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Sample records for mediating vibration-induced chronic

  1. [Skull vibration induced nystagmus test].

    Science.gov (United States)

    Dumas, G; De Waele, C; Hamann, K F; Cohen, B; Negrevergne, M; Ulmer, E; Schmerber, S

    2007-09-01

    To establish during a consensus meeting the fundamental basis, the validity criteria, the main indications and results of the skull vibration induced nystagmus test (SVINT) which explores the vestibule high frequencies. The SVINT is applied on the mastoid process (right and left sides) at 100 Hz during 10 seconds on a sitting upright subject. Total unilateral peripheral lesions (tUVL: operated vestibular shwannomas, vestibular neurectomies) and partial unilateral peripheral lesions (pUVL: preoperative neuromas, Meniere's disease, vestibular neuritis, chemical labyrinthectomies) were studied. Thirty-six patients had brainstem lesions and 173 normal subjects were used as controls. The SVINT is considered positive when the application of the vibrator produces a reproducible sustained nystagmus always beating in the same direction following several trials in various stimulation topographies (on the right and left mastoid). The skull vibratory nystagmus (SVN) begins and ends with the stimulation; the direction of the nystagmus has no secondary reversal. The slow phase velocity (SPV) is>2 degrees /second. In tUVL the SVINT always reveals a lesional nystagmus beating toward the safe side at all frequencies. The mean SVN SPV is 10.8 degrees /s+/-7.5 SD (N=45). The mastoid site was more efficient than the cervical or vertex sites. Mastoïd stimulation efficiency is not correlated with the side of stimulation. The SVN SPV is correlated with the total caloric efficiency on the healthy ear. In pUVL the SVINT is positive in 71 to 76% of cases; the mean SVN. SPV (6.7 degrees /s+/-4.7 SD)(N=30) is significantly lower than in tUVL (P=0.0004). SVINT is positive in 6 to 10% of the normal population, 31% of brain stem lesions and negative in total bilateral vestibular peripheral lesions. SVINT is an effective, rapid and non invasive test used to detect vestibular asymmetry between 20 to 150 Hz stimulation. This test used in important cohorts of patients during the ten last years has

  2. Vibration-induced droplet atomization

    Science.gov (United States)

    Vukasinovic, Bojan

    The atomization of liquid drops is investigated experimentally using laser vibrometry, high-speed imaging, and particle tracking techniques. The spray is generated by a novel vibration-induced droplet atomization (VIDA) process in which a sessile drop is atomized by an underlying vibrating thin metal diaphragm, resulting in rapid ejection of small secondary droplets from the free surface of the primary drop. Under some conditions, the primary drop can be atomized extremely rapidly by a bursting-like mechanism (e.g., a 0.1 ml water drop can be atomized in 0.4 seconds). The present research has focused on four major areas: global characteristics of VIDA process, instability modes and free surface dynamics of the forced drop, mechanisms of the interface breakup, and parametric characterization of the ensuing spray. Prior to atomization, the drop free surface undergoes three transitions: from axisymmetric standing waves to azimuthal waves, to a newly-observed lattice mode, and to a disordered pre-ejection state. The droplet ejection results from localized collapse of surface troughs and initiation and ultimate breakup of momentary liquid spikes. Breakup begins with capillary pinch-off from spike tips and can be followed by additional pinching of liquid droplets. For a relatively low-viscosity liquid, e.g., water, a capillary-wave instability of the spike is observed in some cases, while for a very viscous liquid, e.g., a glycerin/water solution, the first breakup occurs near the stem of the spike, with or without subsequent breakup of the detached, elongated thread. Different mechanisms dominating the primary breakup of the spike are operative in the low- and high-viscosity ejection regimes. When ejection of the secondary droplets is triggered, the evolution and rate of atomization depend on the coupled dynamics of the primary drop and the vibrating diaphragm. Due to these dynamics, the process can be either self-intensifying or self-decaying. The resulting VIDA spray

  3. Seismic features of vibration induced by train

    Institute of Scientific and Technical Information of China (English)

    陈棋福; 李丽; 李纲; 陈凌; 彭文涛; 汤毅; 陈颙; 王夫运

    2004-01-01

    Based on schematically formulation of the vibrations induced by moving trains, this paper analyses the waveforms along the Datong-Qinhuangdao railroad in Northern China recorded in the suburban Huairou district of Beijing on March 8, 2003. It is illustrated that vibrations induced by train, except traditional recognized noises and interference effects, could be used as a seismic source to detect crustal structures with its advantage of abundant frequency spectrum, repeatability and no additional harm to the environment. It will bring lights to the traditional exploration seismology with the further studies of signal processing and interpretation methods, and related models and new observing systems.

  4. CFD Simulations of Vibration Induced Droplet Ejection.

    Science.gov (United States)

    James, Ashley; Smith, Marc K.; Glezer, Ari

    1998-11-01

    Vibration-induced droplet ejection is a process that occurs when a liquid droplet is placed on a vibrating membrane. Above a critical value of the excitation amplitude, Faraday waves form on the surface of the drop. As the amplitude is increased secondary drops are ejected from the wave crests. A Navier-Stokes solver designed to simulate the transient fluid mechanics of the process is presented. The solver is based on a MAC method on a staggered grid. A volume of fluid method is implemented to track the free surface. The volume fraction is advected via a second-order, unsplit method that minimizes numerical diffusion of the interface. Surface tension is incorporated as a continuum surface force. This work is intended to provide a comprehensive description of the fluid dynamics involved in vibration-induced droplet ejection, with the aim of understanding the mechanism behind the ejection process. The evolution of the interface through droplet ejection will be simulated. The dependence of the ejection process on the driving parameters will be evaluated and the resonance characteristics of the drop will be determined. The results of the computations will be compared with experimental results.

  5. Characteristics of Vibration Induced by Cavitation

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-yu; TAO Lei; LIU Shu-yan; QIAN Jian-jun

    2005-01-01

    Cavitation-induced vibration characteristics and the relations between the vibration and cavitation are studied. Cavitation vibrations are measured around a model hollow-jet valve by an accelerometer under cavitating and non-cavitating conditions. The measurement data is analyzed by FFT method. The corresponding cavitating flow patterns are photographed by a high-speed camera with an xenon flash lamp. The frequency band of the vibration induced by cavitation is determined. To compare the vibration intensities under different cavitation conditions, a definition of vibration acceleration level is introduced based on power spectral density of the vibration. By the analysis of vibration, the definitions of characteristic cavitation number are suggested. According to these cavitation numbers, the cavitation process is divided into three stages, that is, incipient cavitation, subcavitation and supercavitation.

  6. New principles of construction of electromechanical vibration inducers

    Science.gov (United States)

    Ashmonas, K. A. P.; Bansevichyus, R. Y.; Vaznelis, A. I.; Ragulskis, K. M.

    1973-01-01

    Electromechanical vibration inducers with high reliability and low noise level were created to study premature operating losses in their support bearings. An investigation was also made of the feasibility of developing stable synchronous operation of two vibrational inducers, rigidily fastened to a solid body with and without flexible suspension.

  7. Vibration-induced drop atomization and bursting

    Science.gov (United States)

    James, A. J.; Vukasinovic, B.; Smith, Marc K.; Glezer, A.

    2003-02-01

    A liquid drop placed on a vibrating diaphragm will burst into a fine spray of smaller secondary droplets if it is driven at the proper frequency and amplitude. The process begins when capillary waves appear on the free surface of the drop and then grow in amplitude and complexity as the acceleration amplitude of the diaphragm is slowly increased from zero. When the acceleration of the diaphragm rises above a well-defined critical value, small secondary droplets begin to be ejected from the free-surface wave crests. Then, quite suddenly, the entire volume of the drop is ejected from the vibrating diaphragm in the form of a spray. This event is the result of an interaction between the fluid dynamical process of droplet ejection and the vibrational dynamics of the diaphragm. During droplet ejection, the effective mass of the drop diaphragm system decreases and the resonance frequency of the system increases. If the initial forcing frequency is above the resonance frequency of the system, droplet ejection causes the system to move closer to resonance, which in turn causes more vigorous vibration and faster droplet ejection. This ultimately leads to drop bursting. In this paper, the basic phenomenon of vibration-induced drop atomization and drop bursting will be introduced, demonstrated, and characterized. Experimental results and a simple mathematical model of the process will be presented and used to explain the basic physics of the system.

  8. Trial Study of Vibration-Induced Effects on Spontaneous Potential

    Institute of Scientific and Technical Information of China (English)

    SunWeibin; QiuWeiting; HeZhanxiang

    2003-01-01

    Vibratory excitation generates not only reflections and refractions of wave fields on the subsurface interfaces but also electromagnetic waves with different frequencies. In this paper we address the vibration-induced effects on the spontaneous potential field. The effects of controllable vibration on the spontaneous potential field were studied under real field geologic conditions. Experimental data confirmed that the vibration-induced effects on the spontaneous potential field do exist under field conditions. Monitoring records over a long time interval showed that there existed three information zones in the vibration-induced effects on spontaneous potential field:These are the signal-variant zone, the extreme-stable zone and the relaxation-recovery zone. Combined with different well-site data, it was concluded that the time-variant features of the anomalies in the information zones was closely related to the properties of the subsurface liquid (oil and water).

  9. Predicting vibration-induced displacement for a resonant friction slider

    DEFF Research Database (Denmark)

    Fidlin, A.; Thomsen, Jon Juel

    2001-01-01

    A mathematical model is set up to quantify vibration-induced motions of a slider, sandwiched between friction layers with different coefficients of friction, and equipped with an imbedded resonator that oscillates at high frequency and small amplitude. This model is highly nonlinear, involving non...

  10. How to perform the skull vibration-induced nystagmus test (SVINT).

    Science.gov (United States)

    Dumas, G; Perrin, P; Ouedraogo, E; Schmerber, S

    2016-11-01

    The skull vibration-induced nystagmus test is a robust, nonintrusive and easy to perform test. This test acts as a vestibular Weber test and is performed as a bedside examination. It usually instantaneously reveals vibration-induced nystagmus (VIN) even in long standing or chronic compensated unilateral vestibular lesions. The test requires stimulation at 30, 60 or more efficiently at 100Hz. The vibrator is applied perpendicularly to the skin on a subject sitting up straight on the right and then the left mastoid (level with external acoustic meatus) and vertex. The VIN can be observed under videonystagmoscopy or Frenzel goggles. Either the direct tracing or the VIN slow phase velocity can be recorded on a 2D or 3D videonystagmograph. The patients should be relaxed and not treated by strong sedative medications. This rapid first-line test is not influenced by vestibular compensation and usefully complements other tests in the multifrequency evaluation of the vestibule. It acts as a global vestibular test by stimulating both canal and otolithic structures at 100Hz. It is useful in case of external acoustic meatus or middle ear disease as a substitute for the water caloric test and is preferable in elderly patients with vascular disease or arthritis of the neck to the head-shaking-test or head-impulse-test. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Chronic Renal Allograft Dysfunction Antibody-Mediated: An Update

    Directory of Open Access Journals (Sweden)

    Maurizio Salvadori,

    2014-07-01

    Full Text Available This paper reviews the most important studies on chronic antibody-mediated rejection (cABMR, which is an important cause of late graft dysfunction after renal transplantation. Several antibodies seem to be responsible for chronic rejection; new techniques have allowed us to identify these antibodies in circulation. The pathogenetic role of the antibodies generally includes the complement pathway, but may also be complement-independent. This paper also examines the pathogenesis of chronic endothelial lesions, as well as the histopathological aspects. Antibodies responsible for chronic rejection may preexist before transplantation or may develop after transplantation. The possible therapeutic approaches are poor and principally based on early identification and desensitisation techniques. New B cell targeting drugs are aimed at an improved control of the relevant condition.

  12. Mediators of Yoga and Stretching for Chronic Low Back Pain

    Directory of Open Access Journals (Sweden)

    Karen J. Sherman

    2013-01-01

    Full Text Available Although yoga is an effective treatment for chronic low back pain, little is known about the mechanisms responsible for its benefits. In a trial comparing yoga to intensive stretching and self-care, we explored whether physical (hours of back exercise/week, cognitive (fear avoidance, body awareness, and self-efficacy, affective (psychological distress, perceived stress, positive states of mind, and sleep, and physiological factors (cortisol, DHEA mediated the effects of yoga or stretching on back-related dysfunction (Roland-Morris Disability Scale (RDQ. For yoga, 36% of the effect on 12-week RDQ was mediated by increased self-efficacy, 18% by sleep disturbance, 9% by hours of back exercise, and 61% by the best combination of all possible mediators (6 mediators. For stretching, 23% of the effect was mediated by increased self-efficacy, 14% by days of back exercise, and 50% by the best combination of all possible mediators (7 mediators. In open-ended questions, ≥20% of participants noted the following treatment benefits: learning new exercises (both groups, relaxation, increased awareness, and the benefits of breathing (yoga, benefits of regular practice (stretching. Although both self-efficacy and hours of back exercise were the strongest mediators for each intervention, compared to self-care, qualitative data suggest that they may exert their benefits through partially distinct mechanisms.

  13. Mediators of yoga and stretching for chronic low back pain.

    Science.gov (United States)

    Sherman, Karen J; Wellman, Robert D; Cook, Andrea J; Cherkin, Daniel C; Ceballos, Rachel M

    2013-01-01

    Although yoga is an effective treatment for chronic low back pain, little is known about the mechanisms responsible for its benefits. In a trial comparing yoga to intensive stretching and self-care, we explored whether physical (hours of back exercise/week), cognitive (fear avoidance, body awareness, and self-efficacy), affective (psychological distress, perceived stress, positive states of mind, and sleep), and physiological factors (cortisol, DHEA) mediated the effects of yoga or stretching on back-related dysfunction (Roland-Morris Disability Scale (RDQ)). For yoga, 36% of the effect on 12-week RDQ was mediated by increased self-efficacy, 18% by sleep disturbance, 9% by hours of back exercise, and 61% by the best combination of all possible mediators (6 mediators). For stretching, 23% of the effect was mediated by increased self-efficacy, 14% by days of back exercise, and 50% by the best combination of all possible mediators (7 mediators). In open-ended questions, ≥20% of participants noted the following treatment benefits: learning new exercises (both groups), relaxation, increased awareness, and the benefits of breathing (yoga), benefits of regular practice (stretching). Although both self-efficacy and hours of back exercise were the strongest mediators for each intervention, compared to self-care, qualitative data suggest that they may exert their benefits through partially distinct mechanisms.

  14. Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies

    Science.gov (United States)

    Mazzeo, Anna; Stancanelli, Claudia; Vita, Giuseppe

    2013-01-01

    Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. PMID:23853716

  15. Environmental problems of vibrations induced by railway traffic

    Institute of Scientific and Technical Information of China (English)

    XIA He; CAO Yanmei; De Roeck Guido; Degrande Geert

    2007-01-01

    In this paper, a general review is made on the problems of vibrations of the ground and nearby buildings induced by railway traffic, and on the researches on this sub- ject in theoretical analyses, numerical simulations, and field experiments. The characteristics of ground vibrations induced by railway traffic and their propagation, from the aspects of duration, intensity distribution, vehicle load and speed, are summarized. The vibration influences on the daily life of people, the operation of high-tech devices and the safety of buildings, and the vibration properties of subsoil and buildings adjacent to the underground, ground and elevated railway systems are introduced.

  16. Spray characterization during vibration-induced drop atomization

    Science.gov (United States)

    Vukasinovic, Bojan; Smith, Marc K.; Glezer, Ari

    2004-02-01

    Vibration-induced drop atomization is a process of rapid droplet ejection from a larger liquid drop. This occurs when a liquid drop resting on a thin diaphragm is vibrated under the appropriate forcing conditions using an attached piezoelectric actuator. The resulting spray of small droplets is characterized in this work using high-speed imaging and particle-tracking techniques. The results show that the average spatial and velocity distributions of the spray droplets are fairly axisymmetric during all stages of the atomization. The mean diameter of the droplets depends on the forcing frequency to the -2/3 power. The ejection velocity of the spray droplets depends on both the magnitude and the rate of change of the forcing amplitude. Thus, controlling the characteristics of the forcing signal may lead to strategies for controlling the spray process in specific applications.

  17. Statistical analysis of vibration-induced bone and joint damages.

    Science.gov (United States)

    Schenk, T

    1995-01-01

    Vibration-induced damages to bones and joints are still occupational diseases with insufficient knowledge about causing and moderating factors and resulting damages. For a better understanding of these relationships also retrospective analyses of already acknowledged occupational diseases may be used. Already recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases in the building industry and the building material industry of the GDR are the basis for the here described investigations. The data were gathered from the original documents of the occupational diseases and scaled in cooperation of an industrial engineer and an industrial physician. For the purposes of this investigations the data are to distinguish between data which describe the conditions of the work place (e.g. material, tools and posture), the exposure parameters (e.g. beginning of exposure and latency period) and the disease (e.g. anamnestical and radiological data). These data are treated for the use with sophisticated computerized statistical methods. The following analyses were carried out. Investigation of the connections between the several characteristics, which describe the occupational disease (health damages), including the comparison of the severity of the damages at the individual joints. Investigation of the side dependence of the damages. Investigation of the influence of the age at the beginning of the exposure and the age at the acknowledgement of the occupational disease and herewith of the exposure duration. Investigation of the effect of different occupational and exposure conditions.

  18. An Experimental Investigation of Vibration-Induced Single Droplet Ejection.

    Science.gov (United States)

    Range, Kai; Smith, Marc K.; Glezer, Ari

    1998-11-01

    Vibration-induced droplet atomization occurs when small secondary droplets are ejected from the free surface of a larger droplet placed on a vibrating membrane. To model a single ejection event, a liquid droplet is placed on a small piston and vibrated using an electromagnetic driver. The droplet oscillates in a characteristic mode shape that depends on the driving frequency and amplitude, the properties of the liquid, and the size of the droplet. When the excitation amplitude is large enough, a small secondary droplet is ejected from the primary droplet. Observations of this process using high-speed digital video imaging show that droplet ejection occurs when a small liquid column or jet appears on the primary droplet and a secondary droplet forms on the column by a capillary-pinching mechanism. The liquid column or jet emanates from a crater in the primary droplet. As the driving frequency increases, this crater becomes smaller and the diameter of the ejected droplet decreases. We shall present results showing how the ejected droplet diameter and speed depends on the driving frequency and amplitude, the liquid properties, and the primary droplet volume.

  19. Ejection Dynamics in Vibration-Induced Droplet Atomization

    Science.gov (United States)

    Vukasinovic, Bojan; Smith, Marc K.; Glezer, Ari

    2001-11-01

    A primary sessile liquid drop is atomized into a fine spray of secondary droplets using vibration-induced atomization (VIDA) resulting from forced waves on a free surface of the primary drop. The mechanism of free surface breakup during the VIDA process is investigated using high-speed imaging and laser vibrometry. Secondary droplets result from a localized collapse of surface troughs and the ejection and ultimate breakup of momentary liquid spikes. The characteristic breakup time of these liquid spikes scales with the vibration period and the spike length initially varies like t0.5. The breakup begins with a capillary pinch-off from the tip of the spike that can be followed by additional pinching of liquid droplets. For relatively low-viscosity liquid (e.g., water) a capillary-wave instability of a jet is observed in some cases, while in very viscous liquid (e.g., glycerin-water solution) the first breakup occurs near the stem of the jet. The mechanisms of secondary droplet ejection and the influence of the operating parameters and fluid properties are discussed.

  20. Experimental Study on the Measurement of Water Bottom Vibration Induced by Underwater Drilling Blasting

    OpenAIRE

    Wenbin, Gu; Jianghai, Chen; Zhenxiong, Wang; Zhihua, Wang; Jianqing, Liu; Ming, Lu

    2015-01-01

    Due to the lack of proper instrumentations and the difficulties in underwater measurements, the studies about water bottom vibration induced by underwater drilling blasting are seldom reported. In order to investigate the propagation and attenuation laws of blasting induced water bottom vibration, a water bottom vibration monitor was developed with consideration of the difficulties in underwater measurements. By means of this equipment, the actual water bottom vibration induced by underwater ...

  1. The Relationship between PTSD and Chronic Pain: Mediating Role of Coping Strategies and Depression

    OpenAIRE

    Morasco, Benjamin J.; Lovejoy, Travis I.; Lu, Mary; Turk, Dennis C.; Lewis, Lynsey; Dobscha, Steven K

    2013-01-01

    People with chronic pain and comorbid posttraumatic stress disorder (PTSD) report more severe pain and poorer quality of life than those with chronic pain alone. This study evaluated the extent to which associations between PTSD and chronic pain interference and severity are mediated by pain-related coping strategies and depressive symptoms. Veterans with chronic pain were divided into two groups, those with (n=65) and those without (n=136) concurrent PTSD. All participants completed measures...

  2. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    Science.gov (United States)

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  3. Vibration-induced finger flexion reflex and inhibitory effect of acupuncture on this reflex in cervical spinal cord injury patients.

    Science.gov (United States)

    Takakura, N; Iijima, S; Kanamaru, A; Shibuya, M; Homma, I; Ohashi, M

    1996-12-01

    The vibration-induced finger flexion reflex (VFR) and the inhibitory effect of acupuncture on this reflex were studied in five cervical spinal cord injury patients (C-SCIs). VFR, which is a tonic finger flexion reflex induced by vibratory stimulation on the finger tip, was induced before and after acupuncture was carried out on the same hand. A stainless steel needle was inserted to the Hoku point. As in healthy subjects, VFR was performed and it was significantly inhibited by acupuncture in the C-SCIs; mean maximum VFR was 204.2 +/- S.E. 68.6 g before and 119.8 +/- S.E. 42.2 g after acupuncture. The present results suggest that at least part of the reflex center for VFR is located in the spinal cord and that part of VFR inhibition by acupuncture may be mediated via the spinal cord.

  4. Factors mediating the relationship between intimate partner violence and chronic pain in Chinese women.

    Science.gov (United States)

    Tiwari, Agnes; Fong, Daniel Y T; Chan, Chee-Hon; Ho, Pak-Chung

    2013-03-01

    There is increasing recognition that chronic pain is a problem affecting women survivors of intimate partner violence (IPV), and in Western literature evidence is emerging about significant factors mediating the relationship between IPV and chronic pain. However, little is known about the factors mediating IPV and chronic pain in Chinese women for whom prior research has shown that Chinese culture may influence their response to IPV. This study was conducted to assess the roles of posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, and IPV-related injury on the relationship between IPV and chronic pain in Chinese women, using structural equation modelling (SEM). Data were collected from 308 Chinese women survivors of IPV recruited at community setting (n = 228) and at domestic violence shelters (n = 82). Results showed that only the relationship between psychological abuse severity and chronic pain severity was mediated by PTSD symptom severity (β = .30, 95% CI = 0.14-0.45, p relationship between any types of IPV and chronic pain. Similarly, IPV-related injury severity was not shown to have a significant mediating effect on the relationship between IPV and chronic pain. The findings affirm the importance of recognizing the complex interrelationships among IPV, mental health symptoms, and physical health problems as well as the need for considering PTSD symptoms when designing interventions for abused Chinese women with complaints of chronic pain.

  5. Vibration induced sliding: theory and experiment for a beam with a spring-loaded mass

    DEFF Research Database (Denmark)

    Miranda, Erik; Thomsen, Jon Juel

    1998-01-01

    The study sets up a simple model for predicting vibration induced sliding of mass, and provides quantitative experimental evidence for the validity of the model. The results lend confidence to recent theoretical developments on using vibration induced sliding for passive vibration damping......, and contributes to a further understanding of this nonlinear phenomenon. A mathematical model is set up to describe vibration induced sliding for a base-excited cantilever beam with a spring-loaded pointmass. Approximations simplify the model into two nonlinear ordinary differential equations, describing motions...... of the system at near-resonant excitation of a single beam mode. This simplified model is studied numerically and analytically, and tested against laboratory experiments. The experiments provide evidence that the simplified mathematical model retains those features of the real system that are necessary...

  6. Acceptance as a Mediator for Change in Acceptance and Commitment Therapy for Persons with Chronic Pain?

    Science.gov (United States)

    Cederberg, Jenny Thorsell; Cernvall, Martin; Dahl, JoAnne; von Essen, Louise; Ljungman, Gustaf

    2016-02-01

    Cognitive behavior therapy (CBT) is considered effective for chronic pain, but little is known about active treatment components. Although acceptance correlates with better health outcomes in chronic pain patients, no study has examined its mediating effect in an experimental design. The aim of the present study is to investigate acceptance as a mediator in acceptance and commitment therapy (ACT), a third wave CBT intervention, for chronic pain. A bootstrapped cross product of coefficients approach was used on data from a previously published RCT evaluating ACT for chronic pain. To address the specificity of acceptance as a mediator, anxiety and depression were also tested as mediators. Outcome variables were satisfaction with life and physical functioning. Two change scores, pre-assessment to 6-month follow-up (n = 53) and pre-assessment to 12-month follow-up (n = 32), were used. Acceptance was found to mediate the effect of treatment on change in physical functioning from pre-assessment to follow-up at 6 months. Further, a trend was shown from pre-assessment to follow-up at 12 months. No indirect effect of treatment via acceptance was found for change in satisfaction with life. This study adds to a small but growing body of research using mediation analysis to investigate mediating factors in the treatment of chronic pain. In summary, the results suggest that acceptance may have a mediating effect on change in physical functioning in ACT for persons with chronic pain. However, given the small sample size of the study, these findings need to be replicated.

  7. Vibration-induced displacement using high-frequency resonators and friction layers

    DEFF Research Database (Denmark)

    Thomsen, Jon Juel

    1998-01-01

    A mathematical model is set up to quantify vibration-induced motions of a slider with an imbedded resonator. A simple approximate expression is presented for predicting average velocities of the slider, agreeing fairly well with numerical integration of the full equations of motion. The simple...... expression can be used to the estimate influence of system parameters, and to plan and interpret laboratory experiments....

  8. Chronic alcoholism-mediated metabolic disorders in albino rat testes

    Directory of Open Access Journals (Sweden)

    Shayakhmetova Ganna M.

    2014-09-01

    Full Text Available There is good evidence for impairment of spermatogenesis and reductions in sperm counts and testosterone levels in chronic alcoholics. The mechanisms for these effects have not yet been studied in detail. The consequences of chronic alcohol consumption on the structure and/or metabolism of testis cell macromolecules require to be intensively investigated. The present work reports the effects of chronic alcoholism on contents of free amino acids, levels of cytochrome P450 3A2 (CYP3A2 mRNA expression and DNA fragmentation, as well as on contents of different cholesterol fractions and protein thiol groups in rat testes. Wistar albino male rats were divided into two groups: I - control (intact animals, II - chronic alcoholism (15% ethanol self-administration during 150 days. Following 150 days of alcohol consumption, testicular free amino acid content was found to be significantly changed as compared with control. The most profound changes were registered for contents of lysine (-53% and methionine (+133%. The intensity of DNA fragmentation in alcohol-treated rat testes was considerably increased, on the contrary CYP3A2 mRNA expression in testis cells was inhibited, testicular contents of total and etherified cholesterol increased by 25% and 45% respectively, and protein SH-groups decreased by 13%. Multidirectional changes of the activities of testicular dehydrogenases were detected. We thus obtained complex assessment of chronic alcoholism effects in male gonads, affecting especially amino acid, protein, ATP and NADPH metabolism. Our results demonstrated profound changes in testes on the level of proteome and genome. We suggest that the revealed metabolic disorders can have negative implication on cellular regulation of spermatogenesis under long-term ethanol exposure.

  9. Vibrationally-induced electronic population inversion with strong femtosecond pulses

    CERN Document Server

    Sampedro, Pablo; Sola, Ignacio R

    2016-01-01

    We discover a new mechanism of electronic population inversion using strong femtosecond pulses, where the transfer is mediated by vibrational motion on a light-induced potential. The process can be achieved with a single pulse tuning its frequency to the red of the Franck-Condon window. We show the determinant role that the sign of the slope of the transition dipole moment can play on the dynamics, and extend the method to multiphoton processes with odd number of pulses. As an example, we show how the scheme can be applied to population inversion in Na2.

  10. The relationship between PTSD and chronic pain: mediating role of coping strategies and depression.

    Science.gov (United States)

    Morasco, Benjamin J; Lovejoy, Travis I; Lu, Mary; Turk, Dennis C; Lewis, Lynsey; Dobscha, Steven K

    2013-04-01

    People with chronic pain and comorbid posttraumatic stress disorder (PTSD) report more severe pain and poorer quality of life than those with chronic pain alone. This study evaluated the extent to which associations between PTSD and chronic pain interference and severity are mediated by pain-related coping strategies and depressive symptoms. Veterans with chronic pain were divided into 2 groups, those with (n=65) and those without (n=136) concurrent PTSD. All participants completed measures of pain severity, interference, emotional functioning, and coping strategies. Those with current PTSD reported significantly greater pain severity and pain interference, had more symptoms of depression, and were more likely to meet diagnostic criteria for a current alcohol or substance use disorder (all p-values self-statements. Illness-focused pain coping (i.e., guarding, resting, and asking for assistance) and depressive symptoms jointly mediated the relationship between PTSD and both pain interference (total indirect effect=0.194, p<.001) and pain severity (total indirect effect=0.153, p=.004). Illness-focused pain coping also evidenced specific mediating effects, independent of depression. In summary, specific pain coping strategies and depressive symptoms partially mediated the relationship between PTSD and both pain interference and severity. Future research should examine whether changes in types of coping strategies after targeted treatments predict improvements in pain-related function for chronic pain patients with concurrent PTSD.

  11. Preformed Donor HLA-DP-Specific Antibodies Mediate Acute and Chronic Antibody-Mediated Rejection Following Renal Transplantation

    OpenAIRE

    Jolly, E. C.; Key, T; H. Rasheed; Morgan, H; Butler, A; Pritchard, N.; Taylor, C J; Clatworthy, M. R.

    2012-01-01

    Donor-specific HLA alloantibodies may cause acute and chronic antibody-mediated rejection (AMR) and significantly compromise allograft survival. The clinical relevance of antibodies directed against some HLA class II antigens, particularly HLA-DP, is less clear with conflicting reports on their pathogenicity. We report two patients with high levels of pretransplant donor-specific HLA-DP antibodies who subsequently developed recurrent acute AMR and graft failure. In both cases, there were no o...

  12. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    Science.gov (United States)

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  13. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies.

    Science.gov (United States)

    Leussink, Verena I; Hartung, Hans-Peter; Kieseier, Bernd C; Stettner, Mark

    2016-07-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients.

  14. High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

    Science.gov (United States)

    Padua, L; Paolasso, I; Pazzaglia, C; Granata, G; Lucchetta, M; Erra, C; Coraci, D; De Franco, P; Briani, C

    2013-12-01

    Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  15. Epigenetic Modification Mediates the Increase of LAG-3(+) T Cells in Chronic Osteomyelitis.

    Science.gov (United States)

    Wang, Yicun; Wang, Jun; Meng, Jia; Jiang, Hui; Zhao, Jianning; Qian, Hongbo; Chen, Tao

    2016-12-27

    Immune suppression plays critical roles in the development of chronic osteomyelitis, and the mechanisms underlying the development of immune suppression in chronic osteomyelitis have attracted much attention. LAG-3 is an important suppressor of T cell activation, but the role of LAG-3 in the immune regulation of chronic osteomyelitis is currently unknown. We sought to demonstrate if LAG-3 plays crucial roles in chronic osteomyelitis progression and has effects on immune suppression and exhausting of T cells, and what is the mechanism underlying LAG-3 deregulation in chronic osteomyelitis. We examined the expression of LAG-3 in the T cells of peripheral blood of 50 healthy controls and 50 patients with chronic osteomyelitis by flow cytometry. Clinical data were analyzed to determine the correlation between inflammation index and LAG-3 expression. Moreover, we isolated the CD4(+) T cells from healthy controls and chronic osteomyelitis patients to compare cell proliferation and IFN-γ production. Chromatin immunoprecipitation assays were utilized to analyze the epigenetic modification on LAG-3 expression in T cells. We found that LAG-3 was significantly increased in the T cells of peripheral blood from chronic osteomyelitis patients. Subsequently, clinical data analysis suggested that the higher expression of LAG-3 was associated with severer inflammation situation. Consistently, LAG-3(+)CD4(+) T cells exhibited impaired cell proliferation and IFN-γ secretion. Deregulation of histone methylation mediated the increase of LAG-3(+) T cells during chronic osteomyelitis. Taken together, our study demonstrates the increase of LAG-3(+) T cells and its immune regulatory roles in chronic osteomyelitis progression, suggesting new mechanisms and potential therapeutic targets for chronic osteomyelitis.

  16. Experimental Study on the Measurement of Water Bottom Vibration Induced by Underwater Drilling Blasting

    Directory of Open Access Journals (Sweden)

    Gu Wenbin

    2015-01-01

    Full Text Available Due to the lack of proper instrumentations and the difficulties in underwater measurements, the studies about water bottom vibration induced by underwater drilling blasting are seldom reported. In order to investigate the propagation and attenuation laws of blasting induced water bottom vibration, a water bottom vibration monitor was developed with consideration of the difficulties in underwater measurements. By means of this equipment, the actual water bottom vibration induced by underwater drilling blasting was measured in a field experiment. It shows that the water bottom vibration monitor could collect vibration signals quite effectively in underwater environments. The followed signal analysis shows that the characteristics of water bottom vibration and land ground vibration induced by the same underwater drilling blasting are quite different due to the different geological environments. The amplitude and frequency band of water bottom vibration both exceed those of land ground vibration. Water bottom vibration is mainly in low-frequency band that induced by blasting impact directly acts on rock. Besides the low-frequency component, land vibration contains another higher frequency band component that induced by followed water hammer wave acts on bank slope.

  17. STIM1 controls T cell-mediated immune regulation and inflammation in chronic infection.

    Science.gov (United States)

    Desvignes, Ludovic; Weidinger, Carl; Shaw, Patrick; Vaeth, Martin; Ribierre, Theo; Liu, Menghan; Fergus, Tawania; Kozhaya, Lina; McVoy, Lauren; Unutmaz, Derya; Ernst, Joel D; Feske, Stefan

    2015-06-01

    Chronic infections induce a complex immune response that controls pathogen replication, but also causes pathology due to sustained inflammation. Ca2+ influx mediates T cell function and immunity to infection, and patients with inherited mutations in the gene encoding the Ca2+ channel ORAI1 or its activator stromal interaction molecule 1 (STIM1) are immunodeficient and prone to chronic infection by various pathogens, including Mycobacterium tuberculosis (Mtb). Here, we demonstrate that STIM1 is required for T cell-mediated immune regulation during chronic Mtb infection. Compared with WT animals, mice with T cell-specific Stim1 deletion died prematurely during the chronic phase of infection and had increased bacterial burdens and severe pulmonary inflammation, with increased myeloid and lymphoid cell infiltration. Although STIM1-deficient T cells exhibited markedly reduced IFN-γ production during the early phase of Mtb infection, bacterial growth was not immediately exacerbated. During the chronic phase, however, STIM1-deficient T cells displayed enhanced IFN-γ production in response to elevated levels of IL-12 and IL-18. The lack of STIM1 in T cells was associated with impaired activation-induced cell death upon repeated TCR engagement and pulmonary lymphocytosis and hyperinflammation in Mtb-infected mice. Chronically Mtb-infected, STIM1-deficient mice had reduced levels of inducible regulatory T cells (iTregs) due to a T cell-intrinsic requirement for STIM1 in iTreg differentiation and excessive production of IFN-γ and IL-12, which suppress iTreg differentiation and maintenance. Thus, STIM1 controls multiple aspects of T cell-mediated immune regulation to limit injurious inflammation during chronic infection.

  18. Inflammation mediators in employees in chronic exposure to neurotoxicants

    Directory of Open Access Journals (Sweden)

    Galina Bodienkova

    2014-08-01

    Full Text Available Objectives: The aim of this work is to perform comparative estimation of cytokines levels in chlorinated hydrocarbons and metallic mercury exposure in employees in the dynamics of neurologic disorders formation. Material and Methods: The contents of cytokines IL-1β, IL-2, IL-4, IL-6, TNF-α, INF-γ were determined in blood sera using the method of hardphasic immunoferment analysis. The significance of different average values was assessed using the parametric and non-parametric criteria - Student (in normal distribution and Mann-Whitney tests taking into account the Bonferonni correction (non-difference from normal distribution. Results: It was shown that, a number of inflammation mediators with the dominance, depending on the expositional toxicant and expression of neurological deficiency, take part in the neurointoxication development. Healthy employees show pro-inflammatory responses with different expression degree, which dominate in the immune regulation processes regardless of the expositional factors (metallic mercury vapors and chlorinated hydrocarbons. Conclusions: The production intensity and interconnection between the pro- and anti-inflammatory cytokines may change in the occupational injuries of the nervous system development process. The decrease in the serum concentrations of cytokines along with the increase of clinical manifestation severity may prove dysregulation of the immune system, which promotes maintaining of pathological process and progradient process of neurointoxication. The most obvious is the imbalance of cytokines in the employees exposed to metallic mercury (in all the examined groups that increases neurointoxication in the distant period.

  19. Preformed donor HLA-DP-specific antibodies mediate acute and chronic antibody-mediated rejection following renal transplantation.

    Science.gov (United States)

    Jolly, E C; Key, T; Rasheed, H; Morgan, H; Butler, A; Pritchard, N; Taylor, C J; Clatworthy, M R

    2012-10-01

    Donor-specific HLA alloantibodies may cause acute and chronic antibody-mediated rejection (AMR) and significantly compromise allograft survival. The clinical relevance of antibodies directed against some HLA class II antigens, particularly HLA-DP, is less clear with conflicting reports on their pathogenicity. We report two patients with high levels of pretransplant donor-specific HLA-DP antibodies who subsequently developed recurrent acute AMR and graft failure. In both cases, there were no other donor-specific HLA alloantibodies, suggesting that the HLA-DP-specific antibodies may be directly pathogenic.

  20. Optimism on quality of life in Portuguese chronic patients: moderator/mediator?

    Directory of Open Access Journals (Sweden)

    Estela Vilhena

    2014-07-01

    Full Text Available Objective: optimism is an important variable that has consistently been shown to affect adjustment to quality of life in chronic diseases. This study aims to clarify if dispositional optimism exerts a moderating or a mediating influence on the personality traits-quality of life association, in Portuguese chronic patients. Methods: multiple regression models were used to test the moderation and mediation effects of dispositional optimism in quality of life. A sample of 729 patients was recruited in Portugal's main hospitals and completed self-reported questionnaires assessing socio-demographic and clinical variables, personality, dispositional optimism, quality of life (QoL and subjective well-being (SWB. Results: the results of the regression models showed that dispositional optimism did not moderate the relationships between personality traits and quality of life. After controlling for gender, age, education level and severity of disease perception, the effects of personality traits on QoL and in SWB were mediated by dispositional optimism (partially and completely, except for the links between neuroticism/openness to experience and physical health. Conclusion: dispositional optimism is more likely to play a mediating, rather than a moderating role in personality traits-quality of life pathway in Portuguese chronic patients, suggesting that "the expectation that good things will happen" contributes to a better quality of life and subjective well-being.

  1. Topographic analysis of the skull vibration-induced nystagmus test with piezoelectric accelerometers and force sensors.

    Science.gov (United States)

    Dumas, Georges; Lion, Alexis; Perrin, Philippe; Ouedraogo, Evariste; Schmerber, Sébastien

    2016-03-23

    Vibration-induced nystagmus is elicited by skull or posterior cervical muscle stimulations in patients with vestibular diseases. Skull vibrations delivered by the skull vibration-induced nystagmus test are known to stimulate the inner ear structures directly. This study aimed to measure the vibration transfer at different cranium locations and posterior cervical regions to contribute toward stimulus topographic optimization (experiment 1) and to determine the force applied on the skull with a hand-held vibrator to study the test reproducibility and provide recommendations for good clinical practices (experiment 2). In experiment 1, a 100 Hz hand-held vibrator was applied on the skull (vertex, mastoids) and posterior cervical muscles in 11 healthy participants. Vibration transfer was measured by piezoelectric sensors. In experiment 2, the vibrator was applied 30 times by two experimenters with dominant and nondominant hands on a mannequin equipped to measure the force. Experiment 1 showed that after unilateral mastoid vibratory stimulation, the signal transfer was higher when recorded on the contralateral mastoid than on the vertex or posterior cervical muscles (P<0.001). No difference was observed between the different vibratory locations when vibration transfer was measured on vertex and posterior cervical muscles. Experiment 2 showed that the force applied to the mannequin varied according to the experimenters and the handedness, higher forces being observed with the most experienced experimenter and with the dominant hand (10.3 ± 1.0 and 7.8 ± 2.9 N, respectively). The variation ranged from 9.8 to 29.4% within the same experimenter. Bone transcranial vibration transfer is more efficient from one mastoid to the other mastoid than other anatomical sites. The mastoid is therefore the optimal site for skull vibration-induced nystagmus test in patients with unilateral vestibular lesions and enables a stronger stimulation of the healthy side. In clinical practice

  2. The Mediating Role of Acceptance in Multidisciplinary Cognitive-Behavioral Therapy for Chronic Pain.

    Science.gov (United States)

    Åkerblom, Sophia; Perrin, Sean; Rivano Fischer, Marcelo; McCracken, Lance M

    2015-07-01

    Cognitive-behavioral therapy (CBT) is the most frequently delivered psychological intervention for adults with chronic pain. The treatment yields modest effect sizes, and the mechanisms of action remain understudied and unclear. Efforts are needed to identify treatment mediators that could be used to refine CBT and improve outcomes. The primary aim of this study was to investigate whether pain-related acceptance, from the psychological flexibility model, mediates changes in outcome over time in a CBT-based treatment program. This includes comparing how this variable relates to 3 other variables posited as potential mediators in standard CBT: life control, affective distress, and social support. Participants attended a 5-week outpatient multidisciplinary program with self-report data collected at assessment, posttreatment, and 12-month follow-up. Multilevel structural equation modeling was used to test for mediation in relation to 3 outcomes: pain interference, pain intensity, and depression. Results indicate that effect sizes for the treatment were within the ranges reported in the CBT for pain literature. Pain-related acceptance was not related to pain intensity, which is in line with past empirical evidence and the treatment objectives in acceptance and commitment therapy. Otherwise, pain-related acceptance was the strongest mediator across the different indices of outcome. Accumulated results like these suggest that acceptance of pain may be a general mechanism by which CBT-based treatments achieve improvements in functioning. More specific targeting of pain-related acceptance in treatment may lead to further improvements in outcome. Potential mediators of outcome in a CBT-based treatment for adult chronic pain were investigated using multilevel structural equation modeling. The results highlight the role of pain-related acceptance as an important treatment process even when not explicitly targeted during treatment. These data may help clinicians and researchers

  3. Chronic Low Dose Fructose infusion Does Not Reverse Glucagon-Mediated Decrease in Hepatic Glucose Utilization

    Science.gov (United States)

    Johnson, Paulette M.; Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E; Lacy, D. Brooks; McGuinness, Owen P.

    2013-01-01

    Objective An adaptation to chronic total parenteral nutrition (TPN; 75% of non protein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if chronic fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Material/methods Studies were performed in conscious insulin-treated chronically catheterized pancreatectomized dogs that adapted to TPN for 33 h. They were then assigned to one of 4 groups: TPN (C), TPN + fructose (4.4 μmol·kg−1·min−1, F), TPN+ glucagon (0.2 pmol·kg−1·min−1, GGN), or a TPN + fructose and glucagon (F+GGN) for an additional 63h (33–96h). Insulin, fructose and glucagon were infused into the portal vein. During that period all animals received a fixed insulin infusion 0.4mU· kg−1·min−1 (33–96h) and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mM). Results Chronic fructose infusion was unable to further enhance net hepatic glucose uptake (NHGU; μmol·kg−1·min−1) (31.1±2.8 vs. 36.1±5.0; C vs. F) nor was it able to overcome glucagon-mediated decrease in NHGU (10.0±4.4 vs. 12.2±3.9; GGN vs. F+GGN). Conclusion In summary, chronic fructose infusion cannot augment liver glucose uptake during TPN nor can it overcome the inhibitory effects of glucagon. PMID:20940071

  4. The effect of chronic seaweed subsidies on herbivory: plant-mediated fertilization pathway overshadows lizard-mediated predator pathways.

    Science.gov (United States)

    Piovia-Scott, Jonah; Spiller, David A; Takimoto, Gaku; Yang, Louie H; Wright, Amber N; Schoener, Thomas W

    2013-08-01

    Flows of energy and materials link ecosystems worldwide and have important consequences for the structure of ecological communities. While these resource subsidies typically enter recipient food webs through multiple channels, most previous studies focussed on a single pathway of resource input. We used path analysis to evaluate multiple pathways connecting chronic marine resource inputs (in the form of seaweed deposits) and herbivory in a shoreline terrestrial ecosystem. We found statistical support for a fertilization effect (seaweed increased foliar nitrogen content, leading to greater herbivory) and a lizard numerical response effect (seaweed increased lizard densities, leading to reduced herbivory), but not for a lizard diet-shift effect (seaweed increased the proportion of marine-derived prey in lizard diets, but lizard diet was not strongly associated with herbivory). Greater seaweed abundance was associated with greater herbivory, and the fertilization effect was larger than the combined lizard effects. Thus, the bottom-up, plant-mediated effect of fertilization on herbivory overshadowed the top-down effects of lizard predators. These results, from unmanipulated shoreline plots with persistent differences in chronic seaweed deposition, differ from those of a previous experimental study of the short-term effects of a pulse of seaweed deposition: while the increase in herbivory in response to chronic seaweed deposition was due to the fertilization effect, the short-term increase in herbivory in response to a pulse of seaweed deposition was due to the lizard diet-shift effect. This contrast highlights the importance of the temporal pattern of resource inputs in determining the mechanism of community response to resource subsidies.

  5. Dopaminergic signaling mediates the motivational response underlying the opponent process to chronic but not acute nicotine.

    Science.gov (United States)

    Grieder, Taryn E; Sellings, Laurie H; Vargas-Perez, Hector; Ting-A-Kee, Ryan; Siu, Eric C; Tyndale, Rachel F; van der Kooy, Derek

    2010-03-01

    The mesolimbic dopamine (DA) system is implicated in the processing of the positive reinforcing effect of all drugs of abuse, including nicotine. It has been suggested that the dopaminergic system is also involved in the aversive motivational response to drug withdrawal, particularly for opiates, however, the role for dopaminergic signaling in the processing of the negative motivational properties of nicotine withdrawal is largely unknown. We hypothesized that signaling at dopaminergic receptors mediates chronic nicotine withdrawal aversions and that dopaminergic signaling would differentially mediate acute vs dependent nicotine motivation. We report that nicotine-dependent rats and mice showed conditioned place aversions to an environment paired with abstinence from chronic nicotine that were blocked by the DA receptor antagonist alpha-flupenthixol (alpha-flu) and in DA D(2) receptor knockout mice. Conversely, alpha-flu pretreatment had no effect on preferences for an environment paired with abstinence from acute nicotine. Taken together, these results suggest that dopaminergic signaling is necessary for the opponent motivational response to nicotine in dependent, but not non-dependent, rodents. Further, signaling at the DA D(2) receptor is critical in mediating withdrawal aversions in nicotine-dependent animals. We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals.

  6. Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Dru S Dace

    Full Text Available BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome or chronic forms. Interleukin-10 (IL-10, although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP or Guillain-Barré syndrome.

  7. Mediators and treatment matching in behavior therapy, cognitive therapy and cognitive behavior therapy for chronic insomnia.

    Science.gov (United States)

    Harvey, Allison G; Dong, Lu; Bélanger, Lynda; Morin, Charles M

    2017-10-01

    To examine the mediators and the potential of treatment matching to improve outcome for cognitive behavior therapy (CBT) for insomnia. Participants were 188 adults (117 women; Mage = 47.4 years, SD = 12.6) meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; text rev.; DSM-IV-TR; American Psychiatric Association [APA], 2000) diagnostic criteria for chronic insomnia (Mduration: 14.5 years, SD: 12.8). Participants were randomized to behavior therapy (BT; n = 63), cognitive therapy (CT; n = 65), or CBT (n = 60). The outcome measure was the Insomnia Severity Index (ISI). Hypothesized BT mediators were sleep-incompatible behaviors, bedtime variability (BTv), risetime variability (RTv) and time in bed (TIB). Hypothesized CT mediators were worry, unhelpful beliefs, and monitoring for sleep-related threat. The behavioral processes mediated outcome for BT but not CT. The cognitive processes mediated outcome in both BT and CT. The subgroup scoring high on both behavioral and cognitive processes had a marginally significant better outcome if they received CBT relative to BT or CT. The subgroup scoring relatively high on behavioral but low on cognitive processes and received BT or CBT did not differ from those who received CT. The subgroup scoring relatively high on cognitive but low on behavioral processes and received CT or CBT did not differ from those who received BT. The behavioral mediators were specific to BT relative to CT. The cognitive mediators were significant for both BT and CT outcomes. Patients exhibiting high levels of both behavioral and cognitive processes achieve better outcome if they receive CBT relative to BT or CT alone. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Cyclosporine A (CsA treatment of chronic autoimune-mediated keratoconjunctivitis sicca in dogs

    Directory of Open Access Journals (Sweden)

    Hadži-Milić M.

    2013-01-01

    Full Text Available The paper is a five year retrospective study of the efficacy of 0.2% Cyclosporine A eye cream in the treatment of chronic autoimmunemediated KCS in dogs. 114 dogs of 32 breeds, both sexes, and different ages with chronic autoimmune-mediated KCS were treated with 0.2% Cyclosporine A in the form of eye cream (Optimmune®, Schering - Plough Animal Health applied to the lower lid conjunctiva at a dose of 6 mm length of the cream strip every 12 hours, during 90 days. Dogs treated with CsA had an improved STT score, specially dogs which had STT values >5 mm/min at the start. Improvement of the clinical picture and healing of superficial corneal lesions were also recorded.

  9. [Immunosuppressive treatment after kidney transplant: the frontier of chronic antibody-mediated rejection].

    Science.gov (United States)

    Biancone, Luigi; Lavacca, Antonio; Beltramo, Silvia; Ariaudo, Claudia; Gallo, Ester; Segoloni, Giuseppe Paolo

    2012-01-01

    The recognition of antibody-mediated rejection as an important factor in the reduction of long-term renal graft survival represents a new challenge to the immunosuppressive strategies of recent years, which have been quite successful in reducing the acute rejection rates as well as the side effects of pharmacological immunosuppression. The search for an effective treatment of chronic anti-donor antibody disease has been pursued mostly through limited single-center experiences and therefore in a dispersed fashion, without leading to the definition of a consolidated approach. The most frequently used pharmacological approaches stem from the experience of antibody-mediated acute rejection. In this review we will critically analyze the results reported so far of various intervention strategies and we will discuss future pharmacological novelties targeting the humoral immune response.

  10. A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.

    Science.gov (United States)

    Noerager, Brett D; Xu, Xin; Davis, Virginia A; Jones, Caleb W; Okafor, Svetlana; Whitehead, Alicia; Blalock, J Edwin; Jackson, Patricia L

    2015-12-01

    Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation.

  11. Vibration-Induced Conductivity Fluctuation Measurement for Soil Bulk Density Analysis

    CERN Document Server

    Kishne, Andrea Sz; Chang, Hung-Chih; Kish, Laszlo B

    2007-01-01

    Soil bulk density affects water storage, water and nutrient movement, and plant root activity in the soil profile. Its measurement is difficult in field conditions. Vibration-induced conductivity fluctuation was investigated to quantify soil bulk density with possible field applications in the future. The AC electrical conductivity of soil was measured using a pair of blade-like electrodes while exposing the soil to periodic vibration. The blades were positioned longitudinally and transversally to the direction of the induced vibration to enable the calculation of a normalized index. The normalized index was expected to provide data independent from the vibration strength and to reduce the effect of soil salinity and water content. The experiment was conducted on natural and salinized fine sand at two moisture conditions and four bulk densities. The blade-shaped electrodes improved electrode-soil contact compared to cylindrical electrodes, and thereby, reduced measurement noise. Simulations on a simplified re...

  12. Frequencies in the Vibration Induced by the Rotor Stator Interaction in a Centrifugal Pump Turbine

    DEFF Research Database (Denmark)

    Rodriguez, Cristian; Egusquiza, Eduard; Santos, Ilmar

    2007-01-01

    of the analysis and after it is carried out in one of the units, the vibration levels are reduced The vibration induced by the RSI is predicted considering the sequence of interaction and different amplitudes in the interactions between the same moving blade and different stationary blades, giving a different......The highest vibration levels in large pump turbines are, in general, originated in the rotor stator interaction (RSI). This vibration has specific characteristics that can be clearly observed in the frequency domain: harmonics of the moving blade passing frequency and a particular relationship...... among their amplitudes. It is valuable for the design and condition monitoring to count on these characteristics. A CFD model is an appropriate tool to determine the force and its characteristics. However it is time consuming and needs highly qualified human resources while usually these results...

  13. Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis

    Science.gov (United States)

    Kater, Arnon P.; Dicker, Frank; Mangiola, Massimo; Welsh, Kate; Houghten, Richard; Ostresh, John; Nefzi, Adel; Reed, John C.; Pinilla, Clemencia; Kipps, Thomas J.

    2005-01-01

    Patients with chronic lymphocytic leukemia (CLL) treated with adenovirus CD154 (Ad-CD154, CD40 ligand [CD40L]) gene therapy experienced rapid reductions in leukemia cell counts and lymph node size associated with the induced expression of Fas (CD95). However, CLL cells initially resist CD95-mediated apoptosis within the first 3 days after CD40 ligation in vitro. Thereafter, they become sensitive, which is associated with the CD40-induced expression of the proapoptotic protein B-cell leukemia 2 homology 3 (BH3) interacting domain death agonist (Bid). We hypothesized that the initial resistance to CD95-mediated apoptosis may be due to the high-level expression of X-linked inhibitor of apoptosis protein (XIAP) by CLL cells. Consistent with this, CLL cells from patients 1 day after treatment with autologous Ad-CD154-transduced CLL cells became sensitive to CD95-mediated apoptosis following treatment with a novel XIAP inhibitor, 1540-14. Similarly, 1540-14 specifically enhanced CD95-mediated apoptosis of CLL cells following CD40 ligation in vitro. Immunoblot analyses demonstrated that treatment with 1540-14 allowed CD40-stimulated CLL cells to experience high-level activation of caspases-8 and -3 and cleavage of poly(adenosine diphosphate [ADP]-ribose) polymerase following CD95 ligation. This study demonstrates that distal apoptosis regulators contribute to the initial resistance of CD40-activated CLL cells to CD95-mediated apoptosis and suggests that XIAP inhibitors might enhance the effectiveness of immune-based treatment strategies that target CD40, such as CD154 gene therapy. (Blood. 2005;106:1742-1748) PMID:15914559

  14. Chronic hypobaric hypoxia mediated skeletal muscle atrophy: role of ubiquitin-proteasome pathway and calpains.

    Science.gov (United States)

    Chaudhary, Pooja; Suryakumar, Geetha; Prasad, Rajendra; Singh, Som Nath; Ali, Shakir; Ilavazhagan, Govindsamy

    2012-05-01

    The most frequently reported symptom of exposure to high altitude is loss of body mass and decreased performance which has been attributed to altered protein metabolism affecting skeletal muscles mass. The present study explores the mechanism of chronic hypobaric hypoxia mediated skeletal muscle wasting by evaluating changes in protein turnover and various proteolytic pathways. Male Sprague-Dawley rats weighing about 200 g were exposed to hypobaric hypoxia (7,620 m) for different durations of exposure. Physical performance of rats was measured by treadmill running experiments. Protein synthesis, protein degradation rates were determined by (14)C-Leucine incorporation and tyrosine release, respectively. Chymotrypsin-like enzyme activity of the ubiquitin-proteasome pathway and calpains were studied fluorimetrically as well as using western blots. Declined physical performance by more than 20%, in terms of time taken in exhaustion on treadmill, following chronic hypobaric hypoxia was observed. Compared to 1.5-fold increase in protein synthesis, the increase in protein degradation was much higher (five-folds), which consequently resulted in skeletal muscle mass loss. Myofibrillar protein level declined from 46.79 ± 1.49 mg/g tissue at sea level to 37.36 ± 1.153 (P calpains (three-fold) has been found to be important factors for the enhanced protein degradation rate. The study provided strong evidences suggesting that elevated protein turnover rate lead to skeletal muscle atrophy under chronic hypobaric hypoxia via ubiquitin-proteasome pathway and calpains.

  15. Nociceptive and Inflammatory Mediator Upregulation in a Mouse Model of Chronic Prostatitis

    Science.gov (United States)

    Schwartz, Erica S.; Xie, Amy; La, Jun-Ho; Gebhart, G.F.

    2015-01-01

    Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue, FB) from the prostate revealed that thoracolumbar (TL) and lumbosacral (LS) DRG are the principal sources of somata of prostate afferents. Nociceptive markers (e.g., TRP, TREK and P2X channels) were upregulated in FB-labeled TL and LS somata for up to four weeks after inflaming the prostate (intra-prostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21 and 28 days after zymosan injection. Interleukin-10 and NGF were also significantly upregulated in the prostate throughout the four weeks of inflammation. Open field pain-related behaviors (e.g., rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for study of mechanisms underlying pain in chronic prostatitis. PMID:25915147

  16. Effect of chronic microwave radiation on T cell-mediated immunity in the rabbit

    Science.gov (United States)

    Nageswari, K. Sri; Sarma, K. R.; Rajvanshi, V. S.; Sharan, R.; Sharma, Manju; Barathwal, Vinita; Singh, Vinod

    1991-06-01

    Experiments were conducted to elucidate the effects of chronic low power-level microwave radiation on the immunological systems of rabbits. Fourteen male Belgian white rabbits were exposed to microwave radiation at 5 mW/cm2, 2.1 GHz, 3 h daily, 6 days/week for 3 months in two batches of 7 each in specially designed miniature anechoicchambers. Seven rabbits were subjected to sham exposure for identical duration. The microwave energy was provided through S band standard gain horns connected to a 4K3SJ2 Klystron power amplifier. The first batch of animals were assessed for T lymphocyte-mediated cellular immune response mechanisms and the second batch of animals for B lymphocyte-mediated humoral immune response mechanisms. The peripheral blood samples collected monthly during microwave/sham exposure and during follow-up (5/14 days after termination of exposures, in the second batch animals only) were analysed for T lymphocyte numbers and their mitogen responsiveness to ConA and PHA. Significant suppression of T lymphocyte numbers was noted in the microwave group at 2 months ( Prabbits. From these results it is speculated that the T lymphocytes are sequestered to various lymphoid organs under the influence of microwaves. A sub-population of T cells known as T helper cells (mediating DTH response) are probably not affected by microwave radiation. It is clear from our experiments that although chronic microwave radiation at 5 mW/cm2 leads to suppression of peripheral T lymphocyte numbers, there is no concomitant functional impairment of these cells as evidenced by functional assays.

  17. The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation.

    Science.gov (United States)

    Spyridaki, Eirini C; Simos, Panagiotis; Avgoustinaki, Pavlina D; Dermitzaki, Eirini; Venihaki, Maria; Bardos, Achilles N; Margioris, Andrew N

    2014-11-28

    Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.

  18. Chronic elevation of IL-1β induces diuresis via a cyclooxygenase 2-mediated mechanism.

    Science.gov (United States)

    Boesen, E I

    2013-07-15

    Chronic renal inflammation is an increasingly recognized phenomenon in multiple disease states, but the impact of specific cytokines on renal function is unclear. Previously, we found that 14-day interleukin-1β (IL-1β) infusion increased urine flow in mice. To determine the mechanism by which this occurs, the current study tested the possible involvement of three classical prodiuretic pathways. Chronic IL-1β infusion significantly increased urine flow (6.5 ± 1 ml/day at day 14 vs. 2.3 ± 0.3 ml/day in vehicle group; P < 0.05) and expression of cyclooxygenase (COX)-2, all three nitric oxide synthase (NOS) isoforms, and endothelin (ET)-1 in the kidney (P < 0.05 in all cases). Urinary prostaglandin E metabolite (PGEM) excretion was also significantly increased at day 14 of IL-1β infusion (1.21 ± 0.26 vs. 0.29 ± 0.06 ng/day in vehicle-infused mice; P = 0.001). The selective COX-2 inhibitor celecoxib markedly attenuated urinary PGEM excretion and abolished the diuretic response to chronic IL-1β infusion. In contrast, deletion of NOS3, or inhibition of NOS1 with L-VNIO, did not blunt the diuretic effect of IL-1β, nor did pharmacological blockade of endothelin ETA and ETB receptors with A-182086. Consistent with a primary effect on water transport, IL-1β infusion markedly reduced inner medullary aquaporin-2 expression (P < 0.05) and did not alter urinary Na⁺ or K⁺ excretion. These data indicate a critical role for COX-2 in mediating the effects of chronic IL-1β elevation on the kidney.

  19. Coping mediates the relationship between disease severity and illness intrusiveness among chronically ill patients.

    Science.gov (United States)

    Hundt, Natalie E; Bensadon, Benjamin A; Stanley, Melinda A; Petersen, Nancy J; Kunik, Mark E; Kauth, Michael R; Cully, Jeffrey A

    2015-09-01

    Reducing perceptions of illness intrusiveness may improve quality of life and mental health among patients with cardiopulmonary disease. To better understand relationships between coping style, locus of control, perceived illness intrusiveness, and disease severity, we analyzed data from 227 older Veterans with chronic obstructive pulmonary disease or congestive heart failure. Regressions revealed illness intrusiveness to be associated with younger age and greater disease severity, less internal locus of control, and avoidant/emotion-focused coping. Avoidant/emotion-focused coping but not active coping mediated the relationship between illness severity and illness intrusiveness. Findings suggest that supportive psychological interventions may reduce illness intrusiveness by targeting an avoidant/emotion-focused coping style and associated behaviors. © The Author(s) 2013.

  20. Mediators of Inflammation and Angiogenesis in Chronic Spontaneous Urticaria: Are They Potential Biomarkers of the Disease?

    Directory of Open Access Journals (Sweden)

    Ilaria Puxeddu

    2017-01-01

    Full Text Available In chronic spontaneous urticaria (CSU, different pathophysiological mechanisms, potentially responsible for the development of the disease, have been recently described. It is likely that the activation of skin mast cells with consequent release of histamine and other proinflammatory mediators is responsible for vasodilation in the lesional skin of CSU. However, the underlying causes of mast cell activation in the disease are largely unknown and remain to be identified. Thus, in this review, we discuss new insights in the pathogenesis of CSU, focusing on inflammation and angiogenesis. The understanding of these mechanisms will enable the identification of biomarkers useful for the diagnosis, follow-up, and management of CSU and will allow the development of novel, more specific, and patient-tailored therapies.

  1. Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

    Science.gov (United States)

    Cattaruzza, Fiore; Johnson, Cali; Leggit, Alan; Grady, Eileen; Schenk, A Katrin; Cevikbas, Ferda; Cedron, Wendy; Bondada, Sandhya; Kirkwood, Rebekah; Malone, Brian; Steinhoff, Martin; Bunnett, Nigel; Kirkwood, Kimberly S

    2013-06-01

    Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

  2. Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin.

    Science.gov (United States)

    da Silva, Alexandre A; Hall, John E; Moak, Sydney P; Browning, Jackson; Houghton, Haley J; Micheloni, Giovana C; do Carmo, Jussara M

    2017-05-01

    This study tested whether ganglionic blockade or hepatic vagotomy attenuates the chronic central nervous system (CNS)-mediated antidiabetic and cardiovascular effects of leptin. Male Sprague-Dawley rats were instrumented with telemetry probes and arterial and venous catheters for determination of blood pressure (BP), heart rate (HR), blood sampling, and intravenous (iv) infusions. An intracerebroventricular (ICV) cannula was placed into the brain lateral ventricle for infusion of leptin or vehicle. After control measurements, streptozotocin (STZ) was injected iv (50 mg/kg) to induce diabetes, and 5 days later leptin (n = 6) or saline vehicle (n = 5) was infused ICV for 12 days via osmotic pumps. Beginning on day 6 of leptin treatment, the ganglionic blocker hexamethonium (15 mg·kg(-1)·day(-1) iv) was infused, while leptin infusion was continued, to assess the role of the autonomic nervous system. Induction of diabetes was associated with increases in blood glucose (98 ± 7 to 350 ± 19 mg/dl), food intake (23 ± 3 to 43 ± 3 g/day), decreases in HR (-70 ± 11 beats/min), polyuria, and increased water consumption, which were all completely normalized by ICV leptin infusion. Although hexamethonium attenuated leptin's effect on HR, it failed to impair leptin's ability to restore euglycemia or to prevent the polyuria or increased water intake in STZ-diabetic rats. We also found that after pretreatment with hexamethonium (n = 8), ICV leptin infusion, during continued ganglionic blockade, completely normalized blood glucose in diabetic rats. In addition, selective hepatic vagotomy did not attenuate leptin's ability to restore euglycemia in diabetic rats. These results suggest that leptin's powerful chronic CNS antidiabetic actions are mediated primarily via nonautonomic mechanisms. Copyright © 2017 the American Physiological Society.

  3. Mechanisms of Chronic State of Inflammation as Mediators That Link Obese Adipose Tissue and Metabolic Syndrome

    Science.gov (United States)

    Fuentes, Eduardo; Fuentes, Francisco; Badimon, Lina; Palomo, Iván

    2013-01-01

    The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammatory signalling pathways resulting in the induction of several biological markers of inflammation. Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Adiponectin can either act directly on macrophages to shift polarization and/or prime human monocytes into alternative M2-macrophages with anti-inflammatory properties. Meanwhile, the chronic inflammation in adipose tissue is regulated by a series of transcription factors, mainly PPARs and C/EBPs, that in conjunction regulate the expression of hundreds of proteins that participate in the metabolism and storage of lipids and, as such, the secretion by adipocytes. Therefore, the management of the metabolic syndrome requires the development of new therapeutic strategies aimed to alter the main genetic pathways involved in the regulation of adipose tissue metabolism. PMID:23843680

  4. Clinical Correlates and Mediators of Self-Concept in Youth with Chronic Tic Disorders.

    Science.gov (United States)

    Hanks, Camille E; McGuire, Joseph F; Lewin, Adam B; Storch, Eric A; Murphy, Tanya K

    2016-02-01

    This study investigated the clinical correlates and mediators of self-concept in youth with Chronic Tic Disorders (CTD). Ninety-seven youth aged 6-17 (M = 11.1 ± 2.89; 79.4 % male) with CTD were administered the Yale Global Tic Severity Scale, the Piers-Harris Children's Self-Concept Scale-Second Edition, and self-report and clinician-administered measures assessing behavioral and psychological difficulties and comorbid conditions. Youth with CTD had a slightly below average level of self-concept, with 20 % (n = 19) exhibiting low self-concept. Youth with CTD-only had greater self-concept relative to youth with CTD and obsessive-compulsive disorder (OCD) (p = 0.04) or CTD, OCD, and attention deficit hyperactivity disorder (ADHD) combined (p = 0.009). Medium-to-large-sized associations were observed between youth's self-concept and clinical characteristics (e.g., severity of ADHD, OCD and depressive symptoms). Youth's self-concept partially mediated the relationship between tic severity and depressive symptom severity, and the interaction between tic impairment and youth's reliance on avoidant coping strategies moderated youth's self-concept. Implications, limitations, and recommendations for future interventions are discussed.

  5. Vibration-induced white finger among selected underground rock drillers in British Columbia.

    Science.gov (United States)

    Brubaker, R L; Mackenzie, C J; Hutton, S G

    1986-08-01

    Ninety-five rock drillers who used pneumatic hand-held drills were interviewed and tested. Thirty-seven were excluded because of factors predisposing to the appearance of white fingers other than exposure to industrial hand-drill vibration. Forty-five percent of the remaining 58 drillers suffered from periodic attacks of Raynaud's phenomenon. Symptoms were present in 25% of the drillers exposed for 1-5 years and in 80% of those exposed for greater than or equal to 16 years. Nine percent of the cases were classified as severe. The median latency for the onset of the blanching symptoms was 7.5 years. The prevalence of Raynaud's phenomenon was 4% among a reference group of 56 miners not exposed to hand vibration and corrected for possible predisposing factors. Objective evidence indicated delayed finger rewarming after a combination of digital ischemia and cooling in 75% of the drillers with blanching symptoms and 18% of the referents without symptoms. There was evidence of an increased frequency of vibration-induced white finger among current cigarette smokers. Weighted 4-h equivalent acceleration levels measured from the handles of 26 jack-leg and 13 stoper drills from the same mines as the miners ranged from 15 to 32 m/s2. These levels exceed recommended guidelines of the International Organization for Standardization.

  6. Vibration-Induced Property Change in the Melting and Solidifying Process of Metallic Nanoparticles

    Science.gov (United States)

    Zheng, Yonggang; Ding, Liquan; Ye, Hongfei; Chen, Zhen

    2017-04-01

    Tuning material properties in the 3-D printing process of metallic parts is a challenging task of current interests. Much research has been conducted to understand the effects of controlling parameters such as the particle geometry (size and shape), heating, and cooling ways on the outcome of the printing process. However, nothing has been done to explore the system vibration effect. This letter reports our findings on the vibration-induced property change in the melting and solidifying process of silver nanoparticles with the use of molecular dynamics simulation. We find that the increase of system vibration magnitude would increase the number fraction of disordered atoms, which in turn changes the nanostructure of solidified products. For a given system vibration magnitude, the number fraction of disordered atoms reaches the maximum around the system natural frequency so that the stiffness of solidified products becomes the minimum. Since this trend is not affected by the system size, the above findings reveal a feasible path toward the real-time tuning of material properties for advancing additive manufacturing.

  7. Field experiment of subgrade vibration induced by passing train in a seasonally frozen region of Daqing

    Institute of Scientific and Technical Information of China (English)

    Ling Xianzhang; Zhang Feng; Zhu Zhanyuan; Ding Lin; Hu Qinli

    2009-01-01

    The vibration characteristics and attenuation of the subgrade caused by passing trains in a seasonally frozen region of Daqing, China are investigated. Three field experiments were conducted during different times through the year, in normal, freezing and thawing periods, respectively, and the influence of the season, train speed and train type, is described in this paper. The results show that: (l) the vertical component is the greatest among the three components of the measured vibration near the rail track, and as the distance to the railway track increases, the dominant vibration depends on the season. (2) Compared with the vibration in the normal period, the vertical and longitudinal vibrations increase while the lateral vibration decreases in the freezing period. However, in the thawing period, the vertical and longitudinal vibrations decrease, and the lateral vibration increases. (3) As train speeds increase, the subgrade vibration increases. (4) The vibration induced by a freight train is greater than by a passenger train. These observations provide a better understanding of the vibration and dynamic stability of the subgrade and may be useful in developing criteria for railway and building construction in cold regions.

  8. Stern-Gerlach Experiments on Mn@Sn12: Identification of a Paramagnetic Superatom and Vibrationally Induced Spin Orientation

    Science.gov (United States)

    Rohrmann, Urban; Schäfer, Rolf

    2013-09-01

    Beam deflection experiments in inhomogeneous magnetic fields reveal a new limiting case of the magnetization distribution of isolated clusters. Endohedrally doped clusters are produced in a temperature controlled, cryogenically cooled laser ablation source. Temperature dependent experiments indicate a crucial contribution of molecular vibrations to the spin dynamics of Mn@Sn12. In its vibrational ground state the cluster behaves magnetically like a paramagnetic atom, with quantized spin states. However, excited molecular vibrations induce spin orientation in the magnetic field.

  9. Physical activity as a mediator of the impact of chronic conditions on quality of life in older adults

    Directory of Open Access Journals (Sweden)

    Miller William C

    2007-12-01

    Full Text Available Abstract Background Chronic conditions could negatively affect the quality of life of older adults. This may be partially due to a relative lack of physical activity. We examined whether physical activity mediates the relationship between different chronic conditions and several health outcomes that are important to the quality of life of older adults. Methods The data were taken from the Canadian Community Health Survey (cycle 1.1, a cross-section survey completed in 2001. Only respondents who were 65 years or older were included in our study (N = 22,432. The Health Utilities Index Mark 3 (HUI3 was used to measure overall quality of life, and to measure selected health outcomes (dexterity, mobility, pain, cognition, and emotional wellbeing that are considered to be of importance to the quality of life of older adults. Leisure-time physical activity was assessed by determining weekly energy expenditure (Kcal per week based on the metabolic equivalents of self-reported leisure activities. Linear and logistic regression models were used to determine the mediating effect of leisure-time physical activity while controlling for demographic variables (age and sex, substance use (tobacco use and alcohol consumption, and obesity. Results Having a chronic condition was associated with a relative decrease in health utility scores and a relative increase in mobility limitations, dexterity problems, pain, emotional problems (i.e., decreased happiness, and cognitive limitations. These negative consequences could be partially attributed to a relative lack of physical activity in older adults with a chronic condition (14% mediation for the HUI3 score. The corresponding degree of mediation was 18% for mobility limitations, 5% for pain, and 13% for emotional wellbeing (statistically significant mediation was not observed for the other health attributes. These values varied with respect to the different chronic conditions examined in our study. Conclusion Older

  10. ROS-mediated upregulation of Noxa overcomes chemoresistance in chronic lymphocytic leukemia.

    Science.gov (United States)

    Tonino, S H; van Laar, J; van Oers, M H; Wang, J Y; Eldering, E; Kater, A P

    2011-02-10

    In recent years considerable progress has been made in treatment strategies for chronic lymphocytic leukemia (CLL). However, the disease remains incurable because of the development of chemoresistance. Strategies to overcome resistance mechanisms are therefore highly needed. At least two mechanisms contribute to the development of resistance to drugs; acquired mutations resulting in a dysfunctional p53 response and shifts in the balance between apoptosis-regulating proteins. Platinum-based compounds have been successfully applied in relapsed lymphoma and recently also in high-risk CLL. In this study we investigated the efficacy and mechanism of action of cisplatinum (CDDP) in chemorefractory CLL. Independent of p53-functional status, CDDP acted synergistically with fludarabine (F-ara-A). The response involved generation of reactive oxygen species (ROS), which led to specific upregulation of the proapoptotic BH3-only protein Noxa. Induction of Noxa resulted in cell death by apoptosis as inhibition of caspase activation completely abrogated cell death. Furthermore, drug-resistance upon CD40-ligand stimulation, a model for the protective stimuli provided in lymph nodes, could also be overcome by CDDP/F-ara-A. ROS accumulation resulted in Noxa upregulation mainly at the transcriptional level and this was, at least in part, mediated by the mitogen-activated protein kinase p38. Finally, Noxa RNA-interference markedly decreased sensitivity to CDDP/F-ara-A, supporting a key role for Noxa as mediator between ROS signaling and apoptosis induction. Our data indicate that interference in the cellular redox balance can be exploited to overcome chemoresistance in CLL.

  11. Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

    Science.gov (United States)

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Haskó, György; Čiháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-08

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors. Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T cell-infiltration, profound inflammatory response, fibrosis (measured by qRT-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.

  12. Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity.

    Science.gov (United States)

    Reich, C G; Mihalik, G R; Iskander, A N; Seckler, J C; Weiss, M S

    2013-12-03

    Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity.

  13. Bruton's tyrosine kinase mediated signaling enhances leukemogenesis in a mouse model for chronic lymphocytic leukemia.

    Science.gov (United States)

    Kil, Laurens P; de Bruijn, Marjolein Jw; van Hulst, Jennifer Ac; Langerak, Anton W; Yuvaraj, Saravanan; Hendriks, Rudi W

    2013-01-01

    In chronic lymphocytic leukemia (CLL) signals from the B cell receptor (BCR) play a major role in disease development and progression. In this light, new therapies that specifically target signaling molecules downstream of the BCR continue to be developed. While first studies on the selective small molecule inhibitor of Bruton's tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis. To investigate the requirement of Btk signaling for CLL development, we modulated Btk expression in the IgH.ETμ CLL mouse model, which is based on sporadic expression of the simian oncovirus SV40 T-antigen in mature B cells. To this end, we crossed IgH.ETμ mice on a Btk-deficient background or introduced a human Btk transgene (CD19-hBtk). Here we show that Btk deficiency fully abrogates CLL formation in IgH.ETμ mice, and that leukemias formed in Btk haplo-insufficient mice selectively expressed the wild-type Btk allele on their active X chromosome. Conversely, Btk overexpression accelerated CLL onset, increased mortality, and was associated with selection of non-stereotypical BCRs into CLL clones. Taken together, these data show that Btk expression represents an absolute prerequisite for CLL development and that Btk mediated signaling enhances leukemogenesis in mice. We therefore conclude that in CLL Btk expression levels set the threshold for malignant transformation.

  14. Network excitability in a model of chronic temporal lobe epilepsy critically depends on SK channel-mediated AHP currents.

    Science.gov (United States)

    Schulz, Robert; Kirschstein, Timo; Brehme, Hannes; Porath, Katrin; Mikkat, Ulrike; Köhling, Rüdiger

    2012-01-01

    Hippocampal CA1 pyramidal neurons generate an after-hyperpolarization (AHP) whose medium component is thought to be generated by small-conductance Ca(2+)-activated K(+) channels (SK channels). Neuronal excitability is increased in epilepsy, and the AHP in turn is fundamentally involved in regulation of cellular excitability. We therefore investigated the involvement of the SK channel-mediated AHP in controlling cell and network excitability in the pilocarpine model epilepsy. Both acutely isolated CA1 pyramidal cells and isolated hippocampal slices were investigated in terms of the impact of SK channel-mediated AHP on hyperexcitability. Our findings show that pilocarpine-treated chronically epileptic rats exhibit significantly reduced SK channel-mediated hyperpolarizing outward current which was accompanied by a significant decrease in the somatic AHP. Paradoxically, inhibiting SK channels strongly exacerbated 0-Mg(2+)-induced epileptiform activity in slices from pilocarpine-treated animals, while having a significantly smaller effect in control tissue. This suggests that in chronically epileptic tissue, network excitability very critically depends on the remaining SK-channel mediated AHP. Additional real-time RT-PCR and semiquantitative Western blot experiments revealed that both the SK2 channel transcript and protein were significantly downregulated in the epileptic CA1 region. We conclude that SK2 channels are down-regulated in chronic epilepsy underlying the impaired SK channel function in CA1 pyramidal cells, and a further reduction of the remaining critical mass of SK channels results in an acute network decompensation.

  15. The Skull Vibration-Induced Nystagmus Test of Vestibular Function—A Review

    Science.gov (United States)

    Dumas, Georges; Curthoys, Ian S.; Lion, Alexis; Perrin, Philippe; Schmerber, Sébastien

    2017-01-01

    A 100-Hz bone-conducted vibration applied to either mastoid induces instantaneously a predominantly horizontal nystagmus, with quick phases beating away from the affected side in patients with a unilateral vestibular loss (UVL). The same stimulus in healthy asymptomatic subjects has little or no effect. This is skull vibration-induced nystagmus (SVIN), and it is a useful, simple, non-invasive, robust indicator of asymmetry of vestibular function and the side of the vestibular loss. The nystagmus is precisely stimulus-locked: it starts with stimulation onset and stops at stimulation offset, with no post-stimulation reversal. It is sustained during long stimulus durations; it is reproducible; it beats in the same direction irrespective of which mastoid is stimulated; it shows little or no habituation; and it is permanent—even well-compensated UVL patients show SVIN. A SVIN is observed under Frenzel goggles or videonystagmoscopy and recorded under videonystagmography in absence of visual-fixation and strong sedative drugs. Stimulus frequency, location, and intensity modify the results, and a large variability in skull morphology between people can modify the stimulus. SVIN to 100 Hz mastoid stimulation is a robust response. We describe the optimum method of stimulation on the basis of the literature data and testing more than 18,500 patients. Recent neural evidence clarifies which vestibular receptors are stimulated, how they cause the nystagmus, and why the same vibration in patients with semicircular canal dehiscence (SCD) causes a nystagmus beating toward the affected ear. This review focuses not only on the optimal parameters of the stimulus and response of UVL and SCD patients but also shows how other vestibular dysfunctions affect SVIN. We conclude that the presence of SVIN is a useful indicator of the asymmetry of vestibular function between the two ears, but in order to identify which is the affected ear, other information and careful clinical judgment are

  16. Field measurements and analyses of environmental vibrations induced by high-speed Maglev.

    Science.gov (United States)

    Li, Guo-Qiang; Wang, Zhi-Lu; Chen, Suwen; Xu, You-Lin

    2016-10-15

    Maglev, offers competitive journey-times compared to the railway and subway systems in markets for which distance between the stations is 100-1600km owing to its high acceleration and speed; however, such systems may have excessive vibration. Field measurements of Maglev train-induced vibrations were therefore performed on the world's first commercial Maglev line in Shanghai, China. Seven test sections along the line were selected according to the operating conditions, covering speeds from 150 to 430km/h. Acceleration responses of bridge pier and nearby ground were measured in three directions and analyzed in both the time and frequency domain. The effects of Maglev train speed on vibrations of the bridge pier and ground were studied in terms of their peak accelerations. Attenuation of ground vibration was investigated up to 30m from the track centerline. Effects of guideway configuration were also analyzed based on the measurements through two different test sections with same train speed of 300km/h. The results showed that peak accelerations exhibited a strong correlation with both train speed and distance off the track. Guideway configuration had a significant effect on transverse vibration, but a weak impact on vertical and longitudinal vibrations of both bridge pier and ground. Statistics indicated that, contrary to the commonly accepted theory and experience, vertical vibration is not always dominant: transverse and longitudinal vibrations should also be considered, particularly near turns in the track. Moreover, measurements of ground vibration induced by traditional high-speed railway train were carried out with the same testing devices in Bengbu in the Anhui Province. Results showed that the Maglev train generates significantly different vibration signatures as compared to the traditional high-speed train. The results obtained from this paper can provide good insights on the impact of Maglev system on the urban environment and the quality of human life

  17. The Skull Vibration-Induced Nystagmus Test of Vestibular Function-A Review.

    Science.gov (United States)

    Dumas, Georges; Curthoys, Ian S; Lion, Alexis; Perrin, Philippe; Schmerber, Sébastien

    2017-01-01

    A 100-Hz bone-conducted vibration applied to either mastoid induces instantaneously a predominantly horizontal nystagmus, with quick phases beating away from the affected side in patients with a unilateral vestibular loss (UVL). The same stimulus in healthy asymptomatic subjects has little or no effect. This is skull vibration-induced nystagmus (SVIN), and it is a useful, simple, non-invasive, robust indicator of asymmetry of vestibular function and the side of the vestibular loss. The nystagmus is precisely stimulus-locked: it starts with stimulation onset and stops at stimulation offset, with no post-stimulation reversal. It is sustained during long stimulus durations; it is reproducible; it beats in the same direction irrespective of which mastoid is stimulated; it shows little or no habituation; and it is permanent-even well-compensated UVL patients show SVIN. A SVIN is observed under Frenzel goggles or videonystagmoscopy and recorded under videonystagmography in absence of visual-fixation and strong sedative drugs. Stimulus frequency, location, and intensity modify the results, and a large variability in skull morphology between people can modify the stimulus. SVIN to 100 Hz mastoid stimulation is a robust response. We describe the optimum method of stimulation on the basis of the literature data and testing more than 18,500 patients. Recent neural evidence clarifies which vestibular receptors are stimulated, how they cause the nystagmus, and why the same vibration in patients with semicircular canal dehiscence (SCD) causes a nystagmus beating toward the affected ear. This review focuses not only on the optimal parameters of the stimulus and response of UVL and SCD patients but also shows how other vestibular dysfunctions affect SVIN. We conclude that the presence of SVIN is a useful indicator of the asymmetry of vestibular function between the two ears, but in order to identify which is the affected ear, other information and careful clinical judgment are

  18. High-frequency skull vibration-induced nystagmus test in partial vestibular lesions.

    Science.gov (United States)

    Dumas, Georges; Karkas, Alexandre; Perrin, Philippe; Chahine, Karim; Schmerber, Sébastien

    2011-10-01

    To establish the effectiveness of the skull vibration-induced nystagmus test (SVINT) as a rapid high-frequency stimulation test, in the evaluation of partial unilateral vestibular lesions (pUVL). SVINT (30, 60, and 100 Hz), caloric, and head-shaking tests were performed in 99 patients with pUVL. These results were compared with those in 9 patients with symmetrical partial bilateral labyrinthine malformations, 131 patients with total unilateral vestibular lesions (tUVL), and 95 control subjects. A skull vibratory nystagmus (SVN) was found in 75% of patients with pUVL and 98% with tUVL. In pUVL: SVINT revealed asymmetric responses in 20% of patients where other tests were normal; SVN direction at 100 Hz was opposite to the head-shaking nystagmus direction in 30% and opposite to SVN at 30 Hz in 10% of cases. At 100 Hz, SVN beat toward the safe side in 91% of cases; SVN values at 60 and 100 Hz were higher than those at 30 Hz (p < 0.005). SVN was found in unilateral superior canal dehiscences. Partial bilateral labyrinthine malformations revealed no nystagmus. SVINT complements head-shaking and caloric tests in multifrequency assessment of patients with pUVL, as a global vestibular test. In contrast with tUVL results, SVINT does not always indicate the side of partial lesions, neither does it locate their level on the vestibulo-ocular pathway. This test is useful to reveal a vestibular asymmetry as a bedside examination test and may be used as a "vestibular Weber."

  19. Mechanisms of free-surface breakup in vibration-induced liquid atomization

    Science.gov (United States)

    Vukasinovic, Bojan; Smith, Marc K.; Glezer, Ari

    2007-01-01

    The mechanisms of droplet formation that take place during vibration-induced drop atomization are investigated experimentally. Droplet ejection results from the breakup of transient liquid spikes that form following the localized collapse of free-surface waves. Breakup typically begins with capillary pinch-off of a droplet from the tip of the spike and can be followed by additional pinch-offs of satellite droplets if the corresponding capillary number is sufficiently small (e.g., in low-viscosity liquids). If the capillary number is increased (e.g., in viscous liquids), breakup first occurs near the base of the spike, with or without subsequent breakup of the detached, thread-like spike. The formation of these detached threads is governed by a breakup mechanism that is separated from the tip-dominated capillary pinch-off mechanism by an order of magnitude in terms of dimensionless driving frequency f*. The dependence of breakup time and unbroken spike length on fluid and driving parameters is established over a broad range of dimensionless driving frequencies (10-3

  20. Active Control of Panel Vibrations Induced by a Boundary Layer Flow

    Science.gov (United States)

    Chow, Pao-Liu

    1998-01-01

    In recent years, active and passive control of sound and vibration in aeroelastic structures have received a great deal of attention due to many potential applications to aerospace and other industries. There exists a great deal of research work done in this area. Recent advances in the control of sound and vibration can be found in the several conference proceedings. In this report we will summarize our research findings supported by the NASA grant NAG-1-1175. The problems of active and passive control of sound and vibration has been investigated by many researchers for a number of years. However, few of the articles are concerned with the sound and vibration with flow-structure interaction. Experimental and numerical studies on the coupling between panel vibration and acoustic radiation due to flow excitation have been done by Maestrello and his associates at NASA/Langley Research Center. Since the coupled system of nonlinear partial differential equations is formidable, an analytical solution to the full problem seems impossible. For this reason, we have to simplify the problem to that of the nonlinear panel vibration induced by a uniform flow or a boundary-layer flow with a given wall pressure distribution. Based on this simplified model, we have been able to study the control and stabilization of the nonlinear panel vibration, which have not been treated satisfactorily by other authors. The vibration suppression will clearly reduce the sound radiation power from the panel. The major research findings will be presented in the next three sections. In Section II we shall describe our results on the boundary control of nonlinear panel vibration, with or without flow excitation. Section III is concerned with active control of the vibration and sound radiation from a nonlinear elastic panel. A detailed description of our work on the parametric vibrational control of nonlinear elastic panel will be presented in Section IV. This paper will be submitted to the Journal

  1. Three-dimensional vibration-induced vestibulo-ocular reflex identifies vertical semicircular canal dehiscence.

    Science.gov (United States)

    Aw, Swee Tin; Aw, Grace Elizabeth; Todd, Michael John; Bradshaw, Andrew Philip; Halmagyi, Gabor Michael

    2011-10-01

    Vertical semicircular canal dehiscence (VSCD) due to superior canal dehiscence (SCD) or posterior canal dehiscence (PCD) of the temporal bone causes vestibular and cochlear hypersensitivity to sound. This study aimed to characterize the vibration-induced vestibulo-ocular reflex (ViVOR) in VSCD. ViVORs in one PCD and 17 SCD patients, confirmed by CT imaging reformatted in semicircular canal planes, were measured with dual-search coils as binocular three-dimensional eye rotations induced by skull vibrations from a bone oscillator (B71-10 ohms) at 7 ms, 500 Hz, 135-dB peak-force level (re: 1 μN). The ViVOR eye rotation axes were computed by vector analysis and referenced to known semicircular canal planes. Onset latency of the ViVOR was 11 ms. ViVOR from VSCD was up to nine times greater than normal. The ViVOR's torsional rotation was always contraversive-torsional (the eye's upper pole rotated away from the stimulated ear), i.e. its direction was clockwise from a left and counterclockwise from a right VSCD, thereby lateralizing the side of the VSCD. The ViVORs vertical component distinguishes PCD from SCD, being downwards in PCD and upwards in SCD. In unilateral VSCD, the ViVOR eye rotation axis aligned closest to the dehiscent vertical semicircular canal axis from either ipsilateral or contralateral mastoid vibrations. However, in bilateral VSCDs, the ViVOR eye rotation axis lateralized to the ipsilateral dehiscent vertical semicircular canal axis. ViVOR was evoked in ossicular chain dysfunction, even when air-conducted click vestibulo-ocular reflex (VOR) was absent or markedly reduced. Hence, ViVOR could be a useful measurement to identify unilateral or bilateral VSCD even in the presence of ossicular chain dysfunction.

  2. Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

    Science.gov (United States)

    Slocum, C; Kramer, C; Genco, C A

    2016-07-01

    Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease.

  3. Histamine suppresses regulatory T cells mediated by TGF-β in murine chronic allergic contact dermatitis.

    Science.gov (United States)

    Tamaka, Kyoko; Seike, Masahiro; Hagiwara, Tamio; Sato, Atsushi; Ohtsu, Hiroshi

    2015-04-01

    Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (-/-) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6-trinitro-1-chlorobenzene (TNCB) on HDC (+/+) and HDC (-/-) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF-β1 in this model. Recombinant TGF-β1 or anti-TGF-β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine-regulated TGF-β on the Treg population in CACD. Recombinant TGF-β1 injection promoted the infiltration of Tregs in the skin and the production of IL-10; however, anti-TGF-β1 antibody injection suppressed the number of Tregs in the skin and the production of IL-10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF-β.

  4. Angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium

    Institute of Scientific and Technical Information of China (English)

    DONG Shu-qiang; ZHANG Bao-ren; MEI Ju; XU Zhi-yun; ZOU Liang-jian; HUANG Sheng-dong

    2002-01-01

    Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: Echocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vesseldevelopment assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad.VEGF-B group versus 19±4 and 17±6 in Ad.LacZ and PBS group. Conclusion:Direct intramyocardial administration of Ad.VEGF-B can induce focal angiogenesis and result in improvement in regional myocardial function, which may be useful in patients with ischemic heart disease who are not eligible for conventional therapies.

  5. Hypothalamus as a mediator of chronic migraine: Evidence from high-resolution fMRI.

    Science.gov (United States)

    Schulte, Laura H; Allers, Angie; May, Arne

    2017-05-23

    To identify pathophysiologic mechanisms of migraine chronification using a recently standardized protocol for high-resolution brainstem imaging of trigeminal nociceptive stimulation. Eighteen episodic migraineurs (EMs), 17 chronic migraineurs (CMs), and 19 healthy controls (HCs) underwent painful ammonia stimulation of the left nostril in a 3T MRI scanner. Functional images were acquired with a brainstem-optimized protocol for high-resolution echo-planar imaging. We detected a significantly stronger activation of the anterior right hypothalamus in CMs compared to HCs. To exclude the headache as a prime mediator of the hypothalamic activations, we compared all migraineurs with headaches (EMs and CMs) with all migraineurs without headaches (EMs and CMs) and HCs in a second analysis and found a more posterior region of the hypothalamus to be more activated bilaterally during headaches. Our data corroborate the fact that the hypothalamus plays a crucial role in the pathophysiology of migraine chronification and acute pain stage of migraineurs. While the more posterior part of the hypothalamus seems to be important for the acute pain stage, the more anterior part seems to play an important role in attack generation and migraine chronification. © 2017 American Academy of Neurology.

  6. Differentiation of chronical rhinosinusitis with and without nasal polyposis on basis of symptomatology, course of disease, inflammatory mediators and comorbidity

    OpenAIRE

    Traser, Louisa

    2012-01-01

    Recent cytokine and chemokine research has rapidly expanded our understanding of chronic rhinosinusitis (CRS) and underlined that it is necessary to divide this disease into subgroups. The objective of the present study was to investigate the differentiation of CRS patients with (CRSwNP) and without (CRSsNP) nasal polyposis on basis of symptomatology, course of disease, inflammatory mediators and comorbidity. Nasal Polyps (n=16), tissue samples taken from the paranasal sinuses (n=32) and ...

  7. Health Behaviors and Chronic Conditions Mediate the Protective Effects of Masculinity for Physical Performance in Older Adults.

    Science.gov (United States)

    Ahmed, Tamer; Vafaei, Afshin; Auais, Mohammad; Phillips, Susan P; Guralnik, Jack; Zunzunegui, M V

    2017-04-01

    We estimated the 2-year incidence of poor physical performance according to gender roles and examined mediating pathways related to health behaviors and chronic conditions. Data are from the International Mobility in Aging Study ( n = 1,676). The Bem Sex Role Inventory was used to classify participants into four gender roles as "masculine," "feminine," "androgynous," and "undifferentiated." We found a higher incidence of poor physical performance among participants endorsing the feminine (adjusted incidence rate ratio [IRR] = 2.36, 95% confidence interval (CI) = [1.55, 3.60]) or the undifferentiated role (adjusted IRR = 2.19, 95% CI = [1.45, 3.30]) compared with the androgynous role. Smoking, physical activity, the number of chronic conditions, high body mass index, and depression were mediators of this association but not alcohol consumption. This study provides evidence that gender roles are independently associated with physical performance. Health behaviors and chronic conditions are mediators of the relationship between gender roles and lower extremity physical function.

  8. Numerical investigation of piled raft foundation in mitigating embankment vibrations induced by high-speed trains

    Institute of Scientific and Technical Information of China (English)

    付强; 刘汉龙; 丁选明; 郑长杰

    2015-01-01

    A three-dimensional dynamic finite element model of track-ballast-embankment and piled raft foundation system is established. Dynamic response of a railway embankment to a high-speed train is simulated for two cases: soft ground improved by piled raft foundation, and untreated soft ground. The obtained results are compared both in time domain and frequency domain to evaluate the effectiveness of the ground improvement in mitigating the embankment vibrations induced by high-speed trains. The results show that ground improving methods can significantly reduce the embankment vibrations at all considered train speeds(36-432 km/h). The ground response to a moving load is dictated largely by the relationship between load speed and characteristic value of wave velocities of the ground medium. At low speeds, the ground response from a moving load is essentially quasi-static. That is, the displacements fields are essential the static fields under the load simply moving with it. For the soft ground, the displacement on the ballast surface is large at all observed train speeds. For the model case where the ground is improved by piled raft foundation, the peak displacement is reduced at all considered train speeds compared with the case without ground improvement. Based on the effect of energy-dissipating of ballast-embankment-ground system with damping, the train-induced vibration waves moving in ballast and embankment are trapped and dissipated, and thus the vibration amplitudes of dynamic displacement outside the embankment are significantly reduced. But for the vibration amplitude of dynamic velocity, the vibration waves in embankment are absorbed or reflected back, and the velocity amplitudes at the ballast and embankment surface are enhanced. For the change of the vibration character of embankment and ballast, the bearing capacity and dynamic character are improved. Therefore, both of the static and dynamic displacements are reduced by ground improvement; the dynamic

  9. Numerical investigation of piled raft foundation in mitigating embankment vibrations induced by high-speed trains

    Institute of Scientific and Technical Information of China (English)

    付强; 刘汉龙; 丁选明; 郑长杰

    2015-01-01

    A three-dimensional dynamic finite element model of track-ballast-embankment and piled raft foundation system is established. Dynamic response of a railway embankment to a high-speed train is simulated for two cases: soft ground improved by piled raft foundation, and untreated soft ground. The obtained results are compared both in time domain and frequency domain to evaluate the effectiveness of the ground improvement in mitigating the embankment vibrations induced by high-speed trains. The results show that ground improving methods can significantly reduce the embankment vibrations at all considered train speeds (36− 432 km/h). The ground response to a moving load is dictated largely by the relationship between load speed and characteristic value of wave velocities of the ground medium. At low speeds, the ground response from a moving load is essentially quasi-static. That is, the displacements fields are essential the static fields under the load simply moving with it. For the soft ground, the displacement on the ballast surface is large at all observed train speeds. For the model case where the ground is improved by piled raft foundation, the peak displacement is reduced at all considered train speeds compared with the case without ground improvement. Based on the effect of energy-dissipating of ballast-embankment-ground system with damping, the train-induced vibration waves moving in ballast and embankment are trapped and dissipated, and thus the vibration amplitudes of dynamic displacement outside the embankment are significantly reduced. But for the vibration amplitude of dynamic velocity, the vibration waves in embankment are absorbed or reflected back, and the velocity amplitudes at the ballast and embankment surface are enhanced. For the change of the vibration character of embankment and ballast, the bearing capacity and dynamic character are improved. Therefore, both of the static and dynamic displacements are reduced by ground improvement; the dynamic

  10. Vibration-induced extra torque during electrically-evoked contractions of the human calf muscles

    Directory of Open Access Journals (Sweden)

    Kohn André F

    2010-06-01

    stimulation could be beneficial for many therapeutic interventions and vibration-based exercise programs. The command for the vibration-induced extra torques presumably activates spinal motoneurons following the size principle, which is a desirable feature for stimulation paradigms.

  11. STAT1 mediates differentiation of chronic lymphocytic leukemia cells in response to Bryostatin 1.

    Science.gov (United States)

    Battle, Traci E; Frank, David A

    2003-10-15

    Bryostatin 1 is known to exhibit in vitro and in vivo activity against chronic lymphocytic leukemia (CLL) cells by inducing their further maturation into plasma-like cells. Signal transducer and activator of transcription (STAT) proteins play a central role in B-lymphocyte growth and function and are aberrantly phosphorylated on serine residues in CLL cells. To determine whether STAT transcription factors are important in Bryostatin 1-induced differentiation of CLL cells, primary CLL cells were examined for signaling events following exposure to Bryostatin 1 in vitro. Western analysis and electrophoretic mobility shift assays revealed that Bryostatin 1 induced tyrosine phosphorylation and DNA binding of STAT1, yet there was no effect on constitutive serine phosphorylation of STAT1. Bryostatin 1-induced STAT1 activation occurred in a manner that was dependent on protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Janus tyrosine kinase (JAK) activation. Evidence indicates that Bryostatin 1 induces STAT1 activation through an interferon gamma (IFN gamma) autocrine loop. However, STAT1 activation by IFN gamma stimulation alone was not sufficient to induce differentiation. This insufficiency is due to the broader effect on gene expression caused by Bryostatin 1 compared with IFN gamma, as demonstrated by microarray analysis. Both up-regulation of CD22 expression and immunoglobulin M (IgM) production, markers of CLL differentiation, were inhibited by a decoy oligonucleotide for STAT1, indicating that STAT1 is necessary for Bryostatin 1-induced differentiation of CLL cells. This study implicates STAT transcription factors as important mediators of Bryostatin 1-induced differentiation of CLL cells and could possibly lead to improved therapeutic approaches for the treatment of CLL.

  12. A type I interferon signature characterizes chronic antibody-mediated rejection in kidney transplantation.

    Science.gov (United States)

    Rascio, Federica; Pontrelli, Paola; Accetturo, Matteo; Oranger, Annarita; Gigante, Margherita; Castellano, Giuseppe; Gigante, Maddalena; Zito, Anna; Zaza, Gianluigi; Lupo, Antonio; Ranieri, Elena; Stallone, Giovanni; Gesualdo, Loreto; Grandaliano, Giuseppe

    2015-09-01

    Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss. To uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of peripheral blood mononuclear cells (PBMCs) and, separately, of CD4(+) T lymphocytes isolated from CAMR patients, compared to kidney transplant recipients with normal graft function and histology. We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls), and 8 transplant recipients with clinical and histological evidence of interstitial fibrosis/tubular atrophy. Messenger RNA and microRNA profiling of PBMCs and CD4(+) T lymphocytes was performed using Agilent microarrays in eight randomly selected patients per group from CAMR and control subjects. Results were evaluated statistically and by functional pathway analysis (Ingenuity Pathway Analysis) and validated in the remaining subjects. In PBMCs, 45 genes were differentially expressed between the two groups, most of which were up-regulated in CAMR and were involved in type I interferon signalling. In the same patients, 16 microRNAs were down-regulated in CAMR subjects compared to controls: four were predicted modulators of six mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signalling. To further confirm this result, we investigated the transcriptomic profiles of CD4(+) T lymphocytes in an independent group of patients, observing that the activation of type I interferon signalling was a specific hallmark of CAMR. In addition, in CAMR patients, we detected a reduction of circulating BDCA2(+) dendritic cells, the natural type I interferon-producing cells, and their recruitment into the graft along with increased expression of MXA, a type I interferon-induced protein, at the tubulointerstitial and vascular level. Finally, interferon alpha mRNA expression was significantly increased in CAMR compared to control

  13. Chronic Illnesses and Depressive Symptoms Among Older People: Functional Limitations as a Mediator and Self-Perceptions of Aging as a Moderator.

    Science.gov (United States)

    Han, Jina

    2017-05-01

    This research examined the mediation of functional limitations in the relationship between chronic illnesses and depressive symptoms among older Americans along with tests for the moderation of self-perceptions of aging. Data from the Health and Retirement Study (2008, 2010, and 2012) were used. Longitudinal mediation models were tested using a sample of 3,382 Americans who responded to psychosocial questions and were over 65 years old in 2008. Functional limitations mediated the linkage between chronic illnesses and depressive symptoms. Negative self-perceptions of aging exacerbated the effects of chronic illnesses on depressive symptoms. Health care professionals should be aware of depressive symptoms in older adults reporting chronic illnesses and particularly in those reporting functional limitations. To decrease the risk of depressive symptoms caused by chronic illnesses, negative self-perceptions of aging may need to be challenged.

  14. Skull vibration-induced nystagmus test in unilateral superior canal dehiscence and otosclerosis: a vestibular Weber test.

    Science.gov (United States)

    Dumas, Georges; Lion, Alexis; Karkas, Alexandre; Perrin, Philippe; Perottino, Flavio; Schmerber, Sébastien

    2014-06-01

    The skull vibration-induced nystagmus test (SVINT) acts as a vestibular Weber test and reveals a vibration-induced nystagmus (VIN), elicited mainly on the vertex location, with a horizontal or torsional component beating more often toward the side of the lesion in superior canal dehiscence (SCD) than in otosclerosis (OS). In SCD, the VIN vertical component is most often up-beating. These results suggest more a global vestibular contribution than the sole stimulation of the superior semicircular canal. This study aimed to evaluate the possible occurrence of nystagmus during SVINT in unilateral conductive hearing loss related to SCD or OS. The slow-phase velocities (SPVs) of the VIN horizontal, torsional, and vertical components were recorded in patients with a unilateral otologic lesion (17 SCD, 38 OS) and 12 control subjects. Vibratory stimulations (60 Hz, 100 Hz) were applied on the vertex and on each mastoid. In SCD, VIN was observed in 82% of patients with a primarily torsional, horizontal, and vertical (up-beating) component in 40%, 30%, and 30%, respectively. Horizontal and torsional components beat toward the side of the lesion more often than in OS. Higher SPVs were observed after vertex stimulation. In OS, VIN was sparse with low amplitude and was not systematically lateralized to a specific side.

  15. The Longitudinal Effects of Chronic Mediated Exposure to Political Violence on Ideological Beliefs About Political Conflicts Among Youths.

    Science.gov (United States)

    Gvirsman, Shira Dvir; Huesmann, L Rowell; Dubow, Eric F; Landau, Simha F; Boxer, Paul; Shikaki, Khalil

    This study examines the effects of chronic (i.e., repeated and cumulative) mediated exposure to political violence on ideological beliefs regarding political conflict. It centers on these effects on young viewers, from preadolescents to adolescents. Ideological beliefs refers here to support of war, perception of threat to one's nation, and normative beliefs concerning aggression toward the out-group. A longitudinal study was conducted on a sample of Israeli and Palestinian youths who experience the Israeli-Palestinian conflict firsthand (N = 1,207). Two alternative hypotheses were tested: that chronic exposure via the media increases support for war and aggression and elevates feeling of threat, or that chronic exposure via the media strengthens preexisting beliefs. Results demonstrated that higher levels of exposure were longitudinally related to stronger support for war. Regarding normative beliefs about aggression and threat to one's nation, mediated exposure reinforced initial beliefs, rendering the youths more extreme in their attitudes. These results mostly support the conceptualization of the relation between media violence and behaviors as "reciprocally determined" or "reinforcing spirals." The results are also discussed in light of the differences found between the effect of exposure to political violence firsthand and exposure via the media.

  16. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement

    Directory of Open Access Journals (Sweden)

    Toussirot E

    2013-04-01

    Full Text Available Éric Toussirot,1–4 Fabrice Michel,5 Matthieu Béreau,6 Delphine Binda1,7 1Clinical Investigation Center – Biotherapy CBT-506, University Hospital of Besançon, Besançon, France; 2Department of Rheumatology, University Hospital of Besançon, Besançon, France; 3Department of Therapeutics, University of Franche-Comté, Besançon, France; 4Equipe d'Acceuil 4266 Pathogens and Inflammation, Structure Fédérative de Recherche–Fédération de Recherche 4234, University of Franche-Comté, Besançon, France; 5Department of Physical Medicine and Rehabilitation, University Hospital of Besançon, Besançon, France; 6Department of Neurology, University Hospital of Besançon, Besançon, France; 7Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1098, Blood Transfusion Center, Besançon, France Abstract: Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit shared by interleukin (IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 with their cell surface receptors, and thus blocks T helper (Th-1 IL-12 and Th-17 IL-23 inflammatory pathways. Ustekinumab has been evaluated in the treatment of various chronic immune-mediated diseases including, psoriasis, psoriatic arthritis, Crohn's disease, and multiple sclerosis. It led to a rapid and durable improvement in psoriasis area and severity index in patients with moderate to severe psoriasis. Ustekinumab also improved joint symptoms of psoriatic arthritis. Results in Crohn's disease were more mitigated, albeit with a symptomatic improvement in patients refractory to tumor necrosis factor-α inhibitors. Ustekinumab did not reduce the number of magnetic resonance imaging brain lesions in multiple sclerosis. The most common adverse events to have been observed during clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headaches, and injection site reactions. A pooled analysis of

  17. SIRT1 is a Highly Networked Protein That Mediates the Adaptation to Chronic Physiological Stress

    Science.gov (United States)

    Clark-Knowles, Katherine V.; Caron, Annabelle Z.; Gray, Douglas A.

    2013-01-01

    SIRT1 is a NAD+-dependent protein deacetylase that has a very large number of established protein substrates and an equally impressive list of biological functions thought to be regulated by its activity. Perhaps as notable is the remarkable number of points of conflict concerning the role of SIRT1 in biological processes. For example, evidence exists suggesting that SIRT1 is a tumor suppressor, is an oncogene, or has no effect on oncogenesis. Similarly, SIRT1 is variably reported to induce, inhibit, or have no effect on autophagy. We believe that the resolution of many conflicting results is possible by considering recent reports indicating that SIRT1 is an important hub interacting with a complex network of proteins that collectively regulate a wide variety of biological processes including cancer and autophagy. A number of the interacting proteins are themselves hubs that, like SIRT1, utilize intrinsically disordered regions for their promiscuous interactions. Many studies investigating SIRT1 function have been carried out on cell lines carrying undetermined numbers of alterations to the proteins comprising the SIRT1 network or on inbred mouse strains carrying fixed mutations affecting some of these proteins. Thus, the effects of modulating SIRT1 amount and/or activity are importantly determined by the genetic background of the cell (or the inbred strain of mice), and the effects attributed to SIRT1 are synthetic with the background of mutations and epigenetic differences between cells and organisms. Work on mice carrying alterations to the Sirt1 gene suggests that the network in which SIRT1 functions plays an important role in mediating physiological adaptation to various sources of chronic stress such as calorie restriction and calorie overload. Whether the catalytic activity of SIRT1 and the nuclear concentration of the co-factor, NAD+, are responsible for modulating this activity remains to be determined. However, the effect of modulating SIRT1 activity must

  18. Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

    Science.gov (United States)

    Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

    2012-01-01

    Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.

  19. P2X7 Receptor Mediates Spinal Microglia Activation of Visceral Hyperalgesia in a Rat Model of Chronic Pancreatitis.

    Science.gov (United States)

    Liu, Pei-Yi; Lee, I-Hui; Tan, Ping-Heng; Wang, Yen-Po; Tsai, Chia-Fen; Lin, Han-Chieh; Lee, Fa-Yauh; Lu, Ching-Liang

    2015-11-01

    Molecular mechanisms underlying the activated spinal microglia in association with the pain in chronic pancreatitis (CP) remain unknown. We tested whether P2X7R on spinal microglia mediates the pathogenesis of visceral pain using a CP rat model. The CP model was induced via intraductal injection of 2% trinitrobenzene sulfonic acid into male Sprague-Dawley rats. Hyperalgesia was assessed based on the mechanical sensitivity to Von-Frey filaments (VFFs), and nocifensive behaviors were measured in response to electrical stimulation of the pancreas. Three weeks after CP induction, spinal cord samples were harvested for immunostaining, immunoblot, and real-time polymerase chain reaction analyses of the P2X7R. Changes in nocifensive behaviors and associated molecular effectors were assessed by blocking spinal cord P2X7R pharmacologically using the selective P2X7R antagonist brilliant blue G (BBG) or genetically using short interfering RNA (siRNA). CP induced a significant up-regulation of spinal P2X7R expression, which colocalized with a microglial marker (OX-42). Intrathecal administration of BBG significantly attenuated CP-related visceral hyperalgesia in response to VFF-mediated or electrical stimulation of the pancreas, which was associated with suppressed spinal expression of P2X7R and inhibited activation of spinal microglia. Intrathecal injection of siRNA to knock down P2X7R expression in the spinal cord would suppress the nociceptive behaviors in CP rats. Spinal microglia P2X7R mediates central sensitization of chronic visceral pain in CP. BBG may represent an effective drug for the treatment of chronic pain in CP patients.

  20. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  1. The mediating effect of chronic pain on the relationship between obesity and physical function and disability in older adults.

    Science.gov (United States)

    Fowler-Brown, Angela; Wee, Christina C; Marcantonio, Edward; Ngo, Long; Leveille, Suzanne

    2013-12-01

    To determine the extent to which bodily pain mediates the effect of obesity on disability and physical function. Cross-sectional analysis. Population-based sample of residents in the greater Boston area. Community-dwelling adults aged 70 and older (N=736). Body mass index (BMI), obtained from measured height and weight, was categorized as normal weight (19.0-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30.0 kg/m2). Main outcome measures were the Physical Component Summary of the Medical Outcomes Study 12-item Short-Form Survey (PCS), activity of daily living (ADL) disability, and Short Physical Performance Battery (SPPB) score. Chronic pain was assessed according to the number of weight-bearing joint sites that had pain (hips, knees, feet and pain all over). Older obese adults had greater ADL disability and lower SPPB and PCS scores than their nonobese counterparts, although in sex-stratified adjusted analyses, obesity was adversely associated with outcomes only in women. Obesity was associated with greater number of pain sites; and more pain sites were associated with greater odds of disability. Mediation analysis suggests that pain is a significant mediator (22-44%) of the adverse effect of obesity on disability and physical function in women. Bodily pain may be an important treatable mediator of the adverse effect of obesity on disability and physical function in women. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

  2. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

    Science.gov (United States)

    Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

    2011-03-23

    Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

  3. Chronic baclofen desensitizes GABA(B)-mediated G-protein activation and stimulates phosphorylation of kinases in mesocorticolimbic rat brain.

    Science.gov (United States)

    Keegan, Bradley M T; Beveridge, Thomas J R; Pezor, Jeffrey J; Xiao, Ruoyu; Sexton, Tammy; Childers, Steven R; Howlett, Allyn C

    2015-08-01

    The GABAB receptor is a therapeutic target for CNS and neuropathic disorders; however, few preclinical studies have explored effects of chronic stimulation. This study evaluated acute and chronic baclofen treatments on GABAB-activated G-proteins and signaling protein phosphorylation as indicators of GABAB signaling capacity. Brain sections from rats acutely administered baclofen (5 mg/kg, i.p.) showed no significant differences from controls in GABAB-stimulated GTPγS binding in any brain region, but displayed significantly greater phosphorylation/activation of focal adhesion kinase (pFAK(Tyr397)) in mesocorticolimbic regions (caudate putamen, cortex, hippocampus, thalamus) and elevated phosphorylated/activated glycogen synthase kinase 3-β (pGSK3β(Tyr216)) in the prefrontal cortex, cerebral cortex, caudate putamen, nucleus accumbens, thalamus, septum, and globus pallidus. In rats administered chronic baclofen (5 mg/kg, t.i.d. for five days), GABAB-stimulated GTPγS binding was significantly diminished in the prefrontal cortex, septum, amygdala, and parabrachial nucleus compared to controls. This effect was specific to GABAB receptors: there was no effect of chronic baclofen treatment on adenosine A1-stimulated GTPγS binding in any region. Chronically-treated rats also exhibited increases in pFAK(Tyr397) and pGSK3β(Tyr216) compared to controls, and displayed wide-spread elevations in phosphorylated dopamine- and cAMP-regulated phosphoprotein-32 (pDARPP-32(Thr34)) compared to acutely-treated or control rats. We postulate that those neuroadaptive effects of GABAB stimulation mediated by G-proteins and their sequelae correlate with tolerance to several of baclofen's effects, whereas sustained signaling via kinase cascades points to cross-talk between GABAB receptors and alternative mechanisms that are resistant to desensitization. Both desensitized and sustained signaling pathways should be considered in the development of pharmacotherapies targeting the GABA

  4. Development of a perpendicular vibration-induced electrical discharge machining process for fabrication of partially wavy inner structures

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Chul; Park, Sang Hu; Min, June Kee; Ha, Man Yeong; Shin, Bo Sung [Pusan National University, Busan (Korea, Republic of); Cho, Jong Rae [Korea Maritime University, Busan (Korea, Republic of)

    2016-05-15

    Heat transfer enhancement is an important issue in energy systems. To improve the efficiency of a cooling channel used inside injection molds, turbine blades, and high-temperature devices, channels with various shapes, such as wavy, elliptical, and twisted, have been studied. A cooling channel with a partially wavy inner structure has shown outstanding cooling performance despite a small increase in friction factor. However, generating a partially wavy inner structure inside a channel through conventional machining processes is not easy. To address this problem, we developed a new process called Perpendicular vibration-induced electrical discharge machining (PV-EDM). A specific electrode and one- and random-directional vibrating devices controlled by a pneumatic load were designed for the PV-EDM process. Experimental results showed that local shaping on the inner wall of a channel is possible, which confirmed the possibility of application of this process to actual industrial problems.

  5. Anharmonicity of lattice vibrations induced by charged nickel additions in A sup 2 B sup 6 semiconductors

    CERN Document Server

    Sokolov, V I; Shirokov, E A; Kislov, A N

    2002-01-01

    Paper presents the results of investigations into lattice vibrations induced by nickel impurities charged negatively as to the lattice in ZnSe:Ni, ZnO:Ni, ZnS:Ni, CdS:Ni semiconductors. To investigate into vibrations one applies a sensitive technique of field exciton-oscillation spectroscopy. One observes experimentally oscillating reiterations of the impurity exciton head line including the intensive peaks of combined repetitions up to the 8-th order. The experimental results are discussed on the basis of the model estimations of oscillations of a lattice with a charged impurity centre, as well as, on the ground of calculations for oscillations of monoatomic chain with high anharmonicity. Charged impurity centres are shown to induce new oscillations of lattice - impurity anharmonic modes

  6. [Reduction of exercise-mediated endothelial dysfunction markers in sedentary adults with chronic spinal cord injury].

    Science.gov (United States)

    Rosety-Rodriguez, Manuel; Camacho-Molina, Alejandra; Rosety, Ignacio; Fornieles, Gabriel; Rosety, Miguel A; Ordoñez, Francisco Javier

    2015-01-20

    Recent studies have found increased markers of endothelial activation in men with chronic spinal cord injury. This study was conducted to determine the effects of arm-cranking exercise on endothelial dysfunction in male adults with chronic SCI. A prospective randomized study of 17 sedentary adult males with chronic SCI at or under T5 level. Nine performed a supervised exercise program at a moderate intensity (arm-cranking: 12 weeks, 3 sessions/week). Plasma levels of endothelin-1, soluble intercellular adhesion molecule type 1 (sICAM-1), and soluble vascular adhesion molecule type 1 (sVCAM-1) were assessed by ELISA. Outcome measurements also included physical fitness and total body fat mass percentage. We observed both in the randomized and in the before-after studies a significant reduction of the levels of endothelin-1 and sICAM-1. Furthermore, significant improvements of both physical fitness and body composition were also found. Arm-cranking exercise improved endothelial dysfunction in adult males with chronic SCI. Long-term studies are still required to determine whether the correction of endothelial dysfunction improves the clinical outcomes of adults with chronic SCI. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  7. Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

    Science.gov (United States)

    Baker, B S; Powles, A V; Malkani, A K; Lewis, H; Valdimarsson, H; Fry, L

    1991-07-01

    The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

  8. Cytotoxic T lymphocytes mediate chronic inflammation of the nasal mucosa of patients with atypical allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Shuqi Qiu

    2011-01-01

    Full Text Available Background : The prevalence of chronic rhinitis is increasing rapidly; its pathogenesis is to be further understood; immune inflammation is one of the possible causative factors. Antigen specific CD8+ T cells play a critical role in the induction of chronic inflammation. Aims : This study aimed to investigate the role of antigen specific CD8+ T cells in the pathogenesis of chronic atypical allergic rhinitis. Material and Methods : Nasal mucosal epithelial surface scratching samples were obtained from patients with chronic obstruction atypical allergic rhinitis. Exosomes were purified from the scratching samples and examined by immune gold electron microscopy. The effect of exosomes on modulating dendritic cell′s properties, the effect of exosome-pulsed dendritic cells on naïve T cell differentiation and the antigen specific CD8+ T cell activation were observed by cell culture models. Results : Exosomes purified from patients with chronic atypical allergic rhinitis carried microbial products, Staphylococcal enterotoxin B (SEB, and airborne antigen, Derp1. Dendritic cells pulsed by SEB/Derp1-carrying exosomes showed high levels of CD80, CD86 and the major histocompatibility class I (MHCI. Exosome-pulsed dendritic cells could induce the naïve CD3+ T cells to differentiate into CD8+ T cells. Upon the exposure to a specific antigen, the CD8+ T cells released granzyme B and perforin; more than 30% antigen specific CD8+ T cells proliferated. Conclusions : Antigen specific CD8+ T cells play an important role in the pathogenesis of chronic obstruction atypical allergic rhinitis.

  9. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Zhong, Xiao-Ming; Xian, Yan-Fang; Ip, Siu-Po

    2014-03-15

    Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine.

  10. Chronic corticosterone-mediated dysregulation of microRNA network in prefrontal cortex of rats: relevance to depression pathophysiology.

    Science.gov (United States)

    Dwivedi, Y; Roy, B; Lugli, G; Rizavi, H; Zhang, H; Smalheiser, N R

    2015-11-17

    Stress plays a major role in inducing depression, which may arise from interplay between complex cascades of molecular and cellular events that influence gene expression leading to altered connectivity and neural plasticity. In recent years, microRNAs (miRNAs) have carved their own niche owing to their innate ability to induce disease phenotype by regulating expression of a large number of genes in a cohesive and coordinated manner. In this study, we examined whether miRNAs and associated gene networks have a role in chronic corticosterone (CORT; 50 mg  kg(-1) × 21 days)-mediated depression in rats. Rats given chronic CORT showed key behavioral features that resembled depression phenotype. Expression analysis revealed differential regulation of 26 miRNAs (19 upregulated, 7 downregulated) in prefrontal cortex of CORT-treated rats. Interaction between altered miRNAs and target genes showed dense interconnected molecular network, in which multiple genes were predicated to be targeted by the same miRNA. A majority of altered miRNAs showed binding sites for glucocorticoid receptor element, suggesting that there may be a common regulatory mechanism of miRNA regulation by CORT. Functional clustering of predicated target genes yielded disorders such as developmental, inflammatory and psychological that could be relevant to depression. Prediction analysis of the two most prominently affected miRNAs miR-124 and miR-218 resulted into target genes that have been shown to be associated with depression and stress-related disorders. Altogether, our study suggests miRNA-mediated novel mechanism by which chronic CORT may be involved in depression pathophysiology.

  11. Psychological flexibility as a mediator of improvement in Acceptance and Commitment Therapy for patients with chronic pain following whiplash.

    Science.gov (United States)

    Wicksell, Rikard K; Olsson, Gunnar L; Hayes, Steven C

    2010-11-01

    Cognitive behavior therapy (CBT) has made important contributions to chronic pain management, but the process by which it is effective is not clear. Recently, strong arguments have been raised concerning the need for theory driven research to e.g. identify mechanisms of change in CBT and enhance the effectiveness of this type of treatment. However, the number of studies addressing these issues is still relatively scarce. Furthermore, the arrival of varieties of CBT with seemingly different process targets increases the need for such information. The present study explored the processes of change in a previously reported successful randomized controlled trial evaluating the effectiveness of an exposure-based form of behavioral and cognitive therapy, Acceptance and Commitment Therapy (ACT), on improvement in pain-related disability and life satisfaction for patients suffering from whiplash-associated disorder (WAD). Several process variables relevant to theories underlying traditional CBT were included: pain, distress, kinesiophobia, self-efficacy, and the process primarily targeted by ACT: psychological inflexibility. Mediation analyses were performed using a non-parametric cross-product of the coefficients approach. Results illustrated that pain intensity, anxiety, depression, kinesiophobia, and self-efficacy did not have significant mediating effects on the dependent variables. In contrast, significant indirect effects were seen for psychological inflexibility on pain-related disability (pre- to post-change scores) and life satisfaction (pre- to post; pre- to 4-month follow-up change scores). Although tentative, these results support the mediating role of psychological inflexibility in ACT-oriented interventions aimed at improving functioning and life satisfaction in people with chronic pain. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. All rights reserved.

  12. Mediators for internalizing problems in adolescents of parents with chronic medical condition

    NARCIS (Netherlands)

    Sieh, D.S.; Oort, F.J.; Visser-Meily, J.M.A.; Meijer, A.M.

    2014-01-01

    Parents’ chronic medical condition (CMC) is related to internalizing problem behavior in adolescents. Following the transactional stress and coping (TSC) model of Hocking and Lochman, our study examines whether the effect of illness and demographic parameters on the child’s internalizing problems is

  13. Mediators of the Association Between Low Socioeconomic Status and Chronic Kidney Disease in the United States

    NARCIS (Netherlands)

    Vart, Priya; Gansevoort, Ronald; Crews, Deidra C.; Reijneveld, Sijmen A.; Bultmann, Ute

    2015-01-01

    Using data collected from 9,823 participants in the 2007-2008 and 2009-2010 cycles of the National Health and Nutrition Examination Survey, we formally investigated potentially modifiable factors linking low socioeconomic status (SES) to chronic kidney disease (CKD) for their presence and magnitude

  14. Mediators for internalizing problems in adolescents of parents with chronic medical condition

    NARCIS (Netherlands)

    D.S. Sieh; F.J. Oort; J.M.A. Visser-Meily; A.M. Meijer

    2014-01-01

    Parents’ chronic medical condition (CMC) is related to internalizing problem behavior in adolescents. Following the transactional stress and coping (TSC) model of Hocking and Lochman, our study examines whether the effect of illness and demographic parameters on the child’s internalizing problems is

  15. Differential role of lipocalin-2 during immune-complex mediated acute and chronic inflammation

    Science.gov (United States)

    Shashidharamurthy, Rangaiah; Machiah, Deepa; Aitken, Jesse D; Putty, Kalyani; Srinivasan, Gayathri; Chassaing, Benoit; Parkos, Charles A; Selvaraj, Periasamy; Vijay-Kumar, Matam

    2013-01-01

    Objectives Lipocalin-2 (Lcn2) is an innate immune protein expressed by a variety of cells and is highly upregulated during several pathological conditions including immune-complex (IC) mediated inflammatory/autoimmune disorders. However, the function of Lcn2 during IC-mediated inflammation is largely unknown. Therefore our objective was to investigate the role of Lcn2 in IC-mediated diseases. Methods The upregulation of Lcn2 was determined by ELISA in three different mouse models of IC-mediated autoimmune disease: systemic lupus erythematosus, collagen-induced arthritis and serum-induced arthritis. The in vivo role of Lcn2 during IC-mediated inflammation was investigated using Lcn2 knockout (Lcn2KO) mice and their wild type (WT) littermates. Results Lcn2 levels were significantly elevated in all the three autoimmune disease models. Further, in an acute skin inflammation model, Lcn2KO mice demonstrated a 50% reduction in inflammation with histopathological analysis revealing strikingly reduced immune cell infiltration compared to WT mice. Administration of recombinant Lcn2 to Lcn2KO mice restored inflammation to levels observed in WT mice. Neutralization of Lcn2 using a monoclonal antibody significantly reduced inflammation in WT mice. In contrast, Lcn2KO mice developed more severe serum-induced arthritis compared to WT mice. Histological analysis revealed extensive tissue and bone destruction with significantly reduced neutrophil infiltration but considerably more macrophage migration in Lcn2KO mice when compared to WT. Conclusion These results demonstrate that Lcn2 may regulate immune cell recruitment to the site of inflammation, a process essential for the controlled initiation, perpetuation and resolution of inflammatory processes. Thus, Lcn2 may present a promising target in the treatment of IC-mediated inflammatory/autoimmune diseases. PMID:23280250

  16. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  17. Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies

    Directory of Open Access Journals (Sweden)

    Francisco J. Carvajal

    2016-01-01

    Full Text Available N-Methyl-D-aspartate receptors (NMDARs have two opposing roles in the brain. On the one hand, NMDARs control critical events in the formation and development of synaptic organization and synaptic plasticity. On the other hand, the overactivation of NMDARs can promote neuronal death in neuropathological conditions. Ca2+ influx acts as a primary modulator after NMDAR channel activation. An imbalance in Ca2+ homeostasis is associated with several neurological diseases including schizophrenia, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These chronic conditions have a lengthy progression depending on internal and external factors. External factors such as acute episodes of brain damage are associated with an earlier onset of several of these chronic mental conditions. Here, we will review some of the current evidence of how traumatic brain injury can hasten the onset of several neurological conditions, focusing on the role of NMDAR distribution and the functional consequences in calcium homeostasis associated with synaptic dysfunction and neuronal death present in this group of chronic diseases.

  18. GOT1-mediated anaplerotic glutamine metabolism regulates chronic acidosis stress in pancreatic cancer cells.

    Science.gov (United States)

    Abrego, Jaime; Gunda, Venugopal; Vernucci, Enza; Shukla, Surendra K; King, Ryan J; Dasgupta, Aneesha; Goode, Gennifer; Murthy, Divya; Yu, Fang; Singh, Pankaj K

    2017-08-01

    The increased rate of glycolysis and reduced oxidative metabolism are the principal biochemical phenotypes observed in pancreatic ductal adenocarcinoma (PDAC) that lead to the development of an acidic tumor microenvironment. The pH of most epithelial cell-derived tumors is reported to be lower than that of plasma. However, little is known regarding the physiology and metabolism of cancer cells enduring chronic acidosis. Here, we cultured PDAC cells in chronic acidosis (pH 6.9-7.0) and observed that cells cultured in low pH had reduced clonogenic capacity. However, our physiological and metabolomics analysis showed that cells in low pH deviate from glycolytic metabolism and rely more on oxidative metabolism. The increased expression of the transaminase enzyme GOT1 fuels oxidative metabolism of cells cultured in low pH by enhancing the non-canonical glutamine metabolic pathway. Survival in low pH is reduced upon depletion of GOT1 due to increased intracellular ROS levels. Thus, GOT1 plays an important role in energy metabolism and ROS balance in chronic acidosis stress. Our studies suggest that targeting anaplerotic glutamine metabolism may serve as an important therapeutic target in PDAC. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Microbubble-mediated ultrasound promotes accumulation of bone marrow mesenchymal stem cell to the prostate for treating chronic bacterial prostatitis in rats

    OpenAIRE

    2016-01-01

    Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared wit...

  20. A case report of vibration-induced hand comorbidities in a postwoman

    Directory of Open Access Journals (Sweden)

    Violante Francesco S

    2011-02-01

    Full Text Available Abstract Background Prolonged exposure to hand-transmitted vibration is associated with an increased occurrence of symptoms and signs of disorders in the vascular, neurological and osteoarticular systems of the upper limbs. However, the available epidemiological evidence is derived from studies on high vibration levels caused by vibratory tools, whereas little is known about possible upper limb disorders caused by chronic exposure to low vibration levels emitted by fixed sources. Case presentation We present the case of a postwoman who delivered mail for 15 years using a low-powered motorcycle. The woman was in good health until 2002, when she was diagnosed with bilateral Raynaud's phenomenon. In March 2003 a bilateral carpal tunnel syndrome was electromyographically diagnosed; surgical treatment was ineffective. Further examinations in 2005 highlighted the presence of chronic tendonitis (right middle finger flexor. Risk assessment From 1987, for 15 years, our patient rode her motorcycle for 4 h/day, carrying a load of 20-30 kg. For about a quarter of the time she drove over country roads. Using the information collected about the tasks carried out every day by the postwoman and some measurements performed on both handles of the motorcycle, as well as on both iron parts of the handlebars, we reconstructed the woman's previous exposure to hand-arm vibration. 8-hour energy-equivalent frequency weighted acceleration was about 2.4 m/s2. The lifetime dose was 1.5 × 109(m2/s4hd. Conclusions The particular set of comorbidities presented by our patient suggests a common pathophysiological basis for all the diseases. Considering the level of exposure to vibrations and the lack of specific knowledge on the effects of vibration in women, we hypothesize an association between the work exposure and the onset of the diseases.

  1. Identification of NURR1 as a mediator of MIF signaling during chronic arthritis: effects on glucocorticoid-induced MKP1.

    Science.gov (United States)

    Ralph, Jennifer A; Ahmed, Afsar U; Santos, Leilani L; Clark, Andrew R; McMorrow, Jason; Murphy, Evelyn P; Morand, Eric F

    2010-11-01

    Elucidation of factors regulating glucocorticoid (GC) sensitivity is required for the development of "steroid-sparing" therapies for chronic inflammatory diseases, including rheumatoid arthritis (RA). Accumulating evidence suggests that macrophage migration inhibitory factor (MIF) counterregulates the GC-induction of anti-inflammatory mediators, including mitogen-activated protein kinase phosphatase 1 (MKP1), a critical mitogen-activated protein kinase signaling inhibitor. This observation has yet to be extended to human disease; the molecular mechanisms remain unknown. We investigated NURR1, a GC-responsive transcription factor overexpressed in RA, as a MIF signaling target. We reveal abrogation by recombinant MIF (rMIF) of GC-induced MKP1 expression in RA fibroblast-like synoviocytes (FLS). rMIF enhanced NURR1 expression, artificial NBRE (orphan receptor DNA-binding site) reporter transactivation, and reversed GC-inhibition of NURR1. NURR1 expression was reduced during experimental arthritis in MIF-/- synovium, and silencing MIF reduced RA FLS NURR1 mRNA. Consistent with NBRE identification on the MKP1 gene, MKP1 mRNA was reduced in FLS that ectopically express NURR1, and silencing NURR1 enhanced MKP1 mRNA in RA FLS. rMIF enhanced NBRE binding on the MKP1 gene, and the absence of the NBRE prevented NURR1-repressive effects on basal and GC-induced MKP1 transactivation. This study defines NURR1 as a novel MIF target in chronic inflammation and demonstrates a role for NURR1 in regulating the anti-inflammatory mediator, MKP1. We propose a MIF-NURR1 signaling axis as a regulator of the GC sensitivity of MKP1.

  2. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats.

    Science.gov (United States)

    Zhu, Yongjun; Cui, Hongwang; Xia, Yunfeng; Gan, Hua

    2016-01-01

    Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL-positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD.

  3. Patient-provider relationship as mediator between adult attachment and self-management in primary care patients with multiple chronic conditions.

    Science.gov (United States)

    Brenk-Franz, Katja; Strauß, Bernhard; Tiesler, Fabian; Fleischhauer, Christian; Schneider, Nico; Gensichen, Jochen

    2017-06-01

    The conceptual model of attachment theory has been applied to understand the predispositions of patients in medical care and the patient-provider relationship. In patients with chronic conditions insecure attachment was connected to poorer self-management. The patient-provider relationship is associated with a range of health related outcomes and self-management skills. We determined whether the quality of the patient-provider relationship mediates the link between adult attachment and self-management among primary care patients with multiple chronic diseases. 209 patients with a minimum of three chronic diseases (including type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 from eight general practices were included in the APRICARE cohort study. Adult attachment was measured via self-report (ECR-RD), self-management skills by the FERUS and the patient-provider relationship by the PRA-D. The health status and chronicity were assessed by the GP. Multiple mediation analyses were used to examine whether aspects of the patient-provider relationship (communication, information, affectivity) are a mediators of associations between adult attachment and self-management. The analysis revealed that the quality of the patient-provider relationship mediated the effect of attachment on self-management in patients with multiple chronic conditions. Particularly the quality of communication and information over the course of treatment has a significant mediating influence. A personalized, attachment-related approach that promotes active patient-provider communication and gives information about the treatment to the patient may improve self-management skills in patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The Association between Chronic Widespread Musculoskeletal Pain, Depression and Fatigue Is Genetically Mediated.

    Directory of Open Access Journals (Sweden)

    Andrea Burri

    Full Text Available Chronic widespread muscoloskeletal pain (CWP is prevalent in the general population and associated with high health care costs, so understanding the risk factors for chronic pain is important for both those affected and for society. In the present study we investigated the underlying etiological structure of CWP to understand better the association between the major clinical features of fatigue, depression and dihydroepiandrosterone sulphate (DHEAS using a multivariate twin design.Data were available in 463 UK female twin pairs including CWP status and information on depression, chronic fatigue and serum DHEAS levels. High to moderate heritabilities for all phenotypes were obtained (42.58% to 74.24%. The highest phenotypic correlation was observed between fatigue and CWP (r = 0.45, and the highest genetic correlation between CWP and fatigue (rg = 0.78. Structural equation modeling revealed the AE Cholesky model to provide the best model of the observed data. In this model, two additive genetic factors could be detected loading heavily on CWP-A2 explaining 40% of the variance and A3 20%. The factor loading heaviest on DHEAS showed only a small loading on the other phenotypes and none on fatigue at all. Furthermore, one distinct non-shared environmental factor loading specifically on CWP-but not on any of the other phenotypes-could be detected suggesting that the association between CWP and the other phenotypes is due only to genetic factors.Our results suggest that CWP and its associated features share a genetic predisposition but that they are relatively distinct in their environmental determinants.

  5. Treatment of chronical myocardial ischemia by adenovirus-mediated hypatocyte growth factor gene transfer in minipigs

    Institute of Scientific and Technical Information of China (English)

    YUAN Biao; ZHANG YouRong; ZHAO Zhong; WU DanLi; YUAN LiZhen; WU Bin; WANG LiSheng; HUANG Jun

    2008-01-01

    Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adeno-virus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we estab-lished a minipig model of chronically ischemic myocardium in which an Ameroid constrictor was placed around the left circumflex branch of the coronary artery (LCX). A total of 18 minipigs were ran-domly divided into 3 groups: a surgery control group, a model group and an Ad-HGF treatment group implanted with Ameroid constrictor. Ad-HGF or the control agent was injected directly into the ischemic myocardium, and an improvement in heart function and blood supply were evaluated. The results showed that myocardial perfusion remarkably improved in the Ad-HGF group compared with that in both the control and model groups. Four weeks after the treatment, the density of newly formed blood vessels was higher and the number of collateral blood vessels was greater in the Ad-HGF group than in the model group. The area of myocardial ischemia reduced evidently and the left ventricular ejection fraction improved significantly in the Ad-HGF group. These results suggest that HGF gene therapy may become a novel approach in the treatment of chronically ischemic myocardium.

  6. Treatment of chronical myocardial ischemia by adenovirus-mediated hepatocyte growth factor gene transfer in minipigs

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adeno- virus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we estab- lished a minipig model of chronically ischemic myocardium in which an Ameroid constrictor was placed around the left circumflex branch of the coronary artery (LCX). A total of 18 minipigs were ran- domly divided into 3 groups: a surgery control group, a model group and an Ad-HGF treatment group implanted with Ameroid constrictor. Ad-HGF or the control agent was injected directly into the ischemic myocardium, and an improvement in heart function and blood supply were evaluated. The results showed that myocardial perfusion remarkably improved in the Ad-HGF group compared with that in both the control and model groups. Four weeks after the treatment, the density of newly formed blood vessels was higher and the number of collateral blood vessels was greater in the Ad-HGF group than in the model group. The area of myocardial ischemia reduced evidently and the left ventricular ejection fraction improved significantly in the Ad-HGF group. These results suggest that HGF gene therapy may become a novel approach in the treatment of chronically ischemic myocardium.

  7. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity.

  8. Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts: Validation of Human Histological and Molecular Phenotypes.

    Science.gov (United States)

    Adam, B A; Smith, R N; Rosales, I A; Matsunami, M; Afzali, B; Oura, T; Cosimi, A B; Kawai, T; Colvin, R B; Mengel, M

    2017-04-26

    Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0.92). This three-gene set correlated with classic features of AMR, including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association between three-gene set expression and AMR and highlighted the ambiguity of v lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR). Elevated three-gene set expression corresponded with the development of immunopathological evidence of rejection and often preceded it. Many recipients demonstrated mixed AMR and TCMR, suggesting that this represents the natural pattern of rejection. These data provide NHP animal model validation of recent updates to the Banff classification including the assessment of molecular markers for diagnosing AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Temporal changes in integrin-mediated cardiomyocyte adhesion secondary to chronic cardiac volume overload in rats

    Science.gov (United States)

    Stewart, James A.; Gardner, Jason D.; Brower, Gregory L.

    2013-01-01

    Previous studies have established integrins as cell surface receptors that mediate cardiomyocyte-extracellular matrix (ECM) attachments. This study sought to determine the contributions of the myocardial β1- and β3-integrin subunits to ventricular dilatation and coronary flow regulation using a blood-perfused isolated heart preparation. Furthermore, cardiomyocyte adhesion to collagen types I and IV, fibronectin, and laminin with and without a β1-integrin subunit neutralizing antibody was assessed during the course of remodeling secondary to a sustained cardiac volume overload, including the onset of heart failure. Isolated cardiomyocytes were obtained during the initial, compensated, and decompensated phases of remodeling resulting from an aortocaval fistula created in 8-wk-old male Sprague-Dawley rats. Blocking the β1-integrin subunit in isolated normal hearts produced ventricular dilatation, whereas this was not the case when the β3-subunit was blocked. Substantial reductions in cardiomyocyte adhesion coincided with the previously documented development of ventricular dilatation and decreased contractility postfistula, with the β1-integrin contribution to adhesion ranging from 28% to 73% over the course of remodeling being essentially substrate independent. In contrast, both integrin subunits were found to be involved in regulating coronary vascular resistance. It is concluded that marked reductions in integrin-mediated cardiomyocyte adhesion to the ECM play a significant role in the progression of adverse myocardial remodeling that leads to heart failure. Furthermore, although both the β1- and β3-integrin subunits were involved in regulating coronary vascular resistance, only inhibition of β1-integrin-mediated adhesion resulted in ventricular dilatation of the normal heart. PMID:24163072

  10. Effect and its clinical significance of different dose of glucocorticoids on inflammation mediators in patients with acute exacerbation of chronic obstructive pulmonary diseases

    Institute of Scientific and Technical Information of China (English)

    钟佰强

    2014-01-01

    Objective To explore the effect and its clinical significance of different dose of glucocorticoids on inflammation mediators in patients with acute exacerbation of chronic obstructive pulmonary diseases.Methods 45 patients admitted to our hospitals from March 2007 to March 2011were randomly divided into 3 groups:methylprednisolone40 mg group(methylprednisolone 40mg,iv,qd),meth-

  11. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia

    Science.gov (United States)

    Shingai, Masashi; Nishimura, Yoshiaki; Klein, Florian; Mouquet, Hugo; Donau, Olivia K.; Plishka, Ronald; Buckler-White, Alicia; Seaman, Michael; Piatak, Michael; Lifson, Jeffrey D.; Dimitrov, Dimiter; Nussenzweig, Michel C.; Martin, Malcolm A.

    2013-11-01

    Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS. However, earlier studies of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies administered to infected individuals or humanized mice reported poor control of virus replication and the rapid emergence of resistant variants. A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals. These neutralizing antibodies target different regions of the HIV-1 envelope glycoprotein including the CD4-binding site, glycans located in the V1/V2, V3 and V4 regions, and the membrane proximal external region of gp41 (refs 9, 10, 11, 12, 13, 14). Here we have examined two of the new antibodies, directed to the CD4-binding site and the V3 region (3BNC117 and 10-1074, respectively), for their ability to block infection and suppress viraemia in macaques infected with the R5 tropic simian-human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques. Either antibody alone can potently block virus acquisition. When administered individually to recently infected macaques, the 10-1074 antibody caused a rapid decline in virus load to undetectable levels for 4-7days, followed by virus rebound during which neutralization-resistant variants became detectable. When administered together, a single treatment rapidly suppressed plasma viraemia for 3-5weeks in some long-term chronically SHIV-infected animals with low CD4+ T-cell levels. A second cycle of anti-HIV-1 monoclonal antibody therapy, administered to two previously treated animals, successfully controlled virus rebound. These results indicate that immunotherapy or a combination of immunotherapy plus conventional antiretroviral drugs might be useful as a treatment for chronically HIV-1-infected

  12. NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation.

    Science.gov (United States)

    Miranda, Adrian; Mickle, Aaron; Bruckert, Mitchell; Kannampalli, Pradeep; Banerjee, Banani; Sengupta, Jyoti N

    2014-12-05

    NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD>20 mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH 4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Vibration-induced drop atomization and the numerical simulation of low-frequency single-droplet ejection

    Science.gov (United States)

    James, Ashley J.; Smith, Marc K.; Glezer, Ari

    2003-02-01

    Vibration-induced droplet ejection is a novel way to create a spray. In this method, a liquid drop is placed on a vertically vibrating solid surface. The vibration leads to the formation of waves on the free surface. Secondary droplets break off from the wave crests when the forcing amplitude is above a critical value. When the forcing frequency is small, only low-order axisymmetric wave modes are excited, and a single secondary droplet is ejected from the tip of the primary drop. When the forcing frequency is high, many high-order non-axisymmetric modes are excited, the motion is chaotic, and numerous small secondary droplets are ejected simultaneously from across the surface of the primary drop. In both frequency regimes a crater may form that collapses to create a liquid spike from which droplet ejection occurs. An axisymmetric, incompressible, Navier Stokes solver was developed to simulate the low-frequency ejection process. A volume-of-fluid method was used to track the free surface, with surface tension incorporated using the continuum-surface-force method. A time sequence of the simulated interface shape compared favourably with an experimental sequence. The dynamics of the droplet ejection process was investigated, and the conditions under which ejection occurs and the effect of the system parameters on the process were determined.

  14. A Single Cell Extraction Chip Using Vibration-Induced Whirling Flow and a Thermo-Responsive Gel Pattern

    Directory of Open Access Journals (Sweden)

    Takeshi Hayakawa

    2014-09-01

    Full Text Available We propose a single cell extraction chip with an open structure, which utilizes vibration-induced whirling flow and a single cell catcher. By applying a circular vibration to a micropillar array spiral pattern, a whirling flow is induced around the micropillars, and target cells are transported towards the single cell catcher placed at the center of the spiral. The single cell catcher is composed of a single-cell-sized hole pattern of thermo-responsive gel. The gel swells at low temperatures (≲32 ◦C and shrinks at high temperatures (≳32 ◦C, therefore, its volume expansion can be controlled by an integrated microheater. When the microheater is turned on, a single cell is trapped by the hole pattern of the single cell catcher. Then, when the microheater is turned off, the single cell catcher is cooled by the ambient temperature. The gel swells at this temperature, and the hole closes to catch the single cell. The caught cell can then be released into culture wells on a microtiter plate by heating the gel again. We conducted single cell extraction with the proposed chip and achieved a 60% success rate, of which 61% cells yielded live cells.

  15. Regarding "A new method for predicting nonlinear structural vibrations induced by ground impact loading" [Journal of Sound and Vibration, 331/9 (2012) 2129-2140

    Science.gov (United States)

    Cartmell, Matthew P.

    2016-09-01

    The Editor wishes to make the reader aware that the paper "A new method for predicting nonlinear structural vibrations induced by ground impact loading" by Jun Liu, Yu Zhang, Bin Yun, Journal of Sound and Vibration, 331 (2012) 2129-2140, did not contain a direct citation of the fundamental and original work in this field by Dr. Mark Svinkin. The Editor regrets that this omission was not noted at the time that the above paper was accepted and published.

  16. Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism

    Directory of Open Access Journals (Sweden)

    Radhika Kandaswamy

    2016-08-01

    Full Text Available Chronic lymphocytic leukemia (CLL is an adult B cell malignancy. Genome-wide association studies show that variation at 15q15.1 influences CLL risk. We deciphered the causal variant at 15q15.1 and the mechanism by which it influences tumorigenesis. We imputed all possible genotypes across the locus and then mapped highly associated SNPs to areas of chromatin accessibility, evolutionary conservation, and transcription factor binding. SNP rs539846 C>A, the most highly associated variant (p = 1.42 × 10−13, odds ratio = 1.35, localizes to a super-enhancer defined by extensive histone H3 lysine 27 acetylation in intron 3 of B cell lymphoma 2 (BCL2-modifying factor (BMF. The rs539846-A risk allele alters a conserved RELA-binding motif, disrupts RELA binding, and is associated with decreased BMF expression in CLL. These findings are consistent with rs539846 influencing CLL susceptibility through differential RELA binding, with direct modulation of BMF expression impacting on anti-apoptotic BCL2, a hallmark of oncogenic dependency in CLL.

  17. Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain.

    Science.gov (United States)

    Jhaveri, Maulik D; Sagar, Devi R; Elmes, Steven J R; Kendall, David A; Chapman, Victoria

    2007-08-01

    The endocannabinoid system consists of cannabinoid CB(1) and CB(2) receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB(1) receptors. Following the recent evidence for CB(2) receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB(2) receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB(2) receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB(2) receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action.

  18. Neuronal plasticity in chronic pancreatitis is mediated via the neurturin/GFRα2 axis.

    Science.gov (United States)

    Demir, Ihsan Ekin; Wang, Kun; Tieftrunk, Elke; Giese, Nathalia A; Xing, Baocai; Friess, Helmut; Kehl, Timo; Ceyhan, Güralp O

    2012-11-01

    The glial cell line-derived neurotrophic factor (GDNF) family member neurturin (NRTN) and its receptor GFRα2 play a deciding role in the normal development of pancreatic parasympathetic innervation. In this study, we aimed at investigating the role of NRTN/GFRα2 axis in pancreatic neuropathy in human chronic pancreatitis (CP). Expression of NRTN/GFRα2 was compared between normal human pancreas (NP) and CP tissues via immunohistochemistry, immunoblotting, and quantitative RT-PCR and correlated to abdominal pain sensation. To elucidate the impact of NRTN in pancreatic neuroplasticity, neuronal phenotype and glial density were quantified via an in vitro neuroplasticity assay in dissociated newborn rat dorsal root ganglia (DRG) cultured 1) in CP tissue extracts depleted from NRTN, 2) in NP, 3) in untreated CP tissue extracts, and 4) CP extracts in which nerve growth factor, glial cell derived-neurotrophic factor, or TGF-β(1) was depleted. NRTN and GFRα2 were highly upregulated in CP, especially in intrapancreatic nerves and the extracellular matrix. CP tissue demonstrated increased amounts of mature multimeric NRTN and elevated levels of GFRα2. The noticeable neurotrophic effect of CP tissue extracts on DRG neurons was diminished upon blockade of NRTN from these extracts. However, blockade of NRTN from CP extracts did not influence the density of DRG glia cells. In conclusion, the NRTN/GFRα2 axis is activated during the course of CP and represents a major key player in the reactive neural alterations in CP. This is the first study to provide functional evidence for the contribution of neurotrophic factors to neuroplasticity in CP.

  19. ERK signaling mediates enhanced angiotensin Ⅱ-induced rat aortic constriction following chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    GUO Xue-ling; DENG Yan; SHANG Jin; LIU Kui; XU Yong-jian; LIU Hui-guo

    2013-01-01

    Background Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension.The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin Ⅱ (Ang Ⅱ) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK),myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).Methods Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles.Phosphorylation of ERK1/2,MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 μmol/L).Results CIH-exposure resulted in more body weight gain and elevated blood pressure,which could be attenuated by pretreatment with PD98059.Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang Ⅱ (Emax:(138.56±5.78)% versus (98.45±5.31)% of KCI; pD2:7.98±0.14 versus 8.14±0.05,respectively).CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2increased).CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC.In parallel to greater increases in phosphorylation of ERK1/2,MYPT1 and MLC,Ang Ⅱ-induced aortic constriction was significantly enhanced in CIH rats,which was largely reversed by PD98059.However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.Conclusion These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang Ⅱ,presumably owing to more activated ERK1/2 signaling pathway.

  20. Targeting p53-deficient chronic lymphocytic leukemia cells in vitro and in vivo by ROS-mediated mechanism.

    Science.gov (United States)

    Liu, Jinyun; Chen, Gang; Pelicano, Helene; Liao, Jianwei; Huang, Jie; Feng, Li; Keating, Michael J; Huang, Peng

    2016-11-01

    Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Loss of p53 function in CLL cells due to chromosome 17p deletion or p53 mutations often leads to a more malignant disease phenotype and is associated with drug resistance and poor clinical outcome. Thus, development of novel therapeutic strategies to effectively target CLL cells with p53 deficiency is clinically important. Here we showed that p53-null CLL cells were highly sensitive to ROS-mediated cell killing due to their intrinsic ROS stress. We further demonstrated that a natural compound phenethyl isothiocyanate (PEITC) was able to effectively kill CLL cells with loss of p53, even under the protection of stromal cells. In p53-defficient CLL cells, PEITC induced a rapid depletion of glutathione and a severe accumulation of ROS, leading to massive leukemia cell death in the stromal microenvironment. The drug-induced cell death was associated with a significant decrease of in MCL-1 survival molecule. We further showed that ROS-mediated cell death was the key mechanism by which PEITC induced cytotoxicity, since such cell death could be prevented by addition of antioxidant NAC. Importantly, in vivo study showed that PEITC was able to induce substantial leukemia cell death in mice. Treatment of CLL mice harboring TCL1-Tg:p53-/- genotype with PEITC significantly prolonged the median survival time of the animals. Our study identifies a vulnerability of p53-null CLL cells with high sensitivity to ROS-generating agents, and suggests that PEITC may potentially be useful for clinical treatment of CLL with 17p deletion and p53 mutations.

  1. Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

    Directory of Open Access Journals (Sweden)

    Irene Mavroudi

    2012-01-01

    Full Text Available Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients.

  2. Vibration Induced Microfluidic Atomization

    Science.gov (United States)

    Yeo, Leslie; Qi, Aisha; Friend, James

    2008-11-01

    We demonstrate rapid generation of micron aerosol droplets in a microfluidic device in which a fluid drop is exposed to surface vibration as it sits atop a piezoelectric substrate. Little, however, is understood about the processes by which these droplets form due to the complex hydrodynamic processes that occur across widely varying length and time scales. Through experiments, scaling theory and numerical modelling, we elucidate the interfacial destabilization mechanisms that lead to droplet formation. Droplets form due to the axisymmetric break-up of cylindrical liquid jets ejected as a consequence of interfacial destabilization. Their 10 μm size correlates with the jet radius and the instability wavelength, both determined from a viscous-capillary dominant force balance and confirmed through a numerical solution. With the exception of drops that spread into thin films with thicknesses on the order of the boundary layer dimension, the free surface is always observed to vibrate at the capillary-viscous resonance frequency despite the surface vibration frequency being several orders larger. This is contrary to common assumptions used in deriving subharmonic models resulting in a Mathieu equation, which has commonly led to spurious predictions in the droplet size.

  3. Acceptance and commitment therapy for chronic pain: evidence of mediation and clinically significant change following an abbreviated interdisciplinary program of rehabilitation.

    Science.gov (United States)

    Vowles, Kevin E; Witkiewitz, Katie; Sowden, Gail; Ashworth, Julie

    2014-01-01

    There is an emerging body of evidence regarding interdisciplinary acceptance and commitment therapy in the rehabilitative treatment of chronic pain. This study evaluated the reliability and clinical significance of change following an open trial that was briefer than that examined in previous work. In addition, the possible mediating effect of psychological flexibility, which is theorized to underlie the acceptance and commitment therapy model, was examined. Participants included 117 completers of an interdisciplinary program of rehabilitation for chronic pain. Assessment took place at treatment onset and conclusion, and at a 3-month follow-up when 78 patients (66.7%) provided data. At the 3-month follow-up, 46.2% of patients achieved clinically significant change, and 58.9% achieved reliable change, in at least 1 key measure of functioning (depression, pain anxiety, and disability). Changes in measures of psychological flexibility significantly mediated changes in disability, depression, pain-related anxiety, number of medical visits, and the number of classes of prescribed analgesics. These results add to the growing body of evidence supporting interdisciplinary acceptance and commitment therapy for chronic pain, particularly with regard to the clinical significance of an abbreviated course of treatment. Further, improvements appear to be mediated by changes in the processes specified within the theoretical model. Outcomes of an abbreviated interdisciplinary treatment for chronic pain based on a particular theoretical model are presented. Analyses indicated that improvements at follow-up mediated change in the theorized treatment process. Clinically significant change was indicated in just under half of participants. These data may be helpful to clinicians and researchers interested in intervention approaches and mechanisms of change. Copyright © 2014 American Pain Society. All rights reserved.

  4. Pain behavior mediates the relationship between perceived injustice and opioid prescription for chronic pain: a Collaborative Health Outcomes Information Registry study

    Science.gov (United States)

    Carriere, Junie S; Martel, Marc-Olivier; Kao, Ming-Chih; Sullivan, Michael JL; Darnall, Beth D

    2017-01-01

    Background and purpose Perceived injustice has been defined as an appraisal regarding the severity and irreparability of loss associated with pain, blame and a sense of unfairness. Recent findings have identified perceived injustice as an important risk factor for pain-related outcomes. Studies suggest that perceived injustice is associated with opioid prescription in patients with pain conditions. However, the mechanisms by which perceived injustice is linked to opioid prescription are not well understood. The primary objective of this study was to examine the potential mediating roles of pain intensity, depressive symptoms and pain behavior in the association between perceived injustice and opioid prescription among patients with chronic pain. Methods This cross-sectional study used a sample of 344 patients with chronic pain being treated at a tertiary pain treatment center. Participants completed measures of perceived injustice, pain intensity, depressive symptoms, pain behavior and opioid prescription. Bootstrapped multiple mediation analyses were used to examine the mediating role of patients’ pain intensity, depressive symptoms and pain behavior in the association between perceived injustice and opioid prescription. Results Consistent with previous research, we found a significant association between perceived injustice and opioid prescription. Interestingly, results revealed that pain behavior was the only variable that mediated the association between perceived injustice and opioid prescription. Conclusion This study was the first to examine the mechanisms by which perceived injustice is associated with opioid prescription in patients with chronic pain. We found that pain behavior, rather than pain intensity and depressive symptoms, mediated the association between perceived injustice and opioid prescription. Future research in this area should employ a longitudinal research design in order to arrive at clearer causal conclusions about the relationships

  5. Vibration-induced multifocal neuropathy in forestry workers: electrophysiological findings in relation to vibration exposure and finger circulation.

    Science.gov (United States)

    Bovenzi, M; Giannini, F; Rossi, S

    2000-11-01

    contribute to peripheral nerve disorders occurring in forestry workers who operate chain saws. The findings of this study suggest the existence of an exposure-effect relationship for vibration-induced neuropathy. Different underlying mechanisms are likely to be involved in the pathogenesis of the neurological and vascular components of the hand-arm vibration syndrome.

  6. TALEN-mediated functional correction of X-linked chronic granulomatous disease in patient-derived induced pluripotent stem cells.

    Science.gov (United States)

    Dreyer, Anne-Kathrin; Hoffmann, Dirk; Lachmann, Nico; Ackermann, Mania; Steinemann, Doris; Timm, Barbara; Siler, Ulrich; Reichenbach, Janine; Grez, Manuel; Moritz, Thomas; Schambach, Axel; Cathomen, Toni

    2015-11-01

    X-linked chronic granulomatous disease (X-CGD) is an inherited disorder of the immune system. It is characterized by a defect in the production of reactive oxygen species (ROS) in phagocytic cells due to mutations in the NOX2 locus, which encodes gp91phox. Because the success of retroviral gene therapy for X-CGD has been hampered by insertional activation of proto-oncogenes, targeting the insertion of a gp91phox transgene into potential safe harbor sites, such as AAVS1, may represent a valid alternative. To conceptually evaluate this strategy, we generated X-CGD patient-derived induced pluripotent stem cells (iPSCs), which recapitulate the cellular disease phenotype upon granulocytic differentiation. We examined AAVS1-specific zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) for their efficacy to target the insertion of a myelo-specific gp91phox cassette to AAVS1. Probably due to their lower cytotoxicity, TALENs were more efficient than ZFNs in generating correctly targeted iPSC colonies, but all corrected iPSC clones showed no signs of mutations at the top-ten predicted off-target sites of both nucleases. Upon differentiation of the corrected X-CGD iPSCs, gp91phox mRNA levels were highly up-regulated and the derived granulocytes exhibited restored ROS production that induced neutrophil extracellular trap (NET) formation. In conclusion, we demonstrate that TALEN-mediated integration of a myelo-specific gp91phox transgene into AAVS1 of patient-derived iPSCs represents a safe and efficient way to generate autologous, functionally corrected granulocytes.

  7. Utrophin A is essential in mediating the functional adaptations of mdx mouse muscle following chronic AMPK activation.

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    Al-Rewashdy, Hasanen; Ljubicic, Vladimir; Lin, Wei; Renaud, Jean-Marc; Jasmin, Bernard J

    2015-03-01

    Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin along muscle fibers. An attractive therapeutic avenue for DMD consists in the upregulation of utrophin A, a protein with high sequence identity and functional redundancy with dystrophin. Recent work has shown that pharmacological interventions that induce a muscle fiber shift toward a slower, more oxidative phenotype with increased expression of utrophin A confer morphological and functional improvements in mdx mice. Whether such improvements result from the increased expression of utrophin A per se or are linked to other beneficial adaptations associated with the slow, oxidative phenotype remain to be established. To address this central issue, we capitalized on the use of double knockout (dKO) mice, which are mdx mice also deficient in utrophin. We first compared expression of signaling molecules and markers of the slow, oxidative phenotype in muscles of mdx versus dKO mice and found that both strains exhibit similar phenotypes. Chronic activation of 5' adenosine monophosphate-activated protein kinase with 5-amino-4-imidazolecarboxamide riboside (AICAR) resulted in expression of a slower, more oxidative phenotype in both mdx and dKO mice. In mdx mice, this fiber type shift was accompanied by clear functional improvements that included reductions in central nucleation, IgM sarcoplasmic penetration and sarcolemmal damage resulting from eccentric contractions, as well as in increased grip strength. These important morphological and functional adaptations were not seen in AICAR-treated dKO mice. Our findings show the central role of utrophin A in mediating the functional benefits associated with expression of a slower, more oxidative phenotype in dystrophic animals.

  8. Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke.

    Science.gov (United States)

    Meadmore, Katie L; Hughes, Ann-Marie; Freeman, Chris T; Cai, Zhonglun; Tong, Daisy; Burridge, Jane H; Rogers, Eric

    2012-06-07

    Novel stroke rehabilitation techniques that employ electrical stimulation (ES) and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients' voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL), a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants' arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC) algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test) at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this.

  9. Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke

    Directory of Open Access Journals (Sweden)

    Meadmore Katie L

    2012-06-01

    Full Text Available Abstract Background Novel stroke rehabilitation techniques that employ electrical stimulation (ES and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients’ voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL, a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. Methods Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants’ arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. Results From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. Conclusions The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this.

  10. Disruption of Sirtuin 1-Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Yao, Hongwei; Sundar, Isaac K; Huang, Yadi; Gerloff, Janice; Sellix, Michael T; Sime, Patricia J; Rahman, Irfan

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death, and it is characterized by abnormal inflammation and lung function decline. Although the circadian molecular clock regulates inflammatory responses, there is no information available regarding the impact of COPD on lung molecular clock function and its regulation by sirtuin 1 (SIRT1). We hypothesize that the molecular clock in the lungs is disrupted, leading to increased inflammatory responses in smokers and patients with COPD and its regulation by SIRT1. Lung tissues, peripheral blood mononuclear cells (PBMCs), and sputum cells were obtained from nonsmokers, smokers, and patients with COPD for measurement of core molecular clock proteins (BMAL1, CLOCK, PER1, PER2, and CRY1), clock-associated nuclear receptors (REV-ERBα, REV-ERBβ, and RORα), and SIRT1 by immunohistochemistry, immunofluorescence, and immunoblot. PBMCs were treated with the SIRT1 activator SRT1720 followed by LPS treatment, and supernatant was collected at 6-hour intervals. Levels of IL-8, IL-6, and TNF-α released from PBMCs were determined by ELISA. Expression of BMAL1, PER2, CRY1, and REV-ERBα was reduced in PBMCs, sputum cells, and lung tissues from smokers and patients with COPD when compared with nonsmokers. SRT1720 treatment attenuated LPS-mediated reduction of BMAL1 and REV-ERBα in PBMCs from nonsmokers. Additionally, LPS differentially affected the timing and amplitude of cytokine (IL-8, IL-6, and TNF-α) release from PBMCs in nonsmokers, smokers, and patients with COPD. Moreover, SRT1720 was able to inhibit LPS-induced cytokine release from cultured PBMCs. In conclusion, disruption of the molecular clock due to SIRT1 reduction contributes to abnormal inflammatory response in smokers and patients with COPD.

  11. Crosstalk between the unfolded protein response and NF-κB-mediated inflammation in the progression of chronic kidney disease.

    Science.gov (United States)

    Mohammed-Ali, Zahraa; Cruz, Gaile L; Dickhout, Jeffrey G

    2015-01-01

    The chronic inflammatory response is emerging as an important therapeutic target in progressive chronic kidney disease. A key transcription factor in the induction of chronic inflammation is NF-κB. Recent studies have demonstrated that sustained activation of the unfolded protein response (UPR) can initiate this NF-κB signaling phenomenon and thereby induce chronic kidney disease progression. A key factor influencing chronic kidney disease progression is proteinuria and this condition has now been demonstrated to induce sustained UPR activation. This review details the crosstalk between the UPR and NF-κB pathways as pertinent to chronic kidney disease. We present potential tools to study this phenomenon as well as potential therapeutics that are emerging to regulate the UPR. These therapeutics may prevent inflammation specifically induced in the kidney due to proteinuria-induced sustained UPR activation.

  12. Functional upregulation of STIM-1/Orai-1-mediated store-operated Ca2+ contributing to the hypertension development elicited by chronic EtOH consumption.

    Science.gov (United States)

    Bomfim, Guilherme Henrique Souza; Méndez-López, Iago; Arranz-Tagarro, Juan Alberto; Carbonel, Adriana Aparecida Ferraz; Roman-Campos, Danilo; Padín, Juan Fernando; García, Antonio García; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito

    2017-02-01

    Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca²⁺) handling. Store-operated Ca2+ entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling between STIM-1 (ER Ca2+ sensor) and Orai-1 (channel pore) is a key mechanism to control SOCE through of store-operated Ca2+ channels (SOCCs). However, the role of STIM-1/Orai-1-mediated SOCE and its cross-talk with EtOH-triggered vascular remodeling and hypertension remain poorly understood. We address this subject in the present study by evaluating how chronic EtOH consumption induces alterations in Ca²⁺ handling via SOCE. Male Wistar Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days). Systolic blood pressure (SBP) and EtOH concentration were measured; cardiovascular remodeling was assessed by histomorphometry; and function/expression of STIM-1/Orai-1-mediated Ca2+ influx were evaluated by isometric contraction and western blot experiments. Compared to the WKY-Control, our results show that: (1) chronic EtOH consumption caused a significant elevation of SBP in both strains; (2) cardiac hypertrophy and hypertrophic aortic wall remodeling much more pronounced in WKY-EtOH; (3) decreased capacity of ER to store and release Ca2+ ; (4) increased STIM-1/Orai-1-mediated SOCCs activation, which was selectively inhibited by YM-58483; and (5) increased expression of STIM-1 in WKY-EtOH and SHR-Control rats. These findings suggest that hypertrophic aortic remodeling and abnormal contraction triggered mainly by Ca2+ overload via STIM-1/Orai-1-mediated SOCE through SOCCs are involved hypertension developed by EtOH consumption.

  13. Chemical Composition and Anti-Candidiasis Mediated Wound Healing Property of Cymbopogon nardus Essential Oil on Chronic Diabetic Wounds

    Science.gov (United States)

    Kandimalla, Raghuram; Kalita, Sanjeeb; Choudhury, Bhaswati; Dash, Suvakanta; Kalita, Kasturi; Kotoky, Jibon

    2016-01-01

    Poor wound healing is one of the major complication of diabetic patients which arises due to different factors like hyperglycemia, oxidative stress, vascular insufficiency and microbial infections. Candidiasis of diabetic wounds is a difficult to treat condition and potentially can lead to organ amputation. There are a few number of medications available in market to treat this chronic condition; which demands for alternative treatment options. In traditional system of medicine like Ayurveda, essential oil extracted from leaves of Cymbopogon nardus L. (Poaceae) has been using for the treatment of microbial infections, inflammation and pain. In this regard, we have evaluated anti-Candida and anti-inflammatory activity mediated wound healing property of C. nardus essential oil (EO-CN) on candidiasis of diabetic wounds. EO-CN was obtained through hydro-distillation and subjected to Gas chromatography–mass spectroscopy (GC–MS) analysis for chemical profiling. Anti-Candida activity of EO-CN was tested against Candida albicans, C. glabrata and C. tropicalis by in vitro zone of inhibition and minimum inhibitory concentration (MIC) assays. Anti-candidiasis ability of EO-CN was evaluated on C. albicans infected diabetic wounds of mice through measuring candida load on the 7th, 14th, and 21st day of treatment. Further progression in wound healing was confirmed by measuring the inflammatory marker levels and histopathology of wounded tissues on last day of EO-CN treatment. A total of 95 compounds were identified through GC–MS analysis, with major compounds like citral, 2,6-octadienal-, 3,7-dimethyl-, geranyl acetate, citronellal, geraniol, and citronellol. In vitro test results demonstrated strong anti-Candida activity of EO-CN with a MIC value of 25 μg/ml against C. albicans, 50 μg/ml against C. glabrata and C. tropicalis. EO-CN treatment resulted in significant reduction of candida load on diabetic wounds. Acceleration in wound healing was indicated by declined

  14. Chemical Composition and Anti-Candidiasis Mediated Wound Healing Property of Cymbopogon nardus Essential Oil on Chronic Diabetic Wounds.

    Science.gov (United States)

    Kandimalla, Raghuram; Kalita, Sanjeeb; Choudhury, Bhaswati; Dash, Suvakanta; Kalita, Kasturi; Kotoky, Jibon

    2016-01-01

    Poor wound healing is one of the major complication of diabetic patients which arises due to different factors like hyperglycemia, oxidative stress, vascular insufficiency and microbial infections. Candidiasis of diabetic wounds is a difficult to treat condition and potentially can lead to organ amputation. There are a few number of medications available in market to treat this chronic condition; which demands for alternative treatment options. In traditional system of medicine like Ayurveda, essential oil extracted from leaves of Cymbopogon nardus L. (Poaceae) has been using for the treatment of microbial infections, inflammation and pain. In this regard, we have evaluated anti-Candida and anti-inflammatory activity mediated wound healing property of C. nardus essential oil (EO-CN) on candidiasis of diabetic wounds. EO-CN was obtained through hydro-distillation and subjected to Gas chromatography-mass spectroscopy (GC-MS) analysis for chemical profiling. Anti-Candida activity of EO-CN was tested against Candida albicans, C. glabrata and C. tropicalis by in vitro zone of inhibition and minimum inhibitory concentration (MIC) assays. Anti-candidiasis ability of EO-CN was evaluated on C. albicans infected diabetic wounds of mice through measuring candida load on the 7th, 14th, and 21st day of treatment. Further progression in wound healing was confirmed by measuring the inflammatory marker levels and histopathology of wounded tissues on last day of EO-CN treatment. A total of 95 compounds were identified through GC-MS analysis, with major compounds like citral, 2,6-octadienal-, 3,7-dimethyl-, geranyl acetate, citronellal, geraniol, and citronellol. In vitro test results demonstrated strong anti-Candida activity of EO-CN with a MIC value of 25 μg/ml against C. albicans, 50 μg/ml against C. glabrata and C. tropicalis. EO-CN treatment resulted in significant reduction of candida load on diabetic wounds. Acceleration in wound healing was indicated by declined levels of

  15. Substance P and Calcitonin Gene Related Peptide Mediate Pain in Chronic Pancreatitis and Their Expression is Driven by Nerve Growth Factor

    Science.gov (United States)

    Liu, LianSheng; Shenoy, Mohan; Pasricha, Pankaj Jay

    2014-01-01

    Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the up-regulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin gene-related peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin gene-related peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic

  16. 5-HT7 receptor-mediated meningeal dilatation induced by 5-carboxamidotryptamine in rats is not altered by 5-HT depletion and chronic corticosterone treatment.

    Science.gov (United States)

    Martínez-García, E; Sánchez-Maldonado, C; Terrón, J A

    2011-01-01

    Low brain serotonin levels and high circulating levels of corticosterone are features of migraine. The 5-HT7 receptor was shown to mediate dilator responses to the 5-HT1B/1D and 5-HT7 receptor agonist, 5-carboxamidotryptamine in the middle meningeal artery of rats. Here we analyzed the effect of serotonin depletion and chronic corticosterone treatment on 5-HT7 receptor-mediated dilatation induced by 5-carboxamidotryptamine in the middle meningeal artery of anesthetized rats. Two weeks before experiments, male Wistar rats received i.c.v. injections of vehicle or the neurotoxin, 5,7-dihydroxytryptamine; upon recovery, animals received a chronic s.c. treatment (2 weeks) with vehicle (1 ml/kg/day) or corticosterone (20 mg/kg/day). At the end of treatments, animals were anesthetized and prepared for recording of blood pressure and blood flow in the middle meningeal artery, and i.v. drug administration. All animals received the 5-HT1B/1D receptor antagonist GR-127935 (1 mg/kg, i.v.) alone or combined with the 5-HT7 receptor antagonist, SB-269970 (1 mg/kg, i.v.). Topical 5-carboxamidotryptamine (0.01-1000 microM) to the exposed dura mater encephala produced decreases in diastolic blood pressure, variable changes in meningeal blood flow and increases in conductance (i.e. dilatation) in the middle meningeal artery. Meningeal dilator responses to 5-carboxamidotryptamine did not differ among treatment groups. In all cases, the combined treatment with GR-127935 + SB-269970 inhibited hypotensive and meningeal dilator responses to 5- carboxamidotryptamine. Together, these data do not support the notion that 5-HT7 receptors mediating dilatation in the middle meningeal artery are regulated by low brain serotonin levels and/or chronically high circulating levels of corticosterone. Further studies are required to elucidate the potential impact of these conditions and the role of 5-HT7 receptors in migraine.

  17. [Which route leads from chronic back pain to depression? A path analysis on direct and indirect effects using the cognitive mediators catastrophizing and helplessness/hopelessness in a general population sample].

    Science.gov (United States)

    Fahland, R A; Kohlmann, T; Hasenbring, M; Feng, Y-S; Schmidt, C O

    2012-12-01

    Chronic pain and depression are highly comorbid; however, the longitudinal link is only partially understood. This study examined direct and indirect effects of chronic back pain on depression using path analysis in a general population sample, focussing on cognitive mediator variables. Analyses are based on 413 participants (aged 18-75 years) in a population-based postal survey on back pain who reported chronic back pain at baseline. Follow-up data were collected after 1 year. Depression was measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Fear-avoidance-beliefs (FABQ), catastrophizing and helplessness/hopelessness (KRSS) were considered as cognitive mediators. Data were analyzed using path analysis. Chronic back pain had no direct effect on depression at follow-up when controlling for cognitive mediators. A mediating effect emerged for helplessness/hopelessness but not for catastrophizing or fear-avoidance beliefs. These results support the cognitive mediation hypothesis which assumes that psychological variables mediate the association between pain and depression. The importance of helplessness/hopelessness is of relevance for the treatment of patients with chronic back pain.

  18. Racial/Ethnic Disparities in Influenza Vaccination of Chronically Ill US Adults: The Mediating Role of Perceived Discrimination in Health Care.

    Science.gov (United States)

    Bleser, William K; Miranda, Patricia Y; Jean-Jacques, Muriel

    2016-06-01

    Despite well-established programs, influenza vaccination rates in US adults are well below federal benchmarks and exhibit well-documented, persistent racial and ethnic disparities. The causes of these disparities are multifactorial and complex, though perceived racial/ethnic discrimination in health care is 1 hypothesized mechanism. To assess the role of perceived discrimination in health care in mediating influenza vaccination RACIAL/ETHNIC disparities in chronically ill US adults (at high risk for influenza-related complications). We utilized 2011-2012 data from the Aligning Forces for Quality Consumer Survey on health and health care (n=8127), nationally representative of chronically ill US adults. Logistic regression marginal effects examined the relationship between race/ethnicity and influenza vaccination, both unadjusted and in multivariate models adjusted for determinants of health service use. We then used binary mediation analysis to calculate and test the significance of the percentage of this relationship mediated by perceived discrimination in health care. Respondents reporting perceived discrimination in health care had half the uptake as those without discrimination (32% vs. 60%, P=0.009). The change in predicted probability of vaccination given perceived discrimination experiences (vs. none) was large but not significant in the fully adjusted model (-0.185; 95% CI, -0.385, 0.014). Perceived discrimination significantly mediated 16% of the unadjusted association between race/ethnicity and influenza vaccination, though this dropped to 6% and lost statistical significance in multivariate models. The causes of persistent racial/ethnic disparities are complex and a single explanation is unlikely to be sufficient. We suggest reevaluation in a larger cohort as well as potential directions for future research.

  19. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling

    Directory of Open Access Journals (Sweden)

    Angelini Daniel J

    2013-01-01

    Full Text Available Abstract Background Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in explaining this differential response. Methods We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung. Results Chronic hypoxia increased both mean pulmonary artery pressure (mPAP and right ventricular (RV hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue. Conclusions The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.

  20. Chronic medical conditions and mental health in older people : disability and psychosocial resources mediate specific mental health effects

    NARCIS (Netherlands)

    Ormel, J; Kempen, GIJM; Penninx, BWJH; Brilman, EI; Beekman, ATF; VanSonderen, E

    1997-01-01

    Background. This study describes the differences in psychological distress, disability and psychosocial resources between types of major medical conditions and sensory impairments (collectively denoted as CMCs); and tests whether disability and psychosocial resources mediate CMC-specific mental heal

  1. Chronic medical conditions and mental health in older people : disability and psychosocial resources mediate specific mental health effects

    NARCIS (Netherlands)

    Ormel, J; Kempen, GIJM; Penninx, BWJH; Brilman, EI; Beekman, ATF; VanSonderen, E

    Background. This study describes the differences in psychological distress, disability and psychosocial resources between types of major medical conditions and sensory impairments (collectively denoted as CMCs); and tests whether disability and psychosocial resources mediate CMC-specific mental

  2. The presence of plasmid-mediated resistance genes among uropathogenes isolated from diabetic and non-diabetic patients with chronic pyelonephritis

    Directory of Open Access Journals (Sweden)

    O.I. Chub

    2016-08-01

    Full Text Available Increased multidrug resistance of extended-spectrum beta-lactamases (ESBLs compromises the efficacy of treatment of urinary tract infections. The objective of this study is to determine the prevalence of ESBL-producing uropathogens from patients with chronic pyelonephritis (CP and to evaluate the risk factors of these types of infections. Screening for the presence of plasmid-mediated ESBL was performed by polymerase chain reaction. Out of 105 patients, 22 (20.9% revealed strains with resistance genes: 11 (36.7%, 11 (36.7% and 8 (26.7% were identified to carry bla(TEM, bla(SHV and bla(CTX-M beta-lactamase genes, respectively. We have demonstrated that prevalence of the resistance among patients with CP combined with type 2 DM was 31.3%, while among patients with CP without type 2 DM was 27.4%; however the difference between these groups was not significant. The main factors related with appearance of plasmid-mediated resistance genes were age range above 55 years, Chronic Kidney Disease stage ІІІ and ІV, in-patient treatment history, history of using antibiotics last year. Isolation and detection of ESBL-producing strains are essential fоr the sеlection оf the mоst effеctive antibiоtic for the empiric trеatment.

  3. A novel ATM/TP53/p21-mediated checkpoint only activated by chronic γ-irradiation.

    Directory of Open Access Journals (Sweden)

    Lili Cao

    Full Text Available Different levels or types of DNA damage activate distinct signaling pathways that elicit various cellular responses, including cell-cycle arrest, DNA repair, senescence, and apoptosis. Whereas a range of DNA-damage responses have been characterized, mechanisms underlying subsequent cell-fate decision remain elusive. Here we exposed cultured cells and mice to different doses and dose rates of γ-irradiation, which revealed cell-type-specific sensitivities to chronic, but not acute, γ-irradiation. Among tested cell types, human fibroblasts were associated with the highest levels of growth inhibition in response to chronic γ-irradiation. In this context, fibroblasts exhibited a reversible G1 cell-cycle arrest or an irreversible senescence-like growth arrest, depending on the irradiation dose rate or the rate of DNA damage. Remarkably, when the same dose of γ-irradiation was delivered chronically or acutely, chronic delivery induced considerably more cellular senescence. A similar effect was observed with primary cells isolated from irradiated mice. We demonstrate a critical role for the ataxia telangiectasia mutated (ATM/tumor protein p53 (TP53/p21 pathway in regulating DNA-damage-associated cell fate. Indeed, blocking the ATM/TP53/p21 pathway deregulated DNA damage responses, leading to micronucleus formation in chronically irradiated cells. Together these results provide insights into the mechanisms governing cell-fate determination in response to different rates of DNA damage.

  4. Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.

    Science.gov (United States)

    Ghiassy, Bentolhoda; Rahimi, Nastaran; Javadi-Paydar, Mehrak; Gharedaghi, Mohammad Hadi; Norouzi-Javidan, Abbas; Dehpour, Ahmad R

    2017-01-01

    Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.

  5. The mediating role of cytokine IL-6 on the relationship of FEV1 upon 6-minute walk distance in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Baldi S

    2014-10-01

    Full Text Available Simonetta Baldi,1 Paul E Jose,2 Claudio Bruschi,1 Gian Domenico Pinna,3 Roberto Maestri,3 Antonella Rezzani,1 Ezio Bellinzona,1 Claudio Fracchia,1 Elena Dacosto,1 Paola Crotti,1 Silvia Montemartini1 1Department of Pneumology, Scientific Institute of Montescano, Salvatore Maugeri Foundation IRCCS, Montescano, Pavia, Italy; 2School of Psychology, Victoria University, Wellington, New Zealand; 3Department of Biomedical Engineering, Scientific Institute of Montescano, Salvatore Maugeri Foundation IRCCS, Montescano, Pavia, ItalyObjectives: To explore the mediating role of protein interleukin-6 (IL-6 on the relationship between forced expiratory volume in 1 second (FEV1 and 6-minute walk distance (6MWD and, further, to determine whether status variables (such as age, sex, and body mass index [BMI] operate as moderators of this mediation relationship.Design: Moderated mediation model.Setting: An inpatient pulmonary rehabilitation center in Italy.Participants: All 153 patients involved in the screening of a randomized controlled clinical trial (ClinicalTrials.gov identifier: NCT01253941 were included in this study. All patients were Global initiative for chronic Obstructive Lung Disease (GOLD stages I–IV and were aged 70.1±9.1 years.Measurements: At run-in phase of the protocol, clinical and functional screening included BMI, fasting plasma levels of protein (IL-6, spirometry, and standardized 6-minute walking test, measured at the start of the respiratory rehabilitation program.Methods: The size of the indirect effect of the initial variable (FEV1 upon the outcome variable (6MWD through the intervening variable (IL-6 was computed and tested for statistical significance. Moderated mediation analyses were subsequently conducted with age, sex, and BMI.Results: FEV1 averaged 53.4%±21.2%, and 6MWD 66.4%±41.3% of predicted. Median protein IL-6 was 6.68 pg/mL (interquartile range: 5.96. A bootstrapped mediation test supported the predicted indirect

  6. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction.

    Science.gov (United States)

    Kim, D-M; Leem, Y-H

    2016-06-02

    Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6 h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19 m/min, 1 h/day, 6 days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4 days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis: chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation?

    Directory of Open Access Journals (Sweden)

    Joseli Lannes-Vieira

    2003-04-01

    Full Text Available In Chagas disease, during the acute phase, the establishment of inflammatory processes is crucial for Trypanosoma cruzi control in target tissues and for the establishment of host/parasite equilibrium. However, in about 30% of the patients, inflammation becomes progressive, resulting in chronic disease, mainly characterized by myocarditis. Although several hypothesis have been raised to explain the pathogenesis of chagasic myocardiopathy, including the persistence of the parasite and/or participation of autoimmune processes, the molecular mechanisms underlying the establishment of the inflammatory process leading to parasitism control but also contributing to the maintenance of T. cruzi-elicited chronic myocarditis remain unsolved. Trying to shed light on these questions, we have for several years been working with murine models for Chagas disease that reproduce the acute self-resolving meningoencephalitis, the encephalitis resulting of reactivation described in immunodeficient individuals, and several aspects of the acute and chronic myocarditis. In the present review, our results are summarized and discussed under the light of the current literature. Furthermore, rational therapeutic intervention strategies based on integrin-mediated adhesion and chemokine receptor-driven recruitment of leukocytes are proposed to control T. cruzi-elicited unbalanced inflammation.

  8. Chronic loss of noradrenergic tone produces β-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens.

    Science.gov (United States)

    Gaval-Cruz, Meriem; Goertz, Richard B; Puttick, Daniel J; Bowles, Dawn E; Meyer, Rebecca C; Hall, Randy A; Ko, Daijin; Paladini, Carlos A; Weinshenker, David

    2016-01-01

    Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs.

  9. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Directory of Open Access Journals (Sweden)

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  10. Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of alcohol-related mortality in traumatic brain injury?

    Science.gov (United States)

    Lai, Xiao-ping; Yu, Xiao-jun; Qian, Hong; Wei, Lai; Lv, Jun-yao; Xu, Xiao-hu

    2013-01-01

    Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.

  11. Microbubble-mediated ultrasound promotes accumulation of bone marrow mesenchymal stem cell to the prostate for treating chronic bacterial prostatitis in rats.

    Science.gov (United States)

    Yi, Shanhong; Han, Guangwei; Shang, Yonggang; Liu, Chengcheng; Cui, Dong; Yu, Shuangjiang; Liao, Bin; Ao, Xiang; Li, Guangzhi; Li, Longkun

    2016-01-22

    Chronic bacterial prostatitis (CBP) is an intractable disease. Although bone marrow mesenchymal stem cells (BMMSCs) are able to regulate inflammation in CBP, the effect of microbubble-mediated ultrasound- induced accumulation of BMMSCs on CBP remains unclear. To address this gap, a model of CBP was established in SD rats, which were then treated with BMMSCs alone (BMMSC group), BMMSCs with ultrasound (ultrasound group), BMMSCs with microbubble-mediated ultrasound (MMUS group) and compared with a healthy control group. A therapeutic-ultrasound apparatus was used to treat the prostate in the presence of circulating microbubbles and BMMSCs. The BMMSC distribution was assessed with in vivo imaging, and the prostate structure with light microscopy. Real-time quantitative RT-PCR, ELISA, and immunohistochemistry were used to assess the expressions of TNF-α and IL-1β. More BMMSCs were found in the prostate in the MMUS group than in the CBP, ultrasound, and BMMSC groups. Inflammatory cell infiltration, fibrous tissue hyperplasia, and tumor-like epithelial proliferation were significantly reduced in the MMUS group, as were the mRNA and protein expressions of TNF-α and IL-1β. Microbubble-mediated ultrasound-induced accumulation of BMMSCs can inhibit inflammation and decrease TNF-α and IL-1β expressions in the prostate of CBP rats, suggesting that this method may be therapeutic for CPB.

  12. MicroRNA-mediated GABA Aα-1 receptor subunit down-regulation in adult spinal cord following neonatal cystitis-induced chronic visceral pain in rats.

    Science.gov (United States)

    Sengupta, Jyoti N; Pochiraju, Soumya; Pochiraju, Soumiya; Kannampalli, Pradeep; Bruckert, Mitchell; Addya, Sankar; Yadav, Priyanka; Miranda, Adrian; Shaker, Reza; Banerjee, Banani

    2013-01-01

    The nociceptive transmission under pathological chronic pain conditions involves transcriptional and/or translational alteration in spinal neurotransmitters, receptor expressions, and modification of neuronal functions. Studies indicate the involvement of microRNA (miRNA) - mediated transcriptional deregulation in the pathophysiology of acute and chronic pain. In the present study, we tested the hypothesis that long-term cross-organ colonic hypersensitivity in neonatal zymosan-induced cystitis is due to miRNA-mediated posttranscriptional suppression of the developing spinal GABAergic system. Cystitis was produced by intravesicular injection of zymosan (1% in saline) into the bladder during postnatal (P) days P14 through P16 and spinal dorsal horns (L6-S1) were collected either on P60 (unchallenged groups) or on P30 after a zymosan re-challenge on P29 (re-challenged groups). miRNA arrays and real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significant, but differential, up-regulation of mature miR-181a in the L6-S1 spinal dorsal horns from zymosan-treated rats compared with saline-treated controls in both the unchallenged and re-challenged groups. The target gene analysis demonstrated multiple complementary binding sites in miR-181a for GABA(A) receptor subunit GABA(Aα-1) gene with a miRSVR score of -1.83. An increase in miR-181a concomitantly resulted in significant down-regulation of GABA(Aα-1) receptor subunit gene and protein expression in adult spinal cords from rats with neonatal cystitis. Intrathecal administration of the GABA(A) receptor agonist muscimol failed to attenuate the viscero-motor response (VMR) to colon distension in rats with neonatal cystitis, whereas in adult zymosan-treated rats the drug produced significant decrease in VMR. These results support an integral role for miRNA-mediated transcriptional deregulation of the GABAergic system in neonatal cystitis-induced chronic pelvic pain. Copyright © 2012 International

  13. Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection

    Directory of Open Access Journals (Sweden)

    Anne Searls De Groot

    2014-10-01

    Full Text Available Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4+ and CD8+ T cells by stimulating regulatory T cells (Tregs educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a TCR-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses that cause acute infection. Furthermore, an HCV epitope that activates Tregs in chronically infected patients, but not clearers, shares a TCR-face with numerous human sequences. To boost weak CD4+ T cell responses associated with persistent infection, vaccines for HIV and HCV must circumvent potential Treg activation that can handicap efficacy. Epitope-driven approaches to vaccine design that involve careful consideration of the T cell subsets primed during immunization will advance HIV and HCV vaccine development.

  14. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems.

  15. Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

    Science.gov (United States)

    Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

    2016-01-01

    Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.

  16. Salivary inflammatory mediators and metalloproteinase 3 in patients with chronic severe periodontitis before and after periodontal phase I therapy

    OpenAIRE

    Reina, Silvia Lorena; Hoyos, Fernando; Carranza, Nelson; Borda, Enri Santiago

    2015-01-01

    The role of IL-1β, PGE2 and MMP-3 in the pathogenesis of periodontal disease is well researched. This study aimed to asses and compared the salivary IL-1β, PGE2 and MMP-3 levels in patients with untreated chronic severe periodontitis and those treated with periodontal phase I therapy and periodontally healthy individuals as controls, in relationship to the presence of salivary anti-β1 IgA. Fil: Reina, Silvia Lorena. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacolo...

  17. Salivary inflammatory mediators and metalloproteinase 3 in patients with chronic severe periodontitis before and after periodontal phase I therapy

    OpenAIRE

    Reina, Silvia Lorena; Hoyos, Fernando; Carranza, Nelson; Borda, Enri Santiago

    2015-01-01

    The role of IL-1β, PGE2 and MMP-3 in the pathogenesis of periodontal disease is well researched. This study aimed to asses and compared the salivary IL-1β, PGE2 and MMP-3 levels in patients with untreated chronic severe periodontitis and those treated with periodontal phase I therapy and periodontally healthy individuals as controls, in relationship to the presence of salivary anti-β1 IgA. Fil: Reina, Silvia Lorena. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacolo...

  18. The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Jun Shen

    2016-01-01

    Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.

  19. A new paradigm about HERV-K102 particle production and blocked release to explain cortisol mediated immunosenescence and age-associated risk of chronic disease.

    Science.gov (United States)

    Laderoute, Marian P

    2015-12-01

    The majority of chronic diseases in the aging adult are thought to relate to immune aging characterized by dominant immunosuppression and paradoxically, concomitant inflammation. This is known collectively as immunosenescence. The main change thought to be controlling immune aging is the age-related decline in dehydroepiandrosterone (DHEA) and corresponding increase in cortisol; the net effect which decreases the DHEA/cortisol ratio. Exactly how this translates to immunosuppression and concomitant inflammation remains unclear. Recently a new component of the human innate immune system has been discovered. Human endogenous retrovirus K102 (HERV-K102) is a replication-competent foamy retrovirus unique to humans which has been implicated in chronic diseases. Accumulating evidence suggests that HERV-K102 may defend the host against viral infections, as well as against breast and other cancers. Particles are produced in activated monocytes and released into vacuoles but do not bud through the cell surface. This renders macrophages foamy, while the release of particles is only through cell lysis. New evidence presented here suggests DHEA but not DHEA-S may specifically bind and inactivate alpha-fetoprotein (AFP). AFP is a well-established immunosuppressive factor which importantly, also blocks cell lysis induction in macrophages through the 67 kilodalton (kD) AFP receptor (AFPr). Here, it is proposed that a decreased DHEA/cortisol ratio may favor the accumulation of foamy macrophages reflecting the cortisol induction of HERV-K102 particle production concomitant with the blocked release of particles by secreted AFP. This is a new paradigm to explain how cortisol-mediated immunosenescence can result in the persistence of foamy macrophages, and how this relates to risk of chronic disease.

  20. HIF‑1 signaling pathway involving iNOS, COX‑2 and caspase‑9 mediates the neuroprotection provided by erythropoietin in the retina of chronic ocular hypertension rats.

    Science.gov (United States)

    Gui, Dongmei; Li, Yanfeng; Chen, Xiaolong; Gao, Dianwen; Yang, Yang; Li, Xun

    2015-02-01

    This study aimed to investigate the impacts of erythropoietin (EPO) on the electroretinogram b‑wave (ERG‑b), and on the mRNA and protein expression levels of hypoxia‑inducible factor‑1α (HIF‑1α), inducible nitric oxide synthase (iNOS), cyclooxygenase‑2 (COX‑2) and caspase‑9 in chronic ocular hypertension rats. Episcleral vein cauterization (EVC) was used to establish the chronic ocular hypertension rat model based on the intraocular pressure (IOP) value. ERG‑b and mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 in normal, EVC‑treated and EVC combined with EPO (EVC+EPO)‑treated rats were measured by electroretinography, RT‑PCR and western blotting, respectively. Moreover, the correlations of HIF‑1α with IOP, ERG‑b, iNOS, COX‑2 and caspase‑9 were evaluated. The mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 in EVC‑treated rats were increased significantly compared with normal rats. The peak expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 were respectively obtained 7, 7, 7 and 14 days postoperatively. Compared with EVC‑treated rats, EPO administration weakened the mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9. The mRNA expression level of HIF‑1α demonstrated a significant positive correlation with IOP and ERG‑b. HIF‑1α was positively correlated with iNOS, COX‑2 and caspase‑9 at the mRNA and protein levels. The protective effect of EPO on the retina of chronic ocular hypertension rats may be mediated by the HIF‑1 signaling pathway involving iNOS, COX‑2 and caspase‑9.

  1. Efficacy of a randomized controlled self-regulation based physical activity intervention for chronic fatigue: Mediation effects of physical activity progress and self-regulation skills.

    Science.gov (United States)

    Marques, M M; de Gucht, V; Leal, I; Maes, S

    2017-03-01

    Examine the medium-term effects of a brief physical activity (PA) self-regulation (SR) based intervention (4-STEPS program) for chronic fatigue, and explore the mediating effects of PA related variables and SR skills. A two-arm randomized controlled trial (Usual Care vs 4-STEPS) was carried out. The 4-STEPS program consisted of Motivational Interviewing and SR-skills training. Fatigue severity (primary outcome) and impact, PA, health-related quality of life (HrQoL), and somatic and psychological distress were assessed at baseline, post-treatment (12weeks) and 12months follow-up. Ninety-one patients (45 intervention and 46 controls) were included. At follow-up, there were significant treatment effects on fatigue severity (g=0.72) and fatigue impact, leisure-time PA, and physical and psychological HrQoL. No significant effects were found for number of daily steps and somatic and psychological distress. Fatigue severity at follow-up was partially mediated by post-treatment progress on a personal PA goal (effect ratio=18%). Results suggest that a brief intervention, focusing on the formulation and pursuit of personal PA goals and the use of SR skills, produces sustained benefits for fatigue severity. Despite these promising results, dropout was high and the intervention was not beneficial for all secondary outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema)-mediated by cancer cell production of PGE2?

    Science.gov (United States)

    Dehle, Francis C; Mukaro, Violet R; Jurisevic, Craig; Moffat, David; Ahern, Jessica; Hodge, Greg; Jersmann, Hubertus; Reynolds, Paul N; Hodge, Sandra

    2013-01-01

    In chronic obstructive pulmonary disease (COPD/emphysema) we have shown a reduced ability of lung and alveolar (AM) macrophages to phagocytose apoptotic cells (defective 'efferocytosis'), associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the airway. It is unknown whether this defect is present in cancer (no COPD) and if so, whether this results from soluble mediators produced by cancer cells. We investigated efferocytosis in AM (26 controls, 15 healthy smokers, 37 COPD, 20 COPD+ non small cell lung cancer (NSCLC) and 8 patients with NSCLC without COPD) and tumor and tumor-free lung tissue macrophages (21 NSCLC with/13 without COPD). To investigate the effects of soluble mediators produced by lung cancer cells we then treated AM or U937 macrophages with cancer cell line supernatant and assessed their efferocytosis ability. We qualitatively identified Arachidonic Acid (AA) metabolites in cancer cells by LC-ESI-MSMS, and assessed the effects of COX inhibition (using indomethacin) on efferocytosis. Decreased efferocytosis was noted in all cancer/COPD groups in all compartments. Conditioned media from cancer cell cultures decreased the efferocytosis ability of both AM and U937 macrophages with the most pronounced effects occurring with supernatant from SCLC (an aggressive lung cancer type). AA metabolites identified in cancer cells included PGE2. The inhibitory effect of PGE2 on efferocytosis, and the involvement of the COX-2 pathway were shown. Efferocytosis is decreased in COPD/emphysema and lung cancer; the latter at least partially a result of inhibition by soluble mediators produced by cancer cells that include PGE2.

  3. Defective lung macrophage function in lung cancer ± chronic obstructive pulmonary disease (COPD/emphysema-mediated by cancer cell production of PGE2?

    Directory of Open Access Journals (Sweden)

    Francis C Dehle

    Full Text Available In chronic obstructive pulmonary disease (COPD/emphysema we have shown a reduced ability of lung and alveolar (AM macrophages to phagocytose apoptotic cells (defective 'efferocytosis', associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the airway. It is unknown whether this defect is present in cancer (no COPD and if so, whether this results from soluble mediators produced by cancer cells. We investigated efferocytosis in AM (26 controls, 15 healthy smokers, 37 COPD, 20 COPD+ non small cell lung cancer (NSCLC and 8 patients with NSCLC without COPD and tumor and tumor-free lung tissue macrophages (21 NSCLC with/13 without COPD. To investigate the effects of soluble mediators produced by lung cancer cells we then treated AM or U937 macrophages with cancer cell line supernatant and assessed their efferocytosis ability. We qualitatively identified Arachidonic Acid (AA metabolites in cancer cells by LC-ESI-MSMS, and assessed the effects of COX inhibition (using indomethacin on efferocytosis. Decreased efferocytosis was noted in all cancer/COPD groups in all compartments. Conditioned media from cancer cell cultures decreased the efferocytosis ability of both AM and U937 macrophages with the most pronounced effects occurring with supernatant from SCLC (an aggressive lung cancer type. AA metabolites identified in cancer cells included PGE2. The inhibitory effect of PGE2 on efferocytosis, and the involvement of the COX-2 pathway were shown. Efferocytosis is decreased in COPD/emphysema and lung cancer; the latter at least partially a result of inhibition by soluble mediators produced by cancer cells that include PGE2.

  4. The association of headache frequency with pain interference and the burden of disease is mediated by depression and sleep quality, but not anxiety, in chronic tension type headache.

    Science.gov (United States)

    Palacios-Ceña, María; Fernández-Muñoz, Juan J; Castaldo, Matteo; Wang, Kelun; Guerrero-Peral, Ángel; Arendt-Nielsen, Lars; Fernández-de-Las-Peñas, César

    2017-12-01

    A better understanding of potential relationship between mood disorders, sleep quality, pain, and headache frequency may assist clinicians in determining optimal therapeutic programs. The aim of the current study was to analyze the effects of sleep quality, anxiety, depression on potential relationships between headache intensity, burden of headache, and headache frequency in chronic tension type headache (CTTH). One hundred and ninety-three individuals with CTTH participated. Headache features were collected with a 4-weeks headache diary. The Hospital Anxiety and Depression Scale was used for assessing anxiety and depression. Headache Disability Inventory evaluated the burden of headache. Pain interference was determined with the bodily pain domain (SF-36 questionnaire). Sleep quality was assessed with Pittsburgh Sleep Quality Index. Path analyses with maximum likelihood estimations were conducted to determine the direct and indirect effects of depression, anxiety, and sleep quality on the frequency of headaches. Two paths were observed: the first with depression and the second with sleep quality as mediators. Direct effects were noted from sleep quality, emotional burden of disease and pain interference on depression, and from depression to headache frequency. The first path showed indirect effects of depression from emotional burden and from sleep quality to headache frequency (first model R (2) = 0.12). Direct effects from the second path were from depression and pain interference on sleep quality and from sleep quality on headache frequency. Sleep quality indirectly mediated the effects of depression, emotional burden and pain interference on headache frequency (second model R (2) = 0.18). Depression and sleep quality, but not anxiety, mediated the relationship between headache frequency and the emotional burden of disease and pain interference in CTTH.

  5. Effects of Long-term Use of the Heat-clearing, Diuresis-promoting and Collateral-mediating Chinese Drugs on Changes of Proteinuria in Patients with Chronic Nephritis

    Institute of Scientific and Technical Information of China (English)

    Zou Xi; Xiong Ningning

    2006-01-01

    Purpose:To observe and evaluate the effects of long-term use of the heat-clearing,diuresis-promoting and collateral-mediating Chinese drugs on changes of proteinuria in patients with chronic nephritis,to analyze the influence of renal function,blood pressure,proteinuria and TCM syndrome types on therapeutic effects of the therapy,and to analyze the indications and effects of the heat-clearing,diuresis-promoting and collateral-mediating Chinese drugs when added with small dosage of Lei Gong year with the heat-clearing,diuresis-promoting and collateral-mediating Chinese drugs.Result:A one-year treatment showed obvious reduction of proteinuria in patients with chronic nephritis.Conclusions:1)The heat-clearing,diuresis-promoting and collateral-mediating Chinese drugs are effective for a long-term treatment of proteinuria in patients with chronic nephritis.2)Additional use of Lei Gong Teng can help control proteinuria.3)Damp-heat deeply accumulated in the kidney is one of the pathologic characteristics for chronic nephritis with the damp-heat syndrome.

  6. Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes involves AMPK-mediated energetic re-programming.

    Science.gov (United States)

    Martinez Marignac, Veronica L; Smith, Sarah; Toban, Nader; Bazile, Miguel; Aloyz, Raquel

    2013-12-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the western world. Although promising new therapies for this incurable disease are being tested in clinical trials, the therapeutic relevance of metabolic rewiring in chronic lymphocytic leukemia (CLL) is poorly understood. The aim of this study was to identify targetable metabolic differences in primary CLL lymphocytes by the use of Dasatinib. Dasatinib is a multi-tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML) and is being tested in clinical trials for several cancers including CLL. This drug has been shown to be beneficial to CML patients suffering from diabetes by reducing their glucose plasma levels. In keeping with this previous observation, we report that Dasatinib induced glucose use while reducing lactate production, suggesting that this tyrosine kinase inhibitor decreases aerobic glycolysis and shifts glucose use in primary CLL lymphocytes. Our results suggest that primary CLL lymphocytes (independently of traditional prognostic factors) can be stratified in two subsets by their sensitivity to Dasatinib in vitro. Increased glucose use induced by Dasatinib or by inhibition of mitochondrial respiration was not sufficient to sustain survival and ATP levels in CLL samples sensitive to Dasatinib. The two subsets of primary CLL lymphocytes are characterized as well by a differential dependency on mitochondrial respiration and the use of anabolic or catabolic processes to cope with induced metabolic/energetic stress. Differential metabolic reprogramming between subsets is supported by the contrasting effect on the survival of Dasatinib treated CLL lymphocytes with pharmacological inhibition of two master metabolic regulators (mTorc1 and AMPK) as well as induced autophagy. Alternative metabolic organization between subsets is further supported by the differential basal expression (freshly purified lymphocytes) of active AMPK, regulators of glucose metabolism and

  7. Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain.

    Science.gov (United States)

    Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A; Wang, Jun Ming

    2015-07-01

    Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex, and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus, or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase-3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage and

  8. Decreased apoptosis in advanced-stage/high-grade hepatocellular carcinoma complicating chronic hepatitis C is mediated through the downregulation of p21 ras

    Institute of Scientific and Technical Information of China (English)

    Nahed Baddour; Ebtehal Farrag; Ahmed Zeid; Essam Bedewy; Yousry Taher

    2013-01-01

    Objective and background:Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type Ⅰ,p21 ras has a different role in advanced stages,as it has been found to be downregulated.The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis.Material and methods:Thirty-five cases each of chronic HCV hepatitis type 4 (group Ⅰ) and cirrhosis with hepatocellular carcinoma (HCC) complicating chronic HCV hepatitis (groups Ⅱ and Ⅲ) were immunohistochemically evaluated using a p21 ras polyclonal antibody.The apoptotic index was determined in histologic sections using the terminal deoxynucleotidyl transferase-mediated d-UTP biotin nick end labeling (TUNEL) assay.Results:Significant differences (P=0.001) were detected in p21 ras protein expression between the three groups.A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases,and p21 ras expression was decreased in the HCC group.p21 ras expression correlated with stage (r=0.64,P=0.001) and grade (r=-0.65,P=0.001) in the HCC group and grade in the HCV group (r=0.44,P=0.008).Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs (P=0.01 each).The TUNEL values were negatively correlated with stage in the HCC group (r=-0.85,P=0.001).The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups (r=0.89,P=0.001 and r=-0.53,P=0.001,respectively).The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group (r=0.63,P=0.001) and HCV group (r=0.88,P=0.001).Conclusions:p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression,which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.

  9. Keratinocyte expression of inflammatory mediators plays a crucial role in substance P-induced acute and chronic pain

    Directory of Open Access Journals (Sweden)

    Wei Tzuping

    2012-07-01

    Full Text Available Abstract Tibia fracture in rats followed by cast immobilization leads to nociceptive, trophic, vascular and bone-related changes similar to those seen in Complex Regional Pain Syndrome (CRPS. Substance P (SP mediated neurogenic inflammation may be responsible for some of the signs of CRPS in humans. We therefore hypothesized that SP acting through the SP receptor (NK1 leads to the CRPS-like changes found in the rat model. In the present study, we intradermally injected rats with SP and monitored hindpaw mechanical allodynia, temperature, and thickness as well as tissue levels of tumor necrosis factor-α (TNF-α, interleukin 1β (IL-1β, interleukin 6 (IL-6, and nerve growth factor-β (NGF for 72 h. Anti-NGF antibody was utilized to block the effects of SP-induced NGF up-regulation. Fracture rats treated with the selective NK1 receptor antagonist LY303870 prior to cast removal were assessed for BrdU, a DNA synthesis marker, incorporation in skin cells to examine cellular proliferation. Bone microarchitecture was measured using micro computed tomography (μCT. We observed that: (1 SP intraplantar injection induced mechanical allodynia, warmth and edema as well as the expression of nociceptive mediators in the hindpaw skin of normal rats, (2 LY303870 administered intraperitoneally after fracture attenuated allodynia, hindpaw unweighting, warmth, and edema, as well as cytokine and NGF expression, (3 LY303870 blocked fracture-induced epidermal thickening and BrdU incorporation after fracture, (4 anti-NGF antibody blocked SP-induced allodynia but not warmth or edema, and (5 LY303870 had no effect on bone microarchitecture. Collectively our data indicate that SP acting through NK1 receptors supports the nociceptive and vascular components of CRPS, but not the bone-related changes.

  10. The power of food: mediating social relationships in the care of chronically ill elderly people in urban Indonesia

    Directory of Open Access Journals (Sweden)

    Peter van Eeuwijk

    2008-03-01

    Full Text Available La préparation de nourriture et de boissons est considérée comme une activité vitale dans les soins pour personnes âgées souffrant d’une maladie chronique en Indonésie urbaine. Seuls de proches membres de la famille préparent et servent les repas aux patients âgés. La majorité de ceux-ci prennent part aux repas quotidiens conjointement avec la famille qui représentent pour eux des arènes d’interaction sociale et une source d’informations essentielles. Le commensalisme et le fait que les personnes âgées continuent de participer au partage rituel de nourriture dans le cadre de festivités et de cérémonies sont ainsi des éléments importants pour la construction de leur identité sociale et leur inclusion dans la société. Néanmoins, beaucoup des patients âgés inclus dans cette étude étaient atteints de maladies chroniques – telles que l’hypertonie, le diabète et le rhumatisme – et nécessitant un suivi diététique. Ainsi la maladie change la qualité de la relation entre le personnel soignant et les patients âgés et dépendants en introduisant les notions de confiance et de contrôle. Le patient doit faire confiance au traitement spécial, c’est-à-dire au régime sain qui lui est proposé par l’aide soignante. Celle-ci, de son côté, exerce un pouvoir de contrôle en surveillant l’alimentation du malade et par là, le respect des mesures préventives et thérapeutiques qui lui sont imposées.The preparation of food and drink is regarded as pivotal to care of chronically sick elderly people in urban Indonesia. Their meals are cooked solely by close household members. The majority of the elderly sick take part in the joint daily meals that serve as important arenas of social interaction and information sources. Continued commensality and participation in the sharing of food during festivities and ceremonies thus represents a vital source of social identity and social involvement for older people

  11. STUDY ON VIBRATION SENSITIVITY DIFFERENT BODY AREAS IN PATIENTS WITH VIBRATION-INDUCER DISEASES EXPOSED TO A LOCAL VIBRATION AND IN PATIENTS WITH AN OCCUPATIONAL NEUROSENSORIC DULLNESS OF HEARING

    OpenAIRE

    Kartapoltseva, N.

    2008-01-01

    The pathological disorders in the state of the peripheral nerves based on the data of the vibration sensitivity studies were observed to be in both the patients with the vibration-induced diseases as a result of the local vibration exposure and in the patients with an occupational neurosensoric dullness of hearing. This may assume a total effect mechanism of the physical factors on the human organism. In the former case the alterations observedshowed a more pronounced character.

  12. The BH3-only protein Puma plays an essential role in p53-mediated apoptosis of chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Zhu, Hai-Jia; Liu, Ling; Fan, Lei; Zhang, Li-Na; Fang, Cheng; Zou, Zhi-Jian; Li, Jian-Yong; Xu, Wei

    2013-12-01

    The purpose of this study was to explore the characteristics and functions of BH3-only proteins Puma, Noxa and Bim in the prognosis, therapy and drug resistance of chronic lymphocytic leukemia (CLL). Puma, Noxa and Bim mRNAs were evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction, and correlations between their expression levels and CLL prognostic markers were analyzed. Primary CLL samples were treated in vitro with fludarabine to investigate the role of Puma, Noxa and Bim in the response to chemotherapeutic drugs which act through activation of the p53 pathway. We found that a low expression level of Puma was associated with some markers of poor prognosis. However, the level of Noxa or Bim was not different in patients with CLL with variant clinical features and prognostic factors. Puma expression was up-regulated after fludarabine treatment in primary CLL cells, but there was no significant difference for Noxa and Bim. Up-regulation of Puma occurred only in CLL cells with functional p53. CLL cells with p53 abnormalities were deficient in the activation of Puma by chemotherapeutics. These results suggest that a lack of Puma induction may contribute to the development of resistance to anticancer agents in CLL.

  13. Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress.

    Science.gov (United States)

    Han, Qiu-Qin; Yang, Liu; Huang, Hui-Jie; Wang, Ya-Lin; Yu, Rui; Wang, Jing; Pilot, Adam; Wu, Gen-Cheng; Liu, Qiong; Yu, Jin

    2017-01-01

    While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR) protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT), increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

  14. Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress

    Directory of Open Access Journals (Sweden)

    Qiu-Qin Han

    2017-05-01

    Full Text Available While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT, increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

  15. Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.

    Science.gov (United States)

    Ince, S; Avdatek, F; Demirel, H H; Arslan-Acaroz, D; Goksel, E; Kucukkurt, I

    2016-06-01

    Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100 mg l(-1) , approximately 1/50 of oral LD50 ) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg(-1) for 60 days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic-treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200 mg kg(-1) , reversed arsenic-induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic-induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats.

  16. B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways.

    Science.gov (United States)

    Allen, Jessica L; Fore, Matthew S; Wooten, Jenna; Roehrs, Philip A; Bhuiya, Nazmim S; Hoffert, Todd; Sharf, Andrew; Deal, Allison M; Armistead, Paul; Coghill, James; Gabriel, Don A; Irons, Robert; Essenmacher, Amber; Shea, Thomas C; Richards, Kristy; Cutler, Corey; Ritz, Jerome; Serody, Jonathan; Baldwin, Albert S; Sarantopoulos, Stefanie

    2012-09-20

    Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD). Patients with cGVHD have delayed B-cell reconstitution and elevated BAFF to B-cell ratios compared to patients without cGVHD. The mechanisms promoting and sustaining B-cell activation in this disease, however, remain unknown. As BAFF increases murine B-cell metabolism and survival and maintains autoreactive B-cell clones, we performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than 1 year from the time of allogeneic hematopoietic stem cell transplantation. We found that B cells from patients with active cGVHD were in a heightened metabolic state and were resistant to apoptosis. Exogenous BAFF treatment amplified cell size and survival in B cells from these patients. We found significantly increased signaling through ERK and AKT that associated with decreased levels of proapoptotic Bim, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. Thus, we identify a role for BAFF in the pathogenesis of cGVHD and define B-cell activation and survival pathways suitable for novel therapeutic development in cGVHD.

  17. Chronic pre-treatment with memantine prevents amyloid-beta protein-mediated long-term potentiation disruption

    Institute of Scientific and Technical Information of China (English)

    Fushun Li; Xiaowei Chen; Feiming Wang; Shujun Xu; Lan Chang; Roger Anwyl; Qinwen Wang

    2013-01-01

    Previous studies indicate that memantine, a low-affinity N-methyl-D-aspartate receptor antagonist, exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic effects and mechanisms of memantine were investigated further using electrophysiological methods. The results showed that 7-day intraperitoneal application of memantine, at doses of 5 mg/kg or 20 mg/kg, did not alter hippocampal long-term potentiation induction in rats, while 40 mg/kg memantine presented potent long-term potentiation inhibition. Then further in vitro studys were carried out in 5 mg/kg and 20 mg/kg memantine treated rats. We found that 20 mg/kg memantine attenuated the potent long-term potentiation inhibition caused by exposure to amyloid-β protein in the dentate gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-β protein triggered long-term potentiation inhibition to improve synaptic plasticity.

  18. Use of minimally invasive gingival biopsies in the study of inflammatory mediators expression and their correlation with gingival fluid in patients with chronic periodontitis

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    Karina Schittine Bezerra Lomba

    2015-01-01

    Full Text Available Background: There are no studies comparing the gingival crevicular fluid (GCF cytokines expression with its corresponding values from the same tissue′s sites. Such comparison might be of great value since most of the cytokine function is related to cell and/or tissue receptors. Aims: Our aim was to use minimally invasive biopsies to evaluate the expression of interferon-gamma, interleukin 1 (IL-1 β, IL-6, IL-17A, IL-17F, and their correlation with the expression in gingival fluid in patients with chronic periodontitis. Materials and Methods: The collection of gingival fluid comprised 22 samples from 11 patients (mean age 46.73 ± 10.16 standard deviation years with chronic periodontitis. The collection of biopsies comprised 22 samples from the same patients. Gingival fluid and biopsy were taken from the same site in one shallow and one deep site per patient. Gingival fluid samples were collected with periopaper ® and analyzed using Luminex ® . Biopsies were taken with a 2 mm diameter punch and analyzed for the same mediators using immunohistochemistry. Results: The gingival fluid showed higher amounts for IL-1-β in deep sites. Immunohistochemical markers were observed in the analyzed cells groups, both in deep and shallow sites, without significant differences between them. In the comparative analysis between immunohistochemical markers and GCF, IL-1-β showed high concordance in shallow and deep sites. Conclusions: The use of a standardized punch of 2 mm diameter for periodontal tissue biopsies seems to be suitable for immunohistochemistry analysis and showed that the GCF may not express all the markers in the same proportion at the corresponding tissue.

  19. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet

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    Chao Kang

    2017-05-01

    Full Text Available Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI responsible for the development of obesity. Capsaicin (CAP is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA measurements, and phylogenetic reconstruction of unobserved states (PICRUSt analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS-producing family S24_7. Predicted function analysis (PICRUSt showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1 by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.

  20. Novel X-linked inhibitor of apoptosis inhibiting compound as sensitizer for TRAIL-mediated apoptosis in chronic lymphocytic leukaemia with poor prognosis.

    Science.gov (United States)

    Frenzel, Lukas P; Patz, Michaela; Pallasch, Christian P; Brinker, Reinhild; Claasen, Julia; Schulz, Alexandra; Hallek, Michael; Kashkar, Hamid; Wendtner, Clemens-Martin

    2011-01-01

    Given that aggressive DNA damaging chemotherapy shows suboptimal efficacy in chronic lymphocytic leukaemia (CLL), alternative therapeutic approaches are needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce tumour-specific apoptosis. However, apoptosis might be inhibited by elevated levels of X-linked inhibitor of apoptosis (XIAP). Use of XIAP-inhibiting compounds might sensitize primary CLL cells towards TRAIL-mediated apoptosis. A novel small molecule, compound A (CA), an inhibitor of XIAP, was used in combination with TRAIL to induce apoptosis in primary CLL cells (n = 48). XIAP was significantly more highly expressed in primary CLL cells (n = 28) compared to healthy B cells (n = 16) (P = 0·02). Our data obtained by specific knock-down of XIAP by siRNA identified XIAP as the key factor conferring resistance to TRAIL in CLL. Combined treatment with CA/TRAIL significantly increased apoptosis compared to untreated (P = 8·5 × 10⁻¹⁰), solely CA (P = 4·1 × 10⁻¹²) or TRAIL treated (P = 4·8 × 10⁻¹⁰) CLL cells. CA rendered 40 of 48 (83·3%) primary CLL samples susceptible to TRAIL-mediated apoptosis. In particular, cells derived from patients with poor prognosis CLL (ZAP-70(+) , IGHV unmutated, 17p-) were highly responsive to this drug combination. Our highly-effective XIAP inhibitor CA, in concert with TRAIL, shows potential for the treatment of CLL cases with poor prognosis and therefore warrants further clinical investigation.

  1. A novel gain-of-function STAT1 mutation resulting in basal phosphorylation of STAT1 and increased distal IFN-γ-mediated responses in chronic mucocutaneous candidiasis.

    Science.gov (United States)

    Martinez-Martinez, Laura; Martinez-Saavedra, Maria Teresa; Fuentes-Prior, Pablo; Barnadas, Maria; Rubiales, Maria Victoria; Noda, Judith; Badell, Isabel; Rodríguez-Gallego, Carlos; de la Calle-Martin, Oscar

    2015-12-01

    Gain-of-function STAT1 mutations have recently been associated with autosomal dominant chronic mucocutaneous candidiasis (CMC). The purpose of this study was to characterize the three members of a non-consanguineous family, the father and his two sons, who presented with recurrent oral thrush and ocular candidiasis since early childhood. The three patients had reduced levels of IL-17-producing T cells. This reduction affected specifically IL-17(+)IFN-γ(-) T cells, because the levels of IL-17(+)IFN-γ(+) T cells were similar to controls. We found that PBMC (peripheral blood mononuclear cells) from the patients did not respond to Candida albicans ex vivo. Moreover, after polyclonal activation, patients' PBMC produced lower levels of IL-17 and IL-6 and higher levels of IL-4 than healthy controls. Genetic analyses showed that the three patients were heterozygous for a new mutation in STAT1 (c.894A>C, p.K298N) that affects a highly conserved residue of the coiled-coil domain of STAT1. STAT1 phosphorylation levels were significantly higher in patients' cells than in healthy controls, both in basal conditions and after IFN-γ stimulation, suggesting a permanent activation of STAT1. Cells from the patients also presented increased IFN-γ-mediated responses measured as MIG and IP-10 production. In conclusion, we report a novel gain-of-function mutation in the coiled-coil domain of STAT1, which increases STAT1 phosphorylation and impairs IL-17-mediated immunity. The mutation is responsible for CMC in this family with autosomal dominant inheritance of the disease.

  2. Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Th1 cell-mediated immune response.

    Science.gov (United States)

    Whary, M T; Morgan, T J; Dangler, C A; Gaudes, K J; Taylor, N S; Fox, J G

    1998-07-01

    Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-gamma) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-gamma in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected with Helicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response to H. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.

  3. Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

    Science.gov (United States)

    Yang, Fu-Qiang; Rao, Gui-Rong; Wang, Gui-Qiang; Li, Yue-Qi; Xie, Yao; Zhang, Zhan-Qing; Deng, Cun-Liang; Mao, Qing; Li, Jun; Zhao, Wei; Wang, Mao-Rong; Han, Tao; Chen, Shi-Jun; Pan, Chen; Tan, De-Ming; Shang, Jia; Zhang, Ming-Xiang; Zhang, Yue-Xin; Yang, Ji-Ming; Chen, Guang-Ming

    2017-01-01

    AIM To assess the efficacy and safety of in vivo electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, n = 109) or LAM + placebo (control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12 (start of treatment with vaccine or placebo, SOT), 16, 24, and 36 (end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir (ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeAg seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy. PMID:28127204

  4. Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats.

    Science.gov (United States)

    Zhang, Ning; Hu, Yan; Ding, Chunchun; Zeng, Wenjing; Shan, Wen; Fan, Hui; Zhao, Yan; Shi, Xue; Gao, Lili; Xu, Ting; Wang, Ruiwen; Gao, Dongyan; Yao, Jihong

    2017-02-05

    Salvianolic acid B (SalB), a water-soluble polyphenol extracted from Radix Salvia miltiorrhiza, has been reported to possess many pharmacological activities. This study investigated the hepatoprotective effects of SalB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels. Moreover, SalB treatment ameliorated ethanol-induced hepatic inflammation by decreasing the levels of hepatotoxic cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Importantly, SalB pretreatment significantly increased the expression of SIRT1 and downregulated the expression of inflammatory mediator C-reactive protein (CRP) and lipoprotein carbohydrate response element-binding protein (ChREBP). In vitro, SalB significantly reversed ethanol-induced down-regulation of SIRT1 and increased CRP and ChREBP expression. Interestingly, the effects of SalB on SIRT1, CRP and ChREBP were mostly abolished by treatment with either SIRT1 siRNA or EX527, a specific inhibitor of SIRT1, indicating that SalB decreased CRP and ChREBP expression by activating SIRT1. SalB exerted anti-steatotic and anti-inflammatory effects against alcoholic liver injury by inducing SIRT1-mediated inhibition of CRP and ChREBP expression.

  5. The antinociceptive effects of JWH-015 in chronic inflammatory pain are produced by nitric oxide-cGMP-PKG-KATP pathway activation mediated by opioids.

    Directory of Open Access Journals (Sweden)

    Roger Negrete

    , triggered by NOS1 and mediated by endogenous opioids. These findings suggest that the activation of this pathway might be an interesting therapeutic target for the treatment of chronic inflammatory pain with cannabinoids.

  6. Curcumin induces ABCA1 expression and apolipoprotein A-I-mediated cholesterol transmembrane in the chronic cerebral hypoperfusion aging rats.

    Science.gov (United States)

    Tian, Mingyuan; Zhang, Xiong; Wang, Linhui; Li, Yu

    2013-01-01

    Cerebral hypoperfusion or aging often results in the disturbances of cholesterol and lipoprotein, which have been well depicted as a common pathological status contributing to neurodegenerative diseases such as vascular dementia (VaD) and Alzheimer's dementia (AD). The pathway of the liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. Curcumin, a kind of phenolic compound, has been widely used. It has been reported that curcumin can reduce the levels of cholesterol in serum, but the underlying mechanisms are poorly understood. In this study, we evaluated the effects of curcumin on the cholesterol level in brain, vascular cognitive impairment and explored whether the mechanisms for those effects are through activating LXR-β/RXR-α and ABCA1 expression and apoA-I. With a Morris water test, we found that curcumin treatment could attenuate cognitive impairment. With HE and Nissl staining, we found that curcumin could significantly ameliorate the abnormal changes of pyramidal neurons. Meanwhile, the expression of LXR-β, RXR-α, ABCA1 and apoA-I mRNA and protein were increased in a dose-dependent manner after curcumin treatment. Interestingly, both serum HDL cholesterol and total cholesterol levels were statistically higher in the curcumin treatment group than those other groups. We conclude that curcumin has the ability to activate permissive LXR-β/RXR-α signaling and thereby modulate ABCA1 and apoA-I-mediated cholesterol transmembrane transportation, which is a new preventive and therapeutic strategy for cerevascular diseases.

  7. Effect of room temperature on tests for diagnosing vibration-induced white finger: finger rewarming times and finger systolic blood pressures.

    Science.gov (United States)

    Ye, Ying; Griffin, Michael J

    2017-08-01

    This study investigates the effects of room temperature on two standard tests used to assist the diagnosis of vibration-induced white finger (VWF): finger rewarming times and finger systolic blood pressures. Twelve healthy males and twelve healthy females participated in four sessions to obtain either finger skin temperatures (FSTs) during cooling and rewarming of the hand or finger systolic blood pressures (FSBPs) after local cooling of the fingers to 15 and 10 °C. The measures were obtained with the room temperature at either 20 or 28 °C. There were lower baseline finger skin temperatures, longer finger rewarming times, and lower finger systolic blood pressures with the room temperature at 20 than 28 °C. However, percentage reductions in FSBP at 15 and 10 °C relative to 30 °C (i.e. %FSBP) did not differ between the two room temperatures. Females had lower baseline FSTs, longer rewarming times, and lower FSBPs than males, but %FSBPs were similar in males and females. Finger rewarming times after cold provocation are heavily influenced by room temperature and gender. For evaluating peripheral circulatory function using finger rewarming times, the room temperature must be strictly controlled, and a different diagnostic criterion is required for females. The calculation of percentage changes in finger systolic blood pressure at 15 and 10 °C relative to 30 °C reduces effects of both room temperature and gender, and the test may be used in conditions where the ±1 °C tolerance on room temperature required by the current standard cannot be achieved.

  8. Blunted inflammation mediated by NF-κB activation in hippocampus alleviates chronic normobaric hypoxia-induced anxiety-like behavior in rats.

    Science.gov (United States)

    Fan, Junming; Fan, Xiaofang; Li, Yang; Guo, Jinbin; Xia, Dongmei; Ding, Lu; Zheng, Qingqing; Wang, Wei; Xue, Feng; Chen, Ran; Liu, Shouting; Hu, Lianggang; Gong, Yongsheng

    2016-04-01

    This study aims to investigate whether inflammation mediated by NF-κB activation is involved in the induction of anxiety-like behavior in chronic normobaric hypoxia (CNH) exposed rats and to investigate the underlying mechanism. To this end, rats were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO2) of ∼ 10%, 23 h/d, continues for 2 weeks. Anxiety-like behavior was tested by elevated plus maze and open field, inflammatory response, nucleus translocation of NF-κB, and signaling pathway in hippocampus were examined. CNH induced a significant increase of anxiety- like behavior and inflammation responses, which were ameliorated by NF-κB inhibitor, PDTC pretreatment, suggesting that the anxiogenic effect induced by inflammation is through NF-κB activation. CNH treatment significantly increased nucleus translocation of p65 and p105 in hippocampus, which was suppressed by PDTC pretreatment. In addition, CNH treatment significantly increased Iba-1, iNOS, COX-2, and p-PKA in hippocampus, which were blocked by PDTC pretreatment, suggesting CNH may activate microglia cells in hippocampus through NF-κB pathway. In conclusion, our results illustrate a mechanism that, activation of NF-κB in hippocampus may trigger the proinflammatory response of microglia cells, and iNOS-PKA pathway may involve in anxiogenic effect in CNH exposed rats.

  9. Anti-inflammatory/regulatory cytokine microenvironment mediated by IL-4 and IL-10 coordinates the immune response in hemophilia A patients infected chronically with hepatitis C virus.

    Science.gov (United States)

    Pimentel, João Paulo; Chaves, Daniel Gonçalves; Araújo, Ana Ruth Silva; de Araújo, Erbênia Maria Martins; da Silva Fraporti, Liziara; Neves, Walter Luiz Lima; Tarragô, Andrea Monteiro; Torres, Katia Luz; Gentz, Solange Henschke Lima; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana

    2013-06-01

    In the past decades patients with hemophilia were infected commonly by hepatitis C virus (HCV) and a significant number of patients are infected chronically. Focusing on the role of the immune system for controlling and or maintaining HCV infection, the leukocyte and cytokine profiles of peripheral blood from hemophilia A patients and other patients with and without HCV infection were studied. The results demonstrated that hemophilia A is characterized by a general state of circulating leukocytes activation along with an overall increase in the frequency of IL-6 and IL-10 with decrease of IL-8 and IL-12. HCV infection of patients with hemophilia A does not influence further the activation state of circulating leukocytes but is accompanied by lower levels of alanine transaminase (ALT) and a prominent anti-inflammatory/regulatory serum cytokine pattern, mediated by IL-4 and IL-10. Additionally, the results demonstrated that hemophilia A patients infected with HCV displaying No/Low antibody response to C33c and C22 have significant lower viral load and higher serum levels of IL-12 and IL-4. This finding suggests that the differential RIBA reactivity to C33c/C22 HCV core proteins may have a putative value as a prognostic biomarker for the infection in hemophilia A patients.

  10. Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.

    Science.gov (United States)

    Kang, Chao; Wang, Bin; Kaliannan, Kanakaraju; Wang, Xiaolan; Lang, Hedong; Hui, Suocheng; Huang, Li; Zhang, Yong; Zhou, Ming; Chen, Mengting; Mi, Mantian

    2017-05-23

    Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of

  11. MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation.

    Science.gov (United States)

    Iwasaki, Kenta; Yamamoto, Takayuki; Inanaga, Yukiko; Hiramitsu, Takahisa; Miwa, Yuko; Murotani, Kenta; Narumi, Shuji; Watarai, Yoshihiko; Katayama, Akio; Uchida, Kazuharu; Kobayashi, Takaaki

    2017-02-01

    De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p biomarkers to evaluate immune response and kidney allograft status.

  12. Relative contributions of parent substance use and childhood maltreatment to chronic homelessness, depression, and substance abuse problems among homeless women: mediating roles of self-esteem and abuse in adulthood.

    Science.gov (United States)

    Stein, Judith A; Leslie, Michelle Burden; Nyamathi, Adeline

    2002-10-01

    This study, using latent variable methodology, explores simultaneously the relative effects of childhood abuse and early parental substance abuse on later chronic homelessness, depression, and substance abuse problems in a sample of homeless women. We also examine whether self-esteem and recent violence can serve as mediators between the childhood predictors and the dysfunctional outcomes. The sample consists of 581 homeless women residing in shelters or sober living centers in Los Angeles (54% African-American, 23% Latina, 22% White, mean age=33.5 years). Multiple-indicator latent variables served as predictors and outcomes in structural models. Childhood abuse was indicated by sexual, physical, and verbal abuse. Childhood abuse directly predicted later physical abuse, chronic homelessness, depression, and less self-esteem. Parent substance use directly predicted later substance use problems among the women. Recent physical abuse predicted chronic homelessness, depression, and substance use problems. Greater self-esteem predicted less depression and fewer substance use problems. Childhood abuse also had significant indirect effects on depression, chronic homelessness, and drug and alcohol problems mediated through later physical abuse and self-esteem. Although there was a strong relationship between childhood abuse and parent drug use, childhood abuse was the more pervasive and devastating predictor of dysfunctional outcomes. Childhood abuse predicted a wider range of problems including lower self-esteem, more victimization, more depression, and chronic homelessness, and indirectly predicted drug and alcohol problems. The mediating roles of recent physical abuse and self-esteem suggest salient leverage points for change through empowerment training and self-esteem enhancement in homeless women.

  13. TNF-α type 2 receptor mediates renal inflammatory response to chronic angiotensin II administration with high salt intake in mice.

    Science.gov (United States)

    Singh, Purnima; Bahrami, Laleh; Castillo, Alexander; Majid, Dewan S A

    2013-04-01

    Tumor necrosis factor-alpha (TNF-α) has been implicated in salt-sensitive hypertension and renal injury (RI) induced by angiotensin II (ANG II). To determine the receptor type of TNF-α involved in this mechanism, we evaluated the responses to chronic ANG II infusion (25 ng/min by implanted minipump) given with high-salt diet (HS; 4% NaCl) for 2 wk in gene knockout mice for TNF-α receptor type 1 (TNFR1KO; n = 6) and type 2 (TNFR2KO; n = 6) and compared the responses with those in wild-type (WT; C57BL/6; n = 6) mice. Blood pressure in these mice was measured by implanted radiotelemetry as well as by tail-cuff plethysmography. RI responses were assessed by measuring macrophage cell infiltration (CD68(+) immunohistochemistry), glomerulosclerosis (PAS staining), and interstitial fibrosis (Gomori's trichrome staining) in renal tissues at the end of the treatment period. The increase in mean arterial pressure induced by ANG II + HS treatment was not different in these three groups of mice (TNFR1KO, 114 ± 1 to 161 ± 7 mmHg; TNFR2KO, 113 ± 1 to 161 ± 3 mmHg; WT, 110 ± 3 to 154 ± 3 mmHg). ANG II + HS-induced RI changes were similar in TNFR1KO mice but significantly less in TNFR2KO mice (macrophage infiltration, 0.02 ± 0.01 vs. 1.65 ± 0.45 cells/mm(2); glomerulosclerosis, 26.3 ± 2.6 vs. 35.7 ± 2.2% area; and interstitial fibrosis, 5.2 ± 0.6 vs. 8.1 ± 1.1% area) compared with the RI changes in WT mice. The results suggest that a direct activation of TNF-α receptors may not be required in inducing hypertensive response to chronic ANG II administration with HS intake, but the induction of inflammatory responses leading to renal injury are mainly mediated by TNF-α receptor type 2.

  14. Robust and enduring atorvastatin-mediated memory recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

    Science.gov (United States)

    Zaghi, Gislene Gonçalves Dias; Godinho, Jacqueline; Ferreira, Emilene Dias Fiuza; Ribeiro, Matheus Henrique Dal Molin; Previdelli, Isolde Santos; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

    2016-02-01

    Chronic cerebral hypoperfusion (CCH) is a common condition associated with the development and/or worsening of age-related dementia.We previously reported persistent memory loss and neurodegeneration after CCH in middle-aged rats. Statin-mediated neuroprotection has been reported after acute cerebral ischemia. Unknown, however, is whether statins can alleviate the outcome of CCH. The present study investigated whether atorvastatin attenuates the cognitive and neurohistological outcome of CCH. Rats (12–15 months old) were trained in a non-food-rewarded radial maze, and then subjected to CCH. Atorvastatin (10 mg/kg, p.o.) was administered for 42 days or 15 days, beginning 5 h after the first occlusion stage. Retrograde memory performance was assessed at 7, 14, 21, 28, and 35 days of CCH, and expressed by “latency,” “number of reference memory errors” and “number of working memory errors.” Neurodegeneration was then examined at the hippocampus and cerebral cortex. Compared to sham, CCH caused profound and persistent memory loss in the vehicle-treated groups, as indicated by increased latency (91.2% to 107.3%) and number of errors (123.5% to 2508.2%), effects from which the animals did not spontaneously recover across time. This CCH-induced retrograde amnesia was completely prevented by atorvastatin (latency: −4.3% to 3.3%; reference/working errors: −2.5% to 45.7%), regardless of the treatment duration. This effect was sustained during the entire behavioral testing period (5 weeks), even after discontinuing treatment. This robust and sustained memory-protective effect of atorvastatin occurred in the absence of neuronal rescue (39.58% to 56.45% cell loss). We suggest that atorvastatin may be promising for the treatment of cognitive sequelae associated with CCH.

  15. JAK-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer.

    Science.gov (United States)

    Lu, Chunwan; Talukder, Asif; Savage, Natasha M; Singh, Nagendra; Liu, Kebin

    2017-01-01

    Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration. JAK-STAT inhibitor Ruxolitinib selectively inhibits STAT1 and STAT3 activation and increases CTL infiltration to induce a Tc1/Th1 immune response in the tumor microenvironment in an orthotopic pancreatic cancer mouse model. Ruxilitinib-mediated tumor suppressive efficacy diminishes in T-cell-deficient mice. Pancreatic tumor grows significantly faster in IFNγ-deficient mice. However, neutralizing IFNγ does not alter tumor growth but diminishes Ruxolitinib-induced tumor suppression in vivo, indicating that lymphocytes and IFNγ are essential for Ruxolitinib-induced host antitumor immune response. Both type I and type II interferons upregulate PD-L1 expression through the JAK-STAT signaling pathway in mouse pancreatic tumor cells. Tumor cells respond to activated T cells by activating STAT3. The inhibition of STAT3 downregulates immune suppressive cytokines production by tumor cells, resulting in increased T cell activation and effector function. Consequently, Ruxolitinib significantly improves the efficacy of anti-PD-1 immunotherapy. Our data demonstrate that Ruxolitinib is effective in the inhibition of systemic inflammation in the tumor microenvironment and therefore upregulates CTL infiltration and activation to overcome pancreatic cancer resistance to anti-PD-1 immunotherapy.

  16. Transcription factor FoxO1, the dominant mediator of muscle wasting in chronic kidney disease, is inhibited by microRNA-486.

    Science.gov (United States)

    Xu, Jing; Li, Rongshan; Workeneh, Biruh; Dong, Yanlan; Wang, Xiaonan; Hu, Zhaoyong

    2012-08-01

    Chronic kidney disease (CKD) accelerates muscle protein degradation by stimulating the ubiquitin proteasome system through activation of the E3 ligases, Atrogin-1/MAFbx and MuRF-1. Forkhead transcription factors (FoxOs) can control the expression of these E3 ligases, but the contribution of individual FoxOs to muscle wasting is unclear. To study this we created mice with a muscle-specific FoxO1 deletion. The absence of FoxO1 blocked 70% of the increase in E3 ligase induction by CKD as well as the proteolysis and loss of muscle mass. Thus, FoxO1 has a role in controlling ubiquitin proteasome system-related proteolysis. As microRNA (miR)-486 reportedly dampens FoxO1 expression and its activity,we transfected a miR-486 mimic into primary cultures of myotubes and found this blocked dexamethasone-stimulated protein degradation without influencing protein synthesis.It also decreased FoxO1 protein translation and increased FoxO1 phosphorylation by downregulation of PTEN phosphatase, a negative regulator of p-Akt. To test its efficacy in vivo, we electroporated miR-486 into muscles and found that the expression of the E3 ligases was suppressed and muscle mass increased despite CKD. Thus, FoxO1 is a dominant mediator of CKD-induced muscle wasting, and miR-486 coordinately decreases FoxO1 and PTEN to protect against this catabolic response.

  17. The Effect of Combination Therapy with Rituximab and Intravenous Immunoglobulin on the Progression of Chronic Antibody Mediated Rejection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Gun Hee An

    2014-01-01

    Full Text Available The treatment for chronic active antibody-mediated rejection (CAMR remains controversial. We investigated the efficacy of rituximab (RTX and intravenous immunoglobulin (IVIg for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2 and IVIg (0.4 g/kg for 4 days. The efficacy of RTX/IVIg combination therapy (RIT was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18, and overall ΔeGFR decreased significantly to 0.4± 1.7 mL·min−1·1.73 m−2 per month 6 months after RIT compared to that observed 6 months before RIT (1.8±1.0, P<0.05. Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5±2.5 versus 7.0±3.5 protein/creatinine (g/g, P<0.001. The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT.

  18. The relationship between perceived promotion of autonomy/dependence and pain-related disability in older adults with chronic pain: the mediating role of self-reported physical functioning.

    Science.gov (United States)

    Matos, Marta; Bernardes, Sónia F; Goubert, Liesbet

    2016-08-01

    Chronic pain is prevalent among older adults and is usually associated with high levels of functional disability. Social support for the promotion of functional autonomy and dependence has been associated with pain-related disability and self-reported physical functioning. Nevertheless, these relationships need further inquiry. Our aims were to investigate: (1) the relationship between perceived promotion of autonomy/dependence and pain-related disability and (2) the extent to which self-reported physical functioning mediated these relationships. 118 older adults (Mage = 81.0) with musculoskeletal chronic pain completed the Portuguese versions of the revised formal social support for Autonomy and Dependence in Pain Inventory, the pain severity and interference scales of the Brief Pain Inventory, and the physical functioning scale of the Medical Outcomes Study-Short-Form 36 v2. Higher levels of perceived promotion of autonomy were associated with lower pain-related disability; this relationship was partially mediated by self-reported physical functioning (B = -.767, p autonomy and dependence for managing older adults' experience of chronic pain.

  19. The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

    Directory of Open Access Journals (Sweden)

    Marriott Nliwasa

    Full Text Available Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence.To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy.Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard, and costs were estimated.Of 273 adults recruited, 44.3% (121/273 were HIV-positive and 19.4% (53/273 had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4% with 100% (95% CI: 98.0% to 100% specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2% was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8% was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98; this was lower than Xpert® MTB/RIF (US$ 13.38 but higher than fluorescence smear microscopy (US$ 0.65.The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

  20. CaV3.2 T-type Ca2+ channels mediate the augmented calcium influx in carotid body glomus cells by chronic intermittent hypoxia.

    Science.gov (United States)

    Makarenko, Vladislav V; Ahmmed, Gias U; Peng, Ying-Jie; Khan, Shakil A; Nanduri, Jayasri; Kumar, Ganesh K; Fox, Aaron P; Prabhakar, Nanduri R

    2016-01-01

    Chronic intermittent hypoxia (CIH) is a hallmark manifestation of sleep apnea. A heightened carotid body activity and the resulting chemosensory reflex mediate increased sympathetic nerve activity by CIH. However, the mechanisms underlying heightened carotid body activity by CIH are not known. An elevation of intracellular calcium ion concentration ([Ca(2+)]i) in glomus cells, the primary oxygen-sensing cells, is an essential step for carotid body activation by hypoxia. In the present study, we examined the effects of CIH on the glomus cell [Ca(2+)]i response to hypoxia and assessed the underlying mechanisms. Glomus cells were harvested from adult rats or wild-type mice treated with 10 days of either room air (control) or CIH (alternating cycles of 15 s of hypoxia and 5 min of room air; 9 episodes/h; 8 h/day). CIH-treated glomus cells exhibited an enhanced [Ca(2+)]i response to hypoxia, and this effect was absent in the presence of 2-(4-cyclopropylphenyl)-N-((1R)-1-[5-[(2,2,2-trifluoroethyl)oxo]-pyridin-2-yl]ethyl)acetamide (TTA-A2), a specific inhibitor of T-type Ca(2+) channels, and in voltage-gated calcium channel, type 3.2 (CaV3.2), null glomus cells. CaV3.2 knockout mice exhibited an absence of CIH-induced hypersensitivity of the carotid body. CIH increased reactive oxygen species (ROS) levels in glomus cells. A ROS scavenger prevented the exaggerated TTA-A2-sensitive [Ca(2+)]i response to hypoxia. CIH had no effect on CaV3.2 mRNA levels. CIH augmented Ca(2+) currents and increased CaV3.2 protein in plasma membrane fractions of human embryonic kidney-293 cells stably expressing CaV3.2, and either a ROS scavenger or brefeldin-A, an inhibitor of protein trafficking, prevented these effects. These findings suggest that CIH leads to an augmented Ca(2+) influx via ROS-dependent facilitation of CaV3.2 protein trafficking to the plasma membrane.

  1. Illness representations as mediators of the relationship between dispositional optimism and depression in patients with chronic tinnitus: A cross-sectional study.

    NARCIS (Netherlands)

    Vollmann, Manja; Scharloo, Margreet; Langguth, Berthold; Kalkouskaya, Natallia; Salewski, Christel

    2014-01-01

    Objective: Both dispositional optimism and illness representations are related to psychological health in chronic patients. In a group of chronic tinnitus sufferers, the interplay between these two variables was examined. Specifically, it was tested to what extent the relationship between dispositio

  2. 重车运行引起的周边建筑振动实测与分析%In situ experiment and analysis of building vibration induced by heavy trucks transit

    Institute of Scientific and Technical Information of China (English)

    吴小波

    2011-01-01

    根据现场实测数据,对重车运行引起的周边建筑振动实况和振动特性进行了分析研究.结果表明,地面振动Z振级主要由测点到道路中心的水平距离决定,在距线路一定距离时,车辆的载重对地质点振动的影响为非敏感因素.重车运行对结构虽不易构成安全影响,但对邻近建筑物的振动影响常造成环境振动污染问题.%The features of the environmental vibration induced by heavy trucks transit are studied by in situ experimental method.The analysis results suggest that the degree Z direction environmental vibration is controlled by the level distance from road, and at certain distance away from road, the weight of the trucks is the insensitive factors for environmental vibration.It is not easy to induce the near building damage by the environmental vibration induced by heavy trucks transit,but it must be attention for the effects of the pollution of environmental vibration.

  3. Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Ephraim B. Winzer

    2016-01-01

    Full Text Available Background. Endothelial function is impaired in chronic heart failure (CHF. Statins upregulate endothelial NO synthase (eNOS and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function.

  4. The description of friction of silicon MEMS with surface roughness: virtues and limitations of a stochastic Prandtl–Tomlinson model and the simulation of vibration-induced friction reduction

    Directory of Open Access Journals (Sweden)

    W. Merlijn van Spengen

    2010-12-01

    Full Text Available We have replaced the periodic Prandtl–Tomlinson model with an atomic-scale friction model with a random roughness term describing the surface roughness of micro-electromechanical systems (MEMS devices with sliding surfaces. This new model is shown to exhibit the same features as previously reported experimental MEMS friction loop data. The correlation function of the surface roughness is shown to play a critical role in the modelling. It is experimentally obtained by probing the sidewall surfaces of a MEMS device flipped upright in on-chip hinges with an AFM (atomic force microscope. The addition of a modulation term to the model allows us to also simulate the effect of vibration-induced friction reduction (normal-force modulation, as a function of both vibration amplitude and frequency. The results obtained agree very well with measurement data reported previously.

  5. 管壳式换热器管束流致振动实例分析%Examples Analysis of the Vibration Induced by Shell and Tube Heat Exchanger Tube Bundle Flow

    Institute of Scientific and Technical Information of China (English)

    矫明

    2014-01-01

    Elaborate the vibration mechanism induced by shell and tube heat exchanger tube bundle flow . Based on the Xist and Xvib modules of the HTRI software ,analyze and study the examples of vibration induced by shell and tube heat exchanger tube flow , and compare the advantages , disadvantages and adaptability between the HTRI‐Xist and HTRI‐Xvib analysis .%阐述管壳式换热器管束流致振动的机理,基于HTRI软件的Xist和Xvib模块,进行管壳式换热器管束流致振动实例的分析与研究,并比较了HTRI‐Xist与HTRI‐Xvib分析方法的优缺点及适应性。

  6. Quercetin ameliorates chronic unpredicted stress-mediated memory dysfunction in male Swiss albino mice by attenuating insulin resistance and elevating hippocampal GLUT4 levels independent of insulin receptor expression.

    Science.gov (United States)

    Mehta, Vineet; Parashar, Arun; Sharma, Arun; Singh, Tiratha Raj; Udayabanu, Malairaman

    2017-03-01

    Chronic stress is associated with impaired neuronal functioning, altered insulin signaling, and behavioral dysfunction. Quercetin has shown neuroprotective and antidiabetic effects, besides modulating cognition and insulin signaling. Therefore, in the present study, we explored whether or not quercetin ameliorates stress-mediated cognitive dysfunction and explored the underlying mechanism. Swiss albino male mice were subjected to an array of unpredicted stressors for 21days, during which 30mg/kg quercetin treatment was given orally. The effect of chronic unpredicted stress (CUS) and quercetin treatment on cognition were evaluated using novel object recognition (NOR) and Morris water maze (MWM) tests. Hippocampal neuronal integrity was observed by histopathological examination. Blood glucose, serum corticosterone, and insulin levels were measured by commercial kits and insulin resistance was evaluated in terms of HOMA-IR index. Hippocampal insulin signaling was determined by immunofluorescence staining. CUS induced significant cognitive dysfunction (NOR and MWM) and severely damaged hippocampal neurons, especially in the CA3 region. Quercetin treatment alleviated memory dysfunction and rescued neurons from CUS-mediated damage. Fasting blood glucose, serum corticosterone, and serum insulin were significantly elevated in stressed animals, besides, having significantly higher HOMA-IR index, suggesting the development of insulin resistance. Quercetin treatment alleviated insulin resistance and attenuated altered biochemical parameters. CUS markedly down-regulated insulin signaling in CA3 region and quercetin treatment improved neuronal GLUT4 expression, which seemed to be independent of insulin and insulin receptor levels. These results suggest that intact insulin functioning in the hippocampus is essential for cognitive functions and quercetin improves CUS-mediated cognitive dysfunction by modulating hippocampal insulin signaling. Copyright © 2016 Elsevier Inc. All

  7. CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

    2017-08-01

    CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention.NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated in

  8. Clinical Significance of HLA-DQ Antibodies in the Development of Chronic Antibody-Mediated Rejection and Allograft Failure in Kidney Transplant Recipients.

    Science.gov (United States)

    Lee, Hyeyoung; Min, Ji Won; Kim, Ji-Il; Moon, In-Sung; Park, Ki-Hyun; Yang, Chul Woo; Chung, Byung Ha; Oh, Eun-Jee

    2016-03-01

    With the development of the single antigen beads assay, the role of donor specific alloantibody (DSA) against human leukocyte antigens in kidney transplantation (KT) has been highlighted. This study aimed to investigate the clinical significance of DQ-DSA detected at renal allograft biopsy. We evaluated 263 KT recipients who underwent allograft biopsy and DSA detection at the same time. Among them, 155 patients who were nonsensitized before transplantation were selected to investigate the role of de-novo DQ-DSA. Both the total and nonsensitized subgroup was categorized into 4 groups each according to DSA results as: DQ only, DQ + non-DQ, non-DQ, and no DSA. In the total patient group, post-KT DSA was positive in 79 (30.0%) patients and DQ-DSA was most prevalent (64.6%). In the nonsensitized subgroup, de-novo DSAs were detected in 45 (29.0%) patients and DQ-DSA was also most prevalent (73.3%). The DQ only group showed a significantly longer post-KT duration compared to the other groups (P chronic AMR, only DQ-DSA showed significance in both the total and the nonsensitized subgroup (P chronic tissue injury were more frequently detected in the groups with DQ-DSA. The worst postbiopsy survival was seen in the DQ + non-DQ group of the total patient group, and patients with de-novo DQ-DSA showed poorer graft survival in the nonsensitized subgroup compared to the no DSA group (P failure (P chronic AMR. These findings suggest that the detection of DQ-DSA in nonsensitized patients is significantly associated with the development of chronic AMR and late allograft failure. Therefore monitoring of DQ-DSA not only in sensitized patients, but also nonsensitized patients may be necessary to improve long-term allograft outcomes.

  9. Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats.

    OpenAIRE

    Rath, H. C.; Herfarth, H H; Ikeda, J S; Grenther, W B; Hamm, T. E.; Balish, E.; Taurog, J D; Hammer, R. E.; Wilson, K. H.; Sartor, R B

    1996-01-01

    Genetic and environmental factors are important in the pathogenesis of clinical and experimental chronic intestinal inflammation. We investigated the influence of normal luminal bacteria and several groups of selected bacterial strains on spontaneous gastrointestinal and systemic inflammation in HLA-B27 transgenic rats. Rats maintained germfree for 3-9 mo were compared with littermates conventionalized with specific pathogen-free bacteria. Subsequently, germfree transgenic rats were colonized...

  10. Exposure to chronic hyperglycemic conditions results in Ras-related C3 botulinum toxin substrate 1 (Rac1)-mediated activation of p53 and ATM kinase in pancreatic β-cells.

    Science.gov (United States)

    Sidarala, Vaibhav; Kowluru, Anjaneyulu

    2017-02-21

    Chronic hyperglycemia (HG) promotes pancreatic islet dysfunction which leads to the onset of T2DM. This study is aimed at defining regulatory roles of Rac1, a small G-protein, in the activation of p53 and ATM kinase in pancreatic β-cells, under the duress of HG conditions. We report significant stimulatory effects of HG (20 mM; 24 h) on p53 activation in INS-1 832/13 cells, normal rodent and human islets. Pharmacological inhibition of Rac1 (EHT1864 or NSC23766) significantly suppressed HG-induced p53 activation in INS-1 832/13 cells and rat islets, suggesting novel roles for this small G-protein in the activation of p53. Inhibition of Rac1 geranylgeranylation with simvastatin or GGTI-2147, significantly attenuated HG-induced p53 activation, suggesting requisite roles for this signaling step in HG-mediated effects on β-cells. HG-induced p53 activation was also suppressed by SB203580, a known inhibitor of p38MAPK. Additionally, we observed increased activation of ATM kinase under HG conditions, which was blocked in presence of EHT1864. Furthermore, pharmacological inhibition of ATM kinase (KU55933) reduced activation of ATM kinase, but not p53, suggesting that HG-mediated activation of p53 and ATM could represent independent pro-apoptotic events. In conclusion, these data indicate that sustained activation of Rac1-p38MAPK signaling axis leads to activation of p53 leading to β-cell dysfunction under the duress of chronic hyperglycemic conditions.

  11. Chronic sympathetic activation promotes downregulation of ß-adrenoceptor-mediated effects in the guinea pig heart independently of structural remodeling and systolic dysfunction

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Thiele, Stefanie; Osadchiy, Oleg;

    2011-01-01

    pathway upon chronic infusion of isoproterenol, a ß-adrenoceptor agonist, at a dose producing no structural left ventricular (LV) remodeling and systolic dysfunction. Subcutaneous isoproterenol infusion (400 µg kg(-1) h(-1) over 16 days) to guinea pigs using osmotic minipumps produced no change in cardiac...... weights, LV internal dimensions, myocyte cross-sectional area, extent of interstitial fibrosis, and basal contractile function. Isolated, perfused heart preparations from isoproterenol-treated guinea pigs exhibited attenuated responsiveness to acute ß-adrenoceptor stimulation, as evidenced by reduced LV...

  12. Study of effect on sensitive equipment due to vibrations induced by metro traffic%地铁列车运行引起的振动对精密仪器的影响研究

    Institute of Scientific and Technical Information of China (English)

    刘卫丰; 刘维宁; 马蒙; 李克飞; 王文斌

    2012-01-01

    The effect on the sensitive equipment in the physics laboratory of Peking University due to vibrations induced by metro traffic and the isolation efficiency of floating slab track in tunnels on line 4 were studied by means of a numerical model and in-situ vibration measurement. In this model, based on the analytical solution of dynamic response excited by the moving loads, the vibrations induced by passage of metro trains can be calculated if the transfer function in the frequency-wavenum-ber domain and the moving axle loads in the frequency domain can be obtained. The transfer function is calculated using the three-dimensional coupled periodic finite element-boundary element model in the frequency-wavenumber domain) and the moving axle loads are considered as the contact force between wheel and rail due to the rail unevenness. The in-situ vibration measurement was performed outside and inside the laboratory, and the background vibration, the vibrations induced only by buses and metro trains, and the combined vibrations due to road traffic and metro traffic were measured. The results show that the floating slab track is an effective vibration isolation measure, which can efficiently reduce the vibrations in its work frequency range. At low frequencies the metro train induced vibrations may have effect on the sensitive equipment, and the buses induced vibrations and the combined vibrations due to road traffic and metro traffic affect the sensitive equipment, which can be reduced by the passive isolation measure under the base of equipment.%采用一种数值模型,并结合现场振动实测,对北京地铁4号线列车运行引起的振动对北京大学物理实验室内精密仪器的影响问题进行了研究,并对地铁4号线隧道内浮置板轨道的减振效果进行了探讨.该模型根据移动荷载作用下的动力响应解,把地铁列车运行引起的振动问题归结到计算频率-波数域内的传递函数和频域内移动轴荷载的问

  13. Multiple Ku orthologues mediate DNA non-homologous end-joining in the free-living form and during chronic infection of Sinorhizobium meliloti.

    Science.gov (United States)

    Kobayashi, Hajime; Simmons, Lyle A; Yuan, Daniel S; Broughton, William J; Walker, Graham C

    2008-01-01

    The bacterial non-homologous end-joining (NHEJ) apparatus is a two-component system that uses Ku and LigD to repair DNA double-strand breaks. Although the reaction mechanism has been extensively studied, much less is known about the physiological role of bacterial NHEJ. Recent studies suggest that NHEJ acts under conditions where DNA replication is reduced or absent (such as in a spore or stationary phase). Interestingly, genes encoding Ku and LigD have been identified in a wide range of bacteria that can chronically infect eukaryotic hosts. Strikingly, Sinohizobium meliloti, an intracellular symbiont of legume plants, carries four genes encoding Ku homologues (sku1 to sku4). Deletion analysis of the sku genes indicated that all Ku homologues are functional. One of these genes, sku2, is strongly expressed in free-living cells, as well as in bacteroid cells residing inside of the host plant. To visualize the NHEJ apparatus in vivo, SKu2 protein was fused to yellow fluorescent protein (YFP). Ionizing radiation (IR) induced focus formation of SKu2-YFP in free-living cells in a dosage-dependent manner. Moreover, SKu2-YFP foci formed in response to IR in non-dividing bacteroids, indicating that NHEJ system is functional even during the chronic infection phase of symbiosis.

  14. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Directory of Open Access Journals (Sweden)

    Toshifumi Tezuka

    Full Text Available Plasminogen activator inhibitor (PAI-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp. IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  15. IMD-4690, a Novel Specific Inhibitor for Plasminogen Activator Inhibitor-1, Reduces Allergic Airway Remodeling in a Mouse Model of Chronic Asthma via Regulating Angiogenesis and Remodeling-Related Mediators

    Science.gov (United States)

    Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling. PMID:25785861

  16. Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Muyao Ye

    2016-01-01

    Full Text Available Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs. Methods. Fourteen IgA nephropathy (IgAN patients with chronic tonsillitis (CT and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz for 0 (as the control group, 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core β1,3-galactosyltransferase (C1GALT1 and core β1,3GalT-specific molecular chaperone (Cosmc were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.

  17. The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells.

    Science.gov (United States)

    Fiorcari, Stefania; Brown, Wells S; McIntyre, Bradley W; Estrov, Zeev; Maffei, Rossana; O'Brien, Susan; Sivina, Mariela; Hoellenriegel, Julia; Wierda, William G; Keating, Michael J; Ding, Wei; Kay, Neil E; Lannutti, Brian J; Marasca, Roberto; Burger, Jan A

    2013-01-01

    CLL cell trafficking between blood and tissue compartments is an integral part of the disease process. Idelalisib, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor causes rapid lymph node shrinkage, along with an increase in lymphocytosis, prior to inducing objective responses in CLL patients. This characteristic activity presumably is due to CLL cell redistribution from tissues into the blood, but the underlying mechanisms are not fully understood. We therefore analyzed idelalisib effects on CLL cell adhesion to endothelial and bone marrow stromal cells (EC, BMSC). We found that idelalisib inhibited CLL cell adhesion to EC and BMSC under static and shear flow conditions. TNFα-induced VCAM-1 (CD106) expression in supporting layers increased CLL cell adhesion and accentuated the inhibitory effect of idelalisib. Co-culture with EC and BMSC also protected CLL from undergoing apoptosis, and this EC- and BMSC-mediated protection was antagonized by idelalisib. Furthermore, we demonstrate that CLL cell adhesion to EC and VLA-4 (CD49d) resulted in the phosphorylation of Akt, which was sensitive to inhibition by idelalisib. These findings demonstrate that idelalisib interferes with integrin-mediated CLL cell adhesion to EC and BMSC, providing a novel mechanism to explain idelalisib-induced redistribution of CLL cells from tissues into the blood.

  18. The PI3-kinase delta inhibitor idelalisib (GS-1101 targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL cell to endothelial and marrow stromal cells.

    Directory of Open Access Journals (Sweden)

    Stefania Fiorcari

    Full Text Available CLL cell trafficking between blood and tissue compartments is an integral part of the disease process. Idelalisib, a phosphoinositide 3-kinase delta (PI3Kδ inhibitor causes rapid lymph node shrinkage, along with an increase in lymphocytosis, prior to inducing objective responses in CLL patients. This characteristic activity presumably is due to CLL cell redistribution from tissues into the blood, but the underlying mechanisms are not fully understood. We therefore analyzed idelalisib effects on CLL cell adhesion to endothelial and bone marrow stromal cells (EC, BMSC. We found that idelalisib inhibited CLL cell adhesion to EC and BMSC under static and shear flow conditions. TNFα-induced VCAM-1 (CD106 expression in supporting layers increased CLL cell adhesion and accentuated the inhibitory effect of idelalisib. Co-culture with EC and BMSC also protected CLL from undergoing apoptosis, and this EC- and BMSC-mediated protection was antagonized by idelalisib. Furthermore, we demonstrate that CLL cell adhesion to EC and VLA-4 (CD49d resulted in the phosphorylation of Akt, which was sensitive to inhibition by idelalisib. These findings demonstrate that idelalisib interferes with integrin-mediated CLL cell adhesion to EC and BMSC, providing a novel mechanism to explain idelalisib-induced redistribution of CLL cells from tissues into the blood.

  19. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  20. Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

    Energy Technology Data Exchange (ETDEWEB)

    Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Cerretani, Daniela [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Di Paolo, Marco [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fiaschi, Anna Ida [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Frati, Paola [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy); Neri, Margherita [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Pedretti, Monica [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fineschi, Vittorio, E-mail: vfinesc@tin.it [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy)

    2014-10-01

    Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

  1. Transcriptional evidence for the role of chronic venlafaxine treatment in neurotrophic signaling and neuroplasticity including also Glutamatergic [corrected] - and insulin-mediated neuronal processes.

    Directory of Open Access Journals (Sweden)

    Viola Tamási

    Full Text Available Venlafaxine (VLX, a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD. Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration.Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment.Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2. Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3, glutamatergic transmission (Gria3, Grin2b and Grin2a, neuroplasticity (Camk2g/b, Cd47, synaptogenesis (Epha5a, Gad2 and cognitive processes (Clstn2. Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1. Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1, a mechanism that has recently been linked to neuroprotection, learning and memory.Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in

  2. Nuclear factor-kappa B mediates TRPV4-NO pathway involved in thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats.

    Science.gov (United States)

    Wang, Chao; Ning, Li-Ping; Wang, Yong-Hui; Zhang, Yang; Ding, Xin-Li; Ge, Hong-You; Arendt-Nielsen, Lars; Yue, Shou-Wei

    2011-08-01

    The aim of this study was to test the hypothesis that nuclear factor-kappa B (NF-κB) is involved in TRPV4-NO pathway in thermal hyperalgesia following chronic compression of the dorsal root ganglion (DRG) (the procedure hereafter termed CCD) in rat. Intrathecal administration of two NF-κB inhibitors, pyrrolidine dithiocarbamate (PDTC; 10(-1) to 10(-2)M) and BAY (100-50 μM), both induced significantly dose-dependent increase in the paw withdrawal latency (PWL) and decrease in nitric oxide (NO) content in DRG when compared with control rats. Pretreatment with 4α-phorbol 12,13-didecanoate (4α-PDD, transient receptor potential vanilloid 4 (TRPV4) synthetic activator, 1 nm) attenuated the suppressive effects of PDTC (10(-1)M) and BAY (100 μM) on CCD-induced thermal hyperalgesia and NO production. In addition, Western blot analysis indicated that CCD rats exhibited nuclear NF-κB protein expression and low levels of cytoplasmic inhibitory-kappa B (I-κB) expression; the increase in NF-κB expression and decrease in I-κB expression were reversed after intrathecal injection of PDTC. In conclusion, our data suggested that NF-κB could be involved in TRPV4-NO pathway in CCD-induced thermal hyperalgesia.

  3. RNAi-mediated silencing of TNF-α converting enzyme to down-regulate soluble TNF-α production for treatment of acute and chronic colitis.

    Science.gov (United States)

    Song, Yoonsung; Kim, Ye-Ram; Kim, So Mi; Ul Ain, Qurrat; Jang, Kiseok; Yang, Chul-Su; Kim, Yong-Hee

    2016-10-10

    Elevated level of tumor necrosis factor-α (TNF-α), one of the inflammatory cytokines, is considered to be a potential target for the inflammatory bowel disease (IBD) therapy. Recently, TNF-α converting enzyme (TACE), a sheddase playing an important role in cleaving and releasing bioactive soluble TNF-α, has been challenged with inhibitors to treat inflammatory diseases. Here, we report a novel anti-TNF-α strategy using a short hairpin RNA silencing TACE (shTACE) to prevent and treat colitis. The shTACE formed stable complexes with nona-arginine-based bio-cleavable disulfide bond-linked poly (arginine) (PAs-s) for enhanced gene delivery. Systemically administered shTACE/PAs-s peptoplexes efficiently decreased TNF-α levels, increased survival and alleviated pathophysiological parameters representing colitis severity. Our results demonstrate effectiveness and safety of shTACE/PAs-s peptoplexes with the capacity of overcoming acute and chronic ulcerative colitis through modulation of excessive inflammatory responses in the colon, providing a strong potential as a therapeutic agent for a broad variety of inflammatory diseases.

  4. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

    Science.gov (United States)

    Tao, Weiwei; Dong, Yu; Su, Qiang; Wang, Hanqing; Chen, Yanyan; Xue, Wenda; Chen, Chang; Xia, Baomei; Duan, Jinao; Chen, Gang

    2016-07-15

    Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. The main purpose of the current study was to verify whether liquiritigenin conferred an antidepressant-like effect on the depressive mouse model established by unpredictable chronic mild stress (UCMS) and explore its possible mechanism. The results of depression-related behaviors including sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) indicated that both liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) dramatically improved the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) revealed that treatment with liquiritigenin significantly reduced the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus. Compared with the UCMS group, the administrations of liquiritigenin, increased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and decreased Malondialdehyde (MDA) content. Meanwhile, glucocorticoids (GC) content was reduced in the liquiritigenin group, which suggested that liquiritigenin exhibiting the ameliorative effect on activated hypothalamic-pituitary-adrenal (HPA) axis stimulated with UCMS. Mice treated with liquiritigenin showed restored levels of neurotransmitter norepinephrine (NE) and serotonin (5-HT). Western blot analysis displayed up-regulated expressions of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p- mammalian target of rapamycin (mTOR), p-tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF). Thus, it was supposed that liquiritigenin might be useful for the treatment of chronic depression possibly through PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

  5. Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7.

    Science.gov (United States)

    Xu, Chang; Ma, Xin-Ming; Chen, Hui-Bin; Zhou, Meng-He; Qiao, Hui; An, Shu-Cheng

    2016-10-01

    Neuroimaging studies show that patients with major depression have reduced volume of the orbitofrontal cortex (OFC). Although the serotonin (5-HT) 2A receptor, which is abundant in the OFC, has been implicated in depression, the underlying mechanisms in the development of stress-induced depression remain unclear. Kalirin-7 (Kal7) is an essential component of mature excitatory synapses for maintaining dendritic spines density, size and synaptic functions. The aim of this study was to investigate the role of orbitofrontal 5-HT and 5-HT2A receptors in depressive-like behaviors and their associations with Kal7 and dendritic spines using chronic unpredictable mild stress (CUMS), an established animal model of depression. CUMS had no effect on the levels of 5-HT or the 5-HT2A receptor in the OFC. However, CUMS or microinjection of the 5-HT2A/2C receptor agonist (±)-1-(2, 5-Dimethoxy-4-iodophenyl)- 2-aminopropane hydrochloride (DOI, 5 μg/0.5 μL) into the OFC induced depressive-like behaviors, including anhedonia in the sucrose preference test and behavioral despair in the tail suspension test, a significant reduction in body weight gain and locomotor activity in the open field test, which were accompanied by decreased expression of Kal7 and PSD95 as well as decreased density of dendritic spines in the OFC. These alterations induced by CUMS were reversed by pretreatment with the 5-HT2A receptor antagonist Ketanserin (Ket, 5 μg/0.5 μL into the OFC). These results suggest that CUMS alters structural plasticity through activation of the orbital 5-HT2A receptor and is associated with decreased expression of Kal7, thereby resulting in depressive-like behaviors in rats, suggesting an important role of Kal7 in the OFC in depression.

  6. Phosphoinositide 3-kinase/Akt Pathway Mediates Fip1-like1-platelet-derived Growth Factor Receptor α-induced Cell Infiltration and Activation: Possible Molecular Mechanism for the Malignant Phenotype of Chronic Eosinophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Bin Li

    2015-01-01

    Full Text Available The fip1-like1/platelet-derived growth factor receptor-α fusion gene (F/P is responsible for 14-60% cases of hypereosinophilia syndrome (HES, also known as F/P-positive chronic eosinophilic leukemia (F/P(+ CEL. The major pathogenesis of F/P(+ CEL is known to involve migration and activation of mast cells and eosinophils, leading to severe multi-organ dysfunction, but the mechanism was still unclear. Phosphoinositide 3-kinase (PI3K and serine-threonine protein kinase Akt have been reported to be targets of F/P in the F/P-promoted cell proliferation. They are extensively involved in the migration and adhesion of hematopoietic stem/progenitor cells, and also control cell invasion in some leukemias. The PI3K/Akt pathway is involved in eosinophil/neutrophil activation and infiltration; its possible role in regulating F/P induced cytotoxicity and upregulation of A4-integrin in eosinophils, and inducing eosinophil activation through controlling F/P-induced Nuclear factor-kB activity. Akt was recently shown to be stimulated by F/P, synergistically with stem cell factor, resulting in the induction of MCs migration and excessive activation. PI3K/Akt pathway is also a principal mediator of interleukin-5 (IL-5-induced signal transduction promoting eosinophil trafficking and degranulation, whereas IL-5 is a necessary cytokine for F/P-mediated CEL development. We, therefore, propose the hypothesis that the PI3K/Akt pathway might be vital downstream of F/P to induce target cell activation and tissue infiltration, resulting in the malignant phenotype seen in F/P(+ CEL.

  7. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study

    Directory of Open Access Journals (Sweden)

    Lesuis Nienke

    2012-08-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA, inflammatory bowel disease (IBD, and psoriasis are immune-mediated inflammatory diseases with similarities in pathophysiology, and all can be treated with similar biological agents. Previous studies have shown that there are gender differences with regard to disease characteristics in RA and IBD, with women generally having worse scores on pain and quality of life measurements. The relationship is less clear for psoriasis. Because treatment differences between men and women could explain the dissimilarities, we investigated gender differences in the disease characteristics before treatment initiation and in the biologic treatment prescribed. Methods Data on patients with RA or IBD were collected from two registries in which patients treated with biologic medication were enrolled. Basic demographic data and disease activity parameters were collected from a time point just before the initiation of the biologic treatment. For patients with psoriasis, the data were taken from the 2010 annual report of the Swedish Psoriasis Register for systemic treatment, which included also non-biologic treatment. For all three diseases, the prescribed treatment and disease characteristics were compared between men and women. Results In total, 4493 adult patients were included in the study (1912 with RA, 131 with IBD, and 2450 with psoriasis. Most of the treated patients with RA were women, whereas most of the patients with IBD or psoriasis were men. There were no significant differences between men and women in the choice of biologics. At treatment start, significant gender differences were seen in the subjective disease measurements for both RA and psoriasis, with women having higher (that is, worse scores than men. No differences in objective measurements were found for RA, but for psoriasis men had higher (that is, worse scores for objective disease activity measures. A similar trend to RA was seen in IBD

  8. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  9. Chronic Bronchitis

    Science.gov (United States)

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Chronic bronchitis is one type ...

  10. Chronic Pain

    Science.gov (United States)

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis ...

  11. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  12. Chronic prostatitis

    OpenAIRE

    Le, Brian; Schaeffer, Anthony J.

    2011-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  13. Chronic prostatitis

    OpenAIRE

    Erickson, Bradley A.; Schaeffer, Anthony J.; Le, Brian

    2008-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  14. Vibration-induced liquefaction of granular suspensions.

    Science.gov (United States)

    Hanotin, C; Kiesgen de Richter, S; Marchal, P; Michot, L J; Baravian, C

    2012-05-11

    We investigate the mechanical behavior of granular suspensions subjected to coupled vibrations and shear. At high shear stress, whatever the mechanical vibration energy and bead size, the system behaves like a homogeneous suspension of hard spheres. At low shear stress, in addition to a dependence on bead size, vibration energy drastically influences the viscosity of the material that can decrease by more than 2 orders of magnitude. All experiments can be rationalized by introducing a hydrodynamical Peclet number defined as the ratio between the lubrication stress induced by vibrations and granular pressure. The behavior of vibrated wet and dry granular materials can then be unified by assimilating the hookean stress in dry media to the lubrication stress in suspensions.

  15. 阿托伐他汀对慢性肾衰并贫血患者微炎性反应的影响%Influence of atorvastatin on inflammatory mediators in patients with chronic renal failure combined anemia

    Institute of Scientific and Technical Information of China (English)

    张燕燕; 张晓东; 李瑛; 李辉

    2013-01-01

    目的 分析阿托伐他汀在慢性肾衰并贫血患者维持性血液透析期间对微炎性因子的影响.方法 慢性肾衰并贫血患者按随机数字表法分为两组,对照组60例进行维持性血液透析,观察组60例患者在透析期间联合应用阿托伐他汀治疗,比较两组患者治疗3个月后炎性因子及贫血状况的变化.结果 治疗3个月,观察组患者TC、TG、LDL-C以及HDL-C获得显著改善(P<0.05),分别是(3.41±1.24) mmol/L、(1.35±0.58) mmol/L、(1.63±0.83) mmol/L、(2.61±0.69) mmol/L,且上述指标与同期对照组比较差异有统计学意义(P<0.05).观察组患者hs-CRP、IL-6、TNF-α均较治疗前显著降低(P<0.05),改善明显优于对照组.观察组应用促红细胞生成素剂量显著低于对照组(P<0.05).结论 阿托伐他汀通过改善高脂血症,降低患者体内的微炎性状态,提高其对贫血治疗的敏感性.%Objective To analyze the influence of atorvastatin on inflammatory mediators in patients with chronic renal failure combined anemia.Methods 120 patients with chronic renal failure combined anemia were selected and randomly divided into two groups.The patients in control group underwent regular maintenance hemodialysis(MHD),while the patients in observation group received MHD combined with atorvastatin.Comparison was made between two groups in the aspect of inflammatory mediators and clinical effect of anemia after 3 months.Results After three months treatment,TC,TG,LDL-C,BNP,hs-CRP,IL-6,TNF-α,were significantly decreased after treatment in observation group (P < 0.05),which was (3.41 ± 1.24) mmol/L,(1.35 ± 0.58) mmol/L,(1.63 ± 0.83) mmol/L,(2.61 ±0.69)mmol/L,respectively and they were significantly improved than those in control group after treatment (P < 0.05).The prescribed erythropoietin-stimulating agent dose in observation group was significantly lower than that in the control group(P < 0.05).Conclusion Atorvastatin could lead to lower micro

  16. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Shuit-Mun Wong

    Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  17. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Wong, Shuit-Mun; Liu, Fu-Hwa; Lee, Yueh-Lun; Huang, Huei-Mei

    2016-01-01

    Chronic myeloid leukemia (CML) is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  18. 基于钻头运动诱发套管头振动信号检测的井眼防碰监测方法%Anti-collision monitoring based on detecting casing head vibration induced by drill movements

    Institute of Scientific and Technical Information of China (English)

    何保生; 刘刚; 王平双; 文敏

    2011-01-01

    针对海上加密调整井的井眼防碰问题,设计了一种井筒防碰地面监测预警系统,并进行了现场应用.系统利用加速度传感器监测通过套管传输到套管头上的钻头振动信号,利用数据采集、信号滤波放大和专门编制的监测软件记录分析传感器采集的振动信号,通过对信号的时域、频域分析,确定信号特征与井间相对距离的关系,识别钻头对风险井套管的趋近或碰撞.应用结果表明,该系统能有效感知通过地层、套管传输到套管头的钻头振动信号,并能识别出钻头对风险邻井的趋近,验证了系统在设计理论和方法上的可行性,为加密调整井的井眼防碰、保证钻井安全提供了一种有效的手段.%Now encryption adjustment wells are getting widely used in offshore, and the risk of well collision increases greatly. Well anti-collision is becoming more and more important. An anti-collision monitoring system based on detecting casing head vibration induced by drilling movements has been build and rig-site utilized.The acceleration sensors were fixed on the casing head to fell the vibration, the time domain analysis and frequency domain analysis were used in signal processing to recognize the approach motive of the drilling bit to the risk case of production well. The result of rig-site test shows that the newly disigned monitoring system can recognize the vibration caused by bit work and detecting the drilling bit approaching the case. It also indicates that the anti-collision monitoring system for detecting casing head vibration is practicable.

  19. Understanding anemia of chronic disease.

    Science.gov (United States)

    Fraenkel, Paula G

    2015-01-01

    The anemia of chronic disease is an old disease concept, but contemporary research in the role of proinflammatory cytokines and iron biology has shed new light on the pathophysiology of the condition. Recent epidemiologic studies have connected the anemia of chronic disease with critical illness, obesity, aging, and kidney failure, as well as with the well-established associations of cancer, chronic infection, and autoimmune disease. Functional iron deficiency, mediated principally by the interaction of interleukin-6, the iron regulatory hormone hepcidin, and the iron exporter ferroportin, is a major contributor to the anemia of chronic disease. Although anemia is associated with adverse outcomes, experimental models suggest that iron sequestration is desirable in the setting of severe infection. Experimental therapeutic approaches targeting interleukin-6 or the ferroportin-hepcidin axis have shown efficacy in reversing anemia in either animal models or human patients, although these agents have not yet been approved for the treatment of the anemia of chronic disease.

  20. [Immune-mediated neuropathies].

    Science.gov (United States)

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits.

  1. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    Directory of Open Access Journals (Sweden)

    Khadilkar Satish

    2011-01-01

    Full Text Available The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP. Pure motor (multifocal motor neuropathy, sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy, exclusively distal sensory (distal acquired demyelinating sensory neuropathy and very proximal sensory (chronic immune sensory polyradiculopathy constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc. have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.

  2. [Chronicity, chronicization, systematization of delusions].

    Science.gov (United States)

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

  3. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  4. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  5. 慢病毒介导GDNF过表达对CCI大鼠神经病理性疼痛的影响%Effect of lentiviral vector-mediated GDNF up-regulation on neuropathic pain of chronic constriction injury rats

    Institute of Scientific and Technical Information of China (English)

    丁卓峰; 徐伟; 宋宗斌; 邹望远; 郭曲练

    2014-01-01

    Objective To investigate the effect of intrathecal injection of lentiviral vector-mediated up-regulation of glial cell line-derived neurotrophicfactor (GDNF) on neuropathic pain of chronic constriction injury (CCI) rats.Methods The CCI model was prepared by ligating the sciatic nerve of Sprague-Dawley (SD) rats.Seven days after CCI modeling,a single intrathecal injection of lentiviral vectors (LV)-GDNF was given.Before CCI and 3,5,7,14,and 21 days after CCI modeling,the mechanical pain threshold was tested in rats,and 21 days after surgery,Western blot was used to detect the expression of GDNF protein.Results On 21 days after CCI modeling,GDNF expression was reduced compared to sham group.After intrathecal injection of LV-GDNF,GDNF expression was up-regulated in the spinal cord,and CCI-induced mechanical hyperalgesia in rats was alleviated.Conclusions Intrathecal injection LV-GDNF can up-regulate the expression of GDNF and alleviate neuropathic pain in CCI rats.%目的 观察鞘内注射过表达胶质细胞源性神经生长因子(GDNF)慢病毒载体对慢性缩窄性神经损伤(CCI)大鼠神经病理性疼痛的影响.方法 采用结扎大鼠坐骨神经制备CCI模型.CCI造模成功后第7天鞘内注射GDNF过表达慢病毒载体.CCI造模前及造模后第3、5、7、14、21天测定大鼠机械痛阈,并于术后第21天采用Western免疫印迹法测定脊髓GDNF表达.结果 Western免疫印迹显示CCI组GDNF表达较假手术组减少(P<0.05);鞘内注射GDNF过表达慢病毒载体后,脊髓GDNF表达上调,且CCI大鼠机械痛敏显著降低(P<0.05).结论 上调脊髓GDNF表达可减轻CCI大鼠神经病理性疼痛.

  6. Defective synthesis and release of astrocytic thrombospondin-1 mediates the neuronal TDP-43 proteinopathy, resulting in defects in neuronal integrity associated with chronic traumatic encephalopathy: in vitro studies.

    Science.gov (United States)

    Jayakumar, Arumugam Radhakrishnan; Tong, Xiao Y; Shamaladevi, Nagarajarao; Barcelona, Stephanie; Gaidosh, Gabriel; Agarwal, Apeksha; Norenberg, Michael D

    2017-02-01

    Transactivating DNA-binding protein-43 (TDP-43) inclusions and the accumulation of phosphorylated and ubiquitinated tau proteins (p-tau) have been identified in postmortem brain specimens from patients with chronic traumatic encephalopathy (CTE). To examine whether these proteins contribute to the development of CTE, we utilized an in vitro trauma system known to reproduce many of the findings observed in humans and experimental animals with traumatic brain injury. Accordingly, we examined the role of TDP-43 and Tau in an in vitro model of trauma, and determined whether these proteins contribute to the defective neuronal integrity associated with CNS trauma. Single or multiple episodes of trauma to cultured neurons resulted in a time-dependent increase in cytosolic levels of phosphorylated TDP-43 (p-TDP-43). Trauma to cultured neurons also caused an increase in levels of casein kinase 1 epsilon (CK1ε), and ubiquitinated p-TDP-43, along with a decrease in importin-β (all factors known to mediate the "TDP-43 proteinopathy"). Defective neuronal integrity, as evidenced by a reduction in levels of the NR1 subunit of the NMDA receptor, and in PSD95, along with increased levels of phosphorylated tau were also observed. Additionally, increased levels of intra- and extracellular thrombospondin-1 (TSP-1) (a factor known to regulate neuronal integrity) were observed in cultured astrocytes at early stages of trauma, while at later stages decreased levels were identified. The addition of recombinant TSP-1, conditioned media from cultured astrocytes at early stages of trauma, or the CK1ε inhibitor PF4800567 hydrochloride to traumatized cultured neurons reduced levels of p-TDP-43, and reversed the trauma-induced decline in NR1 subunit of the NMDA receptor and PSD95 levels. These findings suggest that a trauma-induced increase in TDP-43 phosphorylation contributes to defective neuronal integrity, and that increasing TSP-1 levels may represent a useful therapeutic approach for

  7. Chronic pancreatitis in dogs.

    Science.gov (United States)

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  8. Ear infection - chronic

    Science.gov (United States)

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... up. When this happens, infection can occur. A chronic ear infection develops when fluid or an infection ...

  9. Chronic Pelvic Pain

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Chronic Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  10. Employees with Chronic Pain

    Science.gov (United States)

    ... one in five Americans suffer from chronic pain (Sternberg, 2005). What is chronic pain? While acute pain ... nih.gov/disorders/chronic_pain/chronic_pain.htm Sternberg, S. (2005). Chronic pain: The enemy within. Retrieved December ...

  11. Mediatized Humanitarianism

    DEFF Research Database (Denmark)

    Vestergaard, Anne

    2014-01-01

    The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts to legiti......The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts...... legitimation by accountancy, legitimation by institutionalization, and legitimation by compensation. The analysis relates these changes to a problem of trust associated with mediatization through processes of mediation....

  12. [Chronic hepatitis].

    Science.gov (United States)

    Figueroa Barrios, R

    1995-01-01

    Medical literature about chronic hepatitis is reviewed. This unresolving disease caused by viruses, drugs or unknown factors may progress to in cirrhosis and hepatocarcinoma. A classification based on liver biopsy histology into chronic persistent and chronic active types has been largely abandoned and emphasis is placed on recognizing the etiology of the various types. One is associated with continuing hepatitis B virus infection; another is related to chronic hepatitis C virus infection and the third is termed autoinmune, because of the association with positive serum autoantibodies. A fourth type with similar clinical functional and morphologic features is found with some drug reactions. Long term corticoesteroid therapy is usually successful in autoinmune type. Associations between antibodies to liver-kidney microsomes and the hepatitis C virus can cause diagnostic difficulties. Antiviral treatment of chronic hepatitis B and C with interpheron alfa is employed, controlling symptoms and abnormal biochemistry and the progression to cirrhosis and liver cancer in 30 to 40% patients. Alternative therapies or combinations with interpheron are being evaluated waiting for final results.

  13. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  14. Chronic gastritis.

    Science.gov (United States)

    Sipponen, Pentti; Maaroos, Heidi-Ingrid

    2015-06-01

    Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.

  15. Development of a novel enzyme-linked immunosorbent assay targeting a neo-epitope generated by cathepsin-mediated turnover of type III collagen and its application in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Rasmussen, Daniel Guldager Kring; Sand, Jannie Marie Bülow; Karsdal, Morten Asser

    2017-01-01

    fragments (C3C) was developed for assessment in serum and plasma. The assay was biologically validated in serum from patients with chronic obstructive pulmonary disease (COPD). Serological levels of C3C were significantly elevated in patients with COPD compared to healthy controls (p = 0.0006). Levels of C3...

  16. Chronic Pelvic Pain

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  17. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... Information > Children/Pediatric > Chronic Pancreatitis in Children test Chronic Pancreatitis in Children What symptoms would my child ... pancreatitis will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are ...

  18. Chronic Beryllium Disease

    Science.gov (United States)

    ... Science Education & Training Home Conditions Chronic Beryllium Disease Chronic Beryllium Disease Make an Appointment Find a Doctor ... MD, MSPH, FCCP (February 01, 2016) What is chronic beryllium disease (CBD)? Chronic beryllium disease (CBD) is ...

  19. Low back pain - chronic

    Science.gov (United States)

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause ...

  20. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  1. Chronic thyroiditis (Hashimoto disease)

    Science.gov (United States)

    Hashimoto thyroiditis; Chronic lymphocytic thyroiditis; Autoimmune thyroiditis; Chronic autoimmune thyroiditis; Lymphadenoid goiter - Hashimoto; Hypothyroidism - Hashimoto; Type 2 polyglandular autoimmune ...

  2. Axion Mediation

    CERN Document Server

    Baryakhtar, Masha; March-Russell, John

    2013-01-01

    We explore the possibility that supersymmetry breaking is mediated to the Standard Model sector through the interactions of a generalized axion multiplet that gains a F-term expectation value. Using an effective field theory framework we enumerate the most general possible set of axion couplings and compute the Standard Model sector soft-supersymmetry-breaking terms. Unusual, non-minimal spectra, such as those of both natural and split supersymmetry are easily implemented. We discuss example models and low-energy spectra, as well as implications of the particularly minimal case of mediation via the QCD axion multiplet. We argue that if the Peccei-Quinn solution to the strong-CP problem is realized in string theory then such axion-mediation is generic, while in a field theory model it is a natural possibility in both DFSZ- and KSVZ-like regimes. Axion mediation can parametrically dominate gravity-mediation and is also cosmologically beneficial as the constraints arising from axino and gravitino overproduction ...

  3. Mediatized Parenthood

    DEFF Research Database (Denmark)

    Sonne Damkjær, Maja

    2017-01-01

    to parenthood? The dissertation explores this question on the basis of a synchronous study within an overall mediatization perspective. The first part of the dissertation focuses on a conceptualization of the relationship between digital media and parenting as well as an exploration of theoretical perspectives...... and methods that make it possible to study the interactions between the two. Concretely, the dissertation builds on a number of key studies within audience research, which have contributed knowledge about the media’s role in the family and the home. This is done by including three approaches to mediatization......) a family-oriented, b) a peer-oriented, c) an oppositional, and d) non-use. Secondary contribution: Based on qualitative audience research and mediatization theory, the dissertation contributes a conceptualization of the relationship between media and parenthood. This is carried out in a study design...

  4. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  5. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts....... In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  6. 生活事件在老年抑郁症与慢性躯体疾病之间的中介效应及护理对策%Mediating effect of life events between elderly depression and chronic somatic disease and thieir nursing counter-measures

    Institute of Scientific and Technical Information of China (English)

    刘冰; 徐曼; 柴云; 周尚成; 卢丽

    2016-01-01

    Objective:To probe into the explaining function of life events between elderly depression and chronic somatic disease.Methods:A total of 500 old peoples were selected by using the convenient sampling method,and they received the questionnaire investigation by using geriatric mental status scale(GMS),elderly health status and related factors questionnaire,then to do statistical analysis for the survey results.Results:Elderly depression had a significant correlation with the number of chronic somatic diseases(B=1.298,P<0.01),when the num-ber of life events was also added to the mediating effect model,the correlation strength between elderly depres-sion and chronic somatic diseases changed to 0.937,which reduced 27.81%,but the correlation between elderly depression and number of chronic somatic diseases remained significant(B=0.332,P<0.01),which showed that the life events played a partial mediating effect between the elderly depression and chronic somatic disea-ses.In depth analysis found that the“economic difficulties”and“health deterioration”event had partial media-ting effect between the elderly depression and chronic somatic diseases.In addition,the number of chronic so-matic diseases had positively correlation with the “self assessment of economic difficulties”event(r=0.158,P<0.01)and “self rating health deterioration”event(r=0.266,P<0.01).Conclusion:Some life events played a partial mediating effect between the elderly depression and chronic somatic diseases,we should take various measures to prevent elderly depression,reduce the elderly depression patients complicating with more chronic somatic diseases.%[目的]探讨生活事件在老年抑郁症与慢性躯体疾病之间的解释作用。[方法]采用方便抽样方法抽取十堰市4个社区500名老年人,采用老年精神状况量表(GMS)、老年健康状况和相关因素调查表进行问卷调查,并对调查结果进行统计学分析。[结果]老年抑郁症与慢性躯体疾

  7. Expression of Pendrin Periostin in Allergic Rhinitis Chronic Rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Akihiro Ishida

    2012-01-01

    Conclusions: : Production of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin- induced asthma.

  8. Living with Chronic Bronchitis

    Science.gov (United States)

    ... from the NHLBI on Twitter. Living With Chronic Bronchitis If you have chronic bronchitis, you can take steps to control your symptoms. ... and a pneumonia vaccine. If you have chronic bronchitis, you may benefit from pulmonary rehabilitation (PR). PR ...

  9. Chronic inflammatory demyelinating polyneuropathy

    Science.gov (United States)

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... Health care providers also consider CIDP as the chronic form of Guillain-Barré syndrome. The specific triggers ...

  10. Dealing with chronic cancer

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000933.htm Dealing with chronic cancer To use the sharing features on this ... be controlled for a period of time. Controlling Chronic Cancer When you have a chronic cancer, the ...

  11. Evaluation of telomerase expression in chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Balaji T

    2010-01-01

    Full Text Available Background : Human telomerase is a multi subunit ribonucleoprotein enzyme concerned with telomeric lengthening and homeostasis in man. This enzyme has been found to be elevated in inflammatory conditions like rheumatoid arthritis and silica injury lung. Since chronic periodontitis is also an inflammatory condition where immune cells and cytokines mediate tissue destruction, we set out to evaluate telomerase in gingival tissue samples from healthy subjects and chronic periodontitis patients by reverse transcriptase polymerase chain reaction. Materials and Methods : Gingival biopsies were obtained from eight healthy subjects and eight chronic periodontitis patients. Reverse transcriptase polymerase chain reaction (RTPCR was carried out to evaluate telomerase gene expression in the samples. Results : None of the healthy gingival tissue samples expressed the telomerase gene while all the chronic periodontitis samples expressed it. The severe chronic periodontitis samples expressed the gene more intensely than the moderate chronic periodontitis samples. Conclusion : Various mechanisms have been explained to account for telomerase elevation in chronic periodontitis .This study helps us understand the role of telomerase in the pathogenesis of periodontal disease. It could be concluded that telomerase could be used as a marker to assess the severity of inflammation in chronic periodontitis.

  12. Chronic autoimmune urticaria : Where we stand ?

    Directory of Open Access Journals (Sweden)

    Goh C

    2009-01-01

    Full Text Available It is well-recognized that 30-40% of chronic idiopathic urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcåRI and less frequently, by anti-IgE autoantibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. Activation of the classical complement pathway and formation of C5a are important in dermal mast cell activation. C5a is also a neutrophil and eosinophil chemoattractant. Chronic autoimmune urticaria has been found to be associated with autoimmune thyroid disease. The autologous serum skin test is used as a screening test for chronic autoimmune urticaria and has a sensitivity and specificity of about 70 and 80%, respectively. The current gold standard diagnostic test is the basophil histamine release assay. The treatment of chronic autoimmune urticaria, as in chronic idiopathic urticaria, is with H1 antihistamines. Oral corticosteroids may be used during acute flares. Refractory cases have been shown to respond to cyclosporine and other immunomodulators. The prevalence of chronic autoimmune urticaria in Singapore is similar to that reported in Western countries at about 42%. The presence of thyroid autoimmunity appears to be higher than reported, with 22.5% of patients with chronic idiopathic urticaria here, exhibiting presence of thyroid autoantibodies.

  13. The differential effects of gratitude and sleep on psychological distress in patients with chronic pain.

    Science.gov (United States)

    Ng, Mei-Yee; Wong, Wing-Sze

    2013-02-01

    This study aimed to examine the possible cross-sectional mediating role of sleep in the relationship of gratitude with depression and anxiety in patients with chronic pain. A total of 224 patients with chronic pain completed structured questionnaires assessing chronic pain, depression and anxiety symptoms, gratitude, and sleep disturbances. Results of multiple regression analyses yielded a modest mediating effect for sleep on the gratitude-depression link whereas a stronger mediating effect was found for sleep on the gratitude-anxiety link. These data show much of the effect of gratitude on depression was direct whereas sleep exerted a stronger mediating effect on the gratitude-anxiety link.

  14. Immune-mediated canine and feline keratitis.

    Science.gov (United States)

    Andrew, Stacy E

    2008-03-01

    Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.

  15. Chronic mucus hypersecretion

    DEFF Research Database (Denmark)

    Harmsen, L; Thomsen, S F; Sylvan Ingebrigtsen, Truls;

    2010-01-01

    Chronic mucus hypersecretion (CMH) is a common condition in patients with chronic respiratory diseases. Little is known about the incidence, prevalence and determinants of CMH in younger individuals....

  16. Lymphocyte 'homing' and chronic inflammation.

    Science.gov (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  17. Chronic urticaria

    Directory of Open Access Journals (Sweden)

    Sandeep Sachdeva

    2011-01-01

    Full Text Available Chronic urticaria (CU is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the ′idiopathic′ forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.

  18. Nitric oxide and chronic colitis

    Directory of Open Access Journals (Sweden)

    Matthew B Grisham

    1996-01-01

    Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

  19. Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

    Directory of Open Access Journals (Sweden)

    Yan He

    2015-05-01

    Full Text Available It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  20. Curcumin, inflammation, and chronic diseases: how are they linked?

    Science.gov (United States)

    He, Yan; Yue, Yuan; Zheng, Xi; Zhang, Kun; Chen, Shaohua; Du, Zhiyun

    2015-05-20

    It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.

  1. Management and treatment of chronic urticaria (CU).

    Science.gov (United States)

    Maurer, M; Church, M K; Gonçalo, M; Sussman, G; Sánchez-Borges, M

    2015-06-01

    Developments increasing our understanding of chronic urticaria have resulted in the simplification and improvement of available treatments. Currently, many treatments target mast cell mediators, but we can now disrupt mast cell activation with the anti-IgE antibody omalizumab, which has markedly advanced the treatment landscape for patients with difficult-to-treat urticaria. Current guidelines provide a framework for the management and treatment of patients with CU but, as each patient is different, knowledge and experience of specialist dermatologists and allergists are key to effective pharmacotherapy. This article reviews the different therapeutic options for patients with chronic spontaneous urticaria (also called chronic idiopathic urticaria) or chronic inducible urticaria and discusses management of special populations or special circumstances related to CU.

  2. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  3. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B; Nikolajsen, L; Kehlet, Henrik;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies. Udgivelsesdato: 2008-Mar...

  4. [Chronic otitis mediaChronic Otitis Media].

    Science.gov (United States)

    Kohles, N; Schulz, T; Eßer, D

    2015-11-01

    There are 2 different kinds of chronic otitis media: Otitis media chronica mesotympanalis and otitis media chronica epitympanalis (cholesteatoma). The incidence of chronic otitis media as reported in literature differs in a wide range. The incidence rates vary between 0.45 and 46%. Both, otitis media chronica mesotympanalis and cholesteatoma, lead to eardrum perforation due to lengthy and recurring inflammations. Furthermore, chronic otitis media is characterized by frequently recurring otorrhea and conductive hearing loss. Georg Thieme Verlag KG Stuttgart · New York.

  5. Glucocorticoids, chronic stress, and obesity.

    Science.gov (United States)

    Dallman, Mary F; Pecoraro, Norman C; La Fleur, Susanne E; Warne, James P; Ginsberg, Abigail B; Akana, Susan F; Laugero, Kevin C; Houshyar, Hani; Strack, Alison M; Bhatnagar, Seema; Bell, Mary E

    2006-01-01

    Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a chronic stressor, the steroids act in brain in a feed-forward fashion to recruit a stress-response network that biases ongoing autonomic, neuroendocrine, and behavioral outflow as well as responses to novel stressors. We review evidence for the role of glucocorticoids in activating the central stress-response network, and for mediation of this network by corticotropin-releasing factor (CRF). We briefly review the effects of CRF and its receptor antagonists on motor outflows in rodents, and examine the effects of glucocorticoids and CRF on monoaminergic neurons in brain. Corticosteroids stimulate behaviors that are mediated by dopaminergic mesolimbic "reward" pathways, and increase palatable feeding in rats. Moreover, in the absence of corticosteroids, the typical deficits in adrenalectomized rats are normalized by providing sucrose solutions to drink, suggesting that there is, in addition to the feed-forward action of glucocorticoids on brain, also a feedback action that is based on metabolic well being. Finally, we briefly discuss the problems with this network that normally serves to aid in responses to chronic stress, in our current overindulged, and underexercised society.

  6. Chronic neglect and aggression/delinquency: A longitudinal examination.

    Science.gov (United States)

    Logan-Greene, Patricia; Semanchin Jones, Annette

    2015-07-01

    Neglect is the most common form of maltreatment in the United States, yet its impact on development remains understudied, especially for chronic neglect. Chronic neglect is also one of the most costly burdens on child welfare systems. This study examines the effects of chronic neglect, including two subtypes (Failure to Provide and Lack of Supervision) on adolescent aggression and delinquency using a diverse longitudinal sample of youth. Chronic neglect and chronic failure to provide (ages 0-12) predicted aggression/delinquency (age 14) even after controlling for the effects of other maltreatment (ages 0-12). Chronic lack of supervision, however, did not. Gender significantly moderated these effects, suggesting that males are more likely to respond to neglect by becoming aggressive/delinquent. Finally, social problems (age 12) partially mediated for boys, and fully mediated for girls, the connections between chronic neglect and aggression/delinquency, bolstering theorizing that neglect impairs social functioning broadly. Implications include the need for further research on chronic neglect, especially in providing guidance for child welfare systems. Interventions for chronically neglected youth should include social skill development.

  7. TMD and chronic pain: A current view

    Science.gov (United States)

    Furquim, Bruno D'Aurea; Flamengui, Lívia Maria Sales Pinto; Conti, Paulo César Rodrigues

    2015-01-01

    This review aims at presenting a current view on the physiopathologic mechanisms associated with temporomandibular disorders (TMDs). While joint pain is characterized by a well-defined inflammatory process mediated by tumor necrosis factor-α and interleukin, chronic muscle pain presents with enigmatic physiopathologic mechanisms, being considered a functional pain syndrome similar to fibromyalgia, irritable bowel syndrome, interstitial cystitis and chronic fatigue syndrome. Central sensitization is the common factor unifying these conditions, and may be influenced by the autonomic nervous system and genetic polymorphisms. Thus, TMDs symptoms should be understood as a complex response which might get worse or improve depending on an individual's adaptation. PMID:25741834

  8. TMD and chronic pain: A current view

    Directory of Open Access Journals (Sweden)

    Bruno D'Aurea Furquim

    2015-02-01

    Full Text Available This review aims at presenting a current view on the physiopathologic mechanisms associated with temporomandibular disorders (TMDs. While joint pain is characterized by a well-defined inflammatory process mediated by tumor necrosis factor-α and interleukin, chronic muscle pain presents with enigmatic physiopathologic mechanisms, being considered a functional pain syndrome similar to fibromyalgia, irritable bowel syndrome, interstitial cystitis and chronic fatigue syndrome. Central sensitization is the common factor unifying these conditions, and may be influenced by the autonomic nervous system and genetic polymorphisms. Thus, TMDs symptoms should be understood as a complex response which might get worse or improve depending on an individual's adaptation.

  9. Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

    Directory of Open Access Journals (Sweden)

    María L. Breser

    2017-07-01

    Full Text Available Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain.

  10. Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

    Science.gov (United States)

    Breser, María L.; Salazar, Florencia C.; Rivero, Viginia E.; Motrich, Rubén D.

    2017-01-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain. PMID:28824626

  11. Urine Proteomics to Detect Biomarkers for Chronic Allograft Dysfunction

    Science.gov (United States)

    Quintana, Luís F.; Solé-Gonzalez, Amanda; Kalko, Susana G.; Bañon-Maneus, Elisenda; Solé, Manel; Diekmann, Fritz; Gutierrez-Dalmau, Alex; Abian, Joaquin; Campistol, Josep M.

    2009-01-01

    Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction (14 with pure interstitial fibrosis and tubular atrophy and 18 with chronic active antibody-mediated rejection) and 18 control subjects (eight stable recipients and 10 healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibody-mediated rejection group, and an independent validation set confirmed these results. The 14 protein ions that best discriminated between these two groups correctly identified 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction. PMID:19056874

  12. Chronic tophaceous gout

    Directory of Open Access Journals (Sweden)

    Thappa D

    1993-01-01

    Full Text Available A rare case of chronic tophaceous gout, in a 27-year-old female on diuretics for chronic congestive cardiac failure with characteristic histopathological and radiological changes is reported.

  13. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... maintaining good health. Can chronic pancreatitis give my child cancer? If your child has chronic pancreatitis, he or she will be at an increased risk of developing pancreatic cancer compared to the general population. The degree of ...

  14. Chronic granulomatous disease

    Science.gov (United States)

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... In chronic granulomatous disease (CGD), immune system cells called phagocytes are unable to kill some types of bacteria and ...

  15. Chronic mucus hypersecretion

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; von Linstow, Marie-Louise; Nepper-Christensen, Steen;

    2005-01-01

    To investigate if chronic mucus hypersecretion (CMH) can be used as a marker of asthma in young adults.......To investigate if chronic mucus hypersecretion (CMH) can be used as a marker of asthma in young adults....

  16. Chronic Kidney Diseases

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  17. Diet - chronic kidney disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002442.htm Diet - chronic kidney disease To use the sharing features on this page, ... make changes to your diet when you have chronic kidney disease. These changes may include limiting fluids, eating a ...

  18. People Experiencing Chronic Homelessness

    Science.gov (United States)

    ... Goals Ending Chronic Homelessness Share This: Ending Chronic Homelessness Last updated on January 19, 2017 We can ... the USICH newsletter. We know how to end homelessness. Let's do it, together. Sign up for our ...

  19. Childhood adversity and chronicity of mood disorders.

    Science.gov (United States)

    Angst, Jules; Gamma, Alex; Rössler, Wulf; Ajdacic, Vladeta; Klein, Daniel N

    2011-02-01

    To evaluate the potential impact of early childhood problems on the chronicity of mood disorders. A representative cohort from the population was prospectively studied from ages 19/20 to 39/40. Unipolar (UP) and bipolar disorders (BP) were operationally defined applying broad Zurich criteria for bipolarity. Chronicity required the presence of symptoms for more days than not over 2 years prior to an interview, or almost daily occurrence for 1 year. A family history and a history of childhood problems were taken at ages 27/28 and 29/30. Data include the first of multiple self-assessments with the Symptom-Checklist-90 R at age 19/20, and mastery and self-esteem assessed 1 year later. A factor analysis of childhood problems yielded two factors: family problems and conduct problems. Sexual trauma, which did not load on either factor, and conduct problems were unrelated to chronicity of UP or BP or both together. In contrast, childhood family problems increased the risk of chronicity by a factor of 1.7. An anxious personality in childhood and low self-esteem and mastery in early adulthood were also associated with chronicity. Childhood family problems are strong risk factors for the chronicity of mood disorders (UP and BP). The risk may be mediated partly by anxious personality traits, poor coping and low self-esteem.

  20. [Pathophysiology of hypertension in chronic kidney disease].

    Science.gov (United States)

    Sawicka, Magdalena; Jędras, Mirosław

    2014-01-01

    Hypertension is both an important cause and consequence of chronic kidney disease (CKD). It is present in 80-85% of the patients. The article summarizes the main pathogenetic factors of hypertension in CKD such as: sodium retention, increased activity the renin-angiotensin-aldosterone system and sympathetic nervous system, impaired nitric oxide synthesis and endothelium-mediated vasodilatation, oxidative stress, disorders of calcium metabolism and parathyroid hormone secretion, vascular calcification and increased arterial stiffness.

  1. Hypoaminoacidemia Characterizes Chronic Traumatic Brain Injury.

    Science.gov (United States)

    Durham, William J; Foreman, Jack P; Randolph, Kathleen M; Danesi, Christopher P; Spratt, Heidi; Masel, Brian D; Summons, Jennifer R; Singh, Charan K; Morrison, Melissa; Robles, Claudia; Wolfram, Cindy; Kreber, Lisa A; Urban, Randall J; Sheffield-Moore, Melinda; Masel, Brent E

    2017-01-15

    Individuals with a history of traumatic brain injury (TBI) are at increased risk for a number of disorders, including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. However, mediators of the long-term morbidity are uncertain. We conducted a multi-site, prospective trial in chronic TBI patients (∼18 years post-TBI) living in long-term 24-h care environments and local controls without a history of head injury. Inability to give informed consent was exclusionary for participation. A total of 41 individuals (17 moderate-severe TBI, 24 controls) were studied before and after consumption of a standardized breakfast to determine if concentrations of amino acids, cytokines, C-reactive protein, and insulin are potential mediators of long-term TBI morbidity. Analyte concentrations were measured in serum drawn before (fasting) and 1 h after meal consumption. Mean ages were 44 ± 15 and 49 ± 11 years for controls and chronic TBI patients, respectively. Chronic TBI patients had significantly lower circulating concentrations of numerous individual amino acids, as well as essential amino acids (p = 0.03) and large neutral amino acids (p = 0.003) considered as groups, and displayed fundamentally altered cytokine-amino acid relationships. Many years after injury, TBI patients exhibit abnormal metabolic responses and altered relationships between circulating amino acids, cytokines, and hormones. This pattern is consistent with TBI, inducing a chronic disease state in patients. Understanding the mechanisms causing the chronic disease state could lead to new treatments for its prevention.

  2. Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.

    Science.gov (United States)

    Bhatia, Nitish; Jaggi, Amteshwar Singh; Singh, Nirmal; Anand, Preet; Dhawan, Ravi

    2011-07-01

    The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.

  3. Heredity of chronic bronchitis

    DEFF Research Database (Denmark)

    Meteran, Howraman; Backer, Vibeke; Kyvik, Kirsten Ohm

    2014-01-01

    BACKGROUND: Smoking is a major risk factor for lung diseases and lower respiratory symptoms, but since not all smokers develop chronic bronchitis and since chronic bronchitis is also diagnosed in never-smokers, it has been suggested that some individuals are more susceptible to develop chronic...... bronchitis due to genetics. OBJECTIVE: To study the relative influence of genetic and environmental factors on the variation in the susceptibility to chronic bronchitis. METHODS: In a population-based questionnaire study of 13,649 twins, 50-71 years of age, from the Danish Twin Registry, we calculated sex......-specific concordance rates and heritability of chronic bronchitis. The response rate was 75%. RESULTS: The prevalence of chronic bronchitis was 9.3% among men and 8.5% among women. The concordance rate for chronic bronchitis was higher in monozygotic twins than in dizygotic twins among women; 0.30 vs. 0...

  4. Approaching chronic sinusitis.

    Science.gov (United States)

    Sarber, Kathleen M; Dion, Gregory Robert; Weitzel, Erik K; McMains, Kevin C

    2013-11-01

    Chronic sinusitis is a common disease that encompasses a number of syndromes that are characterized by sinonasal mucosal inflammation. Chronic sinusitis can be defined as two or more of the following symptoms lasting for more than 12 consecutive weeks: discolored rhinorrhea, postnasal drip, nasal obstruction, facial pressure or pain, or decreased sense of smell. Chronic sinusitis is further classified as chronic sinusitis with polyposis, chronic sinusitis without polyposis, or allergic fungal sinusitis using physical examination, and histologic and radiographic findings. Treatment methods for chronic sinusitis are based upon categorization of the disease and include oral and inhaled corticosteroids, nasal saline irrigations, and antibiotics in selected patients. Understanding the various forms of chronic sinusitis and managing and ruling out comorbidities are key to successful management of this common disorder.

  5. Mechanisms of platelet-mediated liver regeneration.

    Science.gov (United States)

    Lisman, Ton; Porte, Robert J

    2016-08-04

    Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

  6. Hybrid isolation of micro vibrations induced by reaction wheels

    Science.gov (United States)

    Lee, Dae-Oen; Park, Geeyong; Han, Jae-Hung

    2016-02-01

    As the technology for precision satellite payloads continues to advance, the requirements for the pointing stability of the satellites are becoming extremely high. In many situations, even small amplitude disturbances generated by the onboard components may cause serious degradation in the performance of high precision payloads. In such situations, vibration isolators can be installed to reduce the vibration transmission. In this work, a hybrid vibration isolator comprising passive and active components is proposed to provide an effective solution to the vibration problems caused by the reaction wheel disturbances. Firstly, mathematical modeling and experimental study of a single axis vibration isolator having high damping and high roll-off rate for the high frequency region and active components that enhance isolation performance for narrow frequency bands are presented. This concept is then extended to multi-axis by forming Stewart platform and the performance is experimentally verified. The tests on a flexible testbed show effective vibration isolation by the proposed vibration isolator.

  7. Vibration induced flow in hoppers: DEM 2D polygon model

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A two-dimensional discrete element model (DEM) simulation of cohesive polygonal particles has been developed to assess the benefit of point source vibration to induce flow in wedge-shaped hoppers. The particle-particle interaction model used is based on a multi-contact principle.The first part of the study investigated particle discharge under gravity without vibration to determine the critical orifice size (Be) to just sustain flow as a function of particle shape. It is shown that polygonal-shaped particles need a larger orifice than circular particles. It is also shown that Be decreases as the number of particle vertices increases. Addition of circular particles promotes flow of polygons in a linear manner.The second part of the study showed that vibration could enhance flow, effectively reducing Be. The model demonstrated the importance of vibrator location (height), consistent with previous continuum model results, and vibration amplitude in enhancing flow.

  8. Evaluation of Ground Vibrations Induced by Military Noise Sources

    Science.gov (United States)

    2006-08-01

    vegetation (Eglin AFB, Florida, 2002). b. Typical sensor location. Two high pressure microphones are covered with waterproof bags to protect them from...at the surface of the snow cover itself. The yellow boxes are waterproof digitizers, and the black case and white bucket are used to protect the...measurement set have peak pressure levels above the Army airblast criterion of 138 dB for cosmetic damage, and that the ANSI standard prediction of

  9. An Experimental Investigation of Vibration-Induced Droplet Atomization.

    Science.gov (United States)

    Vukasinovic, Bojan; Smith, Marc K.; Glezer, Ari

    1998-11-01

    The atomization process in a mm-scale liquid droplet placed on a vibrating membrane is investigated experimentally. When the wavelength of the Faraday surface waves is smaller than the characteristic dimension of the droplet, the waves grow in amplitude as the excitation amplitude increases and ultimately begin to eject small secondary droplets from the wave crests. The high membrane acceleration needed to attain ejection (typically 300g) is achieved by driving a light-weight membrane near its resonant frequencies (nominally 1000-6000 Hz). The evolution and rate of the droplet-ejection process depend on a coupled system dynamic between the liquid droplet and the vibrating membrane. Depending on the excitation frequency and amplitude, various types of droplet-ejection processes can occur. For example, when step forcing (with prescribed frequency and amplitude) is applied, rapid atomization occurs. This event is triggered along the circumference of the droplet near the contact line by a strong azimuthal instability. In the present experiments, the droplet-ejection process and the resulting spray characteristics are investigated using high-speed video and two-frame particle tracking velocimetry.

  10. Vibration-Induced Droplet Atomization --- A Theoretical Investigation.

    Science.gov (United States)

    James, Ashley; Smith, Marc K.; Glezer, Ari

    1997-11-01

    The atomization of a liquid droplet placed on a vibrating membrane starts with the development of Faraday free surface waves. As the excitation amplitude increases, the waves grow in amplitude and ultimately begin to eject smaller secondary droplets from the wave crests. The rate of droplet ejection can be large enough to completely drain the primary droplet, an event we call bursting. The evolution of the droplet ejection process depends on a coupled system dynamic between the droplet and the membrane. When droplets are ejected the resonant frequency of the system increases. This changes the acceleration felt by the droplet and, in turn, the rate of droplet ejection. Depending on the excitation frequency and amplitude, various types of bursting or droplet ejection processes may occur. A simple, single degree-of-freedom model of this coupled system is presented. The model is used to illustrate the effect of the excitation frequency and amplitude and the initial droplet size on the acceleration of the membrane and the droplet ejection rate. The results of the model will be compared to our experimental data on droplet ejection. Additional work is directed towards an understanding of the mechanism behind the droplet ejection process.

  11. An Experimental Investigation of Vibration Induced Droplet Atomization*

    Science.gov (United States)

    Vukasinovic, Bojan; Smith, Marc K.; Glezer, Ari

    1999-11-01

    The atomization of a millimeter-scale liquid droplet placed on a vibrating diaphragm is investigated experimentally using high-speed imaging and particle-tracking techniques. Atomization is the result of the rapid ejection of small secondary droplets from the wave crests of a hierarchy of forced surface waves on the primary droplet. The evolution and rate of ejection depend on the coupled dynamics of the primary droplet and the vibrating diaphragm. The present data indicate that secondary droplet ejection results from the collapse of surface craters formed during the evolution of capillary surface waves on the primary droplet. The collapse of the crater and the ensuing ejection of a momentary liquid jet are similar to ejection processes at free surfaces that are induced by the bursting of gas bubbles or the impingement of liquid droplets. The spray characteristics of the ejected droplets are investigated over a broad range of vibrating frequencies (up to 14 kHz) using particle-tracking velocimetry. * Supported by NASA Microgravity Res. Div., Grant NAG3-1949.

  12. Vibration induced phase noise in Mach-Zehnder atom interferometers

    CERN Document Server

    Miffre, A; Büchner, M; Trénec, G; Vigué, J; Miffre, Alain; Jacquey, Marion; B\\"{u}chner, Matthias; Vigu\\'{e}, Jacques

    2006-01-01

    The high inertial sensitivity of atom interferometers has been used to build accelerometers and gyrometers but this sensitivity makes these interferometers very sensitive to the laboratory seismic noise. This seismic noise induces a phase noise which is large enough to reduce the fringe visibility in many cases. We develop here a model calculation of this phase noise in the case of Mach-Zehnder atom interferometers and we apply this model to our thermal lithium interferometer. We are thus able to explain the observed dependence of the fringe visibility with the diffraction order. The dynamical model developed in the present paper should be very useful to further reduce this phase noise in atom interferometers and this reduction should open the way to improved interferometers.

  13. Vibration-Induced Droplet Atomization --- An Experimental Investigation.

    Science.gov (United States)

    Vukasinovic, Bojan; Smith, Marc K.; Glezer, Ari

    1997-11-01

    The atomization of a liquid droplet placed on a vibrating membrane starts with the development of Faraday free surface waves. As the excitation amplitude increases, the waves grow in amplitude and ultimately begin to eject smaller secondary droplets from the wave crests. The rate of droplet ejection can be large enough to completely drain the primary droplet, an event we call bursting. The evolution of the droplet ejection process depends on a coupled system dynamic between the droplet and the membrane. When droplets are ejected the resonant frequency of the system increases. This changes the acceleration felt by the droplet and, in turn, the rate of droplet ejection. Depending on the excitation frequency and amplitude, various types of bursting or droplet ejection processes may occur. In the present experiments, the high acceleration needed to attain ejection (typically 300g) is achieved by driving a light-weight membrane near its resonant frequency (nominally 1000 Hz). The resonant characteristics and the acceleration during the ejection process for various droplet sizes and excitation amplitudes are investigated using a surface-mounted microfabricated accelerometer and a laboratory computer system.

  14. Vibration-induced field fluctuations in a superconducting magnet

    CERN Document Server

    Britton, J W; Bohnet, J G; Uys, H; Biercuk, M J; Bollinger, J J

    2015-01-01

    Superconducting magnets enable precise control of nuclear and electron spins, and are used in experiments that explore biological and condensed matter systems, and fundamental atomic particles. In high-precision applications, a common view is that that slow (<1 Hz) drift of the homogeneous magnetic field limits control and measurement precision. We report on previously undocumented higher-frequency field noise (10 Hz to 200 Hz) that limits the coherence time of 9Be+ electron-spin qubits in the 4.46 T field of a superconducting magnet. We measure a spin-echo T2 coherence time of ~6 ms for the 9Be+ electron-spin resonance at 124 GHz, limited by part-per-billion fractional fluctuations in the magnet's homogeneous field. Vibration isolation of the magnet improved T2 to ~50 ms.

  15. Vibration-induced field fluctuations in a superconducting magnet

    Science.gov (United States)

    Britton, J. W.; Bohnet, J. G.; Sawyer, B. C.; Uys, H.; Biercuk, M. J.; Bollinger, J. J.

    2016-06-01

    Superconducting magnets enable precise control of nuclear and electron spins, and are used in experiments that explore biological and condensed-matter systems, and fundamental atomic particles. In high-precision applications, a common view is that slow (Be+9 electron-spin qubits in the 4.46 -T field of a superconducting magnet. We measure a spin-echo T2 coherence time of ˜6 ms for the Be+9 electron-spin resonance at 124 GHz , limited by part-per-billion fractional fluctuations in the magnet's homogeneous field. Vibration isolation of the magnet improved T2 to ˜50 ms.

  16. Ionic vibration induced transparency and Autler-Townes splitting

    Science.gov (United States)

    Shao, Wenjun; Wang, Fei; Feng, Xun-Li; Oh, C. H.

    2017-04-01

    In this work, the absorption spectrum of a two-level ion in a linear Paul trap is investigated, the ion is supposed to be driven by two orthogonal laser beams, the one along the axial of the trap acts as the control light beam, the other as probe beam. When the frequency of the control laser is tuned to the first red sideband of the ionic transition, the coupling between the internal states of the ion and vibrational mode turns out to be a Jaynes-Cummings (JC) Hamiltonian, which together with the coupling between the probe beam and the two-level ion constructs a Λ -type three-level structure. In this case the transparency window may appear in the absorption spectrum of the probe light, which is induced by the ionic vibration and is very similar to the cavity induced transparency (Rice and Brecha 1996 Opt. Commun. 126 230-5). On the other hand, when the frequency of the control laser is tuned to the first blue sideband of the ionic transition, the two-level ion and vibrational mode are governed by an anti-Jaynes-Cummings (anti-JC) Hamiltonian, the total system including the probe beam forms a V-type three-level structure. And the Autler-Townes splitting in the absorption spectrum is found.

  17. Vibration-induced changes in EMG during human locomotion.

    NARCIS (Netherlands)

    Verschueren, S.M.P.; Swinnen, S.P.; Desloovere, K.; Duysens, J.E.J.

    2003-01-01

    The present study was set up to examine the contribution of Ia afferent input in the generation of electromyographic (EMG) activity. Subjects walked blindfolded along a walkway while tendon vibration was applied continuously to a leg muscle. The effects of vibration were measured on mean EMG

  18. Predictions of experimentally observed stochastic ground vibrations induced by blasting.

    Science.gov (United States)

    Kostić, Srđan; Perc, Matjaž; Vasović, Nebojša; Trajković, Slobodan

    2013-01-01

    In the present paper, we investigate the blast induced ground motion recorded at the limestone quarry "Suva Vrela" near Kosjerić, which is located in the western part of Serbia. We examine the recorded signals by means of surrogate data methods and a determinism test, in order to determine whether the recorded ground velocity is stochastic or deterministic in nature. Longitudinal, transversal and the vertical ground motion component are analyzed at three monitoring points that are located at different distances from the blasting source. The analysis reveals that the recordings belong to a class of stationary linear stochastic processes with Gaussian inputs, which could be distorted by a monotonic, instantaneous, time-independent nonlinear function. Low determinism factors obtained with the determinism test further confirm the stochastic nature of the recordings. Guided by the outcome of time series analysis, we propose an improved prediction model for the peak particle velocity based on a neural network. We show that, while conventional predictors fail to provide acceptable prediction accuracy, the neural network model with four main blast parameters as input, namely total charge, maximum charge per delay, distance from the blasting source to the measuring point, and hole depth, delivers significantly more accurate predictions that may be applicable on site. We also perform a sensitivity analysis, which reveals that the distance from the blasting source has the strongest influence on the final value of the peak particle velocity. This is in full agreement with previous observations and theory, thus additionally validating our methodology and main conclusions.

  19. Perspective: Vibrational-induced steric effects in bimolecular reactions

    Science.gov (United States)

    Liu, Kopin

    2015-02-01

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C-H stretch-excited CHD3(v1 = 1) with F, Cl, and O(3P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O(3P) + CHD3(v1 = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical "negative" lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD3. On the contrary, the interaction between O(3P) and CHD3(v1 = 1) behaves as a "positive" lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD3(v1 = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi's rules, are made.

  20. Chronic alcohol alters rewarded behaviors and striatal plasticity

    OpenAIRE

    DePoy, Lauren; Daut, Rachel; Wright, Tara; Camp, Marguerite; Crowley, Nicole; Noronha, Bianca; Lovinger, David; Holmes, Andrew

    2014-01-01

    Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors. Ex vivo electrophysiological recordings revealed loss in efficacy of DLS synaptically induced activation and absent long-term depression after CIE. CIE increased two-bottle choice drinking and impaired Pavlovian-to-instrumental transfer but not discrimin...

  1. Social inequality in chronic disease outcomes.

    Science.gov (United States)

    Nordahl, Helene

    2014-11-01

    Socioeconomic differences in morbidity and mortality, particularly across educational groups, are widening. Differential exposures to behavioural risk factors have been shown to play an important mediating role on the social inequality in chronic diseases such as heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and lung cancer. However, much less attention has been given to the potential role of interaction, where the same level of exposure to a behavioural risk factor has different effect across socioeconomic groups, creating subgroups that are more vulnerable than others. In this thesis, Paper 1 describes the unique cohort consortium which was established by pooling and harmonising prospective data from existing cohort studies in Denmark. This consortium generated a large study population with long follow-up sufficient to study power demanding questions of mechanisms underlying social inequalities in chronic disease outcomes. In Paper 2 on incidence of coronary heart disease, smoking and body mass index partially mediated the observed educational differences. This result suggested that some of the social inequality in coronary heart disease may be enhanced by differential exposure to behavioural risk factors (i.e. smoking and obesity). In Paper 3 on incidence of stroke, an observed interaction between education and smoking indicated that participants, particularly men, with low level of education may be more vulnerable to the effect of smoking than those with high level of education in terms of ischemic stroke. Finally, Paper 4 revealed that behavioural risk factors, primarily smoking, explained a considerable part of the educational differences in cause-specific mortality. Further, this paper added important knowledge about the considerable part of the mediated effect, which could be due to interaction between education and smoking. In conclusion, the research in this thesis is a practical implementation of contemporary statistical

  2. Biofilms in chronic wounds.

    Science.gov (United States)

    James, Garth A; Swogger, Ellen; Wolcott, Randall; Pulcini, Elinor deLancey; Secor, Patrick; Sestrich, Jennifer; Costerton, John W; Stewart, Philip S

    2008-01-01

    Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference (p<0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.

  3. 考虑发动机系统动力学与动力润滑耦合的活塞拍击分析%Piston slap analysis considering the coupled vibration induced by hydrodynamic lubrication and dynamic behaviors of internal combustion engine

    Institute of Scientific and Technical Information of China (English)

    郑光泽; 袁林

    2015-01-01

    Piston slap is the major mechanical noise source of internal combustion (IC)engine.Piston slap reduction is one of the most important countermeasures to improve the noise and vibration performance of IC engine.The influences of piston skirt and cylinder liner surface roughness on the oil film dynamical behavior and piston slap were analyzed.Based on the parameters of lubricating oil film thickness and surface roughness ratio,an analytical coupled vibration model of piston skirt and cylinder liner was developed.Combined with the vibration model of piston,connecting rod,crank shaft and engine block,an analytical piston slap model which takes the coupled vibration induced by the system dynamic behaviors and hydrodynamic lubrication into account was constructed and its influences on the piston movement and piston slap induced impact force were investigated.The comparison between the presented method and the traditional method which simulates the dynamical characteristics of piston shirt and cylinder liner system by nonlinear dynamical model was discussed.Based on the experimental data,the error of the theoretical model was investigated.%为降低活塞拍击、改善发动机振动噪声性能,考虑活塞-缸套表面粗糙度对润滑状态、活塞运动及活塞拍击影响,基于膜厚比建立活塞缸套动力学分析模型。结合考虑活塞、连杆、曲轴及缸体耦合振动的发动机系统动力学分析模型,建立考虑发动机系统动力学与动力润滑的活塞拍击分析模型,探讨活塞拍击现象。与传统的活塞-缸套非线性动力学分析模型进行对比分析,并结合缸体振动响应实验数据,讨论理论模型误差原因。

  4. A NARRATIVE: MEDITATION IN THE LIVES OF CHILDREN WITH CHRONIC ILLNESS

    Directory of Open Access Journals (Sweden)

    Taunya WIDEMAN-JOHNSTON

    2012-01-01

    Full Text Available The presence of chronic illness in one’s life often entails endless appointments, tests, medications, treatments, and procedures. In the instances of children with chronic illness, they do not know what life consists of without their illness, and consequently, have lived with many restrictions. Children with chronic illness and their families are not only in need of traditional methods and strategies from the medical model but are often in need of additional strategies to support and cope with the nature and effects of the chronic illness. This paper focuses on how mediation, mindfulness, and visualization strategies aid individuals with chronic illness.

  5. Lipid Mediators in the Resolution of Inflammation

    Science.gov (United States)

    Serhan, Charles N.; Chiang, Nan; Dalli, Jesmond; Levy, Bruce D.

    2015-01-01

    Mounting of the acute inflammatory response is crucial for host defense and pivotal to the development of chronic inflammation, fibrosis, or abscess formation versus the protective response and the need of the host tissues to return to homeostasis. Within self-limited acute inflammatory exudates, novel families of lipid mediators are identified, named resolvins (Rv), protectins, and maresins, which actively stimulate cardinal signs of resolution, namely, cessation of leukocytic infiltration, counterregulation of proinflammatory mediators, and the uptake of apoptotic neutrophils and cellular debris. The biosynthesis of these resolution-phase mediators in sensu stricto is initiated during lipid-mediator class switching, in which the classic initiators of acute inflammation, prostaglandins and leukotrienes (LTs), switch to produce specialized proresolving mediators (SPMs). In this work, we review recent evidence on the structure and functional roles of these novel lipid mediators of resolution. Together, these show that leukocyte trafficking and temporal spatial signals govern the resolution of self-limited inflammation and stimulate homeostasis. PMID:25359497

  6. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    Science.gov (United States)

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells.

  7. Chronic Inflammatory Polyneuropathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-02-01

    Full Text Available Thirteen children with chronic inflammatory demyelinating polyneuropathy monitored between 1975 and 2005 are reported from Centre hospitalier universitaire Sainte-Justine, Montreal, Canada.

  8. Prevention trumps treatment of antibody-mediated transplant rejection.

    Science.gov (United States)

    Knechtle, Stuart J; Kwun, Jean; Iwakoshi, Neal

    2010-04-01

    Belying the spectacular success of solid organ transplantation and improvements in immunosuppressive therapy is the reality that long-term graft survival rates remain relatively unchanged, in large part due to chronic and insidious alloantibody-mediated graft injury. Half of heart transplant recipients develop chronic rejection within 10 years - a daunting statistic, particularly for young patients expecting to achieve longevity by enduring the rigors of a transplant. The current immunosuppressive pharmacopeia is relatively ineffective in preventing late alloantibody-associated chronic rejection. In this issue of the JCI, Kelishadi et al. report that preemptive deletion of B cells prior to heart transplantation in cynomolgus monkeys, in addition to conventional posttransplant immunosuppressive therapy with cyclosporine, markedly attenuated not only acute graft rejection but also alloantibody elaboration and chronic graft rejection. The success of this preemptive strike implies a central role for B cells in graft rejection, and this approach may help to delay or prevent chronic rejection after solid organ transplantation.

  9. Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia.

    NARCIS (Netherlands)

    Nizet, T.; Elshout, F.J.J. van den; Heijdra, Y.F.; Ven, M.J.T. van de; Mulder, P.G.H.; Folgering, H.T.M.

    2005-01-01

    STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decrease

  10. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  11. MEDIATION AGREEMENTS LEGAL MODEL

    Directory of Open Access Journals (Sweden)

    Alexander Ponomarev

    2015-07-01

    Full Text Available This article focuses on the legal model of mediation agreements in Russian and international legislation. The authors consider the main provisions of the mediation agreements in civil matters, in particular, is defined by such features of the legal model as the requirements for this type of agreements. In addition, the article discusses the problematic issues of implementation of mediation agreements.

  12. Mediation as Signal

    NARCIS (Netherlands)

    Holler, M.J.; Lindner, I.

    2004-01-01

    This paper analyzes mediation as a signal. Starting from a stylized case, a game theoretical model of one-sided incomplete information, taken from Cho and Kreps (1987), is applied to discuss strategic effects of mediation. It turns out that to reject mediation can be interpreted as a ”negative signa

  13. Mediation in Special Education.

    Science.gov (United States)

    Fielding, Pamela S.

    1990-01-01

    This article presents a perspective for viewing mediation in resolving conflicts between parents and school personnel about the education of handicapped students. The appropriateness of mediation as well as its limitations are discussed, as are current uses of mediation in special education and legal problems and issues arising from its use.…

  14. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  15. Possible neuroimmunomodulation therapy in T-cell-mediated oral diseases

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Sato

    2015-01-01

    Full Text Available Introduction: Recurrent aphthous stomatitis and oral lichen planus are local chronic inflammatory diseases which are implicated in T cell-mediated immunity. According to the systematic review, there is insufficient evidence to support any specific treatment for T-cell mediated oral diseases. The hypothesis: In this paper, we propose a hypothesis that recurrent aphthous stomatitis and oral lichen planus can be treated with selective α7 subunit of nicotinic acetylcholine receptor (α7 -nAChR agonists. Our hypothesis is supported by the following two facts. First, the pathophysiological conditions, T h 1/T h 17 cell activation and autonomic nervous system dysfunction, are observed in T-cell mediated oral diseases as well as in T-cell mediated systemic diseases such as rheumatoid arthritis. Second, the cholinergic anti-inflammatory pathway is inhibited in systemic T-cell mediated chronic inflammatory diseases. On the other hand, treatment with α7 -nAChR agonists which activate the cholinergic anti-inflammatory pathway suppresses neuroinflammation via inhibition of T h 1/T h 17 responses in animal model of systemic T-cell mediated chronic inflammatory diseases. We thus expect that selective α7 -nAChR agonists will be effective for the treatment of T-cell mediated oral diseases. Evaluation of the hypothesis: To test our hypothesis, we need to develop in vivo mouse model of T-cell mediated oral diseases. To evaluate the therapeutic effect of a selective α7 -nAChR agonist, we choose ABT-107 because of its safety and tolerability. We believe that the selective α7 -nAChR agonist, especially ABT-107, may be a therapeutic drug to treat T-cell mediated oral diseases.

  16. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    Science.gov (United States)

    ... Home Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema Recommend on Facebook Tweet Share Compartir ... U.S. Morbidity Number of adults with diagnosed chronic bronchitis in the past year: 9.3 million Percent ...

  17. Anti-cytokine therapy in chronic destructive arthritis.

    NARCIS (Netherlands)

    Berg, W.B. van den

    2001-01-01

    Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are considered to be master cytokines in chronic, destructive arthritis. Therapeutic approaches in rheumatoid arthritis (RA) patients have so far focused mainly on TNF, which is a major inflammatory mediator in RA and a potent inducer of IL-1; ant

  18. Dysautonomic polyneuropathy as a variant of chronic inflammatory "demyelinating" polyneuropathy?

    Science.gov (United States)

    Wolf, Hans-Heinrich; Kornhuber, Malte Erich; Weis, Joachim; Posa, Andreas

    2016-08-01

    This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms.

  19. Acute and Chronic Urticaria: Evaluation and Treatment.

    Science.gov (United States)

    Schaefer, Paul

    2017-06-01

    Urticaria commonly presents with intensely pruritic wheals, sometimes with edema of the subcutaneous or interstitial tissue. It has a lifetime prevalence of about 20%. Although often self-limited and benign, it can cause significant discomfort, continue for months to years, and uncommonly represent a serious systemic disease or life-threatening allergic reaction. Urticaria is caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically; anaphylaxis must be ruled out. Chronic urticaria is idiopathic in 80% to 90% of cases. Only a limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers, if identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses. First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, high-potency antihistamines, and brief corticosteroid bursts may be used as adjunctive treatment. In refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within a year.

  20. Coping with Chronic Illness

    Science.gov (United States)

    Having a long-term, or chronic, illness can disrupt your life in many ways. You may often be tired and in pain. Your illness might affect your ... able to work, causing financial problems. For children, chronic illnesses can be frightening, because they may not ...

  1. Chronic Postoperative Roseomonas Endophthalmitis▿

    OpenAIRE

    Chen, Kuan-Jen; Lai, Chi-Chun; Kuo, Ya-Hui; WU, WEI-CHI; CHEN, TUN-LU

    2008-01-01

    We report one case with chronic postoperative endophthalmitis caused by Roseomonas species. Roseomonas spp. induced chronic endophthalmitis, which might result in misdiagnosis and delayed treatment and causes ocular damage and severe visual loss. This report is the first one related to a case with postoperative endophthalmitis secondary to Roseomonas infection.

  2. Chronic postoperative Roseomonas endophthalmitis.

    Science.gov (United States)

    Chen, Kuan-Jen; Lai, Chi-Chun; Kuo, Ya-Hui; Wu, Wei-Chi; Chen, Tun-Lu

    2009-01-01

    We report one case with chronic postoperative endophthalmitis caused by Roseomonas species. Roseomonas spp. induced chronic endophthalmitis, which might result in misdiagnosis and delayed treatment and causes ocular damage and severe visual loss. This report is the first one related to a case with postoperative endophthalmitis secondary to Roseomonas infection.

  3. [Chronic pancreatitis, acute pancreatitis].

    Science.gov (United States)

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  4. Chronic gastritis - an update.

    Science.gov (United States)

    Varbanova, Mariya; Frauenschläger, Katrin; Malfertheiner, Peter

    2014-12-01

    Helicobacter pylori is the main aetiologic factor for chronic gastritis worldwide. The degree of inflammation and the evolution of this form of chronic gastritis can vary largely depending on bacterial virulence factors, host susceptibility factors and environmental conditions. Autoimmune gastritis is another cause of chronic inflammation in the stomach, which can occur in all age groups. This disease presents typically with vitamin B12 deficiency and pernicious anaemia. The presence of anti-parietal cell antibodies is highly specific for the diagnosis. The role of H. pylori as a trigger for autoimmune gastritis remains uncertain. Other rare conditions for chronic gastritis are chronic inflammatory conditions such as Crohn's disease or on the background of lymphocytic or collagenous gastroenteropathies. Copyright © 2014. Published by Elsevier Ltd.

  5. Chronic granulomatous disease associated with chronic glomerulonephritis

    DEFF Research Database (Denmark)

    Frifelt, J J; Schønheyder, Henrik Carl; Valerius, Niels Henrik

    1985-01-01

    A boy with chronic granulomatous disease (CGD) developed glomerulonephritis at the age of 12 years. The glomerulonephritis progressed to terminal uraemia at age 15 when maintenance haemodialysis was started. The clinical course was complicated by pulmonary aspergillosis and Pseudomonas septicaemia...... from which he eventually died. The glomerulonephritis was of unknown origin, and a possible relationship between CGD and glomerulonephritis is discussed....

  6. Novel immunotherapeutic strategies in chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Mathis, Stéphane; Vallat, Jean-Michel; Magy, Laurent

    2016-02-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic immune-mediated neuropathy: it is clinically heterogeneous (relapsing-remitting form, chronic progressive form, monophasic form or CIDP having a Guillain-Barré syndrome-like onset), but potentially treatable. Although its pathophysiology remains largely unknown, CIDP is considered an immune-mediated neuropathy. Therefore, many immunotherapies have been proposed in this peripheral nervous system disorder, the most known efficient treatments being intravenous immunoglobulin, corticosteroids and plasma exchange. However, these therapies remain unsatisfactory for many patients, so numerous other immunotherapeutic strategies have been evaluated, based on their immunosuppressant or immunomodulatory potency. We have performed a large review of the literature about treatment in CIDP, with a special emphasis on novel and alternative immunotherapeutic strategies.

  7. What Is Chronic Myeloid Leukemia?

    Science.gov (United States)

    ... Chronic Myeloid Leukemia (CML) About Chronic Myeloid Leukemia What Is Chronic Myeloid Leukemia? Cancer starts when cells ... their treatment is the same as for adults. What is leukemia? Leukemia is a cancer that starts ...

  8. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Chronic Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  9. Chronic Pelvic Pain in Women

    Science.gov (United States)

    Chronic pelvic pain in women Overview By Mayo Clinic Staff Chronic pelvic pain is pain in the area below your bellybutton ... your hips that lasts six months or longer. Chronic pelvic pain can have multiple causes. It can be a ...

  10. Immune-mediated diseases in primary sclerosing cholangitis

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Janse, Marcel; Haagsma, Elizabeth B.; van den Berg, Arie P.; Weersma, Rinse K.

    2011-01-01

    Background: Primary sclerosing cholangitis is a chronic cholestatic liver disease. An immune aetiology is suggested by associations between PSC and inflammatory bowel disease. Data on concomitant prevalence of other immune-mediated diseases is limited. Aim: To assess the prevalence of concomitant im

  11. Immune-mediated diseases in primary sclerosing cholangitis

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Janse, Marcel; Haagsma, Elizabeth B.; van den Berg, Arie P.; Weersma, Rinse K.

    2011-01-01

    Background: Primary sclerosing cholangitis is a chronic cholestatic liver disease. An immune aetiology is suggested by associations between PSC and inflammatory bowel disease. Data on concomitant prevalence of other immune-mediated diseases is limited. Aim: To assess the prevalence of concomitant

  12. Mechanisms of conduction block in immune-mediated polyneuropathies

    NARCIS (Netherlands)

    Straver, D.C.G.

    2013-01-01

    Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies. Despite treatment being available, patients suffer from disabling weakness of arm and leg muscles and fatigue. Pathogenesis of MMN and CIDP is unclear, but the development

  13. Central Mechanisms of Abnormal Sympathoexcitation in Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Takuya Kishi

    2012-01-01

    Full Text Available It has been recognized that the sympathetic nervous system is abnormally activated in chronic heart failure, and leads to further worsening chronic heart failure. In the treatment of chronic heart failure many clinical studies have already suggested that the inhibition of the abnormal sympathetic hyperactivity by beta blockers is beneficial. It has been classically considered that abnormal sympathetic hyperactivity in chronic heart failure is caused by the enhancement of excitatory inputs including changes in peripheral baroreceptor and chemoreceptor reflexes and chemical mediators that control sympathetic outflow. Recently, the abnormalities in the central regulation of sympathetic nerve activity mediated by brain renin angiotensin system-oxidative stress axis and/or proinflammatory cytokines have been focused. Central renin angiotensin system, proinflammatory cytokines, and the interaction between them have been determined as the target of the sympathoinhibitory treatment in experimental animal models with chronic heart failure. In conclusion, we must recognize that chronic heart failure is a syndrome with an abnormal sympathoexcitation, which is caused by the abnormalities in the central regulation of sympathetic nerve activity.

  14. The impact of ruxolitinib treatment on inflammation-mediated comorbidities in myelofibrosis and related neoplasms

    DEFF Research Database (Denmark)

    Bjørn, Mads Emil; Hasselbalch, Hans Carl

    2015-01-01

    The inflammation-mediated comorbidities in myelofibrosis (MF) and related neoplasms (MPNs) likely reflect the concurrent immune deregulation and systemic inflammatory nature of the MPNs, emphasizing the link between chronic systemic inflammation, immune deregulation, and the malignant clone. JAK1......-2 inhibitors in MF-patients reduce constitutional symptoms and splenomegaly, but also taget autoimmune and inflammation-mediated comorbidities....

  15. Chronic hypersensitivity pneumonitis

    Science.gov (United States)

    Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

  16. Inflammation in Chronic Wounds.

    Science.gov (United States)

    Zhao, Ruilong; Liang, Helena; Clarke, Elizabeth; Jackson, Christopher; Xue, Meilang

    2016-12-11

    Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research.

  17. Chronic Arsenic poisoning.

    Science.gov (United States)

    Ahsan, Tasnim; Zehra, Kaneez; Munshi, Alia; Ahsan, Samiah

    2009-02-01

    Chronic Arsenic Toxicity may have varied clinical presentations ranging from non-cancerous manifestations to malignancy of skin and different internal organs. Dermal lesions such as hyper pigmentation and hyperkeratosis, predominantly over palms and soles are diagnostic of Chronic Arsenicosis. We report two cases from a family living in Sukkur who presented with classical skin lesions described in Chronic Arsenicosis. The urine, nail and hair samples of these patients contained markedly elevated levels of arsenic. Also the water samples from their household and the neighbouring households were found to have alarming levels of inorganic Arsenic.

  18. 用心率变异性谱分析法研究振动性白指患者自主神经系统对冷刺激的反应%Autonomic Nervous Response to Cold Provocation in Vibration-Induced White Finger(VWF) Patients with HRV Analysis

    Institute of Scientific and Technical Information of China (English)

    罗进; 神原久孝; 朱善宽

    1999-01-01

    目的研究振动性白指患者的自主神经系统对冷刺激的反应.方法 22名振动性白指患者(VWF组)及19名正常对照(对照组)进行了局部冷水刺激实验,记录受试者的心电信号,实验后将记录的心电信号通过处理转化为R-R间期信号,然后对这些R-R间期信号进行功率谱分析,计算标准化的LF(0.02~0.15 Hz)功量(LF%),标准化的HF(0.15~0.40Hz)功量(HF%),以及LF/HF比率.结果冷暴露开始后,VWF组及对照组的HF%与暴露前的水平相比都有显著下降,VWF组的LF/HF比率与暴露前的水平相比有显著增大,而且冷暴露中VWF组的LF/HF比率显著高于对照组的相应的LF/HF比率.结论冷刺激导致VWF组和对照组的副交感神经活动减弱,但对照组还能保持交感与副交感的平衡,而VWF组却不能保持两者平衡,交感神经活动明显占优,冷刺激中VWF组LF/HF比率明显高于对照组的LF/HF比率说明振动性白指患者的交感神经系统对冷刺激可能存在过敏反应.%Objective To evaluate the autonomic nervous response of Vibration-induced white finger(VWF) patients to cold provocation test by power spectral analysis of heart rate variability(HRV).Methods The cold provocation test was conducted in 22 VWF patients and 19 healthy volunteers.ECG was recorded during the experiment,and converted to R-R interval signals after the experiment.The normalized LF[(0.02~0.15) Hz]component power,normalized HF[(0.15~0.40) Hz] component power and the ratio of LF to HF power(LF/HF ratio) were calculated.Results At the beginning of cold exposure,there were a significant decrease of HF% in both groups,and a significant increase of LF/HF ratio in VWF group as compared with pre-exposure value.The LF/HF ratio in VWF group during cold exposure was significantly higher than that in the control group.Conclusion Cold stimuli induced depression of parasympathetic nervous system in both groups,and the sympatho-vagal balance was maintained in the

  19. CHRONIC MUCOCUTANEOUS CANDIDIASIS: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Subhashini

    2015-08-01

    Full Text Available Chronic mucocutaneous candidiasis (CMC is a rare group of overlapping syndromes that have in common a clinical pattern of persistent and diffuse cutaneous or mucosal candidal infections. It is usually associated with multiple endocrine dysf unctions and autoimmune disorders therefore patient needs a complete systemic evaluation. Patients of CMC are also susceptible to other fungal and viral infections due to impaired cell mediated immunity. We report a case of CMC wherein the cutaneous and mu cosal lesions were not associated with any systemic disorder. The patient responded to topical clotrimazole and oral fluconazole.

  20. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...

  1. Chronic Illness & Mental Health

    Science.gov (United States)

    ... is present. For More Information Share Chronic Illness & Mental Health Download PDF Download ePub Order a free hardcopy ... For more information, see the National Institute of Mental Health (NIMH) booklet on Depression at http://www.nimh. ...

  2. Chronic penile strangulation

    Directory of Open Access Journals (Sweden)

    Lopes Roberto I

    2003-01-01

    Full Text Available Chronic penile strangulation is exceedingly rare with only 5 cases previously reported. We report an additional case of progressive penile lymphedema due to chronic intermittent strangulation caused by a rubber band applied to the penile base for 6 years. A 49-year-old man presented incapacity to exteriorize the glans penis. For erotic purposes, he had been using a rubber-enlarging band placed in the penile base for 6 years. With chronic use, he noticed that his penis swelled. Physical examination revealed lymphedema of the penis, phimosis and a stricture in the penile base. The patient was submitted to circumcision and the lymphedema remained stable 10 months postoperatively. Chronic penile incarceration usually causes penile lymphedema and urinary disturbance. Treatment consists of removal of foreign devices and surgical treatment of lymphedema.

  3. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... and oxygen therapy Right-sided heart failure or cor pulmonale (heart swelling and heart failure due to chronic ... PA: Elsevier Saunders; 2016:chap 44. Read More Cor pulmonale Dilated cardiomyopathy Heart failure - overview Lung disease Patient ...

  4. Chronic Kidney Disease (CKD)

    Science.gov (United States)

    ... CKD treated? Kidney-friendly diet for CKD What causes chronic kidney disease (CKD)? Anyone can get CKD. Some people are ... and high blood pressure are the most common causes of CKD. If you have diabetes or high blood pressure, ...

  5. Chronic Conditions Dashboard

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Chronic Conditions Dashboard presents statistical views of information on the prevalence, utilization and Medicare spending for Medicare beneficiaries with...

  6. Chronic Daily Headaches

    Science.gov (United States)

    ... reduce the frequency and intensity of chronic headaches. Biofeedback. You might be able to control headaches by ... reduction techniques, such as yoga, tai chi or meditation. Reduce caffeine. While some headache medications include caffeine ...

  7. Chronic pelvic pain

    African Journals Online (AJOL)

    It affects all spheres of life, from physical and psychological health to relationship intimacy .... pelvic and sexual pain, in the absence of obvious pathology, has a strong .... Uterine orientation, size, mobility and sensitivity can point to a chronic ...

  8. Chronic Fatigue Syndrome

    Science.gov (United States)

    Chronic fatigue syndrome (CFS) is a disorder that causes extreme fatigue. This fatigue is not the kind of tired feeling that ... activities. The main symptom of CFS is severe fatigue that lasts for 6 months or more. You ...

  9. Chronic pelvic pain

    National Research Council Canada - National Science Library

    Slawomir Wozniak

    2016-01-01

    [b][/b][b]Introduction. [/b]Chronic pelvic pain (CPP) affects about 10–40% of women presenting to a physician, and is characterised by pain within the minor pelvis persisting for over 6 months. [b...

  10. Chronic Kidney Disease

    Science.gov (United States)

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  11. Chronic Exertional Compartment Syndrome

    Science.gov (United States)

    ... through the pain; that can lead to permanent muscle or nerve damage. Sometimes chronic exertional compartment syndrome is mistaken for shin splints, a more common cause of leg pain in young people who do a lot of vigorous weight- ...

  12. Chronic Condition Data Warehouse

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Chronic Condition Data Warehouse (CCW) provides researchers with Medicare and Medicaid beneficiary, claims, and assessment data linked by beneficiary across...

  13. Chronic Conditions Chartbook

    Data.gov (United States)

    U.S. Department of Health & Human Services — Chronic Conditions among Medicare Beneficiaries is a chartbook prepared by the Centers for Medicare and Medicaid Services and created to provide an overview of...

  14. CHRONIC UNEXPLAINED OROFACIAL PAIN

    Directory of Open Access Journals (Sweden)

    Aleš Vesnaver

    2002-04-01

    Full Text Available Background. Chronic unexplained orofacial pain is frequently the cause of prolonged suffering for the patient and an unsolvable problem for the therapist. Pathophysiology of the onset of this type of pain is virtually unknown. Still, it is possible to divide chronic orofacial pain into several separate categories, according to its onset, symptoms and therapy. All forms of this type of pain have a strong psychological component.Methods. A retrograde review was conducted, in which patients’ records, treated in 1994 for chronic unexplained orofacial pain, were followed through a 5 year period. The modalities of treatment then and at present were compared.Conclusions. Except for trigeminal neuralgia, where carbamazepine remains the first choice drug, treatment of chronic facial pain has changed considerably.

  15. Zabofloxacin for chronic bronchitis.

    Science.gov (United States)

    Kocsis, B; Szabo, D

    2016-09-01

    Treatment of lower respiratory tract infection poses as an ongoing challenge among respiratory tract diseases. Bacterial infections are causes of acute exacerbations in chronic bronchitis and indications for antibacterial therapy. Several antibiotics were applied to treat bacterial infections in chronic bronchitis, among them fluoroquinolones are considered potent, broad-spectrum agents with excellent tissue penetration. This monograph focuses on zabofloxacin, a novel fluoroquinolone agent recently approved and launched in South Korea, and summarizes the drug's antibacterial efficacy, pharmacokinetic properties and toxicity. Recent advances concerning fluoroquinolones in chronic bronchitis will be discussed, along with a comparison between zabofloxacin and moxifloxacin. Zabofloxacin has proved to be noninferior to moxifloxacin against major community-acquired Gram-positive and Gram-negative respiratory tract pathogens and found to be well tolerated in both oral and parenteral administrations. These features can make it a potential antimicrobial agent in therapy of chronic bronchitis and other lower respiratory tract infections.

  16. Chronic sinusitis (image)

    Science.gov (United States)

    ... and cartilage and lined with a mucous membrane. Sinusitis occurs when the membranes becomes inflamed and painful, ... a result of a blocked sinus opening. Chronic sinusitis is often caused by inflammation and blockage due ...

  17. Sleep and Chronic Disease

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . Sleep About Us About Sleep Key Sleep Disorders Sleep ... Sheets Data & Statistics Projects and Partners Resources Events Sleep and Chronic Disease Recommend on Facebook Tweet Share ...

  18. Chronic inflammatory demyelinative polyneuropathy

    DEFF Research Database (Denmark)

    Said, Gérard; Krarup, Christian

    2013-01-01

    Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired polyneuropathy presumably of immunological origin. It is characterized by a progressive or a relapsing course with predominant motor deficit. The diagnosis rests on the association of non-length-dependent predominantly motor ...

  19. Chronic Conditions PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Chronic Conditions PUFs are aggregated files in which each record is a profile or cell defined by the characteristics of Medicare beneficiaries. A profile is...

  20. Increased interleukin-13 levels in patients with chronic heart failure.

    Science.gov (United States)

    Nishimura, Yuki; Inoue, Teruo; Nitto, Takeaki; Morooka, Toshifumi; Node, Koichi

    2009-01-24

    A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in development and progress of heart failure. However, there is limited information about allergic cytokine interleukin-13 (IL-13). The inflammatory responses mediated by allergic cytokines can cause significant morbidity and mortality when they become chronic. Therefore, we elucidated the role of IL-13 in the pathophysiology of chronic heart failure. We measured plasma IL-13 levels by enzyme-linked immunosorbent assay in 110 patients with chronic heart failure and 20 control subjects. Plasma IL-13 levels were increased in heart failure patients, compared with the controls, in association with NYHA functional class. In addition, IL-13 levels were correlated positively with plasma levels of brain natriuretic peptide and C-reactive protein, and negatively with left ventricular ejection fraction. Plasma IL-13 levels may be useful for evaluating disease severity in chronic heart failure.

  1. Understanding chronic heart failure

    OpenAIRE

    Fenton, Matthew; Burch, Michael

    2007-01-01

    The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chroni...

  2. Tolerance and chronic rejection.

    OpenAIRE

    Womer, K. L.; Lee, R S; Madsen, J. C.; Sayegh, M H

    2001-01-01

    The most common cause of chronic allograft loss is an incompletely understood clinicopathological entity called chronic rejection (CR). Recent reports suggest an improvement in long-term renal allograft survival, although it is not clear from these data whether a true reduction of biopsy-proven CR has occurred. Although newer immunosuppressive medications have greatly reduced the incidence of acute rejection (AR) in the early post-transplantation period, the ideal therapy for both AR and CR w...

  3. Omalizumab for chronic urticaria

    DEFF Research Database (Denmark)

    Ivyanskiy, Ilya; Sand, Carsten; Thomsen, Simon Francis

    2012-01-01

    urticaria. We present a case series of 19 patients with chronic urticaria treated in a university department with omalizumab and give an overview of the existing literature comprising an additional 59 cases as well as a total of 139 patients enrolled in two randomized controlled trials comparing omalizumab...... with placebo. The collective evidence points to omalizumab as a safe and effective treatment option for patients with chronic urticaria who do not sufficiently respond to standard therapy as recommended by existing guidelines....

  4. Chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008430 Effect of gas exchange at maximal intensity on exercise capacity in patients with chronic obstructive pulmonary disease. WANG Haoyan(王浩彦), et al. Dept Respir Dis, Beijing Friendship Hosp, Capital Med Sci Univ, Beijing 100050. Chin J Tuberc Respir Dis 2008;31(6):414-416. Objective To investigate the effect of gas exchange at maximal intensity on exercise capacity in patients with chronic obstructive pulmonary disease (COPD).

  5. Experimental chronic periodontitis morphogenesis

    OpenAIRE

    Schneider S.A.

    2011-01-01

    Morphogenesis of periodontium tissue in a model of chronic periodontitis was studied. Adult Wistar rats wereused in a model; chronic periodontitis was developed through mastication-related loading decrease. Histological assessmentof periodontium tissue was conducted at Days 7, 14, 21 and 30. It was demonstrated that dystrophic tissue changes prevailover the inflammatory one in this particular experimental model. The structural elements of periodontium were involved intothe pathologic process ...

  6. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9...... complex, but our results did not exclude it completely either. Our attempts to demonstrate the presence of these two subunits in the Mediator complex remain inconclusive primarily due to the lack of proper expression of the tagged versions of the proteins. However, we have paved a way to further...

  7. Treatment of Chronic Cough.

    Science.gov (United States)

    Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

    2017-01-01

    Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

  8. A case of chronic inflammatory demyelinating polyneuropathy presented with unilateral ptosis.

    Science.gov (United States)

    Izadi, Sadegh; Karamimagham, Sina; Poursadeghfard, Maryam

    2014-01-01

    Chronic Inflammatory Demyelinating Polyneuropathy is an autoimmune disease with progressive and relapsing courses. The main clinical presentations are diffuse deep tendon hyporeflexia or areflexia and symmetric proximal-distal muscles weakness. Myasthenia gravis is also an immune mediated disease with fluctuating ocular and bulbar symptoms and sometimes weakness. Although both myasthenia gravis and chronic inflammatory demyelinating polyneuropathy are immune mediated disorders, clinical presentations are obviously different in the two diseases. Herein, we will report a case of chronic inflammatory demyelinating polyneuropathy who presented with isolated unilateral ptosis. Initially, the patient was managed as ocular type of myasthenia gravis, but after progression to general limb weakness and areflexia, the diagnosis of chronic inflammatory demyelinating polyneuropathy was made. Although unilateral ptosis is a typical feature of myasthenia gravis, it may be seen as the first presentation of chronic inflammatory demyelinating polyneuropathy as well which mimics myasthenia gravis disease.

  9. Results of a non-specific immunomodulation therapy on chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial

    DEFF Research Database (Denmark)

    Torre-Amione, G.; Anker, S.D.; Bourge, R.C.;

    2008-01-01

    Background Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. Methods We did a double-blind, placebo-controlled s...

  10. Results of a non-specific immunomodulation therapy on chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial

    DEFF Research Database (Denmark)

    Torre-Amione, G.; Anker, S.D.; Bourge, R.C.

    2008-01-01

    Background Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. Methods We did a double-blind, placebo-controlled s...

  11. Urticaria and Allergy-Mediated Conditions.

    Science.gov (United States)

    Jafilan, Lena; James, Charis

    2015-12-01

    Urticaria is a common condition that involves pruritic, raised skin wheals. Although urticaria is a benign, self-limiting condition, it may cause frustration for patients, often because of its chronicity and its tendency to recur. It can also be a life-threatening allergic reaction. Diagnosis is made clinically. It affects 20% of the general population. The first-line treatment for nonremitting cases includes H-1anti-histamines. However, other therapies may be employed. Other allergy-mediated skin conditions include angioedema, contact dermatitis, and atopic dermatitis. Diagnosis is clinical, and management focuses on prevention, avoiding triggers, and treating the itching and inflammation that accompany these conditions.

  12. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives.

    Science.gov (United States)

    Mostafalou, Sara; Abdollahi, Mohammad

    2013-04-15

    Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Fibromyalgia, chronic fatigue syndrome, and myofascial pain.

    Science.gov (United States)

    Bennett, R

    1998-03-01

    Epidemiologic studies continue to provide evidence that fibromyalgia is part of a spectrum of chronic widespread pain. The prevalence of chronic widespread pain is several times higher than fibromyalgia as defined by the 1990 American College of Rheumatology guidelines. There is now compelling evidence of a familial clustering of fibromyalgia cases in female sufferers; whether this clustering results from nature or nature remains to be elucidated. A wide spectrum of fibromyalgia-associated symptomatology and syndromes continues to be described. During the past year the association with interstitial cystitis has been explored, and neurally mediated hypotension has been documented in both fibromyalgia and chronic fatigue syndrome. Abnormalities of the growth hormone-insulin-like growth factor-1 axis have been also documented in both fibromyalgia and chronic fatigue syndrome. The commonly reported but anecdotal association of fibromyalgia with whiplash-type neck trauma was validated in a report from Israel. However, unlike North America, 100% of Israeli patients with posttraumatic fibromyalgia returned to work. Basic research in fibromyalgia continues to pinpoint abnormal sensory processing as being integral to understanding fibromyalgia pain. Drugs such as ketamine, which block N-methyl-D-aspartate receptors (which are often upregulated in central pain states) were shown to benefit fibromyalgia pain in an experimental setting. The combination of fluoxetine and amitriptyline was reported to be more beneficial than either drug alone in patients with fibromyalgia. A high prevalence of autoantibodies to cytoskeletal and nuclear envelope proteins was found in chronic fatigue syndrome, and an increased prevalence of antipolymer antibodies was found in symptomatic silicone breast implant recipients who often have fibromyalgia.

  14. Challenges in pediatric chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Haliloğlu, Göknur; Yüksel, Deniz; Temoçin, Cağri Mesut; Topaloğlu, Haluk

    2016-12-01

    Chronic inflammatory demyelinating neuropathy, a treatable immune-mediated disease of the peripheral nervous system is less common in childhood compared to adults. Despite different sets of diagnostic criteria, lack of a reliable biologic marker leads to challenges in diagnosis, follow-up and treatment. Our first aim was to review clinical presentation, course, response to treatment, and prognosis in our childhood patients. We also aimed to document diagnostic and therapeutic pitfalls and challenges at the bedside. Our original cohort consisted of 23 pediatric patients who were referred to us with a clinical diagnosis of chronic inflammatory demyelinating neuropathy. Seven patients reaching to an alternative diagnosis were excluded. In the remaining patients, diagnostic, treatment and follow-up data were compared in typical patients who satisfied both clinical and electrodiagnostic criteria and atypical patients who failed to meet minimal research chronic inflammatory demyelinating neuropathy electrodiagnostic requirements. Eight of 16 patients (50%) met the minimal chronic inflammatory demyelinating neuropathy research diagnostic requirements. There was only a statistically significant difference (p = 0.010) in terms of European Neuromuscular Centre childhood chronic inflammatory diagnostic mandatory clinical criteria between the two groups. Misdiagnosis due to errors in electrophysiological interpretation (100%, n = 8), cerebrospinal fluid cytoalbuminologic dissociation (100%, n = 4 and/or subjective improvement on any immunotherapy modality (80 ± 19.27%)) was frequent. Pediatric CIDP is challenging in terms of diagnostic and therapeutic pitfalls at the bedside. Diagnostic errors due to electrophysiological interpretation, cerebrospinal fluid cytoalbuminologic dissociation, and/or subjective improvement on immunotherapy should be considered.

  15. Ruimte voor mediation

    NARCIS (Netherlands)

    Combrink-Kuiters, L.; Niemeijer, E.; Voert, M. ter

    2003-01-01

    Dit onderzoek is samen met ADR en mediation Rechterlijke macht gepubliceerd. Het doel was enerzijds na te gaan of, en onder welke condities, mediation in de Nederlandse context een effectief en efficiënt alternatief is voor de gerechtelijke geschillenbeslechting. Anderzijds inzicht te verwerven in d

  16. Teaching Mediated Public Relations.

    Science.gov (United States)

    Kent, Michael L.

    2001-01-01

    Discusses approaches to teaching a mediated public relations course, emphasizing the World Wide Web. Outlines five course objectives, assignments and activities, evaluation, texts, and lecture topics. Argues that students mastering these course objectives will understand ethical issues relating to media use, using mediated technology in public…

  17. Dynamic public service mediation

    NARCIS (Netherlands)

    Hofman, W.; Staalduinen, M. van

    2010-01-01

    This paper presents an approach to dynamic public service mediation. It is based on a conceptual model and the use of search and ranking algorithms. The conceptual model is based on Abstract State Machine theory. Requirements for dynamic service mediation were derived from a real-world case. The con

  18. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors......+ is a nonessential gene, while deletion of med11+ resulted in unviable cells. These results are in line with those obtained in S. cerevisiae. Isolation of S. pombe Mediator by the tandem affinity purification method and Co-IP experiments lead to the conclusion that Med9 and Med11 might not belong to the Mediator...... complex, but our results did not exclude it completely either. Our attempts to demonstrate the presence of these two subunits in the Mediator complex remain inconclusive primarily due to the lack of proper expression of the tagged versions of the proteins. However, we have paved a way to further...

  19. Music, Radio, and Mediatization

    DEFF Research Database (Denmark)

    Krogh, Mads; Michelsen, Morten

    2016-01-01

    Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music– radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...... of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex non- linearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life....

  20. Stimulation of cyclic AMP production in human alveolar macrophages induced by inflammatory mediators and β-sympathicomimetics

    NARCIS (Netherlands)

    F.D. Beusenberg; J.G.C. van Amsterdam (Jan); H.C. Hoogsteden (Henk); P.R.M. Hekking (P. R M); J.W. Brouwers; H.P. Schermers (H.); I.L. Bonta

    1992-01-01

    markdownabstractAbstract We have investigated the effects of inflammatory mediators and β-adrenoceptor agonists on the adenylyl cyclase responsiveness in alveolar macrophages from control subjects, patients suffering from chronic obstructive pulmonary disease (COPD) and asthmatics. Basal cyclic

  1. Expression of cyclooxygenase-1 and 2 in chronic tonsillitis.

    Science.gov (United States)

    Dilek, Fatma Husniye; Sahin, Onder; Tokyol, Cigdem; Mazlum, Mustafa; Aycicek, Abdullah

    2010-01-01

    Prostaglandins are critical mediators of inflammation and affect both humoral and cell-mediated immune responses. Recent findings show that T and B cells express COX-2 upon activation. The purpose of this study is to investigate the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic tonsillitis and to determine the sites of their expression. In addition, their expression in adult patients is compared with that in child patients. Immunohistochemical techniques were used to evaluate the expression of the enzymes COX-1 and COX-2, in chronic tonsillitis tissue specimens from adults (n = 15) and children (n = 15). There was no staining in surface epithelium or reticulated crypt epithelium. COX-1 and COX-2 expressions were observed mainly in the intraepithelial lymphoid cells in reticulated crypt epithelium and subepithelial cells. Also, COX-1 and COX-2 stained cells were found in the germinal center. There was no difference of the expressions of COX-1 and COX-2 among adults and children. The only significant difference noted between the adults and children was that, the adults had rich subepithelial plasma cells. Activated B and T cells express COX-1 and COX-2 in paraffin-embedded tissue sections of chronic tonsillitis. Further studies need to be performed to elucidate expression of COX enzymes and their immunologic role in tonsil diseases. They will play an important role in the treatment of chronic tonsillitis. Additional studies are warranted to study the effects of NSAIDs and selective COX-2 inhibitors in chronic tonsillitis.

  2. Chronic prostatitis: Current concepts

    Directory of Open Access Journals (Sweden)

    Ram Vaidyanathan

    2008-01-01

    Full Text Available Purpose: Chronic prostatitis (CP is a common condition. It causes significant suffering to the patients and constitutes a sizeable workload for the urologists. The purpose of this review is to describe the currently accepted concepts regarding the aspects of CP. Materials and Methods: Relevant papers on the epidemiology, etiology, diagnosis, evaluation and management of CP were identified through a search of MEDLINE using text terms "prostatitis", "chronic prostatitis" and "chronic pelvic pain syndrome". The list of articles thus obtained was supplemented by manual search of bibliographies of the identified articles and also by exploring the MEDLINE option "Related Articles". Results: The salient points of the relevant articles on each aspect of CP have been summarized in the form of a non-systematic narrative review. Conclusion: Chronic prostatitis is caused by a variety of infective and non-infective factors and is characterized by a rather long remitting and relapsing clinical course. The diagnosis is based on symptoms comprising pain and nonspecific urinary and/or ejaculatory disturbances and microbiological tests to localize bacteria and/or leucocytes in segmented urinary tract specimens. The contemporary classification was proposed by the National Institutes of Health/National Institute of Diabetes Digestive Kidney Diseases (NIH/NIDDK. National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI is the patient evaluation tool used extensively in clinical practice and research. Management should be individualized, multimodal and of an appropriate duration.

  3. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  4. Management of chronic paronychia

    Directory of Open Access Journals (Sweden)

    Vineet Relhan

    2014-01-01

    Full Text Available Chronic paronychia is an inflammatory disorder of the nail folds of a toe or finger presenting as redness, tenderness, and swelling. It is recalcitrant dermatoses seen commonly in housewives and housemaids. It is a multifactorial inflammatory reaction of the proximal nail fold to irritants and allergens. Repeated bouts of inflammation lead to fibrosis of proximal nail fold with poor generation of cuticle, which in turn exposes the nail further to irritants and allergens. Thus, general preventive measures form cornerstone of the therapy. Though previously anti-fungals were the mainstay of therapy, topical steroid creams have been found to be more effective in the treatment of chronic paronychia. In recalcitrant cases, surgical treatment may be resorted to, which includes en bloc excision of the proximal nail fold or an eponychial marsupialization, with or without nail plate removal. Newer therapies and surgical modalities are being employed in the management of chronic paronychia. In this overview, we review recent epidemiological studies, present current thinking on the pathophysiology leading to chronic paronychia, discuss the challenges chronic paronychia presents, and recommend a commonsense approach to management.

  5. Chronic daily headaches

    Directory of Open Access Journals (Sweden)

    Fayyaz Ahmed

    2012-01-01

    Full Text Available Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches.

  6. Immune mediated liver failure

    OpenAIRE

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  7. Chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Schölzel, B E; Snijder, R J; Mager, J J; van Es, H W; Plokker, H W M; Reesink, H J; Morshuis, W J; Post, M C

    2014-12-01

    Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

  8. Chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Pereira CA

    2016-09-01

    Full Text Available Carlos AC Pereira,1 Andréa Gimenez,2 Lilian Kuranishi,2 Karin Storrer 2 1Interstitial Lung Diseases Program, 2Pulmonology Postgraduate, Federal University of São Paulo, São Paulo, Brazil Abstract: Hypersensitivity pneumonitis (HSP is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. Keywords: interstitial lung diseases, extrinsic allergic alveolitis, diffuse lung disease, lung immune response, HRCT, farmers lung

  9. Chronic pelvic floor dysfunction.

    Science.gov (United States)

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management.

  10. [Anaemia and chronic diseases].

    Science.gov (United States)

    Chassagne, Philippe; Amalou, Laetitia; Thillard, Anne-Lyse; Gbaguidi, Xavier; Roca, Frédéric

    2015-03-01

    The prevalence of anemia in old patients is 20%. Anemia is mostly multifactorial associated with multiple comorbidities that are frequently observed in people of 65 years or older. Chronic renal failure, inflammatory diseases, nutrient deficiencies and especially iron deficiency are the most associated conditions with anemia. Anemia represents a prognosis marker of general health in old people. Thus anemia is associated with higher rates of morbidities (such as unplanned hospitalizations) and greatest mortality. Therefore anemia could be considered either as a consequence of chronic diseases or a prognosis marker of their severity. The prognosis of chronic cardiac failure is for example worst in anemic patients. Finally anemia is listed as a component of the frailty.

  11. Angiopoietin-2 in chronic renal failure patients on hemodialysis: Relationship with glomerular filtration rate in the predialysis stages

    Directory of Open Access Journals (Sweden)

    Fatma A Attia

    2013-01-01

    Conclusion Circulating angiopoietin-2 is a putative marker and potential mediator of atherosclerosis, is inversely related to glomerular filtration rate, and is increased with advanced chronic kidney disease. Normolipidemia in chronic kidney disease patients does not prevent atherosclerotic burden; this is because of the presence of other markers such as angiopoietin-2.

  12. Role of Inflammatory Mediators in the Pathogenesis of Epilepsy

    Directory of Open Access Journals (Sweden)

    Tadayuki Shimada

    2014-01-01

    Full Text Available Epilepsy is one of the most common chronic brain disorders worldwide, affecting 1% of people across different ages and backgrounds. Epilepsy is defined as the sporadic occurrence of spontaneous recurrent seizures. Accumulating preclinical and clinical evidence suggest that there is a positive feedback cycle between epileptogenesis and brain inflammation. Epileptic seizures increase key inflammatory mediators, which in turn cause secondary damage to the brain and increase the likelihood of recurrent seizures. Cytokines and prostaglandins are well-known inflammatory mediators in the brain, and their biosynthesis is enhanced following seizures. Such inflammatory mediators could be therapeutic targets for the development of new antiepileptic drugs. In this review, we discuss the roles of inflammatory mediators in epileptogenesis.

  13. [Mediation in health].

    Science.gov (United States)

    Decastello, Alice

    2008-02-10

    The author presents mediation as an alternative dispute resolution method. Mediation is a process where the parties are ready to settle their dispute out of court, by way of negotiation and with the involvement of an independent third person as mediator. In the mediation process the mediator shall not decide the dispute, nor examine the default or give legal advice or express his/her opinion - the mediator's duty is to help the parties bring their positions closer and come to a settlement agreement within a short time (120 days). The author gives a summary of the applications of the Hungarian Act on Mediation in Public Health and draws conclusions from the practical experience since entry into force of the legislation and illustrates the advantages of mediation over the court procedure (which may drag on for years). The primary advantages of mediation are that both the mediators and the parties are bound by the obligation of secrecy, the procedure is cheaper than the court proceedings, and the parties can "save their faces" because in mediation the winner-winner formula asserts itself - against lawsuits where the winner-loser positions are confronted. The author also analyses the specific data and information available so far. As for the future, the legislation needs to be amended at several points. It is particularly expedient to regulate the legal relationship between the insurance companies and the health service providers because the liability insurance may not cover the damages the courts adjudicate. And so some of the service providers may go bankrupt as the difference in excess of the upper limit of coverage - it might as well be up to HUF 5 million per case - shall be paid from own budget, to the charge of the upkeep costs. It is also required to review and amend the regulations on expert activities, just as it is inevitable to make data supply compulsory - otherwise it will be impossible to monitor the number of mediation procedures in health. At present

  14. General resonance mediation

    Energy Technology Data Exchange (ETDEWEB)

    McGarrie, Moritz

    2012-07-15

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for {sigma}(visible {yields} hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  15. Psychoneuroendocrinological studies on chronic stress and depression.

    Science.gov (United States)

    Tafet, Gustavo E; Smolovich, Jaime

    2004-12-01

    The adaptive response to stress is characterized by activation of neural and neuroendocrine cascades mediated mainly by the noradrenergic/sympathetic and limbic-hypothalamic-pituitary-adrenal (HPA) systems, respectively. Chronic psychosocial stress has long been associated with the origin and development of depression, where increased levels of cortisol have been observed in both conditions. In this regard, increased levels of cortisol could be directly involved in the mood changes observed in depression, and direct connections between these and alterations of the serotonergic neurotransmission have been also proposed. Therefore, we investigated the potential link between alterations of the limbic-HPA system with the serotonergic hypothesis of depression at both the molecular and clinical levels. Our findings support the notion that chronic psychosocial stress may lead to depression in certain individuals depending on the psychobiological background and their particular psychological resources. Therefore, certain interventions aimed at normalization of the HPA system could potentially prevent the development of depression in chronically stressed subjects. This would be possible through either pharmacological interventions or psychotherapeutic strategies, such as cognitive therapy, aimed at improving resilience and controllability in stressful situations.

  16. Chronic Renal Failure, Cachexia, and Ghrelin

    Directory of Open Access Journals (Sweden)

    A. Laviano

    2010-01-01

    Full Text Available Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  17. Chronic renal failure, cachexia, and ghrelin.

    Science.gov (United States)

    Laviano, A; Krznaric, Z; Sanchez-Lara, K; Preziosa, I; Cascino, A; Rossi Fanelli, F

    2010-01-01

    Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  18. Effects of Chronic Central Arginine Vasopressin (AVP on Maternal Behavior in Chronically Stressed Rat Dams

    Directory of Open Access Journals (Sweden)

    Benjamin C. Nephew

    2012-11-01

    Full Text Available Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3 and mid (day 10 lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing. AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress.

  19. [Histaminergic angioedema and chronic urticaria].

    Science.gov (United States)

    Hacard, Florence; Nosbaum, Audrey; Bensaid, Benoit; Nicolas, Jean-François; Augey, Frédéric; Goujon, Catherine; Bérard, Frédéric

    2015-01-01

    Most angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives. Chronic urticaria is a benign disease, and autoimmune in 40 % of cases. The occurrence of angioedema in chronic urticaria is not a sign of severity. The occurrence of angioedema in chronic urticaria is associated with a longer duration of urticarial disease. NSAIDs and/or systemic corticotherapy are classic triggers of angioedema in chronic urticaria. In the absence of clinical endpoints, there is no need to make further assessment in chronic urticaria good responders to antihistamines.

  20. Chronic obstructive pulmonary disease - adults - discharge

    Science.gov (United States)

    COPD - adults - discharge; Chronic obstructive airways disease - adults - discharge; Chronic obstructive lung disease - adults - discharge; Chronic bronchitis - adults - discharge; Emphysema - adults - discharge; Bronchitis - ...

  1. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2004-01-01

    Implementation of new computer-mediated communication (CMC) systems in organizations is a complex socio-technical endeavour, involving the mutual adaptation of technology and organization over time. Drawing on the analytic concept of sensemaking, this paper provides a theoretical perspective...... that deepens our understanding of how organizations appropriate new electronic communication media. The paper analyzes how a group of mediators in a large, multinational company adapted a new web-based CMC technology (a virtual workspace) to the local organizational context (and vice versa) by modifying...... features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. We found that these mediators exerted considerable influence on how the technology was established and used in the organization. The mediators were not neutral facilitators of a well...

  2. Natural generalized mirage mediation

    CERN Document Server

    Baer, Howard; Serce, Hasan; Tata, Xerxes

    2016-01-01

    In the supersymmetric scenario known as mirage mediation (MM), the soft SUSY breaking terms receive comparable anomaly-mediation and moduli-mediation contributions leading to the phenomenon of mirage unification. The simplest MM SUSY breaking models which are consistent with the measured Higgs mass and sparticle mass constraints are strongly disfavoured by fine-tuning considerations. However, while MM makes robust predictions for gaugino masses, the scalar sector is quite sensitive to specific mechanisms for moduli stabilization and potential uplifting. We suggest here a broader setup of generalized mirage mediation (GMM), where heretofore discrete parameters are allowed as continuous to better parametrize these other schemes. We find that natural SUSY spectra consistent with both the measured value of m(h). as well as LHC lower bounds on superpartner masses are then possible. We explicitly show that models generated from natural GMM may be beyond the reach of even high-luminosity LHC searches. In such a case...

  3. Chronic heart failure

    African Journals Online (AJOL)

    population, and up to 10% in people aged 75 years and older. It is also estimated that ... The first step in the development of heart failure is an injury to the myocardium ... treatment of heart failure by blocking the compensatory mechanisms with ... pulmonary disease, cognitive dysfunction, depression, chronic kidney disease ...

  4. Chronic Kidney Disease

    Science.gov (United States)

    ... of the feet and ankles Causes & Risk FactorsWhat causes CKD?The most common causes of CKD are high blood pressure, diabetes and heart disease. ... caused by CKD.How else is CKD treated?Chronic kidney disease can cause other problems. Talk with your doctor about how ...

  5. Chronic blood pressure control.

    Science.gov (United States)

    Brands, Michael W

    2012-10-01

    Chronic blood pressure is maintained within very narrow limits around an average value. However, the multitude of physiologic processes that participate in blood pressure control present a bewildering array of possibilities to explain how such tight control of arterial pressure is achieved. Guyton and Coleman and colleagues addressed this challenge by creating a mathematical model that integrated the short- and long-term control systems for overall regulation of the circulation. The hub is the renal-body fluid feedback control system, which links cardiac function and vascular resistance and capacitance with fluid volume homeostasis as the foundation for chronic blood pressure control. The cornerstone of that system is renal sodium excretory capability, which is defined by the direct effect of blood pressure on urinary sodium excretion, that is, "pressure natriuresis." Steady-state blood pressure is the pressure at which pressure natriuresis balances sodium intake over time; therefore, renal sodium excretory capability is the set point for chronic blood pressure. However, this often is misinterpreted as dismissing, or minimizing, the importance of nonrenal mechanisms in chronic blood pressure control. This article explains the renal basis for the blood pressure set point by focusing on the absolute dependence of our survival on the maintenance of sodium balance. Two principal threats to sodium balance are discussed: (1) a change in sodium intake or renal excretory capability and (2) a change in blood pressure. In both instances, circulatory homeostasis is maintained because the sodium balance blood pressure set point is reached.

  6. Chronic recurrent multifocal osteomyelitis

    NARCIS (Netherlands)

    Wedman, Jan; van Weissenbruch, Ranny

    2005-01-01

    We report what is, to our best knowledge, the first case of chronic recurrent multifocal osteomyelitis (CRMO) in which the frontal and sphenoid bones were involved. Characterized by a prolonged and fluctuating course of osteomyelitis at different sites, CRMO is self-limited, although sequelae can oc

  7. CHRONIC PROBLEM FAMILIES.

    Science.gov (United States)

    STONE, EDWARD

    THE REPORT POINTS OUT THAT, IN GENERAL, CHRONIC PROBLEM PARENTS GREW UP IN ENVIRONMENTS OF EMOTIONAL IMPOVERISHMENT, INCONSISTENCY, CONFUSION, AND DISORDER, OFTEN WITH DEPRIVATION OF FOOD, CLOTHING, AND SHELTER. THESE PARENTS CATEGORIZE PEOPLE AS THOSE WHO GIVE AND THOSE WHO TAKE. THEY BLAME THEIR PROBLEMS ON EXTERNAL CIRCUMSTANCES NOT UNDER THEIR…

  8. Acetaminophen for Chronic Pain

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Dideriksen, Dorthe; Vaegter, Henrik Bjarke;

    2016-01-01

    strategies for acetaminophen use in chronic pain in both Embase and PubMed, 1,551 hits were obtained. Following cross-reference searches of both trials and 38 reviews, seven studies comparing acetaminophen in continuous dosing regimens of more than two weeks with placebo were included. The review...

  9. The Chronic Responsibility

    DEFF Research Database (Denmark)

    Ravn, Iben M; Frederiksen, Kirsten; Beedholm, Kirsten

    2016-01-01

    behavior to be the main factors influencing susceptibility to chronic diseases. We argue that this discursive construction naturalizes a division between people who can actively manage responsible self-care and those who cannot. Such discourses may serve the interests of those patients who are already...

  10. Diagnosing chronic rhinosinusitis

    DEFF Research Database (Denmark)

    Lange, B; Thilsing, T; Baelum, J

    2013-01-01

    The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic and endo- scopic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies the definition is based on symptoms only. The aim of this study was to evaluate the...

  11. Diagnosing chronic rhinosinusitis

    DEFF Research Database (Denmark)

    Lange, B; Thilsing, T; Baelum, J;

    2013-01-01

    The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic and endo- scopic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies the definition is based on symptoms only. The aim of this study was to evaluate the...

  12. Bilateral chronic subdural hematoma

    DEFF Research Database (Denmark)

    Andersen-Ranberg, Nina Christine; Poulsen, Frantz Rom; Bergholt, Bo

    2016-01-01

    OBJECTIVE Bilateral chronic subdural hematoma (bCSDH) is a common neurosurgical condition frequently associated with the need for retreatment. The reason for the high rate of retreatment has not been thoroughly investigated. Thus, the authors focused on determining which independent predictors ar...

  13. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Eligio Pizzigallo

    2010-08-01

    Full Text Available The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”. Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis. The etiopathogenetic role of EBV is demonstrated only in a well-examined subgroup of patients, while in most of the remaining cases this role should be played by other infectious agents - able to remain in a latent or persistent way in the host – or even by not infectious agents (toxic, neuroendocrine, methabolic, etc.. However, the pathogenetic substrate of the different etiologic forms seems to be the same, much probably represented by the oxidative damage due to the release of pro-inflammatory cytokines as a response to the triggering event (infectious or not infectious. Anyway, recently the scientists turned their’s attention to the genetic predisposition of the subjects affected by the syndrome, so that in the last years the genetic studies, together with those of molecular biology, received a great impulse

  14. DREDed Anomaly Mediation

    CERN Document Server

    Boyda, E; Pierce, A T; Boyda, Ed; Murayama, Hitoshi; Pierce, Aaron

    2002-01-01

    We offer a guide to dimensional reduction (DRED) in theories with anomaly mediated supersymmetry breaking. Evanescent operators proportional to epsilon arise in the bare Lagrangian when it is reduced from d=4 to d= (4-2 epsilon) dimensions. In the course of a detailed diagrammatic calculation, we show that inclusion of these operators is crucial. The evanescent operators conspire to drive the supersymmetry-breaking parameters along anomaly-mediation trajectories across heavy particle thresholds, guaranteeing the ultraviolet insensitivity.

  15. Recombinant adeno-associated virus-mediated inhibiting of interleukin-4 expression in rat model of asthma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Asthma is a chronic disease characterized by reversible airway obstruction, airway hyper- responsiveness, and inflammation of airways. Th2 cells, one sort of CD4+ T lymphocytes, are currently considered to play an important role in the chronic airway inflammation of asthma. Meanwhile, a number of laboratories have clearly established the importance of the Th2-derived cytokine interleukin-4 (IL-4) in mediating the airway inflammatory response. Anti-IL-4 therapy might be beneficial in treatment of chronic asthma.

  16. Chronic Ulcerative Herpes Simplex Virus Infection of the Vulva

    Directory of Open Access Journals (Sweden)

    Kelly Griffith-Bauer

    2012-09-01

    Full Text Available Herpes simplex virus infections in HIV-infected individuals can be clinically unusual and difficult to treat due to underlying problems with cell-mediated immunity and the occurrence of antiviral resistance. Additionally, partial or incomplete restoration of immune function may result in chronic ulcerations that require rotational treatments. In this report, we describe the case of a 38-year-old HIV-positive woman who developed the ulcerative form of chronic herpes simplex infection despite highly active antiretroviral therapy and valacyclovir prophylaxis. Repeated intravenous courses of foscarnet and topical cidofovir finally controlled her erosions as her cell-mediated immunity was slowly restored. This case highlights the challenges that still exist in diagnosing and managing this rare presentation of herpes simplex virus

  17. Chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    V K Vijayan

    2013-01-01

    Full Text Available The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec to FVC (forced vital capacity ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure, hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity, bone disease (osteoporosis and osteopenia, stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease

  18. Chronic obstructive pulmonary disease.

    Science.gov (United States)

    Vijayan, V K

    2013-02-01

    The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations.

  19. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

    Science.gov (United States)

    ... and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart ... and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart ...

  20. Chronic Fatigue Syndrome (CFS): Symptoms

    Science.gov (United States)

    ... CDC.gov . Chronic Fatigue Syndrome (CFS) Share Compartir Symptoms On this Page Primary Symptoms Other Symptoms What's ... a doctor distinguish CFS from other illnesses. Primary Symptoms As the name chronic fatigue syndrome suggests , fatigue ...

  1. Mechanism of Chronic Pain in Rodent Brain Imaging

    Science.gov (United States)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  2. Exhaled nitric oxide levels in children with chronic adenotonsillar disease.

    Science.gov (United States)

    Torretta, S; Marchisio, P; Esposito, S; Garavello, W; Cappadona, M; Clemente, I A; Pignataro, L

    2011-01-01

    Exhaled nitric oxide (eNO) is a highly reactive biological mediator that has recently been associated with chronic tonsillar disease in adults, but there are no published data concerning eNO levels in their pediatric counterparts. The aim of this study is to measure mean eNO levels in children with chronic adenotonsillitis or adenotonsillar hypertrophy, and assess the effects of potential confounding factors. Children aged 3-17 years were divided into three groups (chronic adenotonsillitis, adenotonsillar hypertrophy and controls). Their eNO levels were measured in accordance with the international guidelines, and their other clinical and anamnestic characteristics were recorded. The mean eNO level in the children with chronic adenotonsillitis was slightly higher than that in the other groups, but there was no statistically significant between-group difference. Age (p=0.009), allergy (p=0.05) and body mass index (p=0.03), but not the mean grade of adenoidal or tonsil hypertrophy, were all statistically related to mean eNO levels. These preliminary results indicate the lack of an increase in mean eNO levels in children with chronic adenotonsillar disease, with no substantial difference between children with chronic adenotonsillitis and those with adenotonsillar hypertrophy.

  3. Defining and Measuring Chronic Conditions

    Centers for Disease Control (CDC) Podcasts

    2013-05-20

    This podcast is an interview with Dr. Anand Parekh, U.S. Department of Health and Human Services Deputy Assistant Secretary for Health, and Dr. Samuel Posner, Preventing Chronic Disease Editor in Chief, about the definition and burden of multiple chronic conditions in the United States.  Created: 5/20/2013 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/20/2013.

  4. Neuropsychological functioning in older adults with chronic kidney disease

    OpenAIRE

    Deria, Sirad

    2006-01-01

    Chronic Kidney Disease (CKD) is a condition that disproportionately affects older adults and is associated with high prevalence of vascular diseases and increased risk for the development of cognitive impairment. In the current study, we examined global cognition, verbal memory and executive functioning in older adults with CKD and compared their performance to age- and education-matched healthy controls. We also assessed the role of potential mediators/moderators of cognitive impairment in C...

  5. A CASE REPORT OF CHRONIC MUCOCUTANEOUS CANDIDIASIS IN IRAN

    Directory of Open Access Journals (Sweden)

    M. Moghaddami

    1991-08-01

    Full Text Available A case of chronic mucocutaneous candidiasis due to Candida albicans in a 13 yr-old boy is reported. Evaluation of cell mediated immunity revealed cutaneous anergy to PPD and low level of T-Lymphocytes B-Cell count and immunoglobulin G (IgG were increased and there was a low level of serum iron. The patient was put under treatment with oral administration of Ketoconazole and ferrus sulfate, which resulted in some clinical improvement

  6. HIV and chronic kidney disease.

    Science.gov (United States)

    Naicker, Saraladevi; Rahmanian, Sadaf; Kopp, Jeffrey B

    2015-01-01

    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV

  7. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    Science.gov (United States)

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  8. Chronic elevation of pulmonary microvascular pressure in chronic heart failure reduces bi-directional pulmonary fluid flux.

    Science.gov (United States)

    Dixon, Dani-Louise; Mayne, George C; Griggs, Kim M; De Pasquale, Carmine G; Bersten, Andrew D

    2013-04-01

    Chronic heart failure leads to pulmonary vascular remodelling and thickening of the alveolar-capillary barrier. We examined whether this protective effect may slow resolution of pulmonary oedema consistent with decreased bi-directional fluid flux. Seven weeks following left coronary artery ligation, we measured both fluid flux during an acute rise in left atrial pressure (n = 29) and intrinsic alveolar fluid clearance (n = 45) in the isolated rat lung. Chronic elevation of pulmonary microvascular pressure prevented pulmonary oedema and decreased lung compliance when left atrial pressure was raised to 20 cmH2O, and was associated with reduced expression of endothelial aquaporin 1 (P = 0.03). However, no other changes were found in mediators of fluid flux or cellular fluid channels. In isolated rat lungs, chronic LV dysfunction (LV end-diastolic pressure and infarct circumference) was also inversely related to alveolar fluid clearance (P ≤ 0.001). The rate of pulmonary oedema reabsorption was estimated by plasma volume expansion in eight patients with a previous clinical history of chronic heart failure and eight without, who presented with acute pulmonary oedema. Plasma volume expansion was reduced at 24 h in those with chronic heart failure (P = 0.03). Chronic elevation of pulmonary microvascular pressure in CHF leads to decreased intrinsic bi-directional fluid flux at the alveolar-capillary barrier. This adaptive response defends against alveolar flooding, but may delay resolution of alveolar oedema.

  9. Differential regulation of human cardiac β-adrenergic and muscarinic receptors by chronic β-adrenoceptor antagonist treatment

    OpenAIRE

    Motomura, S.; Deighton, N M; Zerkowski, H.-R.; Khamssi, M.; Brodde, O.-E.

    1990-01-01

    In patients undergoing coronary artery bypass grafting chronic β1-adrenoceptor antagonist treatment increased right atrial β1-adrenoceptor number, did not affect β2-adrenoceptor number and decreased muscarinic M2-receptor number. Concomitantly, the M2-receptor-mediated negative inotropic effect of carbachol was reduced, while the β1-adrenoceptor-mediated positive inotropic effect of noradrenaline was not altered. The β2-adrenoceptor mediated positive inotropic effect of procaterol, however, w...

  10. Extrahepatic immune related manifestations in chronic hepatitis C virus infection.

    Science.gov (United States)

    Tampaki, Maria; Koskinas, John

    2014-09-21

    The association of chronic hepatitis C with immune related syndromes has been frequently reported. There is a great range of clinical manifestations affecting various systems and organs such as the skin, the kidneys, the central and peripheral nervous system, the musculoskeletal system and the endocrine glands. Despite the high prevalence of immune related syndromes in patients with chronic hepatitis C, the exact pathogenesis is not always clear. They have been often associated with mixed cryoglobulinemia, a common finding in chronic hepatitis C, cross reaction with viral antigens, or the direct effect of virus on the affected tissues. The aim of this review is to analyze the reported hepatitis C virus immune mediated syndromes, their prevalence and clinical manifestations and to discuss the most supported theories regarding their pathogenesis.

  11. Alzheimer's disease and chronic periodontitis: is there an association?

    Science.gov (United States)

    Gaur, Sumit; Agnihotri, Rupali

    2015-04-01

    Alzheimer's disease, an affliction of old age, is one of the leading causes for dementia worldwide. Various risk factors including family history, genetics and infections have been implicated in its pathogenesis. The cognitive decline in this condition is mainly a result of the formation of amyloid deposits that provoke neuroinflammation, ultimately resulting in cell death. Recently, an association between peripheral inflammation and Alzheimer's disease was hypothesized. It was suggested that chronic systemic inflammation worsened the inflammatory processes in the brain. This was mainly attributed to increased levels of pro-inflammatory mediators, such as interleukin-1, interleukin -6 and tumor necrosis factor-α in the plasma. As chronic periodontitis is a widespread peripheral immunoinflammatory condition, it has been proposed to play a significant role in the aggravation of Alzheimer's disease. With this background, the current review focuses on the relationship between Alzheimer's disease and chronic periodontitis, and its therapeutic implications.

  12. Treating Chronic Myeloid Leukemia by Phase

    Science.gov (United States)

    ... Myeloid Leukemia (CML) Treating Chronic Myeloid Leukemia Treating Chronic Myeloid Leukemia by Phase Treatment options for people ... a stem cell donor with matching tissue type. Chronic phase The standard treatment for chronic phase CML ...

  13. Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Maria H. Madeira

    2015-01-01

    Full Text Available Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

  14. Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

    Science.gov (United States)

    Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

    2017-07-01

    To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Chronic Inflammation and  T Cells

    Directory of Open Access Journals (Sweden)

    Nathan S Fay

    2016-05-01

    Full Text Available The epithelial tissues of the skin, lungs, reproductive tract, and intestines are the largest physical barriers the body has to protect against infection. Epithelial tissues are woven with a matrix of immune cells programmed to mobilize the host innate and adaptive immune responses. Included among these immune cells are  T cells that are unique in their TCR usage, location, and functions in the body. Stress reception by  T cells as a result of traumatic epithelial injury, malignancy, and/or infection induces  T cell activation. Once activated,  T cells function to repair tissue, induce inflammation, recruit leukocytes, and lyse cells. Many of these functions are mediated via the production of cytokines and growth factors upon  T cell activation. Pathogenesis of many chronic inflammatory diseases involve  T cells; some of which are exacerbated by their presence, while others are improved.  T cells require a delicate balance between their need for acute inflammatory mediators to function normally and the detrimental impact imparted by chronic inflammation. This review will focus on the recent progress made in understanding how epithelial  T cells influence the pathogenesis of chronic inflammatory diseases and how a balance between acute and chronic inflammation impacts  T cell function. Future studies will be important to understand how this balance is achieved.

  16. Metadata based mediator generation

    Energy Technology Data Exchange (ETDEWEB)

    Critchlow, T

    1998-03-01

    Mediators are a critical component of any data warehouse, particularly one utilizing partially materialized views; they transform data from its source format to the warehouse representation while resolving semantic and syntactic conflicts. The close relationship between mediators and databases, requires a mediator to be updated whenever an associated schema is modified. This maintenance may be a significant undertaking if a warehouse integrates several dynamic data sources. However, failure to quickly perform these updates significantly reduces the reliability of the warehouse because queries do not have access to the m current data. This may result in incorrect or misleading responses, and reduce user confidence in the warehouse. This paper describes a metadata framework, and associated software designed to automate a significant portion of the mediator generation task and thereby reduce the effort involved in adapting the schema changes. By allowing the DBA to concentrate on identifying the modifications at a high level, instead of reprogramming the mediator, turnaround time is reduced and warehouse reliability is improved.

  17. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    Jia Luo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  18. Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Mostafalou, Sara; Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca

    2013-04-15

    Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up.

  19. Chronic intestinal pseudoobstruction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok [Seoul National University Children' s Hospital, Seoul (Korea, Republic of)

    1992-03-15

    Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome.

  20. [Chronic inflammatory demyelinating polyradiculoneuropathy].

    Science.gov (United States)

    Franques, J; Azulay, J-P; Pouget, J; Attarian, S

    2010-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating chronic neuropathy of immune origin whose diagnosis is based upon clinical, biological and electrophysiological data; previously critical to the diagnosis the nerve biopsy is now restricted to the rare situations where accurate diagnosis cannot be reached using these data alone. CIDP are mainly idiopathic, but a few associated diseases must be sought for as they require specific attention. Such associated diseases must particularly be discussed when the manifestations are severe or resistant to immunomodulating or immunosuppressive agents. Indeed, idiopathic CIDP are usually responsive to these treatments. The effectiveness of these treatments is limited by the importance of the secondary axonal loss. The dependence or the resistance may sometimes justify the association of several immunomodulating treatments. A single randomized controlled trial support the use of cytotoxic drugs and none with rituximab.

  1. Chronic Stress and Performance

    Science.gov (United States)

    2011-09-01

    to the cannabinoid CB(1) receptor agonist HU-210 following chronic stress. European Journal of Pharmacology, 499(3), 291-295. Holscher, C. (1999...learning and memory, has the highest concentration of GC receptors in the brain and is involved in the stress response. Extensive research has... receptor levels than stressed male rodents (Konkle, 2003; Figueiredo, 2002; Handa, 1994). Males and females react to stress differently, so two models

  2. Renal failure (chronic)

    OpenAIRE

    Clase, Catherine

    2011-01-01

    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  3. Chronic pneumonitis of infancy

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Katsumi; Kamata, Noriko; Okazaki, Eiwa [Department of Radiology, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Moriyama, Sachiko; Funata, Nobuaki [Department of Pathology, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Takita, Junko; Yamada, Hideo; Takayama, Naohide [Department of Pediatrics, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan)

    2002-07-01

    Chronic pneumonitis of infancy (CPI) is a very rare lung disease in infants and young children. We report a 33-day-old infant with CPI, focusing on the radiologic aspects of the disease. Chest radiographs showed variable and non-specific appearances including ground-glass shadowing, consolidation, volume loss, and hyperinflation. Dense alveolar opacities progressed as CPI advanced. The radiologic features of our case reflected pathologic changes. (orig.)

  4. EBV CHRONIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Delia Racciatti

    2010-02-01

    Full Text Available

    The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”.

    Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis

  5. Effect of Tramadol/Acetaminophen on Motivation in Patients with Chronic Low Back Pain.

    Science.gov (United States)

    Tetsunaga, Tomoko; Tetsunaga, Tomonori; Tanaka, Masato; Nishida, Keiichiro; Takei, Yoshitaka; Ozaki, Toshifumi

    2016-01-01

    Background. The contribution of apathy, frequently recognized in individuals with neurodegenerative diseases, to chronic low back pain (LBP) remains unclear. Objectives. To investigate levels of apathy and clinical outcomes in patients with chronic LBP treated with tramadol-acetaminophen. Methods. A retrospective case-control study involving 73 patients with chronic LBP (23 male, 50 female; mean age 71 years) treated with tramadol-acetaminophen (n = 36) and celecoxib (n = 37) was performed. All patients were assessed using the self-reported questionnaires. A mediation model was constructed using a bootstrapping method to evaluate the mediating effects of pain relief after treatment. Results. A total of 35 (55.6%) patients met the criteria for apathy. A four-week treatment regimen in the tramadol group conferred significant improvements in the Apathy scale and numerical rating scale but not in the Rolland-Morris Disability Questionnaire, Pain Disability Assessment Scale, or Pain Catastrophizing Scale. The depression component of the Hospital Anxiety and Depression Scale was lower in the tramadol group than in the celecoxib group. The mediation analysis found that the impact of tramadol-acetaminophen on the change in apathy was not mediated by the pain relief. Conclusions. Tramadol-acetaminophen was effective at reducing chronic LBP and conferred a prophylactic motivational effect in patients with chronic LBP.

  6. Chronic arsenic poisoning.

    Science.gov (United States)

    Hall, Alan H

    2002-03-10

    Symptomatic arsenic poisoning is not often seen in occupational exposure settings. Attempted homicide and deliberate long-term poisoning have resulted in chronic toxicity. Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, and liver disease are common. Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, and hypersplenism may occur. A metallic taste, gastrointestinal disturbances, and Mee's lines may be seen. Bone marrow depression is common. 'Blackfoot disease' has been associated with arsenic-contaminated drinking water in Taiwan; Raynaud's phenomenon and acrocyanosis also may occur. Large numbers of persons in areas of India, Pakistan, and several other countries have been chronically poisoned from naturally occurring arsenic in ground water. Toxic delirium and encephalopathy can be present. CCA-treated wood (chromated copper arsenate) is not a health risk unless burned in fireplaces or woodstoves. Peripheral neuropathy may also occur. Workplace exposure or chronic ingestion of arsenic-contaminated water or arsenical medications is associated with development of skin, lung, and other cancers. Treatment may incklude the use of chelating agents such as dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopanesulfonic acid (DMPS).

  7. Chronic pelvic pain

    Directory of Open Access Journals (Sweden)

    Slawomir Wozniak

    2016-06-01

    Full Text Available [b][/b][b]Introduction. [/b]Chronic pelvic pain (CPP affects about 10–40% of women presenting to a physician, and is characterised by pain within the minor pelvis persisting for over 6 months. [b]Materials and method. [/b]The Medline database was searched using the key words ‘chronic pelvic pain’ and ‘pelvic congestion syndrome’, published in English during the past 15 years. The condition markedly deteriorates the quality of life of the affected. Its aetiology has not been fully described and elucidated, although organic, functional and psychosomatic factors are implicated. Pain associated with parametrial varices was defined as pelvis congestion syndrome (PCS. Since the aetiology of CPP is complex, multi-directional diagnostic procedures are required. [b]Results. [/b]The main diagnostic methods employed are imaging examinations (ultrasound, computer tomography, magnetic resonance. Advances in interventional radiology considerably contributed to the CPP treatment. Currently, embolization of parametrial vessels is one of the most effective methods to relieve pain associated with pelvic congestion syndrome. [b]Conclusions. [/b]Due to the complex aetiology of chronic pelvic pain, the most beneficial effects are obtained when the therapy is based on cooperation of the gynaecologist, physiotherapist, psychologist and interventional radiologist.

  8. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    , respectively. The paper thus takes on aesthetics and the social in a manner closely related to a core argument of STS - namely that the scientific fact, and the social processes of constructing, distributing, and using that fact, are co-constructed (Callon, 1986; Latour, 1993). The paper thus contributes......, it is an important ambition of this paper to go into a methodological discussion of how "that which effectively happens" can be approached. To this end, the paper will combine Hennion's term of the "mediator" with John Laws methodological term of "method assemblages". Method assemblages is a suggested as a way...... of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

  9. The Strategic Mediator

    DEFF Research Database (Denmark)

    Rossignoli, Cecilia; Carugati, Andrea; Mola, Lapo

    2009-01-01

    The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter-organizational relat......The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter......-marketplace assumes the paradoxical role of strategic mediator: an agent who upholds and heightens the fences of the transactions instead of leveling them. The results have implication in shaping how we see the role of technology as strategic or commoditized....

  10. Redox Imbalance in T Cell-Mediated Skin Diseases

    Directory of Open Access Journals (Sweden)

    Saveria Pastore

    2010-01-01

    Full Text Available The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.

  11. Mediated intimacy in families

    DEFF Research Database (Denmark)

    Stougaard, Malthe Kirkhoff

    2006-01-01

    Mediating intimacy between children and their parents is still limited investigated and at the same time, we find that, emerging technologies are about to change and affect the way we interact with each other. In this paper, we report from an empirical study where we investigated the social...... with other types of intimate relations such as strong-tie intimacy (couples cohabiting). However, we also identified several issues of intimacy unique to the special relation between children and their parents. These unique acts of intimacy propose challenges when designing technologies for mediated intimacy...

  12. Mediated moderation of the relation between maternal and adolescent depressive symptoms: role of adolescent physical health.

    Science.gov (United States)

    Ferro, Mark A

    2015-11-01

    To examine the mediating effect of family functioning on the relation between maternal and adolescent depressive symptoms and determine whether the magnitude of the mediating effect is different for adolescents with and without chronic physical health conditions. Data come from the National Longitudinal Survey of Children and Youth. A representative survey of 11,813 adolescents and their mothers was included. Maternal and adolescent depressive symptoms were measured using the 12-item Center for Epidemiological Studies Depression Scale. Family functioning was measured using the McMaster Family Assessment Device. Multilevel multiple-group path analysis was used to examine potential mediating and moderating effects. Family functioning measured when adolescents were 14-15 years mediated the relation between maternal depressive symptoms (measured at 10-13 years) and adolescent depressive symptoms (measured at 16-19 years) for both adolescents with [αβ = 0.02 (0.02, 0.03)] and without chronic health conditions [αβ = 0.01 (0.00, 0.01)]. These findings provided evidence to suggest mediated moderation, Δαβ = 0.02 (0.01, 0.03), that is, the mediating effect of family functioning was significantly larger for adolescents with chronic health conditions. The mediating effect of family functioning in the relation between maternal and adolescent depressive symptoms is larger for adolescents with chronic health conditions. Within the framework of family-centered care, maternal depressive symptoms and family functioning are suitable targets for preventive intervention for adolescents with chronic health conditions.

  13. 莫西沙星溶液雾化吸入对慢性阻塞性肺疾病合并呼吸衰竭患者炎症介质及血气分析指标的影响%Effects of moxifloxacin solution for inhalation on inflammatory mediators and blood gas analysis in patients with chronic obstructive pulmonary disease with respiratory failure

    Institute of Scientific and Technical Information of China (English)

    李锋; 张翼; 尤慧敏

    2015-01-01

    目的 探讨莫西沙星溶液雾化吸入对慢阻肺合并呼吸衰竭患者炎症介质及血气分析的影响.方法 收集嘉善县第一人民医院呼吸科收治的慢阻肺合并呼衰的患者60例,随机分为对照组和实验组,每组各30例,在常规治疗基础上,对照组患者给予吸入用硫酸沙汀胺醇溶液(2 mg/次,每天3次雾化吸入治疗,实验组给予莫西沙星溶液2 mg/次,每天4次雾化吸入治疗,2组患者均治疗2周,对所有患者的血清CRP、TNF-α、IL-10、IL-18水平及动脉血PO2、PCO2 水平进行检测.结果 与对照组治疗后比较,实验组患者血清CRP、TNF-α、IL-18水平较低(P<0.05),血清IL-10水平较高(P<0.05);实验组患者的动脉血PO2 水平较高,PCO2 水平较低(P<0.05).结论 莫西沙星溶液雾化吸入能够显著降低慢阻肺合并呼衰患者血清CRP、TNF-α以及IL-18水平,提高血清IL-10水平,改善PO2 和PCO2.%Objective To analyse effects of moxifloxacin solution for aerosol inhalation on inflammatory mediators and blood gas analysis index in patients with chronic obstructive pulmonary disease with respiratory failure.Methods 60 patients who were diagnosed with chronic obstructive pulmonary disease with respiratory failure in our hospital were collected.All patients were randomly divided into experimental group and control group,30 cases in each group.On the basis of conventional treatment, control group were given sulfate for inhalation shating amine alcohol solution 2mg per times, 3 times per day atomization inhalation treatment,and experimental group was given 2 mg/times, 4 times per day atomization inhalation treatment,two were treated for 2 weeks.After the treatment, the serum levels of CRP,TNF-α,IL-10,IL-18 and arterial blood PO2 ,PCO2 levels were detected in all patients.Results Compared with control group post-treatment, the serum levels of CRP, IL-18 and TNF-αwere lower in experimental group (P<0.05), and the serum level of IL-10 was higher

  14. Chronic Prostatitis/Chronic Pelvic Pain Syndrome Diagnosis and Treatment

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    Cem Nedim Yuceturk

    2014-08-01

    Full Text Available Chronic prostatitis is a chronic syndrome that effects men with a wide range of age. The etiology, natural history and appropriate therapy models are still unclear. According to the classification of National Institutes of Health; 4 types of prostatitis were defined; acute bacterial prostatitis (category I, chronic bacterial prostatitis (category II, chronic nonbacterial prostatitis/chronic pelvic pain syndrome (category III and asymptomatic prostatitis (category IV.Since microorganisms can only be isolated from a small percent of patients, empiric treatment is given to the most of the men. Multidisciplinary approach to the patients with suspected chronic prostatitis will help clinicians to play an active role in the treatment and prevent unnecessary medical therapies. [Archives Medical Review Journal 2014; 23(4.000: 691-702

  15. Chronic inflammatory demyelinating polyradiculoneuropathy associated intracranial hypertension.

    Science.gov (United States)

    Altinkaya, Ayca; Topcular, Baris; Sakalli, Nazan Karagoz; Kuscu, Demet Yandim; Kirbas, Dursun

    2013-06-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated demyelinating neuropathy. In this report, we detail the course of a 58-year-old male patient who had headache and double vision followed by progressive paresthesia and difficulty in walking. The patient had bilateral papilledema and mild leg weakness, absent ankle jerks and loss of sensation in distal parts of his lower and upper extremities. His electromyography (EMG) was concordant with CIDP and lumbar puncture revealed high opening pressure. The polyradiculoneuropathy as well as the papilledema and elevated cerebrospinal fluid (CSF) pressure improved under steroids. The improvement in intracranial hypertension (IHT) and papilledema under steroid treatment suggests that the IHT in this patient might be associated with CIDP.

  16. Role of angiogenesis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Letilovic, Tomislav; Vrhovac, Radovan; Verstovsek, Srdan; Jaksic, Branimir; Ferrajoli, Alessandra

    2006-09-01

    Angiogenesis is a physiologic process of new blood vessels formation mediated by various cytokines called angiogenic and angiostatic factors. Although its potential pathophysiologic role in solid tumors has been extensively studied for more than 3 decades, enhancement of angiogenesis in chronic lymphocytic leukemia (CLL) and other malignant hematological disorders has been recognized more recently. An increased level of angiogenesis has been documented by various experimental methods both in bone marrow and lymph nodes of patients with CLL. Although the role of angiogenesis in the pathophysiology of this disease remains to be fully elucidated, experimental data suggest that several angiogenic factors play a role in the disease progression. Biologic markers of angiogenesis were also shown to be of prognostic relevance in CLL. The current findings provide the rationale for investigating antiangiogenic agents in CLL. In the current review angiogenesis in CLL is discussed and its potential diagnostic and therapeutic applications.

  17. Obinutuzumab for previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Abraham, Jame; Stegner, Mark

    2014-04-01

    Obinutuzumab was approved by the Food and Drug Administration in late 2013 for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). The approval was based on results of an open-label phase 3 trial that showed improved progression-free survival (PFS) with the combination of obinutuzumab plus chlorambucil compared with chlorambucil alone. Obinutuzumab is a monoclonal antibody that targets CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes. After binding to CD20, obinutuzumab mediates B-cell lysis by engaging immune effector cells, directly activating intracellular death signaling pathways, and activating the complement cascade. Immune effector cell activities include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

  18. Extracellular Vesicles in Chronic Obstructive Pulmonary Disease

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    Tsukasa Kadota

    2016-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide. Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown. Extracellular vesicles (EVs, including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell–cell communication tools. They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases. Recently, EVs have attracted considerable attention in pulmonary research. In this review, we summarize the recent findings of EV-mediated COPD pathogenesis. We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD.

  19. Metabolism pathways in chronic lymphocytic leukemia.

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    Rozovski, Uri; Hazan-Halevy, Inbal; Barzilai, Merav; Keating, Michael J; Estrov, Zeev

    2016-01-01

    Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

  20. History of Chronic Subdural Hematoma

    Science.gov (United States)

    2015-01-01

    Trephination or trepanation is an intentional surgical procedure performed from the Stone Age. It looks like escaping a black evil from the head. This technique is still used for treatment of chronic subdural hematoma (SDH). Now, we know the origin, pathogenesis and natural history of this lesion. The author try to explore the history of trephination and modern discovery of chronic SDH. The author performed a detailed electronic search of PubMed. By the key word of chronic SDH, 2,593 articles were found without language restriction in May 2015. The author reviewed the fact and way, discovering the present knowledge on the chronic SDH. The first authentic report of chronic SDH was that of Wepfer in 1657. Chronic SDH was regarded as a stroke in 17th century. It was changed as an inflammatory disease in 19th century by Virchow, and became a traumatic lesion in 20th century. However, trauma is not necessary in many cases of chronic SDHs. The more important prerequisite is sufficient potential subdural space, degeneration of the brain. Modifying Virchow's description, chronic SDH is sometimes traumatic, but most often caused by severe degeneration of the brain. From Wepfer's first description, nearly 350 years passed to explore the origin, pathogenesis, and fate of chronic SDH. The nature of the black evil in the head of the Stone Age is uncovering by many authors riding the giant's shoulder. Chronic SDH should be categorized as a degenerative lesion instead of a traumatic lesion. PMID:27169062