silica and nanostructured titania tubes. This technique permits the synthesis of solids with controlled mesoporosity, where a large variety of molecules that have therapeutic activity can be hosted and further released to specific sites. In this work phenytoin (PH), a drug used in epilepsy treatment, was loaded in ordered mesoporous silica (SBA 15) and nanostructured titania tubes (TiO{sub 2}). The pure materials and those containing PH were characterized by X-ray diffraction, FTIR spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and N{sub 2} adsorption-desorption at 77 K. In order to determine the loading capacity of the antiepileptic drug on these silica- and titania-based materials, the loading and release of PH was investigated using UV-vis spectroscopy. Tubular structures were found for the titania samples, for which the X-ray diffractograms showed to be formed by anatase and rutile phases. On the other hand, an amorphous phase was found in the silica sample. A highly ordered hexagonal structure of 1D cylindrical channels was also observed for this material. Loaded PH showed a good stability inside the used materials as observed by spectroscopy analysis. The adsorption and desorption of PH are faster in nanostructured TiO{sub 2} tubes than in mesoporous silica

  4. Controlled release of phenytoin for epilepsy treatment from titania and silica based materials

    International Nuclear Information System (INIS)

    Lopez, Tessy; Ortiz, Emma; Meza, Doraliz; Basaldella, Elena; Bokhimi, Xim; Magana, Carlos; Sepulveda, Antonio; Rodriguez, Francisco; Ruiz, Javier

    2011-01-01

    Research highlights: → Template technique was used to obtain well ordered nanostructured materials: SBA-15 and titania tubes. → Phenytoin (PH), a drug used in epilepsy treatment, was loaded in these materials to used como PH release. → Loaded PH showed a good stability inside the used materials as observed by spectroscopy analysis. → The load-release PH are faster in nanostructured TiO2 tubes than in mesoporous silica matrix. → There is an inverse effect of the surface area of the structured materials on the amount of released PH. - Abstract: Template technique was used to obtain well ordered nanostructured materials: mesoporous silica and nanostructured titania tubes. This technique permits the synthesis of solids with controlled mesoporosity, where a large variety of molecules that have therapeutic activity can be hosted and further released to specific sites. In this work phenytoin (PH), a drug used in epilepsy treatment, was loaded in ordered mesoporous silica (SBA 15) and nanostructured titania tubes (TiO 2 ). The pure materials and those containing PH were characterized by X-ray diffraction, FTIR spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and N 2 adsorption-desorption at 77 K. In order to determine the loading capacity of the antiepileptic drug on these silica- and titania-based materials, the loading and release of PH was investigated using UV-vis spectroscopy. Tubular structures were found for the titania samples, for which the X-ray diffractograms showed to be formed by anatase and rutile phases. On the other hand, an amorphous phase was found in the silica sample. A highly ordered hexagonal structure of 1D cylindrical channels was also observed for this material. Loaded PH showed a good stability inside the used materials as observed by spectroscopy analysis. The adsorption and desorption of PH are faster in nanostructured TiO 2 tubes than in mesoporous silica matrix.

  5. Outpatient Treatment of the Sexually Motivated Murderer and Potential Murderer.

    Science.gov (United States)

    Schlesinger, Louis B.; Revitch, Eugene

    1990-01-01

    Introduces the psychopathology and psychodynamics of sex murderer (and potential sex murderer) with emphasis on treatment in outpatient setting. Reviews system of classification of murder based on motivational dynamics of the act itself. Presents three cases that demonstrate a treatment failure, successful treatment of a catathymic sex murderer,…

  6. Radionuclides release to three rivers by ore treatment unit at Caldas, Minas Gerais - Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, W.S.; Carmo, R.F. do; Py Junior, D.A., E-mail: pereiraws@gmail.com [Industrias Nucleares do Brasil (INB), Pocos de Caldas, MG (Brazil). Unidade de Tratamento de Minerio. Grupo Multidisciplinar de Radioprotecao; Kelecom, A., E-mail: akelecom@id.uff.br [Universidade Federal Fluminense (LARARA-PLS/GETA/UFF), Niteroi, RJ (Brazil). Laboratorio de Radiobiologia e Radiometria Pedro Lopes dos Santos. Grupo de Estudos em Temas Ambientais; Pereira, J.R.S., E-mail: pereirarsj@gmail.com [Universidade Federal de Alfenas (UNIFAL), Pocos de Caldas, MG (Brazil)

    2013-07-01

    The Ore Treatment Unit (OTU) is a uranium mining and milling plant, situated at Caldas city, Minas Gerais, Brazil that was disabled in the mid 90's. This unit releases controlled effluents to three rivers: Ribeirao das Antas (at point 014, influenced by the waste pile), Ribeirao Soberbo (point 025, influenced by the waste pond) and Corrego da Consulta (at point 076, influenced by the open pit mine). Water samples collected at these points were analyzed for U{sub nat}, {sup 226}Ra, {sup 210}Pb, {sup 232}Th and {sup 228}Ra content in the particulate and soluble fractions, and the behavior of radionuclide releases and their fractions was investigated. U{sub nat} and {sup 228}Ra showed identical behaviors at these three points. U{sub nat} at point 014 (waste pile) behaved different from described in recent literature data. The isotopes of Ra should exhibit the same behavior at each point, but this was not observed at point 025 (waste pond). {sup 232}Th release showed equal activity concentration near the waste pile (point 014) and near the waste pond (point 025), whilst near the open pit mine (point 076) the soluble fraction showed a concentration of activity greater than the particulate fraction. Finally, {sup 210}Pb showed a different behavior at each point. Due to the great differences in behaviors of each radionuclide, it was not possible to establish a temporal pattern of release which requires assessment over a longer period of time. (author)

  7. Radionuclides release to three rivers by ore treatment unit at Caldas, Minas Gerais - Brazil

    International Nuclear Information System (INIS)

    Pereira, W.S.; Carmo, R.F. do; Py Junior, D.A.

    2013-01-01

    The Ore Treatment Unit (OTU) is a uranium mining and milling plant, situated at Caldas city, Minas Gerais, Brazil that was disabled in the mid 90's. This unit releases controlled effluents to three rivers: Ribeirao das Antas (at point 014, influenced by the waste pile), Ribeirao Soberbo (point 025, influenced by the waste pond) and Corrego da Consulta (at point 076, influenced by the open pit mine). Water samples collected at these points were analyzed for U nat , 226 Ra, 210 Pb, 232 Th and 228 Ra content in the particulate and soluble fractions, and the behavior of radionuclide releases and their fractions was investigated. U nat and 228 Ra showed identical behaviors at these three points. U nat at point 014 (waste pile) behaved different from described in recent literature data. The isotopes of Ra should exhibit the same behavior at each point, but this was not observed at point 025 (waste pond). 232 Th release showed equal activity concentration near the waste pile (point 014) and near the waste pond (point 025), whilst near the open pit mine (point 076) the soluble fraction showed a concentration of activity greater than the particulate fraction. Finally, 210 Pb showed a different behavior at each point. Due to the great differences in behaviors of each radionuclide, it was not possible to establish a temporal pattern of release which requires assessment over a longer period of time. (author)

  8. Ability of possible DMS precursors to release DMS during wine aging and in the conditions of heat-alkaline treatment.

    Science.gov (United States)

    Segurel, Marie A; Razungles, Alain J; Riou, Christophe; Trigueiro, Mafalda G L; Baumes, Raymond L

    2005-04-06

    The origin of dimethyl sulfide (DMS) produced during wine aging was examined through different assays. The production of DMS during the model aging of a wine and the concomitant decrease of residual potential DMS (PDMS), as DMS released by heat-alkaline treatment in 0.5 M sodium hydroxide at 100 degrees C for 1 h, were demonstrated. Then, dimethyl sulfoxide (DMSO), methionine sulfoxide (MSO), S-methylmethionine (SMM), and dimethylsulfonium propanoic acid (DMSPA), reported previously as possible DMS precursors, were investigated for their ability to be DMS precursors in wine in the conditions of this model aging and of the heat-alkaline treatment. The results showed that DMSO, MSO, and DMSPA could hardly be DMS precursors in the conditions used, whereas SMM appeared to be a good candidate. Finally, the use of [(2)H(6)]-DMSPA as an internal standard for PDMS determination was proposed, because it provided better reproducibility than [(2)H(6)]-DMS used as an external standard.

  9. Automated radiological scanning of potentially contaminated railroad crossties for free-release or disposal

    International Nuclear Information System (INIS)

    Hochel, R.C.

    1996-06-01

    The Savannah River Site (SRS) has accumulated approximately 300,000 crossties that have been replaced over a 40-year period of maintaining the site's 62 miles of railroad track. The ties reside in a pile on an open area of 2.3 acres near the site's F-Area facilities. A small fraction of the ties are potentially contaminated with radioactivity as a result of past site practices and service. Contamination was possible from occasional leaks in transport-casks moved by rail from the site's five nuclear materials production reactors to its two reprocessing facilities. Casks typically were filled with spent fuel, targets, and water from the reactor disassembly basins, which contained small amounts of fission and neutron activation product radioactivity normal to the operation of nuclear reactors. What to do with the ties has been debated for sometime. Proposals have ranged from simple burial, to bio-remediation, to burning as a fuel in the site's powerhouse, to free-release to off-site markets. In the past, burial was the disposal method of choice; however, the Department of Energy (DOE) order 5820.2A and premium on new space for low-level waste largely rule out burial. Instead, the last option is now cost effective and was begun under a contract with National Environmental Services Corporation started in January, 1996

  10. Fate and potential environmental effects of methylenediphenyl diisocyanate and toluene diisocyanate released into the atmosphere.

    Science.gov (United States)

    Tury, Bernard; Pemberton, Denis; Bailey, Robert E

    2003-01-01

    Information from a variety of sources has been collected and summarized to facilitate an overview of the atmospheric fate and potential environmental effects of emissions of methylenediphenyl diisocyanate (MDI) or toluene diisocyanate (TDI) to the atmosphere. Atmospheric emissions of both MDI and TDI are low, both in terms of concentration and mass, because of their low volatility and the need for careful control over all aspects of their lifecycle from manufacture through disposal. Typical emission losses for TDI are 25 g/t of TDI used in slabstock foam production. MDI emission losses are lower, often less than 1 g/t of MDI used. Dispersion modeling predicts that concentrations at the fenceline or beyond are very low for typical releases. Laboratory studies show that TDI (and by analogy MDI) does not react with water in the gas phase at a significant rate. The primary degradation reaction of these aromatic diisocyanates in the atmosphere is expected to be oxidation by OH radicals with an estimated half-life of one day. Laboratory studies also show that this reaction is not expected to result in increased ground-level ozone accumulation.

  11. Potential for iron oxides to control metal releases in CO2 sequestration scenarios

    Science.gov (United States)

    Berger, P.M.; Roy, W.R.

    2011-01-01

    The potential for the release of metals into groundwater following the injection of carbon dioxide (CO2) into the subsurface during carbon sequestration projects remains an open research question. Changing the chemical composition of even the relatively deep formation brines during CO2 injection and storage may be of concern because of the recognized risks associated with the limited potential for leakage of CO2-impacted brine to the surface. Geochemical modeling allows for proactive evaluation of site geochemistry before CO2 injection takes place to predict whether the release of metals from iron oxides may occur in the reservoir. Geochemical modeling can also help evaluate potential changes in shallow aquifers were CO2 leakage to occur near the surface. In this study, we created three batch-reaction models that simulate chemical changes in groundwater resulting from the introduction of CO2 at two carbon sequestration sites operated by the Midwest Geological Sequestration Consortium (MGSC). In each of these models, we input the chemical composition of groundwater samples into React??, and equilibrated them with selected mineral phases and CO 2 at reservoir pressure and temperature. The model then simulated the kinetic reactions with other mineral phases over a period of up to 100 years. For two of the simulations, the water was also at equilibrium with iron oxide surface complexes. The first model simulated a recently completed enhanced oil recovery (EOR) project in south-central Illinois in which the MGSC injected into, and then produced CO2, from a sandstone oil reservoir. The MGSC afterwards periodically measured the brine chemistry from several wells in the reservoir for approximately two years. The sandstone contains a relatively small amount of iron oxide, and the batch simulation for the injection process showed detectable changes in several aqueous species that were attributable to changes in surface complexation sites. After using the batch reaction

  12. Site-sensitive hazards of potential airborne radioactive release from sources on the Kola peninsula

    International Nuclear Information System (INIS)

    Bergman, R.; Thaning, L.; Baklanov, A.

    1998-02-01

    In this work we focus on cases of airborne releases from some of the sources on the Kola Peninsula - primarily nuclear reactors on submarines and the Kola Nuclear Power Plant (KNPP). The purpose of our study is to illustrate, and discuss some features - dependent on site and release characteristics - of the deposition patterns resulting from assumed unit radioactive releases to the atmosphere from a location at a fjord and from the KNPP in Polyarnye Zori. Using meteorological data for one real weather situation, the analysis is based on simulating the transport in air of assumed radioactive releases and estimating the deposition pattern on local, meso- and regional scales. By allowing unit releases to occur simultaneously from the site at the fjord and from the power plant (and with the same release profile in time) comparisons are made of differences in deposition patterns in and outside the Kola region. In this case study a set of assumed release heights, durations of the release, and particle size distributions are applied to indicate the dependence for the resulting deposition pattern on these parameters

  13. Chiropractic treatment of lateral epicondylitis: a case report utilizing active release techniques.

    Science.gov (United States)

    Gliedt, Jordan A; Daniels, Clinton J

    2014-06-01

    The purpose of this report is to describe the chiropractic management of a case of lateral epicondylitis with active release techniques (ART). A 48-year-old white man presented to a chiropractic clinic with a complaint of left lateral elbow pain that began 2 years previous with insidious onset. The patient reported an inability to play 18 consecutive holes of golf due to the pain. Treatment consisted of 5 sessions of ART (a soft tissue technique that is applied to muscles, fascia, tendons, ligaments, and nerves) applied to the left elbow soft tissue over a duration of 3 weeks. The patient reported an absence of pain and ability to consistently play 18 consecutive holes of golf up to 3 times per week at 4 and 8 weeks post-treatment. This patient with lateral epicondylitis responded favorably to chiropractic treatment using the application of ART, as demonstrated by reduced pain and increased functional outcomes.

  14. Grafting amino drugs to poly(styrene-alt-maleic anhydride) as a potential method for drug release

    Energy Technology Data Exchange (ETDEWEB)

    Khazaei, Ardeshir; Saednia, Shahnaz; Saien, Javad; Abbasi, Fatemeh, E-mail: Khazaei_1326@yahoo.com, E-mail: ssaednia@gmail.com [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of); Kazem-Rostami, Masoud [Young Researchers Club and Elite, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Sadeghpour, Mahdieh [Department of Chemistry, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Borazjani, Maryam Kiani [Faculty of Science, Department of Chemistry, Bushehr Payame Noor University (PNU), Bushehr (Iran, Islamic Republic of)

    2013-07-15

    Drug delivery systems based on polymer-drug conjugates give an improved treatment with lower toxicity or side effects and be used for the treatment of different diseases. Conjugates of biodegradable poly(styrene-alt-maleic anhydride) (PSMA), with a therapeutic agents such as amantadine hydrochloride, amlodipine, gabapentin, zonisamide and mesalamine, were afforded by the formation of the amide bonds of the amino drugs that reacted with the PSMA anhydride groups. The amounts of covalently conjugated drugs were determined by a {sup 1}H NMR spectroscopic method, and the in vitro release rate in buffer solution (pH 1.3) was studied at body temperature 37 Degree-Sign C. In kinetic studies, different dissolution models were examined to obtain drug release data and the collected data were well-fitted to the Korsmeyer-Peppas equation, revealing a dominant Fickian diffusion mechanism for drug release under the in vitro conditions. (author)

  15. Expression of transient receptor potential ankyrin 1 (TRPA1 and its role in insulin release from rat pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    De-Shou Cao

    Full Text Available Several transient receptor potential (TRP channels are expressed in pancreatic beta cells and have been proposed to be involved in insulin secretion. However, the endogenous ligands for these channels are far from clear. Here, we demonstrate the expression of the transient receptor potential ankyrin 1 (TRPA1 ion channel in the pancreatic beta cells and its role in insulin release. TRPA1 is an attractive candidate for inducing insulin release because it is calcium permeable and is activated by molecules that are produced during oxidative glycolysis.Immunohistochemistry, RT-PCR, and Western blot techniques were used to determine the expression of TRPA1 channel. Ca²⁺ fluorescence imaging and electrophysiology (voltage- and current-clamp techniques were used to study the channel properties. TRPA1-mediated insulin release was determined using ELISA.TRPA1 is abundantly expressed in a rat pancreatic beta cell line and freshly isolated rat pancreatic beta cells, but not in pancreatic alpha cells. Activation of TRPA1 by allyl isothiocyanate (AITC, hydrogen peroxide (H₂O₂, 4-hydroxynonenal (4-HNE, and cyclopentenone prostaglandins (PGJ₂ and a novel agonist methylglyoxal (MG induces membrane current, depolarization, and Ca²⁺ influx leading to generation of action potentials in a pancreatic beta cell line and primary cultured pancreatic beta cells. Activation of TRPA1 by agonists stimulates insulin release in pancreatic beta cells that can be inhibited by TRPA1 antagonists such as HC030031 or AP-18 and by RNA interference. TRPA1-mediated insulin release is also observed in conditions of voltage-gated Na⁺ and Ca²⁺ channel blockade as well as ATP sensitive potassium (K(ATP channel activation.We propose that endogenous and exogenous ligands of TRPA1 cause Ca²⁺ influx and induce basal insulin release and that TRPA1-mediated depolarization acts synergistically with K(ATP channel blockade to facilitate insulin release.

  16. Accumulation and release of implanted hydrogen from blisters in Si during the thermal treatment

    International Nuclear Information System (INIS)

    Aleksandrov, P.A.; Baranova, E.K.; Baranova, I.V.; Budaragin, V.V.; Litvinov, V.L.

    2004-01-01

    The processes of accumulation of ion implanted hydrogen in blisters in silicon and its release during the thermal treatment at 350-1020 deg C have been studied by optical techniques. It is established that accumulation of gaseous hydrogen inside blisters takes place at temperatures lower than ∼ 450-500 deg C and is accompanied by the growth of blisters thickness and deformation of their caps. At higher temperatures hydrogen leaves cavities and dissolves in silicon. Due to internal pressure dropping the elasticity deformed top layer partially relaxes, and the blister thickness decreases. Etching of the surface layer reveals the agglomerations of small voids ( [ru

  17. Transformation of the released asbestos, carbon fibers and carbon nanotubes from composite materials and the changes of their potential health impacts.

    Science.gov (United States)

    Wang, Jing; Schlagenhauf, Lukas; Setyan, Ari

    2017-02-20

    Composite materials with fibrous reinforcement often provide superior mechanical, thermal, electrical and optical properties than the matrix. Asbestos, carbon fibers and carbon nanotubes (CNTs) have been widely used in composites with profound impacts not only on technology and economy but also on human health and environment. A large number of studies have been dedicated to the release of fibrous particles from composites. Here we focus on the transformation of the fibrous fillers after their release, especially the change of the properties essential for the health impacts. Asbestos fibers exist in a large number of products and the end-of-the-life treatment of asbestos-containing materials poses potential risks. Thermal treatment can transform asbestos to non-hazardous phase which provides opportunities of safe disposal of asbestos-containing materials by incineration, but challenges still exist. Carbon fibers with diameters in the range of 5-10 μm are not considered to be respirable, however, during the release process from composites, the carbon fibers may be split along the fiber axis, generating smaller and respirable fibers. CNTs may be exposed on the surface of the composites or released as free standing fibers, which have lengths shorter than the original ones. CNTs have high thermal stability and may be exposed after thermal treatment of the composites and still keep their structural integrity. Due to the transformation of the fibrous fillers during the release process, their toxicity may be significantly different from the virgin fibers, which should be taken into account in the risk assessment of fiber-containing composites.

  18. In Situ Forming and H2O2-Releasing Hydrogels for Treatment of Drug-Resistant Bacterial Infections.

    Science.gov (United States)

    Lee, Yunki; Choi, Kyong-Hoon; Park, Kyung Min; Lee, Jong-Min; Park, Bong Joo; Park, Ki Dong

    2017-05-24

    Various types of commercialized wound dressings (e.g., films, foams, gels, and nanofiber meshes) have been clinically used as a physical barrier against bacterial invasion and as wound-healing materials. Although these dressings can protect the wounded tissue from the external environment, they cannot treat the wounds that are already infected with bacteria. Herein, we report in situ H 2 O 2 -releasing hydrogels as an active wound dressing with antibacterial properties for treatment of drug-resistant bacterial infection. In this study, H 2 O 2 was used for two major purposes: (1) in situ gel formation via a horseradish peroxidase (HRP)/H 2 O 2 -triggered cross-linking reaction, and (2) antibacterial activity of the hydrogel via its oxidative effects. We found that there were residual H 2 O 2 in the matrix after in situ HRP-catalyzed gelling, and varying the feed amount of H 2 O 2 (1-10 mM; used to make hydrogels) enabled control of H 2 O 2 release kinetics within a range of 2-509 μM. In addition, although the gelatin-hydroxyphenyl propionic acid (GH) gel called "GH 10" (showing the greatest H 2 O 2 release, 509 μM) slightly decreased cell viability (to 82-84%) of keratinocyte (HaCaT) and fibroblast (L-929) cells in in vitro assays, none of the hydrogels showed significant cytotoxicity toward tissues in in vivo skin irritation tests. When the H 2 O 2 -releasing hydrogels that promote in vivo wound healing, were applied to various bacterial strains in vitro and ex vivo, they showed strong killing efficiency toward Gram-positive bacteria including Staphylococcus aureus, S. epidermidis, and clinical isolate of methicillin-resistant S. aureus (MRSA, drug-resistant bacteria), where the antimicrobial effect was dependent on the concentration of the H 2 O 2 released. The present study suggests that our hydrogels have great potential as an injectable/sprayable antimicrobial dressing with biocompatibility and antibacterial activity against drug-resistant bacteria including

  19. Tapentadol extended-release for treatment of chronic pain: a review

    Directory of Open Access Journals (Sweden)

    Vadivelu N

    2011-08-01

    Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

  20. Pharmaceutical Compounds in Wastewater: Wetland Treatment as a Potential Solution

    Directory of Open Access Journals (Sweden)

    John R. White

    2006-01-01

    Full Text Available Pharmaceutical compounds are being released into the aquatic environment through wastewater discharge around the globe. While there is limited removal of these compounds within wastewater treatment plants, wetland treatment might prove to be an effective means to reduce the discharge of the compounds into the environment. Wetlands can promote removal of these pharmaceutical compounds through a number of mechanisms including photolysis, plant uptake, microbial degradation, and sorption to the soil. We review relevant laboratory research on these various mechanisms and provide data on the few studies that have examined wetland removal. There is a need to document the degree to which various pharmaceutical compounds are removed in full-scale treatment wetlands, as there is a paucity of data on overall pharmaceutical removal rates.

  1. Potential of phytase-mediated iron release from cereal-based foods: a quantitative view

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; Tetens, Inge; Meyer, Anne S.

    2013-01-01

    The major part of iron present in plant foods such as cereals is largely unavailable for direct absorption in humans due to complexation with the negatively charged phosphate groups of phytate (myo-inositol (1,2,3,4,5,6)-hexakisphosphate). Human biology has not evolved an efficient mechanism...... to naturally release iron from iron phytate complexes. This narrative review will evaluate the quantitative significance of phytase-catalysed iron release from cereal foods. In vivo studies have shown how addition of microbially derived phytases to cereal-based foods has produced increased iron absorption via...... phytate complexes, and (3) the extent of phytate dephosphorylation required for iron release from inositol phosphates is warranted. Phytase-mediated iron release can improve iron absorption from plant foods. There is a need for development of innovative strategies to obtain better effects....

  2. Potential for control of Cadra cautella (Walker) by release of fully or partially sterile males

    International Nuclear Information System (INIS)

    Brower, J.H.; Tilton, E.W.

    1975-01-01

    Modifications of the sterile-male release technique appear to offer promise for the control of post-harvest lepidopteran pest populations within storage structures. Theoretical models of release strategies for Cadra cautella showed that each method has an 'ideal' flooding ratio. This ratio represents the best balance between extinction in a few generations and minimization of the total number of insects released. From data reported concerning the population dynamics of Cadra cautella in the field an ideal flooding ratio for fully sterile (S) males to fertile (F) males of 97:1 would achieve extinction in 3 generations. Total numbers of males released per 100 native insects that would be needed to achieve extinction at these flooding ratios would be 14,850, 14,900 and 18,500, respectively. (author)

  3. Bacteriophages-potential for application in wastewater treatment processes

    International Nuclear Information System (INIS)

    Withey, S.; Cartmell, E.; Avery, L.M.; Stephenson, T.

    2005-01-01

    Bacteriophages are viruses that infect and lyse bacteria. Interest in the ability of phages to control bacterial populations has extended from medical applications into the fields of agriculture, aquaculture and the food industry. Here, the potential application of phage techniques in wastewater treatment systems to improve effluent and sludge emissions into the environment is discussed. Phage-mediated bacterial mortality has the potential to influence treatment performance by controlling the abundance of key functional groups. Phage treatments have the potential to control environmental wastewater process problems such as: foaming in activated sludge plants; sludge dewaterability and digestibility; pathogenic bacteria; and to reduce competition between nuisance bacteria and functionally important microbial populations. Successful application of phage therapy to wastewater treatment does though require a fuller understanding of wastewater microbial community dynamics and interactions. Strategies to counter host specificity and host cell resistance must also be developed, as should safety considerations regarding pathogen emergence through transduction

  4. Changes in cognition, arm function and lower body function after Slow-Release Fampridine treatment

    DEFF Research Database (Denmark)

    Jensen, Henrik Boye; Ravnborg, Mads; Mamoei, Sepehr

    2014-01-01

    OBJECTIVE: We aimed to evaluate the effect of slow-release (SR) Fampridine on multiple outcome measures reflecting different domains, and to compare the responsiveness of the Six Spot Step Test (SSST) and the Timed 25 Foot Walk (T25FW). METHODS: For this study 108 participants were included. On day...... 0 they were tested with the T25FW, the SSST, the 9-Hole Peg Test (9-HPT), the 5 Times Sit-To-Stand test (5-STS) and the Symbol Digit Modalities Test (SDMT). Four weeks of treatment with SR Fampridine 10 mg BID was commenced. Participants were tested again after 26-28 days of treatment. RESULTS: Mean...... and cognition. Furthermore, the SSST is more responsive to the effect of SR Fampridine than is the T25FW. ClinicalTrials.gov identifier: NCT01656148....

  5. Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis.

    Science.gov (United States)

    Sosa, Lilian; Clares, Beatriz; Alvarado, Helen L; Bozal, Nuria; Domenech, Oscar; Calpena, Ana C

    2017-10-01

    The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Global analysis and parametric dependencies for potential unintended hydrogen-fuel releases

    Energy Technology Data Exchange (ETDEWEB)

    Harstad, Kenneth; Bellan, Josette [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, M/S 125-109, Pasadena, CA 91109-8099 (United States)

    2006-01-01

    Global, simplified analyses of gaseous-hydrogen releases from a high-pressure vessel and liquid-hydrogen pools are conducted for two purposes: (1) establishing order-of-magnitude values of characteristic times and (2) determining parametric dependencies of these characteristic times on the physical properties of the configuration and on the thermophysical properties of hydrogen. According to the ratio of the characteristic release time to the characteristic mixing time, two limiting configurations are identified: (1) a rich cloud exists when this ratio is much smaller than unity, and (2) a jet exists when this ratio is much larger than unity. In all cases, it is found that the characteristic release time is proportional to the total released mass and inversely proportional to a characteristic area. The approximate size, convection velocity, and circulation time of unconfined burning-cloud releases scale with the cloud mass at powers 1/3, 1/6, and 1/6, respectively, multiplied by an appropriately dimensional constant; the influence of cross flow can only be important if its velocity exceeds that of internal convection. It is found that the fireball lifetime is approximately the maximum of the release time and thrice the convection-associated characteristic time. Transition from deflagration to detonation can occur only if the size of unconfined clouds exceeds by a factor of O(10) that of a characteristic detonation cell, which ranges from 0.015 m under stoichiometric conditions to approximately 1 m under extreme rich/lean conditions. For confined vapor pockets, transition occurs only for pocket sizes larger than the cell size. In jets, the release time is inversely proportional to the initial vessel pressure and has a square root dependence on the vessel temperature. Jet velocities are a factor of 10 larger than convective velocities in fireballs and combustion is possible only in the subsonic, downstream region where entrainment may occur.

  7. Does Gonadotropin Releasing Hormone Agonists plus add-back therapy bring an aurora to orthodontic treatment?

    Directory of Open Access Journals (Sweden)

    Jiang Lingyong

    2012-01-01

    Full Text Available Introduction: Obviously, long therapy time of orthodontic treatment and a number of its adverse effects, such as pain, root resorption, enamel demineralization, periodontal disease, are the main reasons of complaints from patients. It is the first thing for an orthodontist to shorten the period of treatment and decrease the complications of orthodontic treatment as much as possible. The Hypothesis: We hypothesis Gonadotropin Releasing Hormone Agonists (GnRHa and add-back therapy can create the "therapeutic window", namely, the appropriate estrogen level and assuage the adverse effects of estrogen deficiency which should be avoided as much as possible. Evaluation of the Hypothesis: It is generally acknowledged that estrogen has direct regulating role in bone metabolism by acting on osteoblasts and osteoclasts. Estrogen deficiency can increase the rate of orthodontic tooth movement and also bring about some adverse effects. The appropriate estrogen level, which we call the "therapeutic window" in orthodontic treatment, can speed up the orthodontic tooth movement and eliminate the adverse effects as far as possible. GnRHa can be the maker of estrogen deficiency; meanwhile, add-back therapy can remove the adverse effects by estrogen deficiency. So, we believe that GnRHa plus add-back therapy could be a new adjuvant method of orthodontic treatment and be good for orthodontists and patients.

  8. Potential Release Site Sediment Concentrations Correlated to Storm Water Station Runoff through GIS Modeling

    International Nuclear Information System (INIS)

    McLean, C.T.

    2005-01-01

    This research examined the relationship between sediment sample data taken at Potential Release Sites (PRSs) and storm water samples taken at selected sites in and around Los Alamos National Laboratory (LANL). The PRSs had been evaluated for erosion potential and a matrix scoring system implemented. It was assumed that there would be a stronger relationship between the high erosion PRSs and the storm water samples. To establish the relationship, the research was broken into two areas. The first area was raster-based modeling, and the second area was data analysis utilizing the raster based modeling results and the sediment and storm water sample results. Two geodatabases were created utilizing raster modeling functions and the Arc Hydro program. The geodatabase created using only Arc Hydro functions contains very fine catchment drainage areas in association with the geometric network and can be used for future contaminant tracking. The second geodatabase contains sub-watersheds for all storm water stations used in the study along with a geometric network. The second area of the study focused on data analysis. The analytical sediment data table was joined to the PRSs spatial data in ArcMap. All PRSs and PRSs with high erosion potential were joined separately to create two datasets for each of 14 analytes. Only the PRSs above the background value were retained. The storm water station spatial data were joined to the table of analyte values that were either greater than the National Pollutant Discharge Elimination System (NPDES) Multi-Sector General Permit (MSGP) benchmark value, or the Department of Energy (DOE) Drinking Water Defined Contribution Guideline (DWDCG). Only the storm water stations were retained that had sample values greater than the NPDES MSGP benchmark value or the DOE DWDCG. Separate maps were created for each analyte showing the sub-watersheds, the PRSs over background, and the storm water stations greater than the NPDES MSGP benchmark value or the

  9. Discriminated release of phenolic substances from red wine grape skins (Vitis vinifera L.) by multicomponent enzymes treatment

    DEFF Research Database (Denmark)

    Arnous, Anis; Meyer, Anne S.

    2010-01-01

    Detailed insight into the effects of enzymatic treatments on grape phenolics is of significant importance for grape processing for wine making. This study examined the release of phenols during enzymatic (pectinolytic and cellulolytic) degradation of the cell wall polysaccharides in skins of Merlot...... the enzymatic treatment; phenolic acids, including hydroxybenzoic acids and hydroxycinnamic acids, were released as a function of monosaccharides liberation, i.e. as a function of the enzyme catalyzed cell wall degradation of the skins, and with some of the phenolic acids perhaps released from the lignin...

  10. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

  11. Effects of Muscle-Specific Oxidative Stress on Cytochrome c Release and Oxidation-Reduction Potential Properties.

    Science.gov (United States)

    Ke, Yiling; Mitacek, Rachel M; Abraham, Anupam; Mafi, Gretchen G; VanOverbeke, Deborah L; DeSilva, Udaya; Ramanathan, Ranjith

    2017-09-06

    Mitochondria play a significant role in beef color. However, the role of oxidative stress in cytochrome c release and mitochondrial degradation is not clear. The objective was to determine the effects of display time on cytochrome c content and oxidation-reduction potential (ORP) of beef longissimus lumborum (LL) and psoas major (PM) muscles. PM discolored by day 3 compared with LL. On day 0, mitochondrial content and mitochondrial oxygen consumption were greater in PM than LL. However, mitochondrial content and oxygen consumption were lower (P stress can affect cytochrome c release and ORP changes.

  12. Potentiation of glucose-induced insulin release in islets by desHis1[Glu9]glucagon amide

    DEFF Research Database (Denmark)

    Kofod, Hans; Unson, C G; Merrifield, R B

    1988-01-01

    Glucagon and secretin and some of their hybrid analogs potentiate glucose-induced release of insulin from isolated mouse pancreatic islets. It was recently shown that the synthetic glucagon analog, desHis1[Glu9]glucagon amide, does not stimulate the formation of cyclic adenosine monophosphate...... in the rat hepatocyte membrane, but binds well to the glucagon receptor and is a good competitive antagonist of glucagon. In the present study the effect of this analog on isolated islets was examined. desHis1-[Glu9]glucagon amide at 3 x 10(-7) M, in the presence of 0.01 M D-glucose, increased the release...

  13. Release of lungworm larvae from snails in the environment: potential for alternative transmission pathways.

    Directory of Open Access Journals (Sweden)

    Alessio Giannelli

    2015-04-01

    Full Text Available Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis. In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host.Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior. Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior.Results of this study

  14. Potential Impact of Atmospheric Releases at Russian Far East Nuclear Submarine Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Parker, F.; Mahura, A.; Compton, K.; Brown, K.; Takano, M.; Novikov, V.; Soerensen, J. H.; Baklanov, A.

    2003-02-25

    An ''Assessment of the Impact of Russian Nuclear Fleet Operations on Far Eastern Coastal Regions'' is being performed as part of the Radiation Safety of the Biosphere Project (RAD) of the International Institute for Applied Systems Analysis (IIASA) of Laxenburg, Austria. To the best of our knowledge, this is the first comprehensive unclassified analysis of the potential impact of accidents at the Russian Far East nuclear submarine sites near Vladivostok and Petropavlovsk. We have defined the situation there based upon available information and studies commissioned by RAD in collaboration with Russian research institutes including Russian Research Center-''Kurchatov Institute'', Institute of Northern Environmental Problems and Lazurit Central Design Bureau. Further, in our original work, some in collaboration with the staff of the Danish Meteorological Institute (DMI) and members of the Japan Atomic Energy Research Institute, we have calculated the nuclide trajectories from these sites in the atmospheric boundary layer, less than 1.5 kilometers high, and determined their probability of crossing any of the nearby countries as well as Asiatic Russia. We have further determined the concentrations in each of these crossings as well as the total, dry and wet depositions of nuclides on these areas. Finally, we have calculated the doses to the Japanese Island population from typical winter airflow patterns (those most likely to cross the Islands in the minimum times), strong north winds, weak north winds and cyclonic winds for conditions similar to the Chazhma Bay criticality accident (fresh fuel) and for a criticality accident for the same type of reactor with fuel being withdrawn (spent fuel). The maximum individual committed dosages were less than 2 x 10-7 and 2 x 10-3 mSv, respectively. The long-term external doses by radionuclides deposited on the ground and the internal doses by consumption of foods were not evaluated as it is

  15. Potential airborne release from soil-working operations in a contaminated area

    International Nuclear Information System (INIS)

    Sutter, S.L.

    1980-08-01

    Experiments were performed to provide an indication of how much material could be made airborne during soil-working operations in a contaminated area. Approximately 50 kg of contaminated soil were collected, dried, and mixed, and particle size distribution and 137 Cs content were characterized. In four experiments performed in a 2 ft x 2 ft wind tunnel at the Radioactive Aerosol Release Test Facility, soil was pumped into an airstream moving at 3.2, 10.4, 15.2, and 20 mph. These experiments were designed to maximize airborne releases by fluidizing the soil as it was pumped into the wind tunnel. Thus the airborne releases should represent upper limit values for soil-working operations. Airborne concentration and particle size samples were collected and all of the material deposited downstream was collected to calculate a mass balance. The fraction airborne was calculated using these measurements

  16. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

    Science.gov (United States)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Dispersion of radionuclides potentially released from the Atolls of Mururoa and Fangataufa to neighboring archipelagos

    International Nuclear Information System (INIS)

    Osvath, I.

    1999-01-01

    This paper presents a compartmental model developed to simulate dispersion of radionuclides released to the ocean from the atolls of Mururoa and Fangataufa on a scale of 3000 x 1700 km (150 deg. to 300 deg. S latitude, 130 deg. to 160 deg. W longitude), including the Tuamotu, Cook, Society, Gambier and Austral archipelagos

  18. Fluoride release and cariostatic potential of orthodontic adhesives with and without daily fluoride rinsing.

    NARCIS (Netherlands)

    Chin, M.Y.; Sandham, A.; Rumachik, E.N.; Ruben, J.L.; Huysmans, M.C.D.N.J.M.

    2009-01-01

    INTRODUCTION: In this study, we aimed to evaluate the fluoride-release profiles and caries lesion development in an enamel model with brackets cemented with 4 orthodontic adhesives with and without daily fluoride exposure. METHODS: Four orthodontic adhesives (Ketac Cem mu, 3M ESPE, Seefeld, Germany;

  19. Fluoride release and cariostatic potential of orthodontic adhesives with and without daily fluoride rinsing

    NARCIS (Netherlands)

    Chin, Yeen; Sandham, John; Rumachik, Elena N.; Ruben, Jan L.; Huysmans, Marie-Charlotte D. N. J. M.

    2009-01-01

    Introduction: In this study, we aimed to evaluate the fluoride-release profiles and caries lesion development in an enamel model with brackets cemented with 4 orthodontic adhesives with and without daily fluoride exposure. Methods: Four orthodontic adhesives (Ketac Cem mu, 3M ESPE, Seefeld, Germany;

  20. Release of Antibiotic Resistant Bacteria by a Waste Treatment Plant from Romania.

    Science.gov (United States)

    Lupan, Iulia; Carpa, Rahela; Oltean, Andreea; Kelemen, Beatrice Simona; Popescu, Octavian

    2017-09-27

    The occurrence and spread of bacterial antibiotic resistance are subjects of great interest, and the role of wastewater treatment plants has been attracting particular interest. These stations are a reservoir of bacteria, have a large range of organic and inorganic substances, and the amount of bacteria released into the environment is very high. The main purpose of the present study was to assess the removal degree of bacteria with resistance to antibiotics and identify the contribution of a wastewater treatment plant to the microbiota of Someşul Mic river water in Cluj county. The resistance to sulfamethoxazole and tetracycline and some of their representative resistance genes: sul1, tet(O), and tet(W) were assessed in this study. The results obtained showed that bacteria resistant to sulphonamides were more abundant than those resistant to tetracycline. The concentration of bacteria with antibiotic resistance changed after the treatment, namely, bacteria resistant to sulfamethoxazole. The removal of all bacteria and antibiotic-resistant bacteria was 98-99% and the degree of removal of bacteria resistant to tetracycline was higher than the bacteria resistant to sulfamethoxazole compared to total bacteria. The wastewater treatment plant not only contributed to elevating ARG concentrations, it also enhanced the possibility of horizontal gene transfer (HGT) by increasing the abundance of the intI1 gene. Even though the treatment process reduced the concentration of bacteria by two orders of magnitude, the wastewater treatment plant in Cluj-Napoca contributed to an increase in antibiotic-resistant bacteria concentrations up to 10 km downstream of its discharge in Someşul Mic river.

  1. Group I mGlu receptors potentiate synaptosomal [3H]glutamate release independently of exogenously applied arachidonic acid

    International Nuclear Information System (INIS)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J.

    1999-01-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [ 3 H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 μM) increased 4AP-evoked [ 3 H]glutamate release (143.32±2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC 50 =1.60±0.25 μM; E max =147.61±10.96% control) 4AP-evoked [ 3 H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu 1 receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 μM) and was BSA-insensitive. The selective mGlu 5 receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300μM) was without effect. DHPG (100 μM) also potentiated both 30 mM and 50 mM K + -evoked [ 3 H]glutamate release (121.60±12.77% and 121.50±4.45% control, respectively). DHPG (100 μM) failed to influence both 4AP-stimulated 45 Ca 2+ influx and 50 mM K + -induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A 1 receptor, group II/III mGlu receptors or GABA B receptor activity is unlikely since 4AP-evoked [ 3 H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-α-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu 1 receptor-like' receptor potentiates [ 3 H]glutamate release from cerebrocortical synaptosomes in the absence of exogenously applied arachidonic acid. This PKC dependent effect is unlikely to be via modulation of synaptosomal membrane

  2. GPR 120: The Potential Target for Obesity Treatment.

    Science.gov (United States)

    Tanagho, Peter A; Shohdy, Kyrillus S

    2016-01-01

    G protein coupled receptor 120 (GPR120) is a class of receptors in the gastrointestinal tract (GIT) that is implicated in nutrient sensing and body weight regulation. Functions of GPR120 are thought to be mediated by the release of a group of hormones known as incretins, such as glucagon like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). We have searched PubMed with the keywords "GPR120","GLP-1" and "obesity". Relevant studies were retrieved and included in the review. Recently, many exogenous compounds have been investigated in their role in the release of GLP-1 and in causing weight loss in obese rats. However, some results question the putative role of GPR120 in metabolic homeostasis. Herein, we evaluate the potential use of GPR120 as a target receptor in obesity and found it to be ubiquitous throughout the GIT, with various functions in each site. In order to find the optimal drug, the role of GPR120 in each site needs to be defined and selectivity of the potential drug needs to be studied to ensure the success of this growing line of obesity management.

  3. Potential of Biofilters for Treatment of De-Icing Chemicals

    OpenAIRE

    Raspati, Gema Sakti; Lindseth, Hanna Kristine; Muthanna, Tone Merete; Azrague, Kamal

    2018-01-01

    Organic de-icing chemicals, such as propylene glycol and potassium formate, cause environmental degradation in receiving water if left untreated, due to the high organic load resulting in oxygen depletion. Biofilters are commonly used for the treatment of biodegradable organic carbon in water treatment. This study investigated the potential for using biofilters for treating organic de-icing compounds. Lab-scale adsorption tests using filter media made of crushed clay (Filtralite) and granular...

  4. A comparison of measured radionuclide release rates from Three Mile Island Unit-2 core debris for different oxygen chemical potentials

    International Nuclear Information System (INIS)

    Baston, V.F.; Hofstetter, K.J.; Ryan, R.F.

    1987-01-01

    Chemical and radiochemical analyses of reactor coolant samples taken during defueling of the Three Mile Island Unit-2 (TMI-2) reactor provide relevant data to assist in understanding the solution chemistry of the radionuclides retained within the TMI-2 reactor coolant system. Hydrogen peroxide was added to various plant systems to provide disinfection for microbial contamination and has provided the opportunity to observe radionuclide release under different oxygen chemical potentials. A comparison of the radionuclide release rates with and without hydrogen peroxide has been made for these separate but related cases, i.e., the fuel transfer canal and connecting spent-fuel pool A with the TMI-2 reactor plenum in the fuel transfer canal, core debris grab sample laboratory experiments, and the reactor vessel fluid and associated core debris. Correlation and comparison of these data indicate a physical parameter dependence (surface-to-volume ratio) affecting all radionuclide release; however, selected radionuclides also demonstrate a chemical dependence release under the different oxygen chemical potentials. Chemical and radiochemical analyses of reactor coolant samples taken during defueling of the Three Mile Island Unit-2 (TMI-2) reactor provide relevant data to assist in understanding the solution chemistry of the radionuclides retained within the TMI-2 reactor coolant system

  5. The effect of extended release tolterodine used for overactive bladder treatment on female sexual function

    Directory of Open Access Journals (Sweden)

    Athanasios Zachariou

    Full Text Available ABSTRACT Introduction Overactive bladder (OAB is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI questionnaire. 73 patients of group A (control group received no treatment and 85 patients of group B received an anticholinergic regimen – tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment, arousal (3.1±0.2 to 3.1±0.2 respectively, lubrication (3.4±0.3 to 4.3±0.3 respectively, orgasm (3.5±0.3 to 4.5±0.3 respectively, satisfaction (2.6±0.2 to 4.2±0.3 respectively and pain (2.4±0.2 to 4.6±0.4 respectively after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05. Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5 compared to pre-treatment values (17.4±1.4, p0,05 respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.

  6. Medial to posterior release procedure after failure of functional treatment in clubfoot: a prospective study.

    Science.gov (United States)

    Bocahut, Nicolas; Simon, Anne-Laure; Mazda, Keyvan; Ilharreborde, Brice; Souchet, Philippe

    2016-04-01

    Two conservative techniques for clubfoot treatment are still being debated and depend upon the institution's expertise. For >40 years, the current institution has been a pioneer in the development of the physiotherapy method; however, some severe deformities remain resistant to this method which causes pain, sprains, and difficulties wearing shoes. Therefore, a surgical approach was developed simultaneously for the treatment of these residual or recurring clubfeet. The procedure reproduces the same chronological steps by performing forefoot derotation before correcting hindfoot equinus. The aim of the current study was to assess the results of this surgical technique. All clubfeet undergoing surgery between October 1995 and February 2009 were prospectively included. Initial severity was based on Dimeglio's classification and final outcomes on the International Clubfoot Study Group (ICFSG) outcome evaluation system. Last follow-up results were assessed by physical examination and radiographs. A total of 137 patients with severe clubfeet (mean Dimeglio score 12.0) underwent surgery. At the mean follow-up of 10.8 years, mean ICFSG score was 4.3 (range 0-23), and 12 % required revision surgery. The rate of undercorrection and overcorrection was low (17 pes-plano-valgus ft and 11 ft with undercorrection). Eight feet had a fixed deformity. Severe deformities are more resistant to conservative techniques even for institutions with large experience. These deformities require further treatment, including surgery if necessary. The medial to posterior soft-tissue release is a valuable technique with stable results. Level IV.

  7. Alkali Release from Typical Danish Aggregates to Potential ASR Reactive Concrete

    DEFF Research Database (Denmark)

    Thomsen, Hans Christian Brolin; Grelk, Bent; Barbosa, Ricardo Antonio

    Alkali-silica reaction (ASR) in concrete is a well-known deterioration mechanism affecting the long term durability of Danish concrete structures. Deleterious ASR cracking can be significantly reduced or prevented by limiting the total alkali content of concrete under a certain threshold limit......, which in Denmark is recommended to 3 kg/m3 Na2Oeq.. However, this threshold limit does not account for the possible internal contribution of alkali to the concrete pore solution by release from aggregates or external contributions from varies sources. This study indicates that certain Danish aggregates...... are capable of releasing more than 0.46 kg/m3 Na2Oeq. at 13 weeks of exposure in laboratory test which may increase the risk for deleterious cracking due to an increase in alkali content in the concrete....

  8. Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats.

    Science.gov (United States)

    Maeng, L Y; Taha, M B; Cover, K K; Glynn, S S; Murillo, M; Lebron-Milad, K; Milad, M R

    2017-08-01

    Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Objective measures of binaural masking level differences and comodulation masking release based on late auditory evoked potentials

    DEFF Research Database (Denmark)

    Epp, Bastian; Yasin, Ifat; Verhey, Jesko L.

    2013-01-01

    at a fixed physical intensity is varied by introducing auditory cues of (i) interaural target signal phase disparity and (ii) coherent masker level fluctuations in different frequency regions. In agreement with previous studies, psychoacoustical experiments showed that both stimulus manipulations result......The audibility of important sounds is often hampered due to the presence of other masking sounds. The present study investigates if a correlate of the audibility of a tone masked by noise is found in late auditory evoked potentials measured from human listeners. The audibility of the target sound...... in a masking release (i: binaural masking level difference; ii: comodulation masking release) compared to a condition where those cues are not present. Late auditory evoked potentials (N1, P2) were recorded for the stimuli at a constant masker level, but different signal levels within the same set of listeners...

  10. Characterization of the Potential Hazards Associated with Potential RCRA Treatment Noncompliances

    Energy Technology Data Exchange (ETDEWEB)

    Clark, David Lewis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-08-20

    The purpose of this document is to provide a hazard evaluation of the noncompliances and whether any new actions are required to mitigate potential risk to the worker or the public. In short, we have reviewed the noncompliances and have concluded that the possibility of exothermic reactions leading to radioactive release is not credible, and in one case, inconceivable, stemming from the fact that the majority fraction of the waste is compatible with organic absorbents and neutralizers. It is not expected that the noncompliances would generate or produce uncontrolled flammable fumes, gases, extreme heat, pressure, fire, explosions, or violent reactions.

  11. Nanovesicles released by Dictyostelium cells: a potential carrier for drug delivery.

    Science.gov (United States)

    Lavialle, Françoise; Deshayes, Sophie; Gonnet, Florence; Larquet, Eric; Kruglik, Sergei G; Boisset, Nicolas; Daniel, Régis; Alfsen, Annette; Tatischeff, Irène

    2009-10-01

    Nanovesicles released by Dictyostelium discoideum cells grown in the presence of the DNA-specific dye Hoechst 33342 have been previously shown to mediate the transfer of the dye into the nuclei of Hoechst-resistant cells. The present investigation extends this work by conducting experiments in the presence of hypericin, a fluorescent therapeutic photosensitizer assayed for antitumoral photodynamic therapy. Nanovesicles released by Dictyostelium cells exhibit an averaged diameter between 50 and 150 nm, as measured by transmission cryoelectron microscopy. A proteomic analysis reveals a predominance of actin and actin-related proteins. The detection of a lysosomal membrane protein (LIMP II) indicates that these vesicles are likely generated in the late endosomal compartment. The use of the hypericin-containing nanovesicles as nanodevices for in vitro drug delivery was investigated by fluorescence microscopy. The observed signal was almost exclusively located in the perinuclear area of two human cell lines, skin fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by confocal microscopy with specific markers of cell organelles, provided evidence that hypericin was accumulated in the Golgi apparatus. All these data shed a new light on in vitro drug delivery by using cell-released vesicles as carriers.

  12. Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation

    Directory of Open Access Journals (Sweden)

    Andromeda Linan Rico

    2016-12-01

    Full Text Available Enterochromaffin cells (EC synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s involved in EC cell ‘mechanosensation’ and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are ‘mechanosensors’ that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains and tight regulation of 5-HT release by purines. The ‘purinergic hypothesis’ is that MS releases purines to act in an autocrine / paracrine manner to activate excitatory (P2Y1, P2Y4, P2Y6, A2A/A2B or inhibitory (P2Y12, A1, A3 receptors to regulate 5-HT release. MS activates a P2Y1/Gαq/PLC/IP3-IP3R/SERCA Ca2+signaling pathway, an A2A/A2B–Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X3 channel, and an inhibitory P2Y12 -Gi/o/AC-cAMP pathway. In human IBD, P2X3 is down regulated and A2B is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.

  13. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Directory of Open Access Journals (Sweden)

    Marino DiFranco

    Full Text Available Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

  14. Assessment of dairy wastewater treatment and its potential for ...

    African Journals Online (AJOL)

    The extent of pollution of dairy wastewater treated in a septic tank and its potential for biogas production was investigated. Performance of the existing treatment system was assessed through characterization of both raw and treated effluents. From the analysis parameters likeChemical Oxygen Demand (COD), Biochemical ...

  15. Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

    Science.gov (United States)

    Werther, G A; Warne, G L; Ennis, G; Gold, H; Silink, M; Cowell, C T; Quigley, C; Howard, N; Antony, G; Byrne, G C

    1990-02-01

    A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

  16. Pre-treatment and ethanol fermentation potential of olive pulp at different dry matter concentrations

    DEFF Research Database (Denmark)

    Haagensen, Frank Drøscher; Skiadas, Ioannis V.; Gavala, Hariklia N.

    2009-01-01

    potential of the olive pulp, which is the semi solid residue generated from the two-phase processing of the olives for olive oil production. Wet oxidation and enzymatic hydrolysis have been applied aiming at the enhancement of carbohydrates' bioavailability. Different concentrations of enzymes and enzymatic......, implying that wet oxidation is not a recommended pre-treatment process for olive pulp at the conditions tested. It was also showed that increased dry matter concentration did not have a negative effect on the release of sugars, indicating that the cellulose and xylan content of the olive pulp is relatively...

  17. Nanotechnology and HIV: potential applications for treatment and prevention.

    Science.gov (United States)

    Kim, Peter S; Read, Sarah W

    2010-01-01

    HIV/AIDS is a global pandemic and is the leading infectious cause of death among adults. Although antiretroviral (ARV) therapy has dramatically improved the quality of life and increased the life expectancy of those infected with HIV, life-long suppressive treatment is required and a cure for HIV infection remains elusive; frequency of dosing and drug toxicity as well as the development of viral resistance pose additional limitations. Furthermore, preventative measures such as a vaccine or microbicide are urgently needed to curb the rate of new infections. The capabilities inherent to nanotechnology hold much potential for impact in the field of HIV treatment and prevention. This article reviews the potential for the multidisciplinary field of nanotechnology to advance the fields of HIV treatment and prevention. © 2010 John Wiley & Sons, Inc.

  18. Double insemination and gonadotropin-releasing hormone treatment of repeat-breeding dairy cattle.

    Science.gov (United States)

    Stevenson, J S; Call, E P; Scoby, R K; Phatak, A P

    1990-07-01

    Our objective was to determine if double inseminations during the same estrous period of dairy cattle eligible for their third or fourth service (repeat breeders) would improve pregnancy rates equivalent to injections of GnRH given at the time of AI. Repeat-breeding, lactating cows from six herds (five herds in the San Joaquin Valley of central California and one herd in northeast Kansas) were assigned randomly to four treatment groups when detected in estrus: 1) single AI plus no injection, 2) single AI plus 100 micrograms GnRH at AI, 3) double AI plus no injection, or 4) double AI plus 100 micrograms of GnRH at AI. Inseminations were performed according to the a.m.-p.m. rule. The second AI for the double AI treatment was given 12 to 16 h after the first AI. Injections of GnRH were given intramuscularly immediately following the single AI or the first AI of the double AI. Pregnancy rates of cows given a single AI and hormone injection were numerically higher in all six herds than those of their herdmates given only a single AI. In five of six herds, the pregnancy rates of cows given a double AI and hormone injection were numerically higher than pregnancy rates of their herdmates given only a double AI. Overall pregnancy rates for the four treatments were 1) 112/353 (32.1%), 2) 165/406 (41.6%), 3) 119/364 (33.5%), and 4) 135/359 (37.5%). Gonadotropin-releasing hormone increased pregnancy rates of repeat breeders compared with controls given only a single AI. No further benefit beyond the single AI was accrued from the double AI treatment, with or without concurrent hormone administration.

  19. Historical assessment of uranium release by the ore treatment unit - at Caldas, Minas Gerais, Brazil from 1999 to 2011

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, W.S.; Carmo, R.F.; Py Junior, D.A., E-mail: pereiraws@gmail.com [Industrias Nucleares do Brasil (INB), Pocos de Caldas, MG (Brazil). Unidade de Tratamento de Minerio. Grupo Multidisciplinar de Radioprotecao; Kelecom, A., E-mail: akelecom@id.uff.br [Universidade Federal Fluminense (LARARA-PLS/GETA/UFF), Niteroi, RJ (Brazil). Laboratorio de Radiobiologia e Radiometria Pedro Lopes dos Santos. Grupo de Estudos em Temas Ambientais; Pereira, J.R.S., E-mail: pereirarsj@gmail.com [Universidade Federal de Alfenas, Pocos de Caldas, MG (Brazil)

    2013-07-01

    The Ore Treatment Unit (OTU) is located at the source of three rivers: Ribeirao das Antas, Ribeirao do Soberbo and Corrego da Consulta. Each interface of installation with the environment, at the tree rivers, has been monitored for the release of radionuclides. At Ribeirao das Antas a weekly sample collection was made at point 014. At Ribeirao Soberbo there was a weekly sample collection at point 025, and at Corrego da Consulta a monthly collection was carried out at point 076. This work analyses the average annual releases of uranium from the historical series started in 1999 and ended in 2011. Points 014 and 025 showed average release of 0.12 Bq L{sup -1}. Point 076 showed somewhat higher average release, 1.27 Bq L{sup -1}. An Analysis Of Variance test (ANOVA) has been carried out to verify the existence of different means between these collecting points. The averages were considered statistically different. As a complementary analysis, the Student's t test was performed between the averages at considered points. Between points 014 and 025, the averages were considered identical. Between points 014 and 076, the average release at point 076 was considered higher than that at point 014. The same behavior was observed between points 025 and 076. The releases at point 076 were considered higher than those at point 025. Thus it can be concluded that releases at points 014 and 025 are identical and both are lower than releases at point 076. (author)

  20. Historical assessment of uranium release by the ore treatment unit - at Caldas, Minas Gerais, Brazil from 1999 to 2011

    International Nuclear Information System (INIS)

    Pereira, W.S.; Carmo, R.F.; Py Junior, D.A.

    2013-01-01

    The Ore Treatment Unit (OTU) is located at the source of three rivers: Ribeirao das Antas, Ribeirao do Soberbo and Corrego da Consulta. Each interface of installation with the environment, at the tree rivers, has been monitored for the release of radionuclides. At Ribeirao das Antas a weekly sample collection was made at point 014. At Ribeirao Soberbo there was a weekly sample collection at point 025, and at Corrego da Consulta a monthly collection was carried out at point 076. This work analyses the average annual releases of uranium from the historical series started in 1999 and ended in 2011. Points 014 and 025 showed average release of 0.12 Bq L -1 . Point 076 showed somewhat higher average release, 1.27 Bq L -1 . An Analysis Of Variance test (ANOVA) has been carried out to verify the existence of different means between these collecting points. The averages were considered statistically different. As a complementary analysis, the Student's t test was performed between the averages at considered points. Between points 014 and 025, the averages were considered identical. Between points 014 and 076, the average release at point 076 was considered higher than that at point 014. The same behavior was observed between points 025 and 076. The releases at point 076 were considered higher than those at point 025. Thus it can be concluded that releases at points 014 and 025 are identical and both are lower than releases at point 076. (author)

  1. Consequences in Norway of a hypothetical accident at Sellafield: Potential release - transport and fallout

    International Nuclear Information System (INIS)

    Ytre-Eide, M. A.; Standring, W.J.F.; Amundsen, I.; Sickel, M.; Liland, A.; Saltbones, J.; Bartnicki, J.; Haakenstad, H.; Salbu, B.

    2009-03-01

    This report focuses on transport and fallout from 'worst-case' scenarios based on a hypothetical accident at the B215 facility for storing Highly Active Liquors (HAL) at Sellafield. The scenarios involve an atmospheric release of between 0.1-10 % of the total HAL inventory; only transport and fallout of 137 Cs is considered in this case study. Simulations resulted in between 0.1-50 times the maximum 137 Cs fallout experienced in the most contaminated areas in Norway after the Chernobyl accident. (Author)

  2. Objective measures of binaural masking level differences and comodulation masking release based on late auditory evoked potentials.

    Science.gov (United States)

    Epp, Bastian; Yasin, Ifat; Verhey, Jesko L

    2013-12-01

    The audibility of important sounds is often hampered due to the presence of other masking sounds. The present study investigates if a correlate of the audibility of a tone masked by noise is found in late auditory evoked potentials measured from human listeners. The audibility of the target sound at a fixed physical intensity is varied by introducing auditory cues of (i) interaural target signal phase disparity and (ii) coherent masker level fluctuations in different frequency regions. In agreement with previous studies, psychoacoustical experiments showed that both stimulus manipulations result in a masking release (i: binaural masking level difference; ii: comodulation masking release) compared to a condition where those cues are not present. Late auditory evoked potentials (N1, P2) were recorded for the stimuli at a constant masker level, but different signal levels within the same set of listeners who participated in the psychoacoustical experiment. The data indicate differences in N1 and P2 between stimuli with and without interaural phase disparities. However, differences for stimuli with and without coherent masker modulation were only found for P2, i.e., only P2 is sensitive to the increase in audibility, irrespective of the cue that caused the masking release. The amplitude of P2 is consistent with the psychoacoustical finding of an addition of the masking releases when both cues are present. Even though it cannot be concluded where along the auditory pathway the audibility is represented, the P2 component of auditory evoked potentials is a candidate for an objective measure of audibility in the human auditory system. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. REMOVE AND RELEASE OF NUTRIENTS AFTER HYBRID PRE-TREATMENT OF ACTIVATED SLUDGE FOAM

    Directory of Open Access Journals (Sweden)

    Alicja Machnicka

    2017-02-01

    Full Text Available One of the problems in wastewater treatment technologies is the formation of foam/scum on the surface of bioreactors. The foam elimination/destruction can be carried out by various methods among which disintegration is included. Hybrid disintegration (chemical decomposition and hydrodynamic cavitation of the foam microorganisms results in phosphates, ammonium nitrogen, magnesium and potassium transferred from the foam solids into the liquid phase. Application of both methods as a hybrid pre-treatment process caused in an increased concentration of phosphates of about 677 mg PO43- L-1, ammonium nitrogen about 41 mg N-NH4+ L-1. The concentration of Mg2+ and K+ in the solution increased from 6.2 to 31.1 mg Mg2+ L-1 and from 22.4 to 102.0 mg K+ L-1, respectively. The confirmation of physicochemical changes and release of cellular matter as a result of cellular lysis (hybrid disintegration was IR analysis. It was demonstrated that the disintegration of foam permits removal of a part of nutrients in the form of struvite.

  4. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    Science.gov (United States)

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

  5. Combination cancer treatment through photothermally controlled release of selenous acid from gold nanocages.

    Science.gov (United States)

    Cheng, Haoyan; Huo, Da; Zhu, Chunlei; Shen, Song; Wang, Wenxia; Li, Haoxuan; Zhu, Zhihong; Xia, Younan

    2018-04-03

    Selenite, one of the inorganic forms of selenium, is emerging as an attractive chemotherapeutic agent owing to its selectivity in eradicating cancer cells. Here we demonstrate a new formulation of nanomedicine based on selenous acid, which is mixed with lauric acid (a phase-change material with a melting point around 43 °C) and then loaded into the cavities of Au nanocages. The Au nanocages can serve as a carrier during cell endocytosis and then as a photothermal agent to melt the lauric acid upon the irradiation with a near-infrared laser, triggering the swift release of selenous acid. The photothermal and chemo therapies can also work synergistically, leading to enhanced destruction of cancer cells relative to normal cells. Our systematic study suggests that the impaired mitochondrial function arising from the ROS generated through combination treatment is responsible for the cell death. This study offers an appealing candidate that holds great promise for synergistic cancer treatment. Published by Elsevier Ltd.

  6. Evaluation of the potential for significant ammonia releases from Hanford waste tanks

    International Nuclear Information System (INIS)

    Palmer, B.J.; Anderson, C.M.; Chen, G.; Cuta, J.M.; Ferryman, T.A.; Terrones, G.

    1996-07-01

    Ammonia is ubiquitous as a component of the waste stored in the Hanford Site single-shell tanks (SSTs) and double-shell tanks (DSTs). Because ammonia is both flammable and toxic, concerns have been raised about the amount of ammonia stored in the tanks and the possible mechanisms by which it could be released from the waste into the head space inside the tanks as well as into the surrounding atmosphere. Ammonia is a safety issue for three reasons. As already mentioned, ammonia is a flammable gas and may contribute to a flammability hazard either directly, if it reaches a high enough concentration in the tank head space, or by contributing to the flammability of other flammable gases such as hydrogen (LANL 1994). Ammonia is also toxic and at relatively low concentrations presents a hazard to human health. The level at which ammonia is considered Immediately Dangerous to Life or Health (IDLH) is 300 ppm (WHC 1993, 1995). Ammonia concentrations at or above this level have been measured inside the head space in a number of SSTs. Finally, unlike hydrogen and nitrous oxide, ammonia is highly soluble in aqueous solutions, and large amounts of ammonia can be stored in the waste as dissolved gas. Because of its high solubility, ammonia behaves in a qualitatively different manner from hydrogen or other insoluble gases. A broader range of scenarios must be considered in modeling ammonia storage and release

  7. Release of hydrogen sulfide under intermittent flow conditions – the potential of simulation models

    DEFF Research Database (Denmark)

    Matias, Natércia; Matos, Rita Ventura; Ferreira, Filipa

    2018-01-01

    For engineering purposes it is especially useful to be able to predict and control sewer corrosion rates and odor impacts as well as to design effective measures aiming to reduce effects related to hydrogen sulfide formation and release. Doing so, it is important to use modeling tools that are ca......For engineering purposes it is especially useful to be able to predict and control sewer corrosion rates and odor impacts as well as to design effective measures aiming to reduce effects related to hydrogen sulfide formation and release. Doing so, it is important to use modeling tools...... to evaluate the effects of transitions between pressure mains and gravity sewers in the air–liquid mass transfer of hydrogen sulfide at the Ericeira sewer system in Portugal. This network is known to have odor and corrosion problems, especially during summer. Despite the unavoidable uncertainties due...... to the unsteady flow rate and the quantification of air velocity and turbulence, the simulation results obtained with both models have been shown to adequately predict the overall behavior of the system....

  8. Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

    Directory of Open Access Journals (Sweden)

    Lee Choon-Taek

    2010-10-01

    Full Text Available Abstract Background The role of interferon-γ release assay (IGRA in monitoring responses to anti-tuberculosis (TB treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT assay over time during the anti-TB treatment of adults with no underlying disease. Methods We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline and at 1, 3, and 6 months after initiating anti-TB medication. Results Of 67 eligible patients, 59 (88.1% completed the study protocol. All participants were males who were human immunodeficiency virus (HIV-negative and had no chronic diseases. Their median age was 21 years (range, 20-48. Initially, 57 (96.6% patients had positive QFT-GIT results, and 53 (89.8%, 42 (71.2%, and 39 (66.1% had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C at diagnosis were associated with negative reversion of the QFT-GIT assay. Conclusion Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.

  9. Development of transition metal oxide catalysts for treatment of off-gases released during pyrolysis of organic ion exchange resins

    International Nuclear Information System (INIS)

    Sathi Sasidharan, N.; Deshingkar, D.S.; Wattal, P.K.

    2005-08-01

    The spent IX resin wastes arising from nuclear power plants have high radiation level due to fission product 137 Cesium and activation product 60 Cobalt. The pyrolysis and oxidative pyrolysis processes have potential to minimize final waste form volumes of these wastes. The major difficulty in deploying these processes for treatment of spent IX resins is release of off-gases containing large quantities of aromatic hydrocarbons, amines, sulphur dioxide, hydrogen sulphide, carbonyl sulphide etc. As an alternative to high temperature incineration of the pyrolysis off gases, feasibility of using catalytic combustion at moderate temperatures was investigated in the laboratory. Copper chromite, copper oxide-ceric oxide and vanadium pentaoxide catalysts supported on alumina were prepared and tested for oxidation of styrene monomer, toluene, ethyl benzene and trimethyl amine at 22500 hr -1 space velocity and temperature range of 300 to 500 degC. At temperatures over 475 degC, all three catatyst gave oxidation efficiency of over 97% for these compounds over concentration range of few tens of ppm to few thousands ppm. A composite catalyst bed of three catalysts comprising principally of copper chromite is proposed for treatment of IX resin pyrolysis off-gases. (author)

  10. Levonorgestrel-releasing intrauterine system for treatment of heavy menstrual bleeding in adolescents with Glanzmann's Thrombasthenia: illustrated case series.

    Science.gov (United States)

    Lu, Meiqiu; Yang, Xin

    2018-02-27

    Glanzmann's Thrombasthenia (GT) is an inherited genetic disorder caused by defects in the platelet membrane glycoproteins IIb/IIIA, and is associated with heavy menstrual bleeding (HMB). HMB is a common complication in female patients, and many adolescent girls with this disease have issues with HMB beginning at menarche. The available treatment modalities including anti-fibrinolytics, nonsteroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies though are effective, their associated side effects, limited efficacy and the poor compliance is a challenge in management of HMB. Levonorgestrel-releasing intrauterine system (LNG-IUS) has been a potential alternative to overcome this challenge. The use of the LNG-IUS for the management of HMB in adolescents with GT is explored in this case series. Two adolescents diagnosed with GT and received the LNG-IUS as treatment modality for management of HMB is discussed in this case series. For patients with poor compliance to oral hormonal therapies, the use of LNG-IUS is associated with a significant reduction of menstrual blood loss along with improved quality of life. These findings support the use of LNG-IUS to control adolescent GT-related HMB.

  11. Planar Diamond-Based Multiarrays to Monitor Neurotransmitter Release and Action Potential Firing: New Perspectives in Cellular Neuroscience.

    Science.gov (United States)

    Carabelli, Valentina; Marcantoni, Andrea; Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Pasquarelli, Alberto; Olivero, Paolo; Carbone, Emilio

    2017-02-15

    High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical and electrical signals from excitable cells together, with potential for in vivo applications as neural interfaces and prostheses. Here, we will review the electrochemical and physical properties of various DBMs and how these devices have been employed for recording released neurotransmitter molecules and all-or-none action potentials from living cells. Specifically, we will overview how DBMs can resolve localized exocytotic events from subcellular compartments using high-density microelectrode arrays (MEAs), or monitoring oxidizable neurotransmitter release from populations of cells in culture and tissue slices using low-density MEAs. Interfacing DBMs with excitable cells is currently leading to the promising opportunity of recording electrical signals as well as creating neuronal interfaces through the same device. Given the recent increasingly growing development of newly available DBMs of various geometries to monitor electrical activity and neurotransmitter release in a variety of excitable and neuronal tissues, the discussion will be limited to planar DBMs.

  12. Release potential of single-wall carbon nanotubes produced by super-growth method during manufacturing and handling

    International Nuclear Information System (INIS)

    Ogura, Isamu; Sakurai, Hiromu; Mizuno, Kohei; Gamo, Masashi

    2011-01-01

    We investigated the release potential of single-wall carbon nanotubes (CNTs) produced by the super-growth method during their manufacturing and handling processes at a research facility. We generally sampled air at points both outside and inside of protective enclosures such as a glove box and fume hood. Sampling the air outside of the enclosures was intended to evaluate the actual exposure of workers to CNTs, while sampling the air inside the enclosures was performed to quantify the release of CNTs to the air in order to estimate the potential exposure of workers without protection. The results revealed that airborne CNTs were generated when (1) CNTs were separated from the substrates using a spatula and placed in a container in a glove box; (2) an air gun was used to clean the air filters (containing dust that included CNTs) of a vacuum cleaner; (3) a vacuum cleaner was used to collect CNTs (emission with exhaust air from the cleaner); (4) the container of CNTs was opened; and (5) CNTs in the bin of the cleaner were transferred to a container. In these processes, airborne CNTs were only found inside the enclosures, except for a small amount of CNTs released from the glove box when it was opened. Electron microscopic observations of aerosol particles found CNT clusters, which were fragments of CNT forests, with sizes ranging from submicrometers to tens of micrometers.

  13. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

    2014-11-01

    We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Open release versus radiofrequency microtenotomy in the treatment of lateral epicondylitis: a prospective randomized controlled trial.

    Science.gov (United States)

    Hamlin, Katharine; Munro, Christopher; Barker, Scott L; McKenna, Sean; Kumar, Kapil

    2018-01-01

    Optimal surgical treatment of lateral epicondylitis remains uncertain. Recently, radiofrequency microtenotomy (RFMT) has been proposed as a suitable treatment. We compared RFMT with standard open release (OR) in this prospective randomized controlled trial. In total, 41 patients with symptoms for at least 6 months were randomized into two groups: 23 patients had RFMT and 18 had OR. Two patients from RFMT withdrew. Each patient underwent Numerical Rating Scale (NRS) pain score, grip strength and Disabilities of the Arm, Shoulder and Hand (DASH) scores pre-operatively and at 6 weeks. Pain and DASH scores were repeated at 6 months and 12 months. NRS pain scores improved by 4.8 points for RFMT and by 3.9 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Grip strength improved by 31% in the RFMT group compared to 38% in OR. There was no significant difference between the initial and 6 weeks scores or between treatments. At 1 year, DASH was 39.8 points for RFMT and 24.4 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Both groups showed significant improvements and similar benefit to the patient. The results of the present study do not show any benefit of RFMT over the standard OR. As a result of the extra expense of RFMT, we therefore recommend that OR is offered as the standard surgical management.

  15. Role of paliperidone extended-release in treatment of schizoaffective disorder.

    Science.gov (United States)

    Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong Jing; Bossie, Cynthia A

    2010-10-05

    Schizoaffective disorder is characterized by the presence of symptoms of both schizophrenia and a major mood disorder. The coexistence of these symptoms can be difficult to manage, and these patients are generally treated with antipsychotics as well as mood stabilizers and/or antidepressants. Additionally, no established treatment guidelines exist for this disorder. This review describes the combined results of two international, double-blind, placebo-controlled clinical studies of paliperidone extended-release (ER), an atypical antipsychotic recently approved in the US for the treatment of schizoaffective disorder. Subjects in these six-week trials were aged 18-65 years, had a diagnosis of schizoaffective disorder based on the Structural Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Disorders, and were experiencing an acute exacerbation. The subjects from these studies had significant symptomatology as evidenced by a mean (standard deviation) baseline Positive and Negative Syndrome Scale total score of 92.8 (13.0). Based on Young Mania Rating Scale and/or a 21-item Hamilton Rating Scale for Depression score of ≥16 at baseline, 79.5% and 66.9% of subjects presented with prominent manic and depressive symptoms, respectively, and 46.4% presented with mixed symptoms. Approximately half (45%) of subjects were taking adjunctive mood stabilizers and/or antidepressants. Paliperidone ER was found to be effective in improving psychotic and mood symptoms in these subjects. Paliperidone ER was also effective as monotherapy or adjunctive to mood stabilizers and/or antidepressants for subjects with prominent manic, depressive, or mixed symptoms at baseline. No new tolerability signals were observed in this population. To the best of our awareness, these pooled data provide the largest data set of patients with schizoaffective disorder, and extend our knowledge of disease characteristics and treatment response.

  16. Fluocinolone acetonide and its potential in the treatment of chronic diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Haritoglou C

    2013-03-01

    Full Text Available Christos Haritoglou, Aljoscha S Neubauer, Marcus KerntDepartment of Ophthalmology, Ludwig-Maximilians-University, Munich, GermanyAbstract: Diabetic macular edema (DME is a potentially sight-threatening disease that predominantly affects patients with type 2 diabetes. The pathogenesis is complex, with many contributing factors involved. In addition to overexpression of vascular endothelial growth factor in the diabetic eye, there is an inflammatory pathway that contributes to the breakdown of the blood-retina barrier and nonperfusion. In addition to vascular endothelial growth factor inhibitors, clinical and experimental investigations underline the great potential of steroids in the treatment of DME. Fluocinolone acetonide is currently the only corticosteroid approved for the treatment of DME in Europe. It is manufactured as an intravitreal insert, releasing fluocinolone acetonide at a rate of 0.2 µg per day. Phase III clinical studies have demonstrated that the beneficial effect of the fluocinolone acetonide insert lasts up to 3 years. Improvement in visual acuity was especially remarkable in patients with a prolonged duration of DME of at least 3 years at the initiation of therapy. Cataract formation occurs in nearly all phakic eyes treated, and needs to be considered when the indication for treatment is made. Given the efficacy versus potential complications of the insert, fluocinolone acetonide represents a promising second-line treatment option in patients with DME. Fluocinolone appears to be especially beneficial for patients whose options for visual recovery have seemed limited up until now.Keywords: diabetic macular edema, fluocinolone acetonide

  17. Quantitative Analysis of Kr-85 Fission Gas Release from Dry Process for the Treatment of Spent PWR Fuel

    International Nuclear Information System (INIS)

    Park, Geun Il; Cho, Kwang Hun; Lee, Dou Youn; Lee, Jung Won; Park, Jang Jin; Song, Kee Chan

    2007-01-01

    As spent UO 2 fuel oxidizes to U 3 O 8 by air oxidation, a corresponding volume expansion separate grains, releasing the grain-boundary inventory of fission gases. Fission products in spent UO 2 fuel can be distributed in three major regions : the inventory in fuel-sheath gap, the inventory on grain boundaries and the inventory in UO 2 matrix. Release characteristic of fission gases depends on its distribution amount in three regions as well as spent fuel burn-up. Oxidation experiments of spent fuel at 500 .deg. C gives the information of fission gases inventory in spent fuel, and further annealing experiments at higher temperature produces matrix inventory of fission gases on segregated grain. In previous study, fractional release characteristics of Kr- 85 during OREOX (Oxidation and REduction of Oxide fuel) treatment as principal key process for recycling spent PWR fuel via DUPIC cycle have already evaluated as a function of fuel burn-up with 27.3, 35 and 65 MWd/tU. In this paper, new release experiment results of Kr-85 using spent fuel with burn- up of 58 GWd/tU are included to evaluate the fission gas release behavior. As a point of summary in fission gases release behavior, the quantitative analysis of Kr- 85 release characteristics from various spent fuels with different burn-up during voloxidation and OREOX process were reviewed

  18. Allelopatic potential of weeds under the minimalization of soil treatment

    Directory of Open Access Journals (Sweden)

    Mikhail A. Mazirov

    2014-01-01

    Full Text Available The content of water-dispersible phenol substances in rhizosphere both of annual and perennial species of weeds (Cirsium arvense, Sonchus arvensis increases under soil treatment minimalization. The higher content of phenol substances of researched weeds is defined in rhizosphere of Common Couch (Agropyrum repens. The absence of intensive anthropogenic treatment of plowing layer which accumulates the significant mass of weed’s roots in the cause of much more higher allelopathic potential of some species’ of weeds. The high level of saturation by weeds in agrophytocoenosis under non-tillage soil treatment is defines the competitiveness between certain sepsis’ of weeds, especially, at the beginning of the vegetation. In this case, increasing the secretion of phenol substances is one of the physiological screenings of such competitiveness.

  19. METHODOLOGY TO EVALUATE THE POTENTIAL FOR GROUND WATER CONTAMINATION FROM GEOTHERMAL FLUID RELEASES

    Science.gov (United States)

    This report provides analytical methods and graphical techniques to predict potential ground water contamination from geothermal energy development. Overflows and leaks from ponds, pipe leaks, well blowouts, leaks from well casing, and migration from injection zones can be handle...

  20. Effect of aging treatment on the in vitro nickel release from porous oxide layers on NiTi

    Energy Technology Data Exchange (ETDEWEB)

    Huan, Z.; Fratila-Apachitei, L.E., E-mail: e.l.fratila-apachitei@tudelft.nl; Apachitei, I.; Duszczyk, J.

    2013-06-01

    Despite the ability of creating porous oxide layers on nickel–titanium alloy (NiTi) surface for biofunctionalization, the use of plasma electrolytic oxidation (PEO) has raised concerns over the possible increased levels of Ni release. Therefore, the primary aim of this study was to investigate the effect of aging in boiling water on Ni release from porous NiTi surfaces that have been formed by the PEO process. Based on different oxidation conditions, e.g. electrolyte composition and electrical parameters, three kinds of oxide layers with various characteristics were prepared on NiTi substrate. The process was followed by aging in boiling water for different durations. The Ni release was assessed by immersion tests in phosphate buffer saline and the Ni concentration was measured using the flame atomic absorption spectrometry. The results showed that aging in boiling water can significantly reduce the Ni release from oxidized porous samples, given that the duration of the treatment is finely adjusted according to the parameters of the as-formed oxide layer. Surface examination of the samples before and after aging in boiling water suggested that such a treatment is non-destructive while improving the corrosion resistance of oxidized samples, as evidenced by potentiodynamic polarization tests. The results of this study indicate that water boiling may be a suitable post-treatment required to minimize Ni release from porous oxides produced on NiTi by PEO for biomedical applications.

  1. Group I mGlu receptors potentiate synaptosomal [{sup 3}H]glutamate release independently of exogenously applied arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J. [Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom)

    1999-04-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [{sup 3}H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 {mu}M) increased 4AP-evoked [{sup 3}H]glutamate release (143.32{+-}2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC{sub 50}=1.60{+-}0.25 {mu}M; E{sub max}=147.61{+-}10.96% control) 4AP-evoked [{sup 3}H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu{sub 1} receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 {mu}M) and was BSA-insensitive. The selective mGlu{sub 5} receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300{mu}M) was without effect. DHPG (100 {mu}M) also potentiated both 30 mM and 50 mM K{sup +}-evoked [{sup 3}H]glutamate release (121.60{+-}12.77% and 121.50{+-}4.45% control, respectively). DHPG (100 {mu}M) failed to influence both 4AP-stimulated {sup 45}Ca{sup 2+} influx and 50 mM K{sup +}-induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A{sub 1} receptor, group II/III mGlu receptors or GABA{sub B} receptor activity is unlikely since 4AP-evoked [{sup 3}H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-{alpha}-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu{sub 1} receptor-like' receptor potentiates [{sup 3}H]glutamate release from cerebrocortical synaptosomes in the absence of

  2. Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

    Science.gov (United States)

    Soares, William E; Wilson, Donna; Rathlev, Niels; Lee, Joshua D; Gordon, Michael; Nunes, Edward V; O'Brien, Charles P; Friedmann, Peter D

    2018-02-01

    Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders. Copyright © 2018

  3. Safety and Efficacy of Paliperidone Extended-Release in Acute and Maintenance Treatment of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Edoardo Spina

    2011-01-01

    Full Text Available Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER tablet formulation that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and constant drug delivery. Paliperidone ER has demonstrated efficacy in the reduction of acute schizophrenia symptoms in 6-week, placebo-controlled, double-blind trials and clinical benefits were maintained in the longer-term according to extension studies of up to 52 weeks in duration. Compared with quetiapine, paliperidone ER was associated with a more rapid symptom improvement. In addition, it was more effective than placebo in the prevention of symptom recurrence. Paliperidone ER is generally well tolerated with a predictable adverse event profile. Like risperidone, it is associated with a dose-dependent risk of extrapyramidal symptoms and prolactin elevation. Short-and longer-term studies have indicated a low liability for paliperidone ER to cause metabolic (ie, weight gain, hyperglycaemia and lipid dysregulation or cardiovascular adverse effects. Available safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug-drug interactions. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of paliperidone ER in the treatment of schizophrenia in relation to other currently available second-generation antipsychotics, particularly risperidone.

  4. Effect of flash release treatment on phenolic extraction and wine composition.

    Science.gov (United States)

    Morel-Salmi, Cécile; Souquet, Jean-Marc; Bes, Magali; Cheynier, Véronique

    2006-06-14

    The flash release (FR) process, consisting of rapidly heating the grapes and then applying strong vacuum, has been proposed to increase the polyphenol content of red wines. Its impact on polyphenol extraction kinetics and on the polyphenol composition of red juice and wines was studied over two seasons on different grape varieties (Grenache, Mourvedre, Carignan). The FR process allows fast extraction of all phenolic compounds (hydroxycinnamic acids, flavonols, anthocyanins, catechins, proanthocyanidins) and can be used to produce polyphenol-enriched grape juices. However, the concentration of all polyphenols dramatically decreased throughout fermentation when pressing was achieved immediately after FR. The FR wines made with pomace maceration were also enriched in polyphenols compared to the corresponding control wines. Increasing the duration of high-temperature exposure in the FR treatment further increased extraction of phenolic compounds but also accelerated their conversion to derived species. The tannin-to-anthocyanin ratio was particularly low in the wine fermented in the liquid phase, higher after FR than in the control, and even higher after longer heating. FR resulted in an increased tannin-to-anthocyanin ratio and an increased conversion of anthocyanins to tannin-anthocyanin adducts showing the same color properties as anthocyanins. The tannin-to-anthocyanin ratio was particularly low in the wine fermented in the liquid phase that also contained larger amounts of orange sulfite bleaching-resistant pigments.

  5. Chronic Pain Treatment: The Influence of Tricyclic Antidepressants on Serotonin Release and Uptake in Mast Cells

    Directory of Open Access Journals (Sweden)

    Ilonka Ferjan

    2013-01-01

    Full Text Available The involvement of serotonin (5-HT in chronic pain mechanisms is established. 5-HT inhibits central painful stimuli, but recent data suggests that 5-HT could also enhance pain stimulus from the periphery, where mast cells play an important role. We aimed in our study to clarify the influence of selected tricyclic antidepressants (TCAs on mast cell function: secretion, uptake, and reuptake of 5-HT, that could interfere with 5-HT levels and in this way contribute to the generation of pain. As an experimental model, we used isolated rat peritoneal mast cells and incubated them with selected TCAs (clomipramine, amitriptyline, doxepin, and imipramine under different experimental conditions. 5-HT release, uptake, and reuptake were determined spectrofluorometrically. We showed that TCAs were able to inhibit 5-HT secretion from mast cells, as well as uptake of exogenous 5-HT and reuptake of secreted 5-HT back into mast cells. The effects of TCAs were concentration dependent; higher concentrations of TCAs inhibited the secretion of 5-HT induced by compound 48/80, whereas lower concentrations of TCAs inhibited 5-HT uptake. The most effective TCA was halogenated clomipramine. As TCAs are well introduced in chronic pain treatment, the insight into mechanisms of action is important for an understanding of their effect in various pain conditions.

  6. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    Science.gov (United States)

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and Eudra

  7. Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

    Science.gov (United States)

    Bisagno, Verónica; Cadet, Jean Lud

    2014-09-01

    Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

  8. Potential role of gabapentin and extended- release gabapentin in the management of menopausal hot flashes

    Directory of Open Access Journals (Sweden)

    Yadav M

    2013-08-01

    Full Text Available Manisha Yadav, Judith Volkar Center for Specialized Women’s Health, Cleveland Clinic Foundation, Cleveland, Ohio, USA Abstract: About 80% of postmenopausal women experience vasomotor symptoms, such as hot flashes and night sweats – symptoms that are associated with sleep disruption and can lead to fatigue and mood changes. Moreover, hot flashes can be embarrassing for women, causing difficulties at work and in their social lives. Many therapies have been advocated for relief of vasomotor symptoms, but only hormone therapy has been US Food and Drug Administration approved. However, after the Women's Health Initiative Study suggested that there was a correlation between hormone therapy and increased risk for breast cancer and cardiovascular events, many women stopped taking hormone therapy, and many do not want to initiate it. Hormone therapy is also contraindicated in certain women, such as those with a history of hormone-stimulated cancer like breast and uterine cancer. Gabapentin (Neurontin has shown efficacy in relieving vasomotor symptoms and is used as off-label for this indication. A new extended-release formulation of gabapentin has also shown efficacy in treating hot flashes and improving sleep quality with possibly fewer side effects than regular gabapentin. Keywords: Hot flushes, vasomotor symptoms, postmenopausal, hormone-sensitive cancer, non-hormonal therapy, gastric-retentive, Breeze

  9. The Potential Impacts on Aquatic Ecosystems from the Release of Trace Elements in Geothermal Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Cushman, R.M.

    2000-03-14

    Geothermal energy will likely constitute an increasing percentage of our nation's future energy ''mix,'' both for electrical and nonelectrical uses. Associated with the exploitation of geothermal resources is the handling and disposal of fluids which contain a wide variety of potentially toxic trace elements. We present analyses of 14 trace elements found in hydrothermal fluids from various geothermal reservoirs in the western United States. The concentrations of these elements vary over orders of magnitude between reservoirs. Potential impacts are conservatively assessed on the basis of (1) toxicity to freshwater biota, and (2) bioaccumulation in food fish to the point where consumption might be hazardous to human health. Trace element concentrations generally range from benign levels to levels which might prove toxic to freshwater biota and contaminate food fisheries. We stress the need for site-specific analyses and careful handling of geothermal fluids in order to minimize potential impacts.

  10. Releasing Effect of Individual Potential: Formation of Productive Collective and Children's Self-Transcendence in a Chinese School.

    Science.gov (United States)

    Wu, Aruna; Li, Xiao-Wen; Zhang, Qian

    2017-09-01

    We describe the intricate relations between social demand structures and their role in facilitation of individual development of children and teachers in a Chinese classroom. The relationship of an individual to the immediate social group is further qualified by the inclusion in a collective which enables the participants to transform their individual self-structures through taking on social roles in everyday collective activities, which release further potential for their individual development. We describe that releasing effect in the case of an intervention program in a Chinese school for the children of rural migrants re-settled in a city, demonstrating gradually how the inter-individual competitive orientation promoted by autocratic teaching style becomes transformed into collective good oriented joint actions towards excellence in educational endeavors (Jiti). The productive nature of the Jiti makes an ecology with multiple nested and open systems, in which every group and student is producer and consumer of each other, and personal self-transcendence is actualized in the process. The releasing effect is demonstrated through observing the co-emergence of new forms of progressive conduct and new problems, presented in pupils' positive participation in activities. The description of the intervention in a Chinese school provides us with insight on how concrete social inclusion frameworks with the underpinning Chinese philosophy of "acting up to trends" can prevent the emergence of direct animosities and lead to new integration of self and society.

  11. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  12. Ultrasound coupled with Fenton oxidation pre-treatment of sludge to release organic carbon, nitrogen and phosphorus

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Changxiu [School of Environment, Tsinghua University, Beijing 100084 (China); Jiang, Jianguo, E-mail: jianguoj@mail.tsinghua.edu.cn [School of Environment, Tsinghua University, Beijing 100084 (China); Key Laboratory for Solid Waste Management and Environment Safety, Ministry of Education of China (China); Collaborative Innovation Center for Regional Environmental Quality, Tsinghua University, Beijing (China); Li, De' an [School of Environment, Tsinghua University, Beijing 100084 (China)

    2015-11-01

    We focused on the effects of ultrasound and Fenton reagent in ultrasonic coupling Fenton oxidation (U + F) pre-treatment processes on the disintegration of wastewater treatment plant sludge. The results demonstrated that U + F treatment could significantly increase soluble COD, TOC, total N, proteins, total P and PO{sub 4}{sup 3−} concentrations in sludge supernatant. This method was more effective than ultrasonic (U) or Fenton oxidation (F) treatment alone. U + F treatment increased the soluble COD by 2.1- and 1.4-fold compared with U and F alone, respectively. U + F treatment increased the total N and P by 1.7- and 2.2-fold, respectively, compared with F alone. After U + F treatment, sludge showed a considerably finer particle size and looser microstructure based on scanning electron microscopy, and the highest OH· signal intensity increased from 568.7 by F treatment to 1106.3 using electron spin resonance. This demonstrated that U + F treatment induces disintegration of sludge and release of organic carbon, nitrogen and phosphorus better. - Highlights: • Combined ultrasound–Fenton pre-treatment was proposed for sludge disintegration. • Ultrasound–Fenton significantly increased carbon, nitrogen and phosphorus release. • Higher level of OH· was detected after combined disintegration than Fenton.

  13. Ultrasound coupled with Fenton oxidation pre-treatment of sludge to release organic carbon, nitrogen and phosphorus

    International Nuclear Information System (INIS)

    Gong, Changxiu; Jiang, Jianguo; Li, De'an

    2015-01-01

    We focused on the effects of ultrasound and Fenton reagent in ultrasonic coupling Fenton oxidation (U + F) pre-treatment processes on the disintegration of wastewater treatment plant sludge. The results demonstrated that U + F treatment could significantly increase soluble COD, TOC, total N, proteins, total P and PO 4 3− concentrations in sludge supernatant. This method was more effective than ultrasonic (U) or Fenton oxidation (F) treatment alone. U + F treatment increased the soluble COD by 2.1- and 1.4-fold compared with U and F alone, respectively. U + F treatment increased the total N and P by 1.7- and 2.2-fold, respectively, compared with F alone. After U + F treatment, sludge showed a considerably finer particle size and looser microstructure based on scanning electron microscopy, and the highest OH· signal intensity increased from 568.7 by F treatment to 1106.3 using electron spin resonance. This demonstrated that U + F treatment induces disintegration of sludge and release of organic carbon, nitrogen and phosphorus better. - Highlights: • Combined ultrasound–Fenton pre-treatment was proposed for sludge disintegration. • Ultrasound–Fenton significantly increased carbon, nitrogen and phosphorus release. • Higher level of OH· was detected after combined disintegration than Fenton

  14. Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands

    NARCIS (Netherlands)

    Zaaijer, Eline; Goudriaan, Anna E.; Koeter, Maarten W. J.; Booij, Jan; van den Brink, Wim

    2016-01-01

    Background: Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual

  15. The release of endotoxin, TNF and IL-6 during the antibiotic treatment of experimental Gram-negative sepsis

    NARCIS (Netherlands)

    Dofferhoff, A.S.M.; Potthoff, H.; Bom, V.J.J.; Bartels, H.L.; De Vries-Hospers, H.G.; Bijzet, J.; Weits, J.; Buurman, W.; Bleichrodt, R.P.

    1995-01-01

    To evaluate the role of different antibiotics in the release of endotoxin and the production of tumor necrosis factor-α (TNF) and interleukin 6 (IL-6) during the treatment of experimental Escherichia coli septical peritonitis, we obtained serial blood samples from septic rats treated with placebo,

  16. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

    NARCIS (Netherlands)

    Westenberg, HGM; Stein, DJ; Yang, HC; Li, D; Barbato, LM

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to

  17. Treatment of Women With an Endometrial Polyp and Heavy Menstrual Bleeding: A Levonorgestrel-Releasing Intrauterine Device or Hysteroscopic Polypectomy?

    NARCIS (Netherlands)

    van Dijk, Myrthe M.; van Hanegem, Nehalennia; de Lange, Maria E.; Timmermans, Anne

    2015-01-01

    We performed a literature review of reports comparing a levonorgestrel-releasing intrauterine device (LNG-IUD) with transcervical polyp resection (TCRP) as a treatment for heavy menstrual bleeding (HMB). Our second objective was to investigate the effectiveness of LNG-IUD and TCRP in reducing

  18. Augmented simvastatin cytotoxicity using optimized lipid nanocapsules: a potential for breast cancer treatment.

    Science.gov (United States)

    Safwat, Sally; Hathout, Rania M; Ishak, Rania A; Mortada, Nahed D

    2017-03-01

    We noticed paucity in exploiting solutol-based lipid nanocapsules in statins formulations though they carry all favorable properties that are needed for cancer passive targeting such as their small particle size, stealth properties, ability to highly accommodate lipophilic drugs, good internalization and P-gp pump inhibition. The aim of this study was to design and optimize new simvastatin drug delivery systems; lipid nanocapsules intended for administration through the intravenous route as potential treatment for breast cancer. Optimized nanocapsules were prepared by the phase-inversion method according to a D-optimal mixture design, characterized and assessed for their cytotoxicity. Three successful models for particle size, polydispersity index (PDI) and percentage of drug released after 48 h were generated. The prepared lipid nanocapsules acquired spherical and homogenous morphology, good stability and tolerance to sterilization. The obtained release profiles demonstrated desired sustained release pattern. Furthermore, testing selected formulations on human breast cancer adenocarcinoma cells showed augmented cytotoxicity of simvastatin reaching low IC50 values as 1.4 ± 0.02 μg/ml compared to the pure drug. The proposed lipid nanocapsules pose promising candidates as simvastatin carriers intended for the targeting of breast cancer.

  19. Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF-κB activity in Escherichia coli-stimulated urinary bladder cells.

    Science.gov (United States)

    Karlsson, Mattias; Scherbak, Nikolai; Khalaf, Hazem; Olsson, Per-Erik; Jass, Jana

    2012-11-01

    Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  20. Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly

    Directory of Open Access Journals (Sweden)

    Jan-Shun Chang

    2016-06-01

    Full Text Available The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration.

  1. Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential

    Directory of Open Access Journals (Sweden)

    Akinaga Sonoda

    2010-07-01

    Full Text Available Akinaga Sonoda1, Norihisa Nitta1, Ayumi Nitta-Seko1, Shinich Ohta1, Shigeyuki Takamatsu2, Yoshio Ikehata3, Isamu Nagano3, Jun-ichiro Jo4, Yasuhiko Tabata4, Masashi Takahashi1, Osamu Matsui3, Kiyoshi Murata11Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 520-2192, Japan; 2Department of Radiology, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa Ishikawa, 920-8641, Japan; 3Department of Natural Science and Technology, Graduate School of Engineering, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Shogoin kawara-machi 53, Sakyo-ku 606-8507, Kyoto, JapanAbstract: We developed a dextran-magnetite conjugated cisplatin (DM-Cis complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron. The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip and placed magnets subcutaneously (sc. In group 2 we injected saline (ip and placed magnets (sc. In group 3 we injected DM-Cis (ip and placed a sc incision (sham. The control (group 4 received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (µm2 were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 µg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05 in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a

  2. Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment.

    Science.gov (United States)

    de Abreu, Letícia Coli Louvisse; Todaro, Valerio; Sathler, Plinio Cunha; da Silva, Luiz Cláudio Rodrigues Pereira; do Carmo, Flávia Almada; Costa, Cleonice Marques; Toma, Helena Keiko; Castro, Helena Carla; Rodrigues, Carlos Rangel; de Sousa, Valeria Pereira; Cabral, Lucio Mendes

    2016-12-01

    The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50 years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300 nm) with spherical shape and high loading efficiency (93.88 ± 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases.

  3. Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

    Science.gov (United States)

    Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk; Krishnan, Sunil

    2014-01-01

    Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles’ potential clinical applications. PMID:24556077

  4. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Fengyuan Li

    2016-01-01

    Full Text Available Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.

  5. The electric potential of particles in interstellar space released from a nuclear waste payload

    Science.gov (United States)

    Williams, A. C.

    1980-01-01

    Mechanisms for charging a grain in the interplanetary medium include: (1) capture of solar wind electrons; (2) capture of solar wind protons; (3) ejection of electrons through the photoelectric effect due to the solar radiation; (4) escape of beta particles from beta emitters in the grain; and (5) escape of alpha particles from alpha emitters in the grain. The potentials on both nonradioactive and radioactive grains are considered with relation to particle size and time, and the distance from the Sun. Numerical results are presented where the waste mix is assumed to be PW-4b.

  6. Controlled release of liraglutide using thermogelling polymers in treatment of diabetes

    Science.gov (United States)

    Chen, Yipei; Li, Yuzhuo; Shen, Wenjia; Li, Kun; Yu, Lin; Chen, Qinghua; Ding, Jiandong

    2016-01-01

    In treatment of diabetes, it is much desired in clinics and challenging in pharmaceutics and material science to set up a long-acting drug delivery system. This study was aimed at constructing a new delivery system using thermogelling PEG/polyester copolymers. Liraglutide, a fatty acid-modified antidiabetic polypeptide, was selected as the model drug. The thermogelling polymers were presented by poly(ε-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolic acid) (PCGA-PEG-PCGA) and poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA). Both the copolymers were soluble in water, and their concentrated solutions underwent temperature-induced sol-gel transitions. The drug-loaded polymer solutions were injectable at room temperature and gelled in situ at body temperature. Particularly, the liraglutide-loaded PCGA-PEG-PCGA thermogel formulation exhibited a sustained drug release manner over one week in both in vitro and in vivo tests. This feature was attributed to the combined effects of an appropriate drug/polymer interaction and a high chain mobility of the carrier polymer, which facilitated the sustained diffusion of drug out of the thermogel. Finally, a single subcutaneous injection of this formulation showed a remarkably improved glucose tolerance of mice for one week. Hence, the present study not only developed a promising long-acting antidiabetic formulation, but also put forward a combined strategy for controlled delivery of polypeptide. PMID:27531588

  7. Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Eric T Wittbrodt

    2009-11-01

    Full Text Available Eric T Wittbrodt1, Charles Baum2, David A Peura31Takeda Pharmaceuticals North America, Inc., 2Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA; 3University of Virginia, School of Medicine, Charlottesville, VA, USAAbstract: Although proton pump inhibitors (PPI have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD, several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional singlerelease PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods vs placebo (14% for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.Keywords: dexlansoprazole MR, gastroesophageal reflux disease, GERD, erosive esophagitis, TAK-390MR

  8. Harnessing the potential - Atlantic Canada's oil and gas industry : Newfoundland Ocean Industries special releases or publications

    International Nuclear Information System (INIS)

    1998-07-01

    A comprehensive overview of Atlantic Canada's oil and gas industry is presented, demonstrating the importance of oil and gas resources and their related industries to Atlantic Canada. The objective of the report is to provide a basis for a strategy to optimize opportunities within the region from the oil and gas sector. The report reviews the current status of the industry, including the region's resource potential and the oil and gas developments currently underway. The evolution of the oil and gas industry is discussed in terms of value chain components. A broad assessment of the region's supply, labour force, infrastructure, training, and research and development capabilities is presented, followed by a description of the industry's potential, its regulatory framework and the barriers and constraints affecting industry development. Appendices contain a chronological history of major events in Atlantic Canada's oil and gas industry (Appendix A); and overview of the Atlantic Accord and the Canada-Nova Scotia Accord's equalization offset provisions (Appendix B); a value chain matrix, detailing some 60 categories of industry requirements and a capsule assessment of the region's ability to meet them (Appendix C); and a listing of research and development institutions in Atlantic Canada, including their areas of specialization (Appendix D)

  9. Phase and amplitude of ecosystem carbon release and uptake potentials as derived from FLUXNET measurements

    DEFF Research Database (Denmark)

    Falge, E.; Tenhunen, J.; Baldocchi, D.

    2002-01-01

    , as well as for global inversion studies, and can help improve phenological modules in SVAT or biogeochemical models. The results of this study have important validation potential for global carbon cycle modeling. The phasing of respiratory and assimilatory capacity differed within forest types...... in four classes: (1) boreal and high altitude conifers and grasslands: (2) temperate deciduous and temperate conifers; (3) tundra and crops; (4) evergreen Mediterranean and tropical forest,,, Similar results are found for maximum daytime uptake (F-min) and the integral net carbon flux, but temperate......-min are largest for managed grasslands and crops. Largest observed values of F-min varied between -48 and -2 mumol m(-2) s(-1), decreasing in the order C-4-crops > C-3-crops > temperate deciduous forests > temperate conifers > boreal conifers > tundra ecosystems. Due to data restrictions, our analysis centered...

  10. Organic components of nuclear wastes and their potential for altering radionuclide distribution when released to soil

    International Nuclear Information System (INIS)

    McFadden, K.M.

    1980-08-01

    Normal waste processing at the Hanford operations requires the use of many organic materials, chiefly in the form of complexing agents and diluents. These organic materials and their chemical and radiolytic degradation products, have potential for complexing fission products and transuranium elements, both in the waste streams and upon infiltration into soil, perhaps influencing future sorption or migration of the nuclides. Particular complexation characteristics of various nuclides which constitute the major fission products, long-lived isotopes, and the most mobile in radioactive wastes are discussed briefly with regards to their anticipated sorption or mobility in soils. Included in the discussion are Am, Sb, Ce, Cs, Co, Cm, Eu, I, Np, Pm, Pu, Ra, Ru, Sr, Tc, U, and Zr. 107 references

  11. Potential weather modification caused by waste heat release from large dry cooling towers

    International Nuclear Information System (INIS)

    Lee, J.

    1979-01-01

    A numerical model of a cooling tower plume is employed to study the possible atmospheric effects of thermal plumes from natural draft dry cooling towers. Calculations are performed for both single and multiple towers, each of which can dissipate the waste heat from a nominal 1000 MWe power generating unit, and the results are compared with those for wet cooling towers associated with plants of the same generating capacity. Dry cooling tower plumes are found to have a higher potential for inducing convective clouds than wet cooling tower plumes, under most summertime meteorological conditions. This is due to the fact that both the sensible heat and momentum fluxes from a dry tower in summer are approximately one order of magnitude larger than those from a wet cooling tower

  12. Potential Use of Polyacrylamide Encapsulation for Treatment of Petroleum Drilling Cuttings and Hydrocarbon Contaminated Soil

    Directory of Open Access Journals (Sweden)

    Randy H. Adams

    2011-07-01

    Full Text Available Mineral soil of alluvial origin, contaminated with diesel+lubricating oil (1:2, was treated with a commercial polyacrylamide product at 100 % of the distributer recommended dosage, producing a reduction in hydrocarbon concentration (EPA 9074 of 76 % that remained stable during the study period (38 days and even after thermal treatment (60 ºC, 18 hrs.. Increasing the dosage to 150 % did not improve the treatment results, but repeating the treatment (at 100 % resulted in a slight additional reduction (4 %. Similar results were obtained with oil-based drilling cuttings (~60 % reduction at both 100 % and 150 %. Pre-drying of the drilling cuttings prior to treatment did not improve the hydrocarbon reduction, but it did produce smaller, potentially more stable aggregates (0.5 – 1-0 mm in diameter. The treatment of organic soil resulted in a similar reduction in hydrocarbon concentration (65 % and a reduction of acute toxicity (Microtox to below background levels, however this effect was not stable. An additional application (including mixing of the polyacrylamide product resulted in partial disintegration of the organic fibres and release of the stabilized hydrocarbons, measuring an overall increase in hydrocarbon concentration of 19 %.

  13. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    Directory of Open Access Journals (Sweden)

    Neil V. Klinger

    2016-01-01

    Full Text Available Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin’s ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

  14. Distillery spent wash: Treatment technologies and potential applications

    International Nuclear Information System (INIS)

    Mohana, Sarayu; Acharya, Bhavik K.; Madamwar, Datta

    2009-01-01

    Distillery spent wash is the unwanted residual liquid waste generated during alcohol production and pollution caused by it is one of the most critical environmental issue. Despite standards imposed on effluent quality, untreated or partially treated effluent very often finds access to watercourses. The distillery wastewater with its characteristic unpleasant odor poses a serious threat to the water quality in several regions around the globe. The ever-increasing generation of distillery spent wash on the one hand and stringent legislative regulations of its disposal on the other has stimulated the need for developing new technologies to process this effluent efficiently and economically. A number of clean up technologies have been put into practice and novel bioremediation approaches for treatment of distillery spent wash are being worked out. Potential microbial (anaerobic and aerobic) as well as physicochemical processes as feasible remediation technologies to combat environmental pollution are being explored. An emerging field in distillery waste management is exploiting its nutritive potential for production of various high value compounds. This review presents an overview of the pollution problems caused by distillery spent wash, the technologies employed globally for its treatment and its alternative use in various biotechnological sectors

  15. Bone Mass in Young Adulthood Following Gonadotropin-Releasing Hormone Analog Treatment and Cross-Sex Hormone Treatment in Adolescents With Gender Dysphoria

    NARCIS (Netherlands)

    Klink, D.T.; Caris, M.G.; Heijboer, A.C.; van Trotsenburg, M.; Rotteveel, J.

    2015-01-01

    Context: Sex steroids are important for bone mass accrual. Adolescents with gender dysphoria (GD) treated with gonadotropin-releasing hormone analog (GnRHa) therapy are temporarily sex-steroid deprived until the addition of cross-sex hormones (CSH). The effect of this treatment on bone mineral

  16. Anaerobia Treatments of the domestic residual waters. Limitations potentialities

    International Nuclear Information System (INIS)

    Giraldo Gomez, Eugenio

    1993-01-01

    The quick growth of the Latin American cities has prevented that an appropriate covering of public services is achieved for the whole population, One of the undesirable consequences of this situation is the indiscriminate discharge from the domestic and industrial residual waters to the nearest bodies of water with its consequent deterioration and with disastrous consequences about the ecology and the public health. The developed countries have controlled this situation using systems of purification of the residual waters previously to their discharge in the receptor source. The same as the technology of the evacuation of the served waters, they have become numerous efforts for the application of the purification systems used in the countries developed to the socioeconomic, climatic and cultural conditions of our means. One of the results obtained in these efforts is the economic inability of the municipalities to pay the high investment costs and of operation of the traditional systems for the treatment of the residual waters. Contrary to another type of public services, the treatment of the residual waters needs of appropriate technological solutions for the Climatic and socioeconomic means of the developing countries, One of the technological alternatives for the purification of the residual waters that has had a great development in the last decades has been that of the biological treatments in t anaerobia ambient. The objective of this contribution is to present, to author's trial, the limitations and potentialities of this technology type with special emphasis in the case of the domestic residual waters

  17. Volume 1: Calculating potential to emit releases and doses for FEMP's and NOCs; FINAL

    International Nuclear Information System (INIS)

    HILL, J.S.

    1999-01-01

    The purpose of this document is to provide Hanford Site facilities a handbook for estimating potential emissions and the subsequent offsite doses. General guidelines and information are provided to assist personnel in estimating emissions for use with U.S. Department of Energy (DOE) facility effluent monitoring plans (FEMPs) and regulatory notices of construction (NOCs), per 40 Code of Federal Regulations (CFR) Part 61, Subpart H, and Washington Administrative Code (WAC) Chapter 246-247 requirements. This document replaces Unit Dose Calculation Methods and Summary of Facility Effluent Monitoring Plan Determinations (WHC-EP-0498). Meteorological data from 1983 through 1996, 13-year data set, was used to develop the unit dose factors provided by this document, with the exception of two meteorological stations. Meteorological stations 23 and 24, located at Gable Mountain and the 100-F Area, only have data from 1986 through 1996, 10-year data set. The scope of this document includes the following: Estimating emissions and resulting effective dose equivalents (EDE) to a facility's nearest offsite receptor (NOR) for use with NOCs under 40 CFR Part 61, Subpart H, requirements Estimating emissions and resulting EDEs to a facility's or emission unit's NOR for use with NOCs under the WAC Chapter 246-247 requirements Estimating emissions and resulting EDEs to a facility's or emission unit's NOR for use with FEMPs and FEMP determinations under DOE Orders 5400.1 and 5400.5 requirements

  18. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  19. Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

    Science.gov (United States)

    Matsuura, Hiroki; Kimoto, Sohei; Harada, Izumi; Naemura, Satoshi; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

    2016-05-26

    Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

  20. Interferon γ-Induced Nuclear Interleukin-33 Potentiates the Release of Esophageal Epithelial Derived Cytokines.

    Directory of Open Access Journals (Sweden)

    Jing Shan

    Full Text Available Esophageal epithelial cells are an initiating cell type in esophageal inflammation, playing an essential role in the pathogenesis of gastroesophageal reflux disease (GERD. A new tissue-derived cytokine, interleukin-33 (IL-33, has been shown to be upregulated in esophageal epithelial cell nuclei in GERD, taking part in mucosal inflammation. Here, inflammatory cytokines secreted by esophageal epithelial cells, and their regulation by IL-33, were investigated.In an in vitro stratified squamous epithelial model, IL-33 expression was examined using quantitative RT-PCR, western blot, ELISA, and immunofluorescence. Epithelial cell secreted inflammatory cytokines were examined using multiplex flow immunoassay. IL-33 was knocked down with small interfering RNA (siRNA in normal human esophageal epithelial cells (HEECs. Pharmacological inhibitors and signal transducers and activators of transcription 1 (STAT1 siRNA were used to explore the signaling pathways.Interferon (IFNγ treatment upregulated nuclear IL-33 in HEECs. Furthermore, HEECs can produce various inflammatory cytokines, such as IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1, regulated on activation normal T-cell expressed and presumably secreted (RANTES, and granulocyte-macrophage colony-stimulating factor (GM-CSF in response to IFNγ. Nuclear, but not exogenous IL-33, amplified IFN induction of these cytokines. P38 mitogen-activated protein kinase (MAPK and janus protein tyrosine kinases (JAK/STAT1 were the common signaling pathways of IFNγ-mediated induction of IL-33 and other cytokines.Esophageal epithelial cells can actively participate in GERD pathogenesis through the production of various cytokines, and epithelial-derived IL-33 might play a central role in the production of these cytokines.

  1. pH- and thermo-responsive microcontainers as potential drug delivery systems: Morphological characteristic, release and cytotoxicity studies.

    Science.gov (United States)

    Efthimiadou, Eleni K; Tapeinos, Christos; Tziveleka, Leto-Aikaterini; Boukos, Nikos; Kordas, George

    2014-04-01

    Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a potential drug delivery system for cancer therapy. It is well known that cancer cells exhibit notable characteristics such as acidic pH due to glycolytic cycle and higher temperature due to their higher proliferation rate. Based on these characteristics, we constructed a dual pH- and thermo-sensitive material for specific drug release on the pathological tissue. The MC's fabrication is based on a two-step procedure, in which, the first step involves the core synthesis and the second one is related to the shell formation. The core consists of poly(methyl methacrylate (PMMA), while the shell consists of PMMA, poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three different types of MCs were synthesized based on the seed polymerization method. The synthesized MCs were characterized structurally by Fourier transform infrared and morphologically by scanning electron microscopy. Dynamic light scattering was also used to study their behavior in aqueous solution under different pH and temperature conditions. For the loading and release study, the anthracycline drug daunorubicin (DNR) was used as a model drug, and its release properties were evaluated under different pH and thermo-conditions. Cytotoxicity studies were also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast cells. According to our results, the synthesized microcontainers present desired pH and thermo behavior and can be applied in drug delivery systems. It is worth mentioning that the synthesized microcontainers which incorporated the drug DNR exhibit higher toxicity than the free drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.

    Science.gov (United States)

    de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F

    2004-09-14

    Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.

  3. Low Molecular Weight Glucosamine/L-lactide Copolymers as Potential Carriers for the Development of a Sustained Rifampicin Release System: Mycobacterium Smegmatis as a Tuberculosis Model

    Science.gov (United States)

    Ragusa, Jorge Alejandro

    Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged release (>14 days) of RIF from these particles is demonstrated. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism, and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) (reference material) particles did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated an increment in cell death as particle dose increased, but was not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. GluN-LLA particles led to higher uptakes than the PLA particles. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and the particles showed a favorable long term drug release effect in killing intracellular bacteria compared to free RIF. The studies presented and discussed in this dissertation

  4. Pre-treatment and ethanol fermentation potential of olive pulp at different dry matter concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Haagensen, Frank [Bioprocess Science and Technology group, Biocentrum-DTU, Building 227, Technical University of Denmark, 2800 Lyngby (Denmark); Skiadas, Ioannis V.; Gavala, Hariklia N.; Ahring, Birgitte K. [Bioprocess Science and Technology group, Biocentrum-DTU, Building 227, Technical University of Denmark, 2800 Lyngby (Denmark); Copenhagen Institute of Technology (Aalborg University Copenhagen), Section for Sustainable Biotechnology, Department of Biotechnology, Chemistry and Environmental Engineering, Lautrupvang 15, DK 2750 Ballerup (Denmark)

    2009-11-15

    Renewable energy sources have received increased interest from the international community with biomass being one of the oldest and the most promising ones. In the concept of exploitation of agro-industrial residues, the present study investigates the pre-treatment and ethanol fermentation potential of the olive pulp, which is the semi solid residue generated from the two-phase processing of the olives for olive oil production. Wet oxidation and enzymatic hydrolysis have been applied aiming at the enhancement of carbohydrates' bioavailability. Different concentrations of enzymes and enzymatic durations have been tested. Both wet oxidation and enzymic treatment were evaluated based on the ethanol obtained in a subsequent fermentation step by Saccharomyces cerevisiae and Thermoanaerobacter mathranii. It was found that a four-day hydrolysis time was adequate for a satisfactory release of glucose and xylose. The combination of wet oxidation and enzymatic hydrolysis resulted in the glucose and xylose concentration increase of 138 and 444%, respectively, compared to 33 and 15% with only enzymes added. However, the highest ethanol production was obtained when only enzymic pre-treatment was applied, implying that wet oxidation is not a recommended pre-treatment process for olive pulp at the conditions tested. It was also showed that increased dry matter concentration did not have a negative effect on the release of sugars, indicating that the cellulose and xylan content of the olive pulp is relatively easily available. The results of the experiments in batch processes clearly emphasize that the simultaneous saccharification and fermentation (SSF) mode is advantageous in comparison with the separate hydrolysis and fermentation (SHF) mode concerning process contamination. (author)

  5. Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction.

    Science.gov (United States)

    Amenta, F; Tayebati, S K

    2008-01-01

    Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.

  6. Preliminary investigation of the potential for transient vapor release events during in situ vitrification based on thermal- hydraulic modeling

    International Nuclear Information System (INIS)

    Roberts, J.S.; Woosley, S.L.; Lessor, D.L.; Strachan, C.

    1992-07-01

    This study investigates a possible cause of molten glass displacements that occurred during two recent in situ vitrification (ISV) tests. The study was conducted for the US Department of Energy by Pacific Northwest Laboratory. It is hypothesized that these glass displacements are caused by large gas bubbles rising up through the ISV melt and bursting at its surface. These bubbles cause the molten surface to upwell and possibly overflow. When the bubbles burst, molten glass is thrown from the melt surface and the volume of gas contained in the bubble is released into the hood. Both of these phenomena are undesirable because the molten soil ejected from the melt is dangerous to operating personnel and can damage equipment. The sudden gas release can cause a temporary pressurization of the hood, allowing potentially contaminated gas to escape to the atmosphere. This study attempts to explain the conditions necessary for formation of large gas bubbles in the melt so that future glass displacements can be avoided

  7. Preliminary investigation of the potential for transient vapor release events during in situ vitrification based on thermal- hydraulic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, J.S.; Woosley, S.L.; Lessor, D.L.; Strachan, C.

    1992-07-01

    This study investigates a possible cause of molten glass displacements that occurred during two recent in situ vitrification (ISV) tests. The study was conducted for the US Department of Energy by Pacific Northwest Laboratory. It is hypothesized that these glass displacements are caused by large gas bubbles rising up through the ISV melt and bursting at its surface. These bubbles cause the molten surface to upwell and possibly overflow. When the bubbles burst, molten glass is thrown from the melt surface and the volume of gas contained in the bubble is released into the hood. Both of these phenomena are undesirable because the molten soil ejected from the melt is dangerous to operating personnel and can damage equipment. The sudden gas release can cause a temporary pressurization of the hood, allowing potentially contaminated gas to escape to the atmosphere. This study attempts to explain the conditions necessary for formation of large gas bubbles in the melt so that future glass displacements can be avoided.

  8. Dual-layered nanogel-coated hollow lipid/polypeptide conjugate assemblies for potential pH-triggered intracellular drug release.

    Directory of Open Access Journals (Sweden)

    Wen-Hsuan Chiang

    Full Text Available To achieve effective intracellular anticancer drug delivery, the polymeric vesicles supplemented with the pH-responsive outlayered gels as a delivery system of doxorubicin (DOX were developed from self-assembly of the lipid/polypeptide adduct, distearin grafted poly(γ-glutamic acid (poly(γ-GA, followed by sequential deposition of chitosan and poly(γ-GA-co-γ-glutamyl oxysuccinimide-g-monomethoxy poly(ethylene glycol in combination with in situ covalent cross-linking on assembly surfaces. The resultant gel-caged polymeric vesicles (GCPVs showed superior performance in regulating drug release in response to the external pH change. Under typical physiological conditions (pH 7.4 and 37 °C at which the γ-GA/DOX ionic pairings remained mostly undisturbed, the dense outlayered gels of GCPVs significantly reduced the premature leakage of the uncomplexed payload. With the environmental pH being reduced from pH 7.4 to 4.7, the drug liberation was appreciably promoted by the massive disruption of the ionic γ-GA/DOX complexes along with the significant swelling of nanogel layers upon the increased protonation of chitosan chain segments. After being internalized by HeLa cells via endocytosis, GCPVs exhibited cytotoxic effect comparable to free DOX achieved by rapidly releasing the payload in intracellular acidic endosomes and lysosomes. This strongly implies the great promise of such unique GCPVs as an intracellular drug delivery carrier for potential anticancer treatment.

  9. Quantifying Construction Site Sediment Discharge Risk and Treatment Potential

    Science.gov (United States)

    Ferrell, L.; Beighley, R. E.

    2006-12-01

    Dealing with soil erosion and sediment transport can be a significant challenge during the construction process due to the potentially large spatial and temporal extent and conditions of bare soils. Best Management Practices (BMP) are commonly used to eliminate or reduce offsite discharge of sediment. However, few efforts have investigated the time varying risk of sediment discharge from construction sites, which often have dynamic soil conditions and the potential for less than optimal BMP installations. The goal of this research is to improve the design, implementation and effectiveness of sediment and erosion control at construction sites using site specific, temporal distributions of sediment discharge risk. Sediment risk is determined from individual factors leading to sediment expert, such as rainfall frequency, the adequacy of BMP installations, and the extent and duration of bare soil conditions. This research specifically focuses on quantifying: (a) the effectiveness of temporary sediment and control erosion control BMPs in preventing, containing, and/or treating construction site sediment discharge at varying levels of "proper" installation, and (b) sediment discharge potential from construction sites during different phases of construction, (ex., disturbed earth operations). BMPs are evaluated at selected construction sites in southern California and at the Soil Erosion Research Laboratory (SERL) in the Civil and Environmental Engineering department at San Diego State University. SERL experiments are performed on a 3-m by 10-m tilting soil bed with soil depths up to 1 meter, slopes ranging from 0 to 50 percent, and rainfall rates up to 150 mm/hr (6 in/hr). BMP performance is assessed based on experiments where BMPs are installed per manufacture specifications, potential less than optimal installations, and no treatment conditions. Soil conditions are also varied to represent site conditions during different phases of construction (i.e., loose lifts

  10. Release of bisphenol A and its derivatives from orthodontic adhesive systems available on the European market as a potential health risk factor

    Directory of Open Access Journals (Sweden)

    Konrad Małkiewicz

    2015-02-01

    Full Text Available [b]Introduction[/b]. Treatment with fixed orthodontic appliances requires the application of adhesive systems to enable secure fastening of brackets and retainers to the surface of tooth enamel. The orthodontic bonding systems are similar in terms of chemical composition to dental filling materials, the chemical stability of which is not satisfactory. Particularly alarming is the release of bisphenol A and its derivatives to the external environment, which has been well-documented for materials used in conservative dentistry. [b]Objectives[/b]. The aim of the study was an in vitro assessment of the release of biologically harmful bisphenol A and its derivatives from orthodontic adhesives available on the European market, as a potential health risk factor for orthodontic patients. [b]Material and methods[/b]. The study assessed levels of BPA, BPA polymers and Bis-GMA resin in eluates of six commonly used orthodontic adhesives: Light Bond, Transbond XT, Resilence, Aspire, GrĕnGloo and ConTec LC, obtained after one hour, 24 hours, 7 days and 31 days of material sample storage in water. The presence and concentration of the studied chemicals in the obtained solutions were identified using the HPLC method. [b]Results[/b]. The highest (p≤0.05 concentration of BPA at 32.10µg/ml was observed in the Resilence material eluates. The highest concentration of poly-bisphenol A was found in solutions obtained after incubation of ConTec LC adhesive at 371.90µg/ml, whereas the highest amount of Bis-GMA resin (425.07µg/ml was present in Aspire material eluates. [b]Conclusions[/b]. 1 In conditions of the current experiment it was demonstrated that most of the assessed orthodontic adhesive resins available on the European market and released into the outside environment – biologically harmful bisphenol A or its derivatives, posing a potential threat to the patients’ health. 2 Release of BPA and its derivatives into aqueous solutions is the highest in the

  11. Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment.

    Science.gov (United States)

    Lin, Daphne P L; Dass, Crispin R

    2018-03-01

    As both adipocytes and osteoblasts originate from the same pool of mesenchymal stem cells, increasing clinical evidence has emerged of the plasticity between the two lineages. For instance, the downregulation of osteoblast differentiation and upregulation of adipogenesis are common features of conditions such as multiple myeloma, obesity and drug-induced bone loss in diabetes mellitus. However, despite in-vitro and in-vivo observations of adipocyte transdifferentiation into osteoblasts, little is known of the underlying mechanisms. This review summarises the current knowledge of this particular transdifferentiation process whereby the Wnt/β-catenin signalling pathway and Runx2 overexpression have been postulated to play a critical role. Furthermore, due to the possibility of a novel therapy in the treatment of bone conditions, a number of agents with the potential to induce adipo-to-osteoblast transdifferentiation have been investigated such as all-trans retinoic acid, bone morphogenetic protein-9 and vascular endothelial growth factor. © 2018 Royal Pharmaceutical Society.

  12. Cannabidiol as potential treatment in refractory pediatric epilepsy.

    Science.gov (United States)

    Paolino, Maria Chiara; Ferretti, Alessandro; Papetti, Laura; Villa, Maria Pia; Parisi, Pasquale

    2016-01-01

    In recent years there has been great scientific and public interest focused on the therapeutic potential of compounds derived from cannabis for the treatment of refractory epilepsy in children. From in vitro and in vivo studies on animal models, cannabidiol (CBD) appears to be a promising anticonvulsant drug with a favorable side-effect profile. In humans, CBD efficacy and safety is not supported by well-designed trials and its use has been described by anecdotal reports. It will be necessary to investigate CBD safety, pharmacokinetics and interaction with other anti-epileptic drugs (AEDs) alongside performing double-blinded placebo-controlled trials in order to obtain conclusive data on its efficacy and safety in children.

  13. Vitamin D Signaling in Myogenesis: Potential for Treatment of Sarcopenia

    Directory of Open Access Journals (Sweden)

    Akira Wagatsuma

    2014-01-01

    Full Text Available Muscle mass and strength progressively decrease with age, which results in a condition known as sarcopenia. Sarcopenia would lead to physical disability, poor quality of life, and death. Therefore, much is expected of an effective intervention for sarcopenia. Epidemiologic, clinical, and laboratory evidence suggest an effect of vitamin D on muscle function. However, the precise molecular and cellular mechanisms remain to be elucidated. Recent studies suggest that vitamin D receptor (VDR might be expressed in muscle fibers and vitamin D signaling via VDR plays a role in the regulation of myoblast proliferation and differentiation. Understanding how vitamin D signaling contributes to myogenesis will provide a valuable insight into an effective nutritional strategy to moderate sarcopenia. Here we will summarize the current knowledge about the effect of vitamin D on skeletal muscle and myogenic cells and discuss the potential for treatment of sarcopenia.

  14. Autophagy as a potential target for sarcoma treatment.

    Science.gov (United States)

    Min, Li; Choy, Edwin; Pollock, Raphael E; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

    2017-08-01

    Autophagy is a constitutively active, evolutionary conserved, catabolic process for maintaining homeostasis in cellular stress responses and cell survival. Although its mechanism has not been fully illustrated, recent work on autophagy in various types of sarcomas has demonstrated that autophagy exerts an important role in sarcoma cell growth and proliferation, in pro-survival response to therapies and stresses, and in therapeutic resistance of sarcoma. Thus, the autophagic process is being seen as a possibly novel therapeutic target of sarcoma. Additionally, some co-regulators of autophagy have also been investigated as promising biomarkers for the diagnosis and prognosis of sarcoma. In this review, we summarize contemporary advances in the role of autophagy in sarcoma and discuss the potential of autophagy as a new target for sarcoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-03-01

    Full Text Available Maria João Gomes,1 Susana Martins,2,3 Domingos Ferreira,2 Marcela A Segundo,1 Salette Reis1 1REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 3Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark Abstract: Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95% Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%. A high loading efficiency was achieved for finasteride (between 70% and 90%, while less than 30% was

  16. Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

    Science.gov (United States)

    Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

    2018-01-01

    Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the

  17. Changes of the corrosion potential of iron in stagnation and flow conditions and their relationship with metal release.

    Science.gov (United States)

    Fabbricino, Massimiliano; Korshin, Gregory V

    2014-10-01

    This study examined the behavior of corrosion potential (Ecorr) of iron exposed to drinking water during episodes of stagnation and flow. These measurements showed that during stagnation episodes, Ecorr values decrease prominently and consistently. This decrease is initially rapid but it becomes slower as the stagnation time increases. During flow episodes, the Ecorr values increase and reach a quasi-steady state. Experiments with varying concentrations of dissolved oxygen showed that the decrease of Ecorr values characteristic for stagnation is likely to be associated with the consumption of dissolved oxygen by the exposed metal. The corrosion potential of iron and its changes during stagnation were sensitive to the concentrations of sulfate and chloride ions. Measurements of iron release showed that both the absolute values of Ecorr measured prior to or after stagnation episodes were well correlated with the logarithms of concentrations of total iron. The slope of this dependence showed that the observed correlations between Ecorr values and Fe concentrations corresponded to the coupling between the oxidant consumption and changes of Fe redox status. These results demonstrate that in situ Ecorr measurements can be a sensitive method with which to ascertain effects of hydrodynamic conditions and short-term variations of water chemistry on metal release and corrosion in drinking water. This approach is valuable practically because Ecorr measurements are precise, can be carried out in situ with any desired time resolution, do not affect the state of exposed surface in any extent and can be carried out with readily available equipment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Multiplexed and Switchable Release of Distinct Fluids from Microneedle Platforms via Conducting Polymer Nanoactuators for Potential Drug Delivery

    Science.gov (United States)

    Valdés-Ramírez, Gabriela; Windmiller, Joshua R.; Claussen, Jonathan C.; Martinez, Alexandra G.; Kuralay, Filiz; Zhou, Ming; Zhou, Nandi; Polsky, Ronen; Miller, Philip R.; Narayan, Roger; Wang, Joseph

    2013-01-01

    We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually-addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions. PMID:24174709

  19. Potential of Biofilters for Treatment of De-Icing Chemicals

    Directory of Open Access Journals (Sweden)

    Gema Sakti Raspati

    2018-05-01

    Full Text Available Organic de-icing chemicals, such as propylene glycol and potassium formate, cause environmental degradation in receiving water if left untreated, due to the high organic load resulting in oxygen depletion. Biofilters are commonly used for the treatment of biodegradable organic carbon in water treatment. This study investigated the potential for using biofilters for treating organic de-icing compounds. Lab-scale adsorption tests using filter media made of crushed clay (Filtralite and granular activated carbon were conducted. Further, a column filtration experiment testing two different crushed clay size ranges was carried out investigating the effect of filter media depth, nutrient addition, and filtration rate. The surrogate parameter used to monitor the removal of de-icing chemicals was dissolved organic carbon (DOC. The adsorption test showed no significant adsorption of DOC was observed. The column test showed that the most active separation occurred in the first ~20 cm of the filter depth. This was confirmed by results from (1 water quality analysis (i.e., DOC removal and adenosine tri-phosphate (ATP measurement; and (2 calculations based on a filtration performance analysis (Iwasaki model and filter hydraulic evaluation (Lindquist diagram. The results showed that, for the highest C:N:P ratio tested (molar ratio of 24:7:1, 50–60% DOC removal was achieved. The addition of nutrients was found to be important for determining the biofilter performance.

  20. Evaluating Zeta Potential and the Calcite/Aragonite Ratio as Potential Success Indicators for Magnetic Water Treatment

    National Research Council Canada - National Science Library

    Lambert, Kevin

    1999-01-01

    The potential benefits of anti-scale magnetic treatment (AMT) are not realized or reliably predicted because the factors measuring performance of magnetic treatment have either not been identified or are poorly defined...

  1. Potential drug therapies for the treatment of fibromyalgia.

    Science.gov (United States)

    Lawson, Kim

    2016-09-01

    Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non-pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and α2δ ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms.

  2. “In their perception we are addicts”: Social vulnerabilities and sources of support for men released from drug treatment centers in Vietnam

    Science.gov (United States)

    Tomori, Cecilia; Go, Vivian F.; Tuan, Le Nhan; Huong, Nguyen Mai; Binh, Nguyen Thanh; Zelaya, Carla E.; Celentano, David D.; Dat, Do Tuan; Quan, Vu Minh

    2014-01-01

    Background Amid the global transition to treat opioid addiction as an illness, many people who inject drugs (PWID) face heterogeneous legal environments that include both punitive and harm reduction measures. In Vietnam, many PWID, who have a high burden of HIV, are sent to drug treatment centers, or “06 centers”, for compulsory detoxification, vocational training, and labor for up to four years. This study investigates the challenges and facilitators of reentry into community and family life among men who are released from “06 centers” and provides insights and recommendations for developing policies and interventions that address special needs of this vulnerable population. Methods In-depth interviews were conducted in 2011 by trained interviewers among a sample of 43 male PWID released within the past 2 years from “06 centers” in Hanoi, Vietnam to investigate the above issues and to recommend potential interventions. Participants were recruited from outpatient HIV clinics that serve PWID (n=22) and through peer referral from self-help groups for PWID (n=21). Interviews were audiotaped, transcribed, translated, entered into Atlas. TI qualitative data analysis software and analyzed for key themes. Results The interviews revealed persistent drug-related stigmatization, frequently paired with HIV-related stigmatization and discrimination, which hindered employment, increased participants’ social isolation and exacerbated their struggles with addiction. Families were participants’ primary source of financial, employment, and emotional support, but addiction-related family tensions also had negative psychological effects. Participants identified methadone maintenance treatment as an effective means of overcoming addiction, yet few could fully benefit from this treatment due to its limited availability. Conclusion Our study suggests that PWID released from “06 centers” would greatly benefit from the scale-up of community-based harm reduction

  3. "In their perception we are addicts": social vulnerabilities and sources of support for men released from drug treatment centers in Vietnam.

    Science.gov (United States)

    Tomori, Cecilia; Go, Vivian F; Tuan, Le Nhan; Huong, Nguyen Mai; Binh, Nguyen Thanh; Zelaya, Carla E; Celentano, David D; Dat, Do Tuan; Quan, Vu Minh

    2014-09-01

    Amid the global transition to treat opioid addiction as an illness, many people who inject drugs (PWID) face heterogeneous legal environments that include both punitive and harm reduction measures. In Vietnam, many PWID, who have a high burden of HIV, are sent to drug treatment centers, or "06 centers", for compulsory detoxification, vocational training, and labor for up to four years. This study investigates the challenges and facilitators of reentry into community and family life among men who are released from "06 centers" and provides insights and recommendations for developing policies and interventions that address special needs of this vulnerable population. In-depth interviews were conducted in 2011 by trained interviewers among a sample of 43 male PWID released within the past 2 years from "06 centers" in Hanoi, Vietnam to investigate the above issues and to recommend potential interventions. Participants were recruited from outpatient HIV clinics that serve PWID (n=22) and through peer referral from self-help groups for PWID (n=21). Interviews were audiotaped, transcribed, translated, entered into Atlas.TI qualitative data analysis software and analyzed for key themes. The interviews revealed persistent drug-related stigmatization, frequently paired with HIV-related stigmatization and discrimination, which hindered employment, increased participants' social isolation and exacerbated their struggles with addiction. Families were participants' primary source of financial, employment, and emotional support, but addiction-related family tensions also had negative psychological effects. Participants identified methadone maintenance treatment as an effective means of overcoming addiction, yet few could fully benefit from this treatment due to its limited availability. Our study suggests that PWID released from "06 centers" would greatly benefit from the scale-up of community-based harm reduction measures that include addiction and HIV treatment, coupled with

  4. Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

    Science.gov (United States)

    Dannon, Pinhas N; Lowengrub, Katherine; Musin, Ernest; Gonopolski, Yehudit; Kotler, Moshe

    2005-12-01

    Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the

  5. The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.

    Science.gov (United States)

    Cardozo, Linda; Thorpe, Andrew; Warner, Juliet; Sidhu, Manpreet

    2010-08-01

    To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to

  6. Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: an economic evaluation alongside a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Sabina Sanghera

    Full Text Available OBJECTIVE: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS' and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. METHODS: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY estimated using both EQ-5D and SF-6D. RESULTS: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100 and generated 0.002 more QALYs. CONCLUSION: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most cost-effective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial.

  7. Release Report for Building Debris for TA-21 Sewage Treatment Facility

    Energy Technology Data Exchange (ETDEWEB)

    Whicker, Jeffrey Jay [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gillis, Jessica [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ruedig, Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-05-03

    ENV-ES finds that the materials associated with TA-21 Buildings 227 (superstructure only), and 229 (see Figure 1) meet the criteria for unrestricted release to the public for recycle or as sanitary/commercial waste. The interior and exterior of the metal shed, building 387, passed the release criteria collectively; however, results from the roof of the structure were above reference background measurements. Waste management should be consulted for waste disposition options for the roofing metal. These findings are consistent with the requirements of DOE Order 458.1 “Radiation Protection of the Public and the Environment” and LANL Policy 412 “Environmental Radiation Protection.” Sampling and data analysis, as described in this report, were sufficient to meet measurement objectives under the Multi-Agency Radiation Survey and Assessment of Materials and Equipment (MARSAME) manual (2009).

  8. Lipidized prolactin-releasing peptide analogs: A new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Pražienková, Veronika; Zemenová, Jana; Popelová, Andrea; Blechová, Miroslava; Mikulášková, Barbora; Holubová, Martina; Železná, Blanka; Kuneš, Jaroslav

    2016-01-01

    Roč. 22, Suppl S2 (2016), S179-S180 ISSN 1075-2617. [European Peptide Symposium /34./ and International Peptide Symposium /8./. 04.09.2016-09.09.2016, Leipzig] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * food intake * obesity Subject RIV: CE - Biochemistry

  9. Experience with sustained-release melatonin for the treatment of sleep disorders in depression

    Directory of Open Access Journals (Sweden)

    Svetlana Vladimirovna Prokhorova

    2015-01-01

    Full Text Available The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin.Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms, positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients.The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

  10. Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

    Science.gov (United States)

    Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

    2014-12-10

    The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. The involvement of mitochondrial phosphate transporter in accelerating bud dormancy release during chilling treatment of tree peony (Paeonia suffruticosa).

    Science.gov (United States)

    Huang, Xin; Zhu, Wei; Dai, Silan; Gai, Shupeng; Zheng, Guosheng; Zheng, Chengchao

    2008-09-01

    A cDNA clone was isolated from tree peony (Paeonia suffruticosa) subtractive cDNA library of burst buds and characterized with regard to its sequence, expression in response to chilling treatment during the release of bud dormancy, and its function in transgenic Arabidopsis thaliana. The clone, designated as PsMPT, contains 1,615 nucleotides with an open reading frame of 1,119 nucleotides, and the deduced amino acid sequence shows high homology with mitochondrial phosphate transporters (MPTs) from various organisms. The mRNA accumulation of PsMPT in tree peony was strongly induced by chilling treatment during the release of bud dormancy. When the treated plants were transferred to normal growth conditions, the level of PsMPT transcripts induced by sufficient chilling could be maintained high, whereas that induced by insufficient chilling decreased sharply. The transgenic Arabidopsis plants that overexpress PsMPT showed rapid growth and earlier flowering than wild-type plants. ATP contents in the transgenic plants were much higher than that in wild-type plants through various developmental stages. Together, these results suggest that the product of PsMPT is a MPT and might play an important role during the release of bud dormancy in tree peony.

  12. Use of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated heavy menstrual bleeding

    International Nuclear Information System (INIS)

    Uysal, A.; Taner, C.E.; Mun, S.; Celimli, F.H.; Uysal, F.

    2013-01-01

    To evaluate the effects of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated with heavy menstrual bleeding. Methods: The retrospective study was conducted at a tertiary referral hospital in Izmir, Turkey, and comprised data on adenomyosis patients who were implanted with a levonorgestrel-releasing intrauterine device for heavy menstrual bleeding between December 2004 and January 2008. After the insertion of the device, all patients were followed up by transvaginal ultrasonography and serum haemoglobin levels and menstrual patterns were determined at the 6th and 12th month. Data was analysed using SPSS 10. Results: The mean age of the 42 women in the study was 43.2+-0.8 years. At the sixth month, amenorrhoea, oligomenorrhoea, spotting and regular menstrual flow were 9.5% (n=4), 7% (n=3), 19% (n=8), and 64% (n=27), respectively. At the 12th month, the same parametres were 9.5% (n=4), 7% (n=3), 12% (n=5), and 71% (n=30), respectively. Haemoglobin levels had increased and endometrial thickness had decreased, and these differences were statistically significant (p<0.001). Conclusion: The easy-to-use levonorgestrel-releasing intrauterine device can be added to the treatment options as a well-tolerated alternative in cases where a woman who has completed her fertility and does not request a hysterectomy has anaemia associated with adenomyosis. (author)

  13. Review of Natural Compounds for Potential Skin Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tawona N. Chinembiri

    2014-08-01

    Full Text Available Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates. This emphasizes the importance of discovering new compounds that are both safe and effective against melanoma. In vitro testing of melanoma cell lines and murine melanoma models offers the opportunity for identifying mechanisms of action of plant derived compounds and extracts. Common anti-melanoma effects of natural compounds include potentiating apoptosis, inhibiting cell proliferation and inhibiting metastasis. There are different mechanisms and pathways responsible for anti-melanoma actions of medicinal compounds such as promotion of caspase activity, inhibition of angiogenesis and inhibition of the effects of tumor promoting proteins such as PI3-K, Bcl-2, STAT3 and MMPs. This review thus aims at providing an overview of anti-cancer compounds, derived from natural sources, that are currently used in cancer chemotherapies, or that have been reported to show anti-melanoma, or anti-skin cancer activities. Phytochemicals that are discussed in this review include flavonoids, carotenoids, terpenoids, vitamins, sulforaphane, some polyphenols and crude plant extracts.

  14. Colon electrical stimulation: potential use for treatment of obesity.

    Science.gov (United States)

    Sallam, Hanaa S; Chen, Jiande D Z

    2011-09-01

    Obesity is one of the most prevalent health problems in the United States. Current therapeutic strategies for the treatment of obesity are unsatisfactory. We hypothesized the use of colon electrical stimulation (CES) to treat obesity by inhibiting upper gastrointestinal motility. In this preliminary study, we aimed at studying the effects of CES on gastric emptying of solid, intestinal motility, and food intake in dogs. Six dogs, equipped with serosal colon electrodes and a jejunal cannula, were randomly assigned to receive sham-CES or CES during the assessment of: (i) gastric emptying of solids, (ii) postprandial intestinal motility, (iii) autonomic functions, and (iv) food intake. We found that (i) CES delayed gastric emptying of solids by 77%. Guanethidine partially blocked the inhibitory effect of CES on solid gastric emptying; (ii) CES significantly reduced intestinal contractility and the effect lasted throughout the recovery period; (iii) CES decreased vagal activity in both fasting and fed states, increased the sympathovagal balance and marginally increased sympathetic activity in the fasting state; (iv) CES resulted in a reduction of 61% in food intake. CES reduces food intake in healthy dogs and the anorexigenic effect may be attributed to its inhibitory effects on gastric emptying and intestinal motility, mediated via the autonomic mechanisms. Further studies are warranted to investigate the therapeutic potential of CES for obesity.

  15. Release of bisphenol A and its derivatives from orthodontic adhesive systems available on the European market as a potential health risk factor

    Directory of Open Access Journals (Sweden)

    Konrad Małkiewicz

    2015-02-01

    1 In conditions of the current experiment it was demonstrated that most of the assessed orthodontic adhesive resins available on the European market and released into the outside environment – biologically harmful bisphenol A or its derivatives, posing a potential threat to the patients’ health. 2 Release of BPA and its derivatives into aqueous solutions is the highest in the early stages of sample incubation.

  16. Tumor treatment by sustained intratumoral release of cisplatin: effects of drug alone and combined with radiation

    International Nuclear Information System (INIS)

    Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

    1997-01-01

    Purpose: The effect of intratumoral delivery of cisplatin to a mouse tumor model (RIF-1) by means of a biodegradable polymer implant with and without radiation was studied. Methods and Materials: The polymer bis(p-carboxyphenoxy)propane-sebacic acid (CPP:SA; 80:20) and its degradation products have been characterized. Polymer rods (8 x 0.5 mm) containing 17% cisplatin by weight were prepared by extrusion, and the in vitro degradation rate measured. The implants were placed into mouse tumors and their effect (with and without radiation) on tumor growth delay studied. The levels of Pt in the mouse kidney, tumor, and blood plasma at selected intervals after implant were also determined. These results were compared with those obtained when cisplatin was delivered systematically. Results: When cisplatin was delivered by the polymer implants, higher levels were present in the tumor for longer time periods (cf. systemic delivery of the drug). For both nonirradiated and irradiated tumors, those treated with the polymer implants had significantly longer tumor growth delays compared to nonimplanted controls and to systematically treated tumors. Conclusions: The results show that intratumoral delivery of cisplatin is more efficient than systemic delivery. Using the biodegradable polymer implant, higher doses of cisplatin can be tolerated by the animal as the drug is localized within the tumor, and the high levels of the drug in the tumor can be maintained for an extended period of time. When radiation is given in conjunction with cisplatin, the tumor response is supraadditive for all modes of cisplatin administration but is potentiated to a greater extent when cisplatin is delivered through the polymer implant. The greatest effect is seen for treatment with cisplatin delivered by polymer implant combined with fractionated radiation

  17. Fate of stable strontium in the sewage treatment process as an analog for radiostrontium released by nuclear accidents

    International Nuclear Information System (INIS)

    Kamei-Ishikawa, Nao; Ito, Ayumi; Umita, Teruyuki

    2013-01-01

    Highlights: • 76% of the Sr entering the plant was discharged to receiving water. • 21% of the Sr flowing through the plant was transferred to the sewage sludge. •Almost all of the Sr in the sewage sludge was concentrated in incinerated sewage sludge ash. • Activated sludge had a lower sorption capacity for Sr than metals such as Cd. -- Abstract: Radionuclides were widely released into the environment due to the nuclear accident at the Fukushima Daiichi Nuclear Power Plant. Some of these radionuclides have flowed into municipal sewage treatment plants through sewer systems. We have observed the fate of stable Sr in the sewage treatment process as a means to predict the fate of radiostrontium. Concentrations of stable Sr were determined in sewage influent, effluent, dewatered sludge, and incinerated sewage sludge ash collected from a sewage treatment plant once a month from July to December 2011. In the mass balance of Sr in the sewage treatment plant, 76% of the Sr entering the plant was discharged to the receiving water on average. Additionally, 14% of the Sr flowing through the plant was transferred to the sewage sludge and then concentrated in the sludge ash without being released to the atmosphere. We also investigated Sr sorption by activated sludge in a batch experiment. Measurements at 3 and 6 h after the contact showed Sr was sorbed in the activated sludge; however, the measurements indicated Sr desorption from activated sludge occurred 48 h after the contact

  18. Perturbative treatment of potential walls or potential cores in quantum mechanics

    International Nuclear Information System (INIS)

    Mei, W.N.

    1987-01-01

    The general problem involving an infinite potential barrier is treated by first constructing a pseudopotential H' that is shown to reproduce the effect of the barrier. A new procedure is then developed to handle the perturbative effect of H' since the standard formulae become invalid. The case of a finite potential well with large height V/sub o/ can the be solved by reducing it to that of an equivalent infinite barrier. The perturbation parameter turns out to be proportional 1/V/sub o/-E)/sup 1/2/ where E is the energy of the unperturbed state, defying, therefore, the conventional perturbation series treatment that depends on a split-off Hamiltonian for its expansion parameter. These methods are first illustrated with simple examples and then compared to more complex cases. Recently, they have extended this method to the case of degenerate perturbation. The calculation of the hydrogen-like impurity states in quantum well is in progress. Their result should also furnish a check for any specific problem involving a barrier solved by other approximate means such as the variational method

  19. Releasing the constraints on aphasia therapy: the positive impact of gesture and multimodality treatments.

    Science.gov (United States)

    Rose, Miranda L

    2013-05-01

    There is a 40-year history of interest in the use of arm and hand gestures in treatments that target the reduction of aphasic linguistic impairment and compensatory methods of communication (Rose, 2006). Arguments for constraining aphasia treatment to the verbal modality have arisen from proponents of constraint-induced aphasia therapy (Pulvermüller et al., 2001). Confusion exists concerning the role of nonverbal treatments in treating people with aphasia. The central argument of this paper is that given the state of the empirical evidence and the strong theoretical accounts of modality interactions in human communication, gesture-based and multimodality aphasia treatments are at least as legitimate an option as constraint-based aphasia treatment. Theoretical accounts of modality interactions in human communication and the gesture production abilities of individuals with aphasia that are harnessed in treatments are reviewed. The negative effects on word retrieval of restricting gesture production are also reviewed, and an overview of the neurological architecture subserving language processing is provided as rationale for multimodality treatments. The evidence for constrained and unconstrained treatments is critically reviewed. Together, these data suggest that constraint treatments and multimodality treatments are equally efficacious, and there is limited support for constraining client responses to the spoken modality.

  20. Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.

    Directory of Open Access Journals (Sweden)

    Juçara Ribeiro Franca

    Full Text Available The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM. Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a

  1. Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.

    Science.gov (United States)

    Richards, John R; Lapoint, Jeff M; Burillo-Putze, Guillermo

    2018-01-01

    Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits

  2. Surgical treatment of adult scoliosis: is anterior apical release and fusion necessary for the lumbar curve?

    Science.gov (United States)

    Kim, Youngbae B; Lenke, Lawrence G; Kim, Yongjung J; Kim, Young-Woo; Bridwell, Keith H; Stobbs, Georgia

    2008-05-01

    A retrospective study. To analyze radiographic and functional outcomes after posterior segmental spinal instrumentation and fusion (PSSIF) with and without an anterior apical release of the lumbar curve in adult scoliosis patients. No comparison study on PSSIF of adult lumbar scoliosis with apical release versus without has been published. Forty-eight adult patients with lumbar scoliosis (average age at surgery 49.6 years, average follow-up 3.7 years) who underwent PSSIF were analyzed with respect to radiographic change, perioperative and postoperative complications, and Scoliosis Research Society (SRS) outcome scores. Twenty-three patients underwent an anterior apical release of the lumbar curve via a thoracoabdominal approach followed by PSSIF (Group I). The remaining 25 patients underwent a PSSIF of the lumbar curve followed by anterior column support at the lumbosacral region through an anterior paramedian retroperitoneal or posterior transforaminal approach (Group II). Before surgery, Group I showed a somewhat larger lumbar major Cobb angle (63.2 degrees vs. 55.9 degrees , P = 0.07), and both groups demonstrated significant differences in lumbar curve flexibility (26.9% vs. 37.2%, P = 0.02) and thoracolumbar kyphosis (27.0 degrees vs. 15.0 degrees , P = 0.03). After surgery, at the ultimate follow-up, there were no significant differences in major Cobb angle, C7 plumbline to the center sacral vertical line (P = 0.17), C7 plumbline to the posterior superior endplate of S1 (P = 0.44), and sagittal Cobb angles at the proximal junction (P = 0.57), T10-L2 (P = 0.24) and T12-S1 (P = 0.51). There were 4 pseudarthroses in Group I and one in Group II (P = 0.02). Postoperative total normalized SRS outcome scores at ultimate follow-up were significantly higher in Group II (69% vs. 79%, P = 0.01). Posterior segmental spinal instrumentation and fusion without anterior apical release of lumbar curves in adult scoliosis demonstrated better total SRS outcome scores and no

  3. NESHAP Area-Specific Dose-Release Factors for Potential Onsite Member-of-the-Public Locations at SRS using CAP88-PC Version 4.0

    Energy Technology Data Exchange (ETDEWEB)

    Trimor, P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-08-09

    The Environmental Protection Agency (EPA) requires the use of the computer model CAP88-PC to estimate the total effective doses (TED) for demonstrating compliance with 40 CFR 61, Subpart H (EPA 2006), the National Emission Standards for Hazardous Air Pollutants (NESHAP) regulations. As such, CAP88 Version 4.0 was used to calculate the receptor dose due to routine atmospheric releases at the Savannah River Site (SRS). For estimation, NESHAP dose-release factors (DRFs) have been supplied to Environmental Compliance and Area Closure Projects (EC&ACP) for many years. DRFs represent the dose to a maximum receptor exposed to 1 Ci of a specified radionuclide being released into the atmosphere. They are periodically updated to include changes in the CAP88 version, input parameter values, site meteorology, and location of the maximally exposed individual (MEI). In this report, the DRFs were calculated for potential radionuclide atmospheric releases from 13 SRS release points. The three potential onsite MEI locations to be evaluated are B-Area, Three Rivers Landfill (TRL), and Savannah River Ecology Lab Conference Center (SRELCC) with TRL’s onsite workers considered as members-of-the-public, and the potential future constructions of dormitories at SRELCC and Barracks at B-Area. Each MEI location was evaluated at a specified compass sector with different area to receptor distances and was conducted for both ground-level and elevated release points. The analysis makes use of area-specific meteorological data (Viner 2014). The resulting DRFs are compared to the 2014 NESHAP offsite MEI DRFs for three operational areas; A-Area, H-Area, and COS for a release rate of 1 Ci of tritium oxide at 0 ft. elevation. CAP88 was executed again using the 2016 NESHAP MEI release rates for 0 and 61 m stack heights to determine the radionuclide dose at TRL from the center-of-site (COS).

  4. The variability of the potential radiation exposure to man arising from radionuclides released to the ground water

    International Nuclear Information System (INIS)

    Proehl, G.; Mueller, H.

    1994-12-01

    The variability of the potential radiation exposure of the population is estimated if radionuclides (Np-237, Tc-99, I-129, Cs-135, Ra-226, U-238) are released to the ground water which is used by man as drinking water for humans and animals, for irrigation of food and feed crops, and for the production of fish in freshwater bodies. Annual effective dose equivalents are calculated assuming a normalized activity concentration in the water of 1 Bq/l for each radionuclide considered. An important aim is the estimation of the uncertainty of the exposure due to the uncertainty and the variability of the input parameters. The estimated frequency distributions of the input parameters were used as a model input and processed with Latin Hypercube Sampling and a Monte-Carlo technique. This estimation is based on an exposure scenario which reflects the present conditions. The critical group for the exposure due to the use of contaminated ground water are for most radionuclides the children of 1 year, although the activity intake of children is much lower than for adults. However the ingestion dose factors for infants are higher; in many cases the differences are higher than a factor of 5. (orig./HP)

  5. Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

    Science.gov (United States)

    Han, Jing; Yang, Yi; Lu, Junren; Wang, Chenzhong; Xie, Youtao; Zheng, Xuebin; Yao, Zhenjun; Zhang, Chi

    2017-07-24

    In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.

  6. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis.

    Science.gov (United States)

    Kopp, Matthias Volkmar; Brauburger, Jens; Riedinger, Frank; Beischer, Dorothee; Ihorst, Gabriele; Kamin, Wolfgang; Zielen, Stefan; Bez; Friedrichs, Frank; Von Berg, Andrea; Gerhold, Kerstin; Hamelmann, Eckard; Hultsch; Kuehr, Joachim

    2002-11-01

    Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1

  7. Releasing the Constraints on Aphasia Therapy: The Positive Impact of Gesture and Multimodality Treatments

    Science.gov (United States)

    Rose, Miranda L.

    2013-01-01

    Purpose: There is a 40-year history of interest in the use of arm and hand gestures in treatments that target the reduction of aphasic linguistic impairment and compensatory methods of communication (Rose, 2006). Arguments for constraining aphasia treatment to the verbal modality have arisen from proponents of constraint-induced aphasia therapy…

  8. Setting the Standard for Autism Treatments: National Autism Center Releases Groundbreaking Report

    Science.gov (United States)

    Wilczynski, Susan M.; Pollack, Eileen G.

    2009-01-01

    In the United States and throughout the world, one's understanding of autism and other related disorders continues to evolve. Parents, educators, and health professionals today benefit from significant advancements in both the diagnosis and treatment of autism. However, the need to evaluate and select from a list of treatment options can be…

  9. Biomolecular characterization of exosomes released from cancer stem cells: Possible implications for biomarker and treatment of cancer.

    Science.gov (United States)

    Kumar, Dhruv; Gupta, Dwijendra; Shankar, Sharmila; Srivastava, Rakesh K

    2015-02-20

    Cancer recognized as one of the leading irrepressible health issues is contributing to increasing mortality-rate day-by-day. The tumor microenvironment is an important field of cancer to understand the detection, treatment and prevention of cancer. Recently, cancer stem cell (CSC) research has shown promising results aiming towards cancer diagnostics and treatment. Here, we found that prostate and breast cancer stem cells secreted vesicles of endosomal origin, called exosomes showed strong connection between autophagy and exosomes released from CSCs. Exosomes may serve as vesicles to communicate with neoplastic cells (autocrine and paracrine manner) and normal cells (paracrine and endocrine manner) and thereby suppress immune systems and regulate neoplastic growth, and metastasis. They can also be used as biomarkers for various cancers. We detected tetraspanin proteins (CD9, CD63, CD81), Alix and tumor susceptibility gene-101 (TSG101) of exosomal markers from rotenone treated CSCs. We have also detected the induction of autophagy genes, Atg7 and conversion of autophagy marker (LC3-I to LC3-II), and tetraspanin proteins (CD9, CD63, CD81) in rotenone treated CSCs by western blotting. The mRNA expression of CD9, CD63, CD81 and TSG101 analyzed by qRT-PCR showed that the rotenone induced the expression of CD9, CD63, CD81 and TSG101 in CSCs. Electron microscopy of rotenone treated CSCs showed the mitochondrial damage of CSCs as confirmed by the release of exosomes from CSCs. The constituents of exosomes may be useful to understand the mechanism of exosomes formation, release and function, and also serve as a useful biomarker and provide novel therapeutic strategies for the treatment and prevention of cancer.

  10. Fatty acid oxidation products ('green odour') released from perennial ryegrass following biotic and abiotic stress, potentially have antimicrobial properties against the rumen microbiota resulting in decreased biohydrogenation.

    Science.gov (United States)

    Huws, S A; Scott, M B; Tweed, J K S; Lee, M R F

    2013-11-01

    In this experiment, we investigated the effect of 'green odour' products typical of those released from fresh forage postabiotic and biotic stresses on the rumen microbiota and lipid metabolism. Hydroperoxyoctadecatrienoic acid (HP), a combination of salicylic and jasmonic acid (T), and a combination of both (HPT) were incubated in vitro in the presence of freeze-dried ground silage and rumen fluid, under rumen-like conditions. 16S rRNA (16S cDNA) HaeIII-based terminal restriction fragment length polymorphism-based (T-RFLP) dendrograms, canonical analysis of principal coordinates graphs, peak number and Shanon-Weiner diversity indices show that HP, T and HPT likely had antimicrobial effects on the microbiota compared to control incubations. Following 6 h of in vitro incubation, 15.3% of 18:3n-3 and 4.4% of 18:2n-6 was biohydrogenated in control incubations, compared with 1.3, 9.4 and 8.3% of 18:3n-3 for HP, T and HPT treatments, respectively, with negligible 18:2n-6 biohydrogenation seen. T-RFLP peaks lost due to application of HP, T and HPT likely belonged to as yet uncultured bacteria within numerous genera. Hydroperoxyoctadecatrienoic acid, T and HPT released due to plant stress potentially have an antimicrobial effect on the rumen microbiota, which may explain the decreased biohydrogenation in vitro. These data suggest that these volatile chemicals may be responsible for the higher summer n-3 content of bovine milk. © 2013 The Society for Applied Microbiology.

  11. 76 FR 55391 - Notice of Postponement of Release of Draft NTP Monograph on Potential Developmental Effects of...

    Science.gov (United States)

    2011-09-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Notice of Postponement of Release of Draft NTP Monograph... Review Draft Monograph AGENCY: Division of the National Toxicology Program (DNTP), National Institute of... NTP monograph and peer review panel meeting. SUMMARY: The NTP is postponing the release of the Draft...

  12. [Gluteal muscle contracture release for the treatment of gluteal muscle contracture induced knee osteoarthritis: a report of 52 cases].

    Science.gov (United States)

    Wang, Cheng-xiang; Gong, Yu-suo; Li, Sheng-hua; Liu, Hai-ping; Chai, Xi-ping

    2011-07-01

    To investigate clinical efficacy and significance of gluteal muscle contracture release for the treatment of gluteal muscle contracture induced knee osteoarthritis. From January 2008 to June 2010,52 patients with gluteal muscle contracture induced knee osteoarthritis were reviewed. Among the patients,15 patients were male and 37 patients were female, ranging in age from 15 to 45 years, with an average of 35 years. Eighteen patients had left knee osteoarthritis, 30 patients had right osteoarthritis, and 4 patients had double knee osteoarthritis. All the patients were treated with gluteal muscle contracture release. Lysholm knee score was used to evaluate therapeutic effects before and after operation. All the patients were followed up,and the duration ranged from 12 to 37 years,with a mean of 15 months. The Lysholm knee score improved from preoperative (68.12 +/- 0.78) points to postoperative (91.23 +/- 0.47) points at the last follow-up, the difference had statistical difference (t=31.269, Pmuscle contracture release is effective to relieve symptoms of gluteal muscles contracture and knee osteoarthritis. The patients with gluteal muscle contracture should be treated early so as to prevent effects of gluteal muscle contracture on knee joint, slow down degeneration of knee joint at early stage, and prevent occurrence of knee osteoarthritis.

  13. Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse.

    Science.gov (United States)

    Alba, Maria; Fintini, Danilo; Bowers, Cyril Y; Parlow, A F; Salvatori, Roberto

    2005-11-01

    Growth hormone (GH) secretagogues (GHS) stimulate GH secretion in vivo in humans and in animals. They act on the ghrelin receptor, expressed in both the hypothalamus and the pituitary. It is unknown whether GHSs act predominantly by increasing the release of hypothalamic GH-releasing hormone (GHRH) or by acting directly on the somatotroph cells. We studied whether a potent GHS could stimulate growth in the absence of endogenous GHRH. To this end, we used GHRH knockout (GHRH-KO) mice. These animals have proportionate dwarfism due to severe GH deficiency (GHD) and pituitary hypoplasia due to reduced somatotroph cell mass. We treated male GHRH-KO mice for 6 wk (from week 1 to week 7 of age) with GH-releasing peptide-2 (GHRP-2, 10 microg s.c. twice a day). Chronic treatment with GHRP-2 failed to stimulate somatotroph cell proliferation and GH secretion and to promote longitudinal growth. GHRP-2-treated mice showed an increase in total body weight compared with placebo-treated animals, due to worsening of the body composition alterations typical of GHD animals. These data demonstrate that GHRP-2 failed to reverse the severe GHD caused by lack of GHRH.

  14. Heat treatments of irradiated uranium oxide in a pressurised water reactor (P.W.R.): swelling and fission gas release

    International Nuclear Information System (INIS)

    Zacharie, I.

    1997-01-01

    In order to keep pressurised water reactors at a top level of safety, it is necessary to understand the chemical and mechanical interaction between the cladding and the fuel pellet due to a temperature increase during a rapid change in reactor. In this process, the swelling of uranium oxide plays an important role. It comes from a bubble precipitation of fission gases which are released when they are in contact with the outside. Therefore, the aim of this thesis consists in acquiring a better understanding of the mechanisms which come into play. Uranium oxide samples, from a two cycles irradiated fuel, first have been thermal treated between 1000 deg C and 1700 deg C for 5 minutes to ten hours. The gas release amount related to time has been measured for each treatment. The comparison of the experimental results with a numerical model has proved satisfactory: it seems that the gases release, after the formation of intergranular tunnels, is controlled by the diffusion phenomena. Afterwards, the swelling was measured on the samples. The microscopic examination shows that the bubbles are located in the grain boundaries and have a lenticular shape. The swelling can be explained by the bubbles coalescence and a model was developed based on this observation. An equation allows to calculate the intergranular swelling in function of time and temperature. The study gives the opportunity to predict the fission gases behaviour during a fuel temperature increase. (author)

  15. Potential of improving the treatment of tuberculosis through nanomedicine

    CSIR Research Space (South Africa)

    Semete, B

    2012-03-01

    Full Text Available allowing its attachment onto the cell (Trewyn et al., 2008). It is equally admitted that spherical particles offer maximum volume for drug incorporation. We also observed that the use of lactose in the spray dried formulation helped to decrease...: in vivo release of free drugs vs spray dried nanoparticles encapsulating RIF, INH and PZA. A. Samples with high concentration of lactose (5%w/v) and B. samples with low concentration of lactose (4%w/v). C. The multidose indicates a formulation where RIF...

  16. The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

    Science.gov (United States)

    Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

    2015-01-01

    Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

  17. Development of a fast dissolving film of epinephrine hydrochloride as a potential anaphylactic treatment for pediatrics.

    Science.gov (United States)

    Alayoubi, Alaadin; Haynes, Lindsay; Patil, Hemlata; Daihom, Baher; Helms, Richard; Almoazen, Hassan

    2017-12-01

    To develop a fast dissolving film strip containing epinephrine HCl for the potential treatment of pediatric anaphylaxis. Four different films have been prepared by solvent casting technique where the percentages of the polymer (Lycoat RS720) were optimized. The polymer percentages were (20%, 25%, 27% and 30%) of the total formulation weighs. The thickness and elastic modulus of the optimized film was evaluated using dynamic mechanical analyzer. Epinephrine content uniformity was assessed using UV at wavelength 280 nm. For the dissolution test, fast dissolving films (FDFs) were evaluated in 500 Simulated Saliva, with 50 rpm. In vivo taste and disintegration evaluation was performed on six healthy volunteers. Films formed by formulations 1, 2 and 3 were too sticky after drying, while formulation 4 that has 30% polymer content formed smooth, transparent, flexible and uniform film, and therefore, it was selected for further testing. The value of elastic modulus was determined at 1.325 MPa. The thickness of the film at different locations was measured at 0.29 mm. Drug content in film was measured at 93% ±10. More than 90% of epinephrine was released from the film within 7.2 min. Bitterness of epinephrine was masked efficiently according to volunteer's comments with average disintegration time of 20 s. This study presents potential proof for using FDFs as a replacement therapy of epinephrine injections for pediatrics.

  18. Potential of regenerative medicine for treatment of vitiligo patients

    Directory of Open Access Journals (Sweden)

    A. A. Kubanova

    2014-01-01

    Full Text Available The article presents a review of publishes sources on the efficacy of methods such as tissue engineering and cellular transplantation of autologous melanocytes for treatment of vitiligo patients. The article describes general principles of treatment and particular features of current melanocyte transplantation methods.

  19. Delineation of potential hot spots for hyperthermia treatment planning optimisation

    NARCIS (Netherlands)

    Wiersma, J.; van Wieringen, N.; Crezee, H.; van Dijk, J. D. P.

    2007-01-01

    The optimal feed parameters of the generators for a complex-phased hyperthermia array system consisting of 4, 8 or even more applicators cannot be found using only the expertise of the treatment staff or using the limited amount of field and temperature data obtained during treatment. A number of

  20. A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

    Science.gov (United States)

    Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

    2009-01-01

    A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

  1. The release of organic material from clay based buffer materials and its potential implications for radionuclide transport

    International Nuclear Information System (INIS)

    Vilks, P.; Stroes-Gascoyne, S.; Goulard, M.; Haveman, S.A.; Bachinski, D.B.

    1998-01-01

    In the Canadian nuclear fuel waste disposal concept used fuel would be placed in corrosion resistant containers which would be surrounded by clay-based buffer and backfill materials in an engineered vault excavated at 500 to 1000 m depth in crystalline rock formations in the Canadian shield. Organic substances could affect radionuclide mobility due to the effects of redox and complexation reactions that increase solubility and alter mobility. The purpose of this study was to determine whether the buffer and backfill materials, proposed for use in a disposal vault, contain organics that could be leached by groundwater in large enough quantities to affect radionuclide mobility within the disposal vault and surrounding geosphere complex. Buffer material, made from a mixture of 50 wt.% Avonlea sodium bentonite and 50 wt.% silica sand, was extracted with deionized water to determine the release of dissolved organic carbon (DOC), humic acid and fulvic acid. The effect of radiation and heat from the used fuel was simulated by treating samples of buffer before leaching to various amounts of heat (60 and 90 C) for periods of 2, 4 and 6 weeks, and to ionizing radiation with doses of 25 kGy and 50 kGy. The results showed that groundwater would leach significant amounts of organics from buffer that complex with radionuclides such as the actinides, potentially affecting their solubility and transport within the disposal vault and possibly the surrounding geosphere. In addition, the leached organics would likely stimulate microbial growth by several orders of magnitude. Heating and radiation affect the amount and nature of leachable organics. (orig.)

  2. A SERS protocol as a potential tool to access 6-mercaptopurine release accelerated by glutathione-S-transferase.

    Science.gov (United States)

    Wang, Ying; Sun, Jie; Yang, Qingran; Lu, Wenbo; Li, Yan; Dong, Jian; Qian, Weiping

    2015-11-21

    The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.

  3. Weighing the potential effectiveness of various treatments for sleep bruxism.

    Science.gov (United States)

    Huynh, Nelly; Manzini, Christiane; Rompré, Pierre H; Lavigne, Gilles J

    2007-10-01

    Sleep bruxism may lead to a variety of problems, but its pathophysiology has not been completely elucidated. As such, there is no definitive treatment, but certain preventive measures and/or drugs may be used in acute cases, particularly those involving pain. This article is intended to guide clinician scientists to the treatment most appropriate for future clinical studies. To determine the best current treatment, 2 measures were used to compare the results of 10 clinical studies on sleep bruxism, 3 involving oral devices and 7 involving pharmacologic therapy. The first measure, the number needed to treat (NNT), allows several randomized clinical studies to be compared and a general conclusion to be drawn. The second measure, effect size, allows evaluation of the impact of treatment relative to a placebo using different studies of similar design. Taking into account the NNT, the effect size and the power of each study, it can be concluded that the following treatments reduce sleep bruxism: mandibular advancement device, clonidine and occlusal splint. However, the first 2 of these have been linked to adverse effects. The occlusal splint is therefore the treatment of choice, as it reduces grinding noise and protects the teeth from premature wear with no reported adverse effects. The NNT could not be calculated for an alternative pharmacologic treatment, short-term clonazepam therapy, which had a large effect size and reduced the average bruxism index. However, the risk of dependency limits its use over long periods. Assessment of efficacy and safety of the most promising treatments will require studies with larger sample sizes over longer periods.

  4. Evaluation of Potential Drug–Drug Interaction Between Delayed‐Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women

    Science.gov (United States)

    Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I.

    2017-01-01

    Abstract Delayed‐release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti‐inflammatory and neuroprotective properties. This 2‐period crossover study was conducted to evaluate the potential for drug–drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty‐six healthy women were enrolled; 32 completed the study. After the lead‐in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration–time curve over the dosing interval and peak plasma concentration contained within the 0.8–1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol–based OCs may be used with DMF without dose modification. PMID:28783872

  5. Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

    Science.gov (United States)

    Zhu, Bing; Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I

    2017-11-01

    Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  6. Clinical use of extended-release oral treprostinil in the treatment of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Pugliese SC

    2016-01-01

    Full Text Available Steven C Pugliese,1 Todd M Bull1,2 1Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, 2UCD Pulmonary Vascular Disease Center, Division of Pulmonary Sciences and Critical Care Medicine and Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Abstract: The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH. Intravenous (IV epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is great interest in the development of an oral prostacyclin analog that could mimic the benefits of IV therapy. Herein, we highlight the development of oral prostacyclin therapy, focusing on oral treprostinil, the only US Food and Drug Administration approved oral prostacyclin. Recent Phase III clinical trials have shown the drug to improve exercise tolerance in treatment-naïve PAH patients, but not patients on background oral therapy. Oral treprostinil appears to be most efficacious at higher doses, but its side effect profile and complexities with dosing complicate its use. While oral treprostinil’s current therapeutic role in PAH remains unclear, ongoing studies of this class of medication should help clarify their role in the treatment of PAH. Keywords: oral treprostinil, pulmonary arterial hypertension, selexipag

  7. Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty : The Dutch experience

    NARCIS (Netherlands)

    Mul, D; Oostdijk, W; Otten, BJ; Rouwe, C; Jansen, M; Delemarre-van de Waal, HA; Waelkens, JJJ; Drop, SLS

    Final height (FH) data of 96 children (87 girls) treated with GnRH agonist for central precocious puberty were studied. In girls mean FH exceeded initial height prediction by 7.4 (5.7) cm (p <0.001); FH was significantly lower than target height, but still in the genetic target range. When treatment

  8. Botox combined with myofascial release physical therapy as a treatment for myofascial pelvic pain

    Science.gov (United States)

    Scott, Lauren; Wyman, Allison; Mora, Nelsi; Miladinovic, Branko; Bassaly, Renee; Hoyte, Lennox

    2017-01-01

    Purpose To report the effects of combined onabotulinumtoxinA (Botox) injections and myofascial release physical therapy on myofascial pelvic pain (MFPP) by comparing pre- and posttreatment average pelvic pain scores, trigger points, and patient self-reported pelvic pain. Secondary outcomes were to examine posttreatment complications and determine demographic differences between patients with/without an improvement in pain. Materials and Methods This was an Institutional Review Board approved retrospective case series on women over 18 years with MFPP who received Botox and physical therapy between July 2006 and November 2014. Presence of trigger points and pelvic pain scores were determined by digital palpation of the iliococcygeus, puborectalis, obturator internus, and rectus muscles. Average pelvic pain scores (0–10) reflected an average of the scores obtained from palpation of each muscle. Self-reported improvement in pain was recorded as yes/no. Results Fifty women met the inclusion/exclusion criteria. Posttreatment, patients had lower average pelvic pain scores (3.7±4.0 vs. 6.4±1.8, p=0.005), and fewer trigger points (44% vs. 100%, pphysical therapy under anesthesia can be effective in treating women with chronic pelvic pain secondary to MFPP. PMID:28261683

  9. Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

    Science.gov (United States)

    Dang, Nhung T T; Sivakumaran, Haran; Harrich, David; Shaw, Paul N; Davis-Poynter, Nicholas; Coombes, Allan G A

    2014-10-01

    Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to loading efficiencies of about 41-42%. The actual loadings of NVP were around half those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to 23.5%. Approximately 80% of the initial content of TFV was released from the PCL matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was almost double the cumulative release of NVP (40-45%). The release kinetics of both antivirals over 30 days were found to be described most satisfactorily by the Higuchi model. In vitro assay of release media containing combinations of TFV and NVP released from PCL matrices confirmed a potential synergistic/additive effect of the released antivirals on HIV-1 infection of HeLa cells. These findings indicate that PCL matrices loaded with combinations of TFV and NVP provide an effective strategy for the sustained vaginal delivery of antivirals with synergistic/additive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Characterization, treatment and releases of PBDEs and PAHs in a typical municipal sewage treatment plant situated beside an urban river, East China.

    Science.gov (United States)

    Wang, Xiaowei; Xi, Beidou; Huo, Shouliang; Sun, Wenjun; Pan, Hongwei; Zhang, Jingtian; Ren, Yuqing; Liu, Hongliang

    2013-07-01

    Characterization, treatment and releases of eight polybrominated diphenyl ethers (PBDEs) congeners and sixteen polycyclic aromatic hydrocarbons (PAHs) in wastewater were evaluated along the treatment processes of a typical secondary treatment municipal sewage treatment plant (STP) (in Hefei City) situated the beside Nanfei River, East China. The findings showed that the average concentrations of the total PBDEs in raw wastewater and treated effluent were 188.578 and 36.884 ng/L respectively. Brominated diphenyl ether (BDE) 209 congener, the predominant PBDE in the STP and Nanfei River, could be related to the discharge of car-industry-derived wastes. For PAHs, the average concentrations in raw wastewater and treated effluent were 5758.8 and 2240.4 ng/L respectively, with naphthalene, benzo[a]pyrene and indeno[1,2,3-c,d]pyrene being detected at the highest concentrations. PAHs mainly originate from the combustion of biomass/coal and petroleum. The STP reduced about 80% of the PBDEs and 61% of the PAHs, which were eliminated mainly by sedimentation processes. The removal rates of PBDEs/PAHs increased with the increase of their solid-water partitioning coefficients. Accordingly, the STP's effluent, containing some PBDE congeners (e.g., BDE 47, 99 and 209, etc.) and low-molecular-weight PAHs, could be an important contributor of these contaminants' input to Nanfei River. It resulted in a significant increase of PBDE/PAH concentrations and PAH toxicological risk in the river water downstream. About 4.040 kg/yr of PBDEs and 245.324 kg/yr of PAHs could be released into the Nanfei River. The current conventional wastewater treatment processes should be improved to remove the relatively low-molecular-weight PBDEs/PAHs more effectively.

  11. Treatment of idiopathic hypogonadotropic hypogonadism in men with luteinizing hormone-releasing hormone: a comparison of treatment with daily injections and with the pulsatile infusion pump.

    Science.gov (United States)

    Shargil, A A

    1987-03-01

    Thirty husbands in childless couples, aged 24 to 35 years, were treated with luteinizing hormone-releasing hormone (LH-RH) for idiopathic hypogonadotropic hypogonadism (IHH) of peripubertal (incomplete) type. They were azoospermic or oligospermic, with less than 1.5 X 10(6)/ml nonmotile spermatozoa. The diagnosis of IHH was based on clinical and laboratory features and testicular biopsy specimen study and was further supported by results of stimulation tests and gonadotropin-releasing hormone (GnRH) test. Two treatment modalities were used: subcutaneous injections of 500 micrograms LH-RH twice daily; and perpetual subcutaneous injection, via portable infusion pump, of 25 ng/kg LH-RH, at 90-minute intervals. Two patients required a short second period of pulsatile treatment to cause a second pregnancy of their spouses. The pump proved to yield better results, compared with intermittent injections, in respect to endocrine responses, spermatogenesis, and fertility capacity. Normal levels of luteinizing hormone and follicle-stimulating hormone were reached in 2 to 3 weeks and normal testosterone levels in 8 to 10 weeks from the start of treatment. Sperm counts rose to greater than 60 X 10(6)/ml viable spermatozoa with less than 15% of abnormal forms in 3 to 5 months, and the wives conceived. Of a total of 18 deliveries of healthy infants, 12 offspring were identified genetically with their fathers. Four women were still pregnant at the conclusion of the study. The pump was well tolerated, without special operational problems to the patients. Pulsatile treatment is therefore recommended in the treatment of well-diagnosed and carefully selected cases of incomplete IHH.

  12. 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.

  13. Potential sources for the radiation treatment of food

    International Nuclear Information System (INIS)

    Sande, W.E.; Libby, R.A.

    1976-01-01

    The present, near-term, and potential (through year 2000) supply of radiation sources for large-scale radiosterilization applications is discussed. Principal sources considered are 60 Co produced in nuclear power reactors, 137 Cs presently available from ERDA encapsulation operations, and a mixture of 134 Cs- 137 Cs potentially available from the reprocessing of spent nuclear fuel. Some consideration is also given to electron accelerators

  14. Female reproductive potential after treatment for Hodgkin's disease

    International Nuclear Information System (INIS)

    Horning, S.J.; Hoppe, R.T.; Kaplan, H.S.; Rosenberg, S.A.

    1981-01-01

    The probability of maintaining ovarian function, becoming pregnant, and delivering a normal child is important to young women anticipating successful therapy for Hodgkin's disease. In this study, reproductive function was retrospectively examined in 103 women 40 years old or younger who had undergone treatment for Hodgkin's disease with total-lymphoid irradiation (TLI) alone, combination chemotherapy, or combined TLI and chemotherapy. Infertility was directly related to gonadal exposure to therapy and to age at treatment. Twenty women became pregnant after receiving total-nodal irradiation or combination chemotherapy or both. No fetal wastage occurred, and no birth defects were seen in the 24 infants born to these women. Even after intensive treatment programs, women successfully treated for Hodgkin's disease have become pregnant and delivered phenotypically normal children

  15. Present municipal water treatment and potential removal methods

    International Nuclear Information System (INIS)

    Lee, S.Y.; White, S.K.; Bondietti, E.A.

    1982-01-01

    Uranium analyses of raw water, intermediate stage, and treated water samples from 20 municipal water treatment plants indicated that the present treatment practices were not effective in removing uranium from raw waters when the influent concentration was in the range of 0.1 to 16 μg/L uranium. Laboratory batch tests revealed that the water softening and coagulant chemicals commonly used were able to remove more than 90% of the dissolved uranium ( < 100 μg/L) in waters if an optimum pH and dosage were provided. Absorbents, titanium oxide and activated charcoal, were also effective in uranium removal under specific conditions. Strong base anion exchange resin was the most efficient uranium adsorbent, and an anion exchange column is a recommended option for the treatment of private well waters containing uranium at higher than desirable levels

  16. Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications.

    Science.gov (United States)

    Holmes, Emily A; Blackwell, Simon E; Burnett Heyes, Stephanie; Renner, Fritz; Raes, Filip

    2016-01-01

    Mental imagery is an experience like perception in the absence of a percept. It is a ubiquitous feature of human cognition, yet it has been relatively neglected in the etiology, maintenance, and treatment of depression. Imagery abnormalities in depression include an excess of intrusive negative mental imagery; impoverished positive imagery; bias for observer perspective imagery; and overgeneral memory, in which specific imagery is lacking. We consider the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions. Treatment advances capitalizing on the representational format of imagery (as opposed to its content) are reviewed, including imagery rescripting, positive imagery generation, and memory specificity training. Consideration of mental imagery can contribute to clinical assessment and imagery-focused psychological therapeutic techniques and promote investigation of underlying mechanisms for treatment innovation. Research into mental imagery in depression is at an early stage. Work that bridges clinical psychology and neuroscience in the investigation of imagery-related mechanisms is recommended.

  17. Foraging at wastewater treatment works increases the potential for ...

    African Journals Online (AJOL)

    Wastewater treatment works (WWTWs) are known to provide profitable foraging areas for insectivorous bats in Europe and the New World because of their association with high abundance of pollution-tolerant midges (Diptera). However, bats that feed on these insects may also accumulate metal pollutants such as cadmium ...

  18. Outpatient treatment costs and their potential impact on cancer care

    International Nuclear Information System (INIS)

    Isshiki, Takahiro

    2014-01-01

    Cancer creates a tremendous financial burden. Cancer-related costs are categorized into direct, indirect, and psychosocial costs. Although there have been many reports on medical care costs, which are direct, those on other costs are extremely scarce. We estimated travel time and costs required for cancer patients to receive outpatient treatment. We studied 521 cancer patients receiving anti-cancer treatment between February 2009 and December 2012 at the Outpatient Chemotherapy Center of Teikyo University Chiba Medical Center. Address data were extracted from Data Warehouse electronic medical records, and travel distance and time required for outpatient treatment were calculated via MapInfo and ACT Distance Calculator Package. Transportation costs were estimated on the basis of ¥274 (=$3.00) per kilometer. The study design was approved by an ethics review board of Teikyo University (12-851). Average round-trip travel distance, time, and cost for all patients were 26.7 km, 72.5 min, and ¥7,303 ($79.99), respectively. Cancer patients incurred a travel cost of ¥4000–¥9000 ($40.00 to $100.00) for each outpatient treatment. With population aging, seniors living alone and senior households are increasing, and outpatient visits are becoming a common burden

  19. Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

    Directory of Open Access Journals (Sweden)

    Smolej L

    2014-12-01

    Full Text Available Lukáš Smolej 4th Department of Internal Medicine – Hematology, University Hospital Hradec Králové and Charles University in Prague, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic Abstract: Introduction of targeted agents revolutionized the treatment of chronic lymphocytic leukemia (CLL in the past decade. Addition of chimeric monoclonal anti-CD20 antibody rituximab to chemotherapy significantly improved efficacy including overall survival (OS in untreated fit patients; humanized anti-CD52 antibody alemtuzumab and fully human anti-CD20 antibody ofatumumab lead to improvement in refractory disease. Novel small molecule inhibitors such as ibrutinib and idelalisib demonstrated excellent activity and were very recently licensed in relapsed/refractory CLL. Obinutuzumab (GA101 is the newest monoclonal antibody approved for the treatment of CLL. This novel, glycoengineered, type II humanized anti-CD20 antibody is characterized by enhanced antibody-dependent cellular cytotoxicity and direct induction of cell death compared to type I antibodies. Combination of obinutuzumab and chlorambucil yielded significantly better OS in comparison to chlorambucil monotherapy in untreated comorbid patients. These results led to approval of obinuzutumab for the treatment of CLL. Numerous clinical trials combining obinutuzumab with other cytotoxic drugs and novel small molecules are currently under way. This review focuses on the role of obinutuzumab in the treatment of CLL. Keywords: chronic lymphocytic leukemia, anti-CD20 antibodies, chlorambucil, rituximab, ofatumumab, obinutuzumab, overall survival

  20. Lipase-producing fungi for potential wastewater treatment and ...

    African Journals Online (AJOL)

    The use of fungal biomass as a lipase biocatalyst represents an attractive approach for the treatments of oil wastewater as well as for the production of biodiesel from oil and residual grease, due to its greater stability, possibility of reuse, and lower cost. In this work, 20 filamentous fungi were isolated from the grease trap ...

  1. Evaluation Of Biocides for Potential Treatment of Ballast Water

    Science.gov (United States)

    2004-10-01

    gather data on toxicology and ecotoxicology ; (3) provide information on the processes used in the production of the new substance, as well as the...Data Bank 2004 Target Organism Treatment Dosage Citation algae reduced by 92% filamentous algae or common macrophytes (Potamogeton foliosus...Sea Nine 211; RH-25287 Citations Laws and Regulations Shipboard Use DEPA, , . 2000. Ecotoxicological Assessment of Antifouling Biocides and

  2. Mindful Music Listening as a Potential Treatment for Depression

    Science.gov (United States)

    Eckhardt, Kristen J.; Dinsmore, Julie A.

    2012-01-01

    Depression is one of the most common mental health issues. Although drug therapy and cognitive-behavioral therapy remain popular and effective treatments, alternative interventions such as the use of music listening and mindfulness practice as interventions during therapy have gained ground. Research on the use of music listening and mindfulness…

  3. Enobosarm (GTx-024, S-22): a potential treatment for cachexia.

    Science.gov (United States)

    Srinath, Reshmi; Dobs, Adrian

    2014-02-01

    Muscle loss and wasting occurs with aging and in multiple disease states including cancer, heart failure, chronic obstructive pulmonary disease, end-stage liver disease, end-stage renal disease and HIV. Cachexia is defined as a multifactorial syndrome that is associated with anorexia, weight loss and increased catabolism, with increased morbidity and mortality. Currently no therapy is approved for the treatment or prevention of cachexia. Different treatment options have been suggested but many have proven to be ineffective or associated with adverse events. Nonsteroidal selective androgen receptor modulators (SARMs) are a new class of anabolic agents that bind the androgen receptor and exhibit tissue selectivity. Enobosarm (GTx-024, S-22) is a recently developed SARM, developed by GTx, Inc. (TN, USA), which has been tested in Phase I, II and III trials with promising results in terms of improving lean body mass and measurements of physical function and power. Enobosarm has received fast track designation by the US FDA and results from the Phase III trials POWER1 and POWER2 will help determine approval for use in the prevention and treatment of muscle wasting in patients with non-small-cell lung cancer. This article provides an introduction to enobosarm as a new therapeutic strategy for the prevention and treatment of cachexia. A review of the literature was performed using search terms 'cachexia', 'sarcopenia', 'SARM', 'enobosarm' and 'GTx-024' in September 2013 using multiple databases as well as online resources.

  4. VETERINARY PHARMACEUTICALS: POTENTIAL ENVIRONMENTAL IMPACT AND TREATMENT STRATEGIES

    Science.gov (United States)

    In the late 1970s it was recognized that there were increasing occurrences of antibiotic-resistant organisms in Europe and the US. Even in the early stages, concerns were raised that large-scale treatment of farm animals for infectious disease as well as growth enhancement may be...

  5. STUDSVIK's methods for treatment/free release of components and buildings structures from decommissioning of nuclear installations

    International Nuclear Information System (INIS)

    Krause, G.

    2005-01-01

    This paper will describe methods for treatment of retired, large, contaminated components from NPPs. The treatment includes transports, decontamination, segmentation, melting as well recycling of the metal in Sweden. Decontamination and free release of building strictures is also one of services which Studsvik provides for the nuclear industry. For this services different techniques are used for 'shaving' and subsequent measurements of the concrete surfaces. Since the mid of 1980-ies different procedures for decontamination and segmentation as well as pre- and post treatment have been developed and successively applied at Studsvik's melting facility in Sweden. The experience on this sector are permanent used for improvement and development of methods for treatment of both domestic and foreign large components like: heat exchangers, reactors vessel heads, turbine parts, steam generators and boilers. The high metal recycling rate is due to optimized production and results in extremely low percentage of secondary waste. The driving force is to maximize recycling rate of metal to the steel industry and to minimize the volume of the secondary waste and by that owner's costs for final storage in the national repositories. For decontamination of building structures several options are available using shaving or hammering tools to remove the contaminated concrete layers. This treatment is carried out in the closed circuit where removed dust is directly evacuated into the waste collection drums. During and after the decontamination process the treated and surrounding areas are free from dust and risk of cross contamination has been eliminated. The equipment capacity is up to 30 m2/h with simultaneous concrete removal of 3 mm at very high accuracy. It is not necessary of in-housing (tent, containment) of working area. The presentation will focus on methods, equipment used and experience in treatment of components and methods for decontamination of building structures

  6. Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

    Science.gov (United States)

    Sordillo, Peter P; Helson, Lawrence

    2015-01-01

    The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Cytokines and the anorexia of infection: potential mechanisms and treatments.

    Science.gov (United States)

    McCarthy, D O

    2000-04-01

    Anorexia during infection is thought to be mediated by immunoregulatory cytokines such as interleukins 1 and 6 and tumor necrosis factor. This article reviews the potential mechanisms of action by which these cytokines are thought to suppress food intake during infection and examines the proposition that blocking of cytokine activity might be one approach to improving food intake of the infected host.

  8. Approximate Treatment of the Dirac Equation with Hyperbolic Potential Function

    Science.gov (United States)

    Durmus, Aysen

    2018-03-01

    The time independent Dirac equation is solved analytically for equal scalar and vector hyperbolic potential function in the presence of Greene and Aldrich approximation scheme. The bound state energy equation and spinor wave functions expressed by the hypergeometric function have been obtained in detail with asymptotic iteration approach. In order to indicate the accuracy of this different approach proposed to solve second order linear differential equations, we present that in the non-relativistic limit, analytical solutions of the Dirac equation converge to those of the Schrödinger one. We introduce numerical results of the theoretical analysis for hyperbolic potential function. Bound states corresponding to arbitrary values of n and l are reported for potential parameters covering a wide range of interaction. Also, we investigate relativistic vibrational energy spectra of alkali metal diatomic molecules in the different electronic states. It is observed that theoretical vibrational energy values are consistent with experimental Rydberg-Klein-Rees (RKR) results and vibrational energies of NaK, K_2 and KRb diatomic molecules interacting with hyperbolic potential smoothly converge to the experimental dissociation limit D_e=2508cm^{-1}, 254cm^{-1} and 4221cm^{-1}, respectively.

  9. Potential applications of plasma science techniques for water treatment systems

    International Nuclear Information System (INIS)

    Pavlik, D.

    1994-01-01

    The historical evolution of water treatment techniques and their impact on man and his environment are presented. Ancient man recognized the relationship between good water and good health. However, it was not until the late 1800's that man's own contribution to the pollution of water via biological and chemical contamination of the water stream was recognized as having adverse affects on water quality. Since that time virtually every nation has adopted laws and regulations to ensure that safe sources of unpolluted water are available to its citizens. In the United States, water quality is governed by the Clean Water Act of 1972 administered at the federal level by the Environmental Protection Agency (EPA). Further, each state has established its equivalent agency which administers its own laws and regulations. Different biological and chemical biohazards present in the water system are discussed. Biological contaminants include various types of viruses, bacteria, fungii, molds, yeasts, algae, amoebas, and parasites. Chemical contaminates include elemental heavy metals and other organic and inorganic compounds which interfere with normal biological functions. Conventional water treatments for both consumption and sewage effluent commonly employ four different principals: mechanical filtration, quiescent gravity settling, biological oxidation, and chemical treatment. Although these techniques have greatly reduced the incidence of water-borne disease recent studies suggest that more effective means of eliminating biohazards are needed. Regulatory requirements for more aggressive treatment and elimination of residual contaminants present a significant opportunity for the application of various forms of electromagnetic radiation techniques. A comparison between conventional techniques and more advanced methods using various forms of electromagnetic radiation is discussed

  10. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Directory of Open Access Journals (Sweden)

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  11. Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629

    Directory of Open Access Journals (Sweden)

    Silva Federico A

    2006-05-01

    Full Text Available Abstract Background Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. Methods and design A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The

  12. Late effects of breast cancer treatment and potentials for rehabilitation

    Energy Technology Data Exchange (ETDEWEB)

    Ewertz, Marianne (Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark)); Bonde Jensen, Anders (Inst. of Clinical Research, Univ. of Southern Denmark (Denmark))

    2011-02-15

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  13. Retinal stem cells and potential cell transplantation treatments

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2014-11-01

    Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  14. Late effects of breast cancer treatment and potentials for rehabilitation

    International Nuclear Information System (INIS)

    Ewertz, Marianne; Bonde Jensen, Anders

    2011-01-01

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  15. Potential approaches to the treatment of Ewing's sarcoma.

    Science.gov (United States)

    Yu, Hongjiu; Ge, Yonggui; Guo, Lianying; Huang, Lin

    2017-01-17

    Ewing's sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise. There has also been increasing interest in the immune responses of ES patients. Immunotherapies using T cells, NK cells, cancer vaccines and monoclonal antibodies have been considered for ES, especially for recurrent patients. Because understanding the pathogenesis of ES is extremely important for the development of novel treatments, this review focuses on the mechanisms and functions of targeted therapies and immunotherapies in ES. It is anticipated that integrating the knowledge obtained from basic research and translational and clinical studies will lead to the development of novel therapeutic strategies for the treatment of ES.

  16. Event-related potentials reflect the efficacy of pharmaceutical treatments in children and adolescents with attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Ota, Toyosaku; Iida, Junzo; Nakanishi, Yoko; Matsuura, Hiroki; Uratani, Mitsuhiro; Okazaki, Kosuke; Kishimoto, Naoko; Tanaka, Shohei; Kishimoto, Toshifumi

    2016-08-30

    Few objective biological measures of pharmacological treatment efficacy exist for attention deficit/hyperactivity disorder (ADHD). Although we have previously demonstrated that event-related potentials (ERPs) reflect the effects of osmotic-release methylphenidate in treatment of naïve pediatric patients with ADHD, whether this is true for the therapeutic effects of atomoxetine (ATX) is unknown. Here, we used the Japanese version of the ADHD rating-scale IV to evaluate 14 patients with ADHD, and compared their ERP data with 14 age- and sex-matched controls. We measured P300 and mismatch negativity (MMN) components during an auditory oddball task before treatment (treatment naïve) and after 2 months of ATX treatment. Compared with controls, P300 components at baseline were attenuated and prolonged in the ADHD group at Fz (fronto-central), Cz (centro-parietal), Pz (parietal regions), C3 and C4 electrodes. ATX treatment reduced ADHD symptomology, and after 2 months of treatment, P300 latencies at Fz, Cz, Pz, C3, and C4 electrodes were significantly shorter than those at baseline. Moreover, MMN amplitudes at Cz and C3 electrodes were significantly greater than those at baseline. Thus, ERPs may be useful for evaluating the pharmacological effects of ATX in pediatric and adolescent patients with ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Potential sustainable slow release fertilizers obtained by mechanochemical activation of layered double hydroxides and K{sub 2}HPO{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Roger; Wypych, Fernando, E-mail: 1roger.borges@gmail.com [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil); Prevot, Vanessa; Forano, Claude [Universite Blaise Pascal, Clermont-Ferrand (France)

    2016-07-01

    Full text: This study describes the preliminary results on the development of potential sustainable slow-release fertilizer (SSRF), obtained by mechanochemical activation of mixtures of calcined layered double hydroxides (LDH) Mg{sub 2}Al-CO{sub 3} and Mg{sub 2}Fe-CO{sub 3} and K{sub 2}HPO{sub 4}. The effect of LDH temperature of calcination, milling time (using a high-energy balls mill) and LDH:K{sub 2}HPO{sub 4} molar were investigated. The samples were characterized by XRD and FTIR. Phosphate release essays shown that its solubility is reduced, while the solubility of amorphous structures from LDH can be increased, which characterize the expected slow release behavior of a SSRF. (author)

  18. CURCUMIN FOR ALZHEIMER’S DISEASE (AD) POTENTIAL TREATMENT

    OpenAIRE

    Sutiono, Dias Rima; Iasmartua, Steven

    2017-01-01

    Various studies had been conducted regarding the effect of curcumin on AD patients, thus, many of the studies had suggested that curcumin had the potential to prevent and treat AD through several molecular mechanisms including act as anti-inflammatory, anti-oxidant, binding the Aβ plaques, metal chelation, and lowering cholesterol level. One of the prominent characteristics of this neurodegenerative disease is shown by the presence of beta amyloids plaques (Aβ) and inflammation inside the pat...

  19. Enhancement of the sludge disintegration and nutrients release by a treatment with potassium ferrate combined with an ultrasonic process.

    Science.gov (United States)

    Li, Wei; Yu, Najiaowa; Liu, Qian; Li, Yiran; Ren, Nanqi; Xing, Defeng

    2018-09-01

    Sludge disintegration by ultrasound is a promising sludge treatment method. In order to enhance the efficiency of the sludge reduction and hydrolysis, potassium ferrate (K 2 FeO 4 ) (PF) was used. A novel method was developed to improve the sludge disintegration-sludge pretreatment by using PF in combination with an ultrasonic treatment (PF + ULT). After a short-term PF + ULT treatment, 17.23% of the volatile suspended solids (VSS) were reduced after a 900-min reaction time, which is 61.3% higher than the VSS reduction for the raw sludge. The supernatant soluble chemical oxygen demand (SCOD), total nitrogen (TN), volatile fatty acids (VFAs), soluble protein and polysaccharides increased by 522.5%, 1029.4%, 878.4%, 2996.6% and 801.9%, respectively. The constituent parts of the dissolved organic matter of the sludge products were released efficiently, which demonstrated the positive effect caused by the PF + ULT. The enhanced sludge disintegration process further alleviates environmental risk and offers a more efficient and convenient method for utilizing sludge. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsuno, Y.; Yamashita, Y.; Takahashi, M. [Dept. of Radiology, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Katabuchi, H.; Okamura, H. [Dept. of Gynecology and Obstetrics, Kumamoto Univ. School of Medicine, Kumamoto (Japan); Kitano, Y.; Shimamura, T. [Dept. of Gynecology and Obstetrics, Amakusa Chuou General Hospital, Hondo (Japan)

    1999-11-01

    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29{+-}0.11). The size ratio for the hypointense tumors was 0.82{+-}0.14, and 0.82{+-}0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  1. 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

  2. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

    Science.gov (United States)

    Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

    2013-12-01

    The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright

  3. Predicting the effect of gonadotropin-releasing hormone (GnRH) analogue treatment on uterine leiomyomas based on MR imaging

    International Nuclear Information System (INIS)

    Matsuno, Y.; Yamashita, Y.; Takahashi, M.; Katabuchi, H.; Okamura, H.; Kitano, Y.; Shimamura, T.

    1999-01-01

    Purpose: To test the hypothesis that the simple assessment of signal intensity on T2-weighted MR images is predictive of the effect of hormonal treatment with gonadotropin-releasing hormone (GnRH) analogue. Material and methods: The correlation between T2-weighted MR imaging of uterine leiomyomas and histologic findings was evaluated using 85 leiomyomas from 62 females who underwent myomectomy or hysterectomy. We also correlated the pretreatment MR images features obtained in 110 women with 143 leiomyomas with the effect of GnRH analogue treatment. The size (length x width x depth) of the leiomyoma was evaluated before and at 6 months after treatment by ultrasound. Results: The proportion of leiomyoma cell fascicles and that of extracellular matrix affected signal intensities of uterine leiomyomas on T2-weighted MR images. The amount of extracellular matrix was predominant in hypointense leiomyomas on T2-weighted images, while diffuse intermediate signal leiomyomas were predominantly composed of leiomyoma cell fascicles. Marked degenerative changes were noted in leiomyomas with heterogenous hyperintensity. The homogeneously intermediate signal intensity leiomyomas showed significant size reduction after treatment (size ratio; posttreatment volume/pretreatment volume 0.29±0.11). The size ratio for the hypointense tumors was 0.82±0.14, and 0.82±0.18 for the heterogeneously hyperintense tumors. There was a significant difference in the response to treatment between the homogeneously intermediate signal intensity leiomyomas and the hypointense or heterogeneously hyperintense leiomyomas (both p<0.01). Conclusion: Signal intensity on T2-weighted MR images depends on the amount of leiomyoma cell fascicles and extracellular matrix. Simple assessment of the MR signal intensity is useful in predicting the effect of GnRH analogue on uterine leiomyomas. (orig.)

  4. Reduced rates of controlled-release fertilizer lower potential nitrogen leaching from a Wisconsin bare-root tree nursery

    Science.gov (United States)

    Ryosuke Fujinuma; Nick J. Balster; Hyung-Kyung. Lee

    2011-01-01

    Controlled-release fertilizer (CRF) typically increases nitrogen (N) fertilizer uptake and lowers N lost from the rooting zone via leaching. However, questions remain as to whether lower rates of CRF could further increase this efficiency, especially in sandy bare-root nurseries in Wisconsin. We hypothesized that: 1) a reduced CRF application at 60 percent of the...

  5. Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

    Science.gov (United States)

    Steingold, K; De Ziegler, D; Cedars, M; Meldrum, D R; Lu, J K; Judd, H L; Chang, R J

    1987-10-01

    Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic Gn

  6. Well-Defined Poly(Ortho Ester Amides) for Potential Drug Carriers: Probing the Effect of Extra- and Intracellular Drug Release on Chemotherapeutic Efficacy.

    Science.gov (United States)

    Yan, Guoqing; Wang, Jun; Qin, Jiejie; Hu, Liefeng; Zhang, Panpan; Wang, Xin; Tang, Rupei

    2017-07-01

    To compare the chemotherapeutic efficacy determined by extra- and intracellular drug release strategies, poly(ortho ester amide)-based drug carriers (POEAd-C) with well-defined main-chain lengths, are successfully constructed by a facile method. POEAd-C3-doxorubicin (DOX) can be rapidly dissolved to release drug at tumoral extracellular pH (6.5-7.2), while POEAd-C6-DOX can rapidly release drug following gradual swelling at intracellular pH (5.0-6.0). In vitro cytotoxicity shows that POEAd-C3-DOX exhibits more toxic effect on tumor cells than POEAd-C6-DOX at extracellular pH, but POEAd-C6-DOX has stronger tumor penetration and inhibition in vitro and in vivo tumor models. So, POEAd-C6-DOX with the intracellular drug release strategy has stronger overall chemotherapeutic efficacy than POEAd-C3-DOX with extracellular drug release strategy. It is envisioned that these poly(ortho ester amides) can have great potential as drug carriers for efficient chemotherapy with further optimization. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Distribution-based estimates of minimum clinically important difference in cognition, arm function and lower body function after slow release-fampridine treatment of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, H B; Mamoei, Sepehr; Ravnborg, M.

    2016-01-01

    OBJECTIVE: To provide distribution-based estimates of the minimal clinical important difference (MCID) after slow release fampridine treatment on cognition and functional capacity in people with MS (PwMS). METHOD: MCID values were determined after SR-Fampridine treatment in 105 PwMS. Testing...

  8. Cannabidiol: a potential treatment for post Ebola syndrome?

    Science.gov (United States)

    Reznik, Sandra E; Gardner, Eliot L; Ashby, Charles R

    2016-11-01

    Patients recovered from Ebola virus infection may experience short- and long-term physical, neuropsychological and social sequelae, including arthralgia, musculoskeletal pain, ophthalmic inflammation, auditory problems, fatigue, confusion, insomnia, short-term memory impairment, anxiety, depression and anorexia, all lasting from two weeks to more than two years. Currently there are no treatments for post Ebola sequelae. We hypothesize that cannabidiol (CBD) may attenuate some of these post Ebola sequelae, several of which have been postulated to result from inflammation and/or an autoimmune response. CBD has anti-inflammatory actions in various animal models. Clinical studies have shown that oral administration of CBD, compared to placebo, significantly reduces anxiety, has antinociceptive and anticonvulsant actions, and may be therapeutic for insomnia. Overall, CBD has a number of pharmacological effects that may significantly improve the mental and somatic health of patients suffering from post Ebola sequelae. In humans, CBD, at therapeutic doses, does not: 1) elicit dependence or tolerance; 2) significantly alter heart rate or blood pressure; 3) affect gastrointestinal transit; 4) produce significant cognitive or psychomotor impairments. Mild sedation and nausea are the most commonly reported adverse effects associated with CBD.CBD, based on its pharmacological effects and favorable safety profile, should be considered as a treatment for individuals with post Ebola sequelae. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.

    Science.gov (United States)

    Riedlinger, Dorothee; Bahra, Marcus; Boas-Knoop, Sabine; Lippert, Steffen; Bradtmöller, Maren; Guse, Katrin; Seehofer, Daniel; Bova, Roberta; Sauer, Igor M; Neuhaus, Peter; Koch, Arend; Kamphues, Carsten

    2014-08-01

    Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells in vitro and in vivo. Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS-833923 was evaluated in vitro. In addition, the effect of BMS-833923, alone or in combination with gemcitabine, was analyzed in vivo in a murine subcutaneous xenograft model. Expression analysis revealed a significant activation of the Hh-signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a significant decrease in cell proliferation of CCC cells. Moreover, a distinct inhibition of tumor growth could be seen as a result of a combined therapy with BMS-833923 and gemcitabine in CCC xenografts. The results of our study suggest that the Hh pathway plays a relevant role at least in a subset of human CCC. Inhibition of this pathway may represent a possible treatment option for CCC patients in which the Hh pathway is activated. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  10. Blue-Print Autophagy: Potential for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Nadia Ruocco

    2016-07-01

    Full Text Available The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment.

  11. The results of surgical treatment of proximal long segment tracheal stenosis using bilateral hyoid bone cutting with suprahyoid release

    Directory of Open Access Journals (Sweden)

    khadivi E

    2009-10-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Post-intubation tracheal stenosis is a serious problem and surgical resection is the method of choice in long segment tracheal stenosis treatment. The aim of this study was to review the results of surgical treatment of long segment post intubation tracheal stenosis and the role of bilateral hyoid bone cutting in supra- hyoid release technique."n"nMethods: Between 2004 to 2008, 14 patients with proximal long segment tracheal stenosis with resection of more than 40% of trachea length were evaluated regarding surgical technique and post-operative results."n"nResults: The mean age of patients was 22.2±0.4 years. Etiology in all patients were head trauma and prolonged intubation and all patients had tracheostomy at the time of trearment. Average time between surgery and first admission was 4.5±0.5 months. Average length of stenosis and resected segment were 3.6±0.5 and 4.3±0.5cm respectively. Average increased length of trachea after bilateral hyoid bone cutting was 1.1±0.3cm. Postoperative complications occurred in one patient with wound infection, and 4 patients had stenosis recurrence which was treated in 3 patients using multiple dilation. Quality of life 2 years after surgery in 71% of patients were

  12. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  13. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Devi Mukkai Krishnamurty

    2009-07-01

    Full Text Available Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES are used in chronic pancreatitis (CP for correction of pancreatic exocrine insufficiency (PEI as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement

  14. Interferons and their potential in the treatment of ocular inflammation

    Directory of Open Access Journals (Sweden)

    Friederike Mackensen

    2009-10-01

    Full Text Available Friederike Mackensen,1 Regina Max,2 Matthias D Becker31Department of Ophthalmology, 2Department of Internal Medicine, Interdisciplinary Uveitis Center, University of Heidelberg, Germany; 3Department of Ophthalmology, Triemli Hospital Zürich, SwitzerlandAbstract: Since their discovery in the 1950s interferons have been the scope of investigation in many diseases as therapeutic as well as pathogenetic factors. We know they have immune stimulatory and immune regulatory effects. This apparently counter-intuitive mechanism can be summarized as immunomodulatory action and seems to be very effective in a number of ocular inflammatory diseases. We review the current knowledge of interferons in immunity and autoimmunity and show their use in clinical ophthalmologic practice.Keywords: interferon, uveitis, treatment, inflammation

  15. Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

    2016-03-15

    Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Arthroscopic release using F and C method versus conventional open release method in the treatment of gluteal muscle contracture: a comparative study.

    Science.gov (United States)

    Rai, Saroj; Jin, Shengyang; Meng, Chunqing; Chaudhary, Nabin; Tamang, Nira; Wang, Xiaohong; Liu, Xianzhe; Wang, Hong; Yang, Shuhua

    2017-03-16

    Gluteal muscle contracture (GMC), a debilitating disease, usually starts in early childhood after variable dose of injections around the buttock, if left untreated it worsens gradually and persists throughout the life. Because the disease mostly affects adolescents and adults, there is always an aesthetic concerns. Purposeof the study was to introduce the arthroscopic F and C method of GMC release, and to compare its clinical efficiency with conventional open surgery in terms of clinical outcome, rate of complications, patient's satisfactions, and recurrence. Between Jan 2013 and July 2015, 75 patients received an arthroscopic release with F and C release method and 71 patients received conventional open release of GMC. Primary surgeries in 16 years or older patients were included in the study. Two groups were compared clinically using Hip Outcome Scores - Activities of Daily Living Subscale (HOS-ADL), Hip Outcome Scores - Sports Subscale (HOS-Sports), Visual Analogue Scale (VAS), and Ye et al. evaluation criteria. No statistically significant differences were observed in Hip Outcome Scores - Activities of Daily Living Subscale (HOS-ADL) (P = 0.078), Hip Outcome Scores - Sports Subscale (HOS-Sports) (P = 0.340), and Visual Analogue Scale (VAS) (P = 0.524) between the two groups. 74 (98.7%) patients in the arthroscopic surgery group had good to excellent results, whereas 69 (97.1%) patients in the conventional open surgery group had good to excellent results (P = 0.727). No statistically significant difference was observed in recurrence rate (P = 0.612). Statistically significant differences were observed in incision length, use of post-operative analgesia, post-operative off-bed activity, and hospital stay. Complications were significantly higher in the conventional open surgery group (n = 21) than in the arthroscopic surgery group (n = 10) (P = 0.016). More importantly, cosmetic satisfaction was 100% in arthroscopic release group

  17. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems

    DEFF Research Database (Denmark)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil...... the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations...... with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate...

  18. Potential consequences in Norway after a hypothetical accident at Leningrad nuclear power plant. Potential release, fallout and predicted impacts on the environment

    International Nuclear Information System (INIS)

    Nalbandyan, A.; Ytre-Eide, M.A.; Thoerring, H.; Liland, A.; Bartnicki, J.; Balonov, M.

    2012-06-01

    The report describes different hypothetical accident scenarios at the Leningrad nuclear power plant for both RBMK and VVER-1200 reactors. The estimated release is combined with different meteorological scenarios to predict possible fallout of radioactive substances in Norway. For a hypothetical catastrophic accident at an RBMK reactor combined with a meteorological worst case scenario, the consequences in Norway could be considerable. Foodstuffs in many regions would be contaminated above the food intervention levels for radioactive cesium in Norway. (Author)

  19. Potential consequences in Norway after a hypothetical accident at Leningrad nuclear power plant. Potential release, fallout and predicted impacts on the environment

    Energy Technology Data Exchange (ETDEWEB)

    Nalbandyan, A.; Ytre-Eide, M.A.; Thoerring, H.; Liland, A.; Bartnicki, J.; Balonov, M.

    2012-06-15

    The report describes different hypothetical accident scenarios at the Leningrad nuclear power plant for both RBMK and VVER-1200 reactors. The estimated release is combined with different meteorological scenarios to predict possible fallout of radioactive substances in Norway. For a hypothetical catastrophic accident at an RBMK reactor combined with a meteorological worst case scenario, the consequences in Norway could be considerable. Foodstuffs in many regions would be contaminated above the food intervention levels for radioactive cesium in Norway. (Author)

  20. Illustrative assessment of human health issues arising from the potential release of chemotoxic substances from a generic geological disposal facility for radioactive waste.

    Science.gov (United States)

    Wilson, James C; Thorne, Michael C; Towler, George; Norris, Simon

    2011-12-01

    Many countries have a programme for developing an underground geological disposal facility for radioactive waste. A case study is provided herein on the illustrative assessment of human health issues arising from the potential release of chemotoxic and radioactive substances from a generic geological disposal facility (GDF) for radioactive waste. The illustrative assessment uses a source-pathway-receptor methodology and considers a number of human exposure pathways. Estimated exposures are compared with authoritative toxicological assessment criteria. The possibility of additive and synergistic effects resulting from exposures to mixtures of chemical contaminants or a combination of radiotoxic and chemotoxic substances is considered. The case study provides an illustration of how to assess human health issues arising from chemotoxic species released from a GDF for radioactive waste and highlights potential difficulties associated with a lack of data being available with which to assess synergistic effects. It also highlights how such difficulties can be addressed.

  1. Illustrative assessment of human health issues arising from the potential release of chemotoxic substances from a generic geological disposal facility for radioactive waste

    International Nuclear Information System (INIS)

    Wilson, James C; Towler, George; Thorne, Michael C; Norris, Simon

    2011-01-01

    Many countries have a programme for developing an underground geological disposal facility for radioactive waste. A case study is provided herein on the illustrative assessment of human health issues arising from the potential release of chemotoxic and radioactive substances from a generic geological disposal facility (GDF) for radioactive waste. The illustrative assessment uses a source–pathway–receptor methodology and considers a number of human exposure pathways. Estimated exposures are compared with authoritative toxicological assessment criteria. The possibility of additive and synergistic effects resulting from exposures to mixtures of chemical contaminants or a combination of radiotoxic and chemotoxic substances is considered. The case study provides an illustration of how to assess human health issues arising from chemotoxic species released from a GDF for radioactive waste and highlights potential difficulties associated with a lack of data being available with which to assess synergistic effects. It also highlights how such difficulties can be addressed.

  2. Epigenetic Modifications and Potential New Treatment Targets in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Lorena Perrone

    2014-01-01

    Full Text Available Retinopathy is a debilitating vascular complication of diabetes. As with other diabetic complications, diabetic retinopathy (DR is characterized by the metabolic memory, which has been observed both in DR patients and in DR animal models. Evidences have provided that after a period of poor glucose control insulin or diabetes drug treatment fails to prevent the development and progression of DR even when good glycemic control is reinstituted (glucose normalization, suggesting a metabolic memory phenomenon. Recent studies also underline the role of epigenetic chromatin modifications as mediators of the metabolic memory. Indeed, epigenetic changes may lead to stable modification of gene expression, participating in DR pathogenesis. Moreover, increasing evidences suggest that environmental factors such as chronic hyperglycemia are implicated DR progression and may also affect the epigenetic state. Here we review recent findings demonstrating the key role of epigenetics in the progression of DR. Further elucidation of epigenetic mechanisms, acting both at the cis- and trans-chromatin structural elements, will yield new insights into the pathogenesis of DR and will open the way for the discovery of novel therapeutic targets to prevent DR progression.

  3. Potential of resveratrol in the treatment of heart failure.

    Science.gov (United States)

    Raj, Pema; Louis, Xavier Lieben; Thandapilly, Sijo Joseph; Movahed, Ali; Zieroth, Shelley; Netticadan, Thomas

    2014-01-30

    The concept of food has expanded beyond its traditional role of survival and hunger satisfaction, to include a role in the prevention and treatment of disease. Polyphenols are classes of compounds that are synthesized by plants to serve a wide variety of functions including growth pollination and defense. These compounds have recently received increased attention in medical research. In this group, one of the most studied has been resveratrol (3,5,4,-trihydroxystilbene), a polyphenol, which is found predominantly in grapes and berries. Over the past two decades, researchers have studied the ability of resveratrol to prevent or reverse the development of abnormalities in heart structure and function in animal models of heart disease and heart failure. The results from animal studies have been promising, and very recently, this knowledge has been translated into examining the efficacy of resveratrol in humans with heart disease/failure. In this review we will discuss the current status of resveratrol research on cardioprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Neem components as potential agents for cancer prevention and treatment

    Science.gov (United States)

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2016-01-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  5. Emerging potential treatments: new hope for idiopathic pulmonary fibrosis patients?

    Directory of Open Access Journals (Sweden)

    U. Costabel

    2011-09-01

    Full Text Available Currently, there are no approved pharmacological treatments for the management of patients with idiopathic pulmonary fibrosis (IPF in the USA or Europe. Pirfenidone is an orally bio-available small molecule that exhibits antifibrotic and anti-inflammatory properties in a variety of in vitro and animal models. Pirfenidone has been evaluated in four randomised, double-blind, placebo-controlled clinical trials conducted in Japan, North America and Europe. The totality of the data from these trials indicates that pirfenidone is able to reduce the rate of decline in lung function, measured as change in per cent predicted forced vital capacity (FVC or vital capacity. There was also an effect on secondary end-points of progression free survival, categorical change in per cent predicted FVC, and the 6-min walk test. A recent meta-analysis of the three phase III studies in IPF demonstrated that pirfenidone significantly reduced the risk of disease progression by 30%. The efficacy of pirfenidone is associated with an acceptable tolerability and safety profile.

  6. New Insight into Polydopamine@ZIF-8 Nanohybrids: A Zinc-Releasing Container for Potential Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Jingyu Ran

    2018-04-01

    Full Text Available Despite the initial evidence on the role of zinc and zinc transporters in cancer prevention, little attention has been paid to the zinc-derived compounds. In the present work, we reported a strategy to prepare a kind of zinc-releasing container with enhanced biocompatibility and release dynamics using ZIF-8 nanocrystals as the sacrificial templates. Transmission electron microscopy (TEM analysis demonstrated that the ZIF-8 nanocrystals were gradually etched out in the aqueous media within 48 h, resulting in hollow nanocapsules. Notably, we found the self-polymerization of dopamine can form nanoshells around the ZIF-8 nanocrystals, which served as a type of functional membranes during the release of zinc. More interestingly, PDA@ZIF-8–based nanohybrids expressed stronger inhibition to the cancer cell growth, which implied that the nanohybrids could be a drug carrier for chemotherapy. This study broadens the biomedical application of ZIF-8 and also provides a versatile strategy toward the development of multifunctional delivery system.

  7. The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

    Science.gov (United States)

    Achilla, Evanthia; McCrone, Paul

    2013-04-01

    Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long

  8. Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956)- An Assessment of Quantities released, Off-Site Radiation Doses, and Potential Excess Risks of Thyroid Cancer, Volume 1

    International Nuclear Information System (INIS)

    Apostoaei, A.I.; Burns, R.E.; Hoffman, F.O.; Ijaz, T.; Lewis, C.J.; Nair, S.K.; Widner, T.E.

    1999-01-01

    In the early 1990s, concern about the Oak Ridge Reservation's past releases of contaminants to the environment prompted Tennessee's public health officials to pursue an in-depth study of potential off-site health effects at Oak Ridge. This study, the Oak Ridge dose reconstruction, was supported by an agreement between the U.S. Department of Energy (DOE) and the State of Tennessee, and was overseen by a 12-member panel appointed by Tennessee's Commissioner of Health. One of the major contaminants studied in the dose reconstruction was radioactive iodine, which was released to the air by X-10 (now called Oak Ridge National Laboratory) as it processed spent nuclear reactor fuel from 1944 through 1956. The process recovered radioactive lanthanum for use in weapons development. Iodine concentrates in the thyroid gland so health concerns include various diseases of the thyroid, such as thyroid cancer. The large report, ''Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956) - An Assessment of Quantities Released, Off-site Radiation Doses, and Potential Excess Risks of Thyroid Cancer,'' is in two volumes. Volume 1 is the main body of the report, and Volume 1A, which has the same title, consists of 22 supporting appendices. Together, these reports serve the following purposes: (1) describe the methodologies used to estimate the amount of iodine-131 (I-131) released; (2) evaluate I-131's pathway from air to vegetation to food to humans; (3) estimate doses received by human thyroids; (4) estimate excess risk of acquiring a thyroid cancer during ones lifetime; and (5) provide equations, examples of historical documents used, and tables of calculated values. Results indicate that females born in 1952 who consumed milk from a goat pastured a few miles east of X-10 received the highest doses from I-131 and would have had the highest risks of contracting thyroid cancer. Doses from cow's milk are considerably less . Detailed

  9. Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956)- An Assessment of Quantities released, Off-Site Radiation Doses, and Potential Excess Risks of Thyroid Cancer, Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Apostoaei, A.I.; Burns, R.E.; Hoffman, F.O.; Ijaz, T.; Lewis, C.J.; Nair, S.K.; Widner, T.E.

    1999-07-01

    In the early 1990s, concern about the Oak Ridge Reservation's past releases of contaminants to the environment prompted Tennessee's public health officials to pursue an in-depth study of potential off-site health effects at Oak Ridge. This study, the Oak Ridge dose reconstruction, was supported by an agreement between the U.S. Department of Energy (DOE) and the State of Tennessee, and was overseen by a 12-member panel appointed by Tennessee's Commissioner of Health. One of the major contaminants studied in the dose reconstruction was radioactive iodine, which was released to the air by X-10 (now called Oak Ridge National Laboratory) as it processed spent nuclear reactor fuel from 1944 through 1956. The process recovered radioactive lanthanum for use in weapons development. Iodine concentrates in the thyroid gland so health concerns include various diseases of the thyroid, such as thyroid cancer. The large report, ''Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956) - An Assessment of Quantities Released, Off-site Radiation Doses, and Potential Excess Risks of Thyroid Cancer,'' is in two volumes. Volume 1 is the main body of the report, and Volume 1A, which has the same title, consists of 22 supporting appendices. Together, these reports serve the following purposes: (1) describe the methodologies used to estimate the amount of iodine-131 (I-131) released; (2) evaluate I-131's pathway from air to vegetation to food to humans; (3) estimate doses received by human thyroids; (4) estimate excess risk of acquiring a thyroid cancer during ones lifetime; and (5) provide equations, examples of historical documents used, and tables of calculated values. Results indicate that females born in 1952 who consumed milk from a goat pastured a few miles east of X-10 received the highest doses from I-131 and would have had the highest risks of contracting thyroid cancer. Doses from cow

  10. The role of interferon gamma release assays in the monitoring of response to anti-tuberculosis treatment in children.

    Science.gov (United States)

    Shaik, Junaid; Pillay, Manormoney; Jeena, Prakash

    2014-09-01

    Successful control of childhood TB requires early diagnosis, effective chemotherapy and a method of evaluating the response to therapy. Identification of suitable biomarkers that predict the response to anti-TB therapy may allow the duration of treatment to be shortened. The majority of biomarker studies in paediatric TB have focused on the role of T cell-based interferon-gamma (IFN-γ) release assays (IGRAs) in the diagnosis of either latent or active disease. Little has been published on the role of IGRAs in the monitoring response to therapy in children. We reviewed the available literature to ascertain the value of IGRAs in the monitoring of response to anti-TB therapy in children. We explored the results of the few studies that have investigated the role of IGRAs as markers of response to anti-TB treatment in children. We conclude that the role of IGRAs as surrogate markers appears promising. Robust clinical trials are, however, needed to entrench the value of IGRAs as surrogate biomarkers of response to anti-TB therapy in children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    Science.gov (United States)

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  12. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

    Science.gov (United States)

    Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

    2013-11-01

    Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Microcapsular imaging of malignant tumors and radiation induced release of liquid-core microcapsules for their treatment

    International Nuclear Information System (INIS)

    Harada, S.; Ehara, S.; Ishii, K.; Sato, T.; Enatsu, M.; Kamiya, T.; Sera, K.; Goto, S.

    2013-01-01

    accumulation could be detected by CT. These accumulated microcapsules released P-selectin and PSGL-1 in response to the first irradiation. P-selectin, which was released from the microcapsules and whose expression was induced by the first irradiation, showed peak expression 6 h after irradiation: it was 78.2 ± 3.4% with the 1O-Gy radiation dose and 86.3 ± 4.6% with the 20-Gy radiation dose. The microcapsules for radiosensitizing the metastasis were injected 5 h after the first session. Their accumulation was maximum at 3 h after the injection. After the second session, the microcapsules released carboplatin, which increased significant regression of tumors. Thus, better diagnosis and treatment of incipient metastasis are possible with our microcapsules. [1] S. Harada, S. Ehara, K.lshii, el.al. Inl. J. Radial. Oncol. Biol. Phys. 75 (2) (2009) 455-462. (author)

  14. Microcapsular imaging of malignant tumors and radiation induced release of liquid-core microcapsules for their treatment

    Energy Technology Data Exchange (ETDEWEB)

    Harada, S.; Ehara, S. [Department of Radiology, School of Medicine, Iwate Medical University, Iwate (Japan); Ishii, K. [Department of Quantum Science and Energy Engineering, School of Engineering, Tohoku University, Miyagi (Japan); Sato, T.; Enatsu, M.; Kamiya, T. [Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, Gunma (Japan); Sera, K. [Cyclotron Center, Iwate Medical University, Iwate (Japan); Goto, S. [Nishina Memorial Cyclotron Center (NMCC), Japan Radioisotope Association, Iwate (Japan)

    2013-07-01

    metastasis, and their kinetics and accumulation could be detected by CT. These accumulated microcapsules released P-selectin and PSGL-1 in response to the first irradiation. P-selectin, which was released from the microcapsules and whose expression was induced by the first irradiation, showed peak expression 6 h after irradiation: it was 78.2 ± 3.4% with the 1O-Gy radiation dose and 86.3 ± 4.6% with the 20-Gy radiation dose. The microcapsules for radiosensitizing the metastasis were injected 5 h after the first session. Their accumulation was maximum at 3 h after the injection. After the second session, the microcapsules released carboplatin, which increased significant regression of tumors. Thus, better diagnosis and treatment of incipient metastasis are possible with our microcapsules. [1] S. Harada, S. Ehara, K.lshii, el.al. Inl. J. Radial. Oncol. Biol. Phys. 75 (2) (2009) 455-462. (author)

  15. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments

    Science.gov (United States)

    Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

    2016-01-01

    Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an “ageist” approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons. PMID:26828516

  16. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments.

    Science.gov (United States)

    Landi, Francesco; Calvani, Riccardo; Tosato, Matteo; Martone, Anna Maria; Ortolani, Elena; Savera, Giulia; Sisto, Alex; Marzetti, Emanuele

    2016-01-27

    Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an "ageist" approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

  17. Anorexia of Aging: Risk Factors, Consequences, and Potential Treatments

    Directory of Open Access Journals (Sweden)

    Francesco Landi

    2016-01-01

    Full Text Available Older people frequently fail to ingest adequate amount of food to meet their essential energy and nutrient requirements. Anorexia of aging, defined by decrease in appetite and/or food intake in old age, is a major contributing factor to under-nutrition and adverse health outcomes in the geriatric population. This disorder is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of aging, advancing age often promotes its development through various mechanisms. Age-related changes in life-style, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviors and nutritional status. In spite of their importance, problems related to food intake and, more generally, nutritional status are seldom attended to in clinical practice. While this may be the result of an “ageist” approach, it should be acknowledged that simple interventions, such as oral nutritional supplementation or modified diets, could meaningfully improve the health status and quality of life of older persons.

  18. Aβ-degrading enzymes: potential for treatment of Alzheimer disease.

    Science.gov (United States)

    Miners, James Scott; Barua, Neil; Kehoe, Patrick Gavin; Gill, Steven; Love, Seth

    2011-11-01

    There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), insulin-degrading enzyme, and endothelin-converting enzyme reduce Aβ levels and protect against cognitive impairment in mouse models of AD. The activity of several Aβ-degrading enzymes rises with age and increases still further in AD, perhaps as a physiological response to minimize the buildup of Aβ. The age- and disease-related changes in expression of more recently recognized Aβ-degrading enzymes (e.g. NEP-2 and cathepsin B) remain to be investigated, and there is strong evidence that reduced NEP activity contributes to the development of cerebral amyloid angiopathy. Regardless of the role of Aβ-degrading enzymes in the development of AD, experimental data indicate that increasing the activity of these enzymes (NEP in particular) has therapeutic potential in AD, although targeting their delivery to the brain remains a major challenge. The most promising current approaches include the peripheral administration of agents that enhance the activity of Aβ-degrading enzymes and the direct intracerebral delivery of NEP by convection-enhanced delivery. In the longer term, genetic approaches to increasing the intracerebral expression of NEP or other Aβ-degrading enzymes may offer advantages.

  19. Efficacy of Guanfacine Extended Release in the Treatment of Combined and Inattentive Only Subtypes of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Kollins, Scott H.; Wigal, Timothy L.

    2012-01-01

    Abstract Background Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6–17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. Method Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. Results The full analysis set included 631 subjects aged 6–17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). Conclusions The results support the use of GXR in the treatment of core ADHD symptoms

  20. Influence of Nitinol wire surface treatment on oxide thickness and composition and its subsequent effect on corrosion resistance and nickel ion release.

    Science.gov (United States)

    Clarke, B; Carroll, W; Rochev, Y; Hynes, M; Bradley, D; Plumley, D

    2006-10-01

    Medical implants and devices are now used successfully in surgical procedures on a daily basis. Alloys of nickel and titanium, and in particular Nitinol are of special interest in the medical device industry, because of their shape memory and superelastic properties. The corrosion behavior of nitinol in the body is also of critical importance because of the known toxicological effects of nickel. The stability of a NiTi alloy in the physiological environment is dependant primarily on the properties of the mostly TiO(2) oxide layer that is present on the surface. For the present study, a range of nitinol wires have been prepared using different drawing processes and a range of surface preparation procedures. It is clear from the results obtained that the wire samples with very thick oxides also contain a high nickel content in the oxide layer. The untreated samples with the thicker oxides show the lowest pitting potential values and greater nickel release in both long and short-term experiments. It was also found that after long-term immersion tests breakdown potentials increased for samples that exhibited lower values initially. From these results it would appear that surface treatment is essential for the optimum bioperformance of nitinol. (c) 2006 Wiley Periodicals, Inc

  1. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder.

    Science.gov (United States)

    Westenberg, Herman G M; Stein, Dan J; Yang, Haichen; Li, David; Barbato, Luigi M

    2004-02-01

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.

  2. Patient release criteria following radioactive iodine-131 treatment in the light of international practice: where does South Africa fit in?

    Science.gov (United States)

    Mongane, Modisenyane S; Rae, William I D

    2017-10-01

    The release from hospital of patients treated with radioactive iodine-131 (I) remains a controversial issue as a result of the range of guidelines implemented by national regulatory bodies responsible for radiation protection in various countries worldwide. The aim of this study was to review and analyse the literature on patient release criteria (PRC) applied internationally in an attempt to achieve a justifiable approach to setting equivalent criteria in South Africa. In 2016, the South African Department of Health, Directorate: Radiation Control added conditions (numbers 50 and 90), to licences to use radioactive nuclides. These conditions state that patients must be hospitalized when the dose rate at 1 m is above 25 μSv/h, or more than 555 MBq of iodine-131 was administered to the patient. However, these criteria do not consider patients' socioeconomic conditions. A literature survey was carried out of articles detailing PRC from high-income countries as well as those in the middle-income and lower-income groups. Socioeconomic conditions within countries were determined using the International Monetary Fund lists of gross domestic product. The results from the literature have shown that in setting PRC, several countries have considered the socioeconomic conditions prevailing in their countries to achieve harmony between public protection and cost associated with hospitalization. The South African authority conditions must be seen in the context of the approach followed by other countries. Considering the international context, a justifiable, and potentially implementable, guideline or policy for improving individualized and more caring patient management is advocated.

  3. Shortened first-line TB treatment in Brazil: potential cost savings for patients and health services

    NARCIS (Netherlands)

    Trajman, Anete; Bastos, Mayara Lisboa; Belo, Marcia; Calaça, Janaína; Gaspar, Júlia; Dos Santos, Alexandre Martins; Dos Santos, Camila Martins; Brito, Raquel Trindade; Wells, William A.; Cobelens, Frank G.; Vassall, Anna; Gomez, Gabriela B.

    2016-01-01

    Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs. We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment. Data were gathered in

  4. Greenhouse gas emissions and reactive nitrogen releases during the life-cycles of staple food production in China and their mitigation potential

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Longlong [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Ti, Chaopu [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Li, Bolun [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xia, Yongqiu [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Yan, Xiaoyuan, E-mail: yanxy@issas.ac.cn [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China)

    2016-06-15

    Life-cycle analysis of staple food (rice, flour and corn-based fodder) production and assessments of the associated greenhouse gas (GHG) and reactive nitrogen (Nr) releases, from environmental and economic perspectives, help to develop effective mitigation options. However, such evaluations have rarely been executed in China. We evaluated the GHG and Nr releases per kilogram of staple food production (carbon and Nr footprints) and per unit of net economic benefit (CO{sub 2-NEB} and Nr{sub -NEB}), and explored their mitigation potential. Carbon footprints of food production in China were obviously higher than those in some developed countries. There was a high spatial variation in the footprints, primarily attributable to differences in synthetic N use (or CH{sub 4} emissions) per unit of food production. Provincial carbon footprints had a significant linear relationship with Nr footprints, attributed to large contribution of N fertilizer use to both GHG and Nr releases. Synthetic N fertilizer applications and CH{sub 4} emissions dominated the carbon footprints, while NH{sub 3} volatilization and N leaching were the main contributors to the Nr footprints. About 564 (95% uncertainty range: 404–701) Tg CO{sub 2} eq GHG and 10 (7.4–12.4) Tg Nr-N were released every year during 2001–2010 from staple food production. This caused the total damage costs of 325 (70–555) billion ¥, equivalent to nearly 1.44% of the Gross Domestic Product of China. Moreover, the combined damage costs and economic input costs, accounted for 66%-80% of the gross economic benefit generated from food production. A reduction of 92.7 Tg CO{sub 2} eq yr{sup −1} and 2.2 Tg Nr-N yr{sup −1} could be achieved by reducing synthetic N inputs by 20%, increasing grain yields by 5% and implementing off-season application of straw and mid-season drainage practices for rice cultivation. In order to realize these scenarios, an ecological compensation scheme should be established to incentivize

  5. Greenhouse gas emissions and reactive nitrogen releases during the life-cycles of staple food production in China and their mitigation potential

    International Nuclear Information System (INIS)

    Xia, Longlong; Ti, Chaopu; Li, Bolun; Xia, Yongqiu; Yan, Xiaoyuan

    2016-01-01

    Life-cycle analysis of staple food (rice, flour and corn-based fodder) production and assessments of the associated greenhouse gas (GHG) and reactive nitrogen (Nr) releases, from environmental and economic perspectives, help to develop effective mitigation options. However, such evaluations have rarely been executed in China. We evaluated the GHG and Nr releases per kilogram of staple food production (carbon and Nr footprints) and per unit of net economic benefit (CO 2-NEB and Nr -NEB ), and explored their mitigation potential. Carbon footprints of food production in China were obviously higher than those in some developed countries. There was a high spatial variation in the footprints, primarily attributable to differences in synthetic N use (or CH 4 emissions) per unit of food production. Provincial carbon footprints had a significant linear relationship with Nr footprints, attributed to large contribution of N fertilizer use to both GHG and Nr releases. Synthetic N fertilizer applications and CH 4 emissions dominated the carbon footprints, while NH 3 volatilization and N leaching were the main contributors to the Nr footprints. About 564 (95% uncertainty range: 404–701) Tg CO 2 eq GHG and 10 (7.4–12.4) Tg Nr-N were released every year during 2001–2010 from staple food production. This caused the total damage costs of 325 (70–555) billion ¥, equivalent to nearly 1.44% of the Gross Domestic Product of China. Moreover, the combined damage costs and economic input costs, accounted for 66%-80% of the gross economic benefit generated from food production. A reduction of 92.7 Tg CO 2 eq yr −1 and 2.2 Tg Nr-N yr −1 could be achieved by reducing synthetic N inputs by 20%, increasing grain yields by 5% and implementing off-season application of straw and mid-season drainage practices for rice cultivation. In order to realize these scenarios, an ecological compensation scheme should be established to incentivize farmers to gradually adopt knowledge

  6. AXAIR: A Computer Code for SAR Assessment of Plume-Exposure Doses from Potential Process-Accident Releases to Atmosphere

    Energy Technology Data Exchange (ETDEWEB)

    Pillinger, W.L.

    2001-05-17

    This report describes the AXAIR computer code which is available to terminal users for evaluating the doses to man from exposure to the atmospheric plume from postulated stack or building-vent releases at the Savannah River Plant. The emphasis herein is on documentation of the methodology only. The total-body doses evaluated are those that would be exceeded only 0.5 percent of the time based on worst-sector, worst-case meteorological probability analysis. The associated doses to other body organs are given in the dose breakdowns by radionuclide, body organ and pathway.

  7. Corticotropin-releasing hormone expression in patients with intrahepatic cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial experience.

    Science.gov (United States)

    Zhou, Fan; Zhang, Li; He, Mao Mao; Liu, Zheng Fei; Gao, Bing Xin; Wang, Xiao Dong

    2014-08-01

    Corticotropin-releasing hormone (CRH) is one of the most potent vasodilatory factors in the human feto-placental circulation. The expression of CRH was significantly down-regulated in patients with intrahepatic cholestasis of pregnancy (ICP). One hundred pregnant women diagnosed with ICP at 34-34(+6) weeks of gestation agreed to participate in this prospective nested case-control study. Thirty ICP patients were finally recruited in this study, with 16 cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum samples were obtained in diagnosis and at 37-37(+6) weeks of gestation. Placental tissues were obtained from participants after delivery. ELISA, enzymatic colorimetric and Western blotting were used to evaluate the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and CRH in maternal serum and expression of CRH in placenta tissues. The UDCA group had greater reduction in maternal serum ALT, AST and TBA levels in ICP patients (all p < 0.01). Maternal serum CRH concentrations in the UDCA group after treatment (122.10 ± 44.20) pg/ml was significantly higher than pretreatment (95.45 ± 26.47) pg/ml (p < 0.01). After treatment, maternal serum CRH concentrations of the UDCA group (122.10 ± 44.20) pg/ml was significantly higher than in the control group (80.71 ± 41.10) pg/ml (p < 0.01). Placental CRH expression in the UDCA group (2.79 ± 1.72) was significantly higher than in the control group (0.69 ± 0.36) (p < 0.01). Maternal serum and placental CRH expression in ICP patients were up-regulated after treatment of UDCA. The up-regulation of CRH expression after UDCA treatment may play an important role in the therapeutic mechanism of ICP. All patients recruited in this study had severe cholestasis (TBA ≥ 40 µmol/L). Further studies are warranted in

  8. Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment

    Directory of Open Access Journals (Sweden)

    Huss M

    2016-05-01

    Full Text Available Michael Huss,1 Vanja Sikirica,2 Amaia Hervas,3,4 Jeffrey H Newcorn,5 Valerie Harpin,6 Brigitte Robertson71Child and Adolescent Psychiatry, Johannes Gutenberg University Mainz, Mainz, Germany; 2Global Health Economics, Outcomes Research and Epidemiology, Shire, Wayne, PA, USA; 3Child and Adolescent Mental Health Unit, University Hospital Mútua de Terressa, Barcelona, Spain; 4Developmental Disorders Unit (UETD, Hospital San Juan de Dios, Barcelona, Spain; 5Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6Ryegate Children’s Centre, Sheffield Children’s NHS Foundation Trust, Sheffield, UK; 7Global Clinical Development, Shire, Wayne, PA, USAAbstract: Guanfacine extended release (GXR and atomoxetine (ATX are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD. As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT, in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS. Participants were 6–17 years old with ADHD Rating Scale version IV (ADHD-RS-IV scores ≥32 and Clinical Global Impressions – Severity scores ≥4. RCT participants received dose-optimized GXR (1–7 mg/day, ATX (10–100 mg/day, or placebo for 10–13 weeks. RWS participants received dose-optimized GXR (1–7 mg/day for 13 weeks. Participants’ last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH; due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most

  9. Alterations in Ca2+-dependent and Ca2+-independent release of catecholamines in preparations of rat brain produced by ethanol treatment in vivo

    International Nuclear Information System (INIS)

    Lynch, M.A.; Pagonis, C.; Samuel, D.; Littleton, J.M.

    1985-01-01

    Compared to preparations from control animals, superfused striatal slice preparations from brains of rats treated chronically with ethanol released a significantly greater fraction of stored [ 3 H] dopamine on depolarisation in 40 mM K + . Similarly, the electrically-evoked release of [ 3 H]-norepinephrine from cortical slices and of [ 3 H]-dopamine from striatal slices is also increased, although with this mechanism of depolarisation the change is significant only in the case of [ 3 H] norepinephrine release. In contrast to this tendency to enhancement of Ca 2+ -dependent depolarisation-induced release, a reduced fraction of stored [ 3 H]-catecholamines was released from these preparations by the indirect sympathomimetics tyramine and (+)-amphetamine. The catecholamine release induced by these indirect sympathomimetics is largely independent of external Ca 2+ and the results are interpreted as suggesting that chronic alcohol treatment changes the distribution of catecholamine neurotransmitters between storage pools in the nerve terminal which do or do not require Ca 2+ entry for release

  10. [Effectiveness of aftercare treatment after release from prison: A first evaluation of the forensic therapeutic outpatient clinic for serious violent and sexual offenders in Berlin].

    Science.gov (United States)

    Sauter, J; Voss, T; Dahle, K-P

    2015-05-01

    The Forensic Therapeutic Outpatient Clinic (FTA) in Berlin targets the professional aftercare treatment of classified high-risk violent and sexual offenders released from prison or forensic psychiatric hospitals. A comparison sample (n = 32) matched to the patients of the FTA (complete survey n = 32) according to similar criminal histories and diagnoses (ICD-10) was collected from offenders released from prison and forensic psychiatry at a time before the FTA was established. The focus of the study was on recidivism measured by complaints received by police departments during the follow-up period. Sexual recidivism occurred significantly later in the case of released offenders with aftercare treatment compared to those without. Moreover, for the duration of aftercare treatment the general risk of recidivism was approximately 85 % lower; however, after termination of treatment the recidivism rates of both samples converged to almost the same level. Individually adapted measures should be maintained after finishing aftercare treatment; however, because prisoners released from prison are frequently less prepared than patients from forensic psychiatric hospitals, the therapeutic work often reaches its limits in these cases. Therefore, social work should be taken into account right from the start.

  11. Potential for leaching of arsenic from excavated rock after different drying treatments.

    Science.gov (United States)

    Li, Jining; Kosugi, Tomoya; Riya, Shohei; Hashimoto, Yohey; Hou, Hong; Terada, Akihiko; Hosomi, Masaaki

    2016-07-01

    Leaching of arsenic (As) from excavated rock subjected to different drying methods is compared using sequential leaching tests and rapid small-scale column tests combined with a sequential extraction procedure. Although the total As content in the rock was low (8.81 mg kg(-1)), its resulting concentration in the leachate when leached at a liquid-to-solid ratio of 10 L kg(-1) exceeded the environmental standard (10 μg L(-1)). As existed mainly in dissolved forms in the leachates. All of the drying procedures applied in this study increased the leaching of As, with freeze-drying leading to the largest increase. Water extraction of As using the two tests showed different leaching behaviors as a function of the liquid-to-solid ratio, and achieved average extractions of up to 35.7% and 25.8% total As, respectively. Dissolution of As from the mineral surfaces and subsequent re-adsorption controlled the short-term release of As; dissolution of Fe, Al, and dissolved organic carbon played important roles in long-term As leaching. Results of the sequential extraction procedure showed that use of 0.05 M (NH4)2SO4 underestimates the readily soluble As. Long-term water extraction removed almost all of the non-specifically sorbed As and most of the specifically sorbed As. The concept of pollution potential indices, which are easily determined by the sequential leaching test, is proposed in this study and is considered for possible use in assessing efficacy of treatment of excavated rocks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II-releasing polymer nanoparticles for potential use as a drug delivery vector

    Directory of Open Access Journals (Sweden)

    Harris Alesha

    2011-01-01

    Full Text Available Abstract The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu2+, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu2+ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.% and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.

  13. Anaerobic fermentation combined with low-temperature thermal pretreatment for phosphorus-accumulating granular sludge: Release of carbon source and phosphorus as well as hydrogen production potential.

    Science.gov (United States)

    Zou, Jinte; Li, Yongmei

    2016-10-01

    Releases of organic compounds and phosphorus from phosphorus-accumulating granular sludge (PGS) and phosphorus-accumulating flocculent sludge (PFS) during low-temperature thermal pretreatment and anaerobic fermentation were investigated. Meanwhile, biogas production potential and microbial community structures were explored. The results indicate that much more soluble chemical oxygen demand (SCOD) and phosphorus were released from PGS than from PFS via low-temperature thermal pretreatment because of the higher extracellular polymeric substances (EPS) content in PGS and higher ratio of phosphorus reserved in EPS. Furthermore, PGS contains more anaerobes and dead cells, resulting in much higher SCOD and volatile fatty acids release from PGS than those from PFS during fermentation. PGS fermentation facilitated the n-butyric acid production, and PGS exhibited the hydrogen production potential during fermentation due to the presence of hydrogen-producing bacteria. Therefore, anaerobic fermentation combined with low-temperature thermal pretreatment can facilitate the recovery of carbon and phosphorus as well as producing hydrogen from PGS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Terrestrial sedimentary pyrites as a potential source of trace metal release to groundwater – A case study from the Emsland, Germany

    International Nuclear Information System (INIS)

    Houben, Georg J.; Sitnikova, Maria A.; Post, Vincent E.A.

    2017-01-01

    Pyrite is a common minor constituent of terrestrial freshwater sediments and a sink for trace elements. Different amounts and morphological types (framboids and euhedral crystals) of sedimentary pyrites were found in the heavy mineral fraction of cores obtained from several drillholes located in the Emsland region, NW Germany. Their trace element contents were investigated to assess their potential for groundwater contamination after oxidation, e.g. induced by dewatering or autotrophic denitrification. Nickel, arsenic and cadmium were found in significant concentrations in pyrite. Geochemical modeling showed that elevated trace metal concentrations in groundwater, potentially exceeding drinking water standards, should preferentially occur in a less than 1 m thick zone situated around the depth of the redoxcline, where nitrate is reduced by pyrite. This was confirmed by depth-specific groundwater sampling in the Emsland and by previously published studies. The absolute concentration of released trace metals depends on their content in the pyrite but also strongly on the nitrate load of groundwater. - Highlights: • Pyrite from heavy mineral fraction of aquifer sediment analyzed for trace metal content. • Pyrites contain significant concentration of trace metals, such as nickel, arsenic, cadmium. • Trace elements are released by autotrophic denitrification. • Reactive transport model predicts small zone of trace element accumulation. • Release of trace elements strongly dependent on nitrate content of groundwater.

  15. Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zi Gu

    2014-05-01

    Full Text Available The synthesis method of layered double hydroxides (LDHs determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h. After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties.

  16. Effects of surface friction treatment on the in vitro release of constituent metals from the biomedical Co–29Cr–6Mo–0.16N alloy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaoyu [Graduate School of Engineering, Tohoku University, Sendai 980-8577 (Japan); Li, Yunping, E-mail: lyping@csu.edu.cn [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); School of Materials Science and Engineering, Central South University, Changsha (China); Hou, Yuhang [Graduate School of Engineering, Tohoku University, Sendai 980-8577 (Japan); Bian, Huakang; Koizumi, Yuichiro; Chiba, Akihiko [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan)

    2016-07-01

    Due to the ignorance by many researchers on the influence of starting microstructure on the metal release of biomedical materials in human body after implant, in this study, the effect of surface friction treatment on the in vitro release of the constituent elements of the biomedical Co–29Cr–6Mo–0.16N (CCM) alloy is investigated for the first time by immersion test in lactic acid solution combined with electron backscatter diffraction, transmission electron microscope, X-ray diffraction, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy (ICP-EOS). The results indicate that friction treatment on the as-annealed CCM alloy sample surface leads to a planar strain-induced martensitic transformation (SIMT) on sample surface; this greatly accelerates the release of all the constituent elements and, in particular, that of Co as indicated by the ICP-EOS analysis. This increase can be ascribed to a localized deformation that occurred over the entire sample surface, with the dislocation density being high within the SIMTed phase and low in the alloy matrix. - Highlights: • Immersion test of biomedical CCM alloy in lactic acid solution was conducted. • Surface friction on CCM alloy leads to martensitic transformation. • The friction treatment accelerated the release of all the elements especially Co. • Localized deformation accounts for the accelerated release of elements.

  17. (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.

    Science.gov (United States)

    Knoll, J; Miklya, I; Knoll, B; Markó, R; Kelemen, K

    1996-01-01

    The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons). As a catecholaminergic activity enhancer (CAE) substance (-)deprenyl is about ten times more potent than its parent compound, (-)methamphetamine. While the (+)methamphetamine is 3-5 times more potent than (-)methamphetammine in releasing catecholamines, the (-)methamphetamine is the more potent CAE substance. The mechanism of the CAE effect of (-)deprenyl and (-)PPAP, a deprenyl-derived substance devoid of MAO inhibitory potency, was studied in rats by measuring: a) the release of catecholamines from striatum, substantia nigra, tuberculum olfactorium and locus coeruleus; b) the stimulation induced release of 3H-noradrenaline from the isolated brain stem; and c) the antagonistic effect against tetrabenazine-induced depression of learning in the shuttle box. The CAE effect was found to be unrelated: a) to the inhibition of MAO activity; b) to the inhibition of presynaptic catecholamine receptors; c) to the inhibition of the uptake of catecholamines; and d) to the release of catecholamines. It was concluded that (-)deprenyl and (-)PPAP act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons of the brain. We show that both (-)deprenyl and (-)PPAP enhance the inward Ca2+ current in sino-auricular fibers of the frog heart. (-)PPAP was much more potent than either (+)PPAP or (-)deprenyl in this test.

  18. Comparing the Cost of Treatment with Octreotide Long-Acting Release versus Lanreotide in Patients with Metastatic Gastrointestinal Neuroendocrine Tumors.

    Science.gov (United States)

    Ayyagari, Rajeev; Neary, Maureen; Li, Shang; Rokito, Ariel; Yang, Hongbo; Xie, Jipan; Benson, Al B

    2017-11-01

    The 2 somatostatin analogs currently recommended by the National Comprehensive Cancer Network for the treatment of gastrointestinal (GI) neuroendocrine tumors (NETs) include octreotide long-acting release (Sandostatin LAR) for injectable suspension and lanreotide (Somatuline Depot) injection for subcutaneous use. To estimate the costs to payers associated with 30-mg octreotide LAR and 120-mg lanreotide treatment among patients with metastatic GI-NETs. The costs to payers associated with the 2 drugs were estimated by including the costs of each drug, drug administration, and adverse events. The unit drug costs for octreotide LAR and for lanreotide were obtained from ReadyPrice Wholesale Acquisition Cost; the doses were obtained from published studies. The adverse event rates were obtained from 2 phase 3 clinical trials, PROMID and CLARINET. Deterministic one-way sensitivity analyses were used to assess the impact of modifying assumptions and inputs on the results, including the 2017 Average Sales Price (ASP). All costs were estimated in 2016 US dollars, with a constant discount of 3%. The costs to payers associated with the treatment of GI-NETs during 1-, 3-, and 5-year horizons were $74,566, $180,082, and $262,344, respectively, for octreotide LAR and $84,856, $205,562, and $299,667, respectively, for lanreotide. Thus, octreotide LAR was associated with lower costs by $10,290 (1 year), $25,480 (3 years), and $37,323 (5 years) compared with lanreotide. Over a 5-year horizon, the costs of adverse events and administration accounted for 0.72% of the total cost for octreotide LAR and 0.51% of the total cost for lanreotide. Sensitivity analyses confirmed that the main factor affecting the cost difference was the price of the drugs; analyses using the ASP yielded similar results. For the management of metastatic GI-NETs, the cost to payers of treatment with 30-mg octreotide LAR is considerably lower than with 120-mg lanreotide over 1-, 3-, and 5-year horizons. In the

  19. Novel Fabrication of Biodegradable Superabsorbent Microspheres with Diffusion Barrier through Thermo-Chemical Modification and Their Potential Agriculture Applications for Water Holding and Sustained Release of Fertilizer.

    Science.gov (United States)

    Feng, Diejing; Bai, Bo; Wang, Honglun; Suo, Yourui

    2017-07-26

    Synergistic utilization of water and fertilizer has vital contribution to the modern production of agriculture. This work reports on a simple and facile strategy to prepare biodegradable yeast/sodium alginate/poly(vinyl alcohol) superabsorbent microspheres with a diffusion barrier merit by thermo-chemical modification route. The integrated performances, including water absorbency, water retention, water evaporation ratio, leaching loss control, sustained-release behaviors, and degradation in soil, were systematically investigated. The results revealed that the modified microspheres were a triumphant water and fertilizer manager to effectively hold water and control the unexpected leakage of fertilizer for sustained release. Therefore, this work provides a promising approach to ameliorate the utilization efficiency of water and fertilizer in potential agriculture applications.

  20. IE Information Notice No. 85-93: Westinghouse Type DS circuit breakers, potential failure of electric closing feature because of broken spring release latch lever

    International Nuclear Information System (INIS)

    Jordan, E.L.

    1992-01-01

    On April 14, 1985, the Westinghouse Nuclear Services Integration Division (NSID) issued Technical Bulletin No. NSID-TB-85-17 advising their customers of a potential malfunction in Westinghouse Type DS Class 1E circuit breakers because of broken spring release latch levers. These electrically operated type DS breakers will not close electrically when the spring release latch lever has been broken off. Twenty-five broken levers have been reported and evaluated. This evaluation shows concentrations of incidents traceable to manufacturing in the following periods of time: early 1975, April 1976, and early 1978. This circuit breaker failure, as discussed, adversely affects the safety function (closing on demand) when the circuit breaker is used in the Engineered Safety Features Systems. However, this failure mode will not affect the safety trip function when it is used in the reactor protection system

  1. Elevation of plasma gonadotropin concentration in response to mammalian gonadotropin releasing hormone (GRH) treatment of the male brown trout as determined by radioimmunoassay

    International Nuclear Information System (INIS)

    Crim, L.W.; Cluett, D.M.

    1974-01-01

    Rapid increase of the plasma gonadotropin concentration as measured by radioimmunoassay has been demonstrated in response to GRH treatment of the sexually mature male brown trout. Peak gonadotropin values were observed within 15 minutes of GRH treatment, however, the return to baseline values was prolonged compared with the mammalian response. These data support the concept that the brain, operating via releasing hormones, plays a role in the control of pituitary hormone secretion in fish

  2. Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

    International Nuclear Information System (INIS)

    Kruisbrink, J.; Boer, G.J.

    1984-01-01

    Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero

  3. Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential

    Science.gov (United States)

    Masunaga, S; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kondo, N; Maruhashi, A; Ono, K

    2011-01-01

    Objectives The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results 3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. Conclusion Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide. PMID:21586505

  4. Environmental Life Cycle Assessment and Cost Analysis of Bath, NY Wastewater Treatment Plant: Potential Upgrade Implications

    Science.gov (United States)

    Many communities across the U.S. are required to upgrade wastewater treatment plants (WWTP) to meet increasingly stringent nutrient effluent standards. However, increased capital, energy and chemical requirements of upgrades create potential trade-offs between eutrophication pot...

  5. Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies

    Science.gov (United States)

    ... Spotlight on Research Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies By Kirstie Saltsman, Ph.D. | December 15, 2013 In scleroderma, immune cells invade the skin, but the role ...

  6. A Sequential Chemical Extraction and Spectroscopic Assessment of the Potential Bioavailability of Mercury Released From the Inoperative New Idria Mercury Mine, San Benito Co., CA

    Science.gov (United States)

    Jew, A. D.; Luong, P. N.; Rytuba, J. J.; Brown, G. E.

    2012-12-01

    The inoperative New Idria mercury mine in San Benito Co., CA, is a potential point source of Hg to the Central Valley of California. To determine the phases and the potential bioavailability of Hg present in stream bed deposits downstream of the mine, sequential chemical extractions (SCEs) targeting Hg-bearing phases and synchrotron-based spectroscopic and imaging techniques were used on sediment samples taken from the acid mine drainage (AMD) system, Hg sorbed in the laboratory to ferrihydrite (synthetic 2-line and natural), and Hg associated with diatom-rich samples. In all field samples examined, both the wet and dry seasons, removal of > 97% of the Hg required 1M KOH or harsher chemical treatments. X-ray absorption spectroscopy (XAS) showed that HgS was the dominant inorganic Hg phase present, with no detectable Hg associated with the ferrihydrite. Uptake and subsequent SCE analysis of Hg to both synthetic and natural ferrihydrite showed that 1M MgCl2 removed ≥ 90% of the total Hg, suggesting that Hg does not sorb strongly to ferrihydrite. This finding is surprising, because in most settings ferrihydrite is considered to be a strong adsorbent of heavy metals. Due to the lack of Hg sorption to ferrihydrite in field samples, another pool for the non-HgS/HgSe fraction in sediments is needed. SEM analysis of the downstream samples showed that regardless of pH, freshwater diatoms were present. To determine if diatoms were the sink for dissolved Hg in this system, SCE analysis on commercially available and diatom-rich field samples from the New Idria site and Harley Gulch (Lake County, CA) were completed. The vast majority of Hg in diatom-rich samples was removed by 1M KOH, which corresponds to the non-HgS/HgSe fraction of the New Idria field samples. Analysis for carbon and nitrogen in the diatom-rich samples showed no detectable nitrogen, indicating little to no organic material was left in the samples. We therefore infer that Hg in the diatoms is contained in

  7. Gold nanoflowers with mesoporous silica as “nanocarriers” for drug release and photothermal therapy in the treatment of oral cancer using near-infrared (NIR) laser light

    International Nuclear Information System (INIS)

    Song, Wenzhi; Gong, Junxia; Wang, Yuqian; Zhang, Yan; Zhang, Hongmei; Zhang, Weihang; Zhang, Hu; Liu, Xin; Zhang, Tianfu; Yin, Wanzhong; Yang, Wensheng

    2016-01-01

    In this experiment, we successfully developed nanocarriers in the form of gold nanoflowers coated with two layers of silica for the purposes of drug loading and NIR (near-infrared) photothermal therapy for the treatment of oral cancer. The gold nanoflowers converted NIR laser energy into heat energy. The cores were coated with a thin silica layer (AuNFs@SiO_2) to protect the gold nanoflowers from intraparticle ripening. The second layer was mesoporous silica (AuNFs@SiO_2@mSiO_2), which acted as a nanocarrier for anticancer drug (DOX) loads. The mean effective diameter of the nanoparticles was approximately 150–200 nm, whereas the peak absorption of the AuNFs was 684 nm. After the AuNFs were encapsulated by the silica shells, the plasmonic absorption peak of AuNFs@SiO_2 and AuNFs@SiO_2@mSiO_2 exhibited a red shift to 718 nm. When exposed to an 808 nm NIR laser, these crystals showed an obvious photothermal conversion in the NIR region and a highly efficient release of DOX. Biocompatibility was assessed in vitro using Cell Counting Kit-8 assays, and the results showed that the nanocarriers induced no obvious cytotoxicity. This nanomaterial could be considered a new type of material that shows promising potential for photothermal-chemotherapy against malignant tumours, including those of oral cancers.

  8. Gold nanoflowers with mesoporous silica as "nanocarriers" for drug release and photothermal therapy in the treatment of oral cancer using near-infrared (NIR) laser light

    Science.gov (United States)

    Song, Wenzhi; Gong, Junxia; Wang, Yuqian; Zhang, Yan; Zhang, Hongmei; Zhang, Weihang; Zhang, Hu; Liu, Xin; Zhang, Tianfu; Yin, Wanzhong; Yang, Wensheng

    2016-04-01

    In this experiment, we successfully developed nanocarriers in the form of gold nanoflowers coated with two layers of silica for the purposes of drug loading and NIR (near-infrared) photothermal therapy for the treatment of oral cancer. The gold nanoflowers converted NIR laser energy into heat energy. The cores were coated with a thin silica layer (AuNFs@SiO2) to protect the gold nanoflowers from intraparticle ripening. The second layer was mesoporous silica (AuNFs@SiO2@mSiO2), which acted as a nanocarrier for anticancer drug (DOX) loads. The mean effective diameter of the nanoparticles was approximately 150-200 nm, whereas the peak absorption of the AuNFs was 684 nm. After the AuNFs were encapsulated by the silica shells, the plasmonic absorption peak of AuNFs@SiO2 and AuNFs@SiO2@mSiO2 exhibited a red shift to 718 nm. When exposed to an 808 nm NIR laser, these crystals showed an obvious photothermal conversion in the NIR region and a highly efficient release of DOX. Biocompatibility was assessed in vitro using Cell Counting Kit-8 assays, and the results showed that the nanocarriers induced no obvious cytotoxicity. This nanomaterial could be considered a new type of material that shows promising potential for photothermal-chemotherapy against malignant tumours, including those of oral cancers.

  9. Gold nanoflowers with mesoporous silica as “nanocarriers” for drug release and photothermal therapy in the treatment of oral cancer using near-infrared (NIR) laser light

    Energy Technology Data Exchange (ETDEWEB)

    Song, Wenzhi; Gong, Junxia [Jilin University, Department of Stomatology, China-Japan Union Hospital (China); Wang, Yuqian [Jilin University, China-Japan Union Hospital, Scientific Research Center (China); Zhang, Yan [Jilin University, Department of Stomatology, China-Japan Union Hospital (China); Zhang, Hongmei [Jilin University, China-Japan Union Hospital, Scientific Research Center (China); Zhang, Weihang; Zhang, Hu; Liu, Xin; Zhang, Tianfu [Jilin University, Department of Stomatology, China-Japan Union Hospital (China); Yin, Wanzhong, E-mail: yinwanzhong88@hotmail.com [First Clinical Hospital of Jilin University, Department of Otorhinolaryngology (China); Yang, Wensheng, E-mail: wsyang@mail.jlu.edu.cn [College of Chemistry, The Key Laboratory of Surface and Interface Chemistry of Jilin Province (China)

    2016-04-15

    In this experiment, we successfully developed nanocarriers in the form of gold nanoflowers coated with two layers of silica for the purposes of drug loading and NIR (near-infrared) photothermal therapy for the treatment of oral cancer. The gold nanoflowers converted NIR laser energy into heat energy. The cores were coated with a thin silica layer (AuNFs@SiO{sub 2}) to protect the gold nanoflowers from intraparticle ripening. The second layer was mesoporous silica (AuNFs@SiO{sub 2}@mSiO{sub 2}), which acted as a nanocarrier for anticancer drug (DOX) loads. The mean effective diameter of the nanoparticles was approximately 150–200 nm, whereas the peak absorption of the AuNFs was 684 nm. After the AuNFs were encapsulated by the silica shells, the plasmonic absorption peak of AuNFs@SiO{sub 2} and AuNFs@SiO{sub 2}@mSiO{sub 2} exhibited a red shift to 718 nm. When exposed to an 808 nm NIR laser, these crystals showed an obvious photothermal conversion in the NIR region and a highly efficient release of DOX. Biocompatibility was assessed in vitro using Cell Counting Kit-8 assays, and the results showed that the nanocarriers induced no obvious cytotoxicity. This nanomaterial could be considered a new type of material that shows promising potential for photothermal-chemotherapy against malignant tumours, including those of oral cancers.

  10. The Solar Reflectance Index as a Tool to Forecast the Heat Released to the Urban Environment: Potentiality and Assessment Issues

    Directory of Open Access Journals (Sweden)

    Alberto Muscio

    2018-02-01

    Full Text Available Overheating of buildings and urban areas is a more and more severe issue in view of global warming combined with increasing urbanization. The thermal behavior of urban surfaces in the hot seasons is the result of a complex balance of construction and environmental parameters such as insulation level, thermal mass, shielding, and solar reflective capability on one side, and ambient conditions on the other side. Regulations makers and the construction industry have favored the use of parameters that allow the forecasting of the interaction between different material properties without the need for complex analyses. Among these, the solar reflectance index (SRI takes into account solar reflectance and thermal emittance to predict the thermal behavior of a surface subjected to solar radiation through a physically rigorous mathematical procedure that considers assigned air and sky temperatures, peak solar irradiance, and wind velocity. The correlation of SRI with the heat released to the urban environment is analyzed in this paper, as well as the sensitivity of its calculation procedure to variation of the input parameters, as possibly induced by the measurement methods used or by the material ageing.

  11. Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

    Science.gov (United States)

    Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

    2017-09-29

    Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The potential complications of open carpal tunnel release surgery to the ulnar neurovascular bundle and its branches: A cadaveric study.

    Science.gov (United States)

    Boughton, O; Adds, P J; Jayasinghe, J A P

    2010-07-01

    This study investigated the ulnar artery and the ulnar nerve and its branches in the palm to assess how frequently they may be at risk of damage during open carpal tunnel release surgery. Twenty-one formalin-embalmed cadaveric hands were dissected, and the proximity of the ulnar neurovascular bundle to two different lines of incision, the 3rd and 4th interdigital web space axis and the ring finger axis, was assessed and compared. It was found that an incision in the latter (ring finger) axis put the ulnar artery at risk in 12 of 21 specimens, whereas an incision in the former axis (3rd/4th interdigital web space) put the ulnar artery at risk in only two specimens. In 15 hands at least one structure (the ulnar artery or a branch of the ulnar nerve) was at risk in the ring finger axis compared to only seven hands in the axis of the 3rd/4th interdigital web space. We conclude that the ulnar artery and branches of the ulnar nerve are at increased risk of damage with an incision in the axis of the ring finger. The importance of using a blunt dissection technique under direct vision during surgery to identify and preserve these structures and median nerve branches is emphasized. (c) 2010 Wiley-Liss, Inc.

  13. Tuberculin skin testing and treatment modulates interferon-gamma release assay results for latent tuberculosis in migrants.

    Directory of Open Access Journals (Sweden)

    Matthew K O'Shea

    Full Text Available Identifying latent tuberculosis infection (LTBI in people migrating from TB endemic regions to low incidence countries is an important control measure. However, no prospective longitudinal comparisons between diagnostic tests used in such migrant populations are available.To compare commercial interferon (IFN-gamma release assays (IGRAs and the tuberculin skin test (TST for diagnosing LTBI in a migrant population, and the influence of antecedent TST and LTBI treatment on IGRA performance.This cohort study, performed from February to September 2012, assessed longitudinal IGRA and TST responses in Nepalese military recruits recently arrived in the UK. Concomitant T-SPOT.TB, QFT-GIT and TST were performed on day 0, with IGRAs repeated 7 and 200 days later, following treatment for LTBI if necessary.166 Nepalese recruits were prospectively assessed. At entry, 21 individuals were positive by T-SPOT.TB and 8 individuals by QFT-GIT. There was substantial agreement between TST and T-SPOT.TB positives at baseline (71.4% agreement; κ = 0.62; 95% CI:0.44-0.79, but only moderate concordance between positive IGRAs (38.1% agreement; κ = 0.46; 95% CI:0.25-0.67. When reassessed 7 days following TST, numbers of IGRA-positive individuals changed from 8 to 23 for QFT-GIT (p = 0.0074 and from 21 to 23 for T-SPOT.TB (p = 0.87. This resulted in an increase in IGRA concordance to substantial (64.3% agreement; κ = 0.73; 95% CI:0.58-0.88. Thus, in total on day 0 and day 7 after testing, 29 out of 166 participants (17.5% provided a positive IGRA and of these 13 were TST negative. Two hundred days after the study commenced and three months after treatment for LTBI was completed by those who were given chemoprophylaxis, 23 and 21 participants were positive by T-SPOT.TB or QFT-GIT respectively. When individual responses were examined longitudinally within this population 35% of the day 7 QFT-GIT-positive, and 19% T-SPOT.TB-positive individuals, were

  14. Mediation of rapid electrical, metabolic, transpirational, and photosynthetic changes by factors released from wounds. I. variation potentials and putative action potentials in intact plants

    Science.gov (United States)

    S.J. Barres; T.J.Sambeek Perry; Barbara G. Pickard

    1976-01-01

    Damaging representative plants from five angiosperm families by heating or crushing a small portion of a single leaf results in an electrical change which may spread throughout the shoot. In Mimosa similar changes have previously been identified as variation potentials.Except in one of the five plants, a variation...

  15. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product

    Directory of Open Access Journals (Sweden)

    Pergolizzi, J

    2018-02-01

    Full Text Available Joseph V Pergolizzi, Jr,1 Robert Taylor Jr,1 Jo Ann LeQuang,1 Robert B Raffa2,3 On behalf of the NEMA Research Group 1NEMA Research Inc., Naples, FL, USA; 2University of Arizona College of Pharmacy, Tucson, AZ, USA; 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF. ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations. Keywords: oxycodone/naltrexone, abuse-deterrent formulation, abuse-deterrent opioid, oxycodone, abuse liability

  16. Determination of potential radiation exposure via terrestrial food chains by the release of radioactive material from nuclear facilities

    International Nuclear Information System (INIS)

    Handge, P.; Meurin, G.

    1978-01-01

    The radiation exposure level caused by consumption of vegetable and animal products in the environment of nuclear power plants is determined to a large extent by the release of 90 Sr, 134 Cs, and 137 Cs. For long-lived nuclides, especially 90 Sr, transfer from the soil into vegetation makes the essential contribution to plant contamination after several years of power plant operation. The relevant transfer coefficients for the different plant species vary, depending on the soil properties, between 0.02 and 6.0 [pCi/kg fresh weigth of vegetation : pCi/kg dry weight of soil] for Sr and between 1.10 -3 and 0.2 [pCi/kg fresh weight of vegetation : pCi/kg dry weight of soil] for Cs. The sensitivity analysis shows that already a variation of the transfer coefficients for Sr from 0.5 up to 2.5 [pCi/kg fresh weight of vegetation : pCi/kg dry weight of soil] and for Cs from 3.10 -2 up to 2.10 -1 cause variations in the level of radiation exposure for individual exposure pathways by factors fo 2 to 4. Correspondingly higher values are to be expected by still larger transfer of Sr and Cs from the ground to vegetation. For transfer coefficients >- 2.5 [pCi/kg fresh weight of vegetation : pCi/kg dry weight of soil], however, removal of radioactive substances from the ground by the plants must not remain without consideration any longer. (orig./HP) [de

  17. The potential use of ionising energy treatment in Queensland's horticultural industries

    International Nuclear Information System (INIS)

    Heather, N.W.; Sheehy, P.T.; Muirhead, I.F.; Brown, B.I.; Hassall, R.N.

    1985-01-01

    The potential application of ionising energy treatment technology in Queensland falls into three categories: insect disinfestation, disease control and quality improvement. The technology fulfils the requirements of a disinfestation treatment against Queensland fruit fly and other pests of quarantine importance in respect to efficacy, absence of phytotoxicity, absence of residues and, on technical considerations would be an ideal replacement for the fumigant EDB. The report examines the purposes of ionising energy treatment, economic and marketing aspects and research needs

  18. Influence of preseasonal treatment with L-tyrosine-adsorbed allergoids on IgE-mediated histamine release from basophils of children suffering from allergic diseases.

    Science.gov (United States)

    Wegner, F; Fenkes, A; Stemmann, E A; Reinhardt, D

    1981-04-01

    In 10 children suffering from allergic pollinosis and/or asthma, a preseasonal hyposensitization scheme with 3 weekly injections of a glutaraldehyde-modified, tyrosine-adsorbed grass-pollen allergen reduced the histamine release from basophils in response to increasing concentrations of antigen. The decrease in histamine release which occurred 1 week after the injection course was even maintained during the pollen season. The inhibition was only obtained when basophils were incubated with the serum of patients, but not with the serum of normals, indicating that blocking antibodies may have occurred. In contrast to what has been observed in the treated patients' group, 5 patients, who were not included in the hyposensitization scheme, showed identical histamine release curves during the whole investigation period. Specific IgE did not increase after the treatment course and shows the same behaviour as the untreated patients. Thus, as treatment with glutaraldehyde modified, tyrosine-adsorbed allergoids is safe to administer, requires only 3 injections, reduces histamine release from basophils by production of "blocking" antibodies, it appears to be a useful tool in the hyposensitization treatment.

  19. Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis

    Directory of Open Access Journals (Sweden)

    Guo A

    2016-05-01

    Full Text Available Amy Guo,1 Michael Grabner,2 Swetha Rao Palli,2 Jessica Elder,1 Matthew Sidovar,1 Peter Aupperle,1 Stephen Krieger3 1Acorda Therapeutics Inc., Ardsley, New York, NY, USA; 2HealthCore Inc., Wilmington, DE, USA; 3Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER tablets in patients with multiple sclerosis (MS, there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. Purpose: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU associated with D-ER use in a real-world setting. Methods: A retrospective claims database analysis was conducted using the HealthCore Integrated Research DatabaseSM. Adherence (measured by medication possession ratio, or [MPR] and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. Results: Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%. The estimated budget impact range of D-ER was $0.014–$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001 and other outpatient visits (22.8% vs 51.4%, P<0.0001 over the 12-month follow-up. Changes in HRU from follow

  20. Regenerative potential and anti-bacterial activity of tetracycline loaded apatitic nanocarriers for the treatment of periodontitis

    International Nuclear Information System (INIS)

    Madhumathi, K; Sampath Kumar, T S

    2014-01-01

    Current treatment of periodontal infections includes mechanical debridement, administration of antibiotics and bone grafting. Oral administration of antibiotics results in undesirable side effects, while current modes of local administration are affected by problems concerning allergic response to the polymeric carrier agents. We have developed an osteoconductive drug delivery system composed of apatitic nanocarriers capable of providing sustained delivery of drugs in the periodontium. Calcium deficient hydroxyapatite (CDHA) nanocarriers of different Ca/P ratios were synthesized and characterized using the x-ray diffraction method, transmission electron microscopy, inductively coupled plasma atomic emission spectroscopy, Fourier transform infrared spectroscopy and the BET gas isotherm method. Loading and release studies performed with tetracycline showed a sustained release of up to 88% in phosphate buffered saline over a period of five days. Antibacterial activity studies showed that the tetracycline loaded CDHA (TC-CDHA) nanocarriers were effective against S. aureus and E. coli bacteria. The biocompatibility of the TC-CDHA nanocarriers was demonstrated using an alamar blue assay and further characterized by cell uptake studies. Interestingly, cell uptake of drug loaded CDHA also increased the cellular proliferation of human periodontal ligament fibroblast cells. Hence, it can be concluded that the CDHA nanocarriers are ideal drug delivery agents and have bone regenerative potential for local periodontal applications. (paper)

  1. Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options

    Directory of Open Access Journals (Sweden)

    Fernando Cordido

    2010-01-01

    Full Text Available Available anti-obesity pharmacotherapy options remain very limited and development of more effective drugs has become a priority. The potential strategies to achieve weight loss are to reduce energy intake by stimulating anorexigenic signals or by blocking orexigenic signals, and to increase energy expenditure. This review will focus on approved obesity medications, as well as potential new pharmacologic treatment options.

  2. Ozonation and Thermal Pre-Treatment of Municipal Sewage Sludge-Implications for Toxicity and Methane Potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    2013-01-01

    The aim of this study was to determine effects on methane potential and overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 degrees C). In general both treatments produced increased methane potential. Thermal treatment...... by ozone treatment and digestion. No statistical significant reduction in concentrations of included pharmaceuticals could be observed....

  3. Antihyperlipidemic Medication Treatment Patterns and Statin Adherence Among Patients with ASCVD in a Managed Care Plan After Release of the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol.

    Science.gov (United States)

    Bellows, Brandon K; Olsen, Cody J; Voelker, Jennifer; Wander, Curtis

    2016-08-01

    -index antihyperlipidemic classifications were compared between groups using a Stuart-Maxwell test. The change in mean statin adherence (proportion of days covered [PDC]) was compared within and between groups using paired and independent t-tests, respectively. The proportion of adherent patients (PDC ≥ 0.80) in the pre- and post-index periods was compared between groups using a chi-square test. A multivariable logistic regression was used to compare the likelihood of being adherent in the post-index period while controlling for pre-index adherence and other potential confounders. A total of 7,818 adult members with ASCVD in the index period and 1 year before the index period were identified. Of those, 1,841 patients met the criteria to be included in the analysis, and 1,526 patients were matched on antihyperlipidemic classification and included in the antihyperlipidemic treatment patterns analysis. Baseline characteristics were similar, although the guideline implementation group was younger (58.3 vs. 60.5 years, P patterns cohort, 919 patients met inclusion criteria for the statin adherence analysis. Although PDC decreased over time in both groups, significantly more patients in the guideline implementation group were adherent in the post-index period than the historical control group (66.5% vs. 57.3%, respectively; P = 0.005). Additionally, patients in the guideline implementation group were more likely than the historical control to be adherent in the post-index period when adjusting for potential confounders (OR = 1.49, 95% CI = 1.10-2.03; P = 0.011). Since the release of the updated ACC/AHA treatment guideline, more commercial health plan patients with ASCVD used high-intensity statins and fewer used nonstatin cholesterol medications than historical controls. Additionally, since the guideline release, more patients are adherent to statin therapy than historical controls. This study provides managed care organizations with valuable information regarding the effect of the 2013 ACC

  4. The Multidimensional Therapeutic Potential of Targeting the Brain Oxytocin System for the Treatment of Substance Use Disorders.

    Science.gov (United States)

    Bowen, Michael T; Neumann, Inga D

    2017-09-24

    The neuropeptide oxytocin is released both into the blood and within the brain in response to reproductive stimuli, such as birth, suckling and sex, but also in response to social interaction and stressors. Substance use disorders, or addictions, are chronic, relapsing brain disorders and are one of the major causes of global burden of disease. Unfortunately, current treatment options for substance use disorders are extremely limited and a treatment breakthrough is sorely needed. There is mounting preclinical evidence that targeting the brain oxytocin system may provide that breakthrough. Substance use disorders are characterised by a viscous cycle of bingeing and intoxication, followed by withdrawal and negative affect, and finally preoccupation and anticipation that triggers relapse and further consumption. Administration of oxytocin has been shown to have a potential therapeutic benefit at each stage of this addiction cycle for numerous drugs of abuse. This multidimensional therapeutic utility is likely due to oxytocin's interactions with key biological systems that underlie the development and maintenance of addiction. Only a few human trials of oxytocin in addicted populations have been completed with the results thus far being mixed. There are numerous other trials underway, and the results are eagerly awaited. However, the ability to fully harness the potential therapeutic benefit of targeting the brain oxytocin system may depend on the development of molecules that selectively stimulate the oxytocin system, but that have superior pharmacokinetic properties to oxytocin itself.

  5. Preparation of Multifunctional Fe@Au Core-Shell Nanoparticles with Surface Grafting as a Potential Treatment for Magnetic Hyperthermia

    Directory of Open Access Journals (Sweden)

    Ren-Jei Chung

    2014-01-01

    Full Text Available Iron core gold shell nanoparticles grafted with Methotrexate (MTX and indocyanine green (ICG were synthesized for the first time in this study, and preliminarily evaluated for their potential in magnetic hyperthermia treatment. The core-shell Fe@Au nanoparticles were prepared via the microemulsion process and then grafted with MTX and ICG using hydrolyzed poly(styrene-alt-maleic acid (PSMA to obtain core-shell Fe@Au-PSMA-ICG/MTX nanoparticles. MTX is an anti-cancer therapeutic, and ICG is a fluorescent dye. XRD, TEM, FTIR and UV-Vis spectrometry were performed to characterize the nanoparticles. The data indicated that the average size of the nanoparticles was 6.4 ± 09 nm and that the Au coating protected the Fe core from oxidation. MTX and ICG were successfully grafted onto the surface of the nanoparticles. Under exposure to high frequency induction waves, the superparamagnetic nanoparticles elevated the temperature of a solution in a few minutes, which suggested the potential for an application in magnetic hyperthermia treatment. The in vitro studies verified that the nanoparticles were biocompatible; nonetheless, the Fe@Au-PSMA-ICG/MTX nanoparticles killed cancer cells (Hep-G2 via the magnetic hyperthermia mechanism and the release of MTX.

  6. Preparation of Multifunctional Fe@Au Core-Shell Nanoparticles with Surface Grafting as a Potential Treatment for Magnetic Hyperthermia.

    Science.gov (United States)

    Chung, Ren-Jei; Shih, Hui-Ting

    2014-01-24

    Iron core gold shell nanoparticles grafted with Methotrexate (MTX) and indocyanine green (ICG) were synthesized for the first time in this study, and preliminarily evaluated for their potential in magnetic hyperthermia treatment. The core-shell Fe@Au nanoparticles were prepared via the microemulsion process and then grafted with MTX and ICG using hydrolyzed poly(styrene-alt-maleic acid) (PSMA) to obtain core-shell Fe@Au-PSMA-ICG/MTX nanoparticles. MTX is an anti-cancer therapeutic, and ICG is a fluorescent dye. XRD, TEM, FTIR and UV-Vis spectrometry were performed to characterize the nanoparticles. The data indicated that the average size of the nanoparticles was 6.4 ± 09 nm and that the Au coating protected the Fe core from oxidation. MTX and ICG were successfully grafted onto the surface of the nanoparticles. Under exposure to high frequency induction waves, the superparamagnetic nanoparticles elevated the temperature of a solution in a few minutes, which suggested the potential for an application in magnetic hyperthermia treatment. The in vitro studies verified that the nanoparticles were biocompatible; nonetheless, the Fe@Au-PSMA-ICG/MTX nanoparticles killed cancer cells (Hep-G2) via the magnetic hyperthermia mechanism and the release of MTX.

  7. Identifying Toxic Impacts of Metals Potentially Released during Deep-Sea Mining—A Synthesis of the Challenges to Quantifying Risk

    Directory of Open Access Journals (Sweden)

    Chris Hauton

    2017-11-01

    Full Text Available In January 2017, the International Seabed Authority released a discussion paper on the development of Environmental Regulations for deep-sea mining (DSM within the Area Beyond National Jurisdiction (the “Area”. With the release of this paper, the prospect for commercial mining in the Area within the next decade has become very real. Moreover, within nations' Exclusive Economic Zones, the exploitation of deep-sea mineral ore resources could take place on very much shorter time scales and, indeed, may have already started. However, potentially toxic metal mixtures may be released at sea during different stages of the mining process and in different physical phases (dissolved or particulate. As toxicants, metals can disrupt organism physiology and performance, and therefore may impact whole populations, leading to ecosystem scale effects. A challenge to the prediction of toxicity is that deep-sea ore deposits include complex mixtures of minerals, including potentially toxic metals such as copper, cadmium, zinc, and lead, as well as rare earth elements. Whereas the individual toxicity of some of these dissolved metals has been established in laboratory studies, the complex and variable mineral composition of seabed resources makes the a priori prediction of the toxic risk of DSM extremely challenging. Furthermore, although extensive data quantify the toxicity of metals in solution in shallow-water organisms, these may not be representative of the toxicity in deep-sea organisms, which may differ biochemically and physiologically and which will experience those toxicants under conditions of low temperature, high hydrostatic pressure, and potentially altered pH. In this synthesis, we present a summation of recent advances in our understanding of the potential toxic impacts of metal exposure to deep-sea meio- to megafauna at low temperature and high pressure, and consider the limitation of deriving lethal limits based on the paradigm of exposure to

  8. Wastewater Treatment Energy Recovery Potential For Adaptation To Global Change: An Integrated Assessment

    Science.gov (United States)

    Breach, Patrick A.; Simonovic, Slobodan P.

    2018-04-01

    Approximately 20% of wastewaters globally do not receive treatment, whereas wastewater discharges are projected to increase, thereby leading to excessive water quality degradation of surface waters on a global scale. Increased treatment could help alleviate water quality issues by constructing more treatment plants; however, in many areas there exist economic constraints. Energy recovery methods including the utilization of biogas and incineration of biosolids generated during the treatment process may help to alleviate treatment costs. This study explores the potential for investments in energy recovery from wastewater to increase treatment levels and thus improve surface water quality. This was done by examining the relationships between nutrient over-enrichment, wastewater treatment, and energy recovery at a global scale using system dynamics simulation as part of the ANEMI integrated assessment model. The results show that a significant amount of energy can be recovered from wastewater, which helps to alleviate some of the costs of treatment. It was found that wastewater treatment levels could be increased by 34%, helping to offset the higher nutrient loading from a growing population with access to improved sanitation. The production of renewable natural gas from biogas was found to have the potential to prolong the depletion of natural gas resources used to produce electricity and heat. It is recommended that agricultural nutrient discharges be better managed to help reduce nutrient over-enrichment on global scale. To increase the utility of the simulation, a finer spatial scale should be used to consider regional treatment, economic, and water quality characteristics.

  9. Potential for beneficial application of sulfate reducing bacteria in sulfate containing domestic wastewater treatment.

    Science.gov (United States)

    van den Brand, T P H; Roest, K; Chen, G H; Brdjanovic, D; van Loosdrecht, M C M

    2015-11-01

    The activity of sulfate reducing bacteria (SRB) in domestic wastewater treatment plants (WWTP) is often considered as a problem due to H2S formation and potential related odour and corrosion of materials. However, when controlled well, these bacteria can be effectively used in a positive manner for the treatment of wastewater. The main advantages of using SRB in wastewater treatment are: (1) minimal sludge production, (2) reduction of potential pathogens presence, (3) removal of heavy metals and (4) as pre-treatment of anaerobic digestion. These advantages are accessory to efficient and stable COD removal by SRB. Though only a few studies have been conducted on SRB treatment of domestic wastewater, the many studies performed on industrial wastewater provide information on the potential of SRB in domestic wastewater treatment. A key-parameter analyses literature study comprising pH, organic substrates, sulfate, salt, temperature and oxygen revealed that the conditions are well suited for the application of SRB in domestic wastewater treatment. Since the application of SRB in WWTP has environmental benefits its application is worth considering for wastewater treatment, when sulfate is present in the influent.

  10. A potential role for endogenous microflora in dormancy release, cytokinin metabolism and the response to fluridone in Lolium rigidum seeds.

    Science.gov (United States)

    Goggin, Danica E; Emery, R J Neil; Kurepin, Leonid V; Powles, Stephen B

    2015-02-01

    Dormancy in Lolium rigidum (annual ryegrass) seeds can be alleviated by warm stratification in the dark or by application of fluridone, an inhibitor of plant abscisic acid (ABA) biosynthesis via phytoene desaturase. However, germination and absolute ABA concentration are not particularly strongly correlated. The aim of this study was to determine if cytokinins of both plant and bacterial origin are involved in mediating dormancy status and in the response to fluridone. Seeds with normal or greatly decreased (by dry heat pre-treatment) bacterial populations were stratified in the light or dark and in the presence or absence of fluridone in order to modify their dormancy status. Germination was assessed and seed cytokinin concentration and composition were measured in embryo-containing or embryo-free seed portions. Seeds lacking bacteria were no longer able to lose dormancy in the dark unless supplied with exogenous gibberellin or fluridone. Although these seeds showed a dramatic switch from active cytokinin free bases to O-glucosylated storage forms, the concentrations of individual cytokinin species were only weakly correlated to dormancy status. However, cytokinins of apparently bacterial origin were affected by fluridone and light treatment of the seeds. It is probable that resident microflora contribute to dormancy status in L. rigidum seeds via a complex interaction between hormones of both plant and bacterial origin. This interaction needs to be taken into account in studies on endogenous seed hormones or the response of seeds to plant growth regulators. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Nitrogen-Based Diazeniumdiolates: Versatile Nitric Oxide-Releasing Compounds for Biomedical Research and Potential Clinical Applications

    Science.gov (United States)

    Saavedra, Joseph E.; Keefer, Larry K.

    2002-12-01

    Nitric oxide-generating ions of the nitrogen-diazeniumdiolate class with the general structure R1R2N-[N(O)NO]1 have been prepared by exposing primary, secondary, and polyamines to nitric oxide (NO). The resulting complexes regenerate bioactive NO at physiological pH with half-lives ranging from 2 seconds to 20 hours. An important goal in our research is to deliver NO to a specific organ or cell type where it is needed without affecting other NO-sensitive parts of the anatomy. By taking advantage of the remarkable chemical versatility of diazeniumdiolates, we have developed general strategies to prepare either tissue-selective NO donor drugs or materials containing NO delivery agents that can be physically placed near the target sites. Inhibition of blood coagulation, induction of penile erection, relief of pulmonary hypertension, and reversal of cerebral vasospasm are a few examples of their potential clinical applications. See Featured Molecules.

  12. Knowledge-based treatment planning and its potential role in the transition between treatment planning systems.

    Science.gov (United States)

    Masi, Kathryn; Archer, Paul; Jackson, William; Sun, Yilun; Schipper, Matthew; Hamstra, Daniel; Matuszak, Martha

    2017-11-22

    Commissioning a new treatment planning system (TPS) involves many time-consuming tasks. We investigated the role that knowledge-based planning (KBP) can play in aiding a clinic's transition to a new TPS. Sixty clinically treated prostate/prostate bed intensity-modulated radiation therapy (IMRT) plans were exported from an in-house TPS and were used to create a KBP model in a newly implemented commercial application. To determine the benefit that KBP may have in a TPS transition, the model was tested on 2 groups of patients. Group 1 consisted of the first 10 prostate/prostate bed patients treated in the commercial TPS after the transition from the in-house TPS. Group 2 consisted of 10 patients planned in the commercial TPS after 8 months of clinical use. The KBP-generated plan was compared with the clinically used plan in terms of plan quality (ability to meet planning objectives and overall dose metrics) and planning efficiency (time required to generate clinically acceptable plans). The KBP-generated plans provided a significantly improved target coverage (p = 0.01) compared with the clinically used plans for Group 1, but yielded plans of comparable target coverage to the clinically used plans for Group 2. For the organs at risk, the KBP-generated plans produced lower doses, on average, for every normal-tissue objective except for the maximum dose to 0.1 cc of rectum. The time needed for the KBP-generated plans ranged from 6 to 15 minutes compared to 30 to 150 and 15 to 60 minutes for manual planning in Groups 1 and 2, respectively. KBP is a promising tool to aid in the transition to a new TPS. Our study indicates that high-quality treatment plans could have been generated in the newly implemented TPS more efficiently compared with not using KBP. Even after 8 months of the clinical use, KBP still showed an increase in plan quality and planning efficiency compared with manual planning. Copyright © 2017 American Association of Medical Dosimetrists. Published

  13. Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture'…?

    Science.gov (United States)

    Thomson, P J; Goodson, M L; Smith, D R

    2017-11-01

    Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO 2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Potentiation of glucocorticoid release does not modify the long-term effects of a single exposure to immobilization stress.

    Science.gov (United States)

    Dal-Zotto, Silvina; Martí, Octavi; Delgado, Raúl; Armario, Antonio

    2004-12-01

    Previous work has shown that a single exposure of rats to a severe stressor (immobilization, IMO) results, days to weeks later, in a reduced response (desensitization) of the hypothalamic-pituitary-adrenal (HPA) axis to a second exposure to the same stressor. In the present work, we studied the influence of both length of exposure to IMO and circulating levels of corticosterone on the first day on the degree of desensitization of two sets of physiological variables: HPA hormones and food intake. Rats were given SC saline or ACTH administration and then exposed to IMO for 0, 1 or 20 min. Seven days later, all rats were exposed to 20 min IMO. HPA response was followed on both experimental days by repeated blood sampling and food intake was measured on a 24-h basis. Both ACTH administration and IMO activates the HPA axis and IMO reduced food intake for several days. A single previous experience with IMO enhanced the post-IMO return of HPA hormones to basal levels on day 8 and reduced the degree of anorexia. The protective effect of previous IMO on food intake was independent of, whereas that on HPA activation was positively related to, the length of exposure on day 1. Concomitant ACTH administration on day 1 did not modify the observed effects. Long-term protective effects of a single exposure to IMO are observed even with a brief exposure, but they are not potentiated by increasing corticosterone levels during the first exposure.

  15. Potential of development of the mechanical-biological waste treatment; Entwicklungspotenzial der Mechanisch-Biologischen Abfallbehandlung

    Energy Technology Data Exchange (ETDEWEB)

    Grundmann, Thomas; Balhar, Michael [ASA e.V., Ennigerloh (Germany); Abfallwirtschaftsgesellschaft des Kreises Warendorf mbH, Ennigerloh (Germany)

    2013-03-01

    The Consortium Material-Specific Waste Treatment eV (Ennigerloh, Federal Republic of Germany) is an association of plant operators having the opinion that an economic and ecologic waste treatment only can be guaranteed by material-specific processes permanently. Due to the specific treatment processes in plants with mechanical-biological waste treatment (MBA) material flows are resulting being available for the recycling or exploitation. Under this aspect, the authors of the contribution under consideration report on the development potential of the mechanical-biological waste treatment. The state of the art of the technology of mechanical-biological waste treatment in Germany as well as the contribution of this technology to the resource protection and climate protection are described. Further aspects of this contribution are the increase of the energy efficiency and reduction of emissions; further development of the efficient sorting technology; development of integrated total conceptions - MBA-sites as centres for the production of renewable energies.

  16. Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: chemical analysis and potential toxicity.

    Science.gov (United States)

    Bach, Cristina; Dauchy, Xavier; Severin, Isabelle; Munoz, Jean-François; Etienne, Serge; Chagnon, Marie-Christine

    2013-08-15

    The purpose of this study was to investigate the impact of temperature on the release of PET-bottle constituents into water and to assess the potential health hazard using in vitro bioassays with bacteria and human cell lines. Aldehydes, trace metals and other compounds found in plastic packaging were analysed in PET-bottled water stored at different temperatures: 40, 50, and 60°C. In this study, temperature and the presence of CO2 increased the release of formaldehyde, acetaldehyde and antimony (Sb). In parallel, genotoxicity assays (Ames and micronucleus assays) and transcriptional-reporter gene assays for estrogenic and anti-androgenic activity were performed on bottled water extracts at relevant consumer exposure levels. As expected, and in accordance with the chemical formulations specified for PET bottles, neither phthalates nor UV stabilisers were present in the water extracts. However, 2,4-di-tert-butylphenol, a degradation compound of phenolic antioxidants, was detected. In addition, an intermediary monomer, bis(2-hydroxyethyl)terephthalate, was found but only in PET-bottled waters. None of the compounds are on the positive list of EU Regulation No. 10/2011. However, the PET-bottled water extracts did not induce any cytotoxic, genotoxic or endocrine-disruption activity in the bioassays after exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Stress-Induced Synaptic Dysfunction and Neurotransmitter Release in Alzheimer's Disease: Can Neurotransmitters and Neuromodulators be Potential Therapeutic Targets?

    Science.gov (United States)

    Jha, Saurabh Kumar; Jha, Niraj Kumar; Kumar, Dhiraj; Sharma, Renu; Shrivastava, Abhishek; Ambasta, Rashmi K; Kumar, Pravir

    2017-01-01

    The communication between neurons at synaptic junctions is an intriguing process that monitors the transmission of various electro-chemical signals in the central nervous system. Albeit any aberration in the mechanisms associated with transmission of these signals leads to loss of synaptic contacts in both the neocortex and hippocampus thereby causing insidious cognitive decline and memory dysfunction. Compelling evidence suggests that soluble amyloid-β (Aβ) and hyperphosphorylated tau serve as toxins in the dysfunction of synaptic plasticity and aberrant neurotransmitter (NT) release at synapses consequently causing a cognitive decline in Alzheimer's disease (AD). Further, an imbalance between excitatory and inhibitory neurotransmission systems induced by impaired redox signaling and altered mitochondrial integrity is also amenable for such abnormalities. Defective NT release at the synaptic junction causes several detrimental effects associated with altered activity of synaptic proteins, transcription factors, Ca2+ homeostasis, and other molecules critical for neuronal plasticity. These detrimental effects further disrupt the normal homeostasis of neuronal cells and thereby causing synaptic loss. Moreover, the precise mechanistic role played by impaired NTs and neuromodulators (NMs) and altered redox signaling in synaptic dysfunction remains mysterious, and their possible interlink still needs to be investigated. Therefore, this review elucidates the intricate role played by both defective NTs/NMs and altered redox signaling in synaptopathy. Further, the involvement of numerous pharmacological approaches to compensate neurotransmission imbalance has also been discussed, which may be considered as a potential therapeutic approach in synaptopathy associated with AD.

  18. In vivo evaluation of the potential neurotoxicity of aerosols released from mechanical stress of nano-TiO2 additived paints in mice chronically exposed by inhalation

    Science.gov (United States)

    Manixay, S.; Delaby, S.; Gaie-Levrel, F.; Wiart, M.; Motzkus, C.; Bencsik, A.

    2017-06-01

    Engineered Nanomaterials (ENM) provide technical and specific benefits due to their physical-chemical properties at the nanometer scale. For instance, many ENM are used to improve products in the building industry. Nanoscaled titanium dioxide (TiO2) is one of the most used ENM in this industry. Incorporated in different matrix, cement, glass, paints… TiO2 nanoparticles (NPs) provide the final product with anti-UV, air purification and self-cleaning properties, thanks to their photocatalytic activity. However, ageing processes of such products, as photocatalytic paints, during a mechanical stress have been shown to release TiO2 NPs from this matrix associated with sanding dust. Thus, workers who sand painted walls could be exposed to TiO2 NPs through inhalation. As inhalation may lead to a translocation of particulate matter to the brain via olfactory or trigeminal nerves, there is an urgent need for evaluating a potential neurotoxicity. In order to provide new knowledge on this topic, we developed a dedicated experimental set-up using a rodent model exposed via inhalation. The aerosol released from a mechanical stress of photocatalytic paints containing TiO2 NPs was characterized and coupled to an exposition chamber containing group of mice free to move and chronically exposed (2 hours per day for 5 days a week during 8 weeks).

  19. In vivo evaluation of the potential neurotoxicity of aerosols released from mechanical stress of nano-TiO2 additived paints in mice chronically exposed by inhalation

    International Nuclear Information System (INIS)

    Manixay, S; Bencsik, A; Delaby, S; Gaie-Levrel, F; Wiart, M; Motzkus, C

    2017-01-01

    Engineered Nanomaterials (ENM) provide technical and specific benefits due to their physical-chemical properties at the nanometer scale. For instance, many ENM are used to improve products in the building industry. Nanoscaled titanium dioxide (TiO 2 ) is one of the most used ENM in this industry. Incorporated in different matrix, cement, glass, paints… TiO 2 nanoparticles (NPs) provide the final product with anti-UV, air purification and self-cleaning properties, thanks to their photocatalytic activity. However, ageing processes of such products, as photocatalytic paints, during a mechanical stress have been shown to release TiO 2 NPs from this matrix associated with sanding dust. Thus, workers who sand painted walls could be exposed to TiO 2 NPs through inhalation. As inhalation may lead to a translocation of particulate matter to the brain via olfactory or trigeminal nerves, there is an urgent need for evaluating a potential neurotoxicity. In order to provide new knowledge on this topic, we developed a dedicated experimental set-up using a rodent model exposed via inhalation. The aerosol released from a mechanical stress of photocatalytic paints containing TiO 2 NPs was characterized and coupled to an exposition chamber containing group of mice free to move and chronically exposed (2 hours per day for 5 days a week during 8 weeks). (paper)

  20. Synthesis and Biological Evaluation of Novel Furozan-Based Nitric Oxide-Releasing Derivatives of Oridonin as Potential Anti-Tumor Agents

    Directory of Open Access Journals (Sweden)

    Hao Cai

    2012-06-01

    Full Text Available To search for novel nitric oxide (NO releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9h exhibited the most potential anti-tumor activity with IC50 values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.

  1. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  2. Targeted delivery and controlled release of Paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Yu, Baodan; Tan, Li; Zheng, Runhui; Tan, Huo; Zheng, Lixia

    2016-01-01

    A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH 5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy. - Highlights: • Chitosan and hyaluronan modified single-walled carbon nanotubes (SWNTs) were prepared for delivery of Paclitaxel (PTX). • Morphology, drug loading efficiency and drug release amount of the nanotubes were studied. • Cell viability, LDH, intracellular ROS levels and western blotting were evaluated. • The drug delivery system could effectively inhibit A549 cells proliferation.

  3. Targeted delivery and controlled release of Paclitaxel for the treatment of lung cancer using single-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Baodan; Tan, Li; Zheng, Runhui; Tan, Huo, E-mail: tanhuo.2008@163.com; Zheng, Lixia, E-mail: 66593953@qq.com

    2016-11-01

    A new type of drug delivery system (DDS) based on single-walled carbon nanotubes (SWNTs) for controlled-release of the anti-cancer drug Paclitaxel (PTX) was constructed in this study. Chitosan (CHI) was non-covalently attached to the SWNTs to improve biocompatibility. Biocompatible hyaluronan was also combined to the outer CHI layer to realise the specific targeting property. The results showed that the release of PTX was pH-triggered and was better at lower pH (pH 5.5). The modified SWNTs showed a significant improvement in intracellular reactive oxygen species (ROS), which may have enhanced mitogen-activated protein kinase activation and further promoted cell apoptosis. The results of western blotting indicated that the apoptosis-related proteins were abundantly expressed in A549 cells. Lactate dehydrogenase (LDH) release assay and cell viability assay demonstrated that PTX-loaded SWNTs could destroy cell membrane integrity, thus inducing lower cell viability of the A549 cells. Thus, this targeting DDS could effectively inhibit cell proliferation and kill A549 cells, is a promising system for cancer therapy. - Highlights: • Chitosan and hyaluronan modified single-walled carbon nanotubes (SWNTs) were prepared for delivery of Paclitaxel (PTX). • Morphology, drug loading efficiency and drug release amount of the nanotubes were studied. • Cell viability, LDH, intracellular ROS levels and western blotting were evaluated. • The drug delivery system could effectively inhibit A549 cells proliferation.

  4. Greenhouse gas emissions and reactive nitrogen releases during the life-cycles of staple food production in China and their mitigation potential.

    Science.gov (United States)

    Xia, Longlong; Ti, Chaopu; Li, Bolun; Xia, Yongqiu; Yan, Xiaoyuan

    2016-06-15

    Life-cycle analysis of staple food (rice, flour and corn-based fodder) production and assessments of the associated greenhouse gas (GHG) and reactive nitrogen (Nr) releases, from environmental and economic perspectives, help to develop effective mitigation options. However, such evaluations have rarely been executed in China. We evaluated the GHG and Nr releases per kilogram of staple food production (carbon and Nr footprints) and per unit of net economic benefit (CO2-NEB and Nr-NEB), and explored their mitigation potential. Carbon footprints of food production in China were obviously higher than those in some developed countries. There was a high spatial variation in the footprints, primarily attributable to differences in synthetic N use (or CH4 emissions) per unit of food production. Provincial carbon footprints had a significant linear relationship with Nr footprints, attributed to large contribution of N fertilizer use to both GHG and Nr releases. Synthetic N fertilizer applications and CH4 emissions dominated the carbon footprints, while NH3 volatilization and N leaching were the main contributors to the Nr footprints. About 564 (95% uncertainty range: 404-701) TgCO2eqGHG and 10 (7.4-12.4) Tg Nr-N were released every year during 2001-2010 from staple food production. This caused the total damage costs of 325 (70-555) billion ¥, equivalent to nearly 1.44% of the Gross Domestic Product of China. Moreover, the combined damage costs and economic input costs, accounted for 66%-80% of the gross economic benefit generated from food production. A reduction of 92.7TgCO2eqyr(-1) and 2.2TgNr-Nyr(-1) could be achieved by reducing synthetic N inputs by 20%, increasing grain yields by 5% and implementing off-season application of straw and mid-season drainage practices for rice cultivation. In order to realize these scenarios, an ecological compensation scheme should be established to incentivize farmers to gradually adopt knowledge-based managements. Copyright © 2016

  5. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  6. Effect of pre-treatments on methane production potential of energy crops and crop residues

    Energy Technology Data Exchange (ETDEWEB)

    Lehtomaki, A.; Ronkainen; Rintala, J.A. [Jyvaskla Univ. (Finland). Dept. of Biological and Environmental Sciences; Viinikainen, T.A. [Jyvaskla Univ. (Finland). Dept. of Chemistry

    2004-07-01

    Energy crops, that is, crops grown specifically for energy purposes are an alternative to food production in areas with sufficient agricultural land. Crop residues are also a potential source of energy. The anaerobic digestion of solid materials is limited by hydrolysis of complex polymeric substances such as lignocellulose. The methane producing potential of ligno cellulosic material is to pretreat the substrate in order to break up the polymer chains to more easily accessible soluble compounds. In this study, three different substrates were used: sugar beet tops, grass hay, and straw of oats. Biological pretreatments were the following: enzyme treatment, composting, white-rot fungi treatment. Also, pretreatment in water was tried. Chemical pretreatments included peracetic acid treatment, and treatment with two different alkalis. Alkaline pretreatments of hay and sugar beet tops have the potential to improve the methane yield. For instance, the yield of grass hay was increased 15 per cent by one particular alkaline treatment. Straw did not respond to any of the treatments tried. 18 refs., 1 tab., 2 figs.

  7. Mercury in terrestrial forested systems with highly elevated mercury deposition in southwestern China: The risk to insects and potential release from wildfires

    International Nuclear Information System (INIS)

    Zhou, Jun; Wang, Zhangwei; Sun, Ting; Zhang, Huan; Zhang, Xiaoshan

    2016-01-01

    Forests are considered a pool of mercury in the global mercury cycle. However, few studies have investigated the distribution of mercury in the forested systems in China. Tieshanping forest catchment in southwest China was impacted by mercury emissions from industrial activities and coal combustions. Our work studied mercury content in atmosphere, soil, vegetation and insect with a view to estimating the potential for mercury release during forest fires. Results of the present study showed that total gaseous mercury (TGM) was highly elevated and the annual mean concentration was 3.51 ± 1.39 ng m"−"2. Of the vegetation tissues, the mercury concentration follows the order of leaf/needle > root > bark > branch > bole wood for each species. Total ecosystem mercury pool was 103.5 mg m"−"2 and about 99.4% of the mercury resides in soil layers (0–40 cm). The remaining 0.6% (0.50 mg m"−"2) of mercury was stored in biomass. The large mercury stocks in the forest ecosystem pose a serious threat for large pluses to the atmospheric mercury during potential wildfires and additional ecological stress to forest insect: dung beetles, cicada and longicorn, with mercury concentration of 1983 ± 446, 49 ± 38 and 7 ± 5 ng g"−"1, respectively. Hence, the results obtained in the present study has implications for global estimates of mercury storage in forests, risks to forest insect and potential release to the atmosphere during wildfires. - Highlights: • Mercury in air, soil, biomass and insect were studied at a subtropical forest. • 99.4% of the total ecosystem mercury pools was resided in soil layers. • High mercury pools were large pulses to the atmosphere during potential wildfires. • High mercury deposition in forest pose an ecological stress to insect. - Large mercury pools in forest pose a serious threat for large pluses to the atmospheric mercury during potential wildfires and ecological stress to insect.

  8. Does exposure to opioid substitution treatment in prison reduce the risk of death after release? A national prospective observational study in England.

    Science.gov (United States)

    Marsden, John; Stillwell, Garry; Jones, Hayley; Cooper, Alisha; Eastwood, Brian; Farrell, Michael; Lowden, Tim; Maddalena, Nino; Metcalfe, Chris; Shaw, Jenny; Hickman, Matthew

    2017-08-01

    People with opioid use disorder (OUD) in prison face an acute risk of death after release. We estimated whether prison-based opioid substitution treatment (OST) reduces this risk. Prospective observational cohort study using prison health care, national community drug misuse treatment and deaths registers. Recruitment at 39 adult prisons in England (32 male; seven female) accounting for 95% of OST treatment in England during study planning. Adult prisoners diagnosed with OUD (recruited: September 2010-August 2013; first release: September 2010; last release: October 2014; follow-up to February 2016; n = 15 141 in the risk set). At release, participants were classified as OST exposed (n = 8645) or OST unexposed (n = 6496). The OST unexposed group did not receive OST, or had been withdrawn, or had a low dose. Primary outcome: all-cause mortality (ACM) in the first 4 weeks. drug-related poisoning (DRP) deaths in the first 4 weeks; ACM and DRP mortality after 4 weeks to 1 year; admission to community drug misuse treatment in the first 4 weeks. Unadjusted and adjusted Cox regression models (covariates: sex, age, drug injecting, problem alcohol use, use of benzodiazepines, cocaine, prison transfer and admission to community treatment), tested difference in mortality rates and community treatment uptake. During the first 4 weeks after prison release there were 24 ACM deaths: six in the OST exposed group and 18 in the OST unexposed group [mortality rate 0.93 per 100 person-years (py) versus 3.67 per 100 py; hazard ratio (HR) = 0.25; 95% confidence interval (CI) = 0.10-0.64]. There were 18 DRP deaths: OST exposed group mortality rate 0.47 per 100 py versus 3.06 per 100 py in the OST unexposed group (HR = 0.15; 95% CI = 0.04-0.53). There was no group difference in mortality risk after the first month. The OST exposed group was more likely to enter drug misuse treatment in the first month post-release (odds ratio 2.47, 95% CI = 2.31-2.65). The OST

  9. N-nitrosodimethylamine (NDMA) formation potential of amine-based water treatment polymers: Effects of in situ chloramination, breakpoint chlorination, and pre-oxidation.

    Science.gov (United States)

    Park, Sang Hyuck; Padhye, Lokesh P; Wang, Pei; Cho, Min; Kim, Jae-Hong; Huang, Ching-Hua

    2015-01-23

    Recent studies show that cationic amine-based water treatment polymers may be important precursors that contribute to formation of the probable human carcinogen N-nitrosodimethylamine (NDMA) during water treatment and disinfection. To better understand how water treatment parameters affect NDMA formation from the polymers, the effects of in situ chloramination, breakpoint chlorination, and pre-oxidation on the NDMA formation from the polymers were investigated. NDMA formation potential (NDMA-FP) as well as dimethylamine (DMA) residual concentration were measured from poly(epichlorohydrin dimethylamine) (polyamine) and poly(diallyldimethylammonium chloride) (polyDADMAC) solutions upon reactions with oxidants including free chlorine, chlorine dioxide, ozone, and monochloramine under different treatment conditions. The results supported that dichloramine (NHCl2) formation was the critical factor affecting NDMA formation from the polymers during in situ chloramination. The highest NDMA formation from the polymers occurred near the breakpoint of chlorination. Polymer chain breakdown and transformation of the released DMA and other intermediates were important factors affecting NDMA formation from the polymers in pre-oxidation followed by post-chloramination. Pre-oxidation generally reduced NDMA-FP of the polymers; however, the treatments involving pre-ozonation increased polyDADMAC's NDMA-FP and DMA release. The strategies for reducing NDMA formation from the polymers may include the avoidance of the conditions favorable to NHCl2 formation and the avoidance of polymer exposure to strong oxidants such as ozone. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Diffusion and Perfusion MR Imaging in Acute Stroke: Clinical Utility and Potential Limitations for Treatment Selection

    DEFF Research Database (Denmark)

    Bateman, Mathew; Slater, Lee-Anne; Leslie-Mazwi, Thabele M

    2017-01-01

    Magnetic resonance (MR) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) offer unique insight into acute ischemic stroke pathophysiology. These techniques may offer the ability to apply pathophysiology to accurately individualize acute stroke reperfusion treatment, including ...... to be investigated in ongoing randomized controlled trials, and continued research into these techniques will help achieve the goal of tissue-based decision making and individualized acute stroke treatment....... extending the opportunity of reperfusion treatment to well beyond the current time-based treatment windows. This review examines the use of DWI and PWI in the major stroke trials, their current clinical utility, and potential limitations for reperfusion treatment selection. DWI and PWI continue...

  11. Ethanol production potential from fermented rice noodle wastewater treatment using entrapped yeast cell sequencing batch reactor

    Science.gov (United States)

    Siripattanakul-Ratpukdi, Sumana

    2012-03-01

    Fermented rice noodle production generates a large volume of starch-based wastewater. This study investigated the treatment of the fermented rice noodle wastewater using entrapped cell sequencing batch reactor (ECSBR) compared to traditional sequencing batch reactor (SBR). The yeast cells were applied because of their potential to convert reducing sugar in the wastewater to ethanol. In present study, preliminary treatment by acid hydrolysis was performed. A yeast culture, Saccharomyces cerevisiae, with calcium alginate cell entrapment was used. Optimum yeast cell loading in batch experiment and fermented rice noodle treatment performances using ECSBR and SBR systems were examined. In the first part, it was found that the cell loadings (0.6-2.7 × 108 cells/mL) did not play an important role in this study. Treatment reactions followed the second-order kinetics with the treatment efficiencies of 92-95%. In the second part, the result showed that ECSBR performed better than SBR in both treatment efficiency and system stability perspectives. ECSBR maintained glucose removal of 82.5 ± 10% for 5-cycle treatment while glucose removal by SBR declined from 96 to 40% within the 5-cycle treatment. Scanning electron microscopic images supported the treatment results. A number of yeast cells entrapped and attached onto the matrix grew in the entrapment matrix.

  12. Potentiation by choline of basal and electrically evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum

    Science.gov (United States)

    Farber, S. A.; Kischka, U.; Marshall, D. L.; Wurtman, R. J.

    1993-01-01

    We examined the release of acetylcholine (ACh) and dopamine (DA) using a novel probe through which striatal neurons could be both superfused and stimulated electrically in both anesthetized and freely moving awake animals. Optimal stimulation parameters for eliciting ACh release from cholinergic neurons differed from those required for eliciting DA release from dopaminergic terminals: at 0.6 ms pulse duration, 20 Hz and 200 microA, ACh release increased to 357 +/- 30% (P basal release rose from 117 +/- 7% to 141 +/- 5% of initial baseline levels (P basal or evoked DA release although neostigmine (10 microM) significantly elevated basal DA release (from 36.7 fmol/10 min to 71.5 fmol/10 min; P basal (from 106 +/- 7% to 154 +/- 17%; P < 0.05) and electrically evoked (from 146 +/- 13 to 262 +/- 16%; P < 0.01) ACh release.(ABSTRACT TRUNCATED AT 250 WORDS).

  13. New generic approach to the treatment of organophosphate poisoning : Adenosine receptor mediated inhibition of ACh-release

    NARCIS (Netherlands)

    van Helden, HPM; Moor, E; Westerink, BHC; Bruijnzeel, PLB

    1998-01-01

    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and

  14. New generic approach to the treatment of organophosphate poisoning: Adenosine receptor mediated inhibition of ACh-release

    NARCIS (Netherlands)

    Helden, H.P.M. van; Groen, B.; Moor, E.; Westerink, B.H.C.; Bruijnzeel, P.L.B.

    1998-01-01

    Current treatment of acute organophosphate (OP) poisoning includes a combined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and

  15. Evaluating forest product potential as part of planning ecological restoration treatments on forested landscapes

    Science.gov (United States)

    R. James Barbour; Ryan Singleton; Douglas A. Maguire

    2007-01-01

    As landscape-scale assessments and modeling become a more common method for evaluating alternatives in integrated resource management, new techniques are needed to display and evaluate outcomes for large numbers of stands over long periods. In this proof of concept, we evaluate the potential to provide financial support for silvicultural treatments by selling timber...

  16. Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Fabliha Ahmed Chowdhury

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

  17. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

    Directory of Open Access Journals (Sweden)

    Sathish Sundar Dhilip Kumar

    2018-04-01

    Full Text Available Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric (Curcuma longa plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  18. Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases.

    Science.gov (United States)

    Sundar Dhilip Kumar, Sathish; Houreld, Nicolette Nadene; Abrahamse, Heidi

    2018-04-05

    Curcumin, a low molecular weight, lipophilic, major yellow natural polyphenolic, and the most well-known plant-derived compound, is extracted from the rhizomes of the turmeric ( Curcuma longa ) plant. Curcumin has been demonstrated as an effective therapeutic agent in traditional medicine for the treatment and prevention of different diseases. It has also shown a wide range of biological and pharmacological effects in drug delivery, and has actively been used for the treatment of aging-associated diseases, including cardiovascular diseases, atherosclerosis, neurodegenerative diseases, cancer, rheumatoid arthritis, ocular diseases, osteoporosis, diabetes, hypertension, chronic kidney diseases, chronic inflammation and infection. The functional application and therapeutic potential of curcumin in the treatment of aging-associated diseases is well documented in the literature. This review article focuses mainly on the potential role of plant-derived natural compounds such as curcumin, their mechanism of action and recent advances in the treatment of aging-associated diseases. Moreover, the review briefly recaps on the recent progress made in the preparation of nanocurcumins and their therapeutic potential in clinical research for the treatment of aging-associated diseases.

  19. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    DEFF Research Database (Denmark)

    Gomes, M. J.; Martins, S.; Ferreira, D.

    2014-01-01

    with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil...... less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded...... with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds....

  20. Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment

    Directory of Open Access Journals (Sweden)

    Kamonrak Cheewatanakornkool

    2017-11-01

    Full Text Available Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin (DOX conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical shape. However, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character; in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors.

  1. A double-blind comparison of slow-release and standard tablet formulations of fentiazac in the treatment of patients with tendinitis and bursitis.

    Science.gov (United States)

    Ginsberg, F; Famaey, J P

    1985-01-01

    Two double-blind studies were carried out to compare the effectiveness and tolerance of a slow-release tablet formulation of 300 mg fentiazac, given once daily, with the standard tablet formulations of 100 mg, given 4-times daily, or 200 mg, given twice daily. A total of 60 patients suffering from acute bicipital tendinitis and/or subdeltoid bursitis was studied, 15 patients on the slow-release and 15 on one of the two standard tablets in each of the two trials. Patients were assessed on entry and at Days 7 and 14 of treatment. The results in both studies showed that there was significant improvement in tenderness, pain on movement, overall pain and in the range of movement after treatment, there being no significant difference between those receiving the slow-release form or the standard tablets. Tolerance was good in all groups and only a few minor or moderate side-effects, mainly of a gastro-intestinal type, were reported.

  2. Investigation of the potential influence of production treatment chemicals on produced water toxicity

    International Nuclear Information System (INIS)

    Stine, E.R.; Gala, W.R.; Henry, L.R.

    1993-01-01

    Production treatment chemicals represent a diverse collection of chemical classes, added at various points from the wellhead to the final flotation cell, to prevent operational upsets and enhance the separation of oil from water. Information in the literature indicates that while many treatment chemicals are thought to partition into oil and not into the produced water, there are cases where a sufficiently water soluble treatment chemical is added at high enough concentrations to suggest that the treatment chemical may add to the aquatic toxicity of the produced water. A study was conducted to evaluate the potential effect of production treatment chemicals on the toxicity of produced waters using the US EPA Seven-day Mysidopsis bahia Survival, Growth and Fecundity Test. Samples of produced water were collected and tested for toxicity from three platforms under normal operating conditions, followed by repeated sampling and testing after a 72-hour period in which treatment chemical usage was discontinued, to the degree possible. Significant reductions in produced water toxicity were observed for two of the three platforms tested following either cessation of treatment chemical usage, or by comparing the toxicity of samples collected upstream and downstream of the point of treatment chemical addition

  3. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  4. Targeting kit activation: a potential therapeutic approach in the treatment of allergic inflammation

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Metcalfe, Dean D; Gilfillan, Alasdair M

    2007-01-01

    The prevalence of allergic diseases is increasing worldwide. Hence, there is continued need for novel pharmacological therapies for the treatment of these disorders. As the mast cell is one of the essential cells that contributes to the inflammation associated with allergic diseases, this cell type......E-receptor) on the cell surface. These mediators also contribute to the late and chronic stages of allergic inflammation. Thus, the IgE/antigen response has been a major focus in the development of new drugs targeting mast cells. The essential role that stem cell factor (SCF) and its receptor, Kit, play in mast cell...... remains an attractive target for such pharmacological intervention. Mast cells are major players in the early phase of the allergic response since they generate and release a variety of inflammatory mediators following antigen-dependent aggregation of IgE-bound FcepsilonRI (high affinity Ig...

  5. A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer.

    Science.gov (United States)

    Levy, Oren; Brennen, W Nathaniel; Han, Edward; Rosen, David Marc; Musabeyezu, Juliet; Safaee, Helia; Ranganath, Sudhir; Ngai, Jessica; Heinelt, Martina; Milton, Yuka; Wang, Hao; Bhagchandani, Sachin H; Joshi, Nitin; Bhowmick, Neil; Denmeade, Samuel R; Isaacs, John T; Karp, Jeffrey M

    2016-06-01

    Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Modelling Potential Consequences of Different Geo-Engineering Treatments for the Baltic Sea Ecosystem

    Science.gov (United States)

    Schrum, C.; Daewel, U.

    2017-12-01

    From 1950 onwards, the Baltic Sea ecosystem suffered increasingly from eutrophication. The most obvious reason for the eutrophication is the huge amount of nutrients (nitrogen and phosphorus) reaching the Baltic Sea from human activities. However, although nutrient loads have been decreasing since 1980, the hypoxic areas have not decreased accordingly. Thus, geo-engineering projects were discussed and evaluated to artificially ventilate the Baltic Sea deep water and suppress nutrient release from the sediments. Here, we aim at understanding the consequences of proposed geo-engineering projects in the Baltic Sea using long-term scenario modelling. For that purpose, we utilize a 3d coupled ecosystem model ECOSMO E2E, a novel NPZD-Fish model approach that resolves hydrodynamics, biogeochemical cycling and lower and higher trophic level dynamics. We performed scenario modelling that consider proposed geo-engineering projects such as artificial ventilation of Baltic Sea deep waters and phosphorus binding in sediments with polyaluminium chlorides. The model indicates that deep-water ventilation indeed suppresses phosphorus release in the first 1-4 years of treatment. Thereafter macrobenthos repopulates the formerly anoxic bottom regions and nutrients are increasingly recycled in the food web. Consequently, overall system productivity and fish biomass increases and toxic algae blooms decrease. However, deep-water ventilation has no long-lasting effect on the ecosystem: soon after completion of the ventilation process, the system turns back into its original state. Artificial phosphorus binding in sediments in contrast decreases overall ecosystem productivity through permanent removal of phosphorus. As expected it decreases bacterial production and toxic algae blooms, but it also decreases fish production substantially. Contrastingly to deep water ventilation, artificial phosphorus binding show a long-lasting effect over decades after termination of the treatment.

  7. In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin-layer (PRF-a laboratory evaluation of a modern, autologous wound treatment.

    Directory of Open Access Journals (Sweden)

    Daniela Knafl

    Full Text Available Platelet rich fibrin (PRF is an autologous fibrin glue, produced from patients' blood, which, besides intraoperative use, has applications in the treatment of infected wounds. The combination with antimicrobial agents results in a prolonged antibacterial effect allowing for wound dressing change intervals of seven days even in infected wounds. The aim of this study was to evaluate release kinetics of amikacin, teicoplanin or polyhexanide from a PRF-layer.PRF mixed with teicoplanin, amikacin or polyhexanide was sprayed on a silicon gauze patch and put on a colombia agar with bacteria with known minimal inhibitory concentration (MIC and incubated for 24 hours and afterwards transferred to another agar with the same bacterial strain. Inhibition zones were measured every 24 hours. This was repeated on 7 consecutive days. Antibiotic concentrations were calculated by interpolation.More than 1000 mg/L teicoplanin were released within the first 24 hours and 28.22 mg/L after 168 hours. Amikacin release was above 10,000 mg/L within the first 24 hours and still 120.8 mg/L after 120 hours. A release of polyhexanide could be verified for the first 24 hours only. Consequently teicoplanin and amikacin released from PRF showed antimicrobial in-vitro effects for almost a week, whereas an antimicrobial effect of polyhexanide could only be verified for the first 24 hours.Our Results show that a weekly dressing regimen may be justified in wounds treated with PRF plus amikacin or teicoplanin, since bacteria will be eradicated over a considerable period of time after a single application of PRF.

  8. Potential use of fly ash to soil treatment in the Morava region

    Science.gov (United States)

    Bulíková, Lucia; Kresta, František; Rochovanský, Martin

    2017-09-01

    Soil treatment by binders is a standard technology and leads to optimal utilization of excavated soils in road constructions. Soil treatment is controlled in the Czech Republic by EN 14227-15 and Technical Requirement TP 94. Soil treatment using fly ash has not been performed in the Czech Republic, although there is a sufficient normative base. Fly ash produced by burning of hard coal in the Moravian region was tested as a potential binder. Fly ash samples were mixed with loess loams (CI). Tested siliceous fly ash of class F (ASTM C618) did not showed hydraulic properties but it showed positive effect on reducing maximum dry density of mixtures, increasing the IBI value (Immediate bearing index) and decreasing tendency to volume changes when the amount of fly ash was increased. The results of laboratory tests demonstrate the possibility of using fly ashes as a binder for soil treatment.

  9. Occurrence and removal of NDMA and NDMA formation potential in wastewater treatment plants.

    Science.gov (United States)

    Yoon, Suchul; Nakada, Norihide; Tanaka, Hiroaki

    2011-06-15

    N-Nitrosodimethylamine (NDMA) is a potent carcinogen that is formed during disinfection by chlorination or ozonation in wastewater treatment plants (WWTPs). At present, little is known about the occurrence and fate of NDMA and its formation potential (FP) during wastewater treatment. We investigated the fate of NDMA and NDMA FP in 12 WWTPs. NDMA occurred in the influents at a concentration ranging from below the limit of quantification (LOQ NDMA FP (up to 8230 ng/L). The rate of NDMA FP reduction from influent to secondary effluent varied between 85 and 98%, regardless of treatment process. The rate of NDMA removal is due more to the influent properties than to the type of biological treatment process. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. [Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy].

    Science.gov (United States)

    Hulshof, Maarten C C M; Pieters, Bradley R; Koning, Caro C E

    2013-01-01

    The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

  11. Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

    2017-01-01

    We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest...... inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies......% CI: 1.73-4.31, p impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

  12. Release of natural radionuclides in the Czech Republic - from water treatment plants where water from underground water sources is treated

    International Nuclear Information System (INIS)

    Sinaglova, R.

    2014-01-01

    In this abstract author deals with the treatment of drinking water in the Czech Republic with removing of natural radionuclides as well as with treatment of filter cartridges. The advantage of these technologies is that flushing is not required so no wastewater occurs. Used ion exchangers with higher content of uranium are processed in the chemical treatment of uranium ores, managed by DIAMO, state enterprise. (authors)

  13. Urinary Nerve Growth Factor as a Potential Biomarker of Treatment Outcomes in Overactive Bladder Patients

    Directory of Open Access Journals (Sweden)

    Yoon Seok Suh

    2017-12-01

    Full Text Available Purpose The aim of this study was to investigate urinary nerve growth factor (NGF as a biomarker of treatment efficacy and recurrence in overactive bladder (OAB patients. Methods We enrolled 189 OAB subjects who visited our outpatient clinic from February 2010 to February 2015. All subjects with OAB received antimuscarinic treatment. A 3-day voiding diary and questionnaire were collected from each patient. Urinary levels of NGF were evaluated at baseline, the beginning of antimuscarinic treatment, and the end of antimuscarinic treatment. Urinary NGF was normalized to urine creatinine (Cr. Between-group comparisons of baseline characteristics were made using the Mann-Whitney U-test. Multivariate logistic regression analyses were used to predict responses to anticholinergic treatment and recurrence. The Wilcoxon signed-rank test with the Bonferroni correction was used for intragroup comparisons. A receiver operating characteristic curve was used to analyze the utility of this biomarker. Results Urinary levels of NGF/Cr tended to decrease in patients who responded to treatment (n=62, but this was not significant (P=0.260. Urinary NGF levels were higher at baseline in patients who did not experience recurrence than in those who did (P=0.047. In those who did not experience recurrence (n=29, urinary NGF/Cr decreased at the end of treatment compared to baseline, and this reduction was maintained at 12 weeks after the end of treatment (P<0.05. Conclusions Urinary NGF is a potential biomarker for predicting the outcome of antimuscarinic treatment in OAB patients. This may provide useful information when deciding to stop antimuscarinic treatment in responders.

  14. Effects of an acid/alkaline treatment on the release of antioxidants and cellulose from different agro-food wastes.

    Science.gov (United States)

    Vadivel, Vellingiri; Moncalvo, Alessandro; Dordoni, Roberta; Spigno, Giorgia

    2017-06-01

    The present investigation was aimed to evaluate the release of both antioxidants and cellulosic fibre from different agro-food wastes. Cost-effective and easily available agro-food residues (brewers' spent grains, hazelnut shells, orange peels and wheat straw) were selected and submitted to a double-step acid/alkaline fractionation process. The obtained acid and alkaline liquors were analysed for total phenols content and antioxidant capacity. The final fibre residue was analysed for the cellulose, lignin and hemicellulose content. The total phenols content and antioxidant capacity of the acid liquors were higher than the alkaline hydrolysates. Orange peels and wheat straw gave, respectively, the highest (19.70±0.68mg/g dm ) and the lowest (4.70±0.29mg/g dm ) total phenols release. Correlation between antioxidant capacity of the liquors and their origin depended on the analytical assay used to evaluate it. All the acid liquors were also rich in sugar degradation products (mainly furfural). HPLC analysis revealed that the most abundant phenolic compound in the acid liquors was vanillin for brewers' spent grains, hazelnut shells and wheat straw, and p-hydroxybenzoic acid for orange peels. Wheat straw served as the best raw material for cellulose isolation, providing a final residue with a high cellulose content (84%) which corresponded to 45% of the original cellulose. The applied process removed more than 90% of the hemicellulose fraction in all the samples, while delignification degree ranged from 67% (in hazelnut shells), to 93% (in brewers' spent grains). It was not possible to select a unique raw material for the release of highest levels of both total phenols and cellulose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  16. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  17. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in fir