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Sample records for metabolicos inh dnp

  1. Effects of INH, DNP, 2,4-D and CMU on the photosynthetic activity of barley and maize plants; Efecto de cuatro inhibidores metabolicos (INH, DNP, 2, 4-D y CMU) sobre la actividad fotosintetica de plantular de cebada (Hordeum vulgare L.) y Maiz (Zea mais L.)

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, J.; Prieto, M. P.

    1979-07-01

    Determinations of the rate of photosynthesis were made in barley and maize leaves treated with INH, DNP, 2,4-D or CMU. 1 ppm of the chemicals in nutritive solutions was absorbed by roots during 24 or 48 hours in both dark and light conditions. After this period, photosynthetic activity, compensation point and 14{sup C}O{sub 2} assimilation were determined. Results show that INH increases the rate of photosynthesis, DNP and 2,4-D do not alter it sensibly and CMU acts as a strong inhibitor of photosynthesis. Some possible applications for ths obtention of labelled compounds by biosynthesis are discussed. (Author) 87 refs.

  2. Effects of INH, DNP, 2, 4-D and CMU on the sugar content of the barley and maize leaves; Efecto de cuatro inhibidores metabolicos (INH, DNP, 2, 3-D y CMU) sobre el contenido en azucares de hohas de cebada (Hordeum vulgare L.) y Maiz (Zea mais L.)

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, J.; Sancho, P.

    1979-07-01

    1 ppm of the chemicals in nutritive solution was absorbed by barley and maize roots during 24 and 48 hours in dark or light conditioners in order to determine the best conditions. for the obtention of labelled sugars with high specific activity. Results show that the highest specific activity was obtained In maize plants treated with DNP for 24 hours in dark conditions. (Author) 51 refs.

  3. Effects of INH, DNP, 2,4-D and CMU on the photosynthetic activity of barley and maize plants

    International Nuclear Information System (INIS)

    Fernandez, J.; Prieto, M. P.

    1979-01-01

    Determinations of the rate of photosynthesis were made in barley and maize leaves treated with INH, DNP, 2,4-D or CMU. 1 ppm of the chemicals in nutritive solutions was absorbed by roots during 24 or 48 hours in both dark and light conditions. After this period, photosynthetic activity, compensation point and 14 C O 2 assimilation were determined. Results show that INH increases the rate of photosynthesis, DNP and 2,4-D do not alter it sensibly and CMU acts as a strong inhibitor of photosynthesis. Some possible applications for ths obtention of labelled compounds by biosynthesis are discussed. (Author) 87 refs

  4. Effects of INH, DNP, 2, 4-D and CMU on the sugar content of the barley and maize leaves

    International Nuclear Information System (INIS)

    Fernandez, J.; Sancho, P.

    1979-01-01

    1 ppm of the chemicals in nutritive solution was absorbed by barley and maize roots during 24 and 48 hours in dark or light conditioners in order to determine the best conditions for the obtention of labelled sugars with high specific activity. Results show that the highest specific activity was obtained in maize plants treated with DNP for 24 hours in dark conditions. (Author) 51 refs

  5. DNP Communication Function with RTDS

    DEFF Research Database (Denmark)

    Cha, Seung-Tae; Wu, Qiuwei; Saleem, Arshad

    2010-01-01

    A simulation case is implemented on RSCAD for testing their communication. The case has two binary status points (mapped to DNP binary input objects 1 & 2) and two binary control points (mapped to DNP binary output objects 10 and controlled via DNP objects 12). There is also one analog status poi...

  6. The DNP project: Quandaries for nursing scholars.

    Science.gov (United States)

    Dols, Jean Dowling; Hernández, Christina; Miles, Heather

    In the evolving Doctor of Nursing Practice (DNP) movement, there continues to be a lack of agreement about the final scholarly project. This study identifies and describes the faculty practices and challenges related to the DNP project across the United States. In a descriptive research study, 90 DNP program directors responded to an online survey describing the environment of the DNP program with emphasis on the final scholarly project. According to the respondents, 87% of faculty are somewhat or very dissatisfied with the DNP project. Elements that may contribute to the dissatisfaction are the reported lack of faculty knowledge of evidence-based practice and quality improvement, lack of consensus on the DNP project, lack of faculty resources for DNP projects, challenges with clinical sites for the DNP project, and students' scholarly writing skills. It is imperative to have academic/practice faculty oriented to DNP concepts; achieve consensus on the project title, type, depth, and outcomes; and have an ongoing dialog regarding DNP project design, execution, and challenges. Project implementation models need to be appropriate for the escalating DNP enrollment. Program support related to institutional review board relationships, student writing and statistical skills, and program-practice site partnerships are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Enhanced performance large volume dissolution-DNP

    DEFF Research Database (Denmark)

    Bowen, Sean; Ardenkjær-Larsen, Jan Henrik

    2014-01-01

    A systematic study of the performance of the dissolution process in dissolution-DNP is presented. A relatively simple set of modifications is made to the standard Hypersense dissolution system to enable polarization of large volume samples. These consist of a large volume sample cup along with su...

  8. Towards Overhauser DNP in supercritical CO(2).

    Science.gov (United States)

    van Meerten, S G J; Tayler, M C D; Kentgens, A P M; van Bentum, P J M

    2016-06-01

    Overhauser Dynamic Nuclear Polarization (ODNP) is a well known technique to improve NMR sensitivity in the liquid state, where the large polarization of an electron spin is transferred to a nucleus of interest by cross-relaxation. The efficiency of the Overhauser mechanism for dipolar interactions depends critically on fast local translational dynamics at the timescale of the inverse electron Larmor frequency. The maximum polarization enhancement that can be achieved for (1)H at high magnetic fields benefits from a low viscosity solvent. In this paper we investigate the option to use supercritical CO2 as a solvent for Overhauser DNP. We have investigated the diffusion constants and longitudinal nuclear relaxation rates of toluene in high pressure CO2. The change in (1)H T1 by addition of TEMPO radical was analyzed to determine the Overhauser cross-relaxation in such a mixture, and is compared with calculations based on the Force Free Hard Sphere (FFHS) model. By analyzing the relaxation data within this model we find translational correlation times in the range of 2-4ps, depending on temperature, pressure and toluene concentration. Such short correlation times may be instrumental for future Overhauser DNP applications at high magnetic fields, as are commonly used in NMR. Preliminary DNP experiments have been performed at 3.4T on high pressure superheated water and model systems such as toluene in high pressure CO2. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Solid Effect DNP in a Rapid-melt setup

    Science.gov (United States)

    van Bentum, P. J. M.; Sharma, M.; van Meerten, S. G. J.; Kentgens, A. P. M.

    2016-02-01

    Dynamic Nuclear Polarization (DNP) has become a key element in nuclear magnetic resonance (NMR). Recently, we developed a novel approach to DNP enhanced liquid-state NMR based on rapid melting of a solid hyperpolarized sample followed by 'in situ' liquid-state NMR detection. This method allows 1 H detection with fast cycling options for signal averaging. In nonpolar solvents, doped with BDPA radicals, proton enhancement factors were achieved of up to 400. A short recycling delay of about 5 s allows for a fast determination of the hyper-polarization dynamics as function of the microwave frequency and power. Here, we use the rapid melt dnp method to study the mechanisms for DNP in the solid phase in more detail. Solid Effect, Cross Effect, Solid Overhauser and Liquid-state (supercritical) Overhauser DNP enhancement can be observed in the same setup. In this paper, we concentrate on Solid Effect DNP observed with both homogeneous narrow line radicals such as BDPA and with wide line anisotropic nitroxide radicals such as TEMPOL. We find indications that BDPA protons play an important role in Solid Effect DNP with this radical. A simplified spin diffusion model for BDPA can give a semi-quantitative description of the enhancements as function of the microwave power and as function of the proton concentration in the solid solution. For aqueous frozen samples we observe a similar Solid Effect DNP enhancement, which is analyzed within the simplified spin diffusion model.

  10. A Study of the Perceptions of Doctor of Nursing (DNP) Program Administrators regarding the Integration of Acupuncture and Acupressure in DNP Curricula

    Science.gov (United States)

    Voight, Rebecca W.

    2012-01-01

    The purpose of this quantitative descriptive study was to explore the perceptions of DNP administrators regarding the extent acupuncture and acupressure are addressed in DNP curricula. Five research questions were addressed: 1. What are the perspectives of DNP program administrators regarding acupuncture and acupressure? 2. What are the…

  11. Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP): evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users.

    Science.gov (United States)

    Petróczi, Andrea; Ocampo, Jorge A Vela; Shah, Iltaf; Jenkinson, Carl; New, Rachael; James, Ricky A; Taylor, Glenn; Naughton, Declan P

    2015-10-14

    2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were systematically explored for availability of DNP, advice offered on DNP use and user profiles. Ninety-eight pre-workout and weight-loss supplements were purchased and analysed for DNP using liquid-chromatography-mass-spectrometry. Psychosocial variables were captured in an international sample of 35 DNP users (26.06 ± 6.10 years, 94.3 % male) with an anonymous, semi-qualitative self-reported survey. Although an industrial chemical, evidence from the Internet showed that DNP is sold 'as is', in capsules or tablets to suit human consumption, and is used 'uncut'. Analytical results confirmed that DNP is not on the supplement market disguised under fictitious supplement names, but infrequently was present as contaminant in some supplements (14/98) at low concentration (Internet accounts-a highly concealed and lonesome activity in real life. Positive experiences with the expected weight-loss prevail over the negative experiences from side effects (all but two users considered using DNP again) and help with using DNP safely is considered preferable over scare-tactics. Legislation banning DNP sale for human consumption protects the general public but DNP is sold 'as is' and used 'uncut' by determined users who are not dissuaded from experimenting with DNP based on health threats. Further research with stakeholders' active participation is imperative for targeted, proactive public health policies and harm-reduction measures for DNP, and other illicit supplements.

  12. Is the DNP the answer to the nursing faculty shortage? Not likely!

    Science.gov (United States)

    Kelly, Karen

    2010-01-01

    The DNP is being touted as the answer to the faculty shortage. There is no evidence that DNP graduates are any more willing to embrace the low salaries of nursing faculty than PhD graduates. The idea of the DNP as the answer to the faculty shortage is challenged. © 2010 Wiley Periodicals, Inc.

  13. Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP): evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users

    OpenAIRE

    Petróczi, Andrea; Ocampo, Jorge A. Vela; Shah, Iltaf; Jenkinson, Carl; New, Rachael; James, Ricky A.; Taylor, Glenn; Naughton, Declan P.

    2015-01-01

    Background 2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. Methods Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were system...

  14. Suppression of acetylpolyamine oxidase by selected AP-1 members regulates DNp73 abundance: mechanistic insights for overcoming DNp73-mediated resistance to chemotherapeutic drugs.

    Science.gov (United States)

    Bunjobpol, W; Dulloo, I; Igarashi, K; Concin, N; Matsuo, K; Sabapathy, K

    2014-08-01

    Enhanced resistance to chemotherapy has been correlated with high levels of Delta-Np73 (DNp73), an anti-apoptotic protein of the p53 tumor-suppressor family which inhibits the pro-apoptotic members such as p53 and TAp73. Although genotoxic drugs have been shown to induce DNp73 degradation, lack of mechanistic understanding of this process precludes strategies to enhance the targeting of DNp73 and improve treatment outcomes. Antizyme (Az) is a mediator of ubiquitin-independent protein degradation regulated by the polyamine biosynthesis pathway. We show here that acetylpolyamine oxidase (PAOX), a catabolic enzyme of this pathway, upregulates DNp73 levels by suppressing its degradation via the Az pathway. Conversely, downregulation of PAOX activity by siRNA-mediated knockdown or chemical inhibition leads to DNp73 degradation in an Az-dependent manner. PAOX expression is suppressed by several genotoxic drugs, via selected members of the activator protein-1 (AP-1) transcription factors, namely c-Jun, JunB and FosB, which are required for stress-mediated DNp73 degradation. Finally, chemical- and siRNA-mediated inhibition of PAOX significantly reversed the resistant phenotype of DNp73-overexpressing cancer cells to genotoxic drugs. Together, these data define a critical mechanism for the regulation of DNp73 abundance, and reveal that inhibition of PAOX could widen the therapeutic index of cytotoxic drugs and overcome DNp73-mediated chemoresistance in tumors.

  15. On the present and future of dissolution-DNP

    DEFF Research Database (Denmark)

    Ardenkjær-Larsen, Jan Henrik

    2016-01-01

    Dissolution-DNP is a method to create solutions of molecules with nuclear spin polarization close to unity. The many orders of magnitude signal enhancement have enabled many new applications, in particular in vivo MR metabolic imaging. The method relies on solid state dynamic nuclear polarization...... where new ideas will make an impact. Most certainly, the future will take unpredicted directions, but hopefully the thoughts presented here will stimulate new ideas that can further advance the field. (C) 2016 Elsevier Inc. All rights reserved....... at low temperature followed by a dissolution to produce the room temperature solution of highly polarized spins. This work describes the present and future of dissolution-DNP in the mind of the author. The article describes some of the current trends in the field as well as outlines some of the areas...

  16. The development of practice scholarship in DNP programs: a paradigm shift.

    Science.gov (United States)

    Brown, Marie Annette; Crabtree, Katherine

    2013-01-01

    Doctoral education in nursing is undergoing a paradigm shift. The doctor of nursing practice (DNP) degree was conceived to improve practice expertise and accelerate the translation of evidence into practice. The need for doctoral preparation that focuses on both expert practice and practice inquiry acknowledges the complexity of evidence-based practice. The DNP prepares graduates to practice at the most advanced level of nursing and to evaluate current practice approaches, to appraise evidence, and to use this knowledge to create clinical strategies that improve practice and health outcomes. DNP curricula need to evolve through shared best practices grounded in financial sustainability. Because of the evolutionary nature of new programs, there is a need for continuous rapid adjustment of the DNP curriculum. Ideas presented here have evolved with student, faculty, and agency input. Many elements of DNP curricula represent a shared world view of faculty across the county. However, consensus about the DNP project has not been reached and is urgently needed to promote acceptance of the DNP-prepared advanced practice registered nurse. The DNP project allows synthesis of the American Association of Colleges of Nursing DNP Essentials through "real world" translation of evidence into practice. This article proposes that DNP projects be defined as practice improvement partnerships between academia and community agencies. This "win-win" collaboration can improve care while preparing the next generation of nurses for the demands of increasingly complex healthcare environments. © 2013.

  17. A study of the effect of Nigella sativa (Black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits

    Science.gov (United States)

    Hassan, Anwar S.; Ahmed, Jawad H.; Al-Haroon, Sawsan S.

    2012-01-01

    Objective: To investigate the possibility of hepatoprotective effect of Nigella sativa (NS) in INH-induced hepatotoxicity. Materials and Methods: The experiments were carried out on 24 male rabbits. They were divided into 4 groups (6 each); rabbits in group 1 were treated with INH following a standard protocol to induce hepatotoxicity. Rabbits in group 2 received starch. Group 3 received NS 1 g/kg/day before INH treatment. Group 4 rabbits were treated with NS only. Phenobarbital sodium (IP) was given to induce metabolism of INH. INH and NS were given orally. The experiment continued for 12 days; at day 13, animals were sacrificed. Liver function tests, malondialdehyde (MDA) were estimated in serum and in liver homogenates. Liver histopathological examinations were performed. Results: Histopathological changes of hepatotoxicity were found in all INH-treated rabbits. The histopathological findings were normal in three rabbits treated with NS before INH, very mild in two, and with moderate changes in one rabbit. Serum alanine aminotransferase (S.ALT) was elevated after INH treatment and returned back to the control value when NS was given before INH. Similar pattern of effect was noticed with serum aspartate aminotransferase (S.AST), S. total bilirubin, S. MDA, and Serum alkaline phosphatase.In liver homogenate, AST, ALT, and MDA were increased with INH treatment compared to the control, then decreased with NS treatment given before INH Conclusions: NS has hepatoprotective effects against INH-induced hepatotoxicity in rabbits. NS 1 g/kg proved safe, no adverse effects; no histopathological or biological abnormalities were seen. PMID:23248393

  18. Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

    Directory of Open Access Journals (Sweden)

    María Martínez-Hoyos

    2016-06-01

    Full Text Available Despite being one of the first antitubercular agents identified, isoniazid (INH is still the most prescribed drug for prophylaxis and tuberculosis (TB treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI of the enoyl-ACP reductase (InhA has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb, but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR and extensively (XDR drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment.

  19. Building skills in organizational and systems changes: a DNP-FNP clinical curriculum.

    Science.gov (United States)

    Hoyle, Christine; Johnson, Gail

    2015-04-13

    DNP-prepared nurse practitioner leaders play a pivotal role in organizational change and quality improvement consistent with the IHI Triple Aim: improving quality of care, health of populations, and reducing cost. A DNP-FNP curriculum is described, designed to build students' leadership competencies for systems change in healthcare settings.

  20. {sup 13}C DNP of biomolecules dissolved in water

    Energy Technology Data Exchange (ETDEWEB)

    Dollmann, Bjoern C.; Gruss, Konstantin; Jagschies, Lasse; Spiess, Hans W.; Hinderberger, Dariush; Muennemann, Kerstin [Max-Planck-Institute for Polymer Research, Mainz (Germany); Schreiber, Laura M. [Section of Medical Physics, Mainz University Medical Center, Mainz (Germany)

    2010-07-01

    Nuclear magnetic resonance (NMR) and related techniques have become indispensable tools with innumerable applications in physics, chemistry, biology and medicine. One of the main obstacles in NMR is its notorious lack of sensitivity, which is due to the low equilibrium polarization of nuclear spins at ambient temperature. This disadvantage becomes obvious if low {gamma} nuclei are employed for NMR spectroscopy and MR imaging or when small sample volumes should be investigated. However, this obstacle could be overcome by in vitro hyperpolarization of molecules via dynamic nuclear polarization (DNP). One major issue of this approach is the limited lifetime of the hyperpolarized state, which restricts the application and detection of the hyperpolarized molecules to roughly three times T{sub 1}. Therefore a lot of effort is put into the hyperpolarization of biomolecules with long spin lattice relaxation times. In this work, we present direct Overhauser-type DNP enhancement of {sup 13}C in solution at ambient temperatures. For a 5 {mu} l sample of 10 M {sup 13}C-enriched urea with 40 mM TEMPOL dissolved in water we measured a {sup 13}C signal enhancement of -335 in a commercial X-band electromagnet.

  1. Cutaneous drug toxicity from 2,4-dinitrophenol (DNP): Case report and histological description.

    Science.gov (United States)

    Le, Patricia; Wood, Benjamin; Kumarasinghe, Sujith Prasad

    2015-11-01

    The use of 2,4-dinitrophenol (DNP) has regained popularity as a weight loss aid in the last two decades due to increased marketing to bodybuilders and the increasing availability of this banned substance via the Internet. 2,4-DNP is a drug of narrow therapeutic index and toxicity results in hyperthermia, diaphoresis, tachycardia, tachypnoea and possible cardiac arrest and death. Skin toxicity from 2,4-DNP has not been reported since the 1930s. We report a case of a 21-year-old bodybuilding enthusiast who presented with a toxic exanthem after taking 2,4-DNP, and describe the first skin biopsy findings in a case of 2,4-DNP toxicity. © 2014 The Australasian College of Dermatologists.

  2. From Metacognition to Practice Cognition: The DNP e-Portfolio to Promote Integrated Learning.

    Science.gov (United States)

    Anderson, Kelley M; DesLauriers, Patricia; Horvath, Catherine H; Slota, Margaret; Farley, Jean Nelson

    2017-08-01

    Educating Doctor of Nursing Practice (DNP) students for an increasingly complex health care environment requires novel applications of learning concepts and technology. A deliberate and thoughtful process is required to integrate concepts of the DNP program into practice paradigm changes to subsequently improve students' abilities to innovate solutions to complex practice problems. The authors constructed or participated in electronic portfolio development inspired by theories of metacognition and integrated learning. The objective was to develop DNP student's reflection, integration of concepts, and technological capabilities to foster the deliberative competencies related to the DNP Essentials and the foundations of the DNP program. The pedagogical process demonstrates how e-portfolios adapted into the doctoral-level curriculum for DNP students can address the Essentials and foster the development of metacognitive capabilities, which translates into practice changes. The authors suggest that this pedagogical approach has the potential to optimize reflective and deliberative competencies among DNP students. [J Nurs Educ. 2017;56(8):497-500.]. Copyright 2017, SLACK Incorporated.

  3. Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity.

    Science.gov (United States)

    Hassan, Hozeifa M; Yousef, Bashir A; Guo, Hongli; Xiaoxin, Liu; Zhang, Luyong; Jiang, Zhenzhou

    2018-01-01

    Tuberculosis (TB) is one of the oldest infectious diseases that affected humankind and remains one of the world's deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH) in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS) potentially enhanced INH toxicity. These enhancing activities ranged between augmenting the inflammatory stress, oxidative stress, alteration of bile acid homeostasis, and CYP2E1 over-expression. Although pre-treatment with dexamethasone (DEX) helped overcome both inflammatory and oxidative stress which ended-up in alleviation of LPS augmenting effects, but still minor toxicities were being detected, alongside with CYP2E1 over expression. This finding positively indicated the corner-stone role played by CYP2E1 in the pathogenesis of INH/LPS-induced liver damage. Therefore, we examined whether INH/LPS co-treatment with CYP2E1 inhibitor diallyl sulfide (DAS) and DEX can protect against the INH/LPS-induced hepatotoxicity. Our results showed that pre-administration of both DAS and DEX caused significant reduction in serum TBA, TBil, and gamma-glutamyl transferase levels. Furthermore, the histopathological analysis showed that DAS and DEX could effectively reverse the liver lesions seen following INH/LPS treatment and protect against hepatic steatosis as indicated by absence of lipid accumulation. Pre-treatment with DAS alone could not completely block the CYP2E1 protein expression following INH/LPS treatment, as appeared in the immunoblotting and immunohistochemistry results. This is probably due to the fact that the combined enhancement activities of both INH and LPS on CYP2E1 protein expression levels might

  4. Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hozeifa M. Hassan

    2018-03-01

    Full Text Available Tuberculosis (TB is one of the oldest infectious diseases that affected humankind and remains one of the world’s deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS potentially enhanced INH toxicity. These enhancing activities ranged between augmenting the inflammatory stress, oxidative stress, alteration of bile acid homeostasis, and CYP2E1 over-expression. Although pre-treatment with dexamethasone (DEX helped overcome both inflammatory and oxidative stress which ended-up in alleviation of LPS augmenting effects, but still minor toxicities were being detected, alongside with CYP2E1 over expression. This finding positively indicated the corner-stone role played by CYP2E1 in the pathogenesis of INH/LPS-induced liver damage. Therefore, we examined whether INH/LPS co-treatment with CYP2E1 inhibitor diallyl sulfide (DAS and DEX can protect against the INH/LPS-induced hepatotoxicity. Our results showed that pre-administration of both DAS and DEX caused significant reduction in serum TBA, TBil, and gamma-glutamyl transferase levels. Furthermore, the histopathological analysis showed that DAS and DEX could effectively reverse the liver lesions seen following INH/LPS treatment and protect against hepatic steatosis as indicated by absence of lipid accumulation. Pre-treatment with DAS alone could not completely block the CYP2E1 protein expression following INH/LPS treatment, as appeared in the immunoblotting and immunohistochemistry results. This is probably due to the fact that the combined enhancement activities of both INH and LPS on CYP2E1 protein expression

  5. Communication Test for ‘MatrikonOPC Server for SCADA DNP 3’ with RTDS

    DEFF Research Database (Denmark)

    Wu, Qiuwei; Cha, Seung-Tae; Saleem, Arshad

    2010-01-01

    The purpose of the communication test for ‘MatrikonOPC server for SCADA DNP 3’ with RTDS is to verify the data exchange between the ‘MatrikonOPC server for SCADA DNP 3’ and the RTDS using the DNP 3 protocol.The communication test is part of the work for the ‘Wind in Øresund’ project. The objective...... of the ‘Wind in Øresund’ project is to build a demonstration and education system of power system operation and control with a RTDS and a SCADA system....

  6. Can metal ion complexes be used as polarizing agents for solution DNP? A theoretical discussion.

    Science.gov (United States)

    Luchinat, Claudio; Parigi, Giacomo; Ravera, Enrico

    2014-04-01

    Dynamic nuclear polarization (DNP) can be used to dramatically increase the NMR signal intensities in solutions and solids. DNP is usually performed using nitroxide radicals as polarizing agents, characterized by sharp EPR lines, fast rotation, fast diffusion, and favorable distribution of the unpaired electron. These features make the nitroxide radicals ideally suited for solution DNP. Here, we report some theoretical considerations on the different behavior of some inorganic compounds with respect to nitroxide radicals. The relaxation profiles of slow relaxing paramagnetic metal aqua ions [copper(II), manganese(II), gadolinium(III) and oxovanadium(IV)] and complexes have been re-analyzed according to the standard theory for dipolar and contact relaxation, in order to estimate the coupling factor responsible for the maximum DNP enhancement that can be achieved in solution and its dependence on field, temperature and relative importance of outer-sphere versus inner-sphere relaxation.

  7. Quenching of Tryptophan Fluorescence in the Presence of 2,4-DNP, 2,6-DNP, 2,4-DNA and DNOC and Their Mechanism of Toxicity

    Directory of Open Access Journals (Sweden)

    Cristina-Amalia Dumitraş Huţanu

    2013-02-01

    Full Text Available Although they are widely used as insecticides, acaricides and fungicides in the agriculture or as raw materials in the dye industry, dinitrophenols (DNPs are extremely noxious, death cases having been registered. These compounds produce cataracts, lower leucocyte levels, disturb the general metabolism and can cause cancer. It is also assumed that DNPs hinder the proton translocation through the mitochondrial inner membrane and therefore inhibit oxidative phosphorylation. Their fluorescence quenching properties can help understand and explain their toxicity. Fluorescence quenching of tryptophan was tested using different dinitrophenols such as 2,4-dinitrophenol (2,4-DNP, 4,6-dinitro-orthocresol (DNOC, 2-[(2,4-dinitrophenylamino]acetic acid (GlyDNP, 2-(1-methyl-heptyl-4.6-dinitrophenyl crotonate (Karathan, 2-amino-5-[(1-((carboxymethylamino-3-((2,4-dinitrophenylthio-1-oxopropan-2-ylamino]-5-oxopentanoic acid (SDN GSH, 2,4-dinitroanisole (2,4-DNA and 2,4-dinitrobenzoic acid (2,4-DNB. 2,4-DNP and DNOC showed the highest tryptophan fluorescence quenching constant values, these being also the most toxic compounds. The electronic chemical potential value of the most stable complex of 2,4-DNP-with tryptophan is higher than the values of the electronic chemical potentials of complexes corresponding to the derivatives.

  8. Efficient DNP NMR of Membrane Proteins: Sample Preparation Protocols, Sensitivity, and Radical Location

    Science.gov (United States)

    Liao, Shu Y.; Lee, Myungwoon; Wang, Tuo; Sergeyev, Ivan V.; Hong, Mei

    2016-01-01

    Although dynamic nuclear polarization (DNP) has dramatically enhanced solid-state NMR spectral sensitivities of many synthetic materials and some biological macromolecules, recent studies of membrane-protein DNP using exogenously doped paramagnetic radicals as polarizing agents have reported varied and sometimes surprisingly limited enhancement factors. This motivated us to carry out a systematic evaluation of sample preparation protocols for optimizing the sensitivity of DNP NMR spectra of membrane-bound peptides and proteins at cryogenic temperatures of ~110 K. We show that mixing the radical with the membrane by direct titration instead of centrifugation gives a significant boost to DNP enhancement. We quantify the relative sensitivity enhancement between AMUPol and TOTAPOL, two commonly used radicals, and between deuterated and protonated lipid membranes. AMUPol shows ~4 fold higher sensitivity enhancement than TOTAPOL, while deuterated lipid membrane does not give net higher sensitivity for the membrane peptides than protonated membrane. Overall, a ~100 fold enhancement between the microwave-on and microwave-off spectra can be achieved on lipid-rich membranes containing conformationally disordered peptides, and absolute sensitivity gains of 105–160 can be obtained between low-temperature DNP spectra and high-temperature non-DNP spectra. We also measured the paramagnetic relaxation enhancement of lipid signals by TOTAPOL and AMUPol, to determine the depths of these two radicals in the lipid bilayer. Our data indicate a bimodal distribution of both radicals, a surface-bound fraction and a membrane-bound fraction where the nitroxides lie at ~10 Å from the membrane surface. TOTAPOL appears to have a higher membrane-embedded fraction than AMUPol. These results should be useful for membrane-protein solid-state NMR studies under DNP conditions and provide insights into how biradicals interact with phospholipid membranes. PMID:26873390

  9. High resolution observed in 800 MHz DNP spectra of extremely rigid type III secretion needles

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, Pascal [Leibniz-Institut für Molekulare Pharmakologie, Department of Molecular Biophysics (Germany); Mance, Deni [Utrecht University, NMR Research Group, Bijvoet Center for Biomolecular Research (Netherlands); Chevelkov, Veniamin [Leibniz-Institut für Molekulare Pharmakologie, Department of Molecular Biophysics (Germany); Giller, Karin; Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Department of NMR-Based Structural Biology (Germany); Baldus, Marc [Utrecht University, NMR Research Group, Bijvoet Center for Biomolecular Research (Netherlands); Lange, Adam, E-mail: alange@fmp-berlin.de [Leibniz-Institut für Molekulare Pharmakologie, Department of Molecular Biophysics (Germany)

    2016-08-15

    The cryogenic temperatures at which dynamic nuclear polarization (DNP) solid-state NMR experiments need to be carried out cause line-broadening, an effect that is especially detrimental for crowded protein spectra. By increasing the magnetic field strength from 600 to 800 MHz, the resolution of DNP spectra of type III secretion needles (T3SS) could be improved by 22 %, indicating that inhomogeneous broadening is not the dominant effect that limits the resolution of T3SS needles under DNP conditions. The outstanding spectral resolution of this system under DNP conditions can be attributed to its low overall flexibility.

  10. Strategic innovation between PhD and DNP programs: Collaboration, collegiality, and shared resources.

    Science.gov (United States)

    Edwards, Joellen; Rayman, Kathleen; Diffenderfer, Sandra; Stidham, April

    2016-01-01

    At least 111 schools and colleges of nursing across the nation provide both PhD and DNP programs (AACN, 2014a). Collaboration between nurses with doctoral preparation as researchers (PhD) and practitioners (DNP) has been recommended as essential to further the profession; that collaboration can begin during the educational process. The purpose of this paper is to describe the development and implementation of successful DNP and PhD program collaboration, and to share the results of that collaboration in an educational setting. Faculty set strategic goals to maximize the effectiveness and efficiency of both new DNP and existing PhD programs. The goals were to promote collaboration and complementarity between the programs through careful capstone and dissertation differentiation, complementary residency activities, joint courses and inter-professional experiences; promote collegiality in a blended on-line learning environment through shared orientation and intensive on-campus sessions; and maximize resources in program delivery through a supportive organizational structure, equal access to technology support, and shared faculty responsibilities as appropriate to terminal degrees. Successes such as student and faculty accomplishments, and challenges such as managing class size and workload, are described. Collaboration, collegiality and the sharing of resources have strengthened and enriched both programs and contributed to the success of students, faculty. These innovative program strategies can provide a solid foundation for DNP and PhD collaboration. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Faculty and organizational characteristics associated with informatics/health information technology adoption in DNP programs.

    Science.gov (United States)

    Fulton, Cathy R; Meek, Julie A; Walker, Patricia Hinton

    2014-01-01

    Nursing informatics/health information technology are key components of graduate nursing education and an accreditation requirement, yet little is known about the extent to which doctor of nursing practice (DNP) curricula include these content domains. The purpose of this descriptive study was to elicit perceptions of DNP program directors relative to (a) whether and how the American Association of Colleges of Nursing's (AACN's) Essential IV standard has been met in their DNP programs; (b) whether the Technology Informatics Guiding Educational Reform Initiative Foundation's Phase II competencies have been integrated in their programs; and (c) the faculty and organizational characteristics associated with the adoption of the AACN's Essential IV. In 2011, an electronic survey was sent to all 138 DNP program directors identified on the AACN Web site with an 81.2% response rate. Findings include variation in whether and how programs have integrated informatics/health information technology content, a lack of informatics-certified and/or master's-prepared faculty, and a perceived lack of faculty awareness of informatics curricular guidelines. DNP program director and dean awareness and support of faculty informatics education, use of informatics competency guidelines, and national policy and stimulus funding support are recommended to promote curricular inclusion and the engagement of nurses in strong informatics practices. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. EPR and DNP Properties of Certain Novel Single Electron Contrast Agents Intended for Oximetric Imaging

    DEFF Research Database (Denmark)

    Ardenkjær-Larsen, J. H.; Laursen, I; Leunbach, I.

    1998-01-01

    Parameters of relevance to oximetry with Overhauser magnetic resonance imaging (OMRI) have been measured for three single electron contrast agents of the triphenylmethyl type. The single electron contrast agents are stable and water soluble. Magnetic resonance properties of the agents have been...... examined with electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and dynamic nuclear polarization (DNP) at 9.5 mT in water, isotonic saline, plasma, and blood at 23 and 37°C. The relaxivities of the agents are about 0.2–0.4 mM−1s−1and the DNP enhancements extrapolate close...... than 1 μT in water at room temperature. The longitudinal electron spin relaxation rate is calculated from the DNP enhancement curves. The oxygen broadening in water is about 50 μT/mM O2at 37°C. These agents have good properties for oximetry with OMRI....

  13. High resolution observed in 800 MHz DNP spectra of extremely rigid type III secretion needles

    NARCIS (Netherlands)

    Fricke, Pascal; Mance, Deni; Chevelkov, Veniamin; Giller, Karin; Becker, Stefan; Baldus, Marc; Lange, Adam

    2016-01-01

    The cryogenic temperatures at which dynamic nuclear polarization (DNP) solid-state NMR experiments need to be carried out cause line-broadening, an effect that is especially detrimental for crowded protein spectra. By increasing the magnetic field strength from 600 to 800 MHz, the resolution of DNP

  14. 75 FR 64694 - Approval for Expanded Manufacturing Authority; Foreign-Trade Subzone 33E; DNP IMS America...

    Science.gov (United States)

    2010-10-20

    ... Manufacturing Authority; Foreign-Trade Subzone 33E; DNP IMS America Corporation (Thermal Transfer Ribbon Printer..., grantee of FTZ 33, has requested an expansion of the scope of manufacturing authority on behalf of DNP IMS...-6636, 2/10/2010) and the application has been processed pursuant to the FTZ Act and the Board's...

  15. An example of a statistics course in a doctor of nursing practice (DNP) program.

    Science.gov (United States)

    Lauver, Lori; Phalen, Ann Gibbons

    2012-01-01

    The current healthcare environment requires RNs and advanced practice nurses (APNs) to be proficient in critique and utilization of healthcare research to inform an evidence base for practice. Many practicing RNs and APNs lack competency in statistical analysis and interpretation, and knowledge in the conduct of nursing research. Doctor of Nursing Practice (DNP) students need this knowledge to address researchable problems found in their own practice environments and, as leaders in practice, to mentor colleagues and other members of the healthcare team. The authors describe a DNP statistics course including its design and composition and demonstrate how using traditional, data-oriented, and student project approaches yields positive learning outcomes.

  16. Multiple receptor conformers based molecular docking study of fluorine enhanced ethionamide with mycobacterium enoyl ACP reductase (InhA).

    Science.gov (United States)

    Khan, Akib Mahmud; Shawon, Jakaria; Halim, Mohammad A

    2017-10-01

    A major limitation in current molecular docking method is that of failure to account for receptor flexibility. Herein we report multiple receptor conformers based molecular docking as a practical alternative to account for the receptor flexibility. Multiple (forty) conformers of Mycobacterium Enoyl ACP Reductase (InhA) are generated from Molecular Dynamics simulation and twenty crystallographic structures of InhA bound to different inhibitors are obtained from the Protein Data Bank. Fluorine directed modifications are performed to currently available anti-tuberculosis drug ethionamide. The modified drugs are optimized using B3LYP 6-31G (d,p) level of theory. Dipole moment, frontier orbital gap and thermodynamical properties such as electronic energy, enthalpy and Gibbs free energy of these optimized drugs are investigated. These drugs are subsequently docked against the conformers of InhA. Molecular docking against multiple InhA conformations show variation in ligand binding affinity and suggest that Ser94, Gly96, Lys165 and Ile194 amino acids play critical role on strong drug-InhA interaction. Modified drug N1 showed greater binding affinity compared to EN in most conformations. Structure of PDB ID: 2NSD and snapshot conformer at 5.5ns show most favorable binding with N1 compared to other conformers. Fluorine participates in forming fluorine bonds and contributes significantly in increasing binding affinity. Our study reveal that addition of trifluoromethyl group explicitly shows promise in improving thermodynamic properties and in enhancing hydrogen bonding and non-bonded interactions. Molecular dynamics (MD) simulation show that EN and N1 remained in the binding pocket similar to the docked pose of EN-InhA and E1-InhA complexes and also suggested that InhA binds to its inhibitor in inhibitor-induced folding manner. ADMET calculations predict modified drugs to have improved pharmacokinetic properties. Our study concludes that multiple receptor conformers based

  17. The Development of 460 GHz gyrotrons for 700 MHz DNP-NMR spectroscopy

    Science.gov (United States)

    Idehara, T.; Tatematsu, Y.; Yamaguchi, Y.; Khutoryan, E. M.; Kuleshov, A. N.; Ueda, K.; Matsuki, Y.; Fujiwara, T.

    2015-07-01

    Two demountable gyrotrons with internal mode converters were developded as sub-THz radiation sources for 700 MHz DNP (Dynamic Nuclear Polarization) enhanced NMR spectroscopy. Experimental study on the DNP-NMR spectroscopy will be carried out in Osaka University, Institute for Protein Research, as a collaboration with FIR UF. Both gyrotrons operate near 460 GHz and the output CW power measured at the end of transmission system made by circular waveguides is typically 20 to 30 watts. One of them named Gyrotron FU CW GVI (we are using "Gyrotron FU CW GO-1" as an official name in Osaka University) is designed to have a special function of high speed frequency modulation δ f within 100 MHz band. This will expand excitable band width of ESR and increase the number of electron spins contributing to DNP. The other gyrotron, Gyrotron FU CW GVIA ("Gyrotron FU CW GO-II") has a function of frequency tunability Δ f in the range of wider than 1.5 GHz, which is achieved in steady state by changing magnetic field intensity. This function should be used for adjusting the output frequency at the optimal value to achieve the highest enhancement factor of DNP.

  18. Hyperpolarized xenon by d-DNP using the clinical GE SpinLab polarizer system

    DEFF Research Database (Denmark)

    Mariager, Christian Østergaard; Ringgaard, Steffen; Ardenkjær-Larsen, Jan Henrik

    2017-01-01

    Hyperpolarized (HP) 129Xe have been demonstrated as a useful probe for magnetic resonance (MR) lung imaging and show promise for in vivo perfusion imaging and brown adipose tissue characterization. Reports of large polarization enhancements for 129Xe using dynamic nuclearpolarization (DNP) have...

  19. DNP with the free radicals deuterated TEMPO and deuterated oxo-TEMPO

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.

    2004-06-01

    The results of measurements performed to assess the potential of deuterated TEMPO and deuterated oxo-TEMPO for DNP are presented. These free radicals became available only recently. Polarization and relaxation processes of protons and deuterons in various deuterated alcohols and deuterated polymers have been investigated. More than 40% deuteron polarization has been obtained in samples of fully deuterated polystyrene.

  20. DNP with the free radicals deuterated TEMPO and deuterated oxo-TEMPO

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den E-mail: ben.vandenbrandt@psi.ch; Bunyatova, E.I.; Hautle, P.; Konter, J.A

    2004-06-21

    The results of measurements performed to assess the potential of deuterated TEMPO and deuterated oxo-TEMPO for DNP are presented. These free radicals became available only recently. Polarization and relaxation processes of protons and deuterons in various deuterated alcohols and deuterated polymers have been investigated. More than 40% deuteron polarization has been obtained in samples of fully deuterated polystyrene.

  1. Evaluating resilience of DNP3-controlled SCADA systems against event buffer flooding

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Guanhua [Los Alamos National Laboratory; Nicol, David M [UNIV OF IL; Jin, Dong [UNIV OF IL

    2010-12-16

    The DNP3 protocol is widely used in SCADA systems (particularly electrical power) as a means of communicating observed sensor state information back to a control center. Typical architectures using DNP3 have a two level hierarchy, where a specialized data aggregator device receives observed state from devices within a local region, and the control center collects the aggregated state from the data aggregator. The DNP3 communication between control center and data aggregator is asynchronous with the DNP3 communication between data aggregator and relays; this leads to the possibility of completely filling a data aggregator's buffer of pending events, when a relay is compromised or spoofed and sends overly many (false) events to the data aggregator. This paper investigates how a real-world SCADA device responds to event buffer flooding. A Discrete-Time Markov Chain (DTMC) model is developed for understanding this. The DTMC model is validated by a Moebius simulation model and data collected on real SCADA testbed.

  2. A 140 GHz Pulsed EPR/212 MHz NMR Spectrometer for DNP Studies

    Science.gov (United States)

    Smith, Albert A.; Corzilius, Björn; Bryant, Jeffrey A.; DeRocher, Ronald; Woskov, Paul P.; Temkin, Richard J.; Griffin, Robert G.

    2012-01-01

    We described a versatile spectrometer designed for the study of dynamic nuclear polarization (DNP) at low temperatures and high fields. The instrument functions both as an NMR spectrometer operating at 212 MHz (1H frequency) with DNP capabilities, and as a pulsed-EPR operating at 140 GHz. A coiled TE011 resonator acts as both an NMR coil and microwave resonator, and a double balanced (1H, 13C) radio frequency circuit greatly stabilizes the NMR performance. A new 140 GHz microwave bridge has also been developed, which utilizes a four-phase network and ELDOR channel at 8.75 GHz, that is then multiplied and mixed to obtain 140 GHz microwave pulses with an output power of 120 mW. Nutation frequencies obtained are as follows: 6 MHz on S = ½ electron spins, 100 kHz on 1H, and 50 kHz on 13C. We demonstrate basic EPR, ELDOR, ENDOR, and DNP experiments here. Our solid effect DNP results demonstrate an enhancement of 144 and sensitivity gain of 310 using OX063 trityl at 80 K and an enhancement of 157 and maximum sensitivity gain of 234 using Gd-DOTA at 20 K, which is significantly better performance than previously reported at high fields (>3 T). PMID:22975246

  3. Lessons from the Institute for New Heads (INH) Class of 2006: Ten Headships--134 Years of Hard-Earned Experience

    Science.gov (United States)

    Raphel, Annette; Huber, John; Chandler, Carolyn; Vorenberg, Amy; Jones-Wilkins, Andy; Devey, Mark A.; Holford, Josie; Craig, Ian; Elam, Julie

    2016-01-01

    Ten years ago in July 2006, 64 mostly starry-eyed men and women attended the NAIS Institute for New Heads (INH) in order to learn the ropes of headship. These newly minted heads were filled with enthusiasm, commitment, and passion, along with humility and a bit of healthy trepidation. One core group connected under the careful guidance of…

  4. Enhancement of cadmium bioremediation by endophytic bacterium Bacillus sp. L14 using industrially used metabolic inhibitors (DCC or DNP)

    Energy Technology Data Exchange (ETDEWEB)

    Luo Shenglian, E-mail: sllou@hnu.cn [College of Environmental Science and Engineering, Hunan University, Changsha 410082 (China); Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082 (China); State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082 (China); Key Laboratory of Jiangxi Province for Ecological Diagnosis-Remediation and Pollution Control, Nanchang 330063 (China); Xiao Xiao [College of Environmental Science and Engineering, Hunan University, Changsha 410082 (China); Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082 (China); Xi Qiang [State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082 (China); Wan Yong; Chen Liang; Zeng Guangming [College of Environmental Science and Engineering, Hunan University, Changsha 410082 (China); Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082 (China); Liu Chengbin [State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082 (China); Guo Hanjun; Chen Jueliang [College of Environmental Science and Engineering, Hunan University, Changsha 410082 (China); Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Changsha 410082 (China)

    2011-06-15

    Bioremediations of cadmium by endophytic bacterium (EB) L14 (Bacillus sp.) in the presence of industrially used metabolic inhibitors (DCC or DNP) were investigated. In the presence of DCC or DNP, the biomass population of EB L14 was greatly inhibited. However, the cadmium removal of EB L14 increased from 73.6% (in the absence of DCC or DNP) to 93.7% and 80.8%, respectively. The analysis of total and intracellular cadmium concentrations during 24 h of incubation indicated that this enhanced cadmium removal was the inhibition effect of DCC or DNP on the cations export resistance system of EB L14. This unique property strongly indicated the superiority of this endophyte for practical application in cadmium bioremediation in the presence of industrially used metabolic inhibitors.

  5. Triclosan inhibition of mycobacterial InhA in Saccharomyces cerevisiae: yeast mitochondria as a novel platform for in vivo antimycolate assays.

    Science.gov (United States)

    Gurvitz, A

    2010-04-01

    To demonstrate the suitability of yeast to act as a novel biotechnological platform for conducting in vivo inhibition assays using drugs with low efficacies towards their mycobacterial targets, such as occurs in the situation with triclosan and InhA. A surrogate yeast host represented by Saccharomyces cerevisiae etr1Delta cells lacking Etr1p, the 2-trans-enoyl-thioester reductase of mitochondrial type 2 fatty acid synthase (FASII), was designed to rely on the Mycobacterium tuberculosis FASII enzyme InhA. Although InhA is 10,000 times less sensitive to the antimicrobial drug triclosan than is bacterial FabI, the respiratory growth of yeast cells depending on InhA was severely affected on glycerol medium containing triclosan. The yeast system could detect enzyme inhibition despite the use of a drug with only low efficacy. Tuberculosis affects a third of the human population, and InhA is a major drug target for combating this disease. InhA is inhibited by isoniazid, but triclosan-derived compounds are presently being developed as antimycolates. A demonstration of triclosan inhibition of InhA in yeast represents a meaningful variation in studying this effect in mycobacteria, because it occurred without the potentially confusing aspects of perturbing protein-protein interactions which are presumed vital to mycobacterial FASII, inactivating other important enzymes or eliciting a dedicated transcriptional response in Myco. tuberculosis.

  6. Preparation and LSC standardization of ''89 Sr (DNP) using the CIEMAT/NIST method

    International Nuclear Information System (INIS)

    Rodriguez Barquero, L.; Arcos Merino, J.M. Los; Grau Malonda, A.

    1994-01-01

    A procedure for preparation of liquid scintillation counting samples of the strontium DNP complex, labelled with ''89 Sr, is described. The chemical quench, the counting stability and spectral evolution of this compound is studied in six scintillators, Toluene, Toluene-alcohol, Dioxane-naphthalene, HiSafe II, Ultima-Gold and Instagel. The liquid scintillation standardization of ''89Sr-DNP by the CIEMAT/NIST method, using Hisafe II and Ultima-Gold scintillators, has been carried out. The discrepancies between experimental and computed efficiencies are lower than 0.38% and 0.48%, respectively. The solution has been standardized in terms of activity concentration to an overall uncertainty of 0.38%. (Author)

  7. Preparation and LSC Standardization of ''89Sr (DNP) Using the CIEMAT/NIST Method

    International Nuclear Information System (INIS)

    Rodriguez Barquero, L.; Los Arcos Merino, J. M.; Grau Malonda, A.

    1994-01-01

    A procedure for preparation of liquid scintillation counting samples of the strontium DNP complex, labelled with ''89Sr, is described, the chemical quench, the counting stability and spectral evolution of this compound is studied in six scintillators, Toluene, Toluene-alcohol, Dioxane-naphthalene, HiSafe II, Ultima- Gold and Instagel. The liquid scintillation standardization of 89Sr-DNP by the CIEMAT/NIST method, using HiSafe II and Ultima-Gold scintillators, has been carried out. The discrepancies between experimental and computed efficiencies are lower than 0.38% and 0.48%, respectively. The solution has been standardized in terms of activity concentration to an overall uncertainty of 0,38%. (Author) 10 refs

  8. Contribution of katG, ahpC and inhA mutations to the detection of isoniazid-resistant Mycobacterium tuberculosis isolates from Lebanon and Syria

    Directory of Open Access Journals (Sweden)

    F Dabboussi

    2015-01-01

    Conclusions: This study showed that the pyrosequencing applied to katG, inhA promoter and ahpC-oxyR intergenic region was able to detect a relatively large proportion of Syrian INH-resistant MTB isolates (80.7% in Syria. This strategy may be inappropriate for Lebanese strains, as the genetic mechanisms of resistance remain unidentified for approximately half of the isolates, so it is quite possible to detect the presence of other mechanisms of resistance.

  9. Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic.

    Science.gov (United States)

    Isakova, Jainagul; Sovkhozova, Nurmira; Vinnikov, Denis; Goncharova, Zoy; Talaibekova, Elnura; Aldasheva, Nazira; Aldashev, Almaz

    2018-03-22

    The aim of this study was to identify mutations of rpoB, katG, inhA and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium tuberculosis susceptibility to RIF and INH using culture method of absolute concentrations, and commercially available test named "TB-BIOCHIP" (Biochip-IMB, Moscow, Russian Federation). For RIF-resistance, TB-BIOCHIP's sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and 90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533 (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 > Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315→Thr (88.6%) was the most prevalent mutation leading to resistance to INH. In Kyrgyz Republic, the most prevalent mutation in RIF-resistant strains was Ser531 → Leu in rpoB gene, as opposed to Ser315 → Thr in katG gene in INH-resistant Mycobacterium tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium tuberculosis were strains with combined mutations Ser531 → Leu in rpoB gene and Ser315 → Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the advantage of obtaining results in only two days.

  10. Modeling DNP3 Traffic Characteristics of Field Devices in SCADA Systems of the Smart Grid

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Huan [Lehigh Univ., Bethlehem, PA (United States); Cheng, Liang [Lehigh Univ., Bethlehem, PA (United States); Chuah, Mooi Choo [Lehigh Univ., Bethlehem, PA (United States)

    2017-03-08

    In the generation, transmission, and distribution sectors of the smart grid, intelligence of field devices is realized by programmable logic controllers (PLCs). Many smart-grid subsystems are essentially cyber-physical energy systems (CPES): For instance, the power system process (i.e., the physical part) within a substation is monitored and controlled by a SCADA network with hosts running miscellaneous applications (i.e., the cyber part). To study the interactions between the cyber and physical components of a CPES, several co-simulation platforms have been proposed. However, the network simulators/emulators of these platforms do not include a detailed traffic model that takes into account the impacts of the execution model of PLCs on traffic characteristics. As a result, network traces generated by co-simulation only reveal the impacts of the physical process on the contents of the traffic generated by SCADA hosts, whereas the distinction between PLCs and computing nodes (e.g., a hardened computer running a process visualization application) has been overlooked. To generate realistic network traces using co-simulation for the design and evaluation of applications relying on accurate traffic profiles, it is necessary to establish a traffic model for PLCs. In this work, we propose a parameterized model for PLCs that can be incorporated into existing co-simulation platforms. We focus on the DNP3 subsystem of slave PLCs, which automates the processing of packets from the DNP3 master. To validate our approach, we extract model parameters from both the configuration and network traces of real PLCs. Simulated network traces are generated and compared against those from PLCs. Our evaluation shows that our proposed model captures the essential traffic characteristics of DNP3 slave PLCs, which can be used to extend existing co-simulation platforms and gain further insights into the behaviors of CPES.

  11. Continuously Tunable 250 GHz Gyrotron with a Double Disk Window for DNP-NMR Spectroscopy.

    Science.gov (United States)

    Jawla, Sudheer; Ni, Qing Zhe; Barnes, Alexander; Guss, William; Daviso, Eugenio; Herzfeld, Judith; Griffin, Robert; Temkin, Richard

    2013-01-01

    In this paper, we describe the design and experimental results from the rebuild of a 250 GHz gyrotron used for Dynamic Nuclear Polarization enhanced Nuclear Magnetic Resonance spectroscopy on a 380 MHz spectrometer. Tuning bandwidth of approximately 2 GHz is easily achieved at a fixed magnetic field of 9.24 T and a beam current of 95 mA producing an average output power of >10 W over the entire tuning band. This tube incorporates a double disk output sapphire window in order to maximize the transmission at 250.58 GHz. DNP Signal enhancement of >125 is achieved on a 13 C-Urea sample using this gyrotron.

  12. Hur fysiskt aktiva personer värderar och inhämtar information om ergogena kosttillskott

    OpenAIRE

    Johansson, Maja

    2017-01-01

    Sammanfattning Bakgrund Prestations-höjande preparat inom kategorin sportnutrition, så kallat ergogena kosttillskott (EK) löper den största risken att innehålla hälsoskadliga substanser. Eftersom EK kan vara en hälsorisk vill denna studie belysa hur fysiskt aktiva personer förhåller sig till EK. Syfte Att studera hur fysiskt aktiva personer värderar och inhämtar information om EK. Metod En elektronisk enkät skickades via facebook, våren 2017. Totalt 162 enkäter besvarades och data analyserade...

  13. The Effect of Intermolecular Halogen Bond on 19F DNP Enhancement in 1, 4-Diiodotetrafluorobenzene/4-OH-TEMPO Supramolecular Assembly

    Directory of Open Access Journals (Sweden)

    GAO Shan

    2017-12-01

    Full Text Available Halogen bond, as hydrogen bond, is a non-covalent bond. Dynamic nuclear polarization (DNP technique has been used previously to study hydrogen bonds-mediated intermolecular interactions. However, no study has been carried out so far to study the halogen bond-mediated intermolecular interactions with DNP. In this work, 19F DNP polarization efficiency of the halogen bonds existing in supramolecular assembling by 4-OH-TEMPO and 1,4-diiodotetrafluorobenzene (DITFB was studied on a home-made DNP system. The formation of intermolecular halogen bonds appeared to increase 19F DNP polarization efficiency, suggesting that the spin-spin interactions among electrons were weakened by the halogen bonds, resulting in an increased T2e and a larger saturation factor.

  14. Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability.

    Science.gov (United States)

    Shaw, Daniel J; Robb, Kirsty; Vetter, Beatrice V; Tong, Madeline; Molle, Virginie; Hunt, Neil T; Hoskisson, Paul A

    2017-07-05

    Tuberculosis (TB) is a global health problem that affects over 10 million people. There is an urgent need to develop novel antimicrobial therapies to combat TB. To achieve this, a thorough understanding of key validated drug targets is required. The enoyl reductase InhA, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-TB drug isoniazid. To better understand the activity of this protein a series of mutants, targeted to the NADH co-factor binding pocket were created. Residues P193 and W222 comprise a series of hydrophobic residues surrounding the cofactor binding site and mutation of both residues negatively affect InhA function. Construction of an M155A mutant of InhA results in increased affinity for NADH and DD-CoA turnover but with a reduction in V max for DD-CoA, impairing overall activity. This suggests that NADH-binding geometry of InhA likely permits long-range interactions between residues in the NADH-binding pocket to facilitate substrate turnover in the DD-CoA binding region of the protein. Understanding the precise details of substrate binding and turnover in InhA and how this may affect protein-protein interactions may facilitate the development of improved inhibitors enabling the development of novel anti-TB drugs.

  15. The ground and low-lying excited states and feasibility of laser cooling for GaH+ and InH+ cations

    Science.gov (United States)

    Zhang, Qing-Qing; Yang, Chuan-Lu; Wang, Mei-Shan; Ma, Xiao-Guang; Liu, Wen-Wang

    2018-03-01

    The potential energy curves and transition dipole moments of 12Σ+ and 12Π states of GaH+ and InH+ cations are performed by employing ab initio calculations. Based on the potential energy curves, the rotational and vibrational energy levels of the two states are obtained by solving the Schrödinger equation of nuclear movement. The spectroscopic parameters are deduced with the obtained rovibrational energy levels. The spin-orbit coupling effect of the 2Π states for both the GaH+ and InH+ cations are also calculated. The feasibility of laser cooling of GaH+ and InH+ cations are examined by using the results of the electronic and spectroscopic properties. The highly diagonal Franck-Condon factors and appropriate radiative lifetimes are determined by using the potential energy curves and transition dipole moments for the 2Π1/2, 3/2 ↔ 12Σ+ transitions. The results indicate that the 2Π1/2, 3/2 ↔ 12Σ+ transitions of both GaH+ and InH+ cations are appropriate for the close cycle transition of laser cooling. The optical scheme of the laser cooling is constructed for the GaH+ and InH+ cations.

  16. The Testicular Hormones AMH, InhB, INSL3, and Testosterone Can Be Independently Deficient in Older Men.

    Science.gov (United States)

    Chong, Yih Harng; Pankhurst, Michael W; McLennan, Ian S

    2017-04-01

    Late-onset hypogonadism is symptomatically diverse and not fully explained by circulating testosterone level. The adult testes secrete four distinct hormones (testosterone, AMH, INSL3, and InhB) into the circulation. Testosterone and InhB have proven dynamic regulation, with limited information available for AMH and INSL3. During aging, there is cellular senescence, which may underlie the diversity of hypogonadism. This leads to the postulate that the relative levels (profile) of the four testicular hormones in older men are variable and cannot be evaluated by the measurement of one hormone. 111 men aged 19-50 years and 98 men aged 70-90 years were examined. The circulating levels of the testicular hormones were measured using ELISAs, and the variation in the levels of hormones was analyzed by various correlative analyses. All four hormones were largely or totally independent. Some men were deficient in multiple hormones, but no man had multiple elevated hormones. The average hormonal levels were lower in older men, with diverse profiles of the four testicular hormones. Hence, some men had one or more hormones below the reference range, with testosterone the most conserved. Consequently, testosterone levels were not indicative of the complete state of the endocrine testes. The four hormones vary independently of each other, in younger and older men. This indicates that they are regulated dynamically rather than influenced by endocrine cell number. Older men exhibited diverse profiles of low levels of testicular hormones, suggesting that the testes age differently between men. Testosterone alone inadequately describes gonadal states.

  17. Preparation and LSC Standardization of ''89Sr (DNP) Using the CIEMAT/NIST Method; Preparacion del ''89Sr(DNP) y calibracion por centelleo liquido, mediante el metodo CIEMAT/NIST

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Barquero, L.; Los Arcos Merino, J. M.; Grau Malonda, A.

    1994-07-01

    A procedure for preparation of liquid scintillation counting samples of the strontium DNP complex, labelled with ''89Sr, is described, the chemical quench, the counting stability and spectral evolution of this compound is studied in six scintillators, Toluene, Toluene-alcohol, Dioxane-naphthalene, HiSafe II, Ultima- Gold and Instagel. The liquid scintillation standardization of 89Sr-DNP by the CIEMAT/NIST method, using HiSafe II and Ultima-Gold scintillators, has been carried out. The discrepancies between experimental and computed efficiencies are lower than 0.38% and 0.48%, respectively. The solution has been standardized in terms of activity concentration to an overall uncertainty of 0,38%. (Author) 10 refs.

  18. Studies on the MxiH protein in T3SS needles using DNP-enhanced ssNMR spectroscopy.

    Science.gov (United States)

    Fricke, Pascal; Demers, Jean-Philippe; Becker, Stefan; Lange, Adam

    2014-01-13

    Bacterial T3SS needles formed by the protein MxiH are studied using DNP-enhanced ssNMR spectroscopy at 14.1 T (600 MHz). This technique provides spectra of good resolution, allowing us to draw conclusions about the protein dynamics. With the obtained signal enhancement, samples of limited quantity now get within reach of ssNMR studies. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Field-cycled dynamic nuclear polarization (FC-DNP) of {sup 14}N and {sup 15}N nitroxide radicals at low magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Polyon, C [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Lurie, D J [Bio-Medical Physics, School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD (United Kingdom); Youngdee, W [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Thomas, C [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Thomas, I [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand)

    2007-09-21

    Theoretical Overhauser-detected EPR spectra of {sup 14}N and {sup 15}N nitroxide systems in low magnetic field by field-cycled dynamic nuclear polarization (FC-DNP) were described by a combination of DNP theory and a model of FC-DNP. Spectra were simulated at magnetic fields between 0 and 8 mT. The simulations were able to predict both the EPR peak positions and their amplitudes, corresponding to those from FC-DNP experiments with {sup 14}N and {sup 15}N TEMPOL solutions. EPR irradiation was in the 45-133 MHz range while NMR signal detection occurred at a field of 59 mT. At this frequency range, four {pi} transitions of a {sup 14}N system and three {pi} transitions of a {sup 15}N system were observed. The simulation programmes were also used to predict the spectral amplitudes of the FC-DNP with EPR irradiation power in the 1-15 W range. Theoretical FC-DNP systems were in good agreement with experimental results; however, at low magnetic fields the inhomogeneity of our magnet system resulted in the EPR peaks being left-shifted and somewhat broader than those from the theoretical prediction.

  20. DNP-enhanced ultrawideline 207Pb solid-state NMR spectroscopy: an application to cultural heritage science.

    Science.gov (United States)

    Kobayashi, Takeshi; Perras, Frédéric A; Murphy, Anna; Yao, Yao; Catalano, Jaclyn; Centeno, Silvia A; Dybowski, Cecil; Zumbulyadis, Nicholas; Pruski, Marek

    2017-03-14

    Dynamic nuclear polarization (DNP) is used to enhance the (ultra)wideline 207 Pb solid-state NMR spectra of lead compounds of relevance in the preservation of cultural heritage objects. The DNP SSNMR experiments enabled, for the first time, the detection of the basic lead carbonate phase of the lead white pigment by 207 Pb SSNMR spectroscopy. Variable-temperature experiments revealed that the short T' 2 relaxation time of the basic lead carbonate phase hinders the acquisition of the NMR signal at room temperature. We additionally observe that the DNP enhancement is twice as large for lead palmitate (a lead soap, which is a degradation product implicated in the visible deterioration of lead-based oil paintings), than it is for the basic lead carbonate. This enhancement has allowed us to detect the formation of a lead soap in an aged paint film by 207 Pb SSNMR spectroscopy; which may aid in the detection of deterioration products in smaller samples removed from works of art.

  1. 1H DNP at 1.4 T of Water Doped with a Triarylmethyl-Based Radical

    DEFF Research Database (Denmark)

    Wind, Robert A.; Ardenkjær-Larsen, Jan Henrik

    1999-01-01

    Recently a triarylmethyl-based (TAM) radical has been developed for research in biological and other aqueous systems, and in low magnetic fields, 10 mT or less, large 1H dynamic nuclear polarization (DNP) enhancements have been reported. In this paper the DNP properties of this radical have been......, water and put into a 1-mm i.d. and 6-mm long capillary tube. At 26°C the following results were obtained: (I) The relaxivity of the radical is 0.07 (mMs)−1, in accordance with the value extrapolated from low-field results; (II) The leakage factor is 0.63, the saturation factor at maximum power is 0.......85, and the coupling factor is −0.0187. It is shown that these results agree very well with an analysis where the electron–dipolar interactions are the dominant DNP mechanism, and where the relaxation transitions resulting from these interactions are governed by translational diffusion of the water molecules. Finally...

  2. Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability

    OpenAIRE

    Shaw, Daniel J.; Robb, Kirsty; Vetter, Beatrice V.; Tong, Madeline; Molle, Virginie; Hunt, Neil T.; Hoskisson, Paul A.

    2017-01-01

    Tuberculosis (TB) is a global health problem that affects over 10 million people. There is an urgent need to develop novel antimicrobial therapies to combat TB. To achieve this, a thorough understanding of key validated drug targets is required. The enoyl reductase InhA, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-TB drug isoniazid. To better understand the activity of this protein a series of mutants, targeted to t...

  3. UTAUT2 Based Predictions of Factors Influencing the Technology Acceptance of Phablets by DNP

    Directory of Open Access Journals (Sweden)

    Chi-Yo Huang

    2015-01-01

    Full Text Available The smart mobile devices have emerged during the past decade and have become one of the most dominant consumer electronic products. Therefore, exploring and understanding the factors which can influence the acceptance of novel mobile technology have become the essential task for the vendors and distributors of mobile devices. The Phablets, integrated smart devices combining the functionality and characteristics of both tablet PCs and smart phones, have gradually become possible alternatives for smart phones. Therefore, predicting factors which can influence the acceptance of Phablets have become indispensable for designing, manufacturing, and marketing of such mobile devices. However, such predictions are not easy. Meanwhile, very few researches tried to study related issues. Consequently, the authors aim to explore and predict the intentions to use and use behaviors of Phablets. The second generation of the Unified Theory of Acceptance and Use of Technology (UTAUT2 is introduced as a theoretic basis. The Decision Making Trial and Evaluation Laboratory (DEMATEL based Network Process (DNP will be used to construct the analytic framework. In light of the analytic results, the causal relationships being derived by the DEMATEL demonstrate the direct influence of the habit on other dimensions. Also, based on the influence weights being derived, the use intention, hedonic motivation, and performance expectancy are the most important dimensions. The analytic results can serve as a basis for concept developments, marketing strategy definitions, and new product designs of the future Phablets. The proposed analytic framework can also be used for predicting and analyzing consumers’ preferences toward future mobile devices.

  4. Would You Use It With a Seal of Approval? Important Attributes of 2,4-Dinitrophenol (2,4-DNP as a Hypothetical Pharmaceutical Product

    Directory of Open Access Journals (Sweden)

    Emma E. Bleasdale

    2018-04-01

    Full Text Available Background2,4-Dinitrophenol (2,4-DNP is an effective but highly dangerous fat burner, not licensed for human consumption. Death cases reported for 2,4-DNP overdose, particularly among young adults, have raised concerns about the ineffective regulatory control, lack of education and risks associated with impurity, and the unknown concentration of 2,4-DNP purchased on the Internet.MethodsUsing a sequential mixed method design and based on a hypothetical scenario as if 2,4-DNP was a licensed pharmaceutical drug, first we conducted a qualitative study to explore what product attributes people consider when buying a weight-loss aid. Focus group interviews with six females and three males (mean age = 21.6 ± 1.8 years were audiorecorded, transcribed verbatim, and subjected to thematic analysis. Sixteen attributes were identified for the Best–Worst Scale (BWS in the quantitative survey with 106 participants (64% female, mean age = 27.1 ± 11.9 years, focusing on 2,4-DNP. Demographics, weight satisfaction, and risk for eating disorder data were collected.ResultsIn contrast to experienced users such as bodybuilders, our study participants approached 2,4-DNP cautiously. Attributes of 2,4-DNP as a hypothetical weight-loss drug comprised a range of desirable and avoidable features. Of the 16 selected attributes, BWS suggested that long-term side effects were the most and branding was the least important attribute. Effectiveness and short-term side effects were also essential. Those in the >25 year group showed least concerns for legality. Neutral BWS scores for cost, treatment, degree of lifestyle changes required, and specificity required for the hypothetical weight-loss drug to be effective were likely caused by disagreement about their importance among the participants, not indifference.ConclusionWith advances in research, 2,4-DNP as a pharmaceutical drug in the future for treating neurodegenerative diseases and potentially for

  5. Use of the Iowa Model of Research in Practice as a Curriculum Framework for Doctor of Nursing Practice (DNP) Project Completion.

    Science.gov (United States)

    Lloyd, Susan T; D'Errico, Ellen; Bristol, Shirley T

    2016-01-01

    Doctoral education requires academic motivation and persistence on the part of nursing students; commitment to the process is essential and should be linked to programmatic structure. Programmatic issues in doctor of nursing practice (DNP) programs may be barriers to completion of the final project and lead to attrition. A large, private health care university developed an infrastructure for the DNP curriculum and final project utilizing the Iowa Model of Research in Practice. The purpose was to ensure competency fulfillment, retention and timely completion, and implementation of evidence-based practice and translation science utilizing a leadership approach. The program has experienced a high completion rate to date.

  6. The DNP by 2015: A Study of the Institutional, Political, and Professional Issues That Facilitate or Impede Establishing a Post-Baccalaureate Doctor of Nursing Practice Program

    Science.gov (United States)

    Auerbach, David I.; Martsolf, Grant R.; Pearson, Marjorie L.; Taylor, Erin Audrey; Zaydman, Mikhail; Muchow, Ashley; Spetz, Joanne; Dower, Catherine

    2015-01-01

    In 2004, members of the American Association of Colleges of Nursing (AACN) voted to endorse a position statement identifying the doctor of nursing practice (DNP) degree as the most appropriate degree for advanced-practice registered nurses (APRNs) to enter practice. At the same time, AACN members voted to approve the position that all master's…

  7. Ig light chain variability in DNP494-KLH immunised sea bass (Dicentrarchus labrax L.) : evidence for intra-molecular induced suppression

    NARCIS (Netherlands)

    Santos, dos N.M.S.; Hermsen, T.; Rombout, J.H.W.M.; Pilström, L.; Stet, R.J.M.

    2001-01-01

    The coding sequence of the sea bass light chain was obtained by sequential anchored PCR on a head kidney cDNA library of a DNP494-KLH immunised sea bass. The cDNA sequence obtained codes for a leader peptide of 21 aa and a mature IgL chain of 223 aa. Both the amino acid sequence comparisons and

  8. Toxicology Study No. S.0024589d 15, Human Cell Line Activation Test of the Novel Energetic, 3,4 -Dinitropyrazole (DNP)

    Science.gov (United States)

    2016-04-01

    allergy . 3,4-DNP was found to be a sensitizer. 3,4-dinitropyrazole, skin sensitization, human cell line activation test, in vitro Emily N. Reinke SAR 26U U...from Sigma-Aldrich, Inc., to include 2,4- dinitochlorobenzene (DNCB, CASRN 97-00-7), nickel sulfate (NiSO4, CASRN 7786-81-4), and lactic acid (LA

  9. High cell selectivity and low-level antibacterial resistance of designed amphiphilic peptide G(IIKK)(3)I-NH(2).

    Science.gov (United States)

    Chen, Cuixia; Hu, Jing; Zeng, Ping; Chen, Yucan; Xu, Hai; Lu, Jian R

    2014-10-08

    On the basis of cell cultures involving bacterial strains (Escherichia coli 5α and Bacillus subtilis 168) and a mammalian cell line (NIH 3T3), the potent antibacterial activity and distinct selectivity from designed amphiphilic peptides G(IIKK)nI-NH2 (n = 2-4) have been demonstrated. This work extends these studies to multidrug resistant pathogens (ESBL-producing E. coli) and primary human cells (HDFa), followed by the in vivo mouse model investigation of ESBL-producing bacterial infection. G(IIKK)3I-NH2 exhibits high antibacterial activity against the pathogenic strain both in vitro and in vivo while displaying low toxicity toward the primary cells and the mice. Peptide molecules can kill bacteria by selectively interacting with bacterial membranes, causing structural disruptions. Furthermore, multidrug resistant ESBL-producing bacteria do not develop resistance after multiple treatments with G(IIKK)3I-NH2. The high cellular selectivity, low toxicity toward mammalian hosts and noninducing bacterial resistance indicate great potential for developing the peptides as anti-infection agents.

  10. Design, Synthesis and DFT/DNP Modeling Study of New 2-Amino-5-arylazothiazole Derivatives as Potential Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Sraa Abu-Melha

    2018-02-01

    Full Text Available A new series of 2-amino-5-arylazothiazole derivatives has been designed and synthesized in 61–78% yields and screened as potential antibacterial drug candidates against the Gram negative bacterium Escherichia coli. The geometry of the title compounds were being studied using the Material Studio package and semi-core pseudopods calculations (dspp were performed with the double numerica basis sets plus polarization functional (DNP to predict the properties of materials using the hybrid FT/B3LYP method. Modeling calculations, especially the (EH-EL difference and the energetic parameters revealed that some of the title compounds may be promising tools for further research work and the activity is structure dependent.

  11. The interplay between the solid effect and the cross effect mechanisms in solid state 13C DNP at 95 GHz using trityl radicals

    Science.gov (United States)

    Banerjee, Debamalya; Shimon, Daphna; Feintuch, Akiva; Vega, Shimon; Goldfarb, Daniella

    2013-05-01

    The 13C solid state Dynamic Nuclear Polarization (DNP) mechanism using trityl radicals (OX63) as polarizers was investigated in the temperature range of 10-60 K. The solutions used were 6 M 13C urea in DMSO/H2O (50% v/v) with 15 mM and 30 mM OX63. The measurements were carried out at ˜3.5 T, which corresponds to Larmor frequencies of 95 GHz and 36 MHz for the OX63 and the 13C nuclei, respectively. Measurements of the 13C signal intensity as a function of the microwave (MW) irradiation frequency yielded 13C DNP spectra with temperature dependent lineshapes for both samples. The maximum enhancement for the 30 mM sample was reached at 40 K, while that of the 15 mM sample at 20-30 K. Furthermore, the lineshapes observed showed that both the cross effect (CE) and the solid effect (SE) DNP mechanisms are active in this temperature range and that their relative contribution is temperature dependent. Simulations of the spectra with the relative contributions of the CE and SE mechanisms as a fit parameter revealed that for both samples the CE contribution decreases with decreasing temperature while the SE contribution increases. In addition, for the 15 mM sample the contributions of the two mechanisms are comparable from 20 K to 60 K while for the 30 mM the CE dominates in this range, as expected from the higher concentration. The steep decrease of the CE contribution towards low temperatures is however unexpected. The temperature dependence of the OX63 longitudinal relaxation, DNP buildup times and 13C spin lattice relaxation times did not reveal any obvious correlation with the DNP temperature dependence. A similar behavior of the CE and SE mechanism was observed for 1H DNP with the nitroxide radical TEMPOL as a polarizer. This suggests that this effect is a general phenomenon involving a temperature dependent competition between the CE and SE mechanisms, the source of which is, however, still unknown.

  12. Programación de un sistema de adquisición de datos utilizando el sistema embebido DNP/1110;Programming of a data acquisition system using the embedded system dil/netpc DNP/1110

    Directory of Open Access Journals (Sweden)

    Josnier Ramos - Guardarrama,et al.

    2011-06-01

    Full Text Available En el trabajo se presenta una alternativa económica de un sistema de adquisición de datos (SAD basado en el kit de desarrollo DIL/NetPC DNP/1110, el cual esta formado por un microcontrolador de INTEL SA-1110 StrongARM que trabaja a 206 MHz y que tiene incorporado un controlador de Ethernet que permite desarrollar aplicaciones con el uso de la red. El sistema embebido dispone de un sistema operativo Linux, kernel versión 2.4.18. Como parte del diseño se incorporan de forma compacta los elementos necesarios para que el SAD sea capaz de muestrear ocho señales capturadas simultáneamente. De particular interés resulta la programación, presentándose dos variantes de solución: cuando se ejecuta la aplicación con un software que corre en el área de usuario y cuando el control se logra con un módulo del sistema operativo específico para el trabajo del SAD. El sistema está soportado por la integración de software libre y propietario.This work focuses on an economic alternative for developing a data acquisition system (DAS which is made up for The DIL/NetPC DNP/1110, which provides a very compact Intel 206 MHz SA-1110 StrongARM-based low power embedded controller with TCP/IP stack and web server for high-speed embedded networking applications. The embedded system has an operating system Linux, kernel version 2.4.18. The built data acquisition system has the necessary elements to take charge of governing the sampling process of eight signals. Of particular interest it is the programming, being presented two solution variants: when the application is executed with software that it runs in user's area and when the control is achieved with a specific build module of the operating system for the work of the DAS.. The system is supported by the integration of free software and property software.

  13. Programación de un sistema de adquisición de datos utilizando el sistema embebido DNP/1110; Programming of a data acquisition system using the embedded system dil/netpc DNP/1110

    Directory of Open Access Journals (Sweden)

    Josnier Ramos Guardarrama

    2011-06-01

    Full Text Available En el trabajo se presenta una alternativa económica de un sistema de adquisición de datos (SAD basado en el kit dedesarrollo DIL/NetPC DNP/1110, el cual esta formado por un microcontrolador de INTEL SA-1110 StrongARM quetrabaja a 206 MHz y que tiene incorporado un controlador de Ethernet que permite desarrollar aplicaciones con el usode la red. El sistema embebido dispone de un sistema operativo Linux, kernel versión 2.4.18. Como parte del diseñose incorporan de forma compacta los elementos necesarios para que el SAD sea capaz de muestrear ocho señalescapturadas simultáneamente. De particular interés resulta la programación, presentándose dos variantes de solución:cuando se ejecuta la aplicación con un software que corre en el área de usuario y cuando el control se logra con unmódulo del sistema operativo específico para el trabajo del SAD. El sistema está soportado por la integración desoftware libre y propietario.  This work focuses on an economic alternative for developing a data acquisition system (DAS which is made up forThe DIL/NetPC DNP/1110, which provides a very compact Intel 206 MHz SA-1110 StrongARM-based low powerembedded controller with TCP/IP stack and web server for high-speed embedded networking applications. Theembedded system has an operating system Linux, kernel version 2.4.18. The built data acquisition system has thenecessary elements to take charge of governing the sampling process of eight signals. Of particular interest it is theprogramming, being presented two solution variants: when the application is executed with software that it runs inuser's area and when the control is achieved with a specific build module of the operating system for the work of theDAS.. The system is supported by the integration of free software and property software.

  14. [Current situation of primary prophylaxis with isoniazid (INH) in children who are contacts of patients with bacillary pulmonary tuberculosis in Abidjan (Cote d'Ivoire)].

    Science.gov (United States)

    Koné, Z; Coulibaly, G; Daix, A T J; Bakayoko, A S; Samaké, K; Kouassi, D P; Domoua, K M S

    2016-12-01

    The National tuberculosis program (NTP) in Ivory Coast recommends that children under 5 years living in a family environment with contagious tuberculosis patients, should receive Prophylactic treatment with INH (PTI), whatever the result of the tuberculin skin test (positive or negative) and their BCG status (vaccinated or not), at a dose of 5mg/kg/day for 6 months. We conducted this study to check the implementation of this recommendation in three support services of tuberculosis in Abidjan, the economic capital. We conducted a multicenter, cross-sectional and descriptive study over 3 years (2011-2013), on consented patients, adolescents and adults aged at least 15 years, with a first episode of infectious pulmonary tuberculosis, in order to look for information on the INH prophylaxis in children under 5 years living under the same roof. We made patients interviews during their visit for bacteriological sputum controls at the second month of TB treatment. Of a total of 412 patients (53% males and 47% females) with a mean age of 34.5 years and with a low level of instruction (66.5%), we noticed 639 children under 5 years living under the same roof with them. Information on the screening of contact children was given to 71% of interviewed patients (291/412). Of the 339 children examined among 639 contacts, 234 (69%) had received only an intradermoreaction (IDR) and PTI was finally administered to 64% of them (217/339). High proportion of contact children under 5 not examined is a major concern for the NTP and a missed opportunity to prevent additional cases of tuberculosis among children. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Theoretical investigation of the effects of the molar ratio and solvent on the formation of the pyrazole-nitroamine cocrystal explosive 3,4-dinitropyrazole (DNP)/2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20).

    Science.gov (United States)

    Zhu, Shuang-Fei; Zhang, Shu-Hai; Gou, Rui-Jun; Han, Gang; Wu, Chun-Lei; Ren, Fu-de

    2017-11-24

    The effects of the molar ratio, temperature, and solvent on the formation of the cocrystal explosive DNP/CL-20 were investigated using molecular dynamics (MD) simulation. The cocrystal structure was predicted through Monte Carlo (MC) simulation and using first-principles methods. The results showed that the DNP/CL-20 cocrystal might be more stable in the molar ratio 1:1 near to 318 K, and the most probable cocrystal crystallizes in the triclinic crystal system with the space group P[Formula: see text]. Cocrystallization was more likely to occur in methanol and ethanol at 308 K as a result of solvent effects. The optimized structure and the reduced density gradient (RDG) of the DNP/CL-20 complex confirmed that the main driving forces for cocrystallization were a series of hydrogen bonds and van der Waals forces. Analyses of the trigger bonds, the charges on the nitro groups, the electrostatic surface potential (ESP), and the free space per molecule in the cocrystal lattice were carried out to further explore their influences on the sensitivity of CL-20. The results indicated that the DNP/CL-20 complex tended to be more stable and insensitive than pure CL-20. Moreover, an investigation of the detonation performance of the DNP/CL-20 cocrystal indicated that it possesses high power. Graphical abstract DNP/CL-20 cocrystal models with different molar ratios were investigated at different temperatures using molecular dynamics (MD) simulation methods. Binding energies and mechanical properties were probed to determine the stability and performance of each cocrystal model. Solvated DNP/CL-20 models were established by adding solvent molecules to the cocrystal surface. The binding energies of the models in various solvents were calculated in order to identify the most suitable solvent and temperature for preparing the cocrystal explosive DNP/CL-20.

  16. Real-Time DNP NMR Observations of Acetic Acid Uptake, Intracellular Acidification, and of Consequences for Glycolysis and Alcoholic Fermentation in Yeast

    DEFF Research Database (Denmark)

    Jensen, Pernille Rose; Karlsson, Magnus; Lerche, Mathilde Hauge

    2013-01-01

    Uptake and upshot in vivo: Straightforward methods that permit the real-time observation of organic acid influx, intracellular acidification, and concomitant effects on cellular-reaction networks are crucial for improved bioprocess monitoring and control (see scheme). Herein, dynamic nuclear pola...... polarization (DNP) NMR is used to observe acetate influx, ensuing intracellular acidification and the metabolic consequences on alcoholic fermentation and glycolysis in living cells....

  17. El desafío de construir una Psicología del desarrollo crítica en sociedades inhóspitas

    Directory of Open Access Journals (Sweden)

    Carlos Iván Orellana

    2016-12-01

    Full Text Available La Psicología del desarrollo constituye un campo de conocimiento cuya existencia se da por descontada en el imaginario académico de la psicología salvadoreña. No obstante, existe una Psicología del desarrollo dominante que se ve reproducida en textos, clases y discursos, mientras que otra distinta, consecuente con la realidad histórica donde su estudio tiene lugar, aún es una tarea pendiente. Al considerar la descontextualización como uno de los presupuestos fundamentales de la Psicología del desarrollo dominante al uso, en este artículo de carácter teórico se reflexiona sobre esta desde la perspectiva del caso salvadoreño en tanto sociedad inhóspita: aquella que compromete el avance del ciclo vital de la mayoría de la población por, entre otras características, ser violenta y desigual. Son sometidas a escrutinio las conocidas categorías analíticas de la Psicología del desarrollo definidas como influencias normativas y no normativas para mostrar la relatividad y los sesgos de su aplicación usual. Se sostiene que, en el marco de una sociedad inhóspita, una Psicología del desarrollo debe considerar, al menos, procesos de adultización prematura en la niñez y la juventud, la improbabilidad de biografías estables, la vejez precaria así como las características típicas que muestran los miembros del contexto de interés. Se propone avanzar a una Psicología del desarrollo crítica: la necesidad de reacomodar su quehacer y reinventarse epistemológicamente para construir un conocimiento situado, propio y multidisciplinario que supere cegueras, provincianismos y reduccionismos académicos.

  18. Cost-effectiveness and cost-utility of a structured collaborative disease management in the Interdisciplinary Network for Heart Failure (INH) study.

    Science.gov (United States)

    Neumann, Anja; Mostardt, Sarah; Biermann, Janine; Gelbrich, Götz; Goehler, Alexander; Geisler, Benjamin P; Siebert, Uwe; Störk, Stefan; Ertl, Georg; Angerrmann, Christiane E; Wasem, Jürgen

    2015-04-01

    Non-pharmacological treatment programmes are being developed, in which specialised nurses take care of heart failure (HF) patients. Such disease management programmes might increase survival and quality of life in HF patients, but evidence on their cost-effectiveness remains limited. A prospective economic evaluation piggy-backed onto the randomised controlled Interdisciplinary Network for Heart Failure (INH) Study weighted costs of the intervention HeartNetCare -HF™ (HNC) regarding effectiveness, mortality and quality-adjusted life years (QALYs). To consider uncertainty sensitivity analyses were performed. Compared to usual care (UC), HNC revealed 8,284 euro> per death avoided within the 6 month study follow-up period. The cost-utility analysis showed additional costs of 49,335 euro> per QALY. Although HNC did not reduce short-term re-admission rates of HF patients hospitalised for cardiac decompensation within the first 180 days after discharge, HNC might reduce mortality and increase quality of life in these patients at reasonable costs. Therefore, long-term HNC-effects deserve further evaluation.

  19. A well-defined Pd hybrid material for the Z-selective semihydrogenation of alkynes characterized at the molecular level by DNP SENS.

    Science.gov (United States)

    Conley, Matthew P; Drost, Ruben M; Baffert, Mathieu; Gajan, David; Elsevier, Cornelis; Franks, W Trent; Oschkinat, Hartmut; Veyre, Laurent; Zagdoun, Alexandre; Rossini, Aaron; Lelli, Moreno; Lesage, Anne; Casano, Gilles; Ouari, Olivier; Tordo, Paul; Emsley, Lyndon; Copéret, Christophe; Thieuleux, Chloé

    2013-09-09

    Direct evidence of the conformation of a Pd-N heterocyclic carbene (NHC) moiety imbedded in a hybrid material and of the Pd-NHC bond were obtained by dynamic nuclear polarization surface-enhanced NMR spectroscopy (DNP SENS) at natural abundance in short experimental times (hours). Overall, this silica-based hybrid material containing well-defined Pd-NHC sites in a uniform environment displays high activity and selectivity in the semihydrogenation of alkynes into Z-alkenes (see figure). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Food group consumption in an Italian population using the updated food classification system FoodEx2: Results from the Italian Nutrition & HEalth Survey (INHES) study.

    Science.gov (United States)

    Pounis, G; Bonanni, A; Ruggiero, E; Di Castelnuovo, A; Costanzo, S; Persichillo, M; Bonaccio, M; Cerletti, C; Riccardi, G; Donati, M B; de Gaetano, G; Iacoviello, L

    2017-04-01

    Dietary habits evolve over time, being influenced by many factors and complex interactions. This work aimed at evaluating the updated information on food group consumption in Italy. A total of 8944 (4768 women and 4176 men) participants aged >18 years from all over Italy recruited in 2010-13 (Italian Nutrition & HEalth Survey, INHES) was analyzed. The recruitment was performed using computer-assisted-telephone-interviewing and one-day 24-h dietary recall retrieved from all participants. The updated, second version, of FoodEx2 food classification system was applied to extract data on food group consumption. The participation rate was 53%; 6.2% of the participants declared to follow a special diet, the most prevalent being hypo-caloric diets (55.7% of special diets). Men compared to women presented significantly higher intakes of "grains and grain-based products", "meat and meat products", "animal and vegetable fats and oils and primary derivatives" and "alcoholic beverages" (P for allfood imitates and food supplements" (P for allfood group intake among age groups, geographical regions and educational level groups were also identified (P for allfood groups and sub-groups were illustrated in different strata. The present analysis could be considered as an updated source of information for future nutrition research in Italy and in the EU. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  1. Using social network analysis to examine collaborative relationships among PhD and DNP students and faculty in a research-intensive university school of nursing.

    Science.gov (United States)

    Merrill, Jacqueline A; Yoon, Sunmoo; Larson, Elaine; Honig, Judy; Reame, Nancy

    2013-01-01

    The nursing profession has seen a dramatic rise in the number of schools offering both DNP and PhD nursing programs. Information is limited on the impact of this parallel approach in doctoral education on the quality and scope of scholarly interactions or institutional culture.The authors studied collaboration characteristics across the DNP and PhD programs of a research-intensive university school of nursing, before and after programmatic enhancements. An IRB-approved online survey was delivered to faculty and students of both programs at baseline and one year after curricular changes. Response rates were 70% and 74%, respectively. The responses were analyzed by using social network analysis and descriptive statistics to characterize the number and strength of connections between and within student groups, and between students and faculty. At baseline, the flow of communication was centralized primarily through faculty. At Time 2, density of links between students increased and network centralization decreased, suggesting more distributed communication. This nonlinear quantitative approach may be a useful addition to the evaluation strategies for doctoral education initiatives. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Analysis of the applicability of DNP 3.0 (distributed network protocol) in protection, monitoring, control and automation systems of electric power plants and substations; Analise da aplicabilidade do DNP 3.0 (distributed network protocol) em sistemas de protecao, supervisao, controle e automacao de usinas e SEs

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Euro Pinto de; Lippmann Junior, Lourival; Klinguelfus, Mauro Cezar; Oliveira, William Lopes de [Companhia Paranaense de Energia (COPEL), Curitiba, PR (Brazil). LAC

    1995-12-31

    This article presents the analysis of the DNP 3.0 (Distributed Network Protocol) as a feasible alternative of a model to be used in the control and supervision systems communication in the electric power sector. According to the authors, the results of such analysis are very important once the communication record can be considered as a key-piece for the feasibility of general implementation of digital systems in automation, control, supervision and protection systems on the electric power sector 4 refs.; e-mail: william at lac.copel.br

  3. Second sphere coordination in anion binding: Synthesis, characterization, X-ray structure of tris(1,10-phenanthroline)cobalt(III)2,4-dinitrophenolate tetrahydrate, [Co(phen) 3](dnp) 3·4H 2O where dnp = 2,4-dinitrophenolate

    Science.gov (United States)

    Sharma, Raj Pal; Singh, Ajnesh; Ferretti, Valeria; Venugopalan, Paloth

    2009-01-01

    A new cobalt(III) complex salt, [Co(phen) 3](dnp) 3·4H 2O has been synthesized in an effort to utilize [Co(phen) 3] 3+ cation as a new host for di-substituted phenolate (2,4-dinitrophenolate) anion. This cobalt (III) complex salt has been characterized by elemental analyses and spectroscopic techniques (UV/visible, IR, NMR and conductance measurements). Single crystal X-ray structure determination confirmed the composition [Co(phen) 3](dnp) 3·4H 2O. A strong network of hydrogen bonding interactions C-H ...O (phenolate), C-H …O (nitro) involving second sphere coordination and O-H …O hydrogen bonding interactions stabilize the crystal lattice. The formation of a complex salt of definite composition along with solubility product data suggests that [Co(phen) 3] 3+ present in [Co(phen) 3]Cl 3 may be used as an anion receptor for 2,4-dinitrophenolate ion.

  4. Cationic cobaltammines as anion receptors: Synthesis and characterization of [Co(NH 3) 6](4-np) 3.4H 2O, [Co(NH 3) 6](2,4-dnp) 3 and [Co(NH 3) 6](2,4,6-tnp) 3 (where np=nitrophenolate, dnp=dinitrophenolate, tnp, trinitrophenolate), single crystal X-ray structure and packing of [Co(NH 3) 6](4-np) 3.4H 2O

    Science.gov (United States)

    Sharma, Raj Pal; Bala, Ritu; Sharma, Rajni; Venugopalan, Paloth

    2005-10-01

    In an effort to utilize [Co(NH 3) 6] 3+ cation as a new host for mono-, di- and tri-substituted nitrophenolate anions, yellow solids of composition [Co(NH 3) 6](4-np) 3.4H 2O, [Co(NH 3) 6](2,4-dnp) 3, and [Co(NH 3) 6](2,4,6-tnp) 3 were obtained in high yields by reacting sodium salts of 4-np, 2,4-dnp and 2,4,6-tnp (where np=nitrophenolate, dnp=dinitrophenolate and tnp=trinitrophenolate,) with [Co(NH 3) 6]Cl 3 respectively in 3:1 molar ratio in hot aqueous medium. These cobalt(III) complex salts have been characterized by elemental analyses and spectroscopic techniques (UV/Visible, IR and NMR). Single crystal X-ray structure determination of [Co(NH 3) 6](4-np) 3.4H 2O revealed the presence of discrete ions, [Co(NH 3) 6] 3+ and C 6H 4NO 3- in addition to four lattice water molecules in the solid state. A strong network of hydrogen bond interactions (N-H⋯O (phenolate), N-H⋯O (nitro), O-H⋯O (water) stabilize the crystal lattice. The formation of these salts and measurement of solubility products suggests that [Co(NH 3) 6] 3+ present in [Co(NH 3) 6]Cl 3 may be used as anion receptor for the nitrophenolate ions.

  5. Second sphere coordination in anion binding: Synthesis, characterization of [Co(phen) 2CO 3]X· nH 2O where X = o-nitrophenolate(onp), p-nitrophenolate(pnp), 2,4-dinitrophenolate(dnp), 2,4,6-trinitrophenolate(tnp) and single crystal X-ray structures of [Co(phen) 2CO 3](onp)·2H 2O and [Co(phen) 2CO 3](dnp)·4.5H 2O

    Science.gov (United States)

    Singh, Ajnesh; Sharma, Raj Pal; Brandão, Paula; Félix, Vitor; Venugopalan, Paloth

    2008-12-01

    In an effort to utilize [Co(phen) 2CO 3] + cation as a new host for mono-, di- and tri-substituted nitrophenolate anions, red coloured crystals of composition [Co(phen) 2CO 3](onp)·2H 2O, [Co(phen) 2CO 3](pnp), orange coloured precipitated product of [Co(phen) 2CO 3](dnp)·4.5H 2O (which gave red coloured crystals from acetone-water mixture) and orange-yellow coloured precipitated product of [Co(phen) 2CO 3](tnp) were obtained in good yields by reacting sodium salts of o-nitrophenol, p-nitrophenol 2,4-dinitrophenol and 2,4,6-trinitrophenol with [Co(phen) 2CO 3]Cl·5H 2O, respectively in 1:1 molar ratio in aqueous medium. These cobalt(III) complex salts have been characterized by elemental analyses, spectroscopic techniques (UV/Visible, IR and NMR) and conductance measurements. Single crystal X-ray structure determination of [Co(phen) 2CO 3](onp)·2H 2O and [Co(phen) 2CO 3](dnp)·4.5H 2O revealed the presence of discrete ions and lattice water molecules in the solid state. A strong network of hydrogen bond interactions through the weak second sphere coordination (C sbnd H…O (phenolate), C sbnd H…O (nitro), and strong interactions of type O sbnd H…O (water) besides the electrostatic interactions play a very important role in stabilizing the crystal lattice. The studies indicated that complex cation, [Co(phen) 2CO 3] + may preferentially bind nitrophenolate ions in the aqueous medium.

  6. Multipleexo-glycosidases in human serum as detected with the substrate DNP-α-GalNAc. II. Three α-N-acetylgalactosaminidase-like activities in the pH 5 to 8 region.

    Science.gov (United States)

    Albracht, Simon P J; van Pelt, Johannes

    2017-12-01

    With the substrate DNP-α-GalNAc (2,4-dinitrophenyl- N -acetyl-α-d-galactosaminide) three α- N -acetylgalactosaminidase-like activities could be distinguished in serum, in addition to the classical lysosomal enzyme (Naga, EC 3.2.1.49, pH optimum at 4). Two activities had optima in the pH 5 to 6 region and one peaked around pH 8. Like the Naga activity at pH 4, the activity at pH 8 was detectable under standard assay conditions. However, the two activities in the pH 5 to 6 range were not readily apparent in such assays. They could be unmasked as separate activities only when low serum concentrations were used. Addition of 1% saturated ammonium sulphate to the assay medium stimulated these activities. All activities in the pH 5 to 8 range decreased with increasing serum concentration in the assay, suggesting the presence of endogenous inhibitors. The activities between pH 5 and 6 might be similar to an activity described in 1996, which was considerably elevated in serum of patients with great variety of cancers (N. Yamamoto, V.R. Naraparaju, and S.O. Asbell (1996). Deglycosylation of serum vitamin D 3 -binding protein leads to immunosuppression in cancer patients. Cancer Res. 56, 2827-2811).

  7. INFLUENCIA DEL TRATAMIENTO CON AMINAS EN LOS PARAMETROS HEMODINAMICOS y METABOLICOS EN EL SHOCK SEPTICO EXPERIMENTAL

    Directory of Open Access Journals (Sweden)

    Felisa Alonso Garcia,

    2003-01-01

    Full Text Available OBJETIVO: Estudiar las variaciones hemodinámicas y metabólicas de las primeras fases del Shock Séptico Experimental (SSE, inducidas por el tratamiento con distinta asociación de aminas. METODO: Investigación experimental en 22 perros. Se les indujo SSE mediante la administración de endotoxina de E. Coli (Serotipo 0111 B.M. Difco Laboratories. Michigan. USA. En función del tiempo se establecieron 5 fases: Basal ó "t=0" (considerado tiempo 0, SSE ó "t=30" (a los 30 minutos del inicio de la infusión del estímulo séptico, "t = 60", "t = 90" y "t = 120" a los 60, 90 y 120 minutos respectivamente de la administración de la endotoxina. En relación al tratamiento administrado, se distinguieron 3 grupos: Grupo A (n=7: tratamiento de soporte; Grupo B (n=8: Dopamina a 10 mcg/kg/min y Dobutamina a 5 mcg/kg/min (DPDB en la fase "t=60", DPDB más Noradrenalina (NA a 0,5 mcg/kg/min (NA0,5 en la fase "t=90"; DPDB más NA a 1 mcg/kg/min (NA1 en la fase "t=120"; Grupo C (n=7: Dopexamina a 12 mcg/kg/min (DX en la fase "t=60", DX más NA0,5 en la fase "t=90" y DX más NA1 en la fase "t=120". La comparación estadística se realizó mediante: "t" de Student-Fisher, Análisis de la Varianza, Chi Cuadrado y cálculo de la potencia estadística en caso necesario. RESULTADOS: Grupo B respecto al A: DP-DB NA0.5 aumentó la Frecuencia cardiaca (FC; DPDB-NA1 además incrementó la Presión diastólica (TAD. Grupo C respecto al A: DX- NA0,5 aumentó la FC; DX- NA1, incrementó la FC y TAD. CONCLUSIONES: La FC, TAS y TAD, se modificaron significativamente con las diversas asociaciones de aminas, mientras que no se evidenciaron variaciones intergrupo de la glucemia y plaquetas. Los cambios significativos en las últimas fases de la investigación experimental, de la glucemia y de las plaquetas, fueron secundarios a la progresión del shock séptico experimental y no a la diferente terapia recibida en cada grupo (ya que se comportaron de forma independiente al tratamiento administrado.

  8. DNP NMR of carbohydrate converting enzymes

    DEFF Research Database (Denmark)

    Kjeldsen, Christian; Ardenkjær-Larsen, Jan Henrik; Duus, Jens Øllgaard

    relaxation, but even with this limitation, it is possible to obtain detailed reaction parametersin less than one minute. The enzyme investigated was β-galactosidase from E. coli (E.C. 3.2.1.23). It is well described and the mechanism is generally accepted to be a double displacement with a covalently bound...

  9. OBTENCION DE UN CONCENTRADO DE ANTIOXIDANTES PROVENIENTE DE MANZANA DE PIEL Y FRUTOS PEQUEÑOS DE RALEO DE MANZANA SOBRE SINDROME METABOLICO EN UN MODELO ANIMAL MURINO

    OpenAIRE

    POBLETE BUSTAMANTE, MAURICIO ANDRES

    2012-01-01

    Chile, desde finales de 1980, está pasando por un extraordinario momento económico que lo ha llevado a situarse como líder en Latinoamérica según una gran cantidad de indicadores (Desarrollo Humano, nivel de pobreza, Producto Interno Bruto, etc.). Es así que nuestro país fue invitado a formar parte de la Organization Economic Cooperation Development (OECD), grupo de países con un fuerte desarrollo socio-económico, como Estados Unidos, Japón, Noruega, Alemania, Corea del Sur entre otros. En...

  10. Micro tomography prototype by positron emission. Spatial resolution and metabolic studies;Prototipo de microtomografo por emision de positrones. Resolucion espacial y estudios metabolicos

    Energy Technology Data Exchange (ETDEWEB)

    Alva S, H.; Murrieta, T.; Ruiz T, C.; Brandan, M. E.; Martinez D, A.; Rodriguez V, M., E-mail: halva@fisica.unam.m [UNAM, Instituto de Fisica, Circuito de la Investigacion Cientifica s/n, Ciudad Universitaria, 04510 Mexico D. F. (Mexico)

    2010-07-01

    During the past 4 years, the Medical Physics and Dosimetry Group at the Physics Institute, UNAM, has developed a positron emission tomography prototype for small-animal imaging (micro PET). The system is composed of pix elated, cerium-doped lutetium yttrium oxy orthosilicate scintillation crystal arrays coupled to position-sensitive photomultiplier tubes. Detector electronic signals are processed by nuclear instrumentation modules and are digitized by a multichannel data acquisition board. The tomographic reconstruction is performed by filtered backprojection from a set of distortion- and nonuniformity- corrected projections taken at different angles. In this work, the reconstructed spatial resolution was evaluated from the line spread function with a mean value of 2.36 +- 0.44 mm. In addition, the first metabolic studies of 30 g, healthy mice, injected with {sup 1}8{sup F} labeled fluorodeoxyglucose and sodium fluoride are reported. They display normal glucose uptake and skeletal structure, respectively. The micro PET can be a useful tool for radiation detector physics research and its applications in nuclear medicine. (Author)

  11. Application of compartmental metabolic models for determination of retention and excretion functions; Aplicacao de modelos metabolicos para a determinacao de funcoes de excrecao e retencao

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues Junior, O

    1994-07-01

    After an intake of radioactive material, its behaviour in the human body can be described by mathematical models, where organs, tissues or regions of the body are treated as a chain of linked compartments. The mathematical approach for such metabolic models is usually done through a system of differential equations of first order with constant coefficients. The solutions of this system of equations associates the radionuclide intake, with the fraction excreted or retained in the organ of interest. A computer program - called INCORP and for running in PC compatible microcomputers - was developed in order to find the solutions of such system of equations, using an analytical method based on expansion of series of exponential matrices. The metabolic model presented in the ICRP-30 publication was simulated using the INCORP program, in order to find the respective retention and excretion curves for selected radionuclides. (author)

  12. [Treatment results of rifampicin (RFP) resistant isoniazid (INH) susceptible tuberculosis, a hospital based study].

    Science.gov (United States)

    Yoshiyama, Takashi; Ogata, Hideo; Ito, Kunihiko; Aono, Akio; Wada, Masako

    2007-02-01

    To evaluate treatment results of Rifampicin (R) resistant Isoniazid (H) susceptible tuberculosis cases. Cohort analysis of twenty-three H susceptible R resistant tuberculosis cases started treatment in 1985-2004 at Fukujuji Hospital, by the retrospective review. Three cases became Multi-drug resistant tuberculosis (MDR TB), seventeen cases were cured, two cases died, and one case transferred out. One started treatment with HR became MDR, one of the two started treatment with HR+ Ethambutol (E) became MDR and one of them was cured, eight among ten cases started treatment with HR+Pyrazinamide + (E or Streptomycine (S)) were cured, one among the ten died and one among the ten transferred out, one started treatment with RZE was cured, three among the five cases started treatment with three effective drugs without Z were cured, one among the five died, one among the five became MDR. Three cases started treatment with four effective drugs were cured. Among the nineteen cases continued treatment for more than six months, ten cases treated with four or five effective drugs for at least two months were cured, two cases of nine cases treated with three drugs or less became MDR, seven of the nine cases were cured. Among the same nineteen cases, eleven cases not treated with two or less effective drugs were cured, one case treated with two or less effective drugs for six months became MDR and one of them treated with one or two effective drug for one to three months became MDR and some were cured. The used drugs were H, E, Pyrazinamide, Streptomycin, Kanamycin, Ethionamide and New Quinolones. The duration of treatment of cured cases were eleven to twelve months in 3 cases, twelve to eighteen months in 3 cases, eighteen to twenty-four months in 8 cases and more than two years in 3 cases. If the starting regimen is HRZE, we can cure R resistant H susceptible tuberculosis by the use of four effective drugs for more than two months and at least three effective drugs with the total duration of treatment for twelve to twenty-four months.

  13. Arquitectura militar y neoclasicismo : el cuartel de inhábiles de Lugo

    Directory of Open Access Journals (Sweden)

    Adolfo de Abel Vilela

    1993-01-01

    Full Text Available Resulta conocida la importancia que tuvieron los ingenieros militares en la renovación de la arquitectura de la segunda mitad del siglo xviii, en especial durante el reinado de Carlos III (1759-1788, período en el que nos encontramos con una serie de tendencias arquitectónicas que hasta ahora se vienen agrupando bajo el denominador común de neoclasicismo, en el que se incluyen corrientes del barroco romano, en la línea de Maderno, Bernini, Galilei, etc., un estilo más depurado en consonancia con el clasicismo renacentista, y formas mucho más simplificadas que se pueden encuadrar dentro de una arquitectura racionalista.

  14. Large dose hyperpolarized water with dissolution-DNP at high magnetic field

    DEFF Research Database (Denmark)

    Lipsø, Hans Kasper Wigh; Bowen, Sean; Rybalko, Oleksandr

    2016-01-01

    We demonstrate a method for the preparation of hyperpolarized water by dissolution Dynamic Nuclear Polarization at high magnetic field. Protons were polarized at 6.7T and 1.1K to >70% with frequency modulated microwave irradiation at 188GHz. 97.2±0.7% of the radical was extracted from the sample...... was polarized and dissolved in a fluid path compatible with clinical polarizers. The volume of hyperpolarized water produced by this method enables angiography and perfusion measurements in large animals, as well as NMR experiments for studies of e.g. proton exchange and polarization transfer to other nuclei....

  15. The DNP/MPH Dual Degree: An Innovative Graduate Education Program for Advanced Public Health Nursing.

    Science.gov (United States)

    Shaw, Kathy; Harpin, Scott; Steinke, Geraldine; Stember, Marilyn; Krajicek, Marilyn

    2017-03-01

    Strong professional priorities, evolving Affordable Care Act requirements, and a significantly limited public health nursing workforce prompted the University of Colorado College of Nursing to collaborate with the School of Public Health to implement one of the first Doctor of Nursing Practice/Master of Public Health dual degree programs in the nation. Federal grant funding supported the development, implementation, and evaluation of this unique post-baccalaureate dual degree program, for which there were no roadmaps, models, or best practices to follow. Several key issues emerged that serve as lessons learned in creating a new, novel higher education pathway for Advanced Public Health Nursing. This paper highlights two of those: (1) marketing, admission, and matriculation across two programs, and (2) enhancing curricula through distance coursework and interprofessional education. When collaboration with a school of public health is possible, the Doctor of Nursing Practice/Master of Public Health dual degree is an efficient way to prepare public health nurses' with the highest level of public health knowledge, practice, and leadership expertise. © 2016 Wiley Periodicals, Inc.

  16. Experimental Determination of Physical Properties of DNGU, TNBA, LLM-105, HK-56, and DNP

    Science.gov (United States)

    2016-09-01

    1 Fig. 2 UV spectra of samples in this study. Absorbance wavelength maxima are...6 Fig. 4 ATR- FTIR spectra of samples in this study ..........................................7 Fig. 5 DSC trace for...Clausius-Clapeyron plot of estimated vapor pressures at 25, 70, and 100 °C. Attenuated total reflectance (ATR)-Fourier transform infrared ( FTIR

  17. Monitoring of the incorporation of I-138 by inhalation in facilities of metabolic treatment; Vigilancia de la incorporacion de I{sub 1}31 por inhalacion en las instalaciones de tratamientos de metabolicos

    Energy Technology Data Exchange (ETDEWEB)

    Baquero, R.; Anton, D.; Miguel, D. de

    2013-07-01

    The measure of thyroid activity with a surface contamination meter allows you to rule out or confirm the presence of iodine in the thyroid of the nursing staff. You have these teams in all Nuclear Medicine facilities, which can be used with simplicity immediately. To carry out these measures is necessary to have a background environment in which are carried out low, so as the limit of detection got enable check low levels to determine. (Author)

  18. Factors related to glycemic control in IDDM and insulin-treated NIDDM patients in current practice. A comparison of care policies. SIEMTIC Group. Studio Italiano Epidemiologico Multicentrico su Terapia Insulin e Controllo Metabolico.

    Science.gov (United States)

    Garancini, M P; Gallus, G; Cucinotta, D; Rossi, A; Riccardi, G

    1997-11-01

    To evaluate, under routine conditions, the relation between different diabetes care policies and glycemic control through a by-center analysis procedure aimed at reducing some drawbacks of cross-sectional data. A survey on insulin-treated diabetes care management (IDDM and NIDDM) involved 16 Italian randomly selected diabetes outpatient clinics. A total of 2,142 representative patients were investigated. The standardized HbA1c average value of each center was related, by regression models, to some indicators of center care policy (average number of injections, average BMI, proportion of cases with recent fundus oculi examinations, or frequent visits) as well as to patients' average social levels (employment type). Homogeneity in patient admission criteria is assumed among the investigated centers as a basic condition for the procedure validity. Some known imbalance were controlled for both design and analysis. HbA1c showed a univariate inverse relation with daily number of injections in IDDM (P = 0.0009, r2 = 0.56) but not in NIDDM (P = 0.33). It was inversely related to both fundus examination (IDDM P = 0.04; NIDDM P = 0.099) and qualified employment (IDDM P = 0.06; NIDDM P = 0.026). A stepwise regression analysis left in the model insulin injections (P = 0.0002) in IDDM (total r2 = 0.68) and qualified employment (P = 0.016) and fundus examination (P = 0.14) in NIDDM (total r2 = 0.53), after controlling for age, sex, disease duration, insulin therapy starting delay, and insulin dose per kilogram. These results suggest that the confirmed benefits of a multiple-injection regimen in IDDM cannot be simply extrapolated to NIDDM, where patients' awareness and medical attention to complications proved to be the most important factors in current practice.

  19. Offspring of xenogeneically-reconstituted scid scid mice are capable of a primary xenogeneic immune response to DNP-KLH

    NARCIS (Netherlands)

    Greenwood, JD; Bos, NA; Croy, BA

    Human peripheral blood leukocyte (PBL) reconstitution of severe combined immunodeficient (SCID) mice has provided a small animal model system (hu-PBL-SCID) useful for the study of the human immune system and disease pathogenesis. Transfer of xenogeneic PBL from donors other than humans has also been

  20. Effects of DNP on the cell surface properties of marine bacteria and its implication for adhesion to surfaces

    Digital Repository Service at National Institute of Oceanography (India)

    Jain, A.; Nishad, K.K.; Bhosle, N.B.

    of hydrogen peroxide as model antimicrobial agent for examining resisitance mechanisms. Methods Enzymol 310 : 599-608. Haque H, Cutright TJ & Zhang newby BM (2005) Effectiveness of sodium benzoate as a freshwater low toxicity antifoulant when dispersed... and the Environment (D Almorza C A, Brebbia D Sales & V Popov) (Editors),ISBN 1-85312-907- 0. Min Seok chae, Heidi Schraft, Lisbeth Truelstrup Hansen & Robet Mackereth (2006) Effect of physiochemical surface characteristic of Listeria monocytogenes strains...

  1. Measuring absolute spin polarization in dissolution-DNP by Spin PolarimetrY Magnetic Resonance (SPY-MR).

    Science.gov (United States)

    Vuichoud, Basile; Milani, Jonas; Chappuis, Quentin; Bornet, Aurélien; Bodenhausen, Geoffrey; Jannin, Sami

    2015-11-01

    Dynamic nuclear polarization at 1.2 K and 6.7 T allows one to achieve spin temperatures on the order of a few millikelvin, so that the high-temperature approximation (ΔEPolarimetrY Magnetic Resonance (SPY-MR), is illustrated for various pairs of (13)C spins (I, S) in acetate and pyruvate. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Polymorphisms in PARP, IL1B, IL4, IL10, C1INH, DEFB1, and DEFA4 in meningococcal disease in three populations.

    NARCIS (Netherlands)

    Emonts, M.; Vermont, C.L.; Houwing-Duistermaat, J.J.; Haralambous, E.; Gaast-de Jongh, C.E. van der; Hazelzet, J.A.; Faust, S.N.; Betts, H.; Hermans, P.W.M.; Levin, M.; Groot, R. de

    2010-01-01

    The pathogenesis of meningococcal infections involves activation of the complement system, proinflammatory and anti-inflammatory mediators, antimicrobial peptides, and apoptosis. We hypothesized that variations in genes encoding these products are involved in the susceptibility to and severity of

  3. POLYMORPHISMS IN PARP, IL1B, IL4, IL10, C1INH, DEFB1, AND DEFA4 IN MENINGOCOCCAL DISEASE IN THREE POPULATIONS

    NARCIS (Netherlands)

    Emonts, Marieke; Vermont, Clementien L.; Houwing-Duistermaat, Jeanine J.; Haralambous, Elene; Gaast-de Jongh, Christa E.; Hazelzet, Jan A.; Faust, Saul N.; Betts, Helen; Hermans, Peter W. M.; Levin, Michael; de Groot, Ronald

    The pathogenesis of meningococcal infections involves activation of the complement system, proinflammatory and anti-inflammatory mediators, antimicrobial peptides, and apoptosis. We hypothesized that variations in genes encoding these products are involved in the susceptibility to and severity of

  4. El desafío de construir una Psicología del desarrollo crítica en sociedades inhóspitas

    OpenAIRE

    Carlos Iván Orellana

    2016-01-01

    La Psicología del desarrollo constituye un campo de conocimiento cuya existencia se da por descontada en el imaginario académico de la psicología salvadoreña. No obstante, existe una Psicología del desarrollo dominante que se ve reproducida en textos, clases y discursos, mientras que otra distinta, consecuente con la realidad histórica donde su estudio tiene lugar, aún es una tarea pendiente. Al considerar la descontextualización como uno de los presupuestos fundamentales de la Psicología del...

  5. Abordagem racional no planejamento de novos tuberculostáticos: inibidores da InhA, enoil-ACP redutase do M. tuberculosis Rational approach in the new antituberculosis agent design: inhibitors of InhA, the enoyl-ACP reductase from Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Carolina Horta Andrade

    2008-06-01

    Full Text Available Associada à disseminação da infecção causada pelo HIV, a tuberculose (TB é considerada, atualmente, problema mundial de saúde pública devido às proporções que vem assumindo. A resistência micobacteriana aos fármacos utilizados na terapêutica é a principal causa da reincidência da TB. Diante deste quadro alarmante, o desenvolvimento de novos e seletivos fármacos anti-TB se faz urgente e necessário. A biossíntese de ácidos graxos é um processo bioquímico realizado por procariotos e eucariotos, o qual fornece precursores essenciais à montagem de componentes celulares importantes, tais como fosfolipídeos, lipoproteínas, lipopolissacarídeos, ácidos micólicos e envelope celular. As diferenças bioquímicas e funcionais entre o mecanismo biossintético de ácidos graxos em bactérias e mamíferos tornam-no alvo relevante ao planejamento de novos antibacterianos, mais seletivos e menos tóxicos. As enoil-ACP redutases são enzimas cruciais à etapa de alongamento de ácidos graxos, considerados produtos intermediários na biossíntese de ácidos micólicos - os principais componentes da parede celular micobacteriana. Portanto, tais enzimas são tidas como alvos moleculares no planejamento racional de novos tuberculostáticos. Avanços recentes no processo de descoberta de novos agentes anti-TB, particularmente os inibidores da enoil-ACP redutase, serão discutidos nesta revisão.In conjunction with the spread of HIV infection, tuberculosis (TB has been among the worldwide health threats. Mycobacteria resistance to the drugs currently used in the therapeutics is the main cause of TB resurgence. In view of this severe situation, the new and selective anti-TB design is of utmost importance. Fatty acid biosynthesis is a prokariontes and eucariontes biochemical process that supplies essential precursors for the assembly of important cellular components, such as phospholipids, lipoproteins, lipopolysaccharides, mycolic acids and cellular envelope. However, the biochemical and functional differences between the bacterial and mammals' fatty acid synthetic pathway have endowed the mycobacterial enzymes with distinct properties. These provide valuable opportunities for structure- or catalytic mechanism-based design of selective inhibitors as novel anti-TB drugs with improved properties. The enoyl-reductases are essential enzymes in the fatty acids elongation pathway towards the mycolic acids, the main mycobacteria cell wall constituents, biosynthesis and so they are potential targets to the rational new antimycobacteria drug design. This paper highlights recent approaches regarding the design of new anti-TB agents, particularly, the enoyl-ACP reductase inhibitors.

  6. Comportamiento metabolico en el periparto de vacas Hartón del Valle, bajo condiciones de trópico bajo Metabolic behaviour in the peripartum period of dairy cows Hartón del Valle creole breed, under tropical conditions

    Directory of Open Access Journals (Sweden)

    Erika Andrea Hernández

    2011-01-01

    Full Text Available El periodo de periparto o periodo de transición presenta variaciones fisiológicas significativas que inciden en posteriores sucesos productivos (pico de lactancia, reactivación ovárica). El ganado Hartón posee una excelente eficiencia reproductiva (estrecho intervalo entre partos), factor que podría originarse en procesos metabólicos relacionados con un mejor ajuste homeostático. El principal objetivo del presente trabajo fue evaluar la homeostasis en una raza bovina criolla durante el periodo postparto. Para el estudio se emplearon 10 vacas multíparas, muestreadas antes del parto (días 30 y 15 preparto) y diariamente en los tres primeros días del parto; posteriormente a partir del día 5, con intervalos de cinco días y hasta el día 60 postparto. En total para cada animal se analizaron 14 muestras, cada una de ellas correspondió a un periodo analítico. Mediante venipunción coccígea en tubos al vacío con y sin anticoagulante se colectó la muestra de sangre completa. Por centrifugación se obtuvo plasma y suero, los cuales fueron almacenados a -20°C, hasta su análisis. Las determinaciones de hormonas se realizaron mediante radioinmunoanálisis (RIA) de fase sólida. A través de pruebas enzimáticas colorimétricas en equipos automatizados, se determinaron los valores de los metabolitos para cada uno de los periodos definidos. Los valores medios fueron: BHB (β-Hidroxibutirato) 0.39 mmol/L, NEFA (ácidos Grasos No Esterificados) 0.76 mmol/L, triglicéridos 0.42 mmol/L, colesterol 2.43 mmol/L, insulina 4.77 mµl/ml, triyodotironina (T3) 2.69 nmol/L, tetrayodotironina (T4) 57.37 nmol/L, progesterona 5.54 nmol/L, cortisol 32.42 nmol/L. Los valores obtenidos para los diferentes metabolitos se encuentran dentro de los rangos reportados por la literatura para bovinos en condiciones tropicales.The peripartum period or transition period, presents significant physiological changes that affect production in subsequent production events (peak lactation, ovarian resumption). Creole bovine cattle "Hartón del Valle" has an excellent reproductive performance (short iterpartum period); this factor could have been originated from metabolic processes related to an improved homeostatic adjustment. The main aim of this study was to assess the homeostasis in a native cattle breed in the postpartum period. For this study, 10 multiparous cows were used and sampled before birth (days 30 and 15 prepartum) and daily in the first three days of birth, and afterwards from day 5, at intervals of five days and up to-day 60 postpartum. In total, for each animal 14 samples were analyzed which correspond to one analysis period. Using the coccygeal venipuncture technic, in vacuum tubes with and without anticoagulant the complete sample was collected. By centrifugation, plasma and serum were obtained and stored at -20°C until the metabolic analysis was done. Using a radioimmunoassay (RIA) of solid phase, hormone analysis were done. Through enzymatic colorimeter test in automated equipment the values of the metabolites for each of the defined period were determined. The mean values were: BHB (β-Hidroxibutirates) 0.39 mmol/L, NEFA (Non Esterified Fatid Acids) 0.76 mmol/L, triglycerides 0.42 mmol/L, cholesterol 2.43 mmol/L, triiodothyronine (T3) 2.69 nmol/L, tetraiodothyronine (T4) 57.37 nmol/L, insulin 4.77 mµl/ml, progesterone 5.54 nmol/L, cortisol 32.42 nmol/L. The values obtained for the different metabolites were within the biological ranges reported in the literature for cattle of tropical ecosystems.

  7. Synthesis, magnetic and spectral studies of lanthanide(III) chloride complexes of hydrazones of isonicotinic acid hydrazide

    International Nuclear Information System (INIS)

    Agarwal, R.K.; Agarwal, Himanshu; Prasad, Ram

    1996-01-01

    The synthesis, magnetic and spectral properties of trivalent lanthanide chlorides with N-isonicotinamidobenzalaldimine (INH-BENZ), N-isonicotinamidoanisalaldimine (INH-ANSL) and N-isonicotinamido-p-dimethylaminobenzalaldimine (INH-PDAB) are described. 13 refs., 2 tabs

  8. Strategy-aligned fuzzy approach for market segment evaluation and selection: a modular decision support system by dynamic network process (DNP)

    Science.gov (United States)

    Mohammadi Nasrabadi, Ali; Hosseinpour, Mohammad Hossein; Ebrahimnejad, Sadoullah

    2013-05-01

    In competitive markets, market segmentation is a critical point of business, and it can be used as a generic strategy. In each segment, strategies lead companies to their targets; thus, segment selection and the application of the appropriate strategies over time are very important to achieve successful business. This paper aims to model a strategy-aligned fuzzy approach to market segment evaluation and selection. A modular decision support system (DSS) is developed to select an optimum segment with its appropriate strategies. The suggested DSS has two main modules. The first one is SPACE matrix which indicates the risk of each segment. Also, it determines the long-term strategies. The second module finds the most preferred segment-strategies over time. Dynamic network process is applied to prioritize segment-strategies according to five competitive force factors. There is vagueness in pairwise comparisons, and this vagueness has been modeled using fuzzy concepts. To clarify, an example is illustrated by a case study in Iran's coffee market. The results show that success possibility of segments could be different, and choosing the best ones could help companies to be sure in developing their business. Moreover, changing the priority of strategies over time indicates the importance of long-term planning. This fact has been supported by a case study on strategic priority difference in short- and long-term consideration.

  9. Le Ipocolesterolemie

    OpenAIRE

    Antic, Tijana

    2012-01-01

    Ipocolesterolemia o il colesterolo basso è un disordine metabolico caratterizzato da basse concentrazioni di colesterolo nel sangue. Mentre il problema opposto, definito ipercolesterolemia, è piuttosto comune negli abitanti dei Paesi industrializzati a causa dei ben noti eccessi alimentari, livelli di colesterolo particolarmente bassi si registrano soprattutto nelle regioni afflitte da denutrizione. Anche per questo motivo il significato clinico dell'ipocolesterolemia è per certi aspetti anco...

  10. Efectos de un programa de tratamiento multidisciplinar en obesos m??rbidos y obesos con comorbilidades candidatos a cirug??a bari??trica

    OpenAIRE

    Delgado Floody, Pedro; Caama??o Navarrete, Felipe; Jerez Mayorga, Daniel; Campos Jara, Christian Alex; Ram??rez Campillo, Rodrigo; Osorio Poblete, Aldo; Alarc??n Hormaz??bal, Manuel; Thuillier Lepeley, Nicole; Saldivia Mansilla, Claudia

    2015-01-01

    Introducci??n: La obesidad morbida es una enfermedad que debe ser tratada de forma integral (i.e., multi/ interdisciplinar). Para esta condicion la cirugia bariatrica es efectiva y segura en el tratamiento, sin embargo, a mayor peso preoperatorio podria aumentar la morbimortalidad. Objetivo: El objetivo del estudio es determinar los efectos de un programa de tratamiento interdisciplinar sobre parametros metabolicos, antropometricos y la condicion fisica en candidatos a cirugia bariatrica. Mat...

  11. Isoniazid Pharmacokinetics in the Presence of Ofloxacin and Norfloxacin Antibiotics.

    Science.gov (United States)

    Brown, Sinyeofori A; Ezejiofor, Ndidi A; Barikpoar, Ebenezer; Orisakwe, Orish E

    2014-01-21

    The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on isoniazid (INH) pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39 years after an informed consent. The study was carried out in 3 phases with an interval drug wash out period of at least 1 week in between the phases. In phase 1 (INH alone), subject received 300 mg (usual adult dose) of INH. In phase 2 (INH + OXC), 300 mg of INH was coadministered with 200 mg of OXC, and in phase 3 (INH + NXC) each received 300 mg of INH together with 400 mg of NXC after 1-week drug wash period. Drugs were taken orally with 350 mL of water after an overnight fast, and the subject fasted 3 hours after drug. Plasma, saliva, and urine concentration of INH were predetermined at zero hour, then hourly until the eighth hour, 12 hours, 24 hours, and finally at 48 hours. The urine samples were further collected at 72 hours after drug(s) administration using validated methods. Various pharmacokinetics parameters were calculated. Various pharmacokinetic parameters of INH significantly differed when administered alone or in combination with OXC or with NXC. The mean saliva to plasma ratio of INH concentration was 0.14. The bioavailability indices of INH in the saliva and plasma were similar in all the groups. NXC and OXC reduced the extent and rate of absorption of INH. The determination of INH levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.

  12. Physical and chemical properties of chromatin and its fragments formed in the rat thymus during postirradiation autolysis and under the influence of DNA-ase and protease on DNP preparations

    International Nuclear Information System (INIS)

    Ermolaeva, N.V.; Vodolazskaya, N.A.

    1978-01-01

    It has been shown that the thymus chromatin degradation 2-8 hr after irradiation is followed by its cross-splitting and accumulation of several types of fragments differing in the degree of DNA association with the protein. Participation of proteases in the formation of fragments is hardly probable. Acid DNAase is involved in the autolysis perhaps in his maximum later 6 hr after irradiation

  13. Whole-Body Distribution of Donepezil as an Acetylcholinesterase Inhibitor after Oral Administration in Normal Human Subjects: A 11C-donepezil PET Study

    Directory of Open Access Journals (Sweden)

    Ikuko Mochida

    2017-01-01

    Full Text Available Objective(s: It is difficult to investigate the whole-body distribution of an orally administered drug by means of positron emission tomography (PET, owing to the short physical half-life of radionuclides, especially when 11C-labeled compounds are tested. Therefore, we aimed to examine the whole-body distribution of donepezil (DNP as an acetylcholinesterase inhibitor by means of 11C-DNP PET imaging, combined with the oral administration of pharmacological doses of DNP.Methods: We studied 14 healthy volunteers, divided into group A (n=4 and group B (n=10. At first, we studied four females (mean age: 57.3±4.5 y, three of whom underwent 11C-DNP PET scan at 2.5 h after the oral administration of 1 mg and 30 μg of DNP, respectively, while one patient was scanned following the oral administration of 30 μg of DNP (group A. Then, we studied five females and five males (48.3±6.1 y, who underwent 11C-DNP PET scan, without the oral administration of DNP (group B. Plasma DNP concentration upon scanning was measured by tandem mass spectrometry. Arterialized venous blood samples were collected periodically to measure plasma radioactivity and metabolites. In group A, 11C-DNP PET scan of the brain and whole body continued for 60 and 20 min, respectively. Subjects in group B underwent sequential whole-body scan for 60 min. The regional uptake of 11C-DNP was analyzed by measuring the standard uptake value (SUV through setting regions of interest on major organs with reference CT.Results: In group A, plasma DNP concentration was significantly correlated with the orally administered dose of DNP. The mean plasma concentration was 2.00 nM (n=3 after 1 mg oral administration and 0.06 nM (n=4 after 30 μg oral administration. No significant difference in plasma radioactivity or fraction of metabolites was found between groups A and B. High 11C-DNP accumulation was found in the liver, stomach, pancreas, brain, salivary glands, bone marrow, and myocardium in groups A

  14. Whole-Body Distribution of Donepezil as an Acetylcholinesterase Inhibitor after Oral Administration in Normal Human Subjects: A 11C-donepezil PET Study

    Science.gov (United States)

    Mochida, Ikuko; Shimosegawa, Eku; Kanai, Yasukazu; Naka, Sadahiro; Matsunaga, Keiko; Isohashi, Kayako; Horitsugi, Genki; Watabe, Tadashi; Kato, Hiroki; Hatazawa, Jun

    2017-01-01

    Objective(s): It is difficult to investigate the whole-body distribution of an orally administered drug by means of positron emission tomography (PET), owing to the short physical half-life of radionuclides, especially when 11C-labeled compounds are tested. Therefore, we aimed to examine the whole-body distribution of donepezil (DNP) as an acetylcholinesterase inhibitor by means of 11C-DNP PET imaging, combined with the oral administration of pharmacological doses of DNP. Methods: We studied 14 healthy volunteers, divided into group A (n=4) and group B (n=10). At first, we studied four females (mean age: 57.3±4.5 y), three of whom underwent 11C-DNP PET scan at 2.5 h after the oral administration of 1 mg and 30 µg of DNP, respectively, while one patient was scanned following the oral administration of 30 µg of DNP (group A). Then, we studied five females and five males (48.3±6.1 y), who underwent 11C-DNP PET scan, without the oral administration of DNP (group B). Plasma DNP concentration upon scanning was measured by tandem mass spectrometry. Arterialized venous blood samples were collected periodically to measure plasma radioactivity and metabolites. In group A, 11C-DNP PET scan of the brain and whole body continued for 60 and 20 min, respectively. Subjects in group B underwent sequential whole-body scan for 60 min. The regional uptake of 11C-DNP was analyzed by measuring the standard uptake value (SUV) through setting regions of interest on major organs with reference CT. Results: In group A, plasma DNP concentration was significantly correlated with the orally administered dose of DNP. The mean plasma concentration was 2.00 nM (n=3) after 1 mg oral administration and 0.06 nM (n=4) after 30 µg oral administration. No significant difference in plasma radioactivity or fraction of metabolites was found between groups A and B. High 11C-DNP accumulation was found in the liver, stomach, pancreas, brain, salivary glands, bone marrow, and myocardium in groups A and B

  15. Recombinant C1-Inhibitor Effects on Coagulation and Fibrinolysis in Patients with Hereditary Angioedema

    NARCIS (Netherlands)

    Relan, Anurag; Bakhtiari, Kamran; van Amersfoort, Edwin S.; Meijers, Joost C. M.; Hack, C. Erik

    2012-01-01

    Background: Recombinant human C1-inhibitor (rhC1INH; Ruconest (R)) has been developed for treatment of acute angioedema attacks in patients with hereditary angioedema (HAE) due to heterozygous deficiency of C1INH. Previous reports suggest that administration of plasma-derived C1INH products may be

  16. Intestinal absorption of dinitrophenyl-lysine and effect of immunization with dinitrophenylated bovine serum albumin

    International Nuclear Information System (INIS)

    Shimura, Fumio; Shimura, Junko; Shimazaki, Shigeki; Hosoya, Norimasa

    1983-01-01

    The intestinal absorption of dinitrophenyl-lysine (DNP-lys) was studied with a special interest on the role of the immune system in the absorption of small molecules which are recognized as nonself. [ 3 H]-DNP- lys was rapidly absorbed by ligated intestinal loops in situ via a saturable and unique route. When [ 3 H]-DNP-lys was preincubated with the immume serum obtained from rats immunized with dinitrophenylated bovine serum albumin (DNP-BSA), the [ 3 H]-DNP-lys absorption was depressed. The absorption of [ 3 H]-DNP-lys in DNP-BSA-immunized rats was depressed compared to the control. The results obtained suggest that the immune system play a role in avoiding the absorption of small molecules with antigenicity. (author)

  17. Preparation of alginate–chitosan–cyclodextrin micro- and nanoparticles loaded with anti-tuberculosis compounds

    Directory of Open Access Journals (Sweden)

    Albert Ivancic

    2016-08-01

    Full Text Available This paper describes the synthesis and application of alginate–chitosan–cyclodextrin micro- and nanoparticulate systems loaded with isoniazid (INH and isoconazole nitrate (ISN as antimycobacterial compounds. Preparation and morphology of the obtained particles, as well as antimycobacterial activity data of the obtained systems are presented. Docking of isoconazole into the active site of enoyl–acyl carrier protein reductase (InhA of Mycobacetrium tuberculosis was carried out in order to predict the binding affinity and non-covalent interactions stabilizing the InhA–isoconazole complex. To assess these interactions, frontier molecular orbital calculations were performed for the active site of InhA and isoconazole obtained from docking. Isoconazole was predicted to be an active inhibitor of InhA with the analysis of the molecular docking and electron density distribution. It has been detected that alginate–chitosan–cyclodextrin microparticulate systems loaded with INH and ISN are as effective as pure INH applied in higher dosages.

  18. Characterization of recombinant human C1 inhibitor secreted in milk of transgenic rabbits.

    Science.gov (United States)

    van Veen, Harrie A; Koiter, Jaco; Vogelezang, Carla J M; van Wessel, Noucha; van Dam, Tijtje; Velterop, Ingeborg; van Houdt, Kristina; Kupers, Luc; Horbach, Danielle; Salaheddine, Mourad; Nuijens, Jan H; Mannesse, Maurice L M

    2012-12-31

    C1 inhibitor (C1INH) is a single-chain glycoprotein that inhibits activation of the contact system of coagulation and the complement system. C1INH isolated from human blood plasma (pd-hC1INH) is used for the management of hereditary angioedema (HAE), a disease caused by heterozygous deficiency of C1INH, and is a promise for treatment of ischemia-reperfusion injuries like acute myocardial or cerebral infarction. To obtain large quantities of C1INH, recombinant human C1INH (rhC1INH) was expressed in the milk of transgenic rabbits (12 g/l) harboring genomic human C1INH sequences fused to 5' bovine αS(1) casein promoter sequences. Recombinant hC1INH was isolated from milk to a specific activity of 6.1 U/mg and a purity of 99%; by size-exclusion chromatography the 1% impurities consisted of multimers and N-terminal cleaved C1INH species. Mass spectrometric analysis of purified rhC1INH revealed a relative molecular mass (M(r)) of 67,200. Differences in M(r) on SDS PAGE and mass spectrometric analysis between rhC1INH and pd-hC1INH are explained by differential glycosylation (calculated carbohydrate contents of 21% and 28%, respectively), since protein sequencing analysis of rhC1INH revealed intact N- and C-termini. Host-related impurity analysis by ELISA revealed trace amounts of rabbit protein (approximately 10 ppm) in purified batches, but not endogenous rabbit C1INH. The kinetics of inhibition of the target proteases C1s, Factor XIIa, kallikrein and Factor XIa by rhC1INH and pd-hC1INH, indicated comparable inhibitory potency and specificity. Recently, rhC1INH (Ruconest(®)) has been approved by the European Medicines Agency for the treatment of acute attacks of HAE. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Determination of isoniazid concentration in rabbit vertebrae by isotope tracing technique in conjunction with HPLC.

    Science.gov (United States)

    Liu, Peng; Fu, Zhaozong; Jiang, Jianming; Yuan, Liang; Lin, Zhen

    2013-09-01

    Medications compounded with isoniazid (INH) are usually applied to surgical sites at the completion of surgery to locally kill postoperative residual tubercle bacilli. However, the distribution and elimination of INH in the vertebrae in vivo are not known. In this study, isotope tracing was used in conjunction with high-pressure liquid chromatography (HPLC) to address this. INH and technetium-99 m-labeled INH were applied to the vertebrae of rabbits. After 2 and 6 h, osseous tissues containing INH, as determined by radionuclide imaging, were collected for detection with HPLC. The results showed that INH mainly stayed around the vertebrae 6 h after its application and did not permeate widely into the blood or other organs, except for the kidneys. The standard deviations of INH concentrations in the technetium-99 m-INH group were approximately four-fold smaller than those in the INH group. This method of coupling isotope tracing and HPLC can effectively limit experimental error during sample collection, allowing accurate and reliable identification of the concentration levels of INH in osseous tissues in vivo. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Lower cytotoxicity, high stability, and long-term antibacterial activity of a poly(methacrylic acid)/isoniazid/rifampin nanogel against multidrug-resistant intestinal Mycobacterium tuberculosis.

    Science.gov (United States)

    Chen, Tao; Li, Qiang; Guo, Lina; Yu, Li; Li, Zhenyan; Guo, Huixin; Li, Haicheng; Zhao, Meigui; Chen, Liang; Chen, Xunxun; Zhong, Qiu; Zhou, Lin; Wu, Ting

    2016-01-01

    To overcome the undesirable side effects and reduce the cytotoxicity of isoniazid (INH) and rifampin (RMP) in the digestive tract, a poly(methacrylic acid) (PMAA) nanogel was developed as a carrier of INH and RMP. This PMAA/INH/RMP nanogel was prepared as a treatment for intestinal tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB). The morphology, size, and in vitro release properties were evaluated in a simulated gastrointestinal medium, and long-term antibacterial performance, cytotoxicity, stability, and activity of this novel PMAA/INH/RMP nanogel against multidrug-resistant MTB in the intestine were investigated. Our results indicate that the PMAA/INH/RMP nanogel exhibited extended antibacterial activity by virtue of its long-term release of INH and RMP in the simulated gastrointestinal medium. Further, this PMAA/INH/RMP nanogel exhibited lower cytotoxicity than did INH or RMP alone, suggesting that this PMAA/INH/RMP nanogel could be a more useful dosage form than separate doses of INH and RMP for intestinal MTB. The novel aspects of this study include the cytotoxicity study and the three-phase release profile study, which might be useful for other researchers in this field. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  1. Presence of C1-inhibitor polymers in a subset of patients suffering from hereditary angioedema.

    Directory of Open Access Journals (Sweden)

    Daniel Elenius Madsen

    Full Text Available Hereditary angioedema (HAE is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin C1 inhibitor (C1-inh. The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks. Subjects suffering from HAE have been classified in type I patients with decreased functional and antigenic levels of C1-inh, and type II patients with decreased functional but normal antigenic C1-inh levels. However, a few reports have demonstrated that some mutations cause C1-inh polymerization in vitro, and it is speculated that C1-inh polymers may exist in patient plasma, challenging the current classification of HAE patients. To investigate the presence of C1-inh polymers in patient plasma samples, we developed an immunological method, where monoclonal antibodies produced against polymerized C1-inh were applied in native PAGE western blotting. Using this approach we analyzed genuine plasma samples from 31 Danish HAE families, and found that plasma samples from three genotypically distinct HAE type I families (classified upon C1-inh plasma concentrations contained C1-inh polymers. Identical C1-inh polymerization phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del,and one mutation affected helix C (p.Thr167Asn. In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients.

  2. Management of Latent Tuberculosis Infection Among Healthcare Workers: 10-Year Experience at a Single Center.

    Science.gov (United States)

    Arguello Perez, Esther; Seo, Susan K; Schneider, William J; Eisenstein, Cynthia; Brown, Arthur E

    2017-11-29

    The risk of infection with Mycobacterium tuberculosis among healthcare workers (HCWs) is estimated to be higher than the general population. However, HCW acceptance and compliance with available latent tuberculosis infection (LTBI) treatment regimens has been problematic. Recently, regimens have become available that might improve HCW acceptance and compliance with LTBI treatment. A retrospective single-center review of Employee Health and Wellness Services records of all HCWs diagnosed with LTBI was conducted. HCWs diagnosed with LTBI were offered 9-month isoniazid (INH), 4-month rifampin (RIF), weekly rifapentine/isoniazid (RPT/INH) for 12 weeks, or no treatment. Acceptance, completion rates, and side effects were reported for each regimen. Comparisons of regimens were assessed using Fisher exact test. Between 2005 and 2014, 363 of 927 (39%) HCWs diagnosed with LTBI accepted treatment. Of 363, 202 chose INH, 106 RIF, and 55 RPT/INH. Completion rates for each regimen were 58%, 80%, and 87%, respectively. HCWs were significantly more likely to have completed treatment with RIF (P < .0001) or RPT/INH (P < .0001) than INH. Rates of discontinuation owing to side effects were 35% for INH, 21% for RIF, and 10% for RPT/INH. Discontinuation of therapy due to side effects was significantly more frequent in the INH than the RPT/INH group (P = .0042). Completion of RIF and RPT/INH for LTBI in an HCW population is more likely than INH. Rates of discontinuation due to side effects were lower among those taking RPT/INH. Shorter LTBI treatment regimens should be more widely considered for HCWs in the United States. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Distinguishing the preparation and roles of Doctor of Philosophy and Doctor of Nursing Practice graduates: national implications for academic curricula and health care systems.

    Science.gov (United States)

    Melnyk, Bernadette Mazurek

    2013-08-01

    Although the American Association of Colleges of Nursing was clear in defining the role of individuals with the Doctor of Nursing Practice (DNP) degree when it endorsed the DNP as the single-entry degree for advanced practice nurses in 2004, confusion about educational curricula to prepare DNPs continues to exist in academic programs throughout the United States. Further, health care systems are unsure about the role DNP graduates should fulfill in comparison with PhD-prepared individuals. This article discusses the importance of DNP- and PhD-prepared individuals in improving the quality of health care and the health of Americans, how best to resolve the confusion in preparation of DNP and PhD students, and the various roles DNP and PhD graduates should fulfill in real-world settings. A national call to action and future implications for research, academia, and health care settings are highlighted. Copyright 2013, SLACK Incorporated.

  4. Unchanged acetylation of isoniazid by alcohol intake

    DEFF Research Database (Denmark)

    Wilcke, J T R; Døssing, M; Angelo, H R

    2004-01-01

    no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.......SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral...... dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has...

  5. C1-inhibitor polymers activate the FXII-dependent kallikrein-kinin system

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Sidelmann, Johannes Jakobsen; Biltoft, Daniel

    2015-01-01

    attacks. HAE is caused by mutations in the C1-inh encoding gene, and we recently demonstrated that some mutations give rise to the presence of polymerized C1-inh in the plasma of HAE patients. METHODS: C1-inh polymers corresponding to the size of polymers observed in vivo were produced using heat...... denaturation and gel filtration. The ability of these polymers to facilitate FXII activation was assessed in vitro in an FXII activation bandshift assay. After spiking of plasma with C1-inh polymers, kallikrein generation was analyzed in a global kallikrein generation method. Prekallikrein consumption...... in the entire Danish HAE cohort was analyzed using an ELISA method. RESULTS: C1-inh polymers mediated FXII activation, and a dose dependent kallikrein generation in plasma spiked with C1-inh polymers. An increased (pre)kallikrein consumption was observed in plasma samples from HAE patients presenting with C1...

  6. Rhabdomyolysis Induced by Isoniazid in a Patient with Rheumatoid Arthritis and End-stage Renal Disease: A Case Report and Review of the Literature.

    Science.gov (United States)

    Komai, Toshihiko; Sumitomo, Shuji; Teruya, Shuzo; Fujio, Keishi

    2018-03-09

    A 76-year-old man complicated with end-stage renal disease had latent tuberculosis infection (LTBI), and isoniazid (INH) 300 mg daily was started to prevent reactivation of LTBI before using biologic agents for rheumatoid arthritis. On the 8th day after administration of INH, he presented with a fever, petechiae, and myalgia. Serological studies revealed elevated myogenic enzymes and creatinine level. Based on the exclusion of other etiologies, rapid improvement with cessation of INH, and the recurrence of the fever and myalgia with re-administration of a reduced dose of INH, we diagnosed him with INH-induced rhabdomyolysis. Physicians should be aware of rhabdomyolysis induced by INH at a therapeutic dose as an infrequent but potentially fatal adverse drug reaction.

  7. Toward understanding the anticorrosive mechanism of some thiourea derivatives for carbon steel corrosion: A combined DFT and molecular dynamics investigation.

    Science.gov (United States)

    Guo, Lei; Kaya, Savaş; Obot, Ime Bassey; Zheng, Xingwen; Qiang, Yujie

    2017-11-15

    The mutually corroborated density functional theory (DFT) and molecular dynamics (MD) simulation methodology were employed to evaluate the inhibition performance of three thiourea derivatives (Inh1, Inh2, and Inh3) on carbon steel corrosion. Experimental results have shown that the corrosion rate follows the order: Inh3>Inh2>Inh1. Quantum chemical descriptors such as the frontier orbital energies (E HOMO and E LUMO ), the energy gap between E LUMO and E HOMO (ΔE), dipole moment (μ), and Fukui index have been calculated and discussed. Some significant factors such as solvent, temperature, and coverage have been considered when investigating the adsorption of aforementioned thiourea derivatives on Fe(110) surface. Our results provide important atomic/molecular insights into the anticorrosive mechanism of inhibitor molecules, which could help in understanding the organic-metal interface and designing more appropriate organic corrosion inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Unchanged acetylation of isoniazid by alcohol intake

    DEFF Research Database (Denmark)

    Wilcke, J T R; Døssing, M; Angelo, H R

    2004-01-01

    SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral...... dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has...... no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics....

  9. Photothermal therapy combined with dinitrophenyl hapten for the treatment of late stage malignant melanoma

    Science.gov (United States)

    Li, Xiaosong; Du, Nan; Li, Haijun; Long, Shan; Chen, Dianjun; Zhou, Feifan; Xu, Yuanyuan; Wang, Fuli; Chen, Wei R.

    2017-02-01

    To evaluate the efficacy and safety of photothermal with dinitrophenyl hapten (DNP) for patients with malignant melanoma (MM), Patients with pathology confirmed stage III or IV MM were enrolled. Seventy-two patients were randomized into two groups, DNP alone group (n=36) and DNP plus photothermal therapy group (n=36). The results showed that the patients in the combination treatment group had longer median progression-free survival time (19.0m vs. 12.0m, p=0.007). No severe adverse events were observed in both groups. Thus, the combination of photothermal therapy and DNP maybe a new therapeutic strategy for patients with advanced MM.

  10. ORF Alignment: NC_003454 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available . ... nucleatum ATCC 25586] ... Length = 155 ... Query: 21 ... EKDIVITFNGIYGYEKQLRFIDEKLAEDGYSVVNIQY...PTVDDKIVEMTDKYIVPTIDEQV 80 ... EKDIVITFNGIYGYEKQLRFIDEKLAEDGYSVVNIQYPTVDDK...IVEMTDKYIVPTIDEQV Sbjct: 1 ... EKDIVITFNGIYGYEKQLRFIDEKLAEDGYSVVNIQYPTVDDKIVEMTDKYIVPTIDEQV 60 ... Query: 141 DNP

  11. Dinitrosopiperazine-Mediated Phosphorylated-Proteins Are Involved in Nasopharyngeal Carcinoma Metastasis

    Directory of Open Access Journals (Sweden)

    Gongjun Tan

    2014-11-01

    Full Text Available N,N'-dinitrosopiperazine (DNP with organ specificity for nasopharyngeal epithelium, is involved in nasopharyngeal carcinoma (NPC metastasis, though its mechanism is unclear. To reveal the pathogenesis of DNP-induced metastasis, immunoprecipitation was used to identify DNP-mediated phosphoproteins. DNP-mediated NPC cell line (6-10B motility and invasion was confirmed. Twenty-six phosphoproteins were increased at least 1.5-fold following DNP exposure. Changes in the expression levels of selected phosphoproteins were verified by Western-blotting analysis. DNP treatment altered the phosphorylation of ezrin (threonine 567, vimentin (serine 55, stathmin (serine 25 and STAT3 (serine 727. Furthermore, it was shown that DNP-dependent metastasis is mediated in part through ezrin at threonine 567, as DNP-mediated metastasis was decreased when threonine 567 of ezrin was mutated. Strikingly, NPC metastatic tumors exhibited a higher expression of phosphorylated-ezrin at threonine 567 than the primary tumors. These findings provide novel insight into DNP-induced NPC metastasis and may contribute to a better understanding of the metastatic mechanisms of NPC tumors.

  12. Chief nursing officers' perceptions of the Doctorate of Nursing Practice degree.

    Science.gov (United States)

    Swanson, Michelle L; Stanton, Marietta P

    2013-01-01

    Nurse executives practice in a business environment, which requires a skill set that has traditionally not been included in advanced nursing curriculum. The Doctorate of Nursing Practice (DNP) essentials are designed to address this gap in education while maintaining the focus on advanced nursing practice and executive management competency. Current literature supports the appropriateness of the DNP with practice focus areas of advanced practice specialties and nursing leadership. Although certification and educational bodies, and some professional nursing organizations, have embraced the DNP as the terminal degree for non-research-focused nurses, there remains a gap in the literature in regards to the perceptions of validity of the DNP for nurse executives. The purpose of this capstone project was to investigate the perceptions of practicing chief nursing officers (CNOs) in the acute care setting regarding the application of the DNP degree for nurse leaders. Utilizing an online survey, specific perceptions investigated included application and appropriateness of the DNP in a business-based practice model and managing daily nursing operations. CNOs practicing in the acute care setting differed on their responses regarding whether the DNP should be the recommended or the required degree in CNO development programs. CNOs with tenure responded more positively to the perception that the DNP curricula contains advanced nursing knowledge content appropriate to nurse executive practice. Practicing CNOs in the acute care setting do perceive the DNP as an appropriate degree option for nurse executive roles at aggregate, system, and organizational levels. © 2013 Wiley Periodicals, Inc.

  13. Immunogenicity assessment of recombinant human c1-inhibitor: an integrated analysis of clinical studies.

    Science.gov (United States)

    Hack, C Erik; Mannesse, Maurice; Baboeram, Aartie; Oortwijn, Beatrijs; Relan, Anurag

    2012-10-01

    Recombinant human C1-inhibitor (rhC1INH) is used to treat acute angioedema attacks in hereditary angioedema (HAE) due to a genetic C1INH deficiency. Recombinant proteins in general may induce antibody responses and therefore evaluation of such responses in the target population is an essential step in the clinical development program of a recombinant protein. Here we report the assessment of the immunogenicity of rhC1INH in symptomatic HAE patients. Blood samples collected before and after administration of rhC1INH were tested for antibodies against plasma-derived (pd) or rhC1INH, or against host-related impurities (HRI). Above cut-off screening results were confirmed with displacement assays, and also tested for neutralizing anti-C1INH antibodies. Finally, the relation of antibodies to clinical efficacy and safety of rhC1INH was analyzed. Data from 155 HAE patients who received 424 treatments with rhC1INH were analyzed. 1.5% of all pre-exposure tests and 1.3% of all post-exposure tests were above the cut-off level in the screening assay for anti-C1INH antibodies. Six patients (3.9%) had anti-rhC1INH antibodies positive in the confirmatory assay. In two patients, confirmed antibodies were pre-existing with no increase post-exposure; in three patients, the antibodies occurred on a single occasion post-exposure; and in one patient, on subsequent occasions post-exposure. Neutralizing anti-pdC1INH antibodies were not found. Anti-HRI antibodies in the screening assay occurred in <0.7% of the tests before exposure to rhC1INH, in <1.9% after first exposure and in <3.1% after repeat treatment with rhC1INH. Five patients had anti-HRI antibodies positive in the confirmatory assay. In one patient, the antibodies were pre-existing, whereas in three of the 155 rhC1INH-treated patients (1.9%), confirmed anti-HRI antibodies occurred at more time points. Antibody findings were not associated with altered efficacy of rhC1INH or adverse events. These results indicate a reassuring

  14. Isoniazid-Induced Severe Hepatotoxicity: An Infrequent but Preventable Cause of Liver Failure in Children Treated for Latent Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Dan Desrochers

    2011-01-01

    Full Text Available Isoniazid (INH monotherapy has gained widespread acceptance as an efficacious therapy for latent tuberculosis infection (LTBI especially in low-prevalence settings. Although INH related hepatotoxicity is well recognized, progression to severe liver dysfunction requiring care at a transplant center remains unpredictable. We report the management of a five year-old girl who developed progressive liver failure due to INH prophylaxis. This highlights the potential severity of INH related hepatic injury and underscores the significance of vigilant clinical monitoring throughout the duration of the therapy in children.

  15. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

    Science.gov (United States)

    Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

    2017-04-01

    Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively. © 2016 British Society for Immunology.

  16. Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients.

    Directory of Open Access Journals (Sweden)

    Sze Ling Chan

    Full Text Available Isoniazid (INH is part of the first-line-therapy for tuberculosis (TB but can cause drug-induced liver injury (DILI. Several candidate single nucleotide polymorphisms (SNPs have been previously identified but the clinical utility of these SNPs in the prediction of INH-DILI remains uncertain. The aim of this study was to assess the association between selected candidate SNPs and the risk of INH-DILI and to assess the clinical validity of associated variants in a Singaporean population.This was a case-control study where 24 INH-DILI cases and 79 controls were recruited from the TB control unit in a tertiary hospital. Logistic regression was used to test for the association between candidate SNPs and INH-DILI. NAT2 acetylator status was inferred from genotypes and tested for association with INH-DILI. Finally, clinical validity measures were estimated for significant variants.Two SNPs in NAT2 (rs1041983 and rs1495741 and NAT2 slow acetylators (SA were significantly associated with INH-DILI (OR (95% CI = 13.86 (4.30-44.70, 0.10 (0.03-0.33 and 9.98 (3.32-33.80, respectively. Based on an INH-DILI prevalence of 10%, the sensitivity, specificity, positive and negative predictive values of NAT2 SA were 75%, 78%, 28% and 97%, respectively. The population attributable fraction (PAF and number needed to test (NNT for NAT2 SA were estimated to be 0.67 and 4.08, respectively. A model with clinical and NAT2 acetylator status provided significantly better prediction for INH-DILI than a clinical model alone (area under receiver operating characteristic curve = 0.863 vs. 0.766, respectively, p = 0.027.We show the association between NAT2 SA and INH-DILI in a Singaporean population and demonstrated its clinical utility in the prediction of INH-DILI.

  17. Population pharmacokinetics of recombinant human C1 inhibitor in patients with hereditary angioedema.

    Science.gov (United States)

    Farrell, Colm; Hayes, Siobhan; Relan, Anurag; van Amersfoort, Edwin S; Pijpstra, Rienk; Hack, C Erik

    2013-12-01

    To characterize the pharmacokinetics (PK) of recombinant human C1 inhibitor (rhC1INH) in healthy volunteers and hereditary angioedema (HAE) patients. Plasma levels of C1INH following 294 administrations of rhC1INH in 133 subjects were fitted using nonlinear mixed-effects modelling. The model was used to simulate maximal C1INH levels for the proposed dosing scheme. A one-compartment model with Michaelis-Menten elimination kinetics described the data. Baseline C1INH levels were 0.901 [95% confidence interval (CI): 0.839-0.968] and 0.176 U ml(-1) (95% CI: 0.154-0.200) in healthy volunteers and HAE patients, respectively. The volume of distribution of rhC1INH was 2.86 l (95% CI: 2.68-3.03). The maximal rate of elimination and the concentration corresponding to half this maximal rate were 1.63 U ml(-1) h(-1) (95% CI: 1.41-1.88) and 1.60 U ml(-1) (95% CI: 1.14-2.24), respectively, for healthy volunteers and symptomatic HAE patients. The maximal elimination rate was 36% lower in asymptomatic HAE patients. Peak C1INH levels did not change upon repeated administration of rhC1INH. Bodyweight was found to be an important predictor of the volume of distribution. Simulations of the proposed dosing scheme predicted peak C1INH concentrations above the lower level of the normal range (0.7 U ml(-1)) for at least 94% of all patients. The population PK model for C1INH supports a dosing scheme on a 50 U kg(-1) basis up to 84 kg, with a fixed dose of 4200 U above 84 kg. The PK of rhC1INH following repeat administration are consistent with the PK following the first administration. © 2013 The British Pharmacological Society.

  18. Current state of hereditary angioedema management: A patient survey

    Science.gov (United States)

    Busse, Paula; Christiansen, Sandra C.; Li, Henry; Lumry, William; Davis-Lorton, Mark; Bernstein, Jonathan A.; Frank, Michael; Castaldo, Anthony; Long, Janet F.; Zuraw, Bruce L.; Riedl, Marc

    2015-01-01

    Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed. PMID:25976438

  19. Adherence with isoniazid for prevention of tuberculosis among HIV-infected adults in South Africa

    Directory of Open Access Journals (Sweden)

    Muller F James

    2006-06-01

    Full Text Available Abstract Background Tuberculosis (TB is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. Methods Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. Results 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0 of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001. In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043. Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007. Belief in INH safety was associated with a positive test (p = 0.021. In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086. Conclusion Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs.

  20. Dissolution Dynamic Nuclear Polarization of Non-Self-Glassing Agents: Spectroscopy and Relaxation of Hyperpolarized [1-13C]Acetate

    DEFF Research Database (Denmark)

    Flori, Alessandra; Liserani, Matteo; Bowen, Sean

    2015-01-01

    The intrinsic physicochemical properties of the sample formulation are the key factors for efficient hyperpolarization through dissolution dynamic nuclear polarization (dissolution-DNP). We provide a comprehensive characterization of the DNP process for Na-[1-13C]acetate selected as a model for non...

  1. Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization

    DEFF Research Database (Denmark)

    Bowen, Sean; Ardenkjær-Larsen, Jan Henrik

    2013-01-01

    Hyperpolarization by the dissolution dynamic nuclear polarization (DNP) technique permits the generation of high spin polarization of solution state. However, sample formulation for dissolution-DNP is often difficult, as concentration and viscosity must be optimized to yield a dissolved sample...

  2. Advanced coupling of nuclear reactor-gas laser systems. Technical progress report, August 31, 1974--August 31, 1975

    International Nuclear Information System (INIS)

    Verdeyen, J.T.; Miley, G.H.; Wells, W.E.

    1975-01-01

    Research progress on the development of direct nuclear pumped (DNP) lasers is reported. Most of the work was on a Ne--N 2 DNP laser. Some work is reported on He--Ne--O 2 , He--Hg, and the chemical lasers BF 3 --CH 4 and SF 6 --CH 4 . (U.S.)

  3. MEASUREMENT OF AFFINITY IN SERUM SAMPLES OF ANTIGEN-FREE, GERM-FREE AND CONVENTIONAL MICE AFTER HYPERIMMUNIZATION WITH 2,4-DINITROPHENYL KEYHOLE LIMPET HEMOCYANIN, USING SURFACE-PLASMON RESONANCE

    NARCIS (Netherlands)

    BAKKER, R; LASONDER, E; BOS, NA

    We previously investigated the primary and secondary responses and hyperimmunization to the T cell-dependent antigen 2,4-dinitrophenyl keyhole limpet hemocyanin (DNP-KLH) in antigen-free (AF), germ-free (GF) and conventional (CV) mice. Both the absolute and relative numbers of DNP-specific

  4. HUMORAL IMMUNE-RESPONSE TO 2,4-DINITROPHENYL KEYHOLE LIMPET HEMOCYANIN IN ANTIGEN-FREE, GERM-FREE AND CONVENTIONAL BALB/C MICE

    NARCIS (Netherlands)

    BOS, NA; PLOPLIS, VA

    The B cell immune response to 2,4-dinitrophenyl (DNP) keyhole limpet hemocyanin was compared in antigen-free, germ-free and conventional BALB/c mice. The numbers of total and of DNP-specific IgM-, IgG- and IgA-secreting cells in the spleen were determined by enzyme-linked immunosorbent plaque assays

  5. Just Care: Learning from and with Graduate Students in a Doctor of Nursing Practice Program

    Science.gov (United States)

    Boquet, Elizabeth; Kazer, Meredith; Manister, Nancy; Lucas, Owen; Shaw, Michael; Madaffari, Valerie; Gannett, Cinthia

    2015-01-01

    In 2010, Fairfield University, a Jesuit Carnegie Masters Level 1 University located in the Northeast, established its first doctoral-level program: the Doctorate of Nursing Practice (DNP). In a developing program such as the DNP, some of the most pressing concerns of current rhetoric and writing in the disciplines align and interact with the…

  6. Barriers to integrating information technology content in doctor of nursing practice curricula.

    Science.gov (United States)

    Lilly, Kezia; Fitzpatrick, Joyce; Madigan, Elizabeth

    2015-01-01

    To date, there is no benchmark data available on the measurement of program outcomes in doctor of nursing practice (DNP) programs. The purpose of this study was to identify barriers to integration of IT content in the curriculum in DNP programs, perceived IT competencies taught, and DNP faculty perception of competencies. The study location was DNP programs in the United States, and focus was on doctorate-prepared faculty with a DNP or PhD. A descriptive design using an Internet-based survey was done with 113 DNP programs administrators and faculty across the United States. Limitation of the study was that few DNP administrators forwarded the study to faculty, limiting the sample size. For the purpose of this study, the results were limited to responses from DNP administrators, and some comparative data of the faculty were used. Barriers measured included lack of qualified faculty, faculty's limited knowledge or skills in IT, lack of interest, age, lack of time to learn IT, lack of time to use IT, too many work demands, lack of administrative vision, unclear expectations of faculty, lack of technical support to faculty, or lack of resources. Leading barriers to IT implementation were lack of time of faculty, too many other work demands of faculty, lack of resources dedicated to IT, and lack of qualified faculty to teach IT. Further research is necessary on doctorate-prepared faculty and on interventions to overcome these barriers is needed. Published by Elsevier Inc.

  7. Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance

    Directory of Open Access Journals (Sweden)

    L. Michael Carastro

    2014-01-01

    Full Text Available Background. Molecular markers for prostate cancer (PCa risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP in exon 2 of the p73 gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a p73 DNP allele. Methods. We investigated the association between p73 DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls. Results. Although we detected no association between p73 DNP and PCa risk, a significant inverse relationship between p73 DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31–0.99 was detected. Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57–1.00, P=0.053 as well as PCa specific death (HR = 0.69, 95%Cl = 0.45–1.06, P=0.09. Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (P<0.001. Conclusions. Our findings are consistent with an association between p73 DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

  8. Kinetics and mechanism of the oxidation of substituted ...

    Indian Academy of Sciences (India)

    Unknown

    dinitrophenylhydrazine method.12 As per this method, the aldimine is hydrolysed to the aldehyde and then isolated as 2,4-dinitrophenylhydrazone (DNP), vacuum dried, weighed, recrystallized from ethanol and weighed again. The yields of DNP before and after ...

  9. Kerosene/Water/2,4-Dinitrophenol.

    Science.gov (United States)

    Whyman, Derek

    1986-01-01

    Background information/theory, procedures used, and typical results obtained are discussed for a system in which kerosene, water, and 2,4-dinitrophenol (DNP) are used to demonstrate the principles of liquid-liquid extraction in a Graesser rotary contractor. The DNP is almost equal between the two disimilar solvents. (JN)

  10. Dynamical nuclear polarization by means of shallow donors in ZnO quantum dots

    NARCIS (Netherlands)

    Baranov, P.G.; Orlinskii, S.B.; de Mello-Donega, C.|info:eu-repo/dai/nl/125593899; Meijerink, A.|info:eu-repo/dai/nl/075044986; Blok, H.; Schmidt, J.

    2009-01-01

    The almost complete dynamic nuclear polarization (DNP) of nuclear spins has been demonstrated can be achieved in ZnO and AgCl single crystals by saturating the EPR transition of the shallow donor (SD) present in this crystals with using high-frequency (275 and 95 GHz) at low temperatures. DNP

  11. Microwave-gated dynamic nuclear polarization

    DEFF Research Database (Denmark)

    Bornet, Aurélien; Pinon, Arthur; Jhajharia, Aditya

    2016-01-01

    Dissolution dynamic nuclear polarization (D-DNP) has become a method of choice to enhance signals in nuclear magnetic resonance (NMR). Recently, we have proposed to combine cross-polarization (CP) with D-DNP to provide high polarization P((13)C) in short build-up times. In this paper, we show...

  12. ISONIAZID-ASSOCIATED URIC ACID RETENTION IN THE

    African Journals Online (AJOL)

    Mubbashir Ahmed

    Probenecid increases the urinary excretion of uric acid by inhibition of reabsorption [16]. There is considerable evidence that higher concentrations of uric acid in Uromastix hardwickii blood are due to the dominant action of INH. However, it is difficult to say that INH decreases the reabsorption or inhibits the excretion of uric ...

  13. Current scenario

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Current scenario. India , like other parts of the world, is also facing the problem of increase in the incidence of drug resistance in tuberculosis. Multi-drug resistance (MDR, resistance to RIF & INH) and extensively drug resistant strains (X-DR, resistance to RIF, INH, FQs ...

  14. The mutagenicity of isoniazid in salmonella and its effects on DNA repair and synthesis in human fibroblasts

    NARCIS (Netherlands)

    Wade, D.R.; Lohman, P.H.M.; Mattern, I.E.; Berends, F.

    1981-01-01

    A commercial sample of the tuberculostatic drug isoniazid (INH) was found to have a weak mutagenic activity towards Salmonella typhimurium strains TA100 and TA1535. The addition of a rat or mouse liver homogenate to the test system decreased the mutagenic effect of INH. Hydrazine, an impurity of the

  15. Specific, sensitive, precise, and rapid functional chromogenic assay of activated first complement component (C1) in plasma

    DEFF Research Database (Denmark)

    Munkvad, S; Jespersen, J; Sidelmann, Johannes Jakobsen

    1990-01-01

    We present a new functional assay for the first complement component (C1) in plasma, based on its activation by inhibition of the C1-esterase inhibitor (C1-inh) when monospecific antiserum to C1-inh is added to the plasma. After maximal activation, we can determine the concentration of activated ...

  16. The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole

    2013-01-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway...

  17. Angioedema attacks in patients with hereditary angioedema : Local manifestations of a systemic activation process

    NARCIS (Netherlands)

    Hofman, Zonne L M; Relan, Anurag; Zeerleeder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C. Erik

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to

  18. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process

    NARCIS (Netherlands)

    Hofman, Zonne L. M.; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C. Erik

    2016-01-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to

  19. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea

    2015-01-01

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP...

  20. Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Busse, Paula; Bygum, Anette; Edelman, Jonathan

    2014-01-01

    BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typ...

  1. 7__51 - 55_Andrew_Isoniazid

    African Journals Online (AJOL)

    pc

    major adverse effects, including hepatitis, periphe neuropathy, neurotoxicity, hypersensitivity reactio. (fever, skin eruptions or hematologic alterations alo with lupus-like syndrome that is reversible discontinuation of INH. The most notable adve effect is hepatitis. The estimated rate of clin hepatitis in patients given INH alone ...

  2. Safety and Usage of C1-Inhibitor in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Riedl, Marc A; Bygum, Anette; Lumry, William

    2016-01-01

    of this study was to describe safety and usage patterns of pnfC1-INH. METHODS: A multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety...... and usage data on subjects receiving pnfC1-INH for any reason. RESULTS: Of 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment......, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless...

  3. Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid

    2014-01-01

    BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding l......BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose......: There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems...

  4. Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

    Science.gov (United States)

    Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

    2011-08-01

    Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.

  5. Effects of new-generation TMEM16A inhibitors on calcium-activated chloride currents in rabbit urethral interstitial cells of Cajal.

    Science.gov (United States)

    Fedigan, Stephen; Bradley, Eamonn; Webb, Timothy; Large, Roddy J; Hollywood, Mark A; Thornbury, Keith D; McHale, Noel G; Sergeant, Gerard P

    2017-11-01

    Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit Ca 2+ -activated Cl - currents (I ClCa ) that are important for the development of urethral tone. Here, we examined if TMEM16A (ANO1) contributed to this activity by examining the effect of "new-generation" TMEM16A inhibitors, CACC inh -A01 and T16A inh -A01, on I ClCa recorded from freshly isolated rabbit urethral ICC (RUICC) and on contractions of intact strips of rabbit urethra smooth muscle. Real-time quantitative PCR experiments demonstrated that TMEM16A was highly expressed in rabbit urethra smooth muscle, in comparison to TMEM16B and TMEM16F. Single-cell RT-PCR experiments revealed that only TMEM16A was expressed in freshly isolated RUICC. Depolarization-evoked I ClCa in isolated RUICC, recorded using voltage clamp, were inhibited by CACC inh -A01 and T16A inh -A01 with IC 50 values of 1.2 and 3.4 μM, respectively. Similarly, spontaneous transient inward currents (STICs) recorded from RUICC voltage clamped at -60 mV and spontaneous transient depolarizations (STDs), recorded in current clamp, were also inhibited by CACC inh -A01 and T16A inh -A01. In contrast, spontaneous Ca 2+ waves in isolated RUICC were only partially reduced by CACC inh -A01 and T16A inh -A01. Finally, neurogenic contractions of strips of rabbit urethra smooth muscle (RUSM), evoked by electric field stimulation (EFS), were also significantly reduced by CACC inh -A01 and T16A inh -A01. These data are consistent with the idea that TMEM16A is involved with CACCs in RUICC and in contraction of rabbit urethral smooth muscle.

  6. Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of ige antibodies.

    Science.gov (United States)

    Hack, C Erik; Relan, Anurag; Baboeram, Aartie; Oortwijn, Beatrijs; Versteeg, Serge; van Ree, Ronald; Pijpstra, Rienk

    2013-04-01

    Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency. The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions. In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system. 130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2-12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1-3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow's milk allergens was negligible. The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.

  7. In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case

    Directory of Open Access Journals (Sweden)

    Ceyda Tunakan Dalgıç

    2018-01-01

    Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

  8. Low-temperature dynamic nuclear polarization at 9.4 T with a 30 mW microwave source.

    Science.gov (United States)

    Thurber, Kent R; Yau, Wai-Ming; Tycko, Robert

    2010-06-01

    Dynamic nuclear polarization (DNP) can provide large signal enhancements in nuclear magnetic resonance (NMR) by transfer of polarization from electron spins to nuclear spins. We discuss several aspects of DNP experiments at 9.4 T (400 MHz resonant frequency for (1)H, 264 GHz for electron spins in organic radicals) in the 7-80K temperature range, using a 30 mW, frequency-tunable microwave source and a quasi-optical microwave bridge for polarization control and low-loss microwave transmission. In experiments on frozen glycerol/water doped with nitroxide radicals, DNP signal enhancements up to a factor of 80 are observed (relative to (1)H NMR signals with thermal equilibrium spin polarization). The largest sensitivity enhancements are observed with a new triradical dopant, DOTOPA-TEMPO. Field modulation with a 10 G root-mean-squared amplitude during DNP increases the nuclear spin polarizations by up to 135%. Dependencies of (1)H NMR signal amplitudes, nuclear spin relaxation times, and DNP build-up times on the dopant and its concentration, temperature, microwave power, and modulation frequency are reported and discussed. The benefits of low-temperature DNP can be dramatic: the (1)H spin polarization is increased approximately 1000-fold at 7 K with DNP, relative to thermal polarization at 80K. (c) 2010 Elsevier Inc. All rights reserved.

  9. Utilizing Team Debate to Increase Student Abilities for Mentoring and Critical Appraisal of Global Health Care in Doctor of Nursing Practice Programs.

    Science.gov (United States)

    Elliott, Naomi; Farnum, Karen; Beauchesne, Michelle

    2016-01-01

    Although graduates of doctor of nursing practice (DNP) programs are expected to demonstrate competence in advanced clinical scholarship, mentoring, and leadership, little is published about how team debate on a global health care topic supports DNP student learning and skill development. This article reports on an illuminative evaluation of DNP student learning experiences of team debate in the context of a 2-week international school program in Ireland. A focused illuminative evaluation approach involving a cohort of seven DNP students, who had participated in an international school team debate, was used. Data were collected using a Web-based qualitative questionnaire designed to elicit in-depth reflective accounts of DNP students' learning experiences. Content analysis revealed that team debate on a global health care topic enhanced learning in relation to fostering critical thinking and critical appraisal skills; encouraging teamwork; providing opportunities for mentoring, relationship building, and socialization into profession; and, from the DNP student perspective, increasing knowledge and global understanding of health care. This evaluation provides insights for nurse educators into the benefits of introducing team debate as a group activity to enhancing scholarly inquiry and mentoring skills of DNP students. Further research to evaluate team debate in other nurse education programs is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Real-time calculation and visualization of spectra in field-cycled dynamic nuclear polarization spectroscopy.

    Science.gov (United States)

    Deng, Yuanmu; Shet, Keerthi; Li, Haihong; Kuppusamy, Periannan; Zweier, Jay L

    2006-04-01

    Field-cycled dynamic nuclear polarization (FC-DNP), which is based on the Overhauser effect, provides a new way to perform in vivo measurements of free radicals in biological systems. Since it measures the alterations of the nuclear magnetic resonance (NMR) signal in the presence of paramagnetic molecules, a customized program is usually needed in FC-DNP experiments to extract spectral information from the acquired NMR signals. While this program can be designed to calculate the spectrum after all the NMR signals are collected, the batch-processing mode inevitably causes delay and is not convenient for in vivo applications. In this paper, we report the development of a real-time DNP spectrum calculation and visualization program, called RT_DNP, for FC-DNP experiments. A dynamic data exchange (DDE) client was implemented to enable real-time receipt of the system information and the NMR signals from a commercial NMR console. The received NMR signals and experimental parameters were then used to calculate the DNP spectrum during the data acquisition. The real-time DNP spectrum calculation and visualization program was tested in experiments. A seamless integration of the program into a commercial NMR console has been achieved.

  11. Bis-gadolinium complexes for solid effect and cross effect dynamic nuclear polarization

    Energy Technology Data Exchange (ETDEWEB)

    Kaushik, Monu; Corzilius, Bjoern [Goethe-Universitaet Frankfurt am Main, Institut fuer Physikalische und Theoretische Chemie, Institut fuer Biophysikalische Chemie und Biomolekulares Magnetresonanzzentrum (BMRZ) (Germany); Qi, Mian; Godt, Adelheid [Fakultaet fuer Chemie und Centrum fuer Molekulare Materialien (CM2), Universitaet Bielefeld (Germany)

    2017-04-03

    High-spin complexes act as polarizing agents (PAs) for dynamic nuclear polarization (DNP) in solid-state NMR spectroscopy and feature promising aspects towards biomolecular DNP. We present a study on bis(Gd-chelate)s which enable cross effect (CE) DNP owing to spatial confinement of two dipolar-coupled electron spins. Their well-defined Gd..Gd distances in the range of 1.2-3.4 nm allowed us to elucidate the Gd..Gd distance dependence of the DNP mechanism and NMR signal enhancement. We found that Gd..Gd distances above 2.1 nm result in solid effect DNP while distances between 1.2 and 2.1 nm enable CE for {sup 1}H, {sup 13}C, and {sup 15}N nuclear spins. We compare 263 GHz electron paramagnetic resonance (EPR) spectra with the obtained DNP field profiles and discuss possible CE matching conditions within the high-spin system and the influence of dipolar broadening of the EPR signal. Our findings foster the understanding of the CE mechanism and the design of high-spin PAs for specific applications of DNP. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Isoniazid is not a lead compound for its pyridyl ring derivatives, isonicotinoyl amides, hydrazides, and hydrazones: a critical review.

    Science.gov (United States)

    Scior, T; Garcés-Eisele, S J

    2006-01-01

    The relationships between structure, disintegration and antituberculotic in vitro activity were studied for over 200 derivatives of isonicotinic acid hydrazide (isoniazid, INH). Conclusive evidence reflects that many compounds do not withstand the in vitro conditions. A pH dependant partial hydrolysis to INH occurs in the case of hydrazones, in analogy to well-known benzoic acid esters. Hydrazides and amides are cleaved into isonicotinic acid. In general, antimycobacterial potencies drop against INH except for two outliers probably with additional unspecific toxicity of their residues. Analyzing the complexity and heterogeneity of molecular events, trends linked to hydrolysis are found when structural features are clustered. Hammett sigma constants correlate to pK(a) values possessing a twofold descriptive meaning: (i) the cardinal increase of partial positive charge of the reaction center towards nucleophilic water attack and (ii) the ionization crucial for mycobacterial cell permeation through porins or lipid barriers. We review the literature concluding that many so-called "novel leads" are nothing else than precursors of an INH-based scaffold. In addition, INH ring-substitution or analogous backbones never achieve the efficiency of INH, itself a prodrug, which accumulates in Mycobacterium tuberculosis in form of its intrabacterial active principle(s) to which it is an optimal transport vehicle, evidencing that INH is not a promising lead compound at all.

  13. Shortened Activated Partial Thromboplastin Time May Help in Diagnosing Hereditary and Acquired Angioedema.

    Science.gov (United States)

    Bork, Konrad; Witzke, Günther

    2016-01-01

    To evaluate whether activated partial thromboplastin time (APTT) could be used in the laboratory diagnosis of hereditary or acquired angioedema (HAE or AAE) with and without C1 inhibitor (C1-INH) deficiency. In a prospective investigation, APTT and other coagulation parameters were determined in 149 adult patients with various types of angioedema and in 26 healthy participants (HP). Mean APTT was significantly shortened in HAE-C1-INH type I (p angioedema, 4/30 (13.3%) patients with nonhistaminergic angioedema and in 2/26 (7.7%) HP. Thus, a shortened APTT was obtained in 8-9 times more patients with angioedema due to C1-INH deficiency when compared to patients with various forms of angioedema with normal C1-INH and also to HP. A shortened APTT may help to diagnose HAE-C1-INH and AAE-C1-INH when determination of C1-INH is not yet available. © 2016 S. Karger AG, Basel.

  14. High Affinity Inha Inhibitors with Activity Against Drug-Resistant Strains of Mycobacterium Tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan,T.; Truglio, J.; Boyne, M.; Novichenok, P.; Zhang, X.; Stratton, C.; Li, H.; Kaur, T.; Amin, A.; et al.

    2006-01-01

    Novel chemotherapeutics for treating multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) are required to combat the spread of tuberculosis, a disease that kills more than 2 million people annually. Using structure-based drug design, we have developed a series of alkyl diphenyl ethers that are uncompetitive inhibitors of InhA, the enoyl reductase enzyme in the MTB fatty acid biosynthesis pathway. The most potent compound has a Ki{prime} value of 1 nM for InhA and MIC{sub 99} values of 2-3 {micro}g mL{sup -1} (6-10 {micro}M) for both drug-sensitive and drug-resistant strains of MTB. Overexpression of InhA in MTB results in a 9-12-fold increase in MIC{sub 99}, consistent with the belief that these compounds target InhA within the cell. In addition, transcriptional response studies reveal that the alkyl diphenyl ethers fail to upregulate a putative efflux pump and aromatic dioxygenase, detoxification mechanisms that are triggered by the lead compound triclosan. These diphenyl ether-based InhA inhibitors do not require activation by the mycobacterial KatG enzyme, thereby circumventing the normal mechanism of resistance to the front line drug isoniazid (INH) and thus accounting for their activity against INH-resistant strains of MTB.

  15. Assessment of halloysite nanotubes as vehicles of isoniazid.

    Science.gov (United States)

    Carazo, E; Borrego-Sánchez, A; García-Villén, F; Sánchez-Espejo, R; Aguzzi, C; Viseras, C; Sainz-Díaz, C I; Cerezo, P

    2017-12-01

    Equilibrium and thermodynamic aspects of the adsorption of isoniazid (INH) onto halloysite nanotubes (HLNTs) and characteristics of the resultant drug/nanocarrier systems are investigated. Equilibrium studies were performed in aqueous medium at different times, temperatures and drug concentrations. The overall adsorption process was explained as the result of two simple processes: adsorption on the activated sites of HLNTs and precipitation of INH on HLNTs surface. Formation of the INH-loaded HLNTs was spontaneous, endothermic and endoentropic, increasing the thermodynamic stability of the system (ΔH=70.40kJ/mol; ΔS=0.2519kJ/molK). Solid state characterization corroborated the effective interaction between the components that was also described by modeling at molecular level by quantum mechanics calculations along with empirical interatomic potentials. Transmission electron microphotographs confirmed the double allocation and homogeneous distribution of INH in the nanohybrids. FTIR spectra revealed the interaction via hydrogen bonds between the inner hydroxyl groups of HLNTs and N in INH molecules. Loading of INH in the nanohybrids was approximately 20% w/w. Effective loading of INH and activation energies of the interactions enable to propose the designed nanohybrids in the development of modified drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management.

    Science.gov (United States)

    Bork, K; Davis-Lorton, M

    2013-02-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.

  17. Building a Unit-Level Mentored Program to Sustain a Culture of Inquiry for Evidence-Based Practice

    Science.gov (United States)

    2015-03-24

    PhD, DNP, FNP , LTC, AN, USA 5f. WORK UNIT NUMBER N/A 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING...PhD, RN; Patricia A Patrician, PhD, RN FAAN; Dheeraj Raju, PhD, MS, MSIE, Deborah A Murphy PhD; Lori A Loan; Meryia D Throop, PhD, DNP, FNP ...work fax number: 301-619-7911, email: LTC Meryia D. Throop, PhD, DNP, FNP , Chief, Center for Nursing Science and Clinical Inquiry, Tripler Army

  18. The ethics curriculum for doctor of nursing practice programs.

    Science.gov (United States)

    Peirce, Anne Griswold; Smith, Jennifer A

    2008-01-01

    Ethical questions dealt with by nurses who have Doctor of Nursing Practice (DNP) degrees include traditional bioethical questions, but also business and legal ethics. Doctorally prepared nurses are increasingly in positions to make ethical decisions rather than to respond to decisions made by others. The traditional master's-degree advanced practice nursing curriculum does not address the extended expertise and decision-making skills needed by DNP practitioners as they face these new types of ethical dilemmas. We propose that a curricular framework that addresses clinical, research, business, and legal ethics is needed by all DNP students.

  19. Frozen Acrylamide Gels as Dynamic Nuclear Polarization Matrices.

    KAUST Repository

    Viger-Gravel, Jasmine

    2017-05-24

    We show that aqueous acrylamide gels can be used to provide dynamic nuclear polarization (DNP) NMR signal enhancements of around 200 at 9.4 T and 100 K. The enhancements are shown to increase with cross linker concentration and low concentrations of the AMUPol biradical. We show that this DNP matrix can be used in situations where conventional incipient wetness methods fail, such as to obtain DNP surface enhanced NMR spectra from inorganic nanoparticles. In particular, we obtain 113Cd spectra from CdTe-COOH NPs in minutes. The spectra clearly indicate a highly-disordered cadmium rich surface.

  20. The relationship between anxiety and quality of life in children with hereditary angioedema.

    Science.gov (United States)

    Kessel, Aharon; Farkas, Henriette; Kivity, Shmuel; Veszeli, Nóra; Kőhalmi, Kinga V; Engel-Yeger, Batya

    2017-11-01

    The severe life-threatening characteristics of hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) can affect anxiety levels among pediatric patients. This emotional burden together with the physical restrictions of C1-INH-HAE may decrease children's health-related quality of life (HRQoL). (i) To compare anxiety state and trait between children with C1-INH-HAE and healthy controls; (ii) to examine the relationship between the level of anxiety of children with C1-INH-HAE, their disease activity/affected sites and their HRQoL; and (iii) to predict the HRQoL of children with C1-INH-HAE based on their anxiety level and disease activity/affected sites METHODS: Thirty-three children with C1-INH-HAE (aged 5-18 years) and 52 healthy controls were recruited from Israel and Hungary. All children completed the State-Trait Anxiety Inventory for Children (STAIC), the Pediatric Quality of Life Inventory (Peds-QL) demographic questionnaire and a disease activity and site questionnaire . Disease activity was defined as the number of attacks in last year. Both anxiety state and trait were significantly higher among children with C1-INH-HAE as compared to the controls (44.74±10.56 vs 38.76±10.67, Panxiety state (F 56,2 =4.69, P=.001) and trait (F 56,2 =9.06, Panxiety trait was correlated with the number of angioedema-affected sites (r=.52, P=.003). The presence of HAE attacks and higher anxiety trait predicted a lower HRQoL in children with C1-INH-HAE. C1-INH-HAE children have higher anxiety trait and state, which correlate with reduced HRQoL domains. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  1. ELISA to measure neutralizing capacity of anti-C1-inhibitor antibodies in plasma of angioedema patients.

    Science.gov (United States)

    Engel, Ruchira; Rensink, Irma; Roem, Dorina; Brouwer, Mieke; Kalei, Asma; Perry, Dawn; Zeerleder, Sacha; Wouters, Diana; Hamann, Dörte

    2015-11-01

    Neutralizing autoantibodies (NAbs) against plasma serpin C1-inhibitor (C1-inh) are implicated in the rare disorder, acquired angioedema (AAE). There is insufficient understanding of the process of antibody formation and its correlation with disease progression and severity. We have developed an ELISA for detecting neutralizing capacity of anti-C1-inh positive plasma samples that can be used to study changes in NAb repertoire in patient plasma over the course of disease. The ELISA is based on the specific interaction of active C1-inh with its target protease C1s. Decrease in the amount of C1s bound to immobilized C1-inh in the presence of test samples is proportional to the neutralizing capacity of the sample. Assay specificity, intra- and inter-assay variation and assay cut-off are determined using anti-C1-inh antibodies. Assay capability is demonstrated using plasma samples from AAE patients. The assay is specific to a neutralizing anti-C1-inh antibody and shows no interference by a non-neutralizing anti-C1-inh antibody or by the plasma matrix. Intra-assay and inter-assay variations are determined as 17 and 18% respectively. Neutralizing capacity of antibody positive AAE patient plasma samples (n=16) with IgG or IgM type antibodies is readily determined. All samples show positive neutralizing capacity. We have developed a robust, specific and semi-quantitative assay to detect the neutralizing capacity of plasma samples containing anti-C1-inh antibodies. This assay can be an important tool for the study of clinical implications of anti-C1-inh NAbs. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant

    Science.gov (United States)

    Boccon‐Gibod, Isabelle; Launay, David; Gompel, Anne; Kanny, Gisele; Fabien, Vincent; Fain, Oliver

    2017-01-01

    Abstract Introduction The clinical characteristics and icatibant‐treatment outcomes of patients with hereditary angioedema with normal C1 inhibitor (HAE‐nC1 INH) are limited. Methods We retrospectively analyzed data from French HAE patients enrolled in the Icatibant Outcome Survey registry (from July 2009 to September 2013) to compare disease characteristics and the effectiveness and safety of acute icatibant‐treated angioedema attacks in patients with HAE‐nC1 INH, HAE with C1 INH deficiency (type I), or dysfunction (type II). Results One center in Grenoble contributed 22 patients with HAE‐nC1 INH and a family history of HAE while 15 centers across France contributed 153 patients with HAE type I and seven patients with HAE type II. Patients with HAE‐nC1 INH compared to HAE type I, respectively, were more likely to be female (88.1% vs. 63.4%), older at median age of disease onset (21 years vs. 15 years), and have a greater rate of abdominal (80% vs. 61%) and laryngeal (23% vs. 14%) attacks. Icatibant was effective in both groups though the median time to resolution of attack was significantly longer in the HAE‐nC1 INH group (20.0 h, 37 attacks) versus the HAE type I group (14.0 h, 67 attacks). Icatibant was self‐administered for 96.1% of attacks in patients with HAE‐nC1 INH and 75.8% in patients with HAE type I. No serious adverse side effects related to icatibant were reported. Conclusions These data help further define the disease characteristics of HAE‐nC1 INH in the French population and extend the limited data reporting the safe and effective use of icatibant in acute treatment of angioedema in French patients diagnosed with HAE‐nC1 INH. PMID:28250922

  3. Anti-tuberculosis drug concentrations in tuberculosis patients with and without diabetes mellitus.

    Science.gov (United States)

    Kumar, A K Hemanth; Chandrasekaran, V; Kannan, T; Murali, A Lakshmi; Lavanya, J; Sudha, V; Swaminathan, Soumya; Ramachandran, Geetha

    2017-01-01

    The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM). Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC. The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 μg/ml, respectively. TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.

  4. A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.

    Science.gov (United States)

    Pease, Christopher; Hutton, Brian; Yazdi, Fatemeh; Wolfe, Dianna; Hamel, Candyce; Barbeau, Pauline; Skidmore, Becky; Alvarez, Gonzalo G

    2018-03-23

    Tuberculosis (TB) remains a common cause of death globally. A regimen of 12 doses of isoniazid (INH) and rifapentine given once weekly (INH/RPT-3) has recently been recommended by the World Health Organization for the treatment of latent TB infection (LTBI). We aimed to determine whether the INH/RPT-3 regimen had similar or lesser rates of adverse events compared to other LTBI regimens, namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and rifampin plus INH for 3 to 4 months. We searched MEDLINE, Embase, CENTRAL, PubMed, ICTRP, clinicaltrials.gov, and Canadian Agency for Drugs and Technologies in Health's Gray Matters Light for randomized, postmarketing, and comparative nonrandomized studies of patients with confirmed LTBI that reported the frequency of at least 1 adverse event of relevance for a regimen of interest. The search included studies published until March 2017. The frequencies of adverse events were extracted and are presented descriptively. Data from 23 randomized and 55 nonrandomized studies were included. Although inconsistent event reporting and high heterogeneity limited comparisons, the adverse event profile of INH/RPT-3 appeared generally favorable. Flu-like reactions were reported with an increased frequency and hepatotoxicity with a lower frequency than standard treatment. While INH/RPT-3 had an overall low frequency of adverse events compared to INH monotherapy, reporting of adverse events for many regimens was limited meaning results should be interpreted cautiously. Future studies of LTBI treatment would benefit from more complete collection and reporting of adverse events and more consistent definitions of hepatotoxicity. Copyright © 2018 John Wiley & Sons, Ltd.

  5. Depressed activation of the lectin pathway of complement in hereditary angioedema

    DEFF Research Database (Denmark)

    Varga, L; Széplaki, G; Laki, J

    2008-01-01

    ) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured...... by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP...

  6. Docking Simulations and QM/MM Studies between Isoniazid Prodrug, Catalase-Peroxidase (KatG and S315T Mutant from Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    E. F. F. da Cunha

    2007-01-01

    Full Text Available Isoniazid (INH, an antibiotic used to treat tuberculosis (TB, is a prodrug requiring activation by the Mycobacterium tuberculosis KatG (mtKatG. In the present work, theoretical calculations were carried out to locate the most energetically-favorable INH–KatG interaction modes using the experimental structure of a wild type and mutant mtKatG active site. The S315T mutation significantly affects the ability of the enzyme to convert INH to isonicotinic acid in vitro. The results showed that significant changes occur in the INH binding pattern when serine is replaced by threonine.

  7. Magneto and spectral behaviour of lanthanide(III) perchlorate complexes of n-isonicotinamidoanisalaldimine

    International Nuclear Information System (INIS)

    Agarwal, R.K.; Agarwal, Himanshu; Sarin, R.K.

    1996-01-01

    A new series of lanthanide(III) perchlorate complexes of N-isonicotinamidoanisalaldimine (INH-SAL) with the general composition (Ln(INH-SAL) 4 )(ClO) 4 ) 3 (Ln=La, Pr, Nd, Sm, Gd, Tb or Dy) were synthesized and characterized by elemental analyses, conductance, molecular weight, infrared and electronic spectral data. INH-SAL acts as a bidentate (N, O) chelating agents. The tentative coordination number eight has been assigned. Thermal behaviour of some representative chelates has also been investigated. (author). 14 refs., 2 tabs

  8. On complex compounds of molybdenum(5) with nicotinic amide, isonicotinic acid hydrazide and some of its derivatives

    International Nuclear Information System (INIS)

    Azizov, M.M.; Kushakbaev, A.; Parpiev, N.A.

    1977-01-01

    Oxychloride complexes of molybdenum (5) with polyfunctional ligands (L), namely with nicotinamide (NA), isonicotinic acid hydrazide (INH) and its derivatives (ftivazide, saluzide and larusan) have been synthesized and investigated. In ethanol all the ligands independently of their molar ratio form with MoCl 5 a non-electrolite compound MoOCl 3 xL 2 . Infrared spectra of the complexes suggest that in Mo(5) complexeS with NA and INH the central atom is bound through the pyridine nitrogen, whereas in the complexes with INH derivatives it is bound throught the carbonyl group oxygen

  9. Synthesis and structural studies of some trivalent lanthanide complexes of isonicotinic acid hydrazide

    International Nuclear Information System (INIS)

    Rao, T.R.; Khan, I.A.; Aggarwal, R.C.

    1985-01-01

    Trivalent lanthanides have been found to form complexes with isonicotinic acid hydrazide (INH) of the type M(INH) 3 X 3 [X=Cl, SCN; M=La(III), Pr(III), Nd(III), Sm(III) and Gd(III)]. The complexes have been characterized by elemental analysis, molar conductance, magnetic susceptibility, infrared and electronic spectral studies. The nephelauxetic ratio (β), covalency (δ) and bonding parameter (b 1/1 ) have been calculated from the electronic spectra. Infrared spectral studies reveal that INH acts as a neutral bidentate chelating ligand in all the complexes and that thiocyanate is N-bonded. (author)

  10. Dynamic nuclear polarization for magnetic resonance imaging. An in-bore approach

    Energy Technology Data Exchange (ETDEWEB)

    Krummenacker, Jan G.

    2012-07-01

    In this thesis, the development of an in-bore liquid state DNP polarizer for MRI applications operating in flow through mode at a magnetic field strength of 1.5 T was described. After an introductory chapter 1 and a chapter 2 on the theoretical background, chapter 3 dealt chiefly with the challenge of performing liquid state DNP at a high magnetic field of 9.2 T. The feasibility of performing liquid state DNP at this field was demonstrated for various solvents, as well as for metabolites in solution. Chapter 4 then moved to the aim of this work, the application of liquid state DNP for MRI experiments. It introduced the rationale of our approach, the hardware that was developed and demonstrated its performance in a clinical MRI tomograph.

  11. The use of dynamic nuclear polarization in 1H and 13C solid state NMR

    International Nuclear Information System (INIS)

    Duijvestijn, M.J.

    1985-01-01

    The Dynamic Nuclear Polarization (DNP) effect is used at room temperature in combination with 13 C NMR. Due to the low natural abundance of 13 C spins (1%) the signal is very weak, but when the DNP effect is used the 13 C signal can be enhanced and therefore the number of scans and the measuring time considerably reduced. The theory is presented and the experimental set-up is described. Experiments on polystyrene, artificially doped with free radicals are described and it is examined whether the theory of the DNP effect can be used in a quantitative way. Applications of the use of the DNP effect in 13 C NMR are shown. Excellent spectra are presented of artificial and natural diamonds, possibly to be used for diamond characterization purposes. 161 refs.; 61 figs.; 3 tabs

  12. Decomposition of nuclear chromatin of the rat thymus within the postirradiation period

    International Nuclear Information System (INIS)

    Vodolazskaya, N.A.

    1975-01-01

    Fractional composition of DNP histones and of salt extracts of the thymus of rats has been studied 2 to 8 hours after γ-irradiation with 600r (Co 60 ). Simultaneously, histones/DNA ratio has been determined in the nucleoprotein and in its salt-soluble fragments after fractionation of the salt extracts on phosphatecellulose. It has been shown that 2 to 4 hours following the exposure, the histone/DNA ratio in DNP preparations does not vary from the control. Subsequently, however, it slightly decreases. It has been found that the postirradiation DNP decomposition is accompanied by the formation of fragments which, in addition to a free DNA, comprise complexes with the decreased and increased histone/DNA ratio as compared to the original DNP

  13. Recommendations for Creating a Resource Management System to Support the Colombian Army in a New Environment

    Science.gov (United States)

    1992-04-15

    World Military and Social Expenditures. 1991. 4. Republica de Colombia, Departamento Nacional de Planeacion , Documento DNP-2570-UIP-MinHacienda...Center, The Planning. Programmina and Budgeting System (PPBS), Technical Report, 1991. Departamento Nacional de Planeacion de Colombia, Plan ouinuenal

  14. Dynamic nuclear polarization for magnetic resonance imaging. An in-bore approach

    International Nuclear Information System (INIS)

    Krummenacker, Jan G.

    2012-01-01

    In this thesis, the development of an in-bore liquid state DNP polarizer for MRI applications operating in flow through mode at a magnetic field strength of 1.5 T was described. After an introductory chapter 1 and a chapter 2 on the theoretical background, chapter 3 dealt chiefly with the challenge of performing liquid state DNP at a high magnetic field of 9.2 T. The feasibility of performing liquid state DNP at this field was demonstrated for various solvents, as well as for metabolites in solution. Chapter 4 then moved to the aim of this work, the application of liquid state DNP for MRI experiments. It introduced the rationale of our approach, the hardware that was developed and demonstrated its performance in a clinical MRI tomograph.

  15. Microalbuminuria and glycated hemoglobin in children with type 1 ...

    African Journals Online (AJOL)

    % of patients with type 1 diabetes (T1D). The main modifiable DNP initiation and progression factors in susceptible individuals may be sustained hyperglycemia and hypertension. The aim of the present work was to study glycemic control in ...

  16. A regional consortium for doctor of nursing practice education: Integrating improvement science into the curriculum.

    Science.gov (United States)

    Polancich, Shea; Roussel, Linda; Graves, Barbara Ann; O'Neal, Pamela V

    The DNP curriculum prepares the graduate for evidence informed improvement translation through coursework integrating improvement, safety, and translation sciences. Innovative leadership skills are necessary to lead inter-professional unit-based and health system opportunities. Equipping the DNP with the necessary skills and competencies to accomplish any type of improvement translation requires exposure to the tools and techniques of these sciences with an emphasis in didactic content. With a foundational knowledge of the principles for improvement, translation and application will follow. It is imperative theoretical underpinnings of translational science are taught, and that the students be expected to apply these concepts in "real word" circumstances. Thus, the DNP student is afforded opportunities during their DNP program to participate in a "learning lab" for evidence informed improvement translation. In essence, the courses within the program are designed to allow conversion from theory into practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 13

    Science.gov (United States)

    Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Lumata, Lloyd

    2016-12-01

    The nitroxide-based free radical 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) is a widely used polarizing agent in NMR signal amplification via dissolution dynamic nuclear polarization (DNP). In this study, we have thoroughly investigated the effects of 15 N and/or 2 H isotopic labeling of 4-oxo-TEMPO free radical on 13 C DNP of 3 M [1- 13 C] sodium acetate samples in 1 : 1 v/v glycerol : water at 3.35 T and 1.2 K. Four variants of this free radical were used for 13 C DNP: 4-oxo-TEMPO, 4-oxo-TEMPO- 15 N, 4-oxo-TEMPO-d 16 and 4-oxo-TEMPO- 15 N,d 16 . Our results indicate that, despite the striking differences seen in the electron spin resonance (ESR) spectral features, the 13 C DNP efficiency of these 15 N and/or 2 H-enriched 4-oxo-TEMPO free radicals are relatively the same compared with 13 C DNP performance of the regular 4-oxo-TEMPO. Furthermore, when fully deuterated glassing solvents were used, the 13 C DNP signals of these samples all doubled in the same manner, and the 13 C polarization buildup was faster by a factor of 2 for all samples. The data here suggest that the hyperfine coupling contributions of these isotopically enriched 4-oxo-TEMPO free radicals have negligible effects on the 13 C DNP efficiency at 3.35 T and 1.2 K. These results are discussed in light of the spin temperature model of DNP. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. The 12th Annual International Meeting on Simulation Healthcare (IMSH) 2012

    Science.gov (United States)

    2012-03-01

    Hawaii Honolulu HI USA John Berger MD Children’s National Medical Center Washington DC USA Cassandra Bergero RN FNP CNS Lucile Packard...Bigham DNP RN FNP -BC University of Alabama Tuscaloosa AL USA Lisa Bilich BSDH MSEd Eastern Washington University Spokane WA USA Peter Billas MD...of Miami Miller School of Medicine Miami FL USA Barbara DeVoe DNP FNP -BC North Shore Long Island Jewish Center of Innovation Lake Success NY

  19. Hyperpolarized 13C metabolic imaging using dissolution dynamic nuclear polarization

    DEFF Research Database (Denmark)

    Hurd, Ralph E.; Yen, Yi‐Fen; Chen, Albert

    2012-01-01

    This article describes the basic physics of dissolution dynamic nuclear polarization (dissolution‐DNP), and the impact of the resulting highly nonequilibrium spin states, on the physics of magnetic resonance imaging (MRI) detection. The hardware requirements for clinical translation of this techn......This article describes the basic physics of dissolution dynamic nuclear polarization (dissolution‐DNP), and the impact of the resulting highly nonequilibrium spin states, on the physics of magnetic resonance imaging (MRI) detection. The hardware requirements for clinical translation...

  20. Use of a problem-based learning exercise to teach the lean 8-step problem-solving method.

    Science.gov (United States)

    Tovar, Elizabeth G; Warshawsky, Nora

    2015-01-01

    Doctor of nursing practice (DNP) graduates must be prepared to lead quality improvement (QI) initiatives in health care settings; however, effective and feasible teaching strategies pose a challenge for many DNP program faculties. This article describes a successful and practical problem-based learning exercise for students to work through the QI process using the Lean 8-step problem-solving method. Suggestions for faculty and recommendations for future activities are discussed.

  1. Solid Polarized Targets and Applications

    International Nuclear Information System (INIS)

    Crabb, D. G.

    2008-01-01

    Examples are given of dynamically polarized targets in use today and how the subsystems have changed to meet the needs of todays experiments. Particular emphasis is placed on target materials such as ammonia and lithium deuteride. Recent polarization studies of irradiated materials such as butanol, deuterated butanol, polyethylene, and deuterated polyethylene are presented. The operation of two non-DNP target systems as well as applications of traditional DNP targets are briefly discussed

  2. Resonance – Journal of Science Education | Indian Academy of ...

    Indian Academy of Sciences (India)

    Keywords. Mycobacerium tuberculosis; retroviruses; isoniazid; copper complexes of INH. Author Affiliations. Arun Srivastava1. George H Kitzman Professor of Genetics, Chief, Division of Cellular and Molecular Therapy, Departments of Pediatrics, Molecular Genetics & Microbiology, Powell Gene Therapy Center, Assistant ...

  3. Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting

    DEFF Research Database (Denmark)

    Zanichelli, Andrea; Longhurst, Hilary J; Maurer, Marcus

    2016-01-01

    BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures...... being diagnosed as having C1-INH-HAE. RESULTS: In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185...... patients without (1.7 years; P angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct...

  4. De klinische betekenis van de serumconcentraties van isonicotinezuurhydrazide en streptomycine

    NARCIS (Netherlands)

    Graaff, J.L. de

    1965-01-01

    SAMENVATTING EN CONCLUSIES In dit proefschrift worden de resultaten beschreven van een onderzoek naar de invloed van de serumconcentraties van isonicotine- zuurhydrazide (INH) op de therapeutische resultaten bij patienten met longtuberculose. Ook de serumconcentraties van streptomycine (SM) zijn het

  5. (Received October 11, 2012; revised July 2, 2013)

    African Journals Online (AJOL)

    Preferred Customer

    2012-10-11

    1H-pyrrol-2-yl) isonicotinoylhydrazone, Pyr-inh a Schiff base, derived from isoniazid and pyrrole-2- carboxaldehyde. EXPERIMENTAL. Materials. All chemicals were of analytical AR grade and were used as supplied without ...

  6. Some high coordination compounds of lanthanides(III) derived from ...

    African Journals Online (AJOL)

    isonicotinamidosalicyaldimine. Ram K. Agarwal, Himanshu Agarwal. Abstract. A new series of lanthanide(III) nitrates, isothiocyanates and perchlorates coordination complexes of N-isonicotinamidosalicyaldimine (INH-SAL) with the general composition ...

  7. Antiviral Activity of Copper Complexes of Isoniazid against RNA ...

    Indian Academy of Sciences (India)

    Keywords. Mycobacerium tuberculosis; retroviruses; isoniazid; copper complexes of INH. Author Affiliations. Arun Srivastava1. George H Kitzman Professor of Genetics, Chief, Division of Cellular and Molecular Therapy, Departments of Pediatrics, Molecular Genetics & Microbiology, Powell Gene Therapy Center, Assistant ...

  8. Effects of Caffeine on Metabolism and Mitochondria Biogenesis in Rhabdomyosarcoma Cells Compared with 2,4-Dinitrophenol

    Directory of Open Access Journals (Sweden)

    Roger A. Vaughan

    2012-01-01

    Full Text Available Purpose This work investigated if treatment with caffeine or 2,4-dinitrophenol (DNP induce expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α and increase both mitochondrial biosynthesis and metabolism in skeletal muscle. Methods Human rhabdomyosarcoma cells were treated with either ethanol control (0.1% final concentration caffeine, or DNP at 250 or 500 μM for 16 or 24 hours. PGC-1α RNA levels were determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. PGC-1α protein and mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was determined by quantification of extracellular acidification rate and oxygen consumption rate. Results Treatment with either caffeine or DNP induced PGC-1α RNA and protein as well as mitochondrial content compared with control. Treatment with caffeine and DNP also significantly increased oxidative metabolism and total metabolic rate compared with control. Caffeine similarly increased metabolism and mitochondrial content compared with DNP. Conclusion This work identified that both caffeine and DNP significantly induce PGC-1α, and increase both metabolism and mitochondrial content in skeletal muscle.

  9. Activated microglia in the spinal cord underlies diabetic neuropathic pain.

    Science.gov (United States)

    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

    Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. THz Dynamic Nuclear Polarization NMR.

    Science.gov (United States)

    Nanni, Emilio A; Barnes, Alexander B; Griffin, Robert G; Temkin, Richard J

    2011-08-29

    Dynamic nuclear polarization (DNP) increases the sensitivity of nuclear magnetic resonance (NMR) spectroscopy by using high frequency microwaves to transfer the polarization of the electrons to the nuclear spins. The enhancement in NMR sensitivity can amount to a factor of well above 100, enabling faster data acquisition and greatly improved NMR measurements. With the increasing magnetic fields (up to 23 T) used in NMR research, the required frequency for DNP falls into the THz band (140-600 GHz). Gyrotrons have been developed to meet the demanding specifications for DNP NMR, including power levels of tens of watts; frequency stability of a few megahertz; and power stability of 1% over runs that last for several days to weeks. Continuous gyrotron frequency tuning of over 1 GHz has also been demonstrated. The complete DNP NMR system must include a low loss transmission line; an optimized antenna; and a holder for efficient coupling of the THz radiation to the sample. This paper describes the DNP NMR process and illustrates the THz systems needed for this demanding spectroscopic application. THz DNP NMR is a rapidly developing, exciting area of THz science and technology.

  11. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Katalin Susztak

    2005-02-01

    Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  12. Dynamic nuclear polarization of nucleic acid with endogenously bound manganese

    Energy Technology Data Exchange (ETDEWEB)

    Wenk, Patricia [University of Tübingen, Werner Siemens Imaging Center and Department of Preclinical Imaging and Radiopharmacy (Germany); Kaushik, Monu; Richter, Diane [Goethe University, Institute of Physical und Theoretical Chemistry, Institute of Biophysical Chemistry und Center for Biomolecular Magnetic Resonance (BMRZ) (Germany); Vogel, Marc; Suess, Beatrix [Technical University Darmstadt, Department of Biology (Germany); Corzilius, Björn, E-mail: corzilius@em.uni-frankfurt.de [Goethe University, Institute of Physical und Theoretical Chemistry, Institute of Biophysical Chemistry und Center for Biomolecular Magnetic Resonance (BMRZ) (Germany)

    2015-09-15

    We report the direct dynamic nuclear polarization (DNP) of {sup 13}C nuclei of a uniformly [{sup 13}C,{sup 15}N]-labeled, paramagnetic full-length hammerhead ribozyme (HHRz) complex with Mn{sup 2+} where the enhanced polarization is fully provided by the endogenously bound metal ion and no exogenous polarizing agent is added. A {sup 13}C enhancement factor of ε = 8 was observed by intra-complex DNP at 9.4 T. In contrast, “conventional” indirect and direct DNP experiments were performed using AMUPol as polarizing agent where we obtained a {sup 1}H enhancement factor of ε ≈ 250. Comparison with the diamagnetic (Mg{sup 2+}) HHRz complex shows that the presence of Mn{sup 2+} only marginally influences the (DNP-enhanced) NMR properties of the RNA. Furthermore two-dimensional correlation spectra ({sup 15}N–{sup 13}C and {sup 13}C–{sup 13}C) reveal structural inhomogeneity in the frozen, amorphous state indicating the coexistence of several conformational states. These demonstrations of intra-complex DNP using an endogenous metal ion as well as DNP-enhanced MAS NMR of RNA in general yield important information for the development of new methods in structural biology.

  13. Nodes of Ranvier in skin biopsies of patients with diabetes mellitus.

    Science.gov (United States)

    Doppler, Kathrin; Frank, Franziska; Koschker, Ann-Cathrin; Reiners, Karlheinz; Sommer, Claudia

    2017-09-01

    Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers. We analyzed the myelinated fibers of skin biopsies of 35 patients with DNP, 17 patients with diabetes mellitus (DM) without neuropathy, and 30 normal controls. Immunofluorescence of skin sections with antibodies against Caspr, neurofascin, sodium channels, and myelin basic protein was performed to assess paranodal/nodal architecture, segmental demyelination, and myelinated nerve fibers. Staining with antibodies against protein gene product 9.5 was used to quantify unmyelinated nerve fibers. There was an increase of elongated Ranvier nodes and a dispersion of neurofascin at the distal leg in patients with DM with and without neuropathy and at the finger in patients with DNP. An increased dispersion of Caspr was only found in biopsies of the finger in patients with DNP. Skin biopsy may be an appropriate tool to analyze nodes of Ranvier in patients with DM. Structural nodal changes are detectable in DNP and even in diabetic patients without neuropathy. © 2017 Peripheral Nerve Society.

  14. A novel variable field system for field-cycled dynamic nuclear polarization spectroscopy

    Science.gov (United States)

    Shet, Keerthi; Caia, George L.; Kesselring, Eric; Samouilov, Alexandre; Petryakov, Sergey; Lurie, David J.; Zweier, Jay L.

    2010-08-01

    Dynamic nuclear polarization (DNP) is an NMR-based technique which enables detection and spectral characterization of endogenous and exogenous paramagnetic substances measured via transfer of polarization from the saturated unpaired electron spin system to the NMR active nuclei. A variable field system capable of performing DNP spectroscopy with NMR detection at any magnetic field in the range 0-0.38 T is described. The system is built around a clinical open-MRI system. To obtain EPR spectra via DNP, partial cancellation of the detection field B0NMR is required to alter the evolution field B0EPR at which the EPR excitation is achieved. The addition of resistive actively shielded field cancellation coils in the gap of the primary magnet provides this field offset in the range of 0-100 mT. A description of the primary magnet, cancellation coils, power supplies, interfacing hardware, RF electronics and console are included. Performance of the instrument has been evaluated by acquiring DNP spectra of phantoms with aqueous nitroxide solutions (TEMPOL) at three NMR detection fields of 97 G, 200 G and 587 G corresponding to 413 kHz, 851.6 kHz and 2.5 MHz respectively and fixed EPR evolution field of 100 G corresponding to an irradiation frequency of 282.3 MHz. This variable-field DNP system offers great flexibility for the performance of DNP spectroscopy with independent optimum choice of EPR excitation and NMR detection fields.

  15. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

    OpenAIRE

    Farkas, H.; Martinez?Saguer, I.; Bork, K.; Bowen, T.; Craig, T.; Frank, M.; Germenis, A. E.; Grumach, A. S.; Luczay, A.; Varga, L.; Zanichelli, A.; Aberer, Werner; Andrejevic, Sladjana; Aygoeren?P?rs?n, Emel; Banerji, Alena

    2016-01-01

    BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.METHODS: During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), ped...

  16. "Nuts and Bolts" of Laboratory Evaluation of Angioedema.

    Science.gov (United States)

    Farkas, Henriette; Veszeli, Nóra; Kajdácsi, Erika; Cervenak, László; Varga, Lilian

    2016-10-01

    Angioedema, as a distinct disease entity, often becomes a clinical challenge for physicians, because it may cause a life-threatening condition, whereas prompt and accurate laboratory diagnostics may not be available. Although the bedside diagnosis needs to be established based on clinical symptoms and signs, family history, and the therapeutic response, later, laboratory tests are available. Currently, only for five out of the nine different types of angioedema can be diagnosed by laboratory testing, and these occur only in a minority of the patient population. Hereditary angioedema with C1-inhibitor (C1-INH) deficiency type I can be diagnosed by the low C1-INH function and concentration, whereas in type II, C1-INH function is low, but its concentration is normal or even elevated. C1q concentration is normal in both forms. Acquired angioedema with C1-INH deficiency type I is characterized by the low C1-INH function and concentration; however, C1q concentration is also low, and autoantibodies against C1-INH cannot be detected. Complement profile of acquired angioedema with C1-INH deficiency type II is similar to that of type I, but in this form, autoantibodies against C1-INH are present. Hereditary angioedema due to a mutation of the coagulation factor XII can be diagnosed exclusively by mutation analysis of FXII gene. Diagnostic metrics are not available for idiopathic histaminergic acquired angioedema, idiopathic non-histaminergic acquired angioedema, acquired angioedema related to angiotensin-converting enzyme inhibitor, and hereditary angioedema of unknown origin; these angioedemas can be diagnosed by medical and family history, clinical symptoms, and therapeutic response and by excluding the forms previously described. Several potential biomarkers of angioedema are used to date only in research. In the future, they could be utilized into the clinical practice to improve the differential diagnosis, therapy, as well as the prognosis of angioedema.

  17. Precise Null Deletion Mutations of the Mycothiol Synthesis Genes Reveal Their Role in Isoniazid and Ethionamide Resistance in Mycobacterium smegmatis ▿

    Science.gov (United States)

    Xu, Xia; Vilchèze, Catherine; Av-Gay, Yossef; Gómez-Velasco, Anaximandro; Jacobs, William R.

    2011-01-01

    Mycothiol (MSH; AcCys-GlcN-Ins) is the glutathione analogue for mycobacteria. Mutations in MSH biosynthetic genes have been associated with resistance to isoniazid (INH) and ethionamide (ETH) in mycobacteria, but rigorous genetic studies are lacking, and those that have been conducted have yielded different results. In this study, we constructed independent null deletion mutants for all four genes involved in the MSH biosynthesis pathway (mshA, mshB, mshC, and mshD) in Mycobacterium smegmatis and made complementing constructs in integrating plasmids. The resulting set of strains was analyzed for levels of MSH, INH resistance, and ETH resistance. The mshA and mshC single deletion mutants were devoid of MSH production and resistant to INH, whereas the mshB deletion mutant produced decreased levels of MSH yet was sensitive to INH, suggesting that MSH biosynthesis is essential for INH susceptibility in M. smegmatis. Further evidence supporting this conclusion was generated by deleting the gene encoding the MSH S-conjugate amidase (mca) from the ΔmshB null mutant. This double mutant, ΔmshB Δmca, completely abolished MSH production and was resistant to INH. The mshA, mshC, and mshB single deletion mutants were also resistant to ETH, indicating that ETH resistance is modulated by the level of MSH in M. smegmatis. Surprisingly, the mshD deletion mutant lacked MSH production but was sensitive to both INH and ETH. The drug sensitivity was likely mediated by the compensated synthesis of N-formyl-Cys-GlcN-Ins, previously demonstrated to substitute for MSH in an mshD mutant of M. smegmatis. We conclude that MSH or N-formyl-Cys-GlcN-Ins is required for susceptibility to INH or ETH in M. smegmatis. PMID:21502624

  18. Triclosan Derivatives: Towards Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Freundlich, Joel S.; Wang, Feng; Vilchèze, Catherine; Gulten, Gulcin; Langley, Robert; Schiehser, Guy A.; Jacobus, David P.; Jacobs, Jr., William R.; Sacchettini, James C.; (Einstein); (TAM); (Jacobus)

    2009-06-30

    Isoniazid (INH) is a frontline antitubercular drug that inhibits the enoyl acyl carrier protein reductase InhA. Novel inhibitors of InhA that are not cross-resistant to INH represent a significant goal in antitubercular chemotherapy. The design, synthesis, and biological activity of a series of triclosan-based inhibitors is reported, including their promising efficacy against INH-resistant strains of M. tuberculosis. Triclosan has been previously shown to inhibit InhA, an essential enoyl acyl carrier protein reductase involved in mycolic acid biosynthesis, the inhibition of which leads to the lysis of Mycobacterium tuberculosis. Using a structure-based drug design approach, a series of 5-substituted triclosan derivatives was developed. Two groups of derivatives with alkyl and aryl substituents, respectively, were identified with dramatically enhanced potency against purified InhA. The most efficacious inhibitor displayed an IC{sub 50} value of 21 nM, which was 50-fold more potent than triclosan. X-ray crystal structures of InhA in complex with four triclosan derivatives revealed the structural basis for the inhibitory activity. Six selected triclosan derivatives were tested against isoniazid-sensitive and resistant strains of M. tuberculosis. Among those, the best inhibitor had an MIC value of 4.7 {mu}g mL{sup -1} (13 {mu}M), which represents a tenfold improvement over the bacteriocidal activity of triclosan. A subset of these triclosan analogues was more potent than isoniazid against two isoniazid-resistant M. tuberculosis strains, demonstrating the significant potential for structure-based design in the development of next generation antitubercular drugs.

  19. C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

    Science.gov (United States)

    Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

    2012-01-01

    Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Elderly men have low levels of anti-Müllerian hormone and inhibin B, but with high interpersonal variation: a cross-sectional study of the sertoli cell hormones in 615 community-dwelling men.

    Science.gov (United States)

    Chong, Yih Harng; Dennis, Nicola A; Connolly, Martin J; Teh, Ruth; Jones, Gregory T; van Rij, Andre M; Farrand, Stephanie; Campbell, A John; McLennan, Ian S; Mlennan, Ian S

    2013-01-01

    The Sertoli cells of the testes secrete anti-Müllerian hormone (Müllerian inhibiting Substance, AMH) and inhibin B (InhB). AMH triggers the degeneration of the uterine precursor in male embryos, whereas InhB is part of the gonadal-pituitary axis for the regulation of sperm production in adults. However, both hormones are also putative regulators of homeostasis, and age-related changes in these hormones may therefore be important to the health status of elderly men. The levels of AMH in elderly men are unknown, with limited information being available about age-related changes in InhB. We have therefore used ELISAs to measure Sertoli cell hormone levels in 3 cohorts of community-dwelling men in New Zealand. In total, 615 men were examined, 493 of which were aged 65 or older. Serum AMH and InhB levels inversely correlated with age in men older than 50 years (phormone levels between similarly aged men increased with the age of men. AMH and InhB partially correlated with each other as expected (r = 0.48, phormones varied significantly between men, with this variation increasing with age. Elderly men selected for the absence of cardiovascular disease had AMH levels similar to those of young men whereas their InhB levels did not differ from aged-matched controls. These data suggests that Sertoli cell number and function changes with age, but with the extent and nature of the changes varying between men.

  1. Preparation and characterization of magnetic Fe3O4–chitosan nanoparticles loaded with isoniazid

    International Nuclear Information System (INIS)

    Qin, H.; Wang, C.M.; Dong, Q.Q.; Zhang, L.; Zhang, X.; Ma, Z.Y.; Han, Q.R.

    2015-01-01

    A novel and simple method has been proposed to prepare magnetic Fe 3 O 4 –chitosan nanoparticles loaded with isoniazid (Fe 3 O 4 /CS/INH nanocomposites). Efforts have been made to develop isoniazid (INH) loaded chitosan (CS) nanoparticles by ionic gelation of chitosan with tripolyphosphate (TPP). The factors that influence the preparation of chitosan nanoparticles, including the TPP concentration, the chitosan/TPP weight ratio and the chitosan concentration on loading capacity and encapsulation efficiency of chitosan nanoparticles were studied. The magnetic Fe 3 O 4 nanoparticles were prepared by co-precipitation method of Fe 2+ and Fe 3+ . Then the magnetic Fe 3 O 4 /CS/INH nanocomposites were prepared by ionic gelation method. The magnetic Fe 3 O 4 nanoparticles and magnetic Fe 3 O 4 /CS/INH nanocomposites were characterized by XRD, TEM, FTIR and SQUID magnetometry. The in vitro release of Fe 3 O 4 /CS/INH nanocomposites showed an initial burst release in the first 10 h, followed by a more gradual and sustained release for 48 h. It is suggested that the magnetic Fe 3 O 4 /CS/INH nanocomposites may be exploited as potential drug carriers for controlled-release applications in magnetic targeted drugs delivery system. - Highlights: • A novel and simple method for preparation of nanocomposites for biomedicine. • All the materials are non-toxic and biocompatibility. • This paper gives systematic study of the nanocomposites in biomedicine

  2. Comparative Modulation of Levels of Oxidative Stress in the Liver of Anti-Tuberculosis Drug Treated Wistar Rats by Vitamin B12, Beta-Carotene, and Spirulina fusiformis: Role of NF-κB, iNOS, IL-6, and IL-10.

    Science.gov (United States)

    Joseph Martin, Sherry; Evan Prince, Sabina

    2017-11-01

    Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH and RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. INH and RIF were administered to Wistar albino rats for 28 days to induce hepatotoxicity. S. fusiformis, vitamin B12, and beta-carotene were co-administered with INH and RIF and their hepatoprotective, antioxidant, and immunomodulatory roles were studied through blood and liver analysis. Changes induced by INH and RIF in antioxidants, cytokines (IL-6 and IL-10) and expression of Nuclear Factor-κB (NF-κB) and Nitric Oxide Synthase (iNOS) were also studied. Supplement treatment caused restoration of liver function parameters to normal levels along with reversal of inflammatory changes in IL-6 and IL-10 levels. Liver PCNA, iNOS, and NF-κB expression were reduced in the supplement treated tissues compared to INH and RIF treated rats as evidenced by immunohistochemistry and quantitative PCR. Correlation of IL-6 levels, PCNA, and iNOS with NF-κB showed its pivotal role in the inflammatory process. Study shows the pivotal role of NF-kB and the equivalence in antioxidant efficacy of vitamin B12 and beta-carotene compared to Spirulina fusiformis. J. Cell. Biochem. 118: 3825-3833, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Significance of Coexisting Mutations on Determination of the Degree of Isoniazid Resistance in Mycobacterium tuberculosis Strains.

    Science.gov (United States)

    Karunaratne, Galbokka Hewage Roshanthi Eranga; Wijesundera, Sandhya Sulochana; Vidanagama, Dhammika; Adikaram, Chamila Priyangani; Perera, Jennifer

    2018-04-23

    The emergence and spread of drug-resistant tuberculosis (TB) pose a threat to TB control in Sri Lanka. Isoniazid (INH) is a key element of the first-line anti-TB treatment regimen. Resistance to INH is mainly associated with point mutations in katG, inhA, and ahpC genes. The objective of this study was to determine mutations of these three genes in INH-resistant Mycobacterium tuberculosis (MTb) strains in Sri Lanka. Complete nucleotide sequence of the three genes was amplified by polymerase chain reaction and subjected to DNA sequencing. Point mutations in the katG gene were identified in 93% isolates, of which the majority (78.6%) were at codon 315. Mutations at codons 212 and 293 of the katG gene have not been reported previously. Novel mutations were recognized in the promoter region of the inhA gene (C deletion at -34), fabG1 gene (codon 27), and ahpC gene (codon 39). Single S315T mutation in the katG gene led to a high level of resistance, while a low level of resistance with high frequency (41%) was observed when katG codon 315 coexisted with the mutation at codon 463. Since most of the observed mutations of all three genes coexisted with the katG315 mutation, screening of katG315 mutations will be a useful marker for molecular detection of INH resistance of MTb in Sri Lanka.

  4. Epidemiology of Isoniazid Resistance Mutations and Their Effect on Tuberculosis Treatment Outcomes

    Science.gov (United States)

    Huyen, Mai N. T.; Cobelens, Frank G. J.; Buu, Tran N.; Lan, Nguyen T. N.; Dung, Nguyen H.; Kremer, Kristin; Tiemersma, Edine W.

    2013-01-01

    Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in Mycobacterium tuberculosis in codon 315 of the katG and in the promoter region of the inhA gene. Mycobacterium tuberculosis strains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDRplus testing to identify katG and inhA mutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% in katG codon 315 (katG315) and 28.2% in the inhA promoter region. katG315 mutations were significantly associated with pretreatment resistance to streptomycin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse; inhA promoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients, M. tuberculosis katG315 mutations but not inhA mutations are associated with unfavorable treatment outcome. inhA mutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase. PMID:23689727

  5. Inhibin activity in the mare and stallion.

    Science.gov (United States)

    Roser, J F; McCue, P M; Hoye, E

    1994-01-01

    An overnight double antibody RIA, employing a rabbit antiserum raised to bovine 31 kDa inhibin (rAs-#1989, NICHD) and purified bovine 31 kDa inhibin (bINH-I-90/1, NICHD) as trace and standard, was validated to measure immunoreactive inhibin (iINH) concentrations in equine peripheral plasma, follicular fluid (FF), ovarian vein (OV) plasma, testicular tissue extracts (TTE) and testicular vein (TV) plasma. The dynamic relationship of iINH and follicle stimulating hormone (FSH) was investigated during the estrous cycle of the mare and the annual reproductive cycle of the stallion. In the RIA, parallel dose-response curves were observed between the bovine inhibin standard and serial dilutions of equine FF, OV, TTE, TV and plasma. The average recovery of a known amount of purified bovine inhibin added to gelding plasma was approximately 100%. In the inhibin bioassay, serial dilution of equine FF and TTE were observed to be parallel to the bovine inhibin standard. A five-fold difference (p mare and an eight-fold difference (p mares or geldings were undetectable in the RIA. Concentrations of FSH, estradiol and iINH changed significantly in the mare during the estrous cycle (p ovulation, declined rapidly following ovulation and reached a nadir (0.21 +/- 0.03 ng/ml) on day 7 post-ovulation. Plasma iINH and estradiol concentrations followed a similar profile and were found to be positively correlated (r = 0.7064; p < 0.01), whereas iINH and FSH levels demonstrated an inverse relationship (r = -0.7359, p < 0.01) throughout the estrous cycle. Concentrations of FSH were also inversely related (-0.8498, p < 0.01) with estradiol during the cycle. In the stallion, plasma iINH and FSH levels changed significantly during the year (p < 0.05). The iINH profile reflected seasonal changes in testicular activity, with highest concentrations in late spring (3.37 +/- 0.44 ng/ml) and lowest concentrations in the fall (2.21 +/- 0.33 ng/ml). Plasma concentrations of iINH were positively

  6. Convergence and cross talk in urogenital neural circuitries.

    Science.gov (United States)

    Hubscher, C H; Gupta, D S; Brink, T S

    2013-10-01

    Despite common comorbidity of sexual and urinary dysfunctions, the interrelationships between the neural control of these functions are poorly understood. The medullary reticular formation (MRF) contributes to both mating/arousal functions and micturition, making it a good site to test circuitry interactions. Urethane-anesthetized adult Wistar rats were used to examine the impact of electrically stimulating different nerve targets [dorsal nerve of the penis (DNP) or clitoris (DNC); L6/S1 trunk] on responses of individual extracellularly recorded MRF neurons. The effect of bladder filling on MRF neurons was also examined, as was stimulation of DNP on bladder reflexes via cystometry. In total, 236 MRF neurons responded to neurostimulation: 102 to DNP stimulation (12 males), 64 to DNC stimulation (12 females), and 70 to L6/S1 trunk stimulation (12 males). Amplitude thresholds were significantly different at DNP (15.0 ± 0.6 μA), DNC (10.5 ± 0.7 μA), and L6/S1 trunk (54.2 ± 4.6 μA), whereas similar frequency responses were found (max responses near 30-40 Hz). In five males, filling/voiding cycles were lengthened with DNP stimulation (11.0 ± 0.9 μA), with a maximal effective frequency plateau beginning at 30 Hz. Bladder effects lasted ≈ 2 min after DNP stimulus offset. Many MRF neurons receiving DNP/DNC input responded to bladder filling (35.0% and 68.3%, respectively), either just before (43%) or simultaneously with (57%) the voiding reflex. Taken together, MRF-evoked responses with neurostimulation of multiple nerve targets along with different responses to bladder infusion have implications for the role of MRF in multiple aspects of urogenital functions.

  7. Resveratrol inhibits IgE-mediated basophilic mast cell degranulation and passive cutaneous anaphylaxis in mice.

    Science.gov (United States)

    Han, Seon-Young; Bae, Ji-Young; Park, Sin-Hye; Kim, Yun-Ho; Park, Jung Han Yoon; Kang, Young-Hee

    2013-05-01

    Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of β-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nontoxic resveratrol at 1-25 μmol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by ≥5 μmol/L resveratrol. The phosphorylation of protein kinase C (PKC)μ and PKCθ was attenuated by administering resveratrol to DNP-HSA-exposed mast cells, whereas quiescent PKCζ/λ in sensitized cells was dose-dependently activated by resveratrol. Male BALB/c mice were sensitized for 24 h with DNP-IgE and orally administered with resveratrol 1 h before the DNP-HSA challenge. The histamine concentration was enhanced in sensitized mice challenged to DNP-HSA, which was reversed by administration of 10 mg/kg resveratrol. Additionally, it encumbered the tissue activation of Syk, PLCγ, and PKCμ in antigen-exposed mice. Resveratrol decreased IgE-mediated PCA and alleviated allergic edema of mouse ear and dorsal skin. Mast cell degranulation and allergic inflammation, accompanying the induction of monocyte chemotactic protein-1 and macrophage inflammatory protein-2, were inhibited by supplementing resveratrol to antigen-challenged mice. Resveratrol inhibited mast cell-derived, immediate-type allergic reactions, and these responses of resveratrol suggest possible therapeutic strategies in preventing allergic inflammatory diseases.

  8. Sources of phenolic compounds in two catchments of southern Portugal - effect of season, land use and soil type.

    Science.gov (United States)

    Barrico, M L; Nabais, C; Martins, M J; Freitas, H

    2006-10-01

    Water quality monitoring in reservoirs used for human water consumption, carried out by the Alentejo Regional Authorities of the Environment (south Portugal), revealed seasonal peaks of phenolic compounds above the water-quality legislation. The main objectives of this work were to identify the main phenolic compounds present in water and soil leachates, and to determine the sources of the seasonal concentrations of phenolic compounds in two catchments with different land use patterns: Roxo and Santa Clara catchments. The main phenolic compound detected was 2,4-dinitrophenol (2,4-DNP), both in stream water and soil leachates, with concentrations higher in Roxo catchment. Roxo catchment represents a larger agricultural area than Santa Clara, and it is likely that the origin of the 2,4-DNP is associated with the use of pesticides. A peak of 2,4-DNP concentrations was observed in stream water of both catchments during February, when farmers plough their fields and apply pesticides. The 2,4-DNP peak was probably caused by a precipitation event shortly after the application of pesticides, increasing their transfer from land surfaces to adjacent streams. The leaching behaviour of 2,4-DNP was strongly dependent on the type of soil and pH. In soils with high clay content and low pH, 2,4-DNP was easily adsorbed, and its runoff from the soil to adjacent streams was reduced. Ribeira de Santa Vitória, from Roxo catchment, was the only stream showing a high abundance of vegetation, and the lowest concentrations of 2,4-DNP in water. Plants may play a role in removing contaminants from stream water.

  9. Being in control? A thematic content analysis of 14 in-depth interviews with 2,4-dinitrophenol users.

    Science.gov (United States)

    Ainsworth, Neha Prasad; Vargo, Elisabeth Julie; Petróczi, Andrea

    2018-02-01

    2,4-Dinitrophenol (2,4-DNP) is a compound with multiple industrial purposes. Currently unlicensed for human consumption, it is used by the gym-going population for drastic, short-term body fat loss. Nonetheless, physiological mechanisms can lead to potentially fatal hyperthermia. Reported fatal incidents have caused concern and highlighted the need for intervention. Understanding decision-making leading to 2,4-DNP use alongside the perceived outgroup attitudes is vital to forming effective harm minimisation policies targeting current and potential users. First-hand accounts from this elusive population are scarce. Fourteen novel and experienced users (13 male, 1 female) were recruited via "snowballing" techniques. Semi-structured interviews were conducted, comprising 28 questions. Thematic content analysis was conducted using 37 codes. Four characteristic themes emerged: 1. Users considered the Internet to be a crucial multifunctional resource directly impacting their 2,4-DNP use. 2. Users "respected" 2,4-DNP, proactively taking harm reduction measures. 3. Attitudinal polarisation towards 2,4-DNP within the gym-going community was consistent in all accounts. 4. Users perceived outgroup populations to have inherently negative attitudes towards their use. These themes fell under the all-encompassing theme of "being in control". For the first time, this study offers a rich detail of attitudes toward 2,4-DNP use by giving a collective voice to users. The element of control over every aspect of the users' life appears to be a significant contributor to the successful risk-management of 2,4-DNP use. In the absence of an established safe upper limit and effective regulatory control, education is critical to harm minimisation. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Characterization of mutations causing rifampicin and isoniazid resistance of Mycobacterium tuberculosis in Syria.

    Science.gov (United States)

    Madania, Ammar; Habous, Maya; Zarzour, Hana; Ghoury, Ifad; Hebbo, Barea

    2012-01-01

    In order to characterize mutations causing rifampicin and isoniazid resistance of M. tuberculosis in Syria, 69 rifampicin resistant (Rif(r)) and 72 isoniazid resistant (Inh(r)) isolates were screened for point mutations in hot spots of the rpoB, katG and inhA genes by DNA sequencing and real time PCR. Of 69 Rif(r) isolates, 62 (90%) had mutations in the rifampin resistance determining region (RRDR) of the rpoB gene, with codons 531 (61%), 526 (13%), and 516 (8.7%) being the most commonly mutated. We found two new mutations (Asp516Thr and Ser531Gly) described for the first time in the rpoB-RRDR in association with rifampicin resistance. Only one mutation (Ile572Phe) was found outside the rpoB-RRDR. Of 72 Inh(r) strains, 30 (41.6%) had a mutation in katGcodon315 (with Ser315Thr being the predominant alteration), and 23 (32%) harbored the inhA(-15C-->T) mutation. While the general pattern of rpoB-RRDR and katG mutations reflected those found worldwide, the prevalence of the inhA(-15C-->T mutation was above the value found in most other countries, emphasizing the great importance of testing the inhA(-15C-->T) mutation for prediction of isoniazid resistance in Syria. Sensitivity of a rapid test using real time PCR and 3'-Minor groove binder (MGB) probes in detecting Rif(r) and Inh(r) isolates was 90% and 69.4%, respectively. This demonstrates that a small set of MGB-probes can be used in real time PCR in order to detect most mutations causing resistance to rifampicin and isoniazid.

  11. Clonal expansion of Mycobacterium tuberculosis isolates and coexisting drug resistance in patients newly diagnosed with pulmonary tuberculosis in Hanoi, Vietnam.

    Science.gov (United States)

    Hung, Nguyen Van; Ando, Hiroki; Thuy, Tran Thi-Bich; Kuwahara, Tomoko; Hang, Nguyen Thi-Le; Sakurada, Shinsaku; Thuong, Pham Huu; Lien, Luu Thi; Keicho, Naoto

    2013-11-05

    Newly diagnosed patients without anti-tuberculosis (TB) treatment histories have not often undergone drug susceptibility testing (DST), but have received the standard treatment regimen without information about their DST profiles in many countries with inadequate resources. We collected 346 clinical isolates from previously untreated patients with smear-positive active TB in Hanoi, the capital of Vietnam. Of these, 339 were tested for susceptibility to four first-line anti-TB drugs, including isoniazid (INH), rifampicin (RMP), streptomycin (SM), and ethambutol (EMB), using the proportion method. A pyrazinamidase (PZase) test was used to assess pyrazinamide (PZA) resistance. Results of the culture-based drug susceptibility tests were confirmed by those from reverse hybridization-based line probe assays (LiPAs) that detected mutations associated with RMP, INH, PZA, and fluoroquinolone (FQ) resistance. To investigate a diversity of these strains, IS6110-probed restriction fragment length polymorphisms (RFLPs) were analyzed. Nucleotide sequences for furA-katG and fabG1-inhA operons, transcription units responsible for INH resistance, were also determined. Of the isolates tested, 127 (37.5%) were resistant to at least one of the four drugs, which included 93 (27.4%) isolates that were resistant to INH. RFLP analysis identified four clusters defined by similarity of the band patterns, which accounted for 46.1% of the tested isolates. Among the clustered isolates, 37.7% were resistant to INH, most of which (85.4%) carried a g944c mutation, which causes an S315T amino acid substitution, in the katG gene. Our results suggest that drug-resistant strains, particularly those with INH resistance characterized by a single mutation, S315T, are spreading in Hanoi, Vietnam. When RMP resistance is combined with this setting, patients are not easily cured by conventional short-term treatment. We will need to carefully monitor these trends and search for the origins and transmission

  12. Isoniazid-induced status epilepticus in a pediatric patient after inadequate pyridoxine therapy.

    Science.gov (United States)

    Minns, Alicia B; Ghafouri, Nazli; Clark, Richard F

    2010-05-01

    Isoniazid (INH) is an effective treatment for tuberculosis and among the most common causes of drug-induced seizures in the United States. Isoniazid intoxication produces a characteristic clinical syndrome including seizures, metabolic acidosis, and, in severe cases, respiratory depression and coma. A 10-month-old male infant was presented after being found with his father's INH. The patient was brought to a local hospital where he had a witnessed generalized seizure and was given 650 mg pyridoxine intravenously, which was based on a 70 mg/kg recommendation. Five hours after the time of ingestion, the patient developed recurrent generalized seizures. He was given diazepam and then loaded with phenobarbital 20 mg/kg, while awaiting more pyridoxine from the pharmacy. He received an additional 2 g pyridoxine for a suspected ingestion of approximately 2.7 g INH (290 mg/kg total dose), and his seizures subsequently resolved. Treatment of INH toxicity must address correction of gamma-aminobutyric acid deficiency with pyridoxine replacement and management of life-threatening events. For poisonings in which the amount of INH ingested is known, pyridoxine is dosed on a gram-for-gram basis. Several reference textbooks recommend pyridoxine dosing in children to be 70 mg/kg. This was the justification for the initial pyridoxine dose administered in our case. However, after review of the referenced literature, the rationale supporting this recommendation remains unclear. Benzodiazepines should also be given with pyridoxine as they have been shown to have a synergistic effect in terminating seizures in animal models. As soon as possible after INH overdose is suspected or diagnosed, pyridoxine should be administered in a dose approximately equal to the estimated amount of INH ingested regardless of the age of the patient.

  13. Recurrent angioedema associated with hypogonadism or anti-androgen therapy.

    Science.gov (United States)

    Pichler, W J; Lehner, R; Späth, P J

    1989-10-01

    Two male patients with hypogonadism and four female patients who received an anti-androgen as contraceptive (cyproteronacetate) and who had recurrent angioedema are described. In one male patient, augmentation of the plasma androgen level resulted in disappearance of symptoms. In the four female patients, recurrent angioedema and urticaria developed after initiation of the anti-androgen treatment. Cessation of cyproteronacetate and a change to another contraceptive resulted in complete resolution of the previously frequent angioedematous attacks. The women are still symptom free after more than 60 patient's months. These cases suggest that an androgen deficit due to either hypogonadism or to anti-androgen treatment may be another cause of angioedema. One of the two male patients was untreated and presented with 40% normal value of C1-INH. Androgen therapy normalized C1-INH concentration in this male patient. Functional C1-INH in the same patient, studied before and after the beginning of androgen therapy, clearly increased when assessed by inhibition of amidolytic activity of C1-esterase. The other male patient with hypogonadism had already been under androgen treatment for 4 years and had C1-INH levels in the normal range. In the female patients, complement profiles were normal before and after cessation of anti-androgen contraception; however, the C1-INH plasma levels were higher after cessation of anti-androgen anticonception. These results indicate an effect of androgen deficit on the level of C1-INH in circulating plasma but do not prove a role of C1-INH in angioedema associated with diminished androgen plasma levels.

  14. Elderly Men Have Low Levels of Anti-Müllerian Hormone and Inhibin B, but with High Interpersonal Variation: A Cross-Sectional Study of the Sertoli Cell Hormones in 615 Community-Dwelling Men

    Science.gov (United States)

    Chong, Yih Harng; Dennis, Nicola A.; Connolly, Martin J.; Teh, Ruth; Jones, Gregory T.; van Rij, Andre M.; Farrand, Stephanie; Campbell, A. John; MLennan, Ian S.

    2013-01-01

    The Sertoli cells of the testes secrete anti-Müllerian hormone (Müllerian inhibiting Substance, AMH) and inhibin B (InhB). AMH triggers the degeneration of the uterine precursor in male embryos, whereas InhB is part of the gonadal-pituitary axis for the regulation of sperm production in adults. However, both hormones are also putative regulators of homeostasis, and age-related changes in these hormones may therefore be important to the health status of elderly men. The levels of AMH in elderly men are unknown, with limited information being available about age-related changes in InhB. We have therefore used ELISAs to measure Sertoli cell hormone levels in 3 cohorts of community-dwelling men in New Zealand. In total, 615 men were examined, 493 of which were aged 65 or older. Serum AMH and InhB levels inversely correlated with age in men older than 50 years (p<0.001) but not in the younger men. A minority of elderly men had undetectable levels of AMH and InhB. The variation in hormone levels between similarly aged men increased with the age of men. AMH and InhB partially correlated with each other as expected (r = 0.48, p<0.001). However, the ratio of the two Sertoli hormones varied significantly between men, with this variation increasing with age. Elderly men selected for the absence of cardiovascular disease had AMH levels similar to those of young men whereas their InhB levels did not differ from aged-matched controls. These data suggests that Sertoli cell number and function changes with age, but with the extent and nature of the changes varying between men. PMID:23940675

  15. Development of a mobile dynamic nuclear polarizer for continuous flow applications

    Energy Technology Data Exchange (ETDEWEB)

    Ebert, Sandro; Dollmann, Bjoern; Bauer, Christian; Koelzer, Michael; Spiess, Hans W.; Hinderberger, Dariush; Muennemann, Kerstin [Max Planck Institute for Polymer Research, Mainz (Germany); Bluemler, Peter [Johannes Gutenberg University, Institute of Physics, Mainz (Germany)

    2011-07-01

    Despite its wide applicability in natural science, NMR still suffers from its inherently low sensitivity. This could be overcome by hyperpolarization of molecules via dynamic nuclear polarization (DNP). Here, we introduce a mobile DNP polarizer, based on an inexpensive Halbach magnet operating at 0.35 T. It shows an almost vanishing magnetic flux at its outer side and is not disturbing other instruments. It can be placed directly next to a superconducting magnet, thus limiting the transport time of the hyperpolarized sample. It will be shown, that the Halbach magnet has the same DNP performance like an electromagnet. Although DNP methods have found important applications in science, two problems remain: Firstly radicals are needed, which are mostly toxic. This problem becomes crucial with regard to medical applications. Secondly, the sample must be transported from the polarization magnet to the place of detection and polarization losses due to T1 occur. We are currently implementing a flow system to the mobile DNP polarizer, which should overcome both obstacles. The radicals will be immobilized in a gel matrix and the hyperpolarized radical free fluid is pumped subsequently directly in the MRI scanner.

  16. Effect of vitamin B6 deficiency on an antibody production in mice.

    Science.gov (United States)

    Doke, S; Inagaki, N; Hayakawa, T; Tsuge, H

    1997-08-01

    To investigate the effects of vitamin B6 (B6) deficiency on an antibody production in BALB/c mice, the production of specific immunoglobulin (Ig) E antibody against dinitrophenylated ovalbumin (DNP-OVA) were measured by the methods of enzyme linked immunosorbent assay. The mice fed on on a B6 deficient diet for 4 weeks were immunized intraperitoneally with DNP-OVA absorbed to aluminum hydroxide gel. The contents of anti DNP-IgE antibodies in sera of B6 deficient mice significantly increased compared to that of control mice fed on a diet containing B6. In addition, Interleukin-4, which was known to induce IgE production in allergic reactions from splenocytes of B6 deficient mice, was approximately four-fold higher than that in control mice. According to the recovery test to the B6 deficient mice, that is feeding the control diet for 21 days, all values in terms of the body, thymus, and spleen weight, total serum protein, IgG, and anti DNP-IgE content, regained almost the same levels as those of control. These results suggest that B6 deficiency in mice would have relation to the stimulation of specific IgE antibody production against DNP-OVA.

  17. The effect of a metabolic inhibitor upon the properties of the cerebral vasculature during a whole-head saline perfusion of the rat.

    Science.gov (United States)

    Luthert, P J; Greenwood, J; Pratt, O E; Lantos, P L

    1987-01-01

    The effect of the metabolic inhibitor 2,4-dinitrophenol (DNP) has been assessed during a simple in situ Ringer solution perfusion of the rat brain. The preparation was perfused, with or without the addition of DNP, for periods ranging up to 30 min. Following this pre-test perfusion, both the vascular permeability and cerebral perfusate flow were assessed. In the absence of DNP significant barrier disruption had taken place by 10 min and the flow rates showed greater fluctuations with time. In the presence of DNP, however, perfusate flow remained constant and the blood-brain barrier remained intact to [14C]mannitol for at least 10 min, but subsequently the flow rate dropped and the barrier began to show evidence of disruption. The unbound visual marker, Evans Blue, was apparently excluded from all regions other than those that are known to lack a blood-brain barrier. The water content of the brain showed no significant increase until 20 min. Patency of the capillaries was demonstrated by direct visualization of the cerebral vasculature with an Indian ink-gelatin mixture and in some animals there was evidence of incomplete filling following 30 min of perfusion. It is concluded that the use of DNP in the perfusate provides a useful preparation for the short-term study of passive properties of the blood-brain barrier, such as carrier-facilitated diffusion, as well as mechanisms of barrier opening.

  18. Rapid-melt Dynamic Nuclear Polarization

    Science.gov (United States)

    Sharma, M.; Janssen, G.; Leggett, J.; Kentgens, A. P. M.; van Bentum, P. J. M.

    2015-09-01

    In recent years, Dynamic Nuclear Polarization (DNP) has re-emerged as a means to ameliorate the inherent problem of low sensitivity in nuclear magnetic resonance (NMR). Here, we present a novel approach to DNP enhanced liquid-state NMR based on rapid melting of a solid hyperpolarized sample followed by 'in situ' NMR detection. This method is applicable to small (10 nl to 1 μl) sized samples in a microfluidic setup. The method combines generic DNP enhancement in the solid state with the high sensitivity of stripline 1 H NMR detection in the liquid state. Fast cycling facilitates options for signal averaging or 2D structural analysis. Preliminary tests show solid-state 1 H enhancement factors of up to 500 for H2O/D2O/d6-glycerol samples doped with TEMPOL radicals. Fast paramagnetic relaxation with nitroxide radicals, In nonpolar solvents such as toluene, we find proton enhancement factors up to 400 with negligible relaxation losses in the liquid state, using commercially available BDPA radicals. A total recycling delay (including sample freezing, DNP polarization and melting) of about 5 s can be used. The present setup allows for a fast determination of the hyper-polarization as function of the microwave frequency and power. Even at the relatively low field of 3.4 T, the method of rapid melting DNP can facilitate the detection of small quantities of molecules in the picomole regime.

  19. An Alderman-Grant resonator for S-Band Dynamic Nuclear Polarization

    Science.gov (United States)

    Neudert, Oliver; Raich, Hans-Peter; Mattea, Carlos; Stapf, Siegfried; Münnemann, Kerstin

    2014-05-01

    An Alderman-Grant resonator with resonance at 2 GHz (S-Band) was simulated, developed and constructed for Dynamic Nuclear Polarization (DNP) experiments at 73 mT. The resonator fits into magnet bores with a minimum diameter of 20 mm and is compatible with standard 3 mm NMR tubes. The compact resonator design achieves good separation of electric and magnetic fields and therefore can be used with comparatively large sample volumes with only small sample heating effects comparable to those obtained with optimized X- and W-Band DNP setups. The saturation efficiency and sample heating effects were investigated for Overhauser DNP experiments of aqueous solutions of TEMPOL radical, showing relative saturation better than 0.9 and sample heating not exceeding a few Kelvin even at high microwave power and long irradiation time. An application is demonstrated, combining the DNP setup with a commercial fast field cycling NMR relaxometer. Using this resonator design at low microwave frequencies can provide DNP polarization for a class of low-field and time-domain NMR experiments and therefore may enable new applications that benefit from increased sensitivity.

  20. Facile and Selective Synthetic Approach for Ruthenium Complexes Utilizing a Molecular Sieve Effect in the Supporting Ligand

    Directory of Open Access Journals (Sweden)

    Dai Oyama

    2013-12-01

    Full Text Available It is extremely important for synthetic chemists to control the structure of new compounds. We have constructed ruthenium-based mononuclear complexes with the tridentate 2,6-di(1,8-naphthyridin-2-ylpyridine (dnp ligand to investigate a new synthetic approach using a specific coordination space. The synthesis of a family of new ruthenium complexes containing both the dnp and triphenylphosphine (PPh3 ligands, [Ru(dnp(PPh3(X(L]n+ (X = PPh3, NO2−, Cl−, Br−; L = OH2, CH3CN, C6H5CN, SCN−, has been described. All complexes have been spectroscopically characterized in solution, and the nitrile complexes have also been characterized in the solid state through single-crystal X-ray diffraction analysis. Dnp in the present complex system behaves like a “molecular sieve” in ligand replacement reactions. Both experimental data and density functional theory (DFT calculations suggest that dnp plays a crucial role in the selectivity observed in this study. The results provide useful information toward elucidating this facile and selective synthetic approach to new transition metal complexes.

  1. Many-body kinetics of dynamic nuclear polarization by the cross effect

    Science.gov (United States)

    Karabanov, A.; Wiśniewski, D.; Raimondi, F.; Lesanovsky, I.; Köckenberger, W.

    2018-03-01

    Dynamic nuclear polarization (DNP) is an out-of-equilibrium method for generating nonthermal spin polarization which provides large signal enhancements in modern diagnostic methods based on nuclear magnetic resonance. A particular instance is cross-effect DNP, which involves the interaction of two coupled electrons with the nuclear spin ensemble. Here we develop a theory for this important DNP mechanism and show that the nonequilibrium nuclear polarization buildup is effectively driven by three-body incoherent Markovian dissipative processes involving simultaneous state changes of two electrons and one nucleus. We identify different parameter regimes for effective polarization transfer and discuss under which conditions the polarization dynamics can be simulated by classical kinetic Monte Carlo methods. Our theoretical approach allows simulations of the polarization dynamics on an individual spin level for ensembles consisting of hundreds of nuclear spins. The insight obtained by these simulations can be used to find optimal experimental conditions for cross-effect DNP and to design tailored radical systems that provide optimal DNP efficiency.

  2. Health-Related Quality of Life with Subcutaneous C1-Inhibitor for Prevention of Attacks of Hereditary Angioedema.

    Science.gov (United States)

    Lumry, William R; Craig, Timothy; Zuraw, Bruce; Longhurst, Hilary; Baker, James; Li, H Henry; Bernstein, Jonathan A; Anderson, John; Riedl, Marc A; Manning, Michael E; Keith, Paul K; Levy, Donald S; Caballero, Teresa; Banerji, Aleena; Gower, Richard G; Farkas, Henriette; Lawo, John-Philip; Pragst, Ingo; Machnig, Thomas; Watson, Douglas J

    2018-01-31

    Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on

  3. Outcomes of pulmonary tuberculosis in patients with discordant phenotypic isoniazid resistance testing.

    Science.gov (United States)

    Kim, Sukyeon; Lee, Hyun; Park, Hye Yun; Jeon, Kyeongman; Huh, Hee Jae; Lee, Nam Yong; Jeong, Byeong-Ho

    2017-12-01

    The discrepancy rates of drug susceptibility testing (DST) results between solid and liquid media have been reported to range from 2.4 to 7.4% for isoniazid. Most isolate with isoniazid DST discrepancies between solid and liquid media test as susceptible on solid medium and resistant in liquid medium, however, the optimal management of patients with discordant testing is unknown. This study was conducted to evaluate the effect of treatment regimen on treatment outcomes when patients with rifampicin-susceptible pulmonary tuberculosis have isoniazid resistance (INH-R) in liquid medium but isoniazid susceptibility (INH-S) on solid medium. This study was retrospectively conducted by reviewing patient medical records on the liquid compared to solid culture based phenotypic testing at Samsung Medical Center between January 2009 and December 2015. The study population which have INH-R in liquid medium and INH-S on solid medium was divided into two groups: group A (n = 30), which included patients treated for INH-S tuberculosis by discontinuing pyrazinamide (and ethambutol), and group B (n = 56), which included patients treated for INH-R tuberculosis by continuing pyrazinamide and/or adding fluoroquinolone. Unfavorable outcomes included treatment failure and relapse. There were no statistically significant differences between the two groups including demographic data, comorbidities, radiologic data, and treatment duration. However, baseline smear positive rates were more frequent in group A (19/30, 63.3%) than in group B (22/56, 39.3%; P = 0.033). Only three patients had unfavorable outcomes; one was bacteriologically proven treatment failure and the other two were clinically judged as unfavorable outcomes. All of them were in the group A (3/30, 10%); no unfavorable outcomes occurred in the group B (0/56, 0%; P = 0.040). Unfavorable outcomes were less frequent in the group B than in the group A, indicating that treatment regimen modification according to DST

  4. Self-administered C1 esterase inhibitor concentrates for the management of hereditary angioedema: usability and patient acceptance

    Directory of Open Access Journals (Sweden)

    Li HH

    2016-09-01

    Full Text Available Huamin Henry Li Institute for Asthma and Allergy, Chevy Chase, MD, USA Abstract: Hereditary angioedema (HAE is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH. The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze®, Berinert®, and Cetor®; however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE. Keywords: C1-INH concentrate, hereditary angioedema, disease management, first line, prophylaxis, self-administration 

  5. Novelties in the Diagnosis and Treatment of Angioedema.

    Science.gov (United States)

    Cicardi, M; Suffritti, C; Perego, F; Caccia, S

    2016-01-01

    Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis.

  6. Use of a C1 Inhibitor Concentrate in Adults ≥65 Years of Age with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Martinez-Saguer, Inmaculada; Bas, Murat

    2016-01-01

    BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert......(®)/CSL Behring) in patients of any age, including many older adults. METHODS: This observational registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered prospective (post-enrollment) and retrospective (pre-enrollment) usage and adverse event (AE) data on subjects treated with pnfC1-INH....... RESULTS: The registry documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE attacks treated with pnfC1-INH administration were reported among 25 of the 27 (92.6 %) older adults. Among the older adults, mean (standard deviation [SD]) (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH...

  7. In vitro antimycobacterial activity of 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione: A new chemical entity against Mycobacterium tuberculosis.

    Science.gov (United States)

    Rather, Muzafar Ahmad; Bhat, Zubair Shanib; Lone, Ali Mohd; Maqbool, Mubashir; Amin, Shajrul; Bhat, Bilal Ahmad; Ahmad, Zahoor

    2018-03-03

    The presented study reports in vitro antituberculosis potential of 2-(((2-hydroxyphenyl) amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (PAMCHD) against Mycobacterium tuberculosis H37Rv. PAMCHD proved to be tuberculostatic as well as tuberculocidal agent by agar and broth dilution methods with MIC and MBC values equivalent to some standard antituberculosis drugs (ATDs). The dynamics of M. tuberculosis killing revealed its time as well as concentration dependent antituberculosis activity and it sterilized M. tuberculosis culture at or above 10.0 µg/mL concentration. PAMCHD acts either synergistically or additively with ATDs. INH and PAMCHD post-antibiotic effects increased with concentration from 16.18 ± 13.30 and 31.64 ± 13.30 to 127.9 ± 27.60 and 138.71 ± 16.42 hrs respectively from 1x MIC to 8x MIC; no significant difference was observed between INH and PAMCHD PAEs. M. tuberculosis mutation frequency against PAMCHD is lower than those of INH. Mutant prevention concentration (MPC) of INH, RIF and PAMCHD were observed to be 40, 160 and 160 µg/mL respectively and their MPC/MIC values were 128, 2051 and 64 respectively; this lowest MPC/MIC highlights advantage of PAMCHD over RIF and INH. Copyright © 2018. Published by Elsevier B.V.

  8. Study on the serum levels of inhibin in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Fang Aixian; Yang Jianlan

    2009-01-01

    Objective: To investigate the changes of serum inhibin B (inhibin. INH-B) levels in women with polycystic ovary syndrome (PCOS) and the relationship with body mass index (BMI). Methods: Serum insulin-like growth factor-I (IGF-I), fasting insulin (In), and leptin ( with RIA) inhibin B (INH-B) (with ELISA) and luteinizing hormone (LH), follicle-stimulating hormone (FSH), human prolactin (PRL), estradiol (E 2 ) testosterone (T) (with CLIA) levels were measured in 40 patients with PCOS and 40 controls. 24 of the 40 PCOS patients were of the obese group (BMI>25) and 16 were non-obese. Results: Serum leptin, In, LH, T levels were significantly higher but INH-B, IGF levels were significantly lower in obese group than those in non-obese group (P<0.05). There were negative correlations between LH and INH levels (r=-0.730, P<0.05 in obese group but none in non-obese group serum). INH-B, IGF, LH, T levels in non-obese group were significantly higher than those in the controls (P<0.05). Conclusion: Inhibin is closely related to the development of PCOS, the level of serum inhibin is lower in obese patients with PCOS. (authors)

  9. A novel STK1-targeted small-molecule as an "antibiotic resistance breaker" against multidrug-resistant Staphylococcus aureus.

    Science.gov (United States)

    Kant, Sashi; Asthana, Shailendra; Missiakas, Dominique; Pancholi, Vijay

    2017-07-11

    Ser/Thr protein kinase (STK1) plays a critical role in cell wall biosynthesis of and drug resistance in methicillin-resistant Staphylococcus aureus (MRSA). MRSA strains lacking STK1 become susceptible to failing cephalosporins, such as Ceftriaxone and Cefotaxime. STK1, despite being nonessential protein for MRSA survival, it can serve as an important therapeutic agent for combination therapy. Here, we report a novel small molecule quinazoline compound, Inh2-B1, which specifically inhibits STK1 activity by directly binding to its ATP-binding catalytic domain. Functional analyses encompassing in vitro growth inhibition of MRSA, and in vivo protection studies in mice against the lethal MRSA challenge indicated that at high concentration neither Inh2-B1 nor Ceftriaxone or Cefotaxime alone was able to inhibit the growth of bacteria or protect the challenged mice. However, the growth of MRSA was inhibited, and a significant protection in mice against the bacterial challenge was observed at a micromolar concentration of Ceftriaxone or Cefotaxime in the presence of Inh2-B1. Cell-dependent minimal to no toxicity of Inh2-B1, and its abilities to down-regulate cell wall hydrolase genes and disrupt the biofilm formation of MRSA clearly indicated that Inh2-B1 serves as a therapeutically important "antibiotic-resistance-breaker," which enhances the bactericidal activity of Ceftriaxone/Cefotaxime against highly pathogenic MRSA infection.

  10. Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina fusiformis, a candidate food supplement.

    Science.gov (United States)

    Martin, Sherry Joseph; Baskaran, Udhaya Lavinya; Vedi, Mahima; Sabina, Evan Prince

    2014-12-01

    Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.

  11. Complement factor C4 activation in patients with hereditary angioedema

    DEFF Research Database (Denmark)

    Åbom, Anne; Bygum, Anette; Koch, Claus

    2017-01-01

    , that C1-INH-HAE may potentially be overlooked, if screening is performed only by measurement of C4. It has been suggested that measurement of C4 activation products is better suited to avoid false negative results. Our aim was to investigate whether total antigenic C4 or non-functional C4c is a better......Objectives: Low complement factor C4 is usually considered a valuable screening tool for patients with the potentially life-threatening hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients with C1-INH-HAE presenting with normal C4 levels. This means...... measure of the increased C4 activation in C1-INH-HAE patients. Design and methods: Two different monoclonal antibodies (mAb) to human C4 were produced: one had specificity for the β-chain of C4 and would thus react with both functional and non-functional C4, and the other was developed against the factor...

  12. Antimicrobial susceptibility determined by the E test, Löwenstein-Jensen proportion, and DNA sequencing methods among Mycobacterium tuberculosis isolates discrepancies, preliminary results

    Directory of Open Access Journals (Sweden)

    Maria Inês Moura Freixo

    2004-02-01

    Full Text Available Mycobacterium tuberculosis strains resistant to streptomycin (SM, isoniazid (INH, and/or rifampin (RIF as determined by the conventional Löwenstein-Jensen proportion method (LJPM were compared with the E test, a minimum inhibitory concentration susceptibility method. Discrepant isolates were further evaluated by BACTEC and by DNA sequence analyses for mutations in genes most often associated with resistance to these drugs (rpsL, katG, inhA, and rpoB. Preliminary discordant E test results were seen in 75% of isolates resistant to SM and in 11% to INH. Discordance improved for these two drugs (63% for SM and none for INH when isolates were re-tested but worsened for RIF (30%. Despite good agreement between phenotypic results and sequencing analyses, wild type profiles were detected on resistant strains mainly for SM and INH. It should be aware that susceptible isolates according to molecular methods might contain other mechanisms of resistance. Although reproducibility of the LJPM susceptibility method has been established, variable E test results for some M. tuberculosis isolates poses questions regarding its reproducibility particularly the impact of E test performance which may vary among laboratories despite adherence to recommended protocols. Further studies must be done to enlarge the evaluated samples and looked possible mutations outside of the hot spot sequenced gene among discrepant strains.

  13. Multimethod teaching strategies to integrate selected QSEN competencies in a Doctor of Nursing Practice distance education program.

    Science.gov (United States)

    Manning, Mary Lou; Frisby, Anthony J

    2011-01-01

    The Quality and Safety Education for Nurses (QSEN) initiative identified 6 competencies for the education of nurses (patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics) and the related knowledge, skills, and attitudes (KSAs) for each competency. The initial QSEN focus was on competency development during prelicensure nursing education, with subsequent attention on adapting the KSAs for graduate programs that prepare advanced practice nurses for clinical roles. Description of successful QSEN competency integration in Doctor of Nursing Practice (DNP) programs is limited. Although the ultimate goal is executing DNP programs where quality and safety is thoroughly integrated throughout the curricula, the focus of this article is on multimethod teaching strategies to integrate selected QSEN KSAs into an existing online post-master's DNP quality and safety course. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Environmental Conditions Influence the Plant Functional Diversity Effect on Potential Denitrification

    Science.gov (United States)

    Sutton-Grier, Ariana E.; Wright, Justin P.; McGill, Bonnie M.; Richardson, Curtis

    2011-01-01

    Global biodiversity loss has prompted research on the relationship between species diversity and ecosystem functioning. Few studies have examined how plant diversity impacts belowground processes; even fewer have examined how varying resource levels can influence the effect of plant diversity on microbial activity. In a field experiment in a restored wetland, we examined the role of plant trait diversity (or functional diversity, (FD)) and its interactions with natural levels of variability of soil properties, on a microbial process, denitrification potential (DNP). We demonstrated that FD significantly affected microbial DNP through its interactions with soil conditions; increasing FD led to increased DNP but mainly at higher levels of soil resources. Our results suggest that the effect of species diversity on ecosystem functioning may depend on environmental factors such as resource availability. Future biodiversity experiments should examine how natural levels of environmental variability impact the importance of biodiversity to ecosystem functioning. PMID:21311768

  15. Academic and Institutional Review Board Collaboration to Ensure Ethical Conduct of Doctor of Nursing Practice Projects.

    Science.gov (United States)

    Foote, Jan M; Conley, Virginia; Williams, Janet K; McCarthy, Ann Marie; Countryman, Michele

    2015-07-01

    Navigating the regulations to protect human subjects and private health information for Doctor of Nursing Practice (DNP) projects can be a formidable task for students, faculty, and the institutional review board (IRB). Key stakeholders from the University of Iowa College of Nursing and the Human Subjects Office developed a standardized process for DNP students to follow, using a decision algorithm, a student orientation to the human subjects review process conducted by faculty and IRB chairs and staff, and a brief Human Subjects Research Determination form. Over 2 years, 109 students completed the process, and 96.3% of their projects were deemed not to be human subjects research. Every student submitted documentation of adherence to the standardized process. Less time was spent by students, faculty, and the IRB in preparing and processing review requests. The interprofessional collaboration resulted in a streamlined process for the timely review of DNP projects. Copyright 2015, SLACK Incorporated.

  16. Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats.

    Science.gov (United States)

    Shin, T Y; Jeong, H J; Jun, S M; Chae, H J; Kim, H R; Baek, S H; Kim, H M

    1999-11-01

    We investigated the effect of an aqueous extract of Schizonepeta tenuifolia (STAE) on mast cell-mediated immediate-type hypersensitivity. STAE inhibited systemic allergic reaction induced by compound 48/80 in rats dose-dependently. STAE also inhibited plasma histamine levels induced by compound 48/80. STAE inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. In addition, STAE does-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. However, STAE had a significant enhancing effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from RPMC. These results indicate that STAE inhibits immediate-type hypersensitivity and suggest that STAE can selectively activate the TNF-alpha production from RPMC.

  17. E-Mentoring for Doctor of Nursing Practice Students: A Pilot Program.

    Science.gov (United States)

    Harris, Robin; Birk, Stefanie B; Sherman, Jan

    2016-08-01

    The growing number of online Doctor of Nursing Practice (DNP) programs, steady attrition rates, and shortage of faculty created an opportunity to explore the use of distance-mediated mentoring. Twenty first-year DNP Nursing Leadership students were matched with DNP-prepared mentors in a formalized e-mentoring program. The Ideal Mentor Scale was used to determine what students desired most from the mentoring relationship in addition to midpoint and end-of-program surveys. Quantitative analysis revealed mentors and mentees found the relationship to be beneficial (p mentors (92%) noted the program supplied adequate resources, and the majority of students would recommend the program. Having a mentor leads to both mentor- and mentee-perceived benefits. Recommendations include continuing to seek ways to improve the communication and commitment between the mentor and mentee in order to receive reciprocal program benefits. [J Nurs Educ. 2016;55(8):458-462.]. Copyright 2016, SLACK Incorporated.

  18. Environmental conditions influence the plant functional diversity effect on potential denitrification.

    Directory of Open Access Journals (Sweden)

    Ariana E Sutton-Grier

    2011-02-01

    Full Text Available Global biodiversity loss has prompted research on the relationship between species diversity and ecosystem functioning. Few studies have examined how plant diversity impacts belowground processes; even fewer have examined how varying resource levels can influence the effect of plant diversity on microbial activity. In a field experiment in a restored wetland, we examined the role of plant trait diversity (or functional diversity, (FD and its interactions with natural levels of variability of soil properties, on a microbial process, denitrification potential (DNP. We demonstrated that FD significantly affected microbial DNP through its interactions with soil conditions; increasing FD led to increased DNP but mainly at higher levels of soil resources. Our results suggest that the effect of species diversity on ecosystem functioning may depend on environmental factors such as resource availability. Future biodiversity experiments should examine how natural levels of environmental variability impact the importance of biodiversity to ecosystem functioning.

  19. Effect of some organic solvents on oxidative phosphorylation in rat liver mitochondria

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Skonberg, Christian; Hansen, Steen Honoré

    2013-01-01

    The effect of acetone, acetonitrile, dimethyl sulfoxide (DMSO), ethanol and methanol on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria has been studied. All the organic solvents inhibited the oxidative phosphorylation in a concentration dependent manner, but with differences......,4-dinitrophenol (DNP) mediated inhibition of oxidative phosphorylation with potentiation of the action of DNP. Acetonitrile showed the highest potentiation effect followed by acetone, ethanol, methanol, and DMSO in presence of DNP. The use of organic solvents for investigation of the effects of compounds...... in potencies. Among the tested organic solvents, acetonitrile and acetone were more potent than ethanol, methanol, and DMSO. There was no significant difference in oxidative phosphorylation, compared to controls, when the concentrations of acetone was below 1% (v/v), of acetonitrile below 2% (v/v), of DMSO...

  20. Electron paramagnetic resonance and dynamic nuclear polarization of char suspensions: surface science and oximetry

    International Nuclear Information System (INIS)

    Clarkson, R.B.; Odintsov, B.M.; Ceroke, P.J.; Ardenkjaer-Larsen, J.H.; Fruianu, M.; Belford, R.L.

    1998-01-01

    Carbon chars have been synthesized in our laboratory from a variety of starting materials, by means of a highly controlled pyrolysis technique. These chars exhibit electron paramagnetic resonance (EPR) line shapes which change with the local oxygen concentration in a reproducible and stable fashion; they can be calibrated and used for oximetry. Biological stability and low toxicity make chars good sensors for in vivo measurements. Scalar and dipolar interactions of water protons at the surfaces of chars may be utilized to produce dynamic nuclear polarization (DNP) of the 1 H nuclear spin population in conjunction with electron Zeeman pumping. Low-frequency EPR, DNP and DNP-enhanced MRI all show promise as oximetry methods when used with carbon chars. (author)

  1. Instrumentation for cryogenic magic angle spinning dynamic nuclear polarization using 90L of liquid nitrogen per day.

    Science.gov (United States)

    Albert, Brice J; Pahng, Seong Ho; Alaniva, Nicholas; Sesti, Erika L; Rand, Peter W; Saliba, Edward P; Scott, Faith J; Choi, Eric J; Barnes, Alexander B

    2017-10-01

    Cryogenic sample temperatures can enhance NMR sensitivity by extending spin relaxation times to improve dynamic nuclear polarization (DNP) and by increasing Boltzmann spin polarization. We have developed an efficient heat exchanger with a liquid nitrogen consumption rate of only 90L per day to perform magic-angle spinning (MAS) DNP experiments below 85K. In this heat exchanger implementation, cold exhaust gas from the NMR probe is returned to the outer portion of a counterflow coil within an intermediate cooling stage to improve cooling efficiency of the spinning and variable temperature gases. The heat exchange within the counterflow coil is calculated with computational fluid dynamics to optimize the heat transfer. Experimental results using the novel counterflow heat exchanger demonstrate MAS DNP signal enhancements of 328±3 at 81±2K, and 276±4 at 105±2K. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Reactive surface organometallic complexes observed using dynamic nuclear polarization surface enhanced NMR spectroscopy

    KAUST Repository

    Pump, Eva

    2016-08-15

    Dynamic Nuclear Polarization Surface Enhanced NMR Spectroscopy (DNP SENS) is an emerging technique that allows access to high-sensitivity NMR spectra from surfaces. However, DNP SENS usually requires the use of radicals as an exogenous source of polarization, which has so far limited applications for organometallic surface species to those that do not react with the radicals. Here we show that reactive surface species can be studied if they are immobilized inside porous materials with suitably small windows, and if bulky nitroxide bi-radicals (here TEKPol) are used as the polarization source and which cannot enter the pores. The method is demonstrated by obtaining significant DNP enhancements from highly reactive complelxes [(equivalent to Si-O-)W(Me)(5)] supported on MCM-41, and effects of pore size (6.0, 3.0 and 2.5 nm) on the performance are discussed.

  3. 2,4-Dinitrophenol: A threat to Chinese body-conscious groups

    Directory of Open Access Journals (Sweden)

    Han Chih Hencher Lee

    2014-08-01

    Full Text Available 2,4-Dinitrophenol (2,4-DNP, a yellowish compound, has historically been used in the manufacture of dyes, explosives, and fungicides. As it uncouples mitochondrial oxidative phosphorylation, the compound was also used as an antiobesity agent early in the past century. The compound was subsequently banned by the United States Food and Drug Administration in 1938 due to its potentially fatal adverse effects, including hyperthermia, cataract, agranulocytosis, hepatoxicity, nephrotoxicity, and cardiotoxicity. However, the popularity of 2,4-DNP as a slimming aid has appeared to increase again in recent years. The Hong Kong Hospital Authority Toxicology Reference Laboratory recently confirmed two cases of self-administered 2,4-DNP with different clinical presentations to hospitals in the area. Here we describe those two cases, in an attempt to underscore the potential of misuse of this substance by body-conscious groups among the Chinese population.

  4. Dynamic nuclear polarization by frequency modulation of a tunable gyrotron of 260 GHz

    Science.gov (United States)

    Yoon, Dongyoung; Soundararajan, Murari; Cuanillon, Philippe; Braunmueller, Falk; Alberti, Stefano; Ansermet, Jean-Philippe

    2016-01-01

    An increase in Dynamic Nuclear Polarization (DNP) signal intensity is obtained with a tunable gyrotron producing frequency modulation around 260 GHz at power levels less than 1 W. The sweep rate of frequency modulation can reach 14 kHz, and its amplitude is fixed at 50 MHz. In water/glycerol glassy ice doped with 40 mM TEMPOL, the relative increase in the DNP enhancement was obtained as a function of frequency-sweep rate for several temperatures. A 68 % increase was obtained at 15 K, thus giving a DNP enhancement of about 80. By employing λ / 4 and λ / 8 polarizer mirrors, we transformed the polarization of the microwave beam from linear to circular, and achieved an increase in the enhancement by a factor of about 66% for a given power.

  5. Doctor of philosophy and doctor of nursing practice as complementary degrees.

    Science.gov (United States)

    Edwardson, Sandra R

    2010-01-01

    The introduction of the doctor of nursing practice (DNP) has raised serious concerns about the discipline's continuing ability to build its body of knowledge at an appropriate rate. After noting the various concerns that have been raised that the DNP siphons off prospective doctor of philosophy (PhD) students and compromises the standing of schools of nursing in universities, the distinct but complementary roles of nurses with the two preparations are described. Rather than worry about the DNP distracting from the PhD, the argument is made that these two degrees support one another and together can help to advance the creation and translation of knowledge into the practice of the discipline. Similar discussions about the distinction between practice and research in the field of education are noted.

  6. Further evidence for uncoupling action of gamma radiation in excised beam hypocotyl segments

    International Nuclear Information System (INIS)

    Gaur, B.K.; Joshi, V.G.

    1975-01-01

    That ionizing radiations act as uncoupler of oxidative phosphorylation in animal tissue has been well documented in the literature. The present report supports our earlier suggestion for a similar behaviour of gamma radiation in plant system. Mitochondria were extracted from normal and gamma-irradiated hypocotyl segments of 4-day old bean seedlings. Swelling and contraction were initiated by supplying suitable substrates. The changes in turbidity were then recorded spectrophotometrically in the presence and absence of 2,4-dinitrophenol (DNP). Radiation enhanced the swelling per se as well as its rate. The contraction, on the other hand, was markedly reduced. While the effect of DNP alone was qualitatively similar to that of radiation, it was lowered in the pre-irradiated tissue. These observations are discussed in the light of known/proposed mechanisms of action of the classical uncoupler DNP. (orig.) [de

  7. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Science.gov (United States)

    Cerqueira, Fernanda M; Laurindo, Francisco R M; Kowaltowski, Alicia J

    2011-03-31

    Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  8. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Fernanda M Cerqueira

    2011-03-01

    Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  9. La actividad física, el entrenamiento continuo e intervalo: una solución para la salud

    Directory of Open Access Journals (Sweden)

    Ricardo Ortiz-Pulido

    2017-01-01

    Full Text Available El propósito de este documento fue reportar los beneficios de la actividad física, entrenamientointervalo y entrenamiento continuo moderado en adultos sedentarios y físicamente activos.La actividad física involucra cualquier movimiento corporal que produce un aumento en elgasto energético en el metabolismo, mientras que el entrenamiento intervalo y entrenamientocontinuo moderado puede ser utilizado para controlar el programa de cargas de entrenamiento(intensidad, volumen y pausa. Los beneficios que se han reportado cuando se realiza actividadfísica son: el incremento o mantenimiento de la condición física muscular, funciones cognitivas,cardiorespiratoria, equilibrio, peso corporal, control de la obesidad; todos ellos disminuyen losriesgos de enfermedades cardiovasculares, enfernedades crónicorrespiratorias, diabetes, presiónalterial alta, sindrome metabolico, cáncer de colon, depresión y todas las causas de mortalidad.En contraste, la falta de actividad fisica ha ha sido identificada como factor de riesgo y estáasociada a diversas enfemedades no transmisibles a nivel mundial. En este documento puntua-lizamos dos tipos de entrenamiento que han tenido aplicaciones para la salud en adultos. Estetrabajo podría ayudar a promover la salud calidad de vida de la población adulta y eliminar elsedentarismo mediante la prescripción de la actividad física para la salud.

  10. Weaknesses in the reporting of cross-sectional studies according to the STROBE statement: the case of metabolic syndrome in adults from Peru.

    Science.gov (United States)

    Tapia, Jose Carlos; Ruiz, Eloy F; Ponce, Oscar J; Malaga, German; Miranda, Jaime

    2015-12-30

    The inadequate reporting of cross-sectional studies, as in the case of the prevalence of metabolic syndrome, could cause problems in the synthesis of new evidence and lead to errors in the formulation of public policies. To evaluate the reporting quality of the articles regarding metabolic syndrome prevalence in Peruvian adults using the STROBE recommendations. We conducted a thorough literature search with the terms "Metabolic Syndrome", "Sindrome Metabolico" and "Peru" in MEDLINE/PubMed, LILACS, SciELO, LIPECS and BVS-Peru until December 2014. We selected those who were population-based observational studies with randomized sampling that reported prevalence of metabolic syndrome in adults aged 18 or more of both sexes. Information was analysed through the STROBE score per item and recommendation. Seventeen articles were included in this study. All articles met the recommendations related to the report of the study's rationale, design, and provision of summary measures. The recommendations with the lowest scores were those related to the sensitivity analysis (8%, n= 1/17), participant flowchart (18%, n= 3/17), missing data analysis (24%, n= 4/17), and number of participants in each study phase (24%, n= 4/17). Cross-sectional studies regarding the prevalence of metabolic syndrome in peruvian adults have an inadequate reporting on the methods and results sections. We identified a clear need to improve the quality of such studies.

  11. Weaknesses in the reporting of cross-sectional studies according to the STROBE statement

    Science.gov (United States)

    Malaga, German; Miranda, Jaime

    2015-01-01

    Introduction: The inadequate reporting of cross-sectional studies, as in the case of the prevalence of metabolic syndrome, could cause problems in the synthesis of new evidence and lead to errors in the formulation of public policies. Objective: To evaluate the reporting quality of the articles regarding metabolic syndrome prevalence in Peruvian adults using the STROBE recommendations. Methods: We conducted a thorough literature search with the terms "Metabolic Syndrome", "Sindrome Metabolico" and "Peru" in MEDLINE/PubMed, LILACS, SciELO, LIPECS and BVS-Peru until December 2014. We selected those who were population-based observational studies with randomized sampling that reported prevalence of metabolic syndrome in adults aged 18 or more of both sexes. Information was analysed through the STROBE score per item and recommendation. Results: Seventeen articles were included in this study. All articles met the recommendations related to the report of the study's rationale, design, and provision of summary measures. The recommendations with the lowest scores were those related to the sensitivity analysis (8%, n= 1/17), participant flowchart (18%, n= 3/17), missing data analysis (24%, n= 4/17), and number of participants in each study phase (24%, n= 4/17). Conclusion: Cross-sectional studies regarding the prevalence of metabolic syndrome in peruvian adults have an inadequate reporting on the methods and results sections. We identified a clear need to improve the quality of such studies. PMID:26848197

  12. Off-resonance NOVEL

    Science.gov (United States)

    Jain, Sheetal K.; Mathies, Guinevere; Griffin, Robert G.

    2017-10-01

    Dynamic nuclear polarization (DNP) is theoretically able to enhance the signal in nuclear magnetic resonance (NMR) experiments by a factor γe/γn, where γ 's are the gyromagnetic ratios of an electron and a nuclear spin. However, DNP enhancements currently achieved in high-field, high-resolution biomolecular magic-angle spinning NMR are well below this limit because the continuous-wave DNP mechanisms employed in these experiments scale as ω0-n where n ˜ 1-2. In pulsed DNP methods, such as nuclear orientation via electron spin-locking (NOVEL), the DNP efficiency is independent of the strength of the main magnetic field. Hence, these methods represent a viable alternative approach for enhancing nuclear signals. At 0.35 T, the NOVEL scheme was demonstrated to be efficient in samples doped with stable radicals, generating 1H NMR enhancements of ˜430. However, an impediment in the implementation of NOVEL at high fields is the requirement of sufficient microwave power to fulfill the on-resonance matching condition, ω0I = ω1S, where ω0I and ω1S are the nuclear Larmor and electron Rabi frequencies, respectively. Here, we exploit a generalized matching condition, which states that the effective Rabi frequency, ω1S e f f, matches ω0I. By using this generalized off-resonance matching condition, we generate 1H NMR signal enhancement factors of 266 (˜70% of the on-resonance NOVEL enhancement) with ω1S/2π = 5 MHz. We investigate experimentally the conditions for optimal transfer of polarization from electrons to 1H both for the NOVEL mechanism and the solid-effect mechanism and provide a unified theoretical description for these two historically distinct forms of DNP.

  13. Licarin A is a candidate compound for the treatment of immediate hypersensitivity via inhibition of rat mast cell line RBL-2H3 cells.

    Science.gov (United States)

    Matsui, Takuya; Ito, Chihiro; Masubuchi, Satoru; Itoigawa, Masataka

    2015-12-01

    We previously demonstrated that some phenylpropanoids are capable of inhibiting activated mast cells. This study evaluated the anti-allergic effects of licarin A, a neolignan isolated from various plants, on antigen-stimulated rat mast cell line. The inhibitory effects of licarin A on histamine release, tumour necrosis factor-α (TNF-α) and prostaglandin D2 (PGD2) production, and cyclooxygenase-2 (COX-2) expression in dinitrophenyl-human serum albumin (DNP-HSA) rat basophilic leukemia cells (DNP-HSA-stimulated RBL-2H3 cells), were investigated by spectrofluorometry, ELISA and immunoblotting. Licarin A significantly and dose-dependently reduced TNF-α production (IC50 12.6 ± 0.3 μm) in DNP-HSA-stimulated RBL-2H3 cells. Furthermore, the levels of PGD2 secretion in DNP-HSA-stimulated cells pretreated with licarin A were lower than those stimulated with DNP-HSA alone (positive control). Treatment with licarin A at 20 μm produced slight suppression of DNP-HSA-induced increases in COX-2 mRNA and protein levels. We identified several signalling pathways that mediated these pharmacological effects. Licarin A treatment tended to reduce phosphorylated protein kinase C alpha/beta II (PKCα/βII) and p38 mitogen-activated protein kinase (MAPK) protein levels. Our results demonstrate that licarin A reduces TNF-α and PGD2 secretion via the inhibition of PKCα/βII and p38 MAPK pathways; this compound may be useful for attenuating immediate hypersensitivity. © 2015 Royal Pharmaceutical Society.

  14. Risk of Damage to the Somatic Innervation of the Penis during the AdVanceProcedure: An Anatomical Study.

    Science.gov (United States)

    Hogewoning, Cornelis R C; Elzevier, Henk W; Pelger, Rob C M; Bekker, Milou D; DeRuiter, Marco C

    2015-08-01

    One of the methods to treat post radical prostatectomy stress urinary incontinence is the AdVance (American Medical Systems, Minnetonka, MN, USA) male sling procedure. During this procedure, the somatic innervation of the penis may be at risk for injury. Six AdVance procedures were performed in six donated bodies at the Anatomy and Embryology Department of the Leiden University Medical Centre. The pelves were dissected and the shortest distance between the sling and the dorsal nerve of the penis (DNP) was documented. The aim of this study was to describe the anatomical relation between the AdVance male sling and penile nerves based on the dissection of six adult male pelves. The AdVance male sling procedure was conducted in six donated male bodies. After placement, the pelves were dissected and the shortest distance between sling and the DNP was documented. The main outcome measure was the distance between the AdVance male sling and the DNP. The mean distance of the sling to the DNP was 4.1 mm and was found situated directly next to the nerve (distance 0 mm) in 4 out of 12 (33%) hemipelves. The distance of the sling to the obturator neurovascular bundle was 30 mm or more in all six bodies. Damage to the DNP caused by the AdVance male sling procedure appears to be an extremely rare complication, which has not been described in current literature. The proximity of the AdVance to the DNP could, however, pose a risk that should be taken into consideration by physicians and patients when opting for surgery. © 2015 International Society for Sexual Medicine.

  15. Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel.

    Science.gov (United States)

    Kulhari, Hitesh; Pooja, Deep; Shrivastava, Shweta; V G M, Naidu; Sistla, Ramakrishna

    2014-05-01

    The aim of this research work was to develop Bombesin peptide (BBN) conjugated, docetaxel loaded nanocarrier for the treatment of breast cancer. Docetaxel loaded nanoparticles (DNP) were prepared by solvent evaporation method using sodium cholate as surfactant. BBN was conjugated to DNP surface through covalent bonding. Both DNP and BBN conjugated DNP (BDNP) were characterized by various techniques such as dynamic light scattering, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis. The particle diameter and zeta potential of BDNP were 136±3.95 nm and -10.8±2.7 mV, respectively. The change in surface charge and FTIR studies confirmed the formation of amide linkage between BBN and DNP. AFM analysis showed that nanoparticles were spherical in shapes. In nanoparticles, docetaxel was present in its amorphous form as confirmed by DSC and PXRD analysis and was stable during the thermal studies. The formulations showed the sustained release of DTX over the period of 120 h. During cellular toxicity assay in gastrin releasing peptide receptor positive breast cancer cells (MDA-MB-231), BDNP were found to be 12 times more toxic than pure DTX and Taxotere. The IC50 value for DTX, Taxotere, DNP and BDNP was >375, >375, 142.23 and 35.53 ng/ml, respectively. The above studies showed that Bombesin conjugated nanocarrier system could be a promising carrier for active targeting of anticancer drugs in GRP receptor over expressing cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Phototransformations of dinitropyrene isomers on models of the atmospheric particulate matter.

    Science.gov (United States)

    Arce, Rafael; Morel, María

    2013-08-01

    The 1,6 and 1,8-dinitropyrenes (DNP) isomers are strong mutagens and carcinogens encountered in diesel exhaust and airborne particles. Relative photodegradation rates were determined and some products were characterized when these isomers were irradiated adsorbed onto models of the atmospheric matter. These are compared to their photochemical behavior in a polar nonprotic solvent. The 1,8-DNP isomer is three times more reactive than the 1,6-DNP when irradiated adsorbed onto silica gel surfaces, while the reverse order is observed in solution, demonstrating the influence of structural differences and environmental effects on the photoreactivity. Oxygen is a key factor in the formation of pyrenediones from 1,8-DNP in solution and on silica gel which is not the case for 1,6-DNP. The average pore diameter (2.5 versus 6.0 nm) of the silica surfaces induces a significant change in the product distribution and relative yields of 1,8-DNP because pyrenediones or 8-hydroxy-1-nitropyrene are not produced in the smaller pore silica. A 6-hydroxy-1-nitropyrene product is observed both in acidic alumina and silica (6.0 nm) surfaces. On acidic alumina the rates of phototransformation of the isomers are equal, a significant increase in the relative yield of the hydroxynitropyrene product is observed compared to the silica and unidentified products in which the absence of NO 2 and pyrene absorption bands were observed, demonstrating the surface effect on the photodegradation. Overall, the presence of some products indicates the occurrence of a nitro-nitrite rearrangement on the surface with the participation of a pyrenoxy radical as their precursor.

  17. Identification of cyclic peptides for facilitation of transcellular transport of phages across intestinal epithelium in vitro and in vivo.

    Science.gov (United States)

    Yamaguchi, Shunsuke; Ito, Shingo; Kurogi-Hirayama, Mio; Ohtsuki, Sumio

    2017-09-28

    Methodology to enhance intestinal absorption of macromolecular drugs is an important challenge for developing next-generation biomedicines. So far, various cationic cell-penetrating peptides have been reported to facilitate uptake of certain bioactive proteins. However, cyclic peptides might be better candidates, as they are more metabolically stable than linear peptides. Accordingly, we hypothesized that suitable cyclic peptides would promote the absorption of macromolecules across intestinal epithelium. To test this idea, we adopted Caco-2 cell permeability assay as an in vitro human intestinal absorption model, and M13 phage as a model of macromolecules. Successive screenings of a phage library displaying cyclic heptapeptides via a short GGGS linker yielded 3 hits. Among them, phage displaying cyclic heptapeptide DNPGNET (DNP-phage) showed the greatest permeability across a Caco-2 cell monolayer and mouse intestinal epithelium. Interestingly, DNPGNET (DNP) does not contain any basic amino acids. Its isoelectric point (pI) was estimated to be 2.72. It did not reduce the viability or tight-junction integrity of Caco-2 cells at concentrations up to 100μM for 24h. Uptake of either DNP-phage or a fluorescence-labeled DNP derivative (AC-DNPGNET-CGGGS modified with 5/6-FAM at the C-terminal; the cysteines serve to generate the cyclic peptide via disulfide bond formation, and GGGS is the phage linker) by Caco-2 cells was inhibited by low temperature, unlabeled AC-DNPGNET-CGGGS and EIPA, a macropinocytosis inhibitor. Thus, DNP appears to facilitate transcellular permeability of phages via macropinocytosis, but not paracellular diffusion. These findings indicate that DNP is a promising candidate as a carrier to promote intestinal absorption of macromolecular drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Synthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones.

    Science.gov (United States)

    Velezheva, Valeriya; Brennan, Patrick; Ivanov, Pavel; Kornienko, Albert; Lyubimov, Sergey; Kazarian, Konstantin; Nikonenko, Boris; Majorov, Konstantin; Apt, Alexander

    2016-02-01

    We describe the design, synthesis, and in vitro antimycobacterial activity of a series of novel simple hybrid hydrazides and hydrazide-hydrazones combining indole and pyridine nuclei. The compounds are derivatives of 1-acetylindoxyl or substituted indole-3-carboxaldehydes tethered via a hydrazine group by simple C-N or double C=N bonds with 3- and 4-pyridines, 1-oxide 3- and 4-pyridine carbohydrazides. The most active of 15 compounds showed MICs values against an INH-sensitive strain of Mycobacterium tuberculosis H37Rv equal to that of INH (0.05-2 μg/mL). Five compounds demonstrated appreciable activity against the INH-resistant M. tuberculosis CN-40 clinical isolate (MICs: 2-5 μg/mL), providing justification for further in vivo studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin

    DEFF Research Database (Denmark)

    Barnett, AH; Dreyer, M; Lange, Peter

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an open-label, parallel, 24-week multicenter trial. Patients...... uncontrolled on metformin were randomized to adjunctive INH (n = 243) or glibenclamide (n = 233). Before randomization, patients were divided into two HbA(1c) (A1C) arms: > or =8 to 9.5 to ... associated clinical manifestations. CONCLUSIONS: In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated...

  20. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

    DEFF Research Database (Denmark)

    Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1......, patients uncontrolled on sulfonylurea monotherapy were divided into two HbA(1c) (A1C) arms: > or =8 to 9.5 to Patients were randomized to adjunctive premeal INH (n = 225) or metformin (n = 202). The primary efficacy end point was change in A1C from......: In patients with type 2 diabetes poorly controlled on a sulfonylurea (A1C >9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated....

  1. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A

    1998-01-01

    cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development...... beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... of allospecific cytotoxic activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions....

  2. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence

    2012-01-01

    BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic/obstetri......BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic...... section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female...

  3. Gennemgang af en ny type hereditært angioødem med normal komplement C1-inhibitor

    DEFF Research Database (Denmark)

    Okholm-Hansen, Maria Bach; Winther, Anna Hillert; Fagerberg, Christina

    2018-01-01

    Hereditary angio-oedema (HAE) is a rare, potentially fatal disease characterized by recurrent swelling of skin and mucosa. Besides HAE with quantitative (type I) or qualitative (type II) deficiency of complement C1-inhibitor (C1-INH), a new subtype of HAE is now described with normal levels of C1......-INH. This subtype is possibly underdiagnosed, and a treatment regimen and general knowledge about the condition is still in its infancy. The purpose of this article is to inform Danish doctors about the disease to identify more Danish patients.......Hereditary angio-oedema (HAE) is a rare, potentially fatal disease characterized by recurrent swelling of skin and mucosa. Besides HAE with quantitative (type I) or qualitative (type II) deficiency of complement C1-inhibitor (C1-INH), a new subtype of HAE is now described with normal levels of C1...

  4. Program of home telemonitoring in patients with cystic fibrosis over a period of 2 years: a contribution to the rationalization of care.

    Science.gov (United States)

    Bella, S; Murgia, F; Cotognini, C; Alghisi, F; Montemitro, E

    2013-01-01

    In present study we tested the possible presence of a saving for Italian National Health Service (INHS) when using telemonitoring in the follow-up at home of patients with Cystic Fibrosis (CF), in the aim to assess the possible role of Telemedicine in rationalization of hospital admissions. We performed an economic analysis of the costs incurred by the INHS for patients with CF followed at home by telemonitoring, recalled to hospital under suspicion or diagnosis of acute pulmonary recurrence. We calculated, for 19 patients retrieved in the period of the study, a total saving compared to traditional home care of € 132.144,91 in 24 months, corresponding to € 3.303,62/year/patient. The presence of an economic advantage for the INHS is confirmed once again, although not significant. The data from this study are encouraging regarding the possible role of telemedicine in the organization of homecare of CF patients.

  5. Generating highly polarized nuclear spins in solution using dynamic nuclear polarization

    DEFF Research Database (Denmark)

    Wolber, J.; Ellner, F.; Fridlund, B.

    2004-01-01

    A method to generate strongly polarized nuclear spins in solution has been developed, using Dynamic Nuclear Polarization (DNP) at a temperature of 1.2K, and at a field of 3.354T, corresponding to an electron spin resonance frequency of 94GHz. Trityl radicals are used to directly polarize 13C...... and other low-γ nuclei. Subsequent to the DNP process, the solid sample is dissolved rapidly with a warm solvent to create a solution of molecules with highly polarized nuclear spins. Two main applications are proposed: high-resolution liquid state NMR with enhanced sensitivity, and the use...

  6. Cluster formation restricts dynamic nuclear polarization of xenon in solid mixtures

    DEFF Research Database (Denmark)

    Kuzma, N. N.; Pourfathi, M.; Kara, H.

    2012-01-01

    During dynamic nuclear polarization (DNP) at 1.5 K and 5 T, Xe-129 nuclear magnetic resonance (NMR) spectra of a homogeneous xenon/1-propanol/trityl-radical solid mixture exhibit a single peak, broadened by H-1 neighbors. A second peak appears upon annealing for several hours at 125 K. Its charac....... Subsequent DNP system modifications designed to reduce the overheating resulted in four-fold increase of Xe-129 polarization, from 5.3% to 21%. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4751021]...

  7. Real-time cardiac metabolism assessed with hyperpolarized [1-13C]acetate in a large-animal model

    DEFF Research Database (Denmark)

    Flori, Alessandra; Liserani, Matteo; Frijia, Francesca

    2015-01-01

    Dissolution-dynamic nuclear polarization (dissolution-DNP) for magnetic resonance (MR) spectroscopic imaging has recently emerged as a novel technique for noninvasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra- and intracellular short-chain fatty...... acid, we focused on [1-13C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution-DNP procedure of Na[1-13C]acetate for in vivo cardiac applications with a 3 T MR scanner was optimized in pigs during bolus injection of doses of up...

  8. Synthesis of Long-T1 Silicon Nanoparticles for Hyperpolarized 29Si Magnetic Resonance Imaging

    Science.gov (United States)

    Atkins, Tonya M.; Cassidy, Maja C.; Lee, Menyoung; Ganguly, Shreyashi; Marcus, Charles M.; Kauzlarich, Susan M.

    2013-01-01

    We describe the synthesis, materials characterization and dynamic nuclear polarization (DNP) of amorphous and crystalline silicon nanoparticles for use as hyperpolarized magnetic resonance imaging (MRI) agents. The particles were synthesized by means of a metathesis reaction between sodium silicide (Na4Si4) and silicon tetrachloride (SiCl4) and were surface functionalized with a variety of passivating ligands. The synthesis scheme results in particles of diameter ~10 nm with long size-adjusted 29Si spin lattice relaxation (T1) times (> 600 s), which are retained after hyperpolarization by low temperature DNP. PMID:23350651

  9. Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

    Directory of Open Access Journals (Sweden)

    Tadashi Watabe

    Full Text Available PURPOSE: Acetylcholinesterase (AChE inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11C-Donepezil (DNP and the AChE activity in the normal rat, with special focus on the adrenal glands. METHODS: The distribution of (11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g. A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11C-DNP (45.0 ± 10.7 MBq. The whole-body distribution of the (11C-DNP PET was evaluated based on the Vt (total distribution volume by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. RESULTS: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11C-DNP in the body (following the liver (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3, respectively, indicating that the distribution of (11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively, indicating high activity of AChE in the adrenal glands. CONCLUSIONS: We demonstrated the whole-body distribution of (11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

  10. ACE variants interact with the RAS pathway to confer risk and protection against type 2 diabetic nephropathy.

    Science.gov (United States)

    Ahluwalia, Tarunveer Singh; Ahuja, Monica; Rai, Taranjit Singh; Kohli, Harbir Singh; Bhansali, Anil; Sud, Kamal; Khullar, Madhu

    2009-03-01

    Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Among candidate genes examined for susceptibility to diabetic nephropathy, angiotensin-converting enzyme (ACE) gene has been found to be associated with pathogenesis and progression of diabetic nephropathy. However, the role of other renin-angiotensin system (RAS) polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Recent studies also show that ACE haplotypes may be better predictors to disease susceptibility. Thus, in the present study, we evaluated the association of ACE haplotypes and the interactions of ACE, angiotensinogen (AGT), and angiotensin II receptor type I (AGTR1) gene polymorphisms with DNP in Asian Indians. We genotyped seven variants of the RAS pathway genes (ACE, AGT, and AGTR1) in type 2 diabetic cohorts without nephropathy (DM) and with nephropathy (DNP), using allele-specific oligonucleotide-PCR, and PCR-restriction fragment length polymorphism assays. We studied the interaction of these variants with each other and ACE I/D polymorphism. Frequency of ACE D allele and DD genotype (ACE I/D) was significantly higher in DNP (p < 0.005) and was associated with increased risk of nephropathy. The frequency of T allele, MT/TT genotypes (AGT: M235T), and C allele 1166CC genotype (AGTR1: A1166C) was higher and associated with increased risk of DNP (235T, p < 0.0001; 235TT/MT, p < 0.01; 1166C, p < 0.007; 1166CC, p < 0.0001). The ACE locus revealed a near doubling in the prevalence of T-D-G risk haplotype (odds ratio, 1.76) in DNP (0.13) compared to DM (0.08; p < 0.02). ACE haplotypes carrying the I allele were associated with a lower risk of DNP (C-I-A, p < 0.04; C-I-G, p < 0.008). ACE ID/DD genotypes in combination with ACE rs4311, rs4343, and AGT rs699 mutant genotypes increased the risk of DNP development fourfold (p < 0.01). This study provides the first evidence for a disease

  11. Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning.

    Science.gov (United States)

    Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

    2017-03-30

    A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Strategic Planning and Doctor Of Nursing Practice Education: Developing Today's and Tomorrow's Leaders.

    Science.gov (United States)

    Falk, Nancy L; Garrison, Kenneth F; Brown, Mary-Michael; Pintz, Christine; Bocchino, Joseph

    2015-01-01

    Strategic planning and thinking skills are essential for today's nurse leaders. Doctor of nursing practice (DNP) programs provide an opportunity for developing effective nurse strategists. A well-designed strategy course can stimulate intellectual growth at all levels of Bloom's Taxonomy. Discussion forums in online education provide new opportunities for rich interaction among peers en route to development of well-informed strategic plans. An interprofessional perspective adds a rich and vital aspect to doctoral nursing education and it serves to inform strategic plan development. A roadmap for teaching strategic planning to current and future nursing leaders will guide the integration of essential content into DNP programs.

  13. Student Engagement in Online Nursing Courses.

    Science.gov (United States)

    Hampton, Debra; Pearce, Patricia F

    The purposes of this study were to determine the level of engagement of registered nurse (RN) to Bachelor of Science in Nursing (BSN), Master of Science in Nursing (MSN), and Doctor of Nursing Practice (DNP) nursing students enrolled in online nursing degree programs and to understand whether there are generational differences in level of student engagement. Significant differences were noted for engagement level between generations of students, but no significant difference was noted in the engagement level of students from RN to BSN, MSN, or DNP programs.

  14. Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

    Science.gov (United States)

    Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

    2014-01-01

    Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11)C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. The distribution of (11)C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11)C-DNP (45.0 ± 10.7 MBq). The whole-body distribution of the (11)C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11)C-DNP in the body (following the liver) (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3), respectively), indicating that the distribution of (11)C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. We demonstrated the whole-body distribution of (11)C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11)C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

  15. Prevention of isoniazid toxicity by NAT2 genotyping in Senegalese tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Dr.. A. Toure

    2016-01-01

    Full Text Available Isoniazid (INH, recommended by WHO (World Health Organization in the treatment of tuberculosis (TB, is metabolized primarily by the genetically polymorphic N-acetyltransferase 2 (NAT2 enzyme. The human population is divided into three different phenotypic groups according to acetylation rate: slow, intermediate, and fast acetylators. The objective of this study was to explore the relationship between NAT2 genotypes and the serum concentrations of INH. Blood samples from 96 patients with TB were taken for the analysis. NAT2 polymorphisms on coding region were examined by polymerase chain reaction (PCR direct sequencing; the acetylation status was obtained by measuring isoniazid (INH and its metabolite, acetylisoniazid (AcINH in plasma was obtained by using the liquid chromatography coupled to mass spectrometry. TB patients were distributed into two groups of fast and slow acetylators according to the acetylation index calculated based on the plasma concentration of INH in the 3rd hour (T3 after an oral dose. Our PCR analysis identified several alleles, where NAT2*4, NAT2*5A, NAT2*6A, and NAT2*13A were the most important. The concentrations of INH varied between 1.10 mg/L and 13.10 mg/L at the 3rd hour and between 0.1 and 9.5 mg/L at the 6th hour. The use of the acetylating index I3 allowed the classification of tested patients into two phenotypic groups: slow acetylators (44.3% of TB patients, and rapid acetylators (55.7%. Patient’s acetylation profile provides valuable information on their therapeutic, pharmacological, and toxicological responses.

  16. Diagnosis and screening of patients with hereditary angioedema in primary care

    Science.gov (United States)

    Henao, Maria Paula; Kraschnewski, Jennifer L; Kelbel, Theodore; Craig, Timothy J

    2016-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients. PMID:27194914

  17. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Castelli, Roberto

    2016-02-01

    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.

  18. Effect of C1-Esterase-inhibitor in angiotensin-converting enzyme inhibitor-induced angioedema.

    Science.gov (United States)

    Greve, Jens; Bas, Murat; Hoffmann, Thomas K; Schuler, Patrick J; Weller, Patrick; Kojda, Georg; Strassen, Ulrich

    2015-06-01

    The study objective was to generate pilot data to evaluate the effectiveness and safety of C1-esterase-inhibitor concentrate (C1-INH) compared to standard treatment in patients with angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema affecting the upper aerodigestive tract. Proof-of-concept case series with historical control. Adult patients with angioedema in the upper aerodigestive tract presenting to the emergency department were included. After establishing the diagnosis of ACEi-induced angioedema based on patient history and thorough clinical examination, all patients were administered 1,000 international units (IU) of C1-INH intravenously. A historical control group consisting of adult patients with ACEi-induced angioedema who had been treated with intravenous corticosteroids and antihistamines at the same institution over the past 8 years was used for comparison. The most important parameters assessed were the time to complete resolution of symptoms and the need for intubation or tracheotomy. Ten patients were included in the C1-INH group and 47 in the corticosteroid/antihistamine group. The time to complete resolution of symptoms was considerably longer in the historical control group (33.1 ± 19.4 hours) than in the C1-INH group (10.1 ± 3.0 hours). No intubation or tracheotomy was needed in the C1-INH group (0/10 patients), whereas three out of the 47 historical controls required tracheotomy and two were intubated (5/47). The results suggest a role for C1-INH as an effective and safe therapeutic option in patients with ACEi-induced angioedema, which needs to be confirmed by further larger and double-blinded studies. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Preparation and characterization of magnetic Fe{sub 3}O{sub 4}–chitosan nanoparticles loaded with isoniazid

    Energy Technology Data Exchange (ETDEWEB)

    Qin, H.; Wang, C.M.; Dong, Q.Q. [School of Chemistry and Materials Science, Nanjing Normal University Nanjing, Jiangsu 210097 (China); Zhang, L.; Zhang, X. [Nanjing Chest Hospital, Jiangsu 210097 (China); Ma, Z.Y., E-mail: 07197@njnu.edu.cn [School of Chemistry and Materials Science, Nanjing Normal University Nanjing, Jiangsu 210097 (China); Han, Q.R. [School of Chemistry and Materials Science, Nanjing Normal University Nanjing, Jiangsu 210097 (China)

    2015-05-01

    A novel and simple method has been proposed to prepare magnetic Fe{sub 3}O{sub 4}–chitosan nanoparticles loaded with isoniazid (Fe{sub 3}O{sub 4}/CS/INH nanocomposites). Efforts have been made to develop isoniazid (INH) loaded chitosan (CS) nanoparticles by ionic gelation of chitosan with tripolyphosphate (TPP). The factors that influence the preparation of chitosan nanoparticles, including the TPP concentration, the chitosan/TPP weight ratio and the chitosan concentration on loading capacity and encapsulation efficiency of chitosan nanoparticles were studied. The magnetic Fe{sub 3}O{sub 4} nanoparticles were prepared by co-precipitation method of Fe{sup 2+} and Fe{sup 3+}. Then the magnetic Fe{sub 3}O{sub 4}/CS/INH nanocomposites were prepared by ionic gelation method. The magnetic Fe{sub 3}O{sub 4} nanoparticles and magnetic Fe{sub 3}O{sub 4}/CS/INH nanocomposites were characterized by XRD, TEM, FTIR and SQUID magnetometry. The in vitro release of Fe{sub 3}O{sub 4}/CS/INH nanocomposites showed an initial burst release in the first 10 h, followed by a more gradual and sustained release for 48 h. It is suggested that the magnetic Fe{sub 3}O{sub 4}/CS/INH nanocomposites may be exploited as potential drug carriers for controlled-release applications in magnetic targeted drugs delivery system. - Highlights: • A novel and simple method for preparation of nanocomposites for biomedicine. • All the materials are non-toxic and biocompatibility. • This paper gives systematic study of the nanocomposites in biomedicine.

  20. Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors.

    Science.gov (United States)

    Honda-Ogawa, Mariko; Ogawa, Taiji; Terao, Yutaka; Sumitomo, Tomoko; Nakata, Masanobu; Ikebe, Kazunori; Maeda, Yoshinobu; Kawabata, Shigetada

    2013-05-31

    Streptococcus pyogenes is an important human pathogen that causes invasive diseases such as necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome. We investigated the function of a major cysteine protease from S. pyogenes that affects the amount of C1-esterase inhibitor (C1-INH) and other complement factors and aimed to elucidate the mechanism involved in occurrence of streptococcal toxic shock syndrome from the aspect of the complement system. First, we revealed that culture supernatant of a given S. pyogenes strain and recombinant SpeB degraded the C1-INH. Then, we determined the N-terminal sequence of the C1-INH fragment degraded by recombinant SpeB. Interestingly, the region containing one of the identified cleavage sites is not present in patients with C1-INH deficiency. Scanning electron microscopy of the speB mutant incubated in human serum showed the abnormal superficial architecture and irregular oval structure. Furthermore, unlike the wild-type strain, that mutant strain showed lower survival capacity than normal as compared with heat-inactivated serum, whereas it had a significantly higher survival rate in serum without the C1-INH than in normal serum. Also, SpeB degraded multiple complement factors and the membrane attack complex. Flow cytometric analyses revealed deposition of C9, one of the components of membrane the attack complex, in greater amounts on the surface of the speB mutant, whereas lower amounts of C9 were bound to the wild-type strain surface. These results suggest that SpeB can interrupt the human complement system via degrading the C1-INH, thus enabling S. pyogenes to evade eradication in a hostile environment.

  1. Functional, thermodynamics, structural and biological studies of in silico-identified inhibitors of Mycobacterium tuberculosis enoyl-ACP(CoA) reductase enzyme

    Science.gov (United States)

    Martinelli, Leonardo K. B.; Rotta, Mariane; Villela, Anne D.; Rodrigues-Junior, Valnês S.; Abbadi, Bruno L.; Trindade, Rogério V.; Petersen, Guilherme O.; Danesi, Giuliano M.; Nery, Laura R.; Pauli, Ivani; Campos, Maria M.; Bonan, Carla D.; de Souza, Osmar Norberto; Basso, Luiz A.; Santos, Diogenes S.

    2017-04-01

    Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy. van’t Hoff analyses of ligand binding to MtInhA:NADH provided the thermodynamic signatures of non-covalent interactions (ΔH°, ΔS°, ΔG°). Phenotypic screening showed that five compounds inhibited in vitro growth of M. tuberculosis H37Rv strain. Labio_16 and Labio_17 compounds also inhibited the in vitro growth of PE-003 multidrug-resistant strain. Cytotoxic effects on Hacat, Vero and RAW 264.7 cell lines were assessed for the latter two compounds. The Labio_16 was bacteriostatic and Labio_17 bactericidal in an M. tuberculosis-infected macrophage model. In Zebrafish model, Labio_16 showed no cardiotoxicity whereas Labio_17 showed dose-dependent cardiotoxicity. Accordingly, a model was built for the MtInhA:NADH:Labio_16 ternary complex. The results show that the Labio_16 compound is a direct inhibitor of MtInhA, and it may represent a hit for the development of chemotherapeutic agents to treat TB.

  2. Presence of C1-Inhibitor Polymers in a Subset of Patients Suffering from Hereditary Angioedema

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Hansen, Søren Werner Karlskov; Gram, Jørgen Brodersen

    2014-01-01

    phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del),and one mutation...... affected helix C (p.Thr167Asn). In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients....

  3. Evaluation of nano encapsulation techniques in different polymeric system for the delivery of anti-tuberculosis drugs (ATD)

    CSIR Research Space (South Africa)

    Swai, H

    2006-02-01

    Full Text Available .5,6,7,8,9,10,11 The TB nano drug delivery project’s primary objective is, therefore, to develop a home grown TB nano drug delivery system that will address non compliance and MDR-TB. This will significantly contribute to the saving of lives, while...-Chitosan system SEM results Observations The INH-encapsulated alginate/chitosan showed irregular particle shapes with sizes in the nanometre scale. The particles further showed some degree of agglomeration. Alginate (mg) Chitosan (mg) INH (mg) Tin /Tout...

  4. Factor XII-independent activation of the bradykinin-forming cascade

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

    2013-01-01

    . Prolonged incubation of plasma deficient in both factor XII and C1-INH led to conversion of prekallikrein to kallikrein and cleavage of HK, as was seen in plasma from patients with hereditary angioedema but not plasma from healthy subjects. CONCLUSIONS: These results indicate that C1-INH stabilizes...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...

  5. Brazilian energy overview

    International Nuclear Information System (INIS)

    Souza, J.A.M. de.

    1975-01-01

    The Brazilian energy overview compared with the rest of the world is presented, as well as the current situation and prospects for the future. In a first part, the evalution from the past through the present time is considered, and in a second part, attention is given on the future prospects for Brazil and the different countries in connection with the energy field. It is expected that the current per capita energy consumption in Brazil, in all of its various forms, now totalling 6 million kcal/inh, will reach at least 22 million kcal/inh toward the end of this century

  6. Temperature dependence of cross-effect dynamic nuclear polarization in rotating solids

    DEFF Research Database (Denmark)

    Geiger, Michel-Andreas; Orwick-Rydmark, Marcella; Märker, Katharina

    2016-01-01

    Dynamic nuclear polarization exploits electron spin polarization to boost signal-to-noise in magic-angle-spinning (MAS) NMR, creating new opportunities in materials science, structural biology, and metabolomics studies. Since protein NMR spectra recorded under DNP conditions can show improved...

  7. Simulation and Advanced Practice Nursing Education

    Science.gov (United States)

    Blue, Dawn I.

    2016-01-01

    This quantitative study compared changes in level of confidence resulting from participation in simulation or traditional instructional methods for BSN (Bachelor of Science in Nursing) to DNP (Doctor of Nursing Practice) students in a nurse practitioner course when they entered the clinical practicum. Simulation has been used in many disciplines…

  8. Investigating the Tolerance of Tomato (Lycopersicon esculentum Cultivars to Broomrape (Orobanche aegyptiaca pers in Khorassan Razavi

    Directory of Open Access Journals (Sweden)

    M. Zafarian,

    2014-03-01

    Full Text Available To investigate the tolerance of tomato cultivars to Egyptian broomrape (Orobanche aegyptiaca pers., an experiment was conducted in a randomized complete block design with 11 treatments and 3 replications in mazrae Nemoune Astan Quds Razavi in Mashhad, Iran, 2012. Treatment were 11 varieties (Peto early CH, Sterling (Karon, Khorram, Petorak, DNP 3005, PS 6515, SPEEDY, IDEN, VADI STAR, FIRINZEH and DNP 3001 which were transplanted in the field along with broomrape. Sampling was done at two stages: 1- after appearance and establishment of broomrape on tomato root where the dry weight, stem number and node numbers of broomrape on tomato root and tomato dry weight were measured and 2- at the end of growing season where tomato fruit weight and its yield were determined. Result indicated that Sterling and Khorram cultivars did have the least broomrape dry weight, stem number and node numbers of broomrape on tomato root and while produced highest plant dry weight, fruit and yield as compared to the other cultivars. Thus, may be considered as tolerant cultivars. Petorak and DNP 3001 on the other hand, presented the most broomrape dry weight, stem number and node number on tomato root. However, Petorak, Peto early CH and FIRINZEH cultivars produced the least plant weight, fruit and yield and thus, they can be called the sensitive cultivars. DNP 3001 being highly attacked by broomrape produced increased fruit yield and therefore compensated its ill effects.

  9. Doctor of Professional Counseling: The Next Step

    Science.gov (United States)

    Southern, Stephen; Cade, Rochelle; Locke, Don W.

    2012-01-01

    Professional doctorates have been established in the allied health professions by clinicians seeking the highest levels of independent practice. Allied health professional doctorates include nursing practice (DNP), occupational therapy (OTD), psychology (PsyD), social work (DSW), and marriage and family therapy (DMFT). Lessons learned from the…

  10. Fundamental Aspects of Single Molecule and Zeptomole Electroanalysis

    Science.gov (United States)

    2018-04-01

    the Hg UME, fNP is the frequency of NP impacts at a given NP concentration (CNP), NA is Avogadro’s number, DNP is the NP diffusion coefficient, and...strength, which correlates to the same general trend of NP concentration as monitored by NTA. For a stable dispersed colloid, fNP should increase

  11. The influence of administrative leadership: an interview with Dr Karen S. Hill.

    Science.gov (United States)

    Hill, Karen S; Adams, Jeffrey M

    2015-01-01

    This department highlights nursing leaders who have demonstrated a commitment to patient care leadership and innovation in practice, policy, research, education, and theory. This interview profiles Karen Hill, DNP, RN, NEA-BC, FACHE, FAAN, chief operating officer and chief nursing officer of Baptist Health in Lexington, Kentucky, and editor-in-chief of the Journal of Nursing Administration.

  12. Electrically tunable dynamic nuclear spin polarization in GaAs quantum dots at zero magnetic field

    Science.gov (United States)

    Manca, M.; Wang, G.; Kuroda, T.; Shree, S.; Balocchi, A.; Renucci, P.; Marie, X.; Durnev, M. V.; Glazov, M. M.; Sakoda, K.; Mano, T.; Amand, T.; Urbaszek, B.

    2018-04-01

    In III-V semiconductor nano-structures, the electron and nuclear spin dynamics are strongly coupled. Both spin systems can be controlled optically. The nuclear spin dynamics are widely studied, but little is known about the initialization mechanisms. Here, we investigate optical pumping of carrier and nuclear spins in charge tunable GaAs dots grown on 111A substrates. We demonstrate dynamic nuclear polarization (DNP) at zero magnetic field in a single quantum dot for the positively charged exciton X+ state transition. We tune the DNP in both amplitude and sign by variation of an applied bias voltage Vg. Variation of ΔVg on the order of 100 mV changes the Overhauser splitting (nuclear spin polarization) from -30 μeV (-22%) to +10 μeV (+7%) although the X+ photoluminescence polarization does not change sign over this voltage range. This indicates that absorption in the structure and energy relaxation towards the X+ ground state might provide favourable scenarios for efficient electron-nuclear spin flip-flops, generating DNP during the first tens of ps of the X+ lifetime which is on the order of hundreds of ps. Voltage control of DNP is further confirmed in Hanle experiments.

  13. Tunable 13C/1H dual channel matching circuit for dynamic nuclear polarization system with cross-polarization

    DEFF Research Database (Denmark)

    Rybalko, Oleksandr; Bowen, Sean; Zhurbenko, Vitaliy

    2016-01-01

    In this paper we report initial results of design and practical implementation of tuning and matching circuit to estimate a performance of Dynamic Nuclear Polarization (DNP) at a magnetic field of 6.7 T. It is shown that developed circuit for signal observation is compact, easy to make and provides...

  14. Electron paramagnetic resonance and dynamic nuclear polarization of char suspensions: surface science and oximetry

    DEFF Research Database (Denmark)

    Clarkson, R B; Odintsov, B M; Ceroke, P J

    1998-01-01

    ; they can be calibrated and used for oximetry. Biological stability and low toxicity make chars good sensors for in vivo measurements. Scalar and dipolar interactions of water protons at the surfaces of chars may be utilized to produce dynamic nuclear polarization (DNP) of the nuclear spin population...

  15. Stable isotope-resolved analysis with quantitative dissolution dynamic nuclear polarization

    DEFF Research Database (Denmark)

    Lerche, Mathilde Hauge; Yigit, Demet; Frahm, Anne Birk

    2018-01-01

    Metabolite profiles and their isotopomer distributions can be studied non-invasively in complex mixtures with NMR. The advent of dissolution Dynamic Nuclear Polarization (dDNP) and isotope enrichment add sensitivity and resolution to such met-abolic studies. Metabolic pathways and networks can...

  16. Flexibility and conformational change of IgG molecule

    International Nuclear Information System (INIS)

    Alpert, Y.; Ostanevich, Yu.M.

    1982-12-01

    The dynamic behaviour of pig anti-Dnp-immunoglobulin (IgG) investigated by the neutron spin echo technique gave evidence of internal motion of a biological macromolecule. It is suggested that this motion belongs to the wobbling of the Fab parts of the investigated IgG molecule around its so called hinge region. (author)

  17. Studies of interactions between the receptor for immunoglobulin E and other cellular components during signal transduction

    International Nuclear Information System (INIS)

    Estes, K.A.S.

    1988-01-01

    The high affinity receptor for immunoglobulin E (IgE) on rat basophilic leukemia (RBL) cells mediates antigen-triggered cellular degranulation. As a first step in developing a reconstitution system to test the structural requirements of receptors for triggering cellular degranulation, polyethylene glycol-induced membrane fusion methods were used to introduce exogenous IgE receptors into living RBL cells. In cell-cell fusion experiments, RBL cells with rat IgE bound to receptors and containing [5-1,2- 3 H(N)]hydroxytryptamine binoxalate ([ 3 H]5HT) in their secretory granules were fused to cells with receptors occupied by anti-dinitrophenyl (DNP) mouse IgE. [ 3 H]5HT release could be triggered specifically by multivalent DNP antigen. In vesicle-cell fusion experiments, plasma membrane vesicles with receptors occupied by anti-DNP mouse IgE were fused with RBL cells, and DNP antigen was found to trigger [ 3 H]5HT release. Receptors for IgE in reformed vesicles, prepared by solubilizing vesicles and removing the detergent, could also be fused into cells and mediate the stimulation of [ 3 H]5HT release

  18. Theory of coherent dynamic nuclear polarization in quantum dots

    DEFF Research Database (Denmark)

    Neder, Izhar; Rudner, Mark Spencer; Halperin, Bertrand

    2014-01-01

    We consider the production of dynamic nuclear spin polarization (DNP) in a two-electron double quantum dot, in which the electronic levels are repeatedly swept through a singlet-triplet avoided crossing. Our analysis helps to elucidate the intriguing interplay between electron-nuclear hyperfine...

  19. Cluster formation restricts dynamic nuclear polarization of xenon in solid mixtures.

    Science.gov (United States)

    Kuzma, N N; Pourfathi, M; Kara, H; Manasseh, P; Ghosh, R K; Ardenkjaer-Larsen, J H; Kadlecek, S J; Rizi, R R

    2012-09-14

    During dynamic nuclear polarization (DNP) at 1.5 K and 5 T, (129)Xe nuclear magnetic resonance (NMR) spectra of a homogeneous xenon/1-propanol/trityl-radical solid mixture exhibit a single peak, broadened by (1)H neighbors. A second peak appears upon annealing for several hours at 125 K. Its characteristic width and chemical shift indicate the presence of spontaneously formed pure Xe clusters. Microwave irradiation at the appropriate frequencies can bring both peaks to either positive or negative polarization. The peculiar time evolution of (129)Xe polarization in pure Xe clusters during DNP can be modelled as an interplay of spin diffusion and T(1) relaxation. Our simple spherical-cluster model offers a sensitive tool to evaluate major DNP parameters in situ, revealing a severe spin-diffusion bottleneck at the cluster boundaries and a significant sample overheating due to microwave irradiation. Subsequent DNP system modifications designed to reduce the overheating resulted in four-fold increase of (129)Xe polarization, from 5.3% to 21%.

  20. Self-assessment of nursing informatics competencies for doctor of nursing practice students.

    Science.gov (United States)

    Choi, Jeungok; Zucker, Donna M

    2013-01-01

    This study examined the informatics competencies of doctor of nursing practice (DNP) students and whether these competencies differed between DNP students in the post-baccalaureate (BS) and post-master's (MS) tracks. Self-reported informatics competencies were collected from 132 DNP students (68 post-BS and 64 post-MS students) in their first year in the program (2007 to 2010). Students were assessed in 18 areas of 3 competency categories: computer skills, informatics knowledge, and informatics skills. Post-BS students were competent in 4 areas (computer skills in communication, systems, documentation, and informatics knowledge about impact of information management), whereas post-MS students were competent in only 1 area (computer skills in communication). Students in both tracks reported computer skills in decision support as their least competent area. Overall, post-BS students reported slightly higher than or similar competency scores as post-MS students, but scores were statistically significant in only 3 of 18 areas. The assessment indicated that knowledge and skills on informatics competencies need to be improved, especially in computer skills for data access and use of decision support systems. Strategies are suggested to integrate competencies into existing informatics course and DNP curricula. Further studies are recommended using an objective measure of informatics competencies. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Adaptation to a Curriculum Delivered via iPad: The Challenge of Being Early Adopters

    Science.gov (United States)

    Stec, Melissa; Bauer, Melanie; Hopgood, Daniel; Beery, Theresa

    2018-01-01

    This convergent mixed methods study was designed to examine the skills and attitudes toward using an iPad to deliver nursing curriculum and enhance active learning strategies for sophomore Bachelor of Science in Nursing (BSN) and Doctor of Nursing Practice (DNP) students at a Midwestern university. Quantitative data were collected using an…

  2. Restoring Penis Sensation in Patients With Low Spinal Cord Lesions: The Role of the Remaining Function of the Dorsal Nerve in a Unilateral or Bilateral TOMAX Procedure

    NARCIS (Netherlands)

    Overgoor, Max L. E.; Braakhekke, Jan P.; Kon, Moshe; de Jong, Tom P. V. M.

    2015-01-01

    Aims: The recently developed TOMAX-procedure restores unilateral genital sensation, improving sexual health in men with a low spinal lesion (LSL). It connects one dorsal nerve of the penis (DNP) to the intact ipsilateral ilioinguinal nerve. We proposed bilateral neurotization for full sensation of

  3. Dynamic nuclear polarization in perfluorodimethylcyclohexane doped with a perfluoralkyl free radical

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Bubnov, N.N. [A.N. Nesmeyanov Inst. of Organo-element Compounds, Russian Acad. of Sci., Moscow (Russian Federation); Bunyatova, E.I. [Joint Inst. for Nuclear Research, Dubna (Russian Federation); Hautle, P. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Konter, J.A. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Mango, S. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Solodovnikov, S.P. [A.N. Nesmeyanov Inst. of Organo-element Compounds, Russian Acad. of Sci., Moscow (Russian Federation); Tumanski, B.L. [A.N. Nesmeyanov Inst. of Organo-element Compounds, Russian Acad. of Sci., Moscow (Russian Federation)

    1995-03-01

    First results of DNP at 2.5 T and below 0.3 K in F-dimethylcyclohexane (C{sub 8}F{sub 16}), doped with F-2,4-dimethyl-3-ethyl-3-pentyl (C{sub 9}F{sub 19}), are presented. A polarization of the {sup 19}F-nuclei of up to 54% was obtained. ((orig.))

  4. Dynamic nuclear polarization in perfluorodimethylcyclohexane doped with a perfluoralkyl free radical

    Science.gov (United States)

    van den Brandt, B.; Bubnov, N. N.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.; Solodovnikov, S. P.; Tumanski, B. L.

    1995-02-01

    First results of DNP at 2.5 T and below 0.3 K in F-dimethylcyclohexane (C 8F 16), doped with F-2,4-dimethyl-3-ethyl-3-pentyl (C 9F 19), are presented. A polarization of the 19F-nuclei of up to 54% was obtained.

  5. An approach to clinical data management for the doctor of nursing practice curriculum.

    Science.gov (United States)

    Sylvia, Martha; Terhaar, Mary

    2014-01-01

    Strong data management skills are essential to doctor of nursing practice (DNP) education and necessary for DNP practice. Completion of the DNP scholarly project requires application of these skills to understand and address a complex practice, process, or systems problem; develop, implement, and monitor an innovative evidence-based intervention to address that problem; and evaluate the outcomes. The purposes of this paper were to describe the demand and context for clinical data management (CDM) within the DNP curriculum; provide an overview of CDM content; describe the process for content delivery; propose a set of course objectives; and describe initial successes and challenges. A two-pronged approach of consultation and a CDM course were developed. Students who participated in this approach were more likely to create and implement an evaluation plan; apply techniques for data cleansing and manipulation; apply concepts of sample size determination using power analysis; use exploratory data analysis techniques to understand population attributes and sampling bias; apply techniques to adjust for bias; apply statistical significance testing; and present project results in a meaningful way. On the basis of this evaluation, CDM has evolved from an elective to a required course integrated in a thread that crosses the entire curriculum. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. 75 FR 6635 - Foreign-Trade Zone 33-Pittsburgh, Pennsylvania, Expansion of Manufacturing Authority, Subzone 33E...

    Science.gov (United States)

    2010-02-10

    ..., Pennsylvania, Expansion of Manufacturing Authority, Subzone 33E--DNP IMS America Corporation (Thermal Transfer Ribbon Printer Rolls), Mount Pleasant, Pennsylvania An application has been submitted to the Foreign... Pennsylvania, grantee of FTZ 33, requesting an expansion of the scope of manufacturing authority approved...

  7. Recycling and imaging of nuclear singlet hyperpolarization

    DEFF Research Database (Denmark)

    Pileio, Giuseppe; Bowen, Sean; Laustsen, Christoffer

    2013-01-01

    observation of the same batch of polarized nuclei over a period of 30 min and more. We report a recycling protocol in which the enhanced nuclear polarization achieved by dissolution-DNP is observed with full intensity and then returned to singlet order. MRI experiments may be run on a portion of the available...

  8. Effects of curcumin on TTX-R sodium currents of dorsal root ganglion neurons in type 2 diabetic rats with diabetic neuropathic pain.

    Science.gov (United States)

    Meng, Bo; Shen, Lu-Lu; Shi, Xiao-Ting; Gong, Yong-Sheng; Fan, Xiao-Fang; Li, Jun; Cao, Hong

    2015-09-25

    Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. 78 FR 42788 - American Indians Into Nursing; Notice of Competitive Grant Applications for American Indians Into...

    Science.gov (United States)

    2013-07-17

    ... individuals to be Registered Nurses (Associate Degree in Nursing (ADN), Bachelor of Science in Nursing (BSN..., and stipends for living expenses; (3) provide a program that encourages nurses (DNP, MSN, BSN, ADN) to... program agreements between Tribal colleges or universities so as to accommodate ADN to BSN, BSN to MSN...

  10. Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig

    International Nuclear Information System (INIS)

    Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

    1981-01-01

    Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses

  11. Evaluation of uptake and systemicity of 14C - fosthiazate in tomato (Lycopersicon esculentum L.)

    International Nuclear Information System (INIS)

    Mukherjee, Santanu; Srivastava, Anjana; Kumar, Surendra; Srivastava, P.C.

    2009-01-01

    Nematodes are round worm species that are found in almost all habitats. Beneficial species are usually referred to free living nematodes, other nematode species are parasitic and harmful to plants, animals and humans. Soil provides an excellent habitat for nematodes. Plant parasitic nematodes may live within plant roots or inhabit in the rhizosphere. The percent yield loss due to root knot nematodes in vegetable crops has been studied under All India Co-ordinated Research Project (Nematodes). The fosthiazate is a new compound incorporated in the market. The uptake and systemicity of fosthiazate in intact tomato plants was studied through 14 C-labeled fosthiazate in presence and absence of DNP. It was found that fosthiazate function as a systemic nematicide in tomato, the accumulation rate of fosthiazate was found higher in roots and shoots part upto 15 hrs. uptake period and after that accumulation slowly becomes saturated in the absence of DNP. In the presence of DNP (10 -2 mM) the amount of fosthiazate in roots as well as shoots was found to be decreased with respect to the uptake time.There was more inhibition on the uptake of fosthiazate in shoots than roots by DNP. (author)

  12. Frequency-agile gyrotron for electron decoupling and pulsed dynamic nuclear polarization

    Science.gov (United States)

    Scott, Faith J.; Saliba, Edward P.; Albert, Brice J.; Alaniva, Nicholas; Sesti, Erika L.; Gao, Chukun; Golota, Natalie C.; Choi, Eric J.; Jagtap, Anil P.; Wittmann, Johannes J.; Eckardt, Michael; Harneit, Wolfgang; Corzilius, Björn; Th. Sigurdsson, Snorri; Barnes, Alexander B.

    2018-04-01

    We describe a frequency-agile gyrotron which can generate frequency-chirped microwave pulses. An arbitrary waveform generator (AWG) within the NMR spectrometer controls the microwave frequency, enabling synchronized pulsed control of both electron and nuclear spins. We demonstrate that the acceleration of emitted electrons, and thus the microwave frequency, can be quickly changed by varying the anode voltage. This strategy results in much faster frequency response than can be achieved by changing the potential of the electron emitter, and does not require a custom triode electron gun. The gyrotron frequency can be swept with a rate of 20 MHz/μs over a 670 MHz bandwidth in a static magnetic field. We have already implemented time-domain electron decoupling with dynamic nuclear polarization (DNP) magic angle spinning (MAS) with this device. In this contribution, we show frequency-swept DNP enhancement profiles recorded without changing the NMR magnet or probe. The profile of endofullerenes exhibits a DNP profile with a <10 MHz linewidth, indicating that the device also has sufficient frequency stability, and therefore phase stability, to implement pulsed DNP mechanisms such as the frequency-swept solid effect. We describe schematics of the mechanical and vacuum construction of the device which includes a novel flanged sapphire window assembly. Finally, we discuss how commercially available continuous-wave gyrotrons can potentially be converted into similar frequency-agile high-power microwave sources.

  13. Analgesic and Antipyretic Activities of Drymaria cordata (Linn.) Willd ...

    African Journals Online (AJOL)

    Also, D. cordata produced significant (p<0.05) dose-dependent inhibition of temperature elevation in the 2,4-DNP and yeast-induced hyperthermia models with ... that the aqueous whole plant extract of Drymaria cordata possesses analgesic and antipyretic properties mediated through peripheral and central mechanisms.

  14. Untitled

    Indian Academy of Sciences (India)

    ,10-dihalo compounds) and their triplet formation. T Nakayama, K Ibuki and K Hamanoue ... Electron-nuclear cross-relaxation effect on the photochemical reaction of benzaldehyde as studied by CIDNP and DNP Y Yamakage,. Q Meng, S S Ali, ...

  15. Xestospongin C, a novel blocker of IP3 receptor, attenuates the increase in cytosolic calcium level and degranulation that is induced by antigen in RBL-2H3 mast cells

    Science.gov (United States)

    Oka, Tatsuya; Sato, Koichi; Hori, Masatoshi; Ozaki, Hiroshi; Karaki, Hideaki

    2002-01-01

    We evaluated the role of the cross-linking of FcεRI-mediated inositol 1,4,5-triphosphate (IP3) in the increase in cytosolic Ca2+ level ([Ca2+]i) using xestospongin C, a selective membrane permeable blocker of IP3 receptor, in RBL-2H3 mast cells. In the cells sensitized with anti-dinitrophenol (DNP) IgE, DNP-human serum albumin (DNP-HSA) and thapsigargin induced degranulation of β-hexosaminidase and a sustained increase in [Ca2+]i. Xestospongin C (3 – 10 μM) inhibited both of these changes that were induced by DNP-HSA without changing those induced by thapsigargin. In the absence of external Ca2+, DNP-HSA induced a transient increase in [Ca2+]i. Xestospongin C (3 – 10 μM) inhibited this increase in [Ca2+]i. In the cells permeabilized with β-escin, the application of IP3 decreased Ca2+ in the endoplasmic reticulum (ER) as evaluated by mag-fura-2. Xestospongin C (3 – 10 μM) inhibited the effect of IP3. After the depletion of Ca2+ stores due to stimulation with DNP-HSA or thapsigargin, the addition of Ca2+ induced capacitative calcium entry (CCE). Xestospongin C (3 – 10 μM) inhibited the DNP-HSA-induced CCE, whereas it did not affect the thapsigargin-induced CCE. These results suggest that FcεRI-mediated generation of IP3 contributes to Ca2+ release not only in the initial phase but also in the sustained phase of the increase in [Ca2+]i, resulting in prolonged Ca2+ depletion in the ER. The ER Ca2+ depletion may subsequently activate CCE to achieve a continuous [Ca2+]i increase, which is necessary for degranulation in the RBL-2H3 mast cells. Xestospongin C may inhibit Ca2+ release and consequently may attenuate degranulation. PMID:11959799

  16. Inhibition of oxidative phosphorylation for enhancing citric acid production by Aspergillus niger.

    Science.gov (United States)

    Wang, Lu; Zhang, Jianhua; Cao, Zhanglei; Wang, Yajun; Gao, Qiang; Zhang, Jian; Wang, Depei

    2015-01-16

    The spore germination rate and growth characteristics were compared between the citric acid high-yield strain Aspergillus niger CGMCC 5751 and A. niger ATCC 1015 in media containing antimycin A or DNP. We inferred that differences in citric acid yield might be due to differences in energy metabolism between these strains. To explore the impact of energy metabolism on citric acid production, the changes in intracellular ATP, NADH and NADH/NAD+ were measured at various fermentation stages. In addition, the effects of antimycin A or DNP on energy metabolism and citric acid production was investigated by CGMCC 5751. By comparing the spore germination rate and the extent of growth on PDA plates containing antimycin A or DNP, CGMCC 5751 was shown to be more sensitive to antimycin A than ATCC 1015. The substrate-level phosphorylation of CGMCC 5751 was greater than that of ATCC 1015 on PDA plates with DNP. DNP at tested concentrations had no apparent effect on the growth of CGMCC 5751. There were no apparent effects on the mycelial morphology, the growth of mycelial pellets or the dry cell mass when 0.2 mg L(-1) antimycin A or 0.1 mg L(-1) DNP was added to medium at the 24-h time point. The concentrations of intracellular ATP, NADH and NADH/NAD+ of CGMCC 5751 were notably lower than those of ATCC 1015 at several fermentation stages. Moreover, at 96 h of fermentation, the citric acid production of CGMCC 5751 reached up to 151.67 g L(-1) and 135.78 g L(-1) by adding 0.2 mg L(-1) antimycin A or 0.1 mg L(-1) DNP, respectively, at the 24-h time point of fermentation. Thus, the citric acid production of CGMCC 5751 was increased by 19.89% and 7.32%, respectively. The concentrations of intracellular ATP, NADH and NADH/NAD+ of the citric acid high-yield strain CGMCC 5751 were notably lower than those of ATCC 1015. The excessive ATP has a strong inhibitory effect on citric acid accumulation by A. niger. Increasing NADH oxidation and appropriately reducing the concentration of

  17. Poly(L-histidine) based copolymers: Effect of the chemically substituted L-histidine on the physio-chemical properties of the micelles and in vivo biodistribution.

    Science.gov (United States)

    Zhang, Xiaojun; Chen, Dawei; Ba, Shuang; Chang, Jing; Zhou, Jiaying; Zhao, Haixia; Zhu, Jia; Zhao, Xiuli; Hu, Haiyang; Qiao, Mingxi

    2016-04-01

    Even though the Poly(l-histidine) (PHis) based copolymers have been well studied, the effect of the chemically substituted l-histidine on the physio-chemical and biological properties of the micelles has never been elucidated to date. To address this issue, triblock copolymer of poly(ethylene glycol)-poly(D,L-lactide)-poly(2,4-dinitrophenol-L-histidine)(mPEG-b-PLA-b-DNP-PHis) with DNP group substituted to the saturated nitrogen of l-histidine were synthesized. The pH sensitive properties of the copolymer micelles were characterized using an acid-base titration method, fluorescene probe technique, DLS observation, in vitro drug release and cytotoxicity against MCF-7 cells under different pH conditions, respectively. The results suggest that mPEG-b-PLA-b-DNP-PHis copolymers showed similar micellar stability for DOX loaded micelles, increased particle size, and similar pH responsive properties with mPEG-b-PLA-b-PHis copolymers. The subcellular distribution observation demonstrated that mPEG-b-PLA-b-DNP-PHis micelles showed a slightly compromised endo-lysosmal escape of doxorubicin as compared to mPEG-b-PLA-b-PHis micelles. The mPEG-b-PLA-b-DNP-PHis micelles showed higher cellular uptake by MCF-7 cells than mPEG-b-PLA-b-PHis micelles due to the different uptake pathways. Effect of DNP substitution on the in vivo distribution of the copolymer micelles was studied using non-invasive near-infrared fluorescence (NIRF) imaging with mPEG-b-PLA-b-PHis micelles as control. The results indicate that the mPEG-b-PLA-b-DNP-PHis micelles showed a reduced passive targeting to the tumor due to the larger particle size. These results suggest that saturated nitrogen of PHis may serve as a valuable site for chemical modification of the PHis based copolymers because of the little effect on the pH responsive properties. However, selection of the substitution group needs to be considered due to the possible increase of micellar particle size of the micelles, leading to compromised passive

  18. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

    NARCIS (Netherlands)

    Fregonese, Federica; Ahuja, Shama D; Akkerman, Onno W; Arakaki-Sanchez, Denise; Ayakaka, Irene; Baghaei, Parvaneh; Bang, Didi; Bastos, Mayara; Benedetti, Andrea; Bonnet, Maryline; Cattamanchi, Adithya; Cegielski, Peter; Chien, Jung-Yien; Cox, Helen; Dedicoat, Martin; Erkens, Connie; Escalante, Patricio; Falzon, Dennis; Garcia-Prats, Anthony J; Gegia, Medea; Gillespie, Stephen H; Glynn, Judith R; Goldberg, Stefan; Griffith, David; Jacobson, Karen R; Johnston, James C; Jones-López, Edward C; Khan, Awal; Koh, Won-Jung; Kritski, Afranio; Lan, Zhi Yi; Lee, Jae Ho; Li, Pei Zhi; Maciel, Ethel L; Galliez, Rafael Mello; Merle, Corinne S C; Munang, Melinda; Narendran, Gopalan; Nguyen, Viet Nhung; Nunn, Andrew; Ohkado, Akihiro; Park, Jong Sun; Phillips, Patrick P J; Ponnuraja, Chinnaiyan; Reves, Randall; Romanowski, Kamila; Seung, Kwonjune; Schaaf, H Simon; Skrahina, Alena; Soolingen, Dick van; Tabarsi, Payam; Trajman, Anete; Trieu, Lisa; Banurekha, Velayutham V; Viiklepp, Piret; Wang, Jann-Yuan; Yoshiyama, Takashi; Menzies, Dick

    Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and

  19. Comparison of different treatments for isoniazid-resistant tuberculosis : an individual patient data meta-analysis

    NARCIS (Netherlands)

    Fregonese, Federica; Ahuja, Shama D; Akkerman, Onno W; Arakaki-Sanchez, Denise; Ayakaka, Irene; Baghaei, Parvaneh; Bang, Didi; Bastos, Mayara; Benedetti, Andrea; Bonnet, Maryline; Cattamanchi, Adithya; Cegielski, Peter; Chien, Jung-Yien; Cox, Helen; Dedicoat, Martin; Erkens, Connie; Escalante, Patricio; Falzon, Dennis; Garcia-Prats, Anthony J; Gegia, Medea; Gillespie, Stephen H; Glynn, Judith R; Goldberg, Stefan; Griffith, David; Jacobson, Karen R; Johnston, James C; Jones-López, Edward C; Khan, Awal; Koh, Won-Jung; Kritski, Afranio; Lan, Zhi Yi; Lee, Jae Ho; Li, Pei Zhi; Maciel, Ethel L; Galliez, Rafael Mello; Merle, Corinne S C; Munang, Melinda; Narendran, Gopalan; Nguyen, Viet Nhung; Nunn, Andrew; Ohkado, Akihiro; Park, Jong Sun; Phillips, Patrick P J; Ponnuraja, Chinnaiyan; Reves, Randall; Romanowski, Kamila; Seung, Kwonjune; Schaaf, H Simon; Skrahina, Alena; Soolingen, Dick van; Tabarsi, Payam; Trajman, Anete; Trieu, Lisa; Banurekha, Velayutham V; Viiklepp, Piret; Wang, Jann-Yuan; Yoshiyama, Takashi; Menzies, Dick

    BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success,

  20. Novel Isoniazid cocrystals with aromatic carboxylic acids: Crystal engineering, spectroscopy and thermochemical investigations

    Science.gov (United States)

    Diniz, Luan F.; Souza, Matheus S.; Carvalho, Paulo S.; da Silva, Cecilia C. P.; D'Vries, Richard F.; Ellena, Javier

    2018-02-01

    Four novel cocrystals of the anti-tuberculosis drug Isoniazid (INH), including two polymorphs, with the aromatic carboxylic acids p-nitrobenzoic (PNBA), p-cyanobenzoic (PCNBA) and p-aminobenzoic (PABA) were rationally designed and synthesized by solvent evaporation. Aiming to explore the possible supramolecular synthons of this API, these cocrystals were fully characterized by X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR) and thermal (TGA, DSC, HSM) techniques. The cocrystal formation was found to be mainly driven by the synthons formed by the pyridine and hydrazide moieties. In both INH-PABA polymorphs, the COOH acid groups are H-bonded to pyridine and hydrazide groups giving rise to the acid⋯pyridine and acid⋯hydrazide heterosynthons. In INH-PNBA and INH-PCNBA cocrystals these acid groups are only related to the pyridine moiety. In addition to the structural study, supramolecular and Hirshfeld surface analysis were also performed based on the structural data. The cocrystals were identified from the FT-IR spectra and their thermal behaviors were studied by a combination of DSC, TGA and HSM techniques.

  1. [5-(1,3-Diphenyl-1H-pyrazol-4-yl-3-phenyl-4,5-dihydropyrazol-1-yl](pyridin-4-ylmethanone

    Directory of Open Access Journals (Sweden)

    Tarawanti Verma

    2011-01-01

    Full Text Available A novel pyrazoline derivative 2 was synthesized by reaction of an α,β-unsaturated ketone 1 with isonicotinic acid hydrazide (INH in glacial acetic acid. The structure of the title compound 2 was established on basis of IR, 1H-NMR, 13C-NMR and mass spectral data.

  2. Usefulness of C1 Esterase Inhibitor Protein Concentrate in the ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... of this case report is to describe the lifesaving use of a novel C1‑INH protein concentrate in a patient with mild‑to‑moderate dyspnea caused by swelling of the upper airway (larynx) and tongue. Keywords: C1 esterase inhibitor protein, hereditary angioedema, laryngeal edema, oropharyngeal swelling.

  3. Respiratory tract tumors in Syrian hamsters following inhalation of Pu--ZrO2 particles

    International Nuclear Information System (INIS)

    Thomas, R.G.; Smith, D.M.

    1979-01-01

    Inhalation of radionuclide-bearing particles remains one of the most intensely pursued problems concerning the nuclear industry. This route of entry is generally accepted as the most probable, in case of human exposure, with ingestion being the other prominent source of concern. Many laboratory investigations, such as those reported here, continue to evaluate the possible consequences that may present health problems to the public domain. Syrian hamsters of both sexes received either inhaled (INH) PuO 2 /ZrO 2 particles, intravenous (IV) PuO 2 /ZrO 2 microspheres, a combination of INH PuO 2 /ZrO 2 particles and injected PuO 2 /ZrO 2 microspheres, or no radionuclides (controls). The INH particles and IV microspheres were tagged with γ-emitting 57 Co to facilitate whole body counting and establishment of retention curves. Total lung burdens ranged from 8 nCi to 143 nCi. Significant numbers of primary lung tumors (5 to 50% per group) were induced in those animals that received INH exposures. Additional α radiation administered via Pu-laden IV microspheres had little or no effect on tumor production or nonneoplastic, degenerative changes in the respiratory tract

  4. The Effect of Price Competition on Weapon System Acquisition costs

    Science.gov (United States)

    1979-09-01

    Publishers, New York, S1976; Van brne, James C., "ir~ancial Management and Polcy, Pr ntice HPl.ll Inh., Erniewood Clif ffs, N1ew Jersey, 1914; or...differential on the West Coast and a labor requirement of approximately 2 million hours per ship. D-6 APPENDIX E ARMY PROCUREMENT OF LIGHT OBSERVATION

  5. Three cases of intentional isoniazid overdose – a life-threatening ...

    African Journals Online (AJOL)

    status epilepticus, her seizures were refractory to clonazepam and a phenytoin loading dose infusion, but her convulsions decreased during a propofol infusion in the ICU. There was a 48-hour delay before INH toxicity was recognised as the possible cause of her seizures;. 5 g pyridoxine was then administered via an NGT, ...

  6. High Stimulus-Related Information in Barrel Cortex Inhibitory Interneurons.

    Directory of Open Access Journals (Sweden)

    Vicente Reyes-Puerta

    2015-06-01

    Full Text Available The manner in which populations of inhibitory (INH and excitatory (EXC neocortical neurons collectively encode stimulus-related information is a fundamental, yet still unresolved question. Here we address this question by simultaneously recording with large-scale multi-electrode arrays (of up to 128 channels the activity of cell ensembles (of up to 74 neurons distributed along all layers of 3-4 neighboring cortical columns in the anesthetized adult rat somatosensory barrel cortex in vivo. Using two different whisker stimulus modalities (location and frequency we show that individual INH neurons--classified as such according to their distinct extracellular spike waveforms--discriminate better between restricted sets of stimuli (≤6 stimulus classes than EXC neurons in granular and infra-granular layers. We also demonstrate that ensembles of INH cells jointly provide as much information about such stimuli as comparable ensembles containing the ~20% most informative EXC neurons, however presenting less information redundancy - a result which was consistent when applying both theoretical information measurements and linear discriminant analysis classifiers. These results suggest that a consortium of INH neurons dominates the information conveyed to the neocortical network, thereby efficiently processing incoming sensory activity. This conclusion extends our view on the role of the inhibitory system to orchestrate cortical activity.

  7. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Farkas, H; Martinez-Saguer, I; Bork, K

    2017-01-01

    BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagn...

  8. Nꞌ-{[2-(Piperidin-1-ylquinolin-3-yl]methylene}pyridine-4-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Rajiv K. Tonk

    2012-01-01

    Full Text Available Nꞌ-{[2-(piperidin-1-ylquinolin-3-yl]methylene}pyridine-4-carbohydrazide 2 has been synthesized through condensation of 2-(piperidin-1-ylquinoline-3-carbaldehyde 1 with isonicotinic acid hydrazide (INH in absolute ethanol. The structure of the title compound 2 was established on the basis of IR, 1H-NMR, 13C-NMR and mass spectral data.

  9. Wild-type catalase peroxidase vs G279D mutant type: Molecular basis of Isoniazid drug resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Singh, Aishwarya; Singh, Aditi; Grover, Sonam; Pandey, Bharati; Kumari, Anchala; Grover, Abhinav

    2018-01-30

    Mycobacterium tuberculosis katG gene is responsible for production of an enzyme catalase peroxidase that peroxidises and activates the prodrug Isoniazid (INH), a first-line antitubercular agent. INH interacts with catalase peroxidase enzyme within its heme pocket and gets converted to an active form. Mutations occurring in katG gene are often linked to reduced conversion rates for INH. This study is focussed on one such mutation occurring at residue 279, where glycine often mutates to aspartic acid (G279D). In the present study, several structural analyses were performed to study the effect of this mutation on functionality of KatG protein. On comparison, mutant protein exhibited a lower docking score, smaller binding cavity and reduced affinity towards INH. Molecular dynamics analysis revealed the mutant to be more rigid and less compact than the native protein. Essential dynamics analysis determined correlated motions of residues within the protein structure. G279D mutant was found to have many residues that showed related motions and an undesirable effect on the functionality of protein. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Investigation of the Stress Corrosion Cracking Susceptibility of Annealed and Heat Treated Alloy 625 Castings and Forgings in Sea Water

    Science.gov (United States)

    1987-06-01

    across the Helmholts plane to alloy surface gap and into the material. 7.1. 2 SAMLE - PEPARATION The fully heat processed .30 in..h sqoare, 2 inch long...I_.• Ii; V’ ^61 11. FUTURE WORK The preceding testing program left marny questions unanswered. The m3trix of test.s conducted was not inclusive of

  11. Dicty_cDB: Contig-U16207-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available hromosome 2... 40 0.15 DQ078284_1( DQ078284 |pid:none) Ulmus pumila polygalacturonase inh... 40 0.15 AC11698... 0.33 DQ078283_1( DQ078283 |pid:none) Ulmus americana polygalacturonase ... 39 0.

  12. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits

    DEFF Research Database (Denmark)

    Bygum, Anette; Andersen, Klaus Ejner; Mikkelsen, Carsten Sauer

    2009-01-01

    Hereditary angioedema (HAE) is often debilitating with a serious effect on quality of life (QOL). Treatment of acute HAE attacks is usually with C1 esterase inhibitor (C1-INH) concentrates; however, treatment can be delayed by patients' travel time for attending emergency units. We assessed...

  13. A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G

    2015-01-01

    BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable...

  14. Hereditaert angioødem

    DEFF Research Database (Denmark)

    Overgaard Bach, Rasmus; Bygum, Anette

    2009-01-01

    Hereditary angioedema (HAE) is a rare, but potentially life-threatening condition, clinically characterized by recurrent and self-limiting episodes of swelling which affect the skin, gastrointestinal tract and upper airways, and are caused by a lack of complement-C1-inhibitor (C1-INH). Within...

  15. Recombinant human C1-inhibitor in the treatment of acute angioedema attacks

    NARCIS (Netherlands)

    Choi, Goda; Soeters, Maarten R.; Farkas, Henriette; Varga, Lilian; Obtulowicz, Krystyna; Bilo, Barbara; Porebski, Greg; Hack, C. Erik; Verdonk, Rene; Nuijens, Jan; Levi, Marcel

    2007-01-01

    BACKGROUND: Patients with hereditary C1-inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1-inhibitor concentrate. A recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the

  16. Usefulness of C1 esterase inhibitor protein concentrate in the ...

    African Journals Online (AJOL)

    Hereditary angioedema is an autosomal‑dominant disorder caused by mutation of the gene encoding the C1 esterase inhibitor (C1‑INH). It manifests as painless, nonpruritic, nonpitting episodic swelling of the subcutaneous tissues, gastrointestinal, and upper respiratory tracts in the absence of urticaria. An attack typically ...

  17. Enzyme Polymorphism and Genetic Variability of One Colonized and Several Field Populations of Phlebotomus papatasi (Diptera: Psychodidae)

    Science.gov (United States)

    1993-01-01

    255. Nlunsterman. L. E. 1979. Isozymes of- Aedes ae- irypti. phenotypes. linkage. and use in the genetic References Cited .aiialvsis of svinpatric...led. W. J. Tabachnick. 1984. The effect of coloniza- Hvgt. 84. 785-786. tion upon Aedesr aegypte susceptibility to oral inh-c- WHO iWorid Health

  18. Resazurin tube method: rapid, simple, and inexpensive method for detection of drug resistance in the clinical isolates of mycobacterium tuberculosis.

    Science.gov (United States)

    Patil, Santosh S; Mohite, Shivajirao T; Kulkarni, Sunanda A; Udgaonkar, Usha S

    2014-10-01

    Tuberculosis (TB) remains a serious public health problem worldwide. The emergence of drug resistance and multidrug resistance (MDR) has become the main threat to TB treatment and control programs. Rapid detection is critical for the effective treatment of patients. In recent times, a new method using the colorimetric indicator resazurin has been proposed for drug susceptibility of Mycobacterium tuberculosis. In this study, the resazurin reduction assay was adapted to screw cap tubes. Using the Resazurin Tube Method (RTM), a total of 100 clinical isolates were tested against Rifampicin (RIF) and Isoniazide (INH). By visual reading, the minimum inhibitory concentrations (MICs) were obtained after eight days. The results obtained were compared with the gold standard proportion method. Excellent results were obtained for RTM with a sensitivity of 100% for both RIF and INH, with a specificity of 98.7 and 95.3%, respectively. Kappa is the measure of agreement between the RTM and proportion method (PM) for RIF and INH, which was found to be 0.972 and 0.935 for RIF and INH, respectively. The RTM appears to be a reliable method for the rapid and simultaneous detection of MDR-TB and drug susceptibility testing (DST) of M. tuberculosis. It is simple, inexpensive, and with no biohazard risk involved.

  19. The role of interferon-gamma release assays in predicting the emergence of active tuberculosis in the setting of biological treatment: a case report and review of the literature.

    Science.gov (United States)

    Scrivo, Rossana; Sauzullo, Ilaria; Mengoni, Fabio; Riccieri, Valeria; Altieri, Alfonso Maria; Cantoro, Laura; Vullo, Vincenzo; Mastroianni, Claudio Maria; Valesini, Guido

    2016-05-01

    Conversions and reversions of interferon-gamma (IFN-γ) release assays (IGRAs) were observed when these tests were repeated over time in the same individuals, including those treated with biological agents. In most studies, the variability of IFN-γ plasma levels was not paralleled by clinical change, but a few exceptions exist, in which IGRA conversion predicted the emergence of active tuberculosis (TB). We report the case of a Peruvian patient with rheumatoid arthritis (RA) and Crohn's disease scheduled for treatment with adalimumab. TB screening demonstrated latent TB infection (LTBI), and the patient was started on isoniazid (INH) for 9 months. Adalimumab was initiated after 1 month since INH. QuantiFERON-TB Gold In-Tube, one of the IGRAs currently available, was serially repeated to monitor the status of TB infection during treatment with the biological agent. The patient developed active TB preceded by progressively rising levels of released IFN-γ. We came to know that she had withdrawn INH after 2 months on her own initiative. Considering the low rate of INH completion, serial IGRAs may help in the clinical vigilance during prophylaxis as well as anti-TNF treatment, at least in patients presenting other risk factors aside from the state of immunosuppression.

  20. Investigation of isoniazid and ethionamide cross-resistance by whole genome sequencing and association with poor treatment outcomes of multidrug-resistant tuberculosis patients in South Africa

    Directory of Open Access Journals (Sweden)

    L Malinga

    2016-01-01

    Conclusion: Baseline ETH molecular resistance before second-line treatment is a concern. Unfavorable treatment outcomes of patients with ethA, ethR, and inhA mutations highlight the importance of genotypic testing before initiation of treatment containing ETH. The clinical significance of whole genome analysis for early detection of mutations predictive of treatment failure needs further investigation.

  1. CME 9097 (ONLINE).indd

    African Journals Online (AJOL)

    Xpert also detects rifampicin (RIF) resistance, an indicator of more extensive drug resistance, allowing rapid initiation of effective second- line treatment. Definitive .... lower-level resistance and be overcome by higher doses of INH ..... efforts are being made to increase access to new drugs for DR-TB patients with severely.

  2. August Cover 09 Tp

    Indian Academy of Sciences (India)

    Admin

    virus, which causes myeloblastic anemia in young chickens, was used for the following two reasons. First, upon his return to UCSF, Levinson had evaluated the efficacy of the Cu++-INH complex on RSV-induced tumors in susceptible chickens, and had found that it suppressed tumor formation. Second, it was important to ...

  3. Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS

    Science.gov (United States)

    Wali, Adil F.; Avula, Bharathi; Ali, Zulfiqar; Khan, Ikhlas A.; Mushtaq, Ahlam; Rehman, Muneeb U.; Akbar, Seema; Masoodi, Mubashir Hussain

    2015-01-01

    The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt) from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF) induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg) intraperitoneal (i.p.) injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight) distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS) were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids. PMID:26539487

  4. Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS

    Directory of Open Access Journals (Sweden)

    Adil F. Wali

    2015-01-01

    Full Text Available The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg intraperitoneal (i.p. injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids.

  5. Inactivation of factor Xia in vivo: studies in chimpanzees and in humans

    NARCIS (Netherlands)

    Wuillemin, W. A.; Hack, C. E.; Bleeker, W. K.; Biemond, B. J.; Levi, M. [=Marcel M.; ten Cate, H.

    1996-01-01

    C1-inhibitor (C1Inh), antithrombin III (ATIII), alpha 1-antitrypsin (a1AT), and alpha 2-antiplasmin (a2AP) are known inhibitors of factor XIa (FXIa). However, their precise contribution to FXIa inactivation in vivo is not known. We investigated FXIa inactivation in chimpanzees and assessed the

  6. Proteinase inhibitors I and II from potatoes specifically block UV-induced activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminal kinases, and P38 kinase

    International Nuclear Information System (INIS)

    Huang, C.S.; Ma, W.Y.; Ryan, C.A.; Dong, Z.G.

    1997-01-01

    Solar UV irradiation is the causal factor for the increasing incidence of human skin carcinomas. The activation of the transcription factor activator protein-1 (AP-1) has been shown to be responsible for the tumor promoter action of UV light in mammalian cells. We demonstrate that proteinase inhibitor I (Inh I) and II (Inh II) from potato tubers, when applied to mouse epidermal JB6 cells, block UV-induced AP-1 activation. The inhibition appears to be specific for UV-induced signal transduction for AP-1 activation, because these inhibitors did not block UV-induced p53 activation nor did they exhibit any significant influence on epidermal growth factor-induced AP-1 transactivation. Furthermore, the inhibition of UV-induced AP-1 activity occurs through a pathway that is independent of extracellular signal-regulated kinases and c-Jun N-terminal kinases as well as P38 kinases. Considering the important role of AP-1 in tumor promotion, it is possible that blocking UV-induced AP-1 activity by Inh I or Inh II may be functionally linked to irradiation-induced cell transformation

  7. Nylon 4,I: an amorphous polyamide

    NARCIS (Netherlands)

    Gaymans, R.J.; van der Ham, Aloysius G.J.

    1984-01-01

    The melt polymerization of nylon 4, I was studied, starting with nylon-salt and nylon prepolymers (ηinh=0.25). With nylon-salt only low molecular polymers were obtained, while with prepolymers the inherent viscosity could be raised to 0.77 (3h, 270°, vac.). The cyclization of tetra methylene diamine

  8. Localization Improvement in Wireless Sensor Networks Using a New Statistical Channel Model

    DEFF Research Database (Denmark)

    Karimi Alavijeh, Amir; Ramezani, Hossein; Karimi Alavijeh, Ali

    2018-01-01

    In this paper, a statistical channel model is proposed based on the second moment of Received Signal Strength Indicator (RSSI) in an outdoor communication channel. The medium under study is a grass field where the RSSI data are collected in different distances and orientations using a set of in-h...

  9. The Use and Efficacy of Mucolytic Agents

    African Journals Online (AJOL)

    1971-08-28

    Aug 28, 1971 ... TB + lung abcess. 62. 67. 130. 149. 100. 372. INH, PAS, streptomycin. 15. 45. Scleroderma + chr. Chloramphenicol + bronchitis. 95. 103. 109. 111. 100. 231 peripheral vasodilators. 16. 69. Silicosis + emphysema. Chloramphenicol +. + pneumonia. 57. 60. 67. 93. 100. 182. Aminophyllin were on the average ...

  10. A prospective study of tuberculosis drug susceptibility in sabah, malaysia, and an algorithm for management of isoniazid resistance.

    Science.gov (United States)

    Rashid Ali, Muhammad Redzwan S; Parameswaran, Uma; William, Timothy; Bird, Elspeth; Wilkes, Christopher S; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M; Ralph, Anna P

    2015-01-01

    Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.

  11. A Prospective Study of Tuberculosis Drug Susceptibility in Sabah, Malaysia, and an Algorithm for Management of Isoniazid Resistance

    Directory of Open Access Journals (Sweden)

    Muhammad Redzwan S. Rashid Ali

    2015-01-01

    Full Text Available Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9% and nontuberculous Mycobacterium (NTM in three (1.7%. Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB. Seven people (4.5% had isoniazid resistance (INH-R; all were switched to an appropriate second-line regimen for varying durations (4.5–9 months. Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant, 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.

  12. Simultaneous determination of isoniazid and pyrazinamide in ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a new high performance liquid chromatographic (HPLC) method for the simultaneous determination of isoniazid (INH) and pyrazinamide (PZA) in plasma. Methods: A 150 μL aliquot of plasma was mixed with 75 μL of 10 % trichloroacetic acid containing 100 mg/L of acetanilide as the ...

  13. Health-related quality of life in Danish children with hereditary angioedema

    DEFF Research Database (Denmark)

    Aabom, Anne; Nguyen, Dan; Fisker, Niels

    2017-01-01

    -INH-HAE, including possible correlations to disease severity and attack frequency. Methods: All Danish children ages 2-18 years with C1-INH-HAE were invited to complete questionnaires regarding HRQoL; 14 (93%) agreed. Child self-report forms were used for children ages ≥5 years. The instruments used...... scores for healthy children and better than the scores in the only other study dedicated to HRQoL in children. Children with recent attacks had lower scores, whereas HRQoL scores were not correlated to overall disease severity or age. Surprisingly, home therapy was associated with lower HRQoL; however......, home therapy was also correlated to a higher overall severity score and more frequent attacks. There was a strong child-parent agreement in the PedsQL forms, but scores were independent of whether the child had a family history of C1-INH-HAE or sporadic C1-INH-HAE and whether the parent completing...

  14. C-reactive protein and natural IgM antibodies are activators of complement in a rat model of intestinal ischemia and reperfusion

    NARCIS (Netherlands)

    Padilla, Niubel Diaz; van Vliet, Arlene K.; Schoots, Ivo G.; Seron, Mercedes Valls; Maas, M. Adrie; Peltenburg, Esther E. Posno; de Vries, Annebeth; Niessen, Hans W. M.; Hack, C. Erik; van Gulik, Thomas M.

    2007-01-01

    Background. The role of C-reactive protein (CRP), natural immunoglobulin M (IgM), and natural IgM against phosphorylcholine (anti-Pc IgM) was investigated in relation with complement activation in a rat model of intestinal ischemia and reperfusion (II/R). The effect of Cl-esterase inhibitor (C1-Inh)

  15. Synergistic Effect of Azadirachta Indica Extract and Iodide Ions on the Corrosion Inhibition of Aluminium in Acid Media

    Energy Technology Data Exchange (ETDEWEB)

    Arab, S. T.; Al- Turkustani, A. M.; Al- Dhahiri, R. H. [King Abd El- Aziz University, Jeddah (Saudi Arabia)

    2008-06-15

    The synergistic action caused by iodide ions on the corrosion inhibition of aluminium (Al) in 0.5 M HCl in the presence of Azadirachta Indica (AZI) plant extract has been investigated using potintiodynamic polarization and impedance techniques. It is found that AZI extract inhibits the corrosion of aluminium in 0.5 M HCl. The inhibition efficiency increases with the increase in AZI extract concentration, until 24% v/v of AZI extract, then Inh.% is decreased with father increase in AZI extract concentration. The adsorption of this extract in the studied concentration is found to obey Frewendlish adsorption isotherm. The addition of iodide ions enhances the inhibition efficiency to a considerable extent. The increase in Inh.% values in presence of fixed concentration of iodide ions indicates that AZI extract forms an insoluble complex at lower AZI extract concentrations by undergoing a joint adsorption. But at higher concentrations of AZI extract, competitive adsorption is found between iodide ions and the formed complex leading to less Inh.%. The Inh.% decreased in presence of iodide ions with AZI extract than in presence of AZI extract alone at all studied iodide concentrations. The synergism parameter S {sub θ} is defined and calculated from surface coverage values. This parameter in the case of AZI extract is found to be more than unity, indicating that the enhanced inhibition efficiency caused by the addition of iodide ions.

  16. Field Testing of Activated Carbon Mixing and In Situ Stabilization of PCBs in Sediment

    Science.gov (United States)

    2009-05-01

    present. Identify workers with allergies and ensure that appropriate emergency treatment is available. Chemical Hazards Skin and Eye Irritation...Principal Routes of Entry Acute Exposure Effects/Symptoms Chronic Exposure Effects/Symptoms Nickel Skin, Inh, Ing Skin, nasal irritation, respiratory

  17. Cell surface expression and function of the macromolecular C1 complex on the surface of human monocytes

    Directory of Open Access Journals (Sweden)

    Kinga K Hosszu

    2012-03-01

    Full Text Available The synthesis of the subunits of the C1 complex (C1q, C1s, C1r, and its regulator C1 inhibitor (C1-Inh by human monocytes has been previously established. However, surface expression of these molecules by monocytes has not been shown. Using flow cytometry and antigen-capture ELISA, we show here for the first time that, in addition to C1q, PB monocytes and the monocyte-derived U937 cells express C1s and C1r, as well as Factor B and C1-Inh on their surface. C1s and C1r immunoprecipitated with C1q, suggesting that at least some of the C1q on these cells is part of the C1 complex. Furthermore, the C1 complex on U937 cells was able to trigger complement activation via the classical pathway. The presence of C1-Inh may ensure that an unwarranted autoactivation of the C1 complex does not take place. Since C1-Inh closely monitors the activation of the C1 complex in a sterile or infectious inflammatory environment, further elucidation of the role of C1 complex is crucial to dissect its function in monocyte, DC and T cell activities, and its implications in host defense and tolerance.

  18. Evaluation of the Genotype® MTBDRplus assay as a tool for drug resistance surveys

    NARCIS (Netherlands)

    Rigouts, L.; Hoza, A. S.; de Rijk, P.; Torrea, G.; Chonde, T. M.; Basra, D.; Zignol, M.; van Leth, F.; Egwaga, S. M.; van Deun, A.

    2011-01-01

    A national tuberculosis (TB) drug resistance survey in Tanzania. To compare the performance of the Genotype® MTBDRplus line-probe assay (LPA) on smear-positive sputum specimens with conventional culture and isoniazid (INH) plus rifampicin (RMP) drug susceptibility testing (DST). Mycobacterium

  19. Maleta pequeña y relatos cortos: Crónicas de un viajero

    OpenAIRE

    Rodríguez Huertas, Felipe

    2016-01-01

    Este trabajo de grado es un conjunto de crónicas que carácter experiencial, desde las cuales se narran las historias que viven los turistas en sitios inhóspitos como el desierto de la Tatacoa y la selva del Amazonas. Estos textos están orientados a mostrar el desarrollo del periodismo de turismo en Colombia.

  20. Three cases of intentional isoniazid overdose - a life-threatening condition.

    Science.gov (United States)

    Stead, David Francis; Mason, Carolyn Ruth

    2016-08-11

    Currently, isoniazid (INH) overdose seems to be a growing and life-threatening problem, partly due to the recent national roll-out of INHpreventive therapy (IPT) for HIV-positive adults. We present three cases, two of which were fatal, seen at Frere and Cecilia Makiwanehospitals, East London, South Africa over the past 16 months.

  1. Isoniazid prophylaxis for tuberculosis prevention among HIV ...

    African Journals Online (AJOL)

    Objective: To determine the acceptability, compliance and side effects of isoniazid (INH) prophylaxis against tuberculosis among HIV infected police officers (PO) in Dar es Salaam. Design: A nested study from a prospective follow up of a cohort of police officers. Setting: Dar es Salaam, Tanzania. Subjects: One hundred and ...

  2. ORIGINAL ARTICLE

    African Journals Online (AJOL)

    number of MTB strain is less than 39,062,500 and. 4,444,444,444 with selective effect to INH and RIF ..... random generated cycles was used as the empirical data to further assess the simulated results of the ... Basically, the process is a form of pseudo sampling from the original dataset to determine the variability.

  3. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    DEFF Research Database (Denmark)

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  4. CORAL REEF BIOLOGICAL CRITERIA: USING THE CLEAN WATER ACT TO PROTECT A NATIONAL TREASURE

    Science.gov (United States)

    Coral reefs are declining at unprecedented rates worldwide due to multiple interactive stressors including climate change and land-based sources of pollution. The Clean Water Act (CWA) can be a powerful legal instrument for protecting water resources, including the biological inh...

  5. Elucidating the Mechanism of Gain of Toxic Function From Mutant C1 Inhibitor Proteins in Hereditary Angioedema

    Science.gov (United States)

    2017-10-01

    fact , that the plasma level of C1INH was significantly reduced in 75 PiZZ children compared to 35 control children (14%, p ɘ.01). A similar...constructed all plasmids and performed mutagenesis Funding Support: None Name: Astrid Doerner Project Role: Project Scientist Research

  6. Effect of Yushen zhuyun decoction on rats with diminished ovarian ...

    African Journals Online (AJOL)

    10 min) to separate serum samples, and stored at -20 °C until analysis. The serum levels of FSH,. E2, T and P were determined by radioimmunoassay according to the instructions of radioimmunoassay kits. In addition, the serum levels of INH and AMH were determined by. ELISA method following the instructions of ELISA.

  7. Anthraquinone-based demultiplexer and other multiple operations at ...

    Indian Academy of Sciences (India)

    Boolean operations such as NOR, XOR, XNOR, INH – and the most common combinational circuits, i.e., half– and full–adders and –subtractors, multiplexer, demultiplexer.10–18. An important function in information technology is signal multiplexing/demultiplexing. A 2:1 multiplexer. (MUX) is a circuit with two data inputs, ...

  8. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  9. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  10. Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Martin Rao

    2018-04-01

    Full Text Available Background: New tuberculosis (TB drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis. Methods: M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH and rifampicin (RIF. The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU. Results: VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction, while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis. The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction and equalled that of INH (1.5-log CFU reduction. INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3 days vs. 6 days. Conclusions: VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted. Keywords: Mycobacterium tuberculosis, Adjunct host-directed therapy, Tuberculosis, Histone deacetylase inhibitors, Repurposed drugs

  11. Antituberculosis drug resistance patterns in two regions of Turkey: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Oymak Sema F

    2002-12-01

    Full Text Available Abstract Backround The emergence of Mycobacterium tuberculosis strains resistant to antituberculosis agents has recently received increased attention owing largely to the dramatic outbreaks of multi drug resistance tuberculosis (MDR-TB. Methods Patients residing in Zonguldak and Kayseri provinces of Turkey with, pulmonary tuberculosis diagnosed between 1972 and 1999 were retrospectively identified. Drug susceptibility tests had been performed for isoniazid (INH, rifampin (RIF, streptomycin (SM, ethambutol (EMB and thiacetasone (TH after isolation by using the resistance proportion method. Results Total 3718 patients were retrospectively studied. In 1972–1981, resistance rates for to SM and INH were found to be 14.8% and 9.8% respectively (n: 2172. In 1982–1991 period, resistance rates for INH, SM, RIF, EMB and TH were 14.2%, 14.4%, 10.5%, 2.7% and 2.9% (n: 683, while in 1992–1999 period 14.4%, 21.1%, 10.6%, 2.4% and 3.7% respectively (n: 863. Resistance rates were highest for SM and INH in three periods. MDR-TB patients constituted 7.3% and 6.6% of 1982–1991 and 1992–1999 periods (p > 0.05. Conclusion This study demonstrates the importance of resistance rates for TB. Continued surveillance and immediate therapeutic decisions should be undertaken in order to prevent the dissemination of such resistant strains.

  12. A continuous fluorescent assay for the determination of plasma and tissue angiotensin I-converting enzyme activity

    Directory of Open Access Journals (Sweden)

    M.F. Alves

    2005-06-01

    Full Text Available A continuous assay using internally quenched fluorescent peptides with the general sequence Abz-peptidyl-(DnpP-OH (Abz = ortho-aminobenzoic acid; Dnp = 2,4-dinitrophenyl was optimized for the measurement of angiotensin I-converting enzyme (ACE in human plasma and rat tissues. Abz-FRK(DnpP-OH, which was cleaved at the Arg-Lys bond by ACE, was used for the enzyme evaluation in human plasma. Enzymatic activity was monitored by continuous recording of the fluorescence (lambdaex = 320 nm and lambdaem = 420 nm at 37ºC, in 0.1 M Tris-HCl buffer, pH 7.0, with 50 mM NaCl and 10 µM ZnCl2. The assays can be performed directly in the cuvette of the fluorimeter and the hydrolysis followed for 5 to 10 min. ACE measurements in the plasma of 80 healthy patients with Hip-His-Leu and with Abz-FRK(DnpP-OH correlated closely (r = 0.90, P < 0.001. The specificity of the assay was demonstrated by the complete inhibition of hydrolysis by 0.5 µM lisinopril or captopril. Abz-FRK(DnpP-OH cleavage by ACE was monitored in rat lung, kidney, heart, and liver homogenates in the presence of a cocktail of inhibitors containing trans-epoxy-succinyl-L-leucylamido-(4-guanido-butene, pepstatin, phenyl-methylsulfonyl fluoride, N-tosyl-L-phenylalanyl-chloromethyl ketone, and N-tosyl-lysyl-chloromethyl ketone to prevent undesirable hydrolysis. ACE activity in lung, heart and kidney homogenates, but not in liver homogenates, was completely abolished by 0.5 µM lisinopril or captopril. The advantages of the method are the procedural simplicity and the high sensitivity providing a rapid assay for ACE determinations.

  13. Hepatic and extrahepatic synthesis and disposition of dinitrophenyl-S-glutathione in bile duct-ligated rats.

    Science.gov (United States)

    Villanueva, Silvina S M; Ruiz, María L; Soroka, Carol J; Cai, Shi-Ying; Luquita, Marcelo G; Torres, Adriana M; Sánchez Pozzi, Enrique J; Pellegrino, José M; Boyer, James L; Catania, Viviana A; Mottino, Aldo D

    2006-08-01

    The ability of the kidney and small intestine to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for the multidrug resistance-associated proteins (Mrps), was assessed in bile duct-ligated (BDL) rats 1, 7, and 14 days after surgery, using an in vivo perfused jejunum model with simultaneous urine collection. A single i.v. dose of 30 micromol/kg b.wt. of 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its glutathione conjugate DNP-SG and dinitrophenyl cysteinyl glycine derivative, which is the result of gamma-glutamyl-transferase action on DNP-SG, were determined in urine and intestinal perfusate by high-performance liquid chromatography. Intestinal excretion of these metabolites was unchanged at day 1, and decreased at days 7 and 14 (-39% and -33%, respectively) after surgery with respect to shams. In contrast, renal excretion was increased by 114%, 150%, and 128% at days 1, 7, and 14. Western blot studies revealed decreased levels of apical Mrp2 in liver and jejunum but increased levels in renal cortex from BDL animals, these changes being maximal between days 7 and 14. Assessment of expression of basolateral Mrp3 at day 14 postsurgery indicated preserved levels in renal cortex, duodenum, jejunum, distal ileum, and colon. Analysis of expression of glutathione-S-transferases alpha, mu, and pi, as well as activity toward CDNB, indicates that formation of DNP-SG was impaired in liver, preserved in intestine, and increased in renal cortex. In conclusion, increased renal tubular conversion of CDNB to DNP-SG followed by subsequent Mrp2-mediated secretion into urine partially compensates for altered liver function in experimental obstructive cholestasis.

  14. Novel design for centrifugal counter-current chromatography: VI. Ellipsoid column.

    Science.gov (United States)

    Gu, Dongyu; Yang, Yi; Xin, Xuelei; Aisa, Haji Akber; Ito, Yoichiro

    2015-01-01

    A novel ellipsoid column was designed for centrifugal counter-current chromatography. Performance of the ellipsoid column with a capacity of 3.4 mL was examined with three different solvent systems composed of 1-butanol-acetic acid-water (4:1:5, v/v) (BAW), hexane-ethyl acetate-methanol-0.1 M HCl (1:1:1:1, v/v) (HEMH), and 12.5% (w/w) PEG1000 and 12.5% (w/w) dibasic potassium phosphate in water (PEG-DPP) each with suitable test samples. In dipeptide separation with BAW system, both stationary phase retention (Sf) and peak resolution (Rs) of the ellipsoid column were much higher at 0° column angle (column axis parallel to the centrifugal force) than at 90° column angle (column axis perpendicular to the centrifugal force), where elution with the lower phase at a low flow rate produced the best separation yielding Rs at 2.02 with 27.8% Sf at a flow rate of 0.07 ml/min. In the DNP-amino acid separation with HEMW system, the best results were obtained at a flow rate of 0.05 ml/min with 31.6% Sf yielding high Rs values at 2.16 between DNP-DL-glu and DNP-β-ala peaks and 1.81 between DNP-β-ala and DNP-L-ala peaks. In protein separation with PEG-DPP system, lysozyme and myolobin were resolved at Rs of 1.08 at a flow rate of 0.03 ml/min with 38.9% Sf. Most of those Rs values exceed those obtained from the figure-8 column under similar experimental conditions previously reported.

  15. A quasi-optical and corrugated waveguide microwave transmission system for simultaneous dynamic nuclear polarization NMR on two separate 14.1 T spectrometers

    Science.gov (United States)

    Dubroca, Thierry; Smith, Adam N.; Pike, Kevin J.; Froud, Stuart; Wylde, Richard; Trociewitz, Bianca; McKay, Johannes; Mentink-Vigier, Frederic; van Tol, Johan; Wi, Sungsool; Brey, William; Long, Joanna R.; Frydman, Lucio; Hill, Stephen

    2018-04-01

    Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with Boltzmann distributions of nuclear spin states on the order of parts per million in conventional magnetic fields. To overcome this limitation, dynamic nuclear polarization (DNP) can be used to gain up to three orders of magnitude in signal enhancement, which can decrease experimental time by up to six orders of magnitude. In DNP experiments, nuclear spin polarization is enhanced by transferring the relatively larger electron polarization to NMR active nuclei via microwave irradiation. Here, we describe the design and performance of a quasi-optical system enabling the use of a single 395 GHz gyrotron microwave source to simultaneously perform DNP experiments on two different 14.1 T (1H 600 MHz) NMR spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the other configured for solution state NMR experiments. In particular, we describe how the high power microwave beam is split, transmitted, and manipulated between the two spectrometers. A 13C enhancement of 128 is achieved via the cross effect for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at 110 K, while a 31P enhancement of 160 is achieved via the Overhauser effect for triphenylphosphine using the monoradical BDPA under solution NMR conditions at room temperature. The latter result is the first demonstration of Overhauser DNP in the solution state at a field of 14.1 T (1H 600 MHz). Moreover these results have been produced with large sample volumes (∼100 μL, i.e. 3 mm diameter NMR tubes).

  16. The Stature of Boys Is Inversely Correlated to the Levels of Their Sertoli Cell Hormones: Do the Testes Restrain the Maturation of Boys?

    Science.gov (United States)

    Ruffman, Ted; Bilkey, David K.; McLennan, Ian S.

    2011-01-01

    The testes of preadolescent boys appear to be dormant, as they produce only trace levels of testosterone [1]. However, they release supra-adult levels of Müllerian Inhibiting Substance (MIS, anti-Müllerian hormone) and lesser levels of inhibin B (InhB), for unknown reasons [2], [3]. Boys have a variable rate of maturation, which on average is slower than girls. The height of children relative to their parents is an index of their maturity [4], [5]. We report here that a boy's level of MIS and InhB is stable over time and negatively correlates with his height and his height relative to his parent's height. This suggests that boy's with high levels of MIS and InhB are short because they are immature, rather than because they are destined to be short men. The levels of MIS and InhB in the boys did not correlate with known hormonal modulators of growth, and were additive with age and the growth hormone/IGF1 axis as predictors of a boy's height. If MIS and InhB were causal regulators of maturity, then the inter-boy differences in the levels of these hormone produces variation in maturation equivalent to 18-months of development. MIS and InhB may thus account for most of the variation in the rate of male development. If boys lacked these hormones, then an average 5-year-old boy would be over 5 cm taller than age-matched girls, making boys almost as dimorphic as men, for height. This indicates that boys have a high growth potential that is initially suppressed by their testes. The concept of the childhood testes suppressing an adult male feature appears paradoxical. However, the growth of children requires intergenerational transfer of nutrients. Consequently, the MIS/InhB slowing of male growth may have been historically advantageous, as it would minimizes any sex bias in the maternal cost of early child rearing. PMID:21655101

  17. Will availability of inhaled human insulin (Exubera® improve management of type 2 diabetes? The design of the Real World trial

    Directory of Open Access Journals (Sweden)

    Freemantle Nick

    2006-08-01

    Full Text Available Abstract Background Common deterrents to insulin therapy for both physicians and patients are the complexity and burden of daily injections. In January 2006, the first inhaled human insulin (INH, Exubera® (insulinhuman [rDNA origin]InhalationPowder was approved for use in adult patients with type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM in the United States and European Union. Results from the INH clinical trial program have shown comparable efficacy of INH to subcutaneous (SC insulin and superior efficacy versus oral antidiabetic agents; thus providing effective glycemic control in adult patients with T2DM without the requirement for preprandial injections. However, because subjects in those trials were randomized to either INH or an alternative, the studies could not estimate the effect of INH on patient acceptance of insulin therapy. Therefore, traditional study designs cannot provide answers to important and practical questions regarding real world effectiveness, which is influenced by psychological and other access barriers. Methods To overcome these limitations, the Real World Trial was designed to estimate the effect of the availability of INH as a treatment option for glycemic control. A total of approximately 700 patients from Canada, France, Germany, Italy, Spain, United Kingdom, and the United States with T2DM poorly controlled by oral agent therapy will be randomized to two different treatment settings. Patients and clinicians in both groups (A & B may choose from all licensed therapies for diabetes including SC insulin delivered by pens; INH will be an additional treatment option only available in Group A. The Real World Trial (Protocol A2171018 has been registered with ClincalTrials.gov, registration id NCT00134147. Results The primary outcome for the trial will be the difference in mean glycosylated hemoglobin (HbA1c at 6 months between groups. The design was based on a preceding feasibility study examining the

  18. Prueba molecular Genotype® MTBDRplus, una alternativa para la detección rápida de tuberculosis multidrogorresistente Molecular test Genotype® MTBDRplus, an alternative to rapid detection of multidrug resistance tuberculosis

    Directory of Open Access Journals (Sweden)

    Luis Asencios

    2012-03-01

    Full Text Available La prueba molecular Genotype®MTBDRplus, es un método que permite identificar las mutaciones más frecuentes asociadas con la resistencia a las drogas antituberculosas de primera línea: isoniacida (INH y rifampicina (RIF. El objetivo de este estudio fue evaluar el desempeño de la prueba molecular con cultivos y muestras de esputo con baciloscopía positiva. Se evaluó 95 cultivos y 100 esputos con perfiles de resistencia previamente determinados por el método de referencia "proporciones agar en placa" (APP. La prueba molecular a partir de cultivos mostró una sensibilidad de 100%; 97,5% y 96,9% para RIF, INH y multidrogorresistente (MDR respectivamente; mientras que para esputo la sensibilidad fue de 95,7%; 96,8% y 95,2% para RIF, INH y MDR respectivamente. Se concluye que Genotype®MTBDRplus es una herramienta muy útil para la detección rápida de la resistencia a INH y RIF simultáneamente (MDR en un máximo de 72 h a partir de esputo o de cultivo.The Genotype®MTBDRplus molecular test is a method that allows identification of the most frequent mutations associated with resistance to major first-line antituberculosis drugs, Isoniazid (INH and Rifampicin (RFP. The aim of this study was to evaluate the performance of the molecular test with culture and smear- positive sputum samples. We evaluated 95 cultures and 100 sputum samples with resistance profiles previously determined by the reference method "Agar Plate Proportions" (APP. The molecular test from cultures showed a sensitivity of 100 %, 97,5 % and 96,97 % for RIF, INH and MDR respectively while from sputums the sensitivity was 95,65 %, 96,77 % and 95,24 % for RIF, INH and MDR respectively. We conclude that the molecular test Genotype®MTBDRplus is a very useful tool to detect resistance to isoniazid and rifampicin simultaneously (MDR-TB in up to 72 hours from sputum samples or cultures.

  19. Magnitude of gene mutations conferring drug resistance in mycobacterium tuberculosis isolates from lymph node aspirates in ethiopia.

    Science.gov (United States)

    Biadglegne, Fantahun; Tessema, Belay; Rodloff, Arne C; Sack, Ulrich

    2013-01-01

    Resistance to drugs is due to particular genomic mutations in the specific genes of Mycobacterium tuberculosis. Timely genetic characterization will allow identification of resistance mutations that will optimize an effective antibiotic treatment regimen. We determine the magnitude of gene mutations conferring resistance to isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) among tuberculosis (TB) lymphadenitis patients. A cross sectional prospective study was conducted among 226 M.tuberculosis isolates from culture positive lymph node aspirates collected from TB lymphadenitis patients between April 2012 and May 2012. Detection of mutations conferring resistance to drugs was carried out using GenoType(®) MTBDRplus and GenoType® MTBDRsl assay. Out of the 226 strains, mutations conferring resistance to INH, RMP, multidrug resistance tuberculosis (MDR-TB) and EMB were 8, 3, 2 and 2 isolates, respectively. There was no isolated strain that showed mutation in the inhA promoter region gene. All INH resistant strains had mutations in the katG gene at codon 315 with amino acid change of S315T1. Among rifampicin resistant strains, two isolates displayed mutations at codon 531 in the rpoB gene with amino acid change of S531L and one isolate was by omission of wild type probes at Q513L. According to mutations associated with ethambutol resistance, all of the isolates had mutations in the embB gene with aminoacid change of M306I. All isolates resistant to INH, RMP and MDR using BacT/AlerT 3D system were correctly identified by GenoType® MTBDRplus assay. We observed mutations conferring resistance to INH at S315T1 of the katG gene, RMP at S531L and Q513L in the rpoB genes and EMB at M306I of the embB gene. In the absence of conventional drug susceptibility testing, the effort to develop easy, rapid and cost effective molecular assays for drug resistance TB monitoring is definitely desirable and the GenoType® MTBDRplus assay was found to be a useful method for diagnosis

  20. Evaluation of B1 inhomogeneity effect on DCE-MRI data analysis of brain tumor patients at 3T.

    Science.gov (United States)

    Sengupta, Anirban; Gupta, Rakesh Kumar; Singh, Anup

    2017-12-02

    Dynamic-contrast-enhanced (DCE) MRI data acquired using gradient echo based sequences is affected by errors in flip angle (FA) due to transmit B 1 inhomogeneity (B 1 inh). The purpose of the study was to evaluate the effect of B 1 inh on quantitative analysis of DCE-MRI data of human brain tumor patients and to evaluate the clinical significance of B 1 inh correction of perfusion parameters (PPs) on tumor grading. An MRI study was conducted on 35 glioma patients at 3T. The patients had histologically confirmed glioma with 23 high-grade (HG) and 12 low-grade (LG). Data for B 1 -mapping, T 1 -mapping and DCE-MRI were acquired. Relative B 1 maps (B 1rel ) were generated using the saturated-double-angle method. T 1 -maps were computed using the variable flip-angle method. Post-processing was performed for conversion of signal-intensity time (S(t)) curve to concentration-time (C(t)) curve followed by tracer kinetic analysis (K trans , Ve, Vp, Kep) and first pass analysis (CBV, CBF) using the general tracer-kinetic model. DCE-MRI data was analyzed without and with B 1 inh correction and errors in PPs were computed. Receiver-operating-characteristic (ROC) analysis was performed on HG and LG patients. Simulations were carried out to understand the effect of B 1 inhomogeneity on DCE-MRI data analysis in a systematic way. S(t) curves mimicking those in tumor tissue, were generated and FA errors were introduced followed by error analysis of PPs. Dependence of FA-based errors on the concentration of contrast agent and on the duration of DCE-MRI data was also studied. Simulations were also done to obtain K trans of glioma patients at different B 1rel values and see whether grading is affected or not. Current study shows that B 1rel value higher than nominal results in an overestimation of C(t) curves as well as derived PPs and vice versa. Moreover, at same B 1rel values, errors were large for larger values of C(t). Simulation results showed that grade of patients can change

  1. Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics.

    Science.gov (United States)

    Saitta, Kyle S; Zhang, Carmen; Lee, Kang Kwang; Fujimoto, Kazunori; Redinbo, Matthew R; Boelsterli, Urs A

    2014-01-01

    1.  We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2.  Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3.  Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t1/2 of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4.  Using the fluorescent probe 5 (and 6)-carboxy-2',7'-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5.  These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones.

  2. Treatment outcomes for isoniazid-resistant tuberculosis under program conditions in British Columbia, Canada.

    Science.gov (United States)

    Romanowski, Kamila; Chiang, Leslie Y; Roth, David Z; Krajden, Mel; Tang, Patrick; Cook, Victoria J; Johnston, James C

    2017-09-04

    Every year, over 1 million people develop isoniazid (INH) resistant tuberculosis (TB). Yet, the optimal treatment regimen remains unclear. Given increasing prevalence, the clinical efficacy of regimens used by physicians is of interest. This study aims to examine treatment outcomes of INH resistant TB patients, treated under programmatic conditions in British Columbia, Canada. Medical charts were retrospectively reviewed for cases of culture-confirmed INH mono-resistant TB reported to the BC Centre for Disease Control (BCCDC) from 2002 to 2014. Treatment regimens, patient and strain characteristics, and clinical outcomes were analysed. One hundred sixty five cases of INH mono-resistant TB were included in analysis and over 30 different treatment regimens were prescribed. Median treatment duration was 10.5 months (IQR 9-12 months) and treatment was extended beyond 12 months for 26 patients (15.8%). Fifty six patients (22.6%) experienced an adverse event that resulted in a drug regimen modification. Overall, 140 patients (84.8%) had a successful treatment outcome while 12 (7.2%) had an unsuccessful treatment outcome of failure (n = 2; 1.2%), relapse (n = 4; 2.4%) or all cause mortality (n = 6; 3.6%). Our treatment outcomes, while consistent with findings reported from other studies in high resource settings, raise concerns about current recommendations for INH resistant TB treatment. Only a small proportion of patients completed the recommended treatment regimens. High quality studies to confirm the effectiveness of standardized regimens are urgently needed, with special consideration given to trials utilizing fluoroquinolones.

  3. Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

    Science.gov (United States)

    Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

    2017-08-01

    Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

  4. Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs.

    Directory of Open Access Journals (Sweden)

    Selvakumar Subbian

    2011-09-01

    Full Text Available Tuberculosis (TB treatment is hampered by the long duration of antibiotic therapy required to achieve cure. This indolent response has been partly attributed to the ability of subpopulations of less metabolically active Mycobacterium tuberculosis (Mtb to withstand killing by current anti-TB drugs. We have used immune modulation with a phosphodiesterase-4 (PDE4 inhibitor, CC-3052, that reduces tumor necrosis factor alpha (TNF-α production by increasing intracellular cAMP in macrophages, to examine the crosstalk between host and pathogen in rabbits with pulmonary TB during treatment with isoniazid (INH. Based on DNA microarray, changes in host gene expression during CC-3052 treatment of Mtb infected rabbits support a link between PDE4 inhibition and specific down-regulation of the innate immune response. The overall pattern of host gene expression in the lungs of infected rabbits treated with CC-3052, compared to untreated rabbits, was similar to that described in vitro in resting Mtb infected macrophages, suggesting suboptimal macrophage activation. These alterations in host immunity were associated with corresponding down-regulation of a number of Mtb genes that have been associated with a metabolic shift towards dormancy. Moreover, treatment with CC-3052 and INH resulted in reduced expression of those genes associated with the bacterial response to INH. Importantly, CC-3052 treatment of infected rabbits was associated with reduced ability of Mtb to withstand INH killing, shown by improved bacillary clearance, from the lungs of co-treated animals compared to rabbits treated with INH alone. The results of our study suggest that changes in Mtb gene expression, in response to changes in the host immune response, can alter the responsiveness of the bacteria to antimicrobial agents. These findings provide a basis for exploring the potential use of adjunctive immune modulation with PDE4 inhibitors to enhance the efficacy of existing anti-TB treatment.

  5. Mutation of katG in a clinical isolate of Mycobacterium tuberculosis: effects on catalase-peroxidase for isoniazid activation.

    Science.gov (United States)

    Purkan; Ihsanawati; Natalia, D; Syah, Y M; Retnoningrum, D S; Kusuma, H S

    2016-01-01

    Mutations in katG gene are often associated with isoniazid (INH) resistance in Mycobacterium tuberculosis strain. This research was perfomed to identify the katG mutation in clinical isolate (L8) that is resistant to INH at 1 μg/ml. In addition to characterize the catalase-peroxidase of KatG L8 and perform the ab initio structural study of the protein to get a more complete understanding in drug activation and the resistan­ce mechanism. The katG gene was cloned and expressed in Escherichia coli, then followed by characterization of catalase-peroxidase of KatG. The structure modelling was performed to know a basis of alterations in enzyme activity. A substitution of A713G that correspond to Asn238Ser replacement was found in the L8 katG. The Asn238Ser modification leads to a decline in the activity of catalase-peroxidase and INH oxidation of the L8 KatG protein. The catalytic efficiency (Kcat/KM) of mutant KatGAsn238Ser respectively decreases to 41 and 52% for catalase and peroxidase. The mutant KatGAsn238Ser also shows a decrease of 62% in INH oxidation if compared to a wild type KatG (KatGwt). The mutant Asn238Ser might cause instability in the substrate binding­ site of KatG, because of removal of a salt bridge connecting the amine group of Asn238 to the carbo­xyl group of Glu233, which presents in KatGwt. The lost of the salt bridge in the substrate binding site in mutant KatGAsn238Ser created changes unfavorable for enzyme activities, which in turn emerge as INH resistan­ce in the L8 isolate of M. tuberculosis.

  6. Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

    Science.gov (United States)

    Aygören-Pürsün, Emel; Soteres, Daniel; Moldovan, Dumitru; Christensen, Jim; Van Leerberghe, Arthur; Hao, James; Schranz, Jennifer; Jacobson, Kraig W.; Martinez-Saguer, Inmaculada

    2017-01-01

    Background Hereditary angioedema (HAE) is a rare genetic disease causing unpredictable and potentially life-threatening subcutaneous and submucosal edematous attacks. Cinryze® (Shire ViroPharma Inc., Lexington, MA, USA), a nanofiltered C1 inhibitor (C1-INH), is approved in Europe for the treatment, preprocedure prevention, and routine prophylaxis of HAE attacks, and for the routine prophylaxis of attacks in the USA. This phase 3 study assessed the safety and efficacy of 2 C1-INH doses in preventing attacks in children aged 6–11 years. Methods A randomized single-blind crossover study was initiated in March 2014. Results for the first 6 patients completing the study are reported here. After a 12-week qualifying observation period, patients were randomly assigned to 1 of 2 C1-INH doses, 500 or 1,000 U, every 3–4 days for 12 weeks and crossed over to the alternative dose for a second 12-week period. The primary efficacy endpoint was the number of angioedema attacks per month. Results Six females with HAE type I and a median age of 10.5 years received 2 doses of C1-INH (500 and 1,000 U). The mean (SD) difference in the number of monthly angioedema attacks between the baseline observation period and the treatment period was −1.89 (1.31) with 500 U and −1.89 (1.11) with 1,000 U. During the treatment periods, cumulative attack severity, cumulative daily severity, and the number of attacks needing acute treatment were lower. No serious adverse events or study drug discontinuations occurred. Conclusions Interim findings from this study indicate that routine prevention with intravenous administration of C1-INH is efficacious, safe, and well tolerated in children ≥6 years of age. PMID:28662509

  7. Ovulatory and endocrine responses after active immunization of gilts against a synthetic fragment of bovine inhibin.

    Science.gov (United States)

    King, B F; Britt, J H; Esbenshade, K L; Flowers, W L; Sesti, L A; Martin, T L; Ireland, J J

    1993-04-01

    The objective of this study was to determine whether neutralizing endogenous inhibin would affect ovulation rate and serum concentrations of FSH, LH, estradiol-17 beta, and progesterone in gilts. At wk 0, during their second postpubertal estrous cycle, gilts (195 +/- 2.4 d of age) were given a primary immunization against the 1-26 gly-tyr NH-terminal amino acid sequence of bovine inhibin-alpha conjugated to human alpha globulin (INH; n = 10) or against human alpha globulin alone (control; n = 10). The primary immunization mixed with Freund's complete adjuvant contained .915 mg of the inhibin peptide. Booster immunizations in Freund's incomplete adjuvant contained .3 and .183 mg of the inhibin peptide and were given at wk 8 and 12, respectively. Free, unconjugated inhibin was given to INH gilts at 16 wk. Blood samples for determination of hormones were collected every 4 h beginning on d 15 of the first estrous cycle beyond wk 16 (first cycle) and continuing until d 5 of the second estrous cycle following wk 16 (second cycle). Ovulation rate was estimated by laparoscopy during the second cycle. Antibody titers were estimated by determining the percentage of [125I]-INH bound by serum diluted 1:4,000. The antibody titers were 17 +/- 2, 22 +/- 3, and 9 +/- 1% at wk 9, 17, and 23 for INH gilts, respectively, and 0% at all times for control gilts. Duration of three consecutive estrous cycles terminating with the first experimental cycle did not differ between treatments (INH, 20.7 +/- .3 vs control, 20.4 +/- .3 d).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis.

    Science.gov (United States)

    Upadhyay, Seema; Khan, Iliyas; Gothwal, Avinash; Pachouri, Praveen K; Bhaskar, N; Gupta, Umesh D; Chauhan, Devendra S; Gupta, Umesh

    2017-09-01

    First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and 1 H-NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC's interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis. Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, -19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

  9. The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting.

    Science.gov (United States)

    Frigati, L J; Kranzer, K; Cotton, M F; Schaaf, H S; Lombard, C J; Zar, H J

    2011-06-01

    Tuberculosis (TB) is a major cause of morbidity and mortality among children infected with HIV. Strategies to prevent TB in children include isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children. To investigate the combined effect of IPT and ART on TB risk in children infected with HIV. A cohort analysis was done within a prospective, double-blinded, placebo-controlled trial of isoniazid (INH) compared with placebo in children infected with HIV in Cape Town, South Africa, a high TB incidence setting. In May 2004 the placebo arm was terminated and all children were switched to INH. ART was not widely available at the start of the study, but children were started on ART following the establishment of the national ART program in 2004. Data were analysed using Cox proportional hazard regression. After adjusting for age, nutritional status and immunodeficiency at enrolment, INH alone, ART alone and INH combined with ART reduced the risk of TB disease by 0.22 (95% CI 0.09 to 0.53), 0.32 (95% CI 0.07 to 1.55) and 0.11 (95% CI 0.04 to 0.32) respectively. INH reduced the risk of TB disease in children on ART by 0.23 (95% CI 0.05 to 1.00). The finding that IPT may offer additional protection in children on ART has significant public health implications because this offers a possible strategy for reducing TB in children infected with HIV. Widespread use of this strategy will however require screening of children for active TB disease. Trial registration Trial registration-Clinical Trials NCT00330304.

  10. Clinical Pattern and Acute and Long-term Management of Hereditary Angioedema Due to C1-Esterase Inhibitor Deficiency.

    Science.gov (United States)

    Gómez-Traseira, C; Pérez-Fernández, E; López-Serrano, M C; García-Ara, M C; Pedrosa, M; López-Trascasa, M; Caballero, T

    2015-01-01

    Hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-C1-INH) is a life-threatening disease. To describe the clinical characteristics and management of patients with HAE-C1-INH during routine clinical practice. An observational, retrospective study was performed in patients with HAE-C1-INH. Demographic, clinical, and analytical data were collected from 2 periods: period A (October 2009-September 2010) and period B (October 2007-September 2009). We studied 112 patients with HAE-C1-INH (57.1% females). Age at onset of symptoms was 14.4 years (lower in patients who had experienced attacks in the previous year). In period B (n=87), 62.1% of patients presented at least 1 edema attack (median, 3.5 attacks/patient/2 years), and 19.1% of attacks were treated. In period A (n=77), 58.4% of patients were on maintenance therapy. Stanozolol was the most widely used drug (48.9%), with a mean weekly dose of 6.7 mg. At least 1 attack was recorded in 72.7% of patients (median, 3.0 attacks/patient/year), and 31.5% of the attacks were treated. Treatment of acute attacks increased by 12.4%. Age at onset of symptoms is associated with clinical expression of disease. The higher age at onset of symptoms, the fewer number of attacks per patient and year, and the lower dose of attenuated androgens necessary to control the disease than in other series lead us to hypothesize that HAE-C1-INH could have a less severe expression in Spain. Acute attacks seem to be treated increasingly often.

  11. Rapid speciation of 15 clinically relevant mycobacteria with simultaneous detection of resistance to rifampin, isoniazid, and streptomycin in Mycobacterium tuberculosis complex.

    Science.gov (United States)

    Shenai, Shubhada; Rodrigues, Camilla; Mehta, Ajita

    2009-01-01

    To design and standardize an in-house reverse line blot hybridization (RLBH) assay for the accurate identification of 15 clinically relevant species of mycobacteria and for the detection of drug resistance to rifampin (RIF), isoniazid (INH), and streptomycin (STR) in Mycobacterium tuberculosis complex (MTB). Oligonucleotides specific for 15 different species of mycobacteria and wild type and mutant alleles of selected codons in the rpobeta, inhA, katG, rpsL, and rrs genes were designed and immobilized on a membrane. A multiplex PCR was standardized to amplify all target genes. The assay was optimized using ATCC and known mutant strains. Three hundred MTB isolates, 85 non-tuberculous mycobacteria (NTM) isolates, and 48 smear-positive specimens were analyzed. Results were confirmed by PCR restriction enzyme assay and sequencing. Upon RLBH analysis, among the NTM, 14% were identified as Mycobacterium fortuitum, 16% were identified as Mycobacterium abscessus, 20% showed 99% homology with Mycobacterium intracellulare, and 31% showed 98% homology with Mycobacterium simiae. Of the 300 MTB isolates analyzed, 75% RIF-resistant isolates had Ser531Leu mutation in the rpobeta gene. Of the INH-resistant isolates, 89% showed Ser315Thr mutation in the katG gene, whereas 16% showed -15 C-->T mutation in the promoter region of the inhA gene. Among STR-resistant isolates, 75% had A-->G mutation in the rpsL gene at codon 43. RLBH results showed 96-99% concordance with phenotypic culture results. This is a first attempt at combining speciation with detection of drug resistance to RIF, INH, and STR in MTB for accurate and rapid management of mycobacterial infections as well as for compiling genotypic epidemiological data.

  12. BIOCHEMISTRY TEACHING WITH VIRTUAL DYNAMIC METABOLIC DIAGRAMS

    Directory of Open Access Journals (Sweden)

    G. B. Lazzarotto

    2004-05-01

    Full Text Available This work presents a game like educational software (courseware to study metabolic pathways, calledDiagrama Metabolico Din^amico Virtual (DMDV of Krebs Cycle. The experience acquired teachingwith the logical sequence tray games in the FFFCMPAs Biochemistry Course provides the beddingswith the use of this model as education method. With DMDV, students can assembly the sequenceof reactions that describe the desired metabolic pathway, create situational models which can guidehis/her choices, reduce the subject complexity of the scheme in knowledge construction presentingin a graphical way the current interrelations. Biochemistry teachers can use the present software inclassroom as well as distance classes. This product integrates multimedia resources extensively andis distributed in CD-ROM format. The virtual environment will make possible interaction of thestudent with the environment and with colleagues and teachers, through tools as chats and forum.Experience with the use of this method was carried through with two distinct groups of students.The rst group was composed by 11 students, who were more familiar with the content and answereda specic questionnaire to previously evaluate the software. The second group was formed by 24students regularly registered in the FFFCMPAs Biochemistry Course, who used the software as astudy method. The rst group considered DMDV of easy and pleasant navigation. The knowledgeevaluation of the second group students was made by a written test and the analysis of three conceptualmaps constructed by each one of them: one map before initiating the study with the DMDV, thesecond just after the study and the third one two months later. Every conceptual maps producedafter DMDV method showed an expansion of valid concepts if compared with the rst maps. Simplevisual comparison of maps shows that new elements where added. All students who passed throughthe experiment reached a greater than ve grade in the subjects written

  13. Vanadium complexes having [VO]2+, [VO]3+ and [VO2]+ cores with hydrazones of 2,6-diformyl-4-methylphenol: synthesis, characterization, reactivity, and catalytic potential.

    Science.gov (United States)

    Maurya, Mannar R; Haldar, Chanchal; Kumar, Amit; Kuznetsov, Maxim L; Avecilla, Fernando; Costa Pessoa, João

    2013-09-07

    The Schiff bases H3dfmp(L)2 obtained by the condensation of 2,6-diformyl-4-methylphenol and hydrazones [L = isonicotinoylhydrazide (inh), nicotinoylhydrazide (nah) and benzoylhydrazide (bhz)] are prepared and characterized. By reaction of [V(IV)O(acac)2] and the H3dfmp(L)2 in methanol the V(IV)O-complexes [V(IV)O{Hdfmp(inh)2}(H2O)] (1), [V(IV)O{Hdfmp(nah)2}(H2O)] (2) and [V(IV)O{Hdfmp(bhz)2}(H2O)] (3) were obtained. Upon their aerial oxidation in methanol [V(V)O(OMe)(MeOH){Hdfmp(inh)2}] (4), [V(V)O(OMe)(MeOH){Hdfmp(nah)2}] (5) and [V(V)O(OMe)(MeOH){Hdfmp(bhz)2}] (6) were isolated. In the presence of KOH, oxidation of 1-3 results in the formation of [V(V)O2{H2dfmp(inh)2}]n·5H2O (7), K[V(V)O2{Hdfmp(nah)2}] (8) and K[V(V)O2{Hdfmp(bhz)2}] (9). All compounds are characterized in the solid state and in solution, namely by spectroscopic techniques (IR, UV-Vis, EPR, (1)H, (13)C and (51)V NMR), and DFT is also used to calculate the V(IV) hyperfine coupling constants of V(IV)-compounds and (51)V NMR chemical shifts of several V(V)-species and assign them to those formed in solution. Single crystal X-ray analysis of [V(V)O(OMe)(MeOH){Hdfmp(bhz)2}] (6) and [V(V)O2{H2dfmp(inh)2}]n·5H2O (7) confirm the coordination of the ligand in the dianionic (ONO(2-)) enolate tautomeric form, one of the hydrazide moieties remaining non-coordinated. In the case of 7 the free N(pyridine) atom of the inh moiety coordinates to the other vanadium center yielding a polynuclear complex in the solid state. It is also demonstrated that the V(V)O2-complexes are catalyst precursors in the oxidative bromination of styrene by H2O2, therefore acting as functional models of vanadium dependent haloperoxidases. Plausible intermediates involved in the catalytic process are established by UV-Vis, (51)V NMR and DFT studies.

  14. Economic impact of the use of rifaximin 550 mg twice daily for the treatment of overt hepatic encephalopathy in Italy

    Directory of Open Access Journals (Sweden)

    Roggeri DP

    2017-09-01

    Full Text Available Daniela Paola Roggeri, Alessandro Roggeri ProCure Solutions, Nembro, Bergamo, Italy Purpose: Hepatic encephalopathy (HE is associated with a reduced survival, an increased risk of hospitalization for recurrences, and a reduced health-related quality of life. The purpose of the present economic analysis was to evaluate the impact on the Italian National Health Service (INHS expenditure of the treatment with rifaximin 550 mg twice daily (Tixteller®/Tixtar® for the reduction of the recurrences of overt HE, with respect to the current treatment approach. Patients and methods: Costs associated with patients treated with rifaximin 550 mg twice daily were estimated considering the reduction in hospitalizations for HE recurrences revealed by registrative clinical trial (−50% applied to the hospitalization rate (42.5% emerging from an Italian observational real-world study; costs associated with patients not treated with rifaximin were estimated based on the hospitalization rate, resulting from the same Italian observational study. Sensitivity analyses considering possible different discount levels to INHS structures for rifaximin were performed. The INHS perspective for a period of 3 years was considered. Results: The treatment with rifaximin 550 mg twice daily, although increasing drug costs, is associated with a reduction in hospitalizations for HE recurrences that leads to an overall reduction of total costs charged to INHS, which could be estimated, based on the forecasted uptake of the treatment, at about €130,000 in the first year, reaching ~€260,000 in the third year. Considering a possible discount for rifaximin 550 mg to INHS structure of 20%, the total saving at the third year accounts for ~€3,000,000. Moreover, a relevant reduction in the number of hospitalizations and bed days is associated with rifaximin treatment. Conclusion: The treatment with rifaximin 550 mg twice daily, even if associated with an increase in drug expenditure

  15. Waveguide transition with vacuum window for multiband dynamic nuclear polarization systems

    DEFF Research Database (Denmark)

    Rybalko, Oleksandr; Bowen, Sean; Zhurbenko, Vitaliy

    2016-01-01

    broadband than commercially available windows, which are usually optimized for single band operation. It is demonstrated that high-density polyethylene with urethane adhesive can be used as a low loss microwave vacuum window in multiband DNP systems. The overall assembly performance and dimensions are found......A low loss waveguide transition section and oversized microwave vacuum window covering several frequency bands (94 GHz, 140 GHz, 188 GHz) is presented. The transition is compact and was optimized for multiband Dynamic Nuclear Polarization (DNP) systems in a full-wave simulator. The window is more...... using full-wave simulations. The practical aspects of the window implementation in the waveguide are discussed. To verify the design and simulation results, the window is tested experimentally at the three frequencies of interest....

  16. Post-Electrophoretic Identification of Oxidized Proteins

    Directory of Open Access Journals (Sweden)

    Conrad Craig

    2000-01-01

    Full Text Available The oxidative modification of proteins has been shown to play a major role in a number of human diseases. However, the ability to identify specific proteins that are most susceptible to oxidative modifications is difficult. Separation of proteins using polyacrylamide gel electrophoresis (PAGE offers the analytical potential for the recovery, amino acid sequencing, and identification of thousands of individual proteins from cells and tissues. We have developed a method to allow underivatized proteins to be electroblotted onto PVDF membranes before derivatization and staining. Since both the protein and oxidation proteins are quantifiable, the specific oxidation index of each protein can be determined. The optimal sequence and conditions for the staining process are (a electrophoresis, (b electroblotting onto PVDF membranes, (c derivatization of carbonyls with 2,4-DNP, (d immunostaining with anti DNP antibody, and (e protein staining with colloidal gold.

  17. Evidence-based practice for nurse practitioner students: a competency-based teaching framework.

    Science.gov (United States)

    Stiffler, Deborah; Cullen, Deborah

    2010-01-01

    Evidence-based practice (EBP) has become increasingly important in nursing. It has become a dominant philosophy in teaching research courses and it brings a new definition to the translation of science. As more has become known about EBP, it has continued to grow in its importance and significance. EBP is the foundation to many doctor of nursing practice (DNP) programs in both the advanced practice nursing and organizational foci. The purpose of this article is to define evidence-based practice competencies for advanced practice nurses, especially nurse practitioners. A corresponding teaching framework is presented. Additionally, competencies related to the DNP with aggregate systems and organizational foci are suggested. Practical experiences emanating from working within the NP competency development and framework are highlighted and described. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Development of an institutional review board preapproval process for Doctor of Nursing Practice students: process and outcome.

    Science.gov (United States)

    Szanton, Sarah L; Taylor, Holly A; Terhaar, Mary

    2013-01-01

    As Doctor of Nursing Practice (DNP) programs proliferate, effective collaboration with institutional review boards (IRBs) is important to protect human subjects. It is particularly important that faculty and students recognize which DNP students' projects should be considered as "human subjects research" or "quality improvement." The former require IRB review, whereas the latter may be eligible for expedited review or may be considered exempt. We report outcomes following implementation of a combination of didactic training, one-to-one consultation, and a decision support protocol to improve preparation for and collaboration with the IRB at a large university. In the first year of using this protocol, 53% of projects were deemed human subjects research and received IRB review. The other 47% were deemed quality improvement projects and did not require IRB review. We offer our experience as an approach for teaching students how to protect the subjects included in their quality improvement activities. Copyright 2012, SLACK Incorporated.

  19. Dynamic nuclear polarization and optimal control spatial-selective 13C MRI and MRS

    DEFF Research Database (Denmark)

    Vinding, Mads Sloth; Laustsen, Christoffer; Maximov, Ivan I.

    2013-01-01

    Aimed at 13C metabolic magnetic resonance imaging (MRI) and spectroscopy (MRS) applications, we demonstrate that dynamic nuclear polarization (DNP) may be combined with optimal control 2D spatial selection to simultaneously obtain high sensitivity and well-defined spatial restriction. This is ach......Aimed at 13C metabolic magnetic resonance imaging (MRI) and spectroscopy (MRS) applications, we demonstrate that dynamic nuclear polarization (DNP) may be combined with optimal control 2D spatial selection to simultaneously obtain high sensitivity and well-defined spatial restriction....... This is achieved through the development of spatial-selective single-shot spiral-readout MRI and MRS experiments combined with dynamic nuclear polarization hyperpolarized [1-13C]pyruvate on a 4.7T pre-clinical MR scanner. The method stands out from related techniques by facilitating anatomic shaped region...

  20. Quantum chemical studies on the aminopolynitropyrazoles.

    Science.gov (United States)

    Ravi, Pasupala; Gore, Girish Mohan; Tewari, Surya Prakash; Sikder, Arun Kanti

    2011-10-01

    We have explored the geometric and electronic structures, band gap, thermodynamic properties, density, detonation velocity and detonation pressure of aminopolynitropyrazoles using the density functional theory (DFT) at the B3LYP/aug-cc-pVDZ level. The calculated detonation velocity and detonation pressure, stability and sensitivity of model compounds appear to be promising compared to the known explosives 3,4-dinitro-1 H-pyrazole (3,4-DNP), 3,5-dinitro-1 H-pyrazole (3,5-DNP), hexahydro-1,3,5-trinitro-1,3,5-triazinane (RDX) and octahydro-1,3,5,7-tetranitro-l,3,5,7-tetraazocane (HMX). The position of NH(2) group in the polynitropyrazoles presumably determines the structure, stability, sensitivity, density, detonation velocity and detonation pressure.

  1. A 282 GHz Probe for Dynamic Nuclear Polarization

    DEFF Research Database (Denmark)

    Rybalko, Oleksandr; Bowen, Sean; Zhurbenko, Vitaliy

    of the coil is976 MHz. A magnetic field distribution at 108 MHz and 430 MHz was calculated for the RF coil, the results revealedgood homogeneity and intensity along x,y,z axes. Figure 1 shows the general view of the probe and cross section through the microwave container with field distribution. Operating......Introduction In DNP, microwave irradiation of a sample facilitates the transfer of spin polarization from electrons tonuclei. One of the way to improve the DNP enhancement is to transfer microwave power from the mm-wave source tothe sample more effectively. Several methods and techniques...... to efficiently transport microwave energy from the microwave source to the sample have been developed. For example, a corrugated waveguide allows to deliver mm-wave energy from external source to the probe with minimum losses1.The conventional approach at high frequencies is to irradiate the sample directly from...

  2. Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

    International Nuclear Information System (INIS)

    Berg, P. Van Den; Radl, J.; Loewenberg, B.; Swart, A.C.W.

    1976-01-01

    Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP-Rhesus albumin and IgA1lambda-10S human paraprotein. One or more transient homogenous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP-Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. (author)

  3. Opposite effects of total lymphoid irradiation on T cell-dependent and T cell-independent antibody responses

    Energy Technology Data Exchange (ETDEWEB)

    Tanay, A.; Strober, S.

    1984-02-01

    The effect of total lymphoid irradiation (TLI) on the primary antibody response to the dinitrophenylated heterologous protein, keyhole limpet hemocyanin (DNP-KLH), in complete Freund's adjuvant (CFA), and to the trinitrophenylated polysaccharide antigen, Brucella abortus (TNP-BA), was studied in BALB/c mice. The antibody response to both antigens was diminished in comparison with nonirradiated mice when antigens were injected within 3 days after TLI. When the mice were immunized 30 days after completion of TLI the antibody response to DNP-KLH in CFA was still diminished, but the antibody response to TNP-BA was enhanced 5- to 10-fold as compared with that of control animals. The opposite effect of TLI on the two antibody responses was also observed in a syngeneic primary adoptive transfer system.

  4. Post-Electrophoretic Identification of Oxidized Proteins

    Science.gov (United States)

    Conrad, Craig C; Talent, John M; Malakowsky, Christina A

    1999-01-01

    The oxidative modification of proteins has been shown to play a major role in a number of human diseases. However, the ability to identify specific proteins that are most susceptible to oxidative modifications is difficult. Separation of proteins using polyacrylamide gel electrophoresis (PAGE) offers the analytical potential for the recovery, amino acid sequencing, and identification of thousands of individual proteins from cells and tissues. We have developed a method to allow underivatized proteins to be electroblotted onto PVDF membranes before derivatization and staining. Since both the protein and oxidation proteins are quantifiable, the specific oxidation index of each protein can be determined. The optimal sequence and conditions for the staining process are (a) electrophoresis, (b) electroblotting onto PVDF membranes, (c) derivatization of carbonyls with 2,4-DNP, (d) immunostaining with anti DNP antibody, and (e) protein staining with colloidal gold. PMID:12734585

  5. Innovación en hidrocarburos en Colombia

    Directory of Open Access Journals (Sweden)

    Juan Benavides Estévez-Bretón

    2011-01-01

    Full Text Available Este artículo presenta parte del Proyecto DNP- Uniandes sobre Clusters en la industria minero energética. El análisis se centrará en la innovación en hidrocarburos: primero, el planteamiento básico; segundo, los retos y oportunidades, y tercero, las líneas de acción en las que Colombia puede trabajar.//This article presents a fragment of the DNP- Uniandes project on Clusters in the energy mining industry. Specifically, the analysis focuses on innovation in hydrocarbons, starting with the project's basic approach. Next, it exposes the challenges and opportunities present in the Colombian context. Finally, it discusses the lines of action within which Colombia will move forward.

  6. A Secure, Intelligent, and Smart-Sensing Approach for Industrial System Automation and Transmission over Unsecured Wireless Networks

    Science.gov (United States)

    Shahzad, Aamir; Lee, Malrey; Xiong, Neal Naixue; Jeong, Gisung; Lee, Young-Keun; Choi, Jae-Young; Mahesar, Abdul Wheed; Ahmad, Iftikhar

    2016-01-01

    In Industrial systems, Supervisory control and data acquisition (SCADA) system, the pseudo-transport layer of the distributed network protocol (DNP3) performs the functions of the transport layer and network layer of the open systems interconnection (OSI) model. This study used a simulation design of water pumping system, in-which the network nodes are directly and wirelessly connected with sensors, and are monitored by the main controller, as part of the wireless SCADA system. This study also intends to focus on the security issues inherent in the pseudo-transport layer of the DNP3 protocol. During disassembly and reassembling processes, the pseudo-transport layer keeps track of the bytes sequence. However, no mechanism is available that can verify the message or maintain the integrity of the bytes in the bytes received/transmitted from/to the data link layer or in the send/respond from the main controller/sensors. To properly and sequentially keep track of the bytes, a mechanism is required that can perform verification while bytes are received/transmitted from/to the lower layer of the DNP3 protocol or the send/respond to/from field sensors. For security and byte verification purposes, a mechanism needs to be proposed for the pseudo-transport layer, by employing cryptography algorithm. A dynamic choice security buffer (SB) is designed and employed during the security development. To achieve the desired goals of the proposed study, a pseudo-transport layer stack model is designed using the DNP3 protocol open library and the security is deployed and tested, without changing the original design. PMID:26950129

  7. Développement de la polarisation dynamique nucléaire à haut champ magnétique pour la caractérisation des matériaux nanostructurés

    OpenAIRE

    Duong, Tuan Nghia

    2015-01-01

    Solid-state NMR spectroscopy is a powerful analytical technique to characterize the atomic-level structure and dynamics of both ordered and disordered materials. However, its main limitation is the lack of sensitivity, particularly preventing studies on the surface of materials, an important region determining their chemical properties. It has been recently shown that Magic Angle Spinning Dynamic Nuclear Polarization (MAS-DNP) could overcome this difficulty. This technique can provide an enha...

  8. Acute energy restriction triggers Wallerian degeneration in mouse

    DEFF Research Database (Denmark)

    Alvarez, Susana; Moldovan, Mihai; Krarup, Christian

    2008-01-01

    the exposed sciatic nerve by means of a hook electrode. The sciatic nerve was focally immersed over a length of 1 cm in either phosphate buffered saline (PBS), a solution of approximately 4 microM NO obtained from 10 mM of the NO-donor DETA NONOate, or a solution of up to 1 mM DNP. Following 3 hours of 200 Hz...

  9. Volar versus dorsal fixed-angle fixation of dorsally unstable extra-articular distal radius fractures: a biomechanic study.

    Science.gov (United States)

    McCall, Todd A; Conrad, Bryan; Badman, Brian; Wright, Thomas

    2007-01-01

    To evaluate and compare the biomechanic rigidity and strength of 3 fixed-angle plates used to treat extra-articular distal radius fractures that are dorsally unstable. Volar fixed-angle plates were compared with a dorsal fixed-angle nail plate. Three plate constructs were tested: the dorsal nail plate (DNP), distal volar radius (DVR) plate, and locking compression plate (LCP) volar distal radius plate. With anatomic, third-generation, artificial composite radii, dorsally unstable extra-articular distal radius fracture models were made by cutting a wedge osteotomy with an 8-mm dorsal gap 1 cm from the articular surface. These models were then fixed with the 3 implants by the method recommended by the manufacturer. The proximal radii of each specimen were attached to the base of a materials testing machine with a probe centered at the radial side of the lunate fossa. The specimens were loaded at a constant rate to failure under axial compression. Load and displacement were plotted graphically, and the resulting rigidities and strengths of each plate were assessed statistically. The DVR group had significantly greater stiffness than the LCP group. The DVR group had significantly higher maximum loads than both the DNP and LCP groups. There were no significant differences in yield loads. Both the DNP and DVR groups had significantly less displacement at yield than the LCP group. These 3 groups had similar yield loads. However, the LCP was less stiff than the DVR and had more displacement at yield than both the DVR and DNP. The yield load of all 3 implants was much higher than previously described loads for active wrist and finger motion.

  10. Using Standardized Patients to Teach Interprofessional Competencies to Dental Students.

    Science.gov (United States)

    Anders, Patrick L; Scherer, Yvonne Krall; Hatton, Michael; Antonson, Donald; Austin-Ketch, Tammy; Campbell-Heider, Nancy

    2016-01-01

    The aims of this study were to develop, implement, and evaluate a novel interprofessional standardized patient exercise (ISPE) with oral-systemic and interprofessional collaborative practice (IPCP) components. Dental students and doctor of nursing practice (DNP) students at one U.S. university participated in the simulation, which was primarily designed to test their teamwork skills. In spring 2014, DNP students worked in the dental clinics with dental students under the supervision of nursing and dental faculty members. To test the teamwork outcomes for both groups of students, a standardized patient (SP) scenario was designed to include multiple chronic medical diagnoses and an oral-systemic component. The exercise was filmed for later review. Outcomes measures included SP and student self-evaluations and faculty evaluation of student documentation. The primary outcome of interest from a dental standpoint was faculty evaluation of IPCP competencies derived from the Core Competencies of Interprofessional Collaborative Practice and were deemed to be observable by faculty when viewing the videotaped scenario. Eight teams of students participated with an SP trained in the scenario. Each team consisted of a DNP student, a fourth-year dental student, and a second-year dental student. All eligible students in the DNP class (n=20) and eight students from each dental class (approximately 110 each) participated. The results showed that the teams scored highest on the role/responsibilities subscale, indicating students were respectful of each other's roles and expertise and effectively engaged each other to develop strategies to meet the patient's needs. Scores on the three other subscales (values/ethics, interprofessional communication, and teams/teamwork) were also high. These findings appeared to support IPCP as a method to foster knowledge and respect for other roles and responsibilities, improve appreciation of teamwork, and encourage better communication among health

  11. Anti-allergic activity of 2,4,6-trihydroxy-3-geranylacetophenone (tHGA) via attenuation of IgE-mediated mast cell activation and inhibition of passive systemic anaphylaxis.

    Science.gov (United States)

    Tan, Ji Wei; Israf, Daud Ahmad; Harith, Hanis Hazeera; Md Hashim, Nur Fariesha; Ng, Chean Hui; Shaari, Khozirah; Tham, Chau Ling

    2017-03-15

    tHGA, a geranyl acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent ovalbumin-induced allergic airway inflammation in a murine model of allergic asthma by targeting cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including asthma by releasing cysteinyl leukotrienes. The anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the anti-allergic effects of tHGA in cellular and animal models of IgE-mediated mast cell degranulation. For in vitro model of IgE-mediated mast cell degranulation, DNP-IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA to induce degranulation. For IgE-mediated passive systemic anaphylaxis, Sprague Dawley rats were sensitized by intraperitoneal injection of DNP-IgE before challenged with DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-hexosaminidase and histamine) as well as de novo mediators (interleukin-4, tumour necrosis factor-α, prostaglandin D 2 and leukotriene C 4 ). Pre-treatment of tHGA also prevented IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent anti-allergic activity via attenuation of IgE-mediated mast cell degranulation and inhibition of IgE-mediated passive systemic anaphylaxis. Thus, tHGA may have the potential to be developed as a mast cell stabilizer for the treatment of allergic diseases in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Restoring penis sensation in patients with low spinal cord lesions: the role of the remaining function of the dorsal nerve in a unilateral or bilateral TOMAX procedure.

    Science.gov (United States)

    Overgoor, Max L E; Braakhekke, Jan P; Kon, Moshe; De Jong, Tom P V M

    2015-04-01

    The recently developed TOMAX-procedure restores unilateral genital sensation, improving sexual health in men with a low spinal lesion (LSL). It connects one dorsal nerve of the penis (DNP) to the intact ipsilateral ilioinguinal nerve. We proposed bilateral neurotization for full sensation of the glans but this entails cutting both DNPs, risking patients' erection/ejaculation ability. The objective was to select patients for a bilateral TOMAX-procedure by measuring remaining DNP function, and perform the first bilateral cases. In 30 LSL patients with no penile- but normal groin sensation selected for a unilateral TOMAX-procedure the integrity of the sacral-reflex-arc and DNP function was tested pre-operatively using bilateral needle electromyography (EMG)-bulbocavernosus reflex (BCR) measurements, and an interview about reflex erections (RE) ability. In 13 spina bifida- and 17 spinal cord injury patients [median age 29.5 years (range 13-59 years), spinal lesion T12 (incomplete) to sacral], seven (23%) patients reported RE, four (57%) with intact BCR, and of nine (30%) patients with intact BCR, four reported RE (44%). Even patients with a LSL and no penile sensation can have signs of remaining DNP function, but cutting both DNPs to restore full glans sensation in a bilateral TOMAX-procedure might interfere with their RE/ejaculation. To avoid this risk, we propose a selecting-protocol for a unilateral- or bilateral procedure using RE and BCR measurements. Using this protocol, three patients were bilaterally operated with promising preliminary results. Full sensation of the glans could lead to further improvement in sexual function. © 2014 Wiley Periodicals, Inc.

  13. Dynamic nuclear polarization in thin polymer foils and tubes

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    1995-02-01

    First results of DNP at 2.5 T and below 0.3 K in thin polymer foils and tubes with the chemical composition (CX 2) n, [ X = 1H, 2D, 19F ], doped with TEMPO, are presented. Appreciable polarization of protons, deuterons, and 19F-nuclei were obtained. The samples can be handled at room temperature for several hours, and therefore they are suitable for new applications.

  14. Dynamic nuclear polarization in thin polymer foils and tubes

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Bunyatova, E.I. [Joint Inst. for Nuclear Research, Dubna (Russian Federation); Hautle, P. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Konter, J.A. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Mango, S. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1995-03-01

    First results of DNP at 2.5 T and below 0.3 K in thin polymer foils and tubes with the chemical composition (CX{sub 2}){sub n}, [X={sup 1}H, {sup 2}D, {sup 19}F], doped with TEMPO, are presented. Appreciable polarizations of protons, deuterons, and {sup 19}F-nuclei were obtained. The samples can be handled at room temperature for several hours, and therefore they are suitable for new applications. ((orig.))

  15. Dynamic Nuclear Polarization and Relaxation of H and D Atoms in Solid Mixtures of Hydrogen Isotopes

    Science.gov (United States)

    Sheludiakov, S.; Ahokas, J.; Järvinen, J.; Vainio, O.; Lehtonen, L.; Vasiliev, S.; Lee, D. M.; Khmelenko, V. V.

    2017-04-01

    We report on a study of dynamic nuclear polarization and electron and nuclear spin relaxation of atomic hydrogen and deuterium in solid molecular matrices of H2, D2, and HD mixtures. The electron and nuclear spin relaxation times (T_{1e} and T_{1N}) were measured within the temperature range 0.15-2.5 K in a magnetic field of 4.6 T, conditions which ensure a high polarization of electron spins. We found that T_{1e} is nearly temperature independent in this temperature range, while T_{1N} decreased by two orders of magnitude upon raising temperature. Such strong temperature dependence is typical for the nuclear Orbach mechanism of relaxation via the electron spins. We found that the nuclear spins of H atoms in solid D2 and D2{:}HD can be efficiently polarized by the Overhauser effect. Pumping the forbidden transitions of H atoms also leads to DNP, with the efficiency strongly dependent on the concentration of D atoms. This behavior indicates the cross effect mechanism of the DNP and nuclear relaxation, which turns out to be well resolved in the conditions of our experiments. Efficient DNP of H atoms was also observed when pumping the middle D line located in the center of the ESR spectrum. This phenomenon can be explained in terms of clusters or pairs of H atoms with a strong exchange interaction. These clusters have partially allowed transitions in the center of the ESR spectrum, and DNP may be created via the resolved cross effect.

  16. A philicity based analysis of adsorption of small molecules in zeolites

    Indian Academy of Sciences (India)

    Unknown

    A philicity based analysis of adsorption of small molecules in zeolites. 545. Table 1. Pertinent geometrical parameters of 3T cluster calculated using. DFT method at BLYP/DNP level of theory. Parameter. 3T cluster-1(*). 3T cluster2 (*). 3T (**). Bond lengths (Å). O4–H8. 0⋅975. 0⋅973. 0⋅973. Si–O4. 1⋅740. 1⋅746. 1⋅745.

  17. Optically Driven Spin Based Quantum Dots for Quantum Computing

    Science.gov (United States)

    2008-01-01

    is accomplished by a modified optical RKKY (ORKKY) interaction yielding a Heisenberg Hamiltonian coupling between the two spins. High speed state...the Zeeman resonance are cancelled out through feedback via the DNP mechanism (Fig. 3d ). The quantitative enhancement of T2* by this mechanism is...the latter a global-basis interaction. An example of a global-basis interaction between qubits is Heisenberg exchange, where a bases-invariant

  18. UCP2- and non-UCP2-mediated electric current in eukaryotic cells exhibits different properties.

    Science.gov (United States)

    Wang, Ruihua; MoYung, K C; Zhang, M H; Poon, Karen

    2015-12-01

    Using live eukaryotic cells, including cancer cells, MCF-7 and HCT-116, normal hepatocytes and red blood cells in anode and potassium ferricyanide in cathode of MFC could generate bio-based electric current. Electrons and protons generated from the metabolic reaction in both cytosol and mitochondria contributing to the leaking would mediate the generation of electric current. Both resveratrol (RVT) and 2,4-dinitrophenol (DNP) used to induce proton leak in mitochondria were found to promote electric current production in all cells except red blood cells without mitochondria. Proton leak might be important for electric current production by bringing the charge balance in cells to enhance the further electron leak. The induced electric current by RVT can be blocked by Genipin, an inhibitor of UCP2-mediated proton leak, while that induced by DNP cannot. RVT could reduce reactive oxygen species (ROS) level in cells better than that of DNP. In addition, RVT increased mitochondrial membrane potential (MMP), while DNP decreased it. Results highly suggested the existence of at least two types of electric current that showed different properties. They included UCP2-mediated and non-UCP2-mediated electric current. UCP2-mediated electric current exhibited higher reactive oxygen species (ROS) reduction effect per unit electric current production than that of non-UCP2-mediated electric current. Higher UCP2-mediated electric current observed in cancer cells might contribute to the mechanism of drug resistence. Correlation could not be established between electric current production with either ROS and MMP without distinguishing the types of electric current.

  19. Electric Energy Security in the Domestic Theater

    Science.gov (United States)

    2010-06-01

    center communications COM IEC 61850 Substation automation and protection COM IEC 61968/61970 Application level energy management system interfaces...ASHRAE 135 - 2008/ISO 16484 -5 Building automation COM DNP3 Substation and feeder device automation COM IEC 60870 -6 / TASE.2 Inter-control... IEC 62351 Parts 1 -8 Information security for power system control operations COM IEEE C37.118 Phasor measurement unit (PMU)communications

  20. A Secure, Intelligent, and Smart-Sensing Approach for Industrial System Automation and Transmission over Unsecured Wireless Networks.

    Science.gov (United States)

    Shahzad, Aamir; Lee, Malrey; Xiong, Neal Naixue; Jeong, Gisung; Lee, Young-Keun; Choi, Jae-Young; Mahesar, Abdul Wheed; Ahmad, Iftikhar

    2016-03-03

    In Industrial systems, Supervisory control and data acquisition (SCADA) system, the pseudo-transport layer of the distributed network protocol (DNP3) performs the functions of the transport layer and network layer of the open systems interconnection (OSI) model. This study used a simulation design of water pumping system, in-which the network nodes are directly and wirelessly connected with sensors, and are monitored by the main controller, as part of the wireless SCADA system. This study also intends to focus on the security issues inherent in the pseudo-transport layer of the DNP3 protocol. During disassembly and reassembling processes, the pseudo-transport layer keeps track of the bytes sequence. However, no mechanism is available that can verify the message or maintain the integrity of the bytes in the bytes received/transmitted from/to the data link layer or in the send/respond from the main controller/sensors. To properly and sequentially keep track of the bytes, a mechanism is required that can perform verification while bytes are received/transmitted from/to the lower layer of the DNP3 protocol or the send/respond to/from field sensors. For security and byte verification purposes, a mechanism needs to be proposed for the pseudo-transport layer, by employing cryptography algorithm. A dynamic choice security buffer (SB) is designed and employed during the security development. To achieve the desired goals of the proposed study, a pseudo-transport layer stack model is designed using the DNP3 protocol open library and the security is deployed and tested, without changing the original design.

  1. Developing an Acquisition Strategy for the Colombian Navy’s New Strategic Surface Ships

    Science.gov (United States)

    2007-06-01

    37 Departamento Nacional de Planeacion (2006), “Visión Colombia II Centenario: 2019.” Retrieved 14 May 2007 from http...40 Jefatura Oficina Planeacion A.R.C. (July 2006), Plan de Desarrollo 2007–2010, conference presented at Dirección General Marítima, Bogota...Departamento Nacional de Planeacion (2006). “Visión Colombia II Centenario: 2019”. Retrieved 14 May 2007 from http://www.dnp.gov.co/paginas_detalle.aspx?idp=888

  2. Using Honeynets and the Diamond Model for ICS Threat Analysis

    Science.gov (United States)

    2016-05-11

    various Microsoft update servers. While source IP addresses can be spoofed, a cursory examination of payload data showed that the traffic from these...running Microsoft Win- dows. The various external hosts with which they communicate corroborate this assumption. This includes known Windows update ...principally for DNP, a common protocol used within SCADA net- works. The following SiLK query revealed a number of hosts that were engaged in communica

  3. A Secure, Intelligent, and Smart-Sensing Approach for Industrial System Automation and Transmission over Unsecured Wireless Networks

    Directory of Open Access Journals (Sweden)

    Aamir Shahzad

    2016-03-01

    Full Text Available In Industrial systems, Supervisory control and data acquisition (SCADA system, the pseudo-transport layer of the distributed network protocol (DNP3 performs the functions of the transport layer and network layer of the open systems interconnection (OSI model. This study used a simulation design of water pumping system, in-which the network nodes are directly and wirelessly connected with sensors, and are monitored by the main controller, as part of the wireless SCADA system. This study also intends to focus on the security issues inherent in the pseudo-transport layer of the DNP3 protocol. During disassembly and reassembling processes, the pseudo-transport layer keeps track of the bytes sequence. However, no mechanism is available that can verify the message or maintain the integrity of the bytes in the bytes received/transmitted from/to the data link layer or in the send/respond from the main controller/sensors. To properly and sequentially keep track of the bytes, a mechanism is required that can perform verification while bytes are received/transmitted from/to the lower layer of the DNP3 protocol or the send/respond to/from field sensors. For security and byte verification purposes, a mechanism needs to be proposed for the pseudo-transport layer, by employing cryptography algorithm. A dynamic choice security buffer (SB is designed and employed during the security development. To achieve the desired goals of the proposed study, a pseudo-transport layer stack model is designed using the DNP3 protocol open library and the security is deployed and tested, without changing the original design.

  4. Non-Topotactic Transformation of Silicate Nanolayers into Mesostructured MFI Zeolite Frameworks During Crystallization.

    Science.gov (United States)

    Berkson, Zachariah J; Messinger, Robert J; Na, Kyungsu; Seo, Yongbeom; Ryoo, Ryong; Chmelka, Bradley F

    2017-05-02

    Mesostructured MFI zeolite nanosheets are established to crystallize non-topotactically through a nanolayered silicate intermediate during hydrothermal synthesis. Solid-state 2D NMR analyses, with sensitivity enhanced by dynamic nuclear polarization (DNP), provide direct evidence of shared covalent 29 Si-O- 29 Si bonds between intermediate nanolayered silicate moieties and the crystallizing MFI zeolite nanosheet framework. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Genetic analysis of sunflower chlorophyll mutants

    International Nuclear Information System (INIS)

    Mashkina, E.V.; Guskov, E.P.

    2001-01-01

    The method of getting the chlorophyll mutations in sunflower was developed by Y.D. Beletskii in 1969 with the use of N-nitroso-N-methylurea (NMH). Certain concentrations of NMH are known to induce plastid mutations in growing seeds, and their yield depends on the duration of the exposure. The given work presented studies on the influence of rifampicin (R) and 2,4-dinitrophenol (DNP) on the genetic activity NMH, as an inductor of plastid and nuclear mutations

  6. Electrochemical modification of indium tin oxide using di(4-nitrophenyl) iodonium tetrafluoroborate.

    Science.gov (United States)

    Charlton, Matthew R; Suhr, Kristin J; Holliday, Bradley J; Stevenson, Keith J

    2015-01-20

    Optoelectronic applications often rely on indium tin oxide (ITO) as a transparent electrode material. Improvements in the performance of such devices as photovoltaics and light-emitting diodes often requires robust, controllable modification of the ITO surface to enhance interfacial charge transfer properties. In this work, modifier films were deposited onto ITO by the electrochemical reduction of di(4-nitrophenyl) iodonium tetrafluoroborate (DNP), allowing for control over surface functionalization. The surface coverage could be tuned from submonolayer to multilayer coverage by either varying the DNP concentration or the number of cyclic voltammetry (CV) grafting scans. Modification of ITO with 0.8 mM DNP resulted in near-monolayer surface coverage (4.95 × 10(14) molecules/cm(2)). X-ray photoelectron spectroscopy (XPS) analysis confirmed the presence of 4-nitrophenyl (NO2Ph) moieties on the ITO surface through the detection of a NO2 nitrogen signal at 405.6 eV after grafting. Further XPS evidence suggests that the NO2Ph radicals do not bond to the surface indium or tin sites, consistent with modification occurring either through bonding to surface hydroxyl groups or through strong physisorption on ITO. CV in the presence of an electroactive probe and electrochemical impedance spectroscopy (EIS) were used to investigate the electronic effects that modification via DNP has on ITO. Even at submonolayer coverage, the insulating organic films can reduce the current response to ferrocene oxidation and reduction by more than 25% and increase the charge transfer resistance by a factor of 10.

  7. Produção de álcoois superiores por linhagens de Saccharomyces durante a fermentação alcoólica Production of higher alcohols by Saccharomyces strains during alcoholic fermentation

    Directory of Open Access Journals (Sweden)

    L.E. Gutierrez

    1993-12-01

    Full Text Available A produção de álcoois superiores pelas leveduras Saccharomyces cerevisiae M-300-A, Saccharomyces uvarum IZ-1904 e levedura de panificação (Saccharomyces cerevisiae foi estudada em diversas condições de temperatura, concentração de sacarose, pH, fontes de nitrogênio e com inibidor 2-4 dinitrofenol (DNP. Em todas as condições estudadas, a levedura Saccharomyces uvarum IZ-1904 apresentou a menor formação de álcoois superiores enquanto a levedura de panifícação apresentou os teores mais elevados. Com o aumento de temperatura e da concentração de sacarose ocorreu maior formação de álcool isoamílico pelas leveduras estudadas. Em pH 4,5 ocorreu menor produção de álcoois superiores do que em pH 3,0. Na presença do inibidor DNP ocorreu significativa redução (pThe production of higher alcohols by Saccharomyces cerevisiae M-300-A, Saccharomyces uvarum IZ-1904 and baker's yeast (5. cerevisiae was studied under several temperature conditions, sucrose level, pH, nitrogen sources and with 2-4 dinitrophenol (DNP. The yeast IZ-1904 showed lower production of higher alcohols than other yeasts in all conditions studied. With the increase of temperature and higher level of sucrose an increase of isoamyl alcohol production was observed. A lower formation of higher alcohols was observed at pH 4.5 than at pH 3.0. With the addition of DNP occurred a significant reduction in isoamyl alcohol content. The yeasts did not show the sanie production of higher alcohols in relation to urea and ammonium sulfate.

  8. Spectroscopic and theoretical study of the o-vanillin hydrazone of the mycobactericidal drug isoniazid

    Science.gov (United States)

    González-Baró, Ana C.; Pis-Diez, Reinaldo; Parajón-Costa, Beatriz S.; Rey, Nicolás A.

    2012-01-01

    A complete and detailed study of the hydrazone obtained from condensation of antituberculous isoniazid (hydrazide of the isonicotinic acid, INH) and o-vanillin (2-hydroxy-3-methoxybenzaldehyde, o-HVa) is performed. It includes structural and spectroscopic analyses, comparing experimental and theoretical results. The compound was obtained as a chloride of the pyridinic salt (INHOVA +Cl -) but it will be referred as INHOVA for the sake of simplicity. The conformational space was searched and optimized geometries were determined both in gas phase and including solvent effects. Vibrational (IR and Raman), electronic and NMR spectra were registered and assigned with the help of computational methods based on the Density Functional Theory. Isoniazid hydrazones are good candidates for therapeutic agents against tuberculosis with conserved efficiency and lower toxicity and resistance than parent INH.

  9. [THE INFLUENCE OF THE NORMOBARIC HYPOXIA FOR THE BREATHIHG INDEXES OF THE CHILDREN LIVED IN RADIOACTIVE CONTAMINATED TERRITORIES].

    Science.gov (United States)

    Berezovskyi, V A; Lisukha, L M; Stepanova, Ye I; Kolpacov, I Ye

    2015-01-01

    There was conducted a research of the influence the sanogenic level of intermittent normobaric hypoxia (INH) for children lived in radioactively contaminated territories. The research involved 106 children in the age from 6 to 17 with symptoms ofbronchospasm: 55 persons of the main group and 51 persons of the screening group. It was confirmed that after the course of sessions INH (12 % oxygen in nitrogen) the respiratory system has changed. It is known statistically that in the main group the indexes of ventilation lung capacity have increased : vital capacity of the lungs, bronchial obstruction proximal bronchi of large and medium diameter, and distal bronchi small diameter. The bronchospasm has removed completely or partially. It was confirmed significantly that the breath-holding time becomes longer (test Stange) and heart rat reduced in companson with the screening group.

  10. Studies on mycobacterium tuberculosis sensitivity test by using the method of rapid radiometry with appendixes of clinical results

    International Nuclear Information System (INIS)

    Yang Yongqing; Jiang Yimin; Lu Wendong; Zhu Rongen

    1987-01-01

    Three standard strains of mycobacterium tuberculosis (H 37 RV-fully sensitive, SM-R1000 μg/ml, RFP-R 100 μg/ml) were tested with 10 concentration of 5 antitubercular agent, INH, SM, PAS, RFP and EB. 114 isolates of mycobacterium tuberculosis taken from patients were tested with INH, PAS, SM and RFP. They were agreed with the results of standard Lowenstein-Jensen method in 81.7%. 82% of the isolate test were completed within 5 days. The method may be used in routine clinical work. The liquid media prepared by authors do not require human serum albumin and it is less expensive and readily available

  11. Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions.

    Science.gov (United States)

    Rutherford, Merrin E; Hill, Philip C; Triasih, Rina; Sinfield, Rebecca; van Crevel, Reinout; Graham, Stephen M

    2012-10-01

    Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers. These barriers are largely resolvable, and proposed solutions such as the adoption of symptom-based screening and shorter drug regimens are discussed. Integrated multicomponent and site-specific solutions need to be developed and evaluated within a public health framework to overcome the policy-practice gap and provide functional PT programmes for children in endemic settings. © 2012 Blackwell Publishing Ltd.

  12. Hereditary Angioedema: a Challenging Diagnosis for the Gastroenterologist

    Directory of Open Access Journals (Sweden)

    Gábos Gabriella

    2016-12-01

    Full Text Available Hereditary angioedema (HAE caused by a deficiency of C1 esterase inhibitor enzyme (C1-INH is a very rare, autosomal dominantly inherited genetic disorder, characterized by recurrent peripheral angioedema, painful abdominal attacks and episodes of laryngeal edema. Abdominal attacks are frequent symptoms in adult HAE patients, occurring in more than 90% of the cases. Angioedema in the bowel or abdomen can occur in the absence of cutaneous manifestations and may be easily misdiagnosed unless the clinician has a high degree of awareness to include HAE in the differential diagnosis. Misdiagnosis is associated with inadequate treatments, including unnecessary surgical procedures. Any patient who presents recurrent episodes of swelling should be evaluated for HAE caused by C1-INH deficiency. New therapies could save lives and dramatically improve their quality of life.

  13. Hepatoprotective agent tethered isoniazid for the treatment of drug-induced hepatotoxicity: Synthesis, biochemical and histopathological evaluation

    Directory of Open Access Journals (Sweden)

    Charan Singh

    2014-01-01

    Full Text Available The aim of the study was to investigate the protective effect of isoniazid–curcumin conjugate (INH–CRM in INH-induced hepatic injury by biochemical analysis and histology examination of liver in Wistar rats. The biochemical analysis included determination of the levels of plasma cholesterol, triglycerides (TG, albumin content, and lipid peroxidation (MDA. INH–CRM administration resulted in a significant decrease in plasma cholesterol, TG, and MDA levels in the liver tissue homogenate with an elevation in albumin level indicating its hepatoprotective activity. Histology of the liver further confirmed the reduction in hepatic injury. The hepatoprotective with INH–CRM can be attributed to the antioxidant activity of curcumin. The conjugate probably stabilizes the curcumin molecule, preventing its presystemic metabolism thereby enhancing its bioavailability and therefore, its hepatoprotective activity. Thus, the novel INH–CRM has the potential to alleviate INH-induced liver toxicity in antitubercular treatment.

  14. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant

    DEFF Research Database (Denmark)

    Aberer, Werner; Maurer, Marcus; Bouillet, Laurence

    2017-01-01

    BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long......-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option. METHODS: Data on LTP use, attacks, and treatments were recorded. Attack...... characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP. RESULTS: Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while...

  15. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids.

    Science.gov (United States)

    Ngwa, Wilfred; Kumar, Rajiv; Moreau, Michele; Dabney, Raymond; Herman, Allen

    2017-01-01

    Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous ("sea") routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

  16. Biocompatible hyperbranched polyester magnetic nanocarrier for stimuli-responsive drug release.

    Science.gov (United States)

    Zhao, Chili; Han, Qiaorong; Qin, Hong; Yan, Hong; Qian, Zhilei; Ma, Zhenye; Zhang, Xia; Li, Xinghui

    2017-05-01

    A novel biocompatible magnetic nanocomposite drug carrier was developed by first chemically modifying a hyperbranched polyester (HBPE) with dodecenyl succinic anhydride (DDSA) functional groups to produce HBPE-DDSA. The magnetic nanocomposite Fe 3 O 4 /HBPE-DDSA was then synthesized by dispersing superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles within HBPE-DDSA. The structure and magnetic properties of the nanocomposite were characterized by 1 H NMR, MALDI-MS, XRD, FTIR, TEM, and SQUID analyses. Isoniazid (INH) was selected as a model antituberculosis drug to investigate the in vitro drug release properties of Fe 3 O 4 /HBPE-DDSA/INH. The cytotoxicity of the magnetic nanocomposites was assessed by CCK-8 assay. The results indicated that Fe 3 O 4 /HBPE-DDSA is a promising potential drug carrier for a magnetic-targeted drug delivery system.

  17. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

    Directory of Open Access Journals (Sweden)

    Wilfred Ngwa

    2017-09-01

    Full Text Available Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH (air versus traditional intravenous (“sea” routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

  18. Design and Development of Layered Security: Future Enhancements and Directions in Transmission

    Science.gov (United States)

    Shahzad, Aamir; Lee, Malrey; Kim, Suntae; Kim, Kangmin; Choi, Jae-Young; Cho, Younghwa; Lee, Keun-Kwang

    2016-01-01

    Today, security is a prominent issue when any type of communication is being undertaken. Like traditional networks, supervisory control and data acquisition (SCADA) systems suffer from a number of vulnerabilities. Numerous end-to-end security mechanisms have been proposed for the resolution of SCADA-system security issues, but due to insecure real-time protocol use and the reliance upon open protocols during Internet-based communication, these SCADA systems can still be compromised by security challenges. This study reviews the security challenges and issues that are commonly raised during SCADA/protocol transmissions and proposes a secure distributed-network protocol version 3 (DNP3) design, and the implementation of the security solution using a cryptography mechanism. Due to the insecurities found within SCADA protocols, the new development consists of a DNP3 protocol that has been designed as a part of the SCADA system, and the cryptographically derived security is deployed within the application layer as a part of the DNP3 stack. PMID:26751443

  19. Simple spectrophotometric methods for quantification of modafinil us-ing 1,2-naphthoquinone-4-sulphonate and 2,4-dinitrophenol as analyti-cal reagents

    Directory of Open Access Journals (Sweden)

    Burla Sunitha Venkata Seshamamba

    2014-10-01

    Full Text Available Two simple visible spectrophotometric methods are developed and validated for the quantifica-tion of modafinil using 1,2-naphthoquinone-4-sulphonic acid (NQS method and 2,4-dinitrophenol (DNP method as analytical reagents. The NQS method involves the reaction of modafinil with 1,2-naphthoquinone-4-sulphonate in alkaline medium at room conditions to form a yellow colored product exhibiting maximum absorption at 430 nm. DNP method is based on the proton transfer from 2,4-dinitrophenol to modafinil at room conditions and then we have the formation of yellow colored ion-pair complex exhibiting maximum absorption at 475 nm. Dif-ferent variables affecting the reaction were studied and optimized. Under the optimized experi-mental conditions, Beer's law is obeyed in the concentration ranges of 10-100 and 8-60 μg/mL with the detection of limit values of 0.486 and 0.258 μg/mL for NQS method and DNP method, respectively The molar absorptivity and Sandell's sensitivity for both of the methods are report-ed. The methods were validated in terms of accuracy, precision and robustness. The results were satisfactory. The proposed methods were effectively applied to the analysis of the modafinil in their tablet formulations. The recoveries were 99.92% and 99.96% with RSD and 0.863% and 0.722% for NQS and DNS methods, respectively. The assay was not interfered by common ex-cipients.

  20. Suppressive effects of anti-allergic agent suplatast tosilate (IPD-1151T on the expression of co-stimulatory molecules on mouse splenocytes in vivo

    Directory of Open Access Journals (Sweden)

    Masatsugu Kurokawa

    2001-01-01

    Full Text Available The effects of IPD-1151T on the expression of costimulatory molecules, CD40, CD80 and CD86, were investigated in vivo using mice with allergic disorders. BALB/c mice were immunized intraperitoneally with two doses of dinitrophenylated ovalbumin (DNP-OVA at 1-week intervals. These mice then were treated intraperitoneally with 100μg/kg of IPD1151T once a day for 14 days, starting 7 days after the first immunization. On day 21, some mice were challenged intraperitoneally with DNP-OVA and the other mice were not challenged. All mice were autopsied on day 22 and assayed for immunoglobulin E, interleuken (IL-4 and IL-5 productions following DNP-OVA immunization. The intraperitoneal treatment with IPD-1151T strongly suppressed immunoglobulin E contents in serum, which were enhanced by DNA-OVA immunization. IPD-1151T also caused a decrease in both IL-4 and IL-5 levels in splenic lymphocytes. We next examined the influence of IPD1151T on co-stimulatory molecule expression on splenic lymphocytes. IPD-1151T caused suppression of CD40 and CD86 expression; however, the treatments did not affect CD80 expression.

  1. A 250 GHz gyrotron with a 3 GHz tuning bandwidth for dynamic nuclear polarization.

    Science.gov (United States)

    Barnes, Alexander B; Nanni, Emilio A; Herzfeld, Judith; Griffin, Robert G; Temkin, Richard J

    2012-08-01

    We describe the design and implementation of a novel tunable 250 GHz gyrotron oscillator with >10 W output power over most of a 3 GHz band and >35 W peak power. The tuning bandwidth and power are sufficient to generate a >1 MHz nutation frequency across the entire nitroxide EPR lineshape for cross effect DNP, as well as to excite solid effect transitions utilizing other radicals, without the need for sweeping the NMR magnetic field. Substantially improved tunability is achieved by implementing a long (23 mm) interaction cavity that can excite higher order axial modes by changing either the magnetic field of the gyrotron or the cathode potential. This interaction cavity excites the rotating TE(₅,₂,q) mode, and an internal mode converter outputs a high-quality microwave beam with >94% Gaussian content. The gyrotron was integrated into a DNP spectrometer, resulting in a measured DNP enhancement of 54 on the membrane protein bacteriorhodopsin. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. An Academic-Practice Partnership Model to Grow and Sustain Advanced Practice Nursing.

    Science.gov (United States)

    Williams, Tracy E; Howard, Patricia B

    2017-12-01

    The aims of this article were to describe the implementation of an academic-practice partnership for healthcare system workforce development and provide preliminary outcomes of the associated pilot study. The demand for cross-continuum healthcare delivery models necessitates creation of workforce development structures for advanced practice nursing. An academic-practice partnership specified enrollment of 5 cohorts of BSN staff nurses in a 3-year DNP program. Qualitative methods were used to explore pilot data at midpoint of cohort 1 student progression to determine learning outcomes and DNP projects with potential for impact on organization goals. Partnership implementation experiences indicate that contractual agreements and an established evaluation plan are keys to academic-practice partnership success. Pilot study findings suggest that curriculum core courses provide a foundation for designing DNP projects congruent with acute and primary care health system goals. Implementing an academic-practice partnership is a strategy for workforce development to increase retention of advanced practice nurses. Academic-practice partnerships can serve as a catalyst for a paradigm shift for changing models of care, thus enhancing workforce development succession planning for sustainable growth in healthcare systems.

  3. Unsuitability of using the DNPH-coated solid sorbent cartridge for determination of airborne unsaturated carbonyls

    Science.gov (United States)

    Ho, Steven Sai Hang; Ho, K. F.; Liu, W. D.; Lee, S. C.; Dai, W. T.; Cao, J. J.; Ip, H. S. S.

    2011-01-01

    Measurements of aldehydes and ketones are typically conducted by derivatization using sorbent cartridges coated with 2,4-dinitrophenylhydrazine (DNPH). The collected samples are eluted with acetonitrile and analyzed by high-pressure liquid chromatography coupled with an ultra-violet detector (HPLC/UV). This paper intends to examine artifacts about its suitability in identification of unsaturated carbonyls. Kinetic tests for acrolein, crotonaldehyde, methacrolein and methyl vinyl ketone (MVK) showed formations of carbonyl-DNP-hydrazone during sampling, which could further react with DNPH, resulting in undesired UV absorption products [e.g., carbonyl-DNP-hydrazone-DNPH (dimer) and 2(carbonyl-DNP-hydrazone)-DNPH (trimer)]. The dimerization and trimerization occurred for acrolein and MVK whereas only dimerization for crotonaldehyde and methacrolein. The polymerization products undoubtedly affect the integrity of the chromatogram, leading to misidentification and inaccurate quantification. Whether precautions taken during sampling and/or sample treatment could avoid or minimize this artifact has not been thoughtfully investigated. More often, such artifacts are usually overlooked by scientists when the data are reported.

  4. Frequency-agile gyrotron for electron decoupling and pulsed dynamic nuclear polarization.

    Science.gov (United States)

    Scott, Faith J; Saliba, Edward P; Albert, Brice J; Alaniva, Nicholas; Sesti, Erika L; Gao, Chukun; Golota, Natalie C; Choi, Eric J; Jagtap, Anil P; Wittmann, Johannes J; Eckardt, Michael; Harneit, Wolfgang; Corzilius, Björn; Th Sigurdsson, Snorri; Barnes, Alexander B

    2018-04-01

    We describe a frequency-agile gyrotron which can generate frequency-chirped microwave pulses. An arbitrary waveform generator (AWG) within the NMR spectrometer controls the microwave frequency, enabling synchronized pulsed control of both electron and nuclear spins. We demonstrate that the acceleration of emitted electrons, and thus the microwave frequency, can be quickly changed by varying the anode voltage. This strategy results in much faster frequency response than can be achieved by changing the potential of the electron emitter, and does not require a custom triode electron gun. The gyrotron frequency can be swept with a rate of 20 MHz/μs over a 670 MHz bandwidth in a static magnetic field. We have already implemented time-domain electron decoupling with dynamic nuclear polarization (DNP) magic angle spinning (MAS) with this device. In this contribution, we show frequency-swept DNP enhancement profiles recorded without changing the NMR magnet or probe. The profile of endofullerenes exhibits a DNP profile with a agile high-power microwave sources. Copyright © 2018. Published by Elsevier Inc.

  5. Dissemination of Scholarship Across Eight Cohorts of Doctor of Nursing Practice Graduates.

    Science.gov (United States)

    Becker, Kathleen D; Johnson, Shania; Rucker, Denise; Finnell, Deborah S

    2017-12-23

    The aim of this investigation was to evaluate the publication record across eight cohorts of post-master's Doctor of Nursing Practice (DNP) graduates. Dissemination of findings from evidence-based practice is described in the American Association of the Colleges of Nursing (AACN), Doctor of Nursing Practice (DNP) Essential III. Students in DNP programs are expected to generate deliverables (e.g., a manuscript) of evidence to improve practice or patient outcomes. A descriptive study was conducted to determine whether two key manuscripts (i.e., integrative review and an evidence-based quality improvement [EBQI] project) were disseminated in peer reviewed journals, and if so, the length of time from graduation to publication. Co-authorship with faculty advisors and contributors was also examined. The number of EBQI publications outpaces the number of integrative reviews over this span of time. Time to publication from graduation has decreased in recent years. Expecting, rather than encouraging a publishable-ready manuscript as a course deliverable would further student's motivation to disseminate their scholarship. Focused attention on faculty co-authorship may help increase the number of successful student publications for both integrative reviews and EBQI projects and decrease the time from graduation for those publications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. New Security Development and Trends to Secure the SCADA Sensors Automated Transmission during Critical Sessions

    Directory of Open Access Journals (Sweden)

    Aamir Shahzad

    2015-10-01

    Full Text Available Modern technology enhancements have been used worldwide to fulfill the requirements of the industrial sector, especially in supervisory control and data acquisition (SCADA systems as a part of industrial control systems (ICS. SCADA systems have gained popularity in industrial automations due to technology enhancements and connectivity with modern computer networks and/or protocols. The procurement of new technologies has made SCADA systems important and helpful to processing in oil lines, water treatment plants, and electricity generation and control stations. On the other hand, these systems have vulnerabilities like other traditional computer networks (or systems, especially when interconnected with open platforms. Many international organizations and researchers have proposed and deployed solutions for SCADA security enhancement, but most of these have been based on node-to-node security, without emphasizing critical sessions that are linked directly with industrial processing and automation. This study concerns SCADA security measures related to critical processing with specified sessions of automated polling, analyzing cryptography mechanisms and deploying the appropriate explicit inclusive security solution in a distributed network protocol version 3 (DNP3 stack, as part of a SCADA system. The bytes flow through the DNP3 stack with security computational bytes within specified critical intervals defined for polling. We took critical processing knowledge into account when designing a SCADA/DNP3 testbed and deploying a cryptography solution that did not affect communications.

  7. Selective Spectrophotometric Determination of Metformin Hydrochloride in Pharmaceuticals and Urine Using Two Nitrophenols as Chromogenic Agents

    Directory of Open Access Journals (Sweden)

    Kanakapura Basavaiah

    2017-06-01

    Full Text Available Metformin hydrochloride (MFH is an oral anti-diabetic drug of biguanide class. Two selective spectrophotometric methods were presented for the determination of MFH in pharmaceuticals. The methods were based on the measurement of yellow-coloured charge-transfer complexes formed between MFH and two poly-nitrophenols, namely, 2,4-dinitrophenol (DNP method, at 405 nm and picric acid (PA method; at 410 nm in dichloromethane medium. The variables which affect the complex formation were studied and optimized. Beer’s law was obeyed over the concentration ranges: 2.4-48.0 and 3.2-64.0 µg ml-1 with molar absorptivity values of 3.24 × 103 and 2.30 × 103 l mol-1 cm-1, with DNP method and PA method, respectively. The limits of detection (LOD and quantification (LOQ were calculated to be 0.13 and 0.40 µg ml-1 for DNP method and 0.19 and 0.59 µg ml-1 for PA method. Methods were validated for accuracy, precision, robustness, ruggedness and selectivity. The proposed methods were applied to the determination of MFH in tablets. The accuracy and precision of the methods were found excellent. Accuracy of the methods was ascertained by recovery test via standard-addition procedure. The methods were applied to spiked human urine sample without detectable interference from endogenous substances.

  8. Reconceptualizing the core of nurse practitioner education and practice.

    Science.gov (United States)

    Burman, Mary E; Hart, Ann Marie; Conley, Virginia; Brown, Julie; Sherard, Pat; Clarke, Pamela N

    2009-01-01

    The movement to the doctor of nursing practice (DNP) is progressing rapidly with new programs emerging and curricular documents being developed. We argue that the implementation of the DNP is a good move for nursing, provided that we use the opportunity to reconceptualize the core of advanced practice nursing, especially nurse practitioner (NP) practice. Theory and research articles from nursing focused on advanced practice nursing, NPs, and doctoral education. The foundation of NP education is currently based essentially on borrowed or shared content in assessment, pharmacology, and pathophysiology. We argue that the heart and soul of nursing is in health promotion, both in healthy persons and in those dealing with chronic illness. Current master's programs do not prepare NPs to assume high-level practice focused on health promotion and disease management using the latest theoretical developments in health behavior change, behavioral sciences, exercise physiology, nutrition, and medical anthropology. Although these are touched upon in most NP programs, they do not represent the core science of NP education and need to be a critical part of any DNP program. Ultimately, our vision is for NP care to be consistently "different," yet just as essential as physician care, leading to positive outcomes in health promotion and disease management.

  9. Aerobic biodegradation of 2,4-Dinitroanisole by Nocardioides sp. strain JS1661.

    Science.gov (United States)

    Fida, Tekle Tafese; Palamuru, Shannu; Pandey, Gunjan; Spain, Jim C

    2014-12-01

    2,4-Dinitroanisole (DNAN) is an insensitive munition ingredient used in explosive formulations as a replacement for 2,4,6-trinitrotoluene (TNT). Little is known about the environmental behavior of DNAN. There are reports of microbial transformation to dead-end products, but no bacteria with complete biodegradation capability have been reported. Nocardioides sp. strain JS1661 was isolated from activated sludge based on its ability to grow on DNAN as the sole source of carbon and energy. Enzyme assays indicated that the first reaction involves hydrolytic release of methanol to form 2,4-dinitrophenol (2,4-DNP). Growth yield and enzyme assays indicated that 2,4-DNP underwent subsequent degradation by a previously established pathway involving formation of a hydride-Meisenheimer complex and release of nitrite. Identification of the genes encoding the key enzymes suggested recent evolution of the pathway by recruitment of a novel hydrolase to extend the well-characterized 2,4-DNP pathway. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Design and Development of Layered Security: Future Enhancements and Directions in Transmission.

    Science.gov (United States)

    Shahzad, Aamir; Lee, Malrey; Kim, Suntae; Kim, Kangmin; Choi, Jae-Young; Cho, Younghwa; Lee, Keun-Kwang

    2016-01-06

    Today, security is a prominent issue when any type of communication is being undertaken. Like traditional networks, supervisory control and data acquisition (SCADA) systems suffer from a number of vulnerabilities. Numerous end-to-end security mechanisms have been proposed for the resolution of SCADA-system security issues, but due to insecure real-time protocol use and the reliance upon open protocols during Internet-based communication, these SCADA systems can still be compromised by security challenges. This study reviews the security challenges and issues that are commonly raised during SCADA/protocol transmissions and proposes a secure distributed-network protocol version 3 (DNP3) design, and the implementation of the security solution using a cryptography mechanism. Due to the insecurities found within SCADA protocols, the new development consists of a DNP3 protocol that has been designed as a part of the SCADA system, and the cryptographically derived security is deployed within the application layer as a part of the DNP3 stack.

  11. Design and Development of Layered Security: Future Enhancements and Directions in Transmission

    Directory of Open Access Journals (Sweden)

    Aamir Shahzad

    2016-01-01

    Full Text Available Today, security is a prominent issue when any type of communication is being undertaken. Like traditional networks, supervisory control and data acquisition (SCADA systems suffer from a number of vulnerabilities. Numerous end-to-end security mechanisms have been proposed for the resolution of SCADA-system security issues, but due to insecure real-time protocol use and the reliance upon open protocols during Internet-based communication, these SCADA systems can still be compromised by security challenges. This study reviews the security challenges and issues that are commonly raised during SCADA/protocol transmissions and proposes a secure distributed-network protocol version 3 (DNP3 design, and the implementation of the security solution using a cryptography mechanism. Due to the insecurities found within SCADA protocols, the new development consists of a DNP3 protocol that has been designed as a part of the SCADA system, and the cryptographically derived security is deployed within the application layer as a part of the DNP3 stack.

  12. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones

    Science.gov (United States)

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A.; Luan, Gan; Shah, Nirali; Oppegard, Lisa M.; de Souza, Ernane C.; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J.; Drlica, Karl

    2016-01-01

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance. PMID:26984528

  13. Dynamic nuclear polarization using frequency modulation at 3.34 T

    Science.gov (United States)

    Hovav, Y.; Feintuch, A.; Vega, S.; Goldfarb, D.

    2014-01-01

    During dynamic nuclear polarization (DNP) experiments polarization is transferred from unpaired electrons to their neighboring nuclear spins, resulting in dramatic enhancement of the NMR signals. While in most cases this is achieved by continuous wave (cw) irradiation applied to samples in fixed external magnetic fields, here we show that DNP enhancement of static samples can improve by modulating the microwave (MW) frequency at a constant field of 3.34 T. The efficiency of triangular shaped modulation is explored by monitoring the 1H signal enhancement in frozen solutions containing different TEMPOL radical concentrations at different temperatures. The optimal modulation parameters are examined experimentally and under the most favorable conditions a threefold enhancement is obtained with respect to constant frequency DNP in samples with low radical concentrations. The results are interpreted using numerical simulations on small spin systems. In particular, it is shown experimentally and explained theoretically that: (i) The optimal modulation frequency is higher than the electron spin-lattice relaxation rate. (ii) The optimal modulation amplitude must be smaller than the nuclear Larmor frequency and the EPR line-width, as expected. (iii) The MW frequencies corresponding to the enhancement maxima and minima are shifted away from one another when using frequency modulation, relative to the constant frequency experiments.

  14. Optimization of field-cycled PEDRI for in vivo imaging of free radicals

    Energy Technology Data Exchange (ETDEWEB)

    Youngdee, Wiwat [Department of Bio-Medical Physics and Bio-Engineering, University of Aberdeen, Foresterhill, Aberdeen (United Kingdom); Planinsic, Gorazd [Department of Physics, University of Ljubljana, Ljubljana (Slovenia); Lurie, David J. [Department of Bio-Medical Physics and Bio-Engineering, University of Aberdeen, Foresterhill, Aberdeen (United Kingdom)]. E-mail: lurie@abdn.ac.uk

    2001-10-01

    A numerical model of the behaviour of the magnetization in a field-cycled dynamic nuclear polarization (DNP) experiment is presented, with the aim of optimizing pulse sequence parameters in field-cycled proton-electron double-resonance free radical imaging. The model is used to predict the observed enhancement of the NMR signal as a function of the magnetic field strength, EPR irradiation frequency and pulse sequence timing, as well as the properties of the sample including the NMR and EPR relaxation times. The model allowed optimization of parameters in the field-cycled DNP experiment, in particular the EPR irradiation frequency, to find the value which would give the largest difference between NMR signals recorded with and without EPR irradiation. Experiments to verify the model were carried out using aqueous solutions of TEMPOL, which exhibits three hyperfine lines in its EPR spectrum and triarylmethyl (TAM), which has a single, narrow line. It was found that the model predicted very well the variation in DNP enhancement with EPR irradiation power for both samples. The behaviour of the NMR signal with EPR irradiation frequency in studies using TEMPOL was also accurately modelled, with the optimum frequency lying between 60 and 80 MHz, depending on the EPR irradiation power. The optimum frequency obtained from the model also agreed with the experimental data obtained using the TAM free radical, but with this sample the theoretical curves tended to deviate from the experimental data at irradiation frequencies below 70 MHz. (author)

  15. Characterization of Chemical Exchange Using Relaxation Dispersion of Hyperpolarized Nuclear Spins.

    Science.gov (United States)

    Liu, Mengxiao; Kim, Yaewon; Hilty, Christian

    2017-09-05

    Chemical exchange phenomena are ubiquitous in macromolecules, which undergo conformational change or ligand complexation. NMR relaxation dispersion (RD) spectroscopy based on a Carr-Purcell-Meiboom-Gill pulse sequence is widely applied to identify the exchange and measure the lifetime of intermediate states on the millisecond time scale. Advances in hyperpolarization methods improve the applicability of NMR spectroscopy when rapid acquisitions or low concentrations are required, through an increase in signal strength by several orders of magnitude. Here, we demonstrate the measurement of chemical exchange from a single aliquot of a ligand hyperpolarized by dissolution dynamic nuclear polarization (D-DNP). Transverse relaxation rates are measured simultaneously at different pulsing delays by dual-channel 19 F NMR spectroscopy. This two-point measurement is shown to allow the determination of the exchange term in the relaxation rate expression. For the ligand 4-(trifluoromethyl)benzene-1-carboximidamide binding to the protein trypsin, the exchange term is found to be equal within error limits in neutral and acidic environments from D-DNP NMR spectroscopy, corresponding to a pre-equilibrium of trypsin deprotonation. This finding illustrates the capability for determination of binding mechanisms using D-DNP RD. Taking advantage of hyperpolarization, the ligand concentration in the exchange measurements can reach on the order of tens of μM and protein concentration can be below 1 μM, i.e., conditions typically accessible in drug discovery.

  16. Thermosetting polymer for dynamic nuclear polarization: Solidification of an epoxy resin mixture including TEMPO

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Yohei, E-mail: noda.yohei@jaea.go.jp [Quantum Beam Science Centre, Sector of Nuclear Science Research, Japan Atomic Energy Agency, Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Kumada, Takayuki [Quantum Beam Science Centre, Sector of Nuclear Science Research, Kansai Photon Science Institute, Japan Atomic Energy Agency, Kizugawa, Kyoto 619-0215 (Japan); Yamaguchi, Daisuke; Shamoto, Shin-ichi [Quantum Beam Science Centre, Sector of Nuclear Science Research, Japan Atomic Energy Agency, Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan)

    2015-03-11

    We investigated the dynamic nuclear polarization (DNP) of typical thermosetting polymers (two-component type epoxy resins; Araldite{sup ®} Standard or Araldite{sup ®} Rapid) doped with a (2,2,6,6-tetramethylpiperidine-1-yl)oxy (TEMPO) radical. The doping process was developed by carefully considering the decomposition of TEMPO during the solidification of the epoxy resin. The TEMPO electron spin in each two-component paste decayed slowly, which was favorable for our study. Furthermore, despite the dissolved TEMPO, the mixture of the two-component paste successfully solidified. With the resulting TEMPO-doped epoxy-resin samples, DNP experiments at 1.2 K and 3.35 T indicated a magnitude of a proton-spin polarization up to 39%. This polarization is similar to that (35%) obtained for TEMPO-doped polystyrene (PS), which is often used as a standard sample for DNP. To combine this solidification of TEMPO-including mixture with a resin-casting technique enables a creation of polymeric target materials with a precise and complex structure.

  17. Dynamic nuclear polarization of irradiated target materials

    International Nuclear Information System (INIS)

    Seely, M.L.

    1982-01-01

    Polarized nucleon targets used in high energy physics experiments usually employ the method of dynamic nuclear polarization (DNP) to polarize the protons or deuterons in an alcohol. DNP requires the presence of paramagnetic centers, which are customarily provided by a chemical dopant. These chemically doped targets have a relatively low polarizable nucleon content and suffer from loss of polarization when subjected to high doses of ionizing radiation. If the paramagnetic centers formed when the target is irradiated can be used in the DNP process, it becomes possible to produce targets using materials which have a relatively high polarizable nucleon content, but which are not easily doped by chemical means. Furthermore, the polarization of such targets may be much more radiation resistant. Dynamic nuclear polarization in ammonia, deuterated ammonia, ammonium hydroxide, methylamine, borane ammonia, butonal, ethane and lithium borohydride has been studied. These studies were conducted at the Stanford Linear Accelerator Center using the Yale-SLAC polarized target system. Results indicate that the use of ammonia and deuterated ammonia as polarized target materials would make significant increases in polarized target performance possible

  18. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukemia groups (AML-19)

    Science.gov (United States)

    Amadori, Sergio; Suciu, Stefan; Selleslag, Dominik; Stasi, Roberto; Alimena, Giuliana; Baila, Liliana; Rizzoli, Vittorio; Borlenghi, Erika; Gaidano, Gianluca; Magro, Domenico; Torelli, Giuseppe; Muus, Petra; Venditti, Adriano; Cacciola, Emma; Lauria, Francesco; Vignetti, Marco; de Witte, Theo

    2010-01-01

    Summary This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best supportive care or a course of GO according to one of two schedules: 3 mg/m2 on days 1, 3 and 5 (arm A), or GO 6 mg/m2 on day 1 and 3 mg/m2 on day 8 (arm B). Primary endpoint was the rate of disease non-progression (DnP), defined as the proportion of patients either achieving a response or maintaining a stable disease following GO induction in each arm. Fifty-six patients were randomized in the two GO arms (A, n=29; B, n=27). The rate of DnP was 38% (90% confidence interval [CI], 23%–55%) in arm A, and 63% (90% CI, 45%–78%) in arm B. Peripheral cytopenias were the most common adverse events for both regimens. The all-cause early mortality rate was 14% in arm A and 11% in arm B. The day 1+8 schedule, which was associated with the highest rate of DnP, met the statistical criteria to be selected as the preferred regimen for phase III comparison with best supportive care. PMID:20230405

  19. Thermosetting polymer for dynamic nuclear polarization: Solidification of an epoxy resin mixture including TEMPO

    International Nuclear Information System (INIS)

    Noda, Yohei; Kumada, Takayuki; Yamaguchi, Daisuke; Shamoto, Shin-ichi

    2015-01-01

    We investigated the dynamic nuclear polarization (DNP) of typical thermosetting polymers (two-component type epoxy resins; Araldite ® Standard or Araldite ® Rapid) doped with a (2,2,6,6-tetramethylpiperidine-1-yl)oxy (TEMPO) radical. The doping process was developed by carefully considering the decomposition of TEMPO during the solidification of the epoxy resin. The TEMPO electron spin in each two-component paste decayed slowly, which was favorable for our study. Furthermore, despite the dissolved TEMPO, the mixture of the two-component paste successfully solidified. With the resulting TEMPO-doped epoxy-resin samples, DNP experiments at 1.2 K and 3.35 T indicated a magnitude of a proton-spin polarization up to 39%. This polarization is similar to that (35%) obtained for TEMPO-doped polystyrene (PS), which is often used as a standard sample for DNP. To combine this solidification of TEMPO-including mixture with a resin-casting technique enables a creation of polymeric target materials with a precise and complex structure

  20. Potent antimycobacterial activity of the pyridoxal isonicotinoyl hydrazone analog 2-pyridylcarboxaldehyde isonicotinoyl hydrazone: a lipophilic transport vehicle for isonicotinic acid hydrazide.

    Science.gov (United States)

    Ellis, Samantha; Kalinowski, Danuta S; Leotta, Lisa; Huang, Michael L H; Jelfs, Peter; Sintchenko, Vitali; Richardson, Des R; Triccas, James A

    2014-02-01

    The rise in drug-resistant strains of Mycobacterium tuberculosis is a major threat to human health and highlights the need for new therapeutic strategies. In this study, we have assessed whether high-affinity iron chelators of the pyridoxal isonicotinoyl hydrazone (PIH) class can restrict the growth of clinically significant mycobacteria. Screening a library of PIH derivatives revealed that one compound, namely, 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH), exhibited nanomolar in vitro activity against Mycobacterium bovis bacille Calmette-Guérin and virulent M. tuberculosis. Interestingly, PCIH is derived from the condensation of 2-pyridylcarboxaldehyde with the first-line antituberculosis drug isoniazid [i.e., isonicotinic acid hydrazide (INH)]. PCIH displayed minimal host cell toxicity and was effective at inhibiting growth of M. tuberculosis within cultured macrophages and also in vivo in mice. Further, PCIH restricted mycobacterial growth at high bacterial loads in culture, a property not observed with INH, which shares the isonicotinoyl hydrazide moiety with PCIH. When tested against Mycobacterium avium, PCIH was more effective than INH at inhibiting bacterial growth in broth culture and in macrophages, and also reduced bacterial loads in vivo. Complexation of PCIH with iron decreased its effectiveness, suggesting that iron chelation may play some role in its antimycobacterial efficacy. However, this could not totally account for its potent efficacy, and structure-activity relationship studies suggest that PCIH acts as a lipophilic vehicle for the transport of its intact INH moiety into the mammalian cell and the mycobacterium. These results demonstrate that iron-chelating agents such as PCIH may be of benefit in the treatment and control of mycobacterial infection.

  1. Répartition et valorisation des macrophytes envahissantes dans la ...

    African Journals Online (AJOL)

    SARAH

    30 avr. 2016 ... A cet égard, le développement urbain inhérent à l'accroissement démographique et à l'industrialisation (extension du port, déversement ...... 23 p. FAO. 2006 Rapport de synthèse des résultats du projet. TCP/CMR/2908A. Gestion participative et conservation de la diversité des mangroves. Rome. Felfili J.M. ...

  2. Status Asetilator Gen NAT2 pada Pasien Tuberkulosis dan Tuberkulosis dengan Diabetes Melitus di Kupang, Nusa Tenggara Timur

    Directory of Open Access Journals (Sweden)

    Alvinsyah Adhityo Pramono

    2017-03-01

    Full Text Available Indonesia is the second highest country with TB patients in the world. Diabetes mellitus (DM is a comorbid of TB. Arylamine N-acetyltransferase 2 (NAT2, encoded by the NAT2 gene, is an enzyme that metabolizes isoniazid (INH. NAT2 gene has some polimorphysims that may play a role in INH acetylating process. Those who are slow acetylators may develop liver intoxication as a consequence of slow INH metabolism process. Slow acetylator TBDM patients may complicate both TB and DM treatment, causing them to be less optimal. The aim of this study was to explore the acetylator status of TBDM patients in Kupang, Indonesia. A cross-sectional study was conducted by obtaining DNA of 122 TB patients in Kupang in June–November 2011. NAT2 gene was amplified and sequenced to determine the acetylator status. There were 5 TB patients who had a glucose serum level of >200mg/dL and was catagorized as TBDM. Result showed that there was 1 TBDM patient who was a rapid acetylator (NAT2*4/NAT2*4, 2 patients as intermediate acetylators (NAT2*13A/NAT2*6J, and 2 patients as slow acetylators (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B. Meanwhile,  there were 2 TB patients who was rapid acetylators (NAT2*4/NAT2*4 and 3 patients as intermediate acetylators (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J. Slow NAT2 acetylator TBDM patients potentially face more problems during therapy. As INH may cause liver intoxication, these patients may also experience unoptimum DM treatment. Therefore, it is strongly recommended to do a study on the role of pharmacogenomics in TBDM.

  3. Polymorphisms in Isoniazid and Prothionamide Resistance Genes of the Mycobacterium tuberculosis Complex

    KAUST Repository

    Projahn, M.

    2011-06-27

    Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance.

  4. Polysomnographic correlates of inflammatory complement components in young healthy males.

    Science.gov (United States)

    Hussain, M Ejaz; Golam Sarwar, Abu Hasnath M; Alam, Mohd Shoeb; Noohu, Majumi M; Zannat, Wassilatul; Pandi-Perumal, Seithikurippu R; Bahammam, Ahmed S; Manzar, Md Dilshad

    2016-01-01

    A growing body of evidence has delineated the predominant role of humoral mediators of inflammation in linking sleep with immunity. Nonetheless, characterization of the relationship between complement components with inflammatory functions and objective sleep measures has not been performed. In this study we investigated the relationships between objective measures of sleep and complement components with inflammatory functions. Thirty-six healthy male university students (age, 23.94±4.23 years; BMI, 23.44±2.67 kg/m(2)) completed the study. An RMS Quest 32 polysomnograph (PSG) was used for sleep recording. Non-fasting blood was collected before subjects went to bed on the second night in the sleep laboratory to estimate complement component 3 (C-3), complement component 4 (C-4), complement factor-H (Factor-H), C1-inhibitor (C1INH), complement factor I (CFI) and other inflammatory mediators, such as IL-6 and sICAM-1. Multiple linear regression analysis was used to assess the association between PSG sleep measures and inflammatory mediators. Higher values of C-3 and lower values of sICAM-1, C1INH, and CFI (adjusted model, R2=0.211, p<0.041) predicted longer sleep duration. Lower C-3 (adjusted model, R2=0.078, p<0.055) predicted higher N1 (%). Higher levels of C1INH and CFI and lower values of C-4 (model adjusted R2=0.269, p<0.008) predicted higher N3 (%). Higher C-3, higher C-4, lower IL-6, lower C1INH and lower CFI (model adjusted R2=0.296, p<0.007) predicted higher REM (%). Poor sleep measures were associated with increased levels of pro-inflammatory complement components and decreased anti-inflammatory complement components.

  5. Booms petroliers et basculements du rapport de force | Mouhoubi ...

    African Journals Online (AJOL)

    Chacun d'eux ne cherche qu'à instaurer la politique de prix satisfaisant les objectifs inhérents aux stratégies économiques nationales, aux relations internationales ou même s'accaparer de la part la plus importante du surplus pétrolier. Mots-clefs. Boom pétrolier, crise pétrolière, rapport de force, prix dub pétrole. Code Jel ...

  6. Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance

    OpenAIRE

    Alame-Emane , Amel Kevin; Xu , Peng; Pierre-Audigier , C; Cadet-Daniel , Véronique; Shen , X; Sraouia , M; Djoba Siawaya , J F; Takiff , H; Gao , Q; Gicquel , B

    2015-01-01

    International audience; Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern. The objective was to determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP). For this goal, isolates from two major urban centres—Paris (101 strains) and Shanghai (171 strains)—were investigated for t...

  7. Les Hematomes Extra-Duraux Post Traumatiques : Prise En Charge ...

    African Journals Online (AJOL)

    Introduction L\\'hématome extra dural (HED) est une urgence chirurgicale majeure. Son diagnostic et sa prise en charge dans les pays en voie de développement se heurtent à des difficultés inhérentes à la fois à la modestie des plateaux techniques et au coût trop onéreux des soins pour des malades souvent démunis, ...

  8. ISONIAZID INDUCED CLAUSTROPHOBIA?A CASE REPORT

    OpenAIRE

    Prasad, C.E.; Krishnamurthy, Kartikeya; Srinivasulu, T.

    1984-01-01

    SUMMARY A case of claustrophobia in a 45-year old male tuberculous in-patient receiving antituberculous drug is reported. The patient presented with the clinical features of claustrophobia after eighteen months of therapy. Isoniazid was, probably, the most likely cause since. The symptoms recurred on reintroduction of INH containing regimens. There was no recurrence of symptoms on resumption of non-Isoniazid regimen. Neurop3ychi.-Uric side-effects due to Isoniazid are well-known but Phobic ne...

  9. The Potent of Methanol Extracts of Cashew (Anacardium Occidentale L.) Against Methicillin-resistant Staphylococcus Aureus (Mrsa)

    OpenAIRE

    Nursanty, Risa; Yunita, Yunita

    2012-01-01

    Use of antibiotics including misuse and overuse has aided natural bacterial evolution by helping the microbes become resistant such as methicillin-resistant Staphylococcus aureus (MRSA). The MRSA resistant in disease treatment with commonly used antibiotics needs new drug to treat patients. Traditional herb can be alternative treatment such as cashew (Anacardium occidentale L.). Antibacterial activities of methanol extracts of stem cashew with concentration 10%, 20% and 30% showed zone of inh...

  10. Chef, Bureau de gestion de projets | CRDI - Centre de recherches ...

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

    Il lui incombe d'assurer une communication et une amélioration continues ainsi que de cerner et d'atténuer rapidement les risques inhérents aux projets. Le chef, Bureau de gestion de projets, collabore avec les forums sur la gouvernance de la technologie de l'information (TI) à l'établissement des priorités opérationnelles ...

  11. Concurrent object-oriented programming: The MP-Eiffel approach

    OpenAIRE

    Silva, Miguel Augusto Mendes Oliveira e

    2004-01-01

    This article evaluates several possible approaches for integrating concurrency into object-oriented programming languages, presenting afterwards, a new language named MP-Eiffel. MP-Eiffel was designed attempting to include all the essential properties of both concurrent and object-oriented programming with simplicity and safety. A special care was taken to achieve the orthogonality of all the language mechanisms, allowing their joint use without unsafe side-effects (such as inh...

  12. Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis

    OpenAIRE

    LaTonia Taliaferro-Smith; Arumugam Nagalingam; Brandi Brandon Knight; Elaine Oberlick; Neeraj K. Saxena; Dipali Sharma

    2013-01-01

    The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inh...

  13. Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis1 2

    OpenAIRE

    Taliaferro-Smith, LaTonia; Nagalingam, Arumugam; Knight, Brandi Brandon; Oberlick, Elaine; Saxena, Neeraj K; Sharma, Dipali

    2013-01-01

    The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inh...

  14. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

    OpenAIRE

    Chongjun Shi; Nini Zhang; Yang Feng; Jiewei Cao; Xuyi Chen; Bin Liu

    2017-01-01

    Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inh...

  15. Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages.

    Directory of Open Access Journals (Sweden)

    Jonna Idh

    Full Text Available Drugs such as isoniazid (INH and pretomanid (PRT, used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS. The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO in clinical strains of M. tuberculosis.Luciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1 in broth cultures and bacterial survival was analysed by luminometry. NO-dependent intracellular killing in a selection of strains was assessed in interferon gamma/lipopolysaccharide-activated murine macrophages using the NO inhibitor L-NMMA.When M. tuberculosis H37Rv was compared to six clinical isolates and CDC1551, three isolates with inhA mediated INH resistance showed significantly reduced NO-susceptibility in broth culture. All strains showed a variable but dose-dependent susceptibility to RNS donors. Two clinical isolates with increased susceptibility to NO exposure in broth compared to H37Rv were significantly inhibited by activated macrophages whereas there was no effect on growth inhibition when activated macrophages were infected by clinical strains with higher survival to NO exposure in broth. Furthermore, the most NO-tolerant clinical isolate showed increased resistance to PRT both in broth culture and the macrophage model compared to H37Rv in the absence of mutational resistance in genes associated to reduced susceptibility against PRT or NO.In a limited number of clinical M. tuberculosis isolates we found a significant difference in susceptibility to NO between clinical isolates, both in broth cultures and in macrophages. Our results indicate that mycobacterial susceptibility to cellular host defence mechanisms such as NO need to be taken into consideration when designing new therapeutic strategies.

  16. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik

    2016-08-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock

    OpenAIRE

    1991-01-01

    The present study was designed to define the potential of chlorpromazine (CPZ) as a protective agent against lipopolysaccharide (LPS) toxicity in comparison with glucocorticoids, and to obtain initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxic shock. It was found that CPZ protects mice, normal or adrenalectomized, and guinea pigs against lethality of LPS, and inhibited TNF serum levels, like dexamethasone (DEX), a well-known inh...

  18. Grossesse et transplantation rénale: à propos de 10 cas | Boubaker ...

    African Journals Online (AJOL)

    La grossesse chez les patientes transplantées rénales est à risque de complications maternelles mais surtout fœtales. Le risque de survenue de rejet aigue ou chronique inhérent à la grossesse est faible. L'objectif de notre étude était de rapporter les grossesses survenues chez nos transplantées rénales, leurs aspects ...

  19. Genetic Determinants of C1 Inhibitor Deficiency Angioedema Age of Onset.

    Science.gov (United States)

    Gianni, Panagiota; Loules, Gedeon; Zamanakou, Maria; Kompoti, Maria; Csuka, Dorottya; Psarros, Fotis; Magerl, Markus; Moldovan, Dimitru; Maurer, Marcus; Speletas, Matthaios G; Farkas, Henriette; Germenis, Anastasios E

    2017-01-01

    In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1-428G/A to the disease phenotype. We studied 249 C1-INH-HAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1-428G/A, combined or not with that of the functional F12-46C/T polymorphism. Carriers of the G allele of the KLKB1-428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [p < 0.001], depending on the zygocity status), while carriers of both the KLKB1-428G/A and the F12-46C/T polymorphism displayed an 8.8-year delay in disease onset (p < 0.001) and a 64% lower probability of needing long-term prophylactic treatment (p = 0.019). These findings support our initial hypothesis that functional alterations in genes of proteins involved in bradykinin metabolism and function affect the clinical phenotype and possibly contribute to the pathogenesis of C1-INH-HAE. Given that an earlier onset of symptoms is inversely correlated with the subsequent course of the disease and, eventually, the need for long-term prophylaxis, these polymorphisms may be helpful prognostic biomarkers of disease severity. © 2017 S. Karger AG, Basel.

  20. Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

    Science.gov (United States)

    Defendi, Federica; Charignon, Delphine; Ghannam, Arije; Habib, Mohammed; Drouet, Christian

    2016-01-01

    Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. Objectives We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. Methods We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. Results Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98–175μg/mL, n = 51) and in healthy women (90–176μg/mL, n = 74), while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13) or two weeks after AE attack (n = 2), HK cleavage was not fully restored, suggesting its use as a post-attack assay. Conclusion As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management. PMID:27685806