Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H
2015-09-01
Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.
Kakigi, R
1994-09-01
The effects of DNIC (diffuse noxious inhibitory control) in humans were evaluated by means of pain SEPs (somatosensory evoked potentials) and pain visual analogue scale (VAS) following CO2 laser stimulation applied to the left knee while conditioning stimuli (non-noxious and noxious thermal stimuli) applied to the right hand. Pain SEPs were recorded from scalp electrodes following laser stimulation applied to the left knee during various conditions as follows: (1) control (without any interference), (2) non-noxious (dipping the right hand in water at 41 degrees C for 3 min), (3) noxious (dipping the right hand in water at 46 degrees C for 3 min), and (4) after-effect (3-6 min after taking the hand from the water at 46 degrees C). The present pain SEPs findings confirmed the presence of DNIC in humans, and indicates: (1) degree of pain relief was significantly correlated with changes in pain SEPs, particularly a marked decrease in amplitude, and a decrease in VAS; (2) DNIC was more effective on the second pain than the first pain; (3) the effect of DNIC gradually increased over time, but it rapidly disappeared after the conditioning stimuli ceased; and (4) DNIC was not due merely to changes of attention. I propose that the site responsible for DNIC is the brainstem or the spinal cord rather than the cerebral hemisphere.
Bannister, K; Lockwood, S; Goncalves, L; Patel, R; Dickenson, A H
2017-04-01
Following neuropathy α2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR neuronal firing in the presence of conditioning stimulus and was investigated in SNL rats following spinal application of (1) selective serotonin reuptake inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus 5-HT7 receptor antagonist SB269970, or (3) SSRI plus α2 adrenoceptor antagonist atipamezole. DNIC were revealed in SNL animals following spinal application of SSRI, but this effect was abolished upon joint application of SSRI plus SB269970 or atipamezole. We propose that in SNL animals the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT (presumed present following application of SSRI) were mediated via 5-HT7 receptors. The anti-nociception depends upon an underlying tonic noradrenergic inhibitory tone via the α2-adrenoceptor. Following neuropathy enhanced spinal serotonin availability switches the predominant spinal 5-HT receptor-mediated actions but also alters noradrenergic signalling. We highlight the therapeutic complexity of SSRIs and monoamine modulators for the treatment of neuropathic pain. © 2016 European Pain Federation - EFIC®.
The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory controls.
Chebbi, R; Boyer, N; Monconduit, L; Artola, A; Luccarini, P; Dallel, R
2014-06-01
Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting descending inhibitory controls which are pivotal in modulating the activity of spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving supraspinal structures such as the lateral parabrachial nucleus and the subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe magnus (NRM), another supraspinal area which is long known to be important in pain modulation, is involved in DNIC is still a matter of discussion. Here, we reassessed the role of the NRM neurons in DNIC by electrophysiologically recording from wide dynamic range (WDR) neurons in the trigeminal subnucleus oralis and pharmacologically manipulating the NRM OFF- and ON-cells. In control conditions, C-fiber-evoked responses in trigeminal WDR neurons are inhibited by a conditioning noxious heat stimulation applied to the hindpaw. We show that inactivating the NRM by microinjecting the GABAA receptor agonist, muscimol, both facilitates C-fiber-evoked responses of trigeminal WDR neurons and strongly attenuates their inhibition by heat applied to the hindpaw. Interestingly, selective blockade of ON-cells by microinjecting the broad-spectrum excitatory amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be more specifically involved in both the tonic and phasic descending inhibitory controls of trigeminal nociception. Copyright © 2014 Elsevier Inc. All rights reserved.
de Resende, Marcos A.; Silva, Luis Felipe S.; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A.
2014-01-01
Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45°C and 47°C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. PMID:21330219
Effect of ketamine on endogenous pain modulation in healthy volunteers.
Niesters, Marieke; Dahan, Albert; Swartjes, Maarten; Noppers, Ingeborg; Fillingim, Roger B; Aarts, Leon; Sarton, Elise Y
2011-03-01
Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites, modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. The N-methyl-d-aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients. This effect is due to desensitization of sensitized N-methyl-d-aspartate receptors. Additionally, ketamine may modulate or enhance endogenous inhibitory control of pain perception. Diffuse noxious inhibitory control (DNIC) and offset analgesia (OA) are 2 mechanisms involved in descending inhibition. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-hour placebo or S(+)-ketamine (40mg per 70kg) infusion on 2 separate occasions in random order. Upon the termination of the infusion, DNIC and OA responses were obtained. After placebo treatment, significant descending inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (P<0.01); the OA response remained unchanged. These findings suggest that the balance between pain inhibition and pain facilitation was shifted by ketamine towards pain facilitation. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC. Diffuse noxious inhibitory control responses following a 1-hour low-dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
de Resende, Marcos A; Silva, Luis Felipe S; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A
2011-06-01
Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45 °C and 47 °C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. The current study shows that DNIC activates opioid receptors in the MdD, but not the RVM, to produce analgesia. These data are important for understanding clinical studies on DNIC as well as for potential treatment of chronic pain patients. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
Streff, Anouk; Michaux, Gilles; Anton, Fernand
2011-01-01
Hot and ice-water immersions are commonly used for heterotopic noxious counter-stimulation (HNCS) in investigations on endogenous pain modulation. However, coincident sympathetic thermoregulatory activity does not allow to differentiate between perceptual hypoalgesia related to baroreflex sensitivity (BRS) or diffuse noxious inhibitory controls (DNIC). The present study analysed the internal validity of another supposedly less confounded tonic pain model (inter-digital web pinching; IWP) regarding its potential as DNIC trigger. We performed a randomized controlled study in 24 healthy gender-matched drug-free volunteers aged 21-54 (median 25) years. The study protocol comprised the assessment of mechanical and thermal perceptual wind-up before and after an IWP (15N) or hot water immersion trial (HIT; 47.5°C) of 2 min duration. Wind-up was induced either by 10 repetitive (1Hz) contact heat (max. 49°C; 5×5 mm thermode) or ballistic impact stimuli (0.5g at 9 m/s) on the phalanges of the non-dominant hand. Cardiovascular activity, pain experience and corrugator muscle activity were continuously monitored. Although both HNCS forms produced a similar pain experience (45% of scale), a more pronounced cardiovascular activity was observable for the HIT (P<0.01). This indicates a higher baroreceptor activity and stronger contamination of painful water immersion by BRS-related hypoalgesia. Regardless of pain modality, wind-up was significantly reduced by HNCS, although this was stronger for painful water immersion than for noxious pinching (P<0.01). The HNCS types allow a differentiation between BRS-related and DNIC-like hypoalgesia. IWP proved its validity for DNIC induction, being practically non-confounded by BRS. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.
Reliability of temporal summation and diffuse noxious inhibitory control
Cathcart, Stuart; Winefield, Anthony H; Rolan, Paul; Lushington, Kurt
2009-01-01
BACKGROUND: The test-retest reliability of temporal summation (TS) and diffuse noxious inhibitory control (DNIC) has not been reported to date. Establishing such reliability would support the possibility of future experimental studies examining factors affecting TS and DNIC. Similarly, the use of manual algometry to induce TS, or an occlusion cuff to induce DNIC of TS to mechanical stimuli, has not been reported to date. Such devices may offer a simpler method than current techniques for inducing TS and DNIC, affording assessment at more anatomical locations and in more varied research settings. METHOD: The present study assessed the test-retest reliability of TS and DNIC using the above techniques. Sex differences on these measures were also investigated. RESULTS: Repeated measures ANOVA indicated successful induction of TS and DNIC, with no significant differences across test-retest occasions. Sex effects were not significant for any measure or interaction. Intraclass correlations indicated high test-retest reliability for all measures; however, there was large interindividual variation between test and retest measurements. CONCLUSION: The present results indicate acceptable within-session test-retest reliability of TS and DNIC. The results support the possibility of future experimental studies examining factors affecting TS and DNIC. PMID:20011713
Itomi, Yasuo; Tsukimi, Yasuhiro; Kawamura, Toru
2016-08-05
Fibromyalgia is characterized by chronic widespread musculoskeletal pain. A hypofunction in descending pain inhibitory systems is considered to be involved in the chronic pain of fibromyalgia. We examined functional changes in descending pain inhibitory systems in rats with specific alternation of rhythm in temperature (SART) stress, by measuring the strength of diffuse noxious inhibitory controls (DNIC). Hindpaw withdrawal thresholds to mechanical von Frey filament or fiber-specific electrical stimuli by the Neurometer system were used to measure the pain response. To induce DNIC, capsaicin was injected into the intraplantar of the forepaw. SART-stressed rats were established by exposure to repeated cold stress for 4 days. In the control rats, heterotopic intraplantar capsaicin injection increased withdrawal threshold, indicative of analgesia by DNIC. The strength of DNIC was reduced by naloxone (μ-opioid receptor antagonist, intraperitoneally and intracerebroventricularly), yohimbine (α2-adrenoceptor antagonist, intrathecally), and WAY-100635 (5-HT1A receptor antagonist, intrathecally) in the von Frey test. In SART-stressed rats, capsaicin injection did not increase withdrawal threshold in the von Frey test, indicating deficits in DNIC. In the Neurometer test, deficient DNIC in SART-stressed rats were observed only for Aδ- and C-fibers, but not Aβ-fibers stimulation. Analgesic effect of intracerebroventricular morphine was markedly reduced in SART-stressed rats compared with the control rats. Taken together, in SART-stressed rats, capsaicin-induced DNIC were deficient, and a hypofunction of opioid-mediated central pain modulation system may cause the DNIC deficit. Copyright © 2016 Elsevier B.V. All rights reserved.
Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank
2018-05-01
The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.
Tambeli, Claudia H.; Levine, Jon D.; Gear, Robert W.
2009-01-01
The duration of noxious stimulus-induced antinociception (NSIA) has been shown to outlast the pain stimulus that elicited it, however, the mechanism that determines the duration of analgesia is unknown. We evaluated the role of spinal excitatory and inhibitory receptors (NMDA, mGluR-5, mu-opioid, GABA-A, and GABA-B), previously implicated in NSIA initiation, in its maintenance. As in our previous studies, the supraspinal trigeminal jaw-opening reflex (JOR) in the rat was used for nociceptive testing because of its remoteness from the region of drug application, the lumbar spinal cord. NSIA was reversed by antagonists for two inhibitory receptors (GABA-B and mu-opioid) but not by antagonists for either of the two excitatory receptors (NMDA and mGluR-5), indicating that NSIA is maintained by ongoing activity at inhibitory synapses in the spinal cord. Furthermore, spinal administration of the GABA-B agonist baclofen mimicked NSIA in that it could be blocked by prior injection of the mu-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) in nucleus accumbens. CTAP also blocked baclofen antinociception when administered in the spinal cord. We conclude that analgesia induced by noxious stimulation is maintained by activity in spinal inhibitory receptors. PMID:19375225
Granot, Michal; Weissman-Fogel, Irit; Crispel, Yonathan; Pud, Dorit; Granovsky, Yelena; Sprecher, Elliot; Yarnitsky, David
2008-05-01
Descending modulation of pain can be demonstrated psychophysically by dual pain stimulation. This study evaluates in 31 healthy subjects the association between parameters of the conditioning stimulus, gender and personality, and the endogenous analgesia (EA) extent assessed by diffuse noxious inhibitory control (DNIC) paradigm. Contact heat pain was applied as the test stimulus to the non-dominant forearm, with stimulation temperature at a psychophysical intensity score of 60 on a 0-100 numerical pain scale. The conditioning stimulus was a 60s immersion of the dominant hand in cold (12, 15, 18 degrees C), hot (44 and 46.5 degrees C), or skin temperature (33 degrees C) water. The test stimulus was repeated on the non-dominant hand during the last 30s of the conditioning immersion. EA extent was calculated as the difference between pain scores of the two test stimuli. State and trait anxiety and pain catastrophizing scores were assessed prior to stimulation. EA was induced only for the pain-generating conditioning stimuli at 46.5 degrees C (p=0.011) and 12 degrees C (p=0.003). EA was independent of conditioning pain modality, or personality, but a significant gender effect was found, with greater EA response in males. Importantly, pain scores of the conditioning stimuli were not correlated with EA extent. The latter is based on both our study population, and on additional 82 patients, who participated in another study, in which EA was induced by immersion at 46.5 degrees C. DNIC testing, thus, seems to be relatively independent of the stimulation conditions, making it an easy to apply tool, suitable for wide range applications in pain psychophysics.
Noxious inhibition of temporal summation is impaired in chronic tension-type headache.
Cathcart, Stuart; Winefield, Anthony H; Lushington, Kurt; Rolan, Paul
2010-03-01
To examine effects of stress on noxious inhibition and temporal summation (TS) in tension-type headache. Stress is the most commonly reported trigger of a chronic tension-type headache (CTH) episode; however, the mechanisms underlying this are unclear. Stress affects pain processing throughout the central nervous system, including, potentially, mechanisms of TS and diffuse noxious inhibitory controls (DNIC), both of which may be abnormal in CTH sufferers (CTH-S). No studies have examined TS of pressure pain or DNIC of TS in CTH-S to date. Similarly, effects of stress on TS or DNIC of TS have not been reported in healthy subjects or CTH-S to date. The present study measured TS and DNIC of TS in CTH-S and healthy controls (CNT) exposed to an hour-long stressful mental task, and in CTH-S exposed to an hour-long neutral condition. TS was elicited at finger and shoulder via 10 pulses from a pressure algometer, applied before and during stimulation from an occlusion cuff at painful intensity. Algometer pain ratings increased more in the CTH compared with the CNT group, and were inhibited during occlusion cuff more in the CNT compared with CTH groups. Task effects on TS or DNIC were not significant. The results indicate increased TS to pressure pain and impaired DNIC of TS in CTH-S. Stress does not appear to aggravate abnormal TS or DNIC mechanisms in CTH-S.
Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.
Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal
2008-08-15
Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.
Meléndez-Gallardo, J; Eblen-Zajjur, A
2016-09-01
Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.
The neurophysiology of the esophagus.
Woodland, Philip; Sifrim, Daniel; Krarup, Anne Lund; Brock, Christina; Frøkjaer, Jens Brøndum; Lottrup, Christian; Drewes, Asbjørn Mohr; Swanstrom, Lee L; Farmer, Adam D
2013-10-01
This paper reports on the neurophysiology of the esophagus, including on the uneven distribution of innervation in the esophagus, reflected by the increased sensitivity and perception of gastroesophageal reflux disease (GERD) events in the proximal rather than distal esophagus; the role of the enteric nervous system (ENS) in swallowing; the role of the physiological stress-responsive systems, including the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis in mediating esophageal pain; the advances in understanding pain mechanisms and brain structure provided by technological imaging advances; investigations into the efficacy of the descending-pain control system, including diffuse noxious inhibitory control (DNIC); the role of abnormal nervous signaling in afferent pathways in the pathogenesis of Barrett's esophagus (BE); and the contribution of the esophageal mucosa to reflux symptoms. © 2013 New York Academy of Sciences.
Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David
2012-01-30
Methods to cognitively distract subjects from pain and experimental paradigms to induce conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls or DNIC) have each highlighted activity changes in closely overlapping cortical areas. This is the first study, to our knowledge, to compare cortical activation changes during these 2 manipulations in the same experimental set-up. Our study sample included thirty healthy young right handed males capable of expressing CPM. We investigated brief consecutive time windows using 32-channel EEG-based sLORETA, to determine dynamic changes in localized cortical potentials evoked by phasic noxious heat stimuli to the left volar forearm. This was performed under visual cognitive distraction tasks and conditioning hot-water pain to the right hand (CPM), both individually and simultaneously. Previously we have shown that for CPM, there is increased activity in frontal cortical regions followed by reduced activation of the somatosensory areas, suggesting a pain inhibitory role for these frontal regions. We now observed that distraction caused a different extent of cortical activation; greater early activation of frontal areas (DLPFC, OFC and caudal ACC at 250-350 ms post-stimulus), yet lesser reduction in the somatosensory cortices, ACC, PCC and SMA after 350 ms post-stimulus, compared to CPM. Both CPM and distraction reduced subjective pain scores to a similar extent. Combining CPM and distraction further reduced pain ratings compared to CPM and distraction alone, supporting the dissimilarity of the mechanisms of pain modulation under these 2 manipulations. The results are discussed in terms of the differential functional roles of the prefrontal cortex. Copyright © 2011 Elsevier B.V. All rights reserved.
King, Christopher D.; Wong, Fong; Currie, Tom; Mauderli, Andre P.; Fillingim, Roger B.; Riley, Joseph L.
2013-01-01
Females with Irritable Bowel Syndrome (IBS) and Temporomandibular Disorder (TMD) are characterized by enhanced sensitivity to experimental pain. One possible explanation for this observation is deficiencies in pain modulation systems like Diffuse Noxious Inhibitory Control (DNIC). In a few studies that used brief stimuli, chronic pain patients demonstrate reduced DNIC. The purpose of this study was to compare sensitivity to prolonged heat pain and the efficacy of DNIC in controls to IBS and TMD patients. Heat pain (experimental stimulus; 44.0-49.0°C), which was applied to left palm, was continuously rated during three 30-second trials across three separate testing sessions under the following conditions: without a conditioning stimulus; during concurrent immersion of the right foot in a 23.0°C (control); and during noxious cold immersion in a (DNIC; 8.0-16.0°C) water bath. Compared to controls, IBS and TMD patients reported increased sensitivity to heat pain and failed to demonstrate pain inhibition due to DNIC. Controls showed a significant reduction in pain during the DNIC session. These findings support the idea that chronic pain patients are not only more pain sensitive and demonstrate reduced pain inhibition by pain, possibly because of dysfunction of endogenous pain inhibition systems. PMID:19278784
Wilder-Smith, Oliver Hamilton; Schreyer, Tobias; Scheffer, Gert Jan; Arendt-Nielsen, Lars
2010-06-01
Chronic pain is common and undesirable after surgery. Progression from acute to chronic pain involves altered pain processing. The authors studied relationships between presence of chronic pain versus preoperative descending pain control (diffuse noxious inhibitory controls; DNICs) and postoperative persistence and spread of skin and deep tissue hyperalgesia (change in electric/pressure pain tolerance thresholds; ePTT/pPTT) up to 6 months postoperatively. In 20 patients undergoing elective major abdominal surgery under standardized anesthesia, we determined ePTT/pPTT (close to [abdomen] and distant from [leg] incision), eDNIC/pDNIC (change in ePTT/pPTT with cold pressor pain task; only preoperatively), and a 100 mm long pain visual analogue scale (VAS) (0 mm = no pain, 100 mm = worst pain imaginable), both at rest and on movement preoperatively, and 1 day and 1, 3, and 6 months postoperatively. Patients reporting chronic pain 6 months postoperatively had more abdominal and leg skin hyperalgesia over the postoperative period. More inhibitory preoperative eDNIC was associated with less late postoperative pain, without affecting skin hyperalgesia. More inhibitory pDNIC was linked to less postoperative leg deep tissue hyperalgesia, without affecting pain VAS. This pilot study for the first time links chronic pain after surgery, poorer preoperative inhibitory pain modulation (DNIC), and greater postoperative degree, persistence, and spread of hyperalgesia. If confirmed, these results support the potential clinical utility of perioperative pain processing testing.
Thurston, C L; Randich, A
1990-06-11
Occlusion of the abdominal aorta proximal to the renal arteries results in an increase in arterial blood pressure, inhibition of forepaw and hindpaw withdrawal to a noxious mechanical stimulus, and inhibition of the tail-flick reflex to noxious heat. Occlusion of the abdominal aorta distal to the renal arteries does not elevate arterial blood pressure and produces no antinociceptive effects. Occlusion of the vena cava lowers arterial blood pressure and produces no antinociception. The inhibitory effects of occlusion of the abdominal aorta depend upon activation of high pressure baroreceptors since bilateral sinoaortic denervation, but not bilateral vagotomy, eliminates the inhibition with respect to all behavioral measures. The inhibitory effects with respect to the tail-flick reflex also depend upon activation of a descending inhibitory system since reversible cold block of the spinal cord at the level of the second thoracic vertebra eliminates the antinociception. This antinociception is also eliminated following intrathecal administration of the noradrenergic receptor antagonist phentolamine, but not by intrathecal administration of either methysergide or naloxone. These data support the view that activation of high pressure baroreceptors by increases in arterial blood pressure produces antinociception via activation of a spinopetal noradrenergic system.
The plasticity of descending controls in pain: translational probing.
Bannister, Kirsty; Dickenson, A H
2017-07-01
Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems. One pain can inhibit another. In this respect diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous descending inhibitory pathway since they can be easily evoked and quantified in animals and man. The spinal pharmacology of pathways that subserve DNIC are complicated; in the normal situation these descending controls produce a final inhibitory effect through the actions of noradrenaline at spinal α 2 -adrenoceptors, although serotonin, acting on facilitatory spinal 5-HT 3 receptors, influences the final expression of DNIC also. These descending pathways are altered in neuropathy and the effects of excess serotonin may now become inhibitory through activation of spinal 5-HT 7 receptors. Conditioned pain modulation (CPM) is the human counterpart of DNIC and requires a descending control also. Back and forward translational studies between DNIC and CPM, gauged between bench and bedside, are key for the development of analgesic therapies that exploit descending noradrenergic and serotonergic control pathways. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
Klein, Amanda H.; Sawyer, Carolyn M.; Takechi, Kenichi; Davoodi, Auva; Ivanov, Margaret A.; Carstens, Mirela Iodi; Carstens, E
2012-01-01
Menthol is used in pharmaceutical applications because of its desired cooling and analgesic properties. The neural mechanism by which topical application of menthol decreases heat pain is not fully understood. We investigated the effects of topical menthol application on lumbar dorsal horn wide dynamic range and nociceptive-specific neuronal responses to noxious heat and cooling of glaborous hindpaw cutaneous receptive fields. Menthol increased thresholds for responses to noxious heat in a concentration-dependent manner. Menthol had a biphasic effect on cold-evoked responses, reducing the threshold (to warmer temperatures) at a low (1%) concentration and increasing threshold and reducing response magnitude at high (10, 40%) concentrations. Menthol had little effect on responses to innocuous or noxious mechanical stimuli, ruling out a local anesthetic action. Application of 40% menthol to the contralateral hindpaw tended to reduce responses to cooling and noxious heat, suggesting a weak heterosegmental inhibitory effect. These results indicate that menthol has an analgesic effect on heat sensitivity of nociceptive dorsal horn neurons, as well as biphasic effects on cold sensitivity, consistent with previous behavioral observations. PMID:22687951
Influence of oral contraceptives on endogenous pain control in healthy women.
Rezaii, Taraneh; Ernberg, Malin
2010-06-01
This study investigated the influence of oral contraceptives (OC) on diffuse noxious inhibitory control (DNIC) in healthy women. Fifteen women taking OC and 17 normally menstruating women (No-OC) were tested during high and low endogenous estrogens sessions. Saliva was sampled for analysis of endogenous estradiol level. Mechanical pressure (test stimuli) was applied to the masseter muscle and finger. The pain induced by this pressure was assessed on a 0-10 numerical rating scale (NRS) before, during, and after immersion of the contralateral hand in ice-cold water (cold pressor test, CPT) to induce DNIC. For all subjects, pain induced by the test stimuli decreased significantly during the CPT (P < 0.001). The decrease in general was larger in the No-OC group, with a significant difference between groups in the masseter muscle in the low session (P < 0.027). There were no significant differences between groups or sessions in estradiol levels. These results indicate that endogenous pain modulation may be less effective in OC users.
Shafton, Anthony D; Furness, John B; Ferens, Dorota; Bogeski, Goce; Koh, Shir Lin; Lean, Nicholas P; Kitchener, Peter D
2006-07-01
Noxious stimuli that are applied to different somatic sites interact; often one stimulus diminishes the sensation elicited from another site. By contrast, inhibitory interactions between visceral stimuli are not well documented. We investigated the interaction between the effects of noxious distension of the colorectum and noxious stimuli applied to the jejunum, in the rat. Colorectal distension elicited a visceromotor reflex, which was quantified using electromyographic (EMG) recordings from the external oblique muscle of the upper abdomen. The same motor units were activated when a strong pinch was applied to the flank skin. Distension of the jejunum did not provoke an EMG response at this site, but when it was applied during colorectal distension it blocked the EMG response. Jejunal distension also inhibited the response to noxious skin pinch. The inhibition of the visceromotor response to colorectal distension was prevented by local application of tetrodotoxin to the jejunum, and was markedly reduced when nicardipine was infused into the local jejunal circulation. Chronic sub-diaphragmatic vagotomy had no effect on the colorectal distension-induced EMG activity or its inhibition by jejunal distension. The nicotinic antagonist hexamethonium suppressed phasic contractile activity in the jejunum, had only a small effect on the inhibition of visceromotor response by jejunal distension. It is concluded that signals that arise from skin pinch and colorectal distension converge in the central nervous system with pathways that are activated by jejunal spinal afferents; the jejunal signals strongly inhibit the abdominal motor activity evoked by noxious stimuli.
Pohl, M; Collin, E; Bourgoin, S; Clot, A M; Hamon, M; Cesselin, F; Le Bars, D
1992-10-01
The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha-calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres.
Boros, Melinda; Benkó, Rita; Bölcskei, Kata; Szolcsányi, János; Barthó, Loránd; Pethő, Gábor
2013-12-01
The study aimed at validating an increasing-temperature water bath suitable for determining the noxious heat threshold for use in mice. The noxious heat threshold was determined by immersing the tail of the gently held awake mouse into a water container whose temperature was near-linearly increased at a rate of 24°C/min. until the animal withdrew its tail, that is, heating attained the noxious threshold. The effects of standard analgesic, neuroleptic and anxiolytic drugs were investigated in a parallel way on both the noxious heat threshold and the psychomotor activity assessed by the open field test. Morphine, diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses of morphine and diclofenac failed to induce any remarkable effect on psychomotor activity in the open field test while that of metamizol exerted a profound inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses evoking a mild and moderate, respectively, psychomotor inhibition failed to alter the heat threshold. Combination of a subliminal dose of morphine (regarding both antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol, diazepam or droperidol at doses also subliminal regarding the thermal antinociceptive effect elevated the noxious heat threshold without major additional effects in the open field test. It is concluded that the increasing-temperature water bath is suitable for studying the thermal antinociceptive effects of morphine and diclofenac as well as the morphine-sparing action of diclofenac, metamizol, droperidol and diazepam. Behavioural testing is recommended when testing analgesics. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.
Safonov, Dmitry A; Vanag, Vladimir K
2018-05-03
The dynamical regimes of two almost identical Belousov-Zhabotinsky oscillators with both pulsatile (with time delay) and diffusive coupling have been studied theoretically with the aid of ordinary differential equations for four combinations of these types of coupling: inhibitory diffusive and inhibitory pulsatile (IDIP); excitatory diffusive and inhibitory pulsatile; inhibitory diffusive and excitatory pulsatile; and finally, excitatory diffusive and excitatory pulsatile (EDEP). The combination of two types of coupling creates a condition for new feedback, which promotes new dynamical modes for the IDIP and EDEP coupling.
Iwagaki, Noboru; Ganley, Robert P.; Dickie, Allen C.; Polgár, Erika; Hughes, David I.; Del Rio, Patricia; Revina, Yulia; Watanabe, Masahiko; Todd, Andrew J.; Riddell, John S.
2015-01-01
Abstract The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We therefore used a combined electrophysiological/morphological approach to investigate these cells in mice that express green fluorescent protein (GFP) under control of the NPY promoter. We show that GFP is largely restricted to NPY-immunoreactive cells, although it is only expressed by a third of those in lamina I-II. Reconstructions of recorded neurons revealed that they were morphologically heterogeneous, but never islet cells. Many NPY-GFP cells (including cells in lamina III) appeared to be innervated by C fibres that lack transient receptor potential vanilloid-1, and consistent with this, we found that some lamina III NPY-immunoreactive cells were activated by mechanical noxious stimuli. Projection neurons in lamina III are densely innervated by NPY-containing axons. Our results suggest that this input originates from a small subset of NPY-expressing interneurons, with the projection cells representing only a minority of their output. Taken together with results of previous studies, our findings indicate that somatodendritic morphology is of limited value in classifying functional populations among inhibitory interneurons in the dorsal horn. Because many NPY-expressing cells respond to noxious stimuli, these are likely to have a role in attenuating pain and limiting its spread. PMID:26882346
Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.
Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David
2011-07-01
For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone
2018-01-01
The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1’s role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual’s first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and ‘SHAM-VL’), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here. PMID:29630681
Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit
2018-01-01
The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.
Flood, Andrew; Waddington, Gordon; Cathcart, Stuart
2017-01-01
The aim of the current study was to examine the relationship between pain modulatory capacity and endurance exercise performance. Twenty-seven recreationally active males between 18 and 35 years of age participated in the study. Pain modulation was assessed by examining the inhibitory effect of a noxious conditioning stimulus (cuff occlusion) on the perceived intensity of a second noxious stimulus (pressure pain threshold). Participants completed two, maximal voluntary contractions followed by a submaximal endurance time task. Both performance tasks involved an isometric contraction of the non-dominant leg. The main analysis uncovered a correlation between pain modulatory capacity and performance on the endurance time task (r = -.425, p = .027), such that those with elevated pain modulation produced longer endurance times. These findings are the first to demonstrate the relationship between pain modulation responses and endurance exercise performance.
Akiyama, Tasuku; Iodi Carstens, Mirela; Carstens, Earl
2011-01-01
Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABA(A) and GABA(B) antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished) by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli.
The importance of the descending monoamine system for the pain experience and its treatment
Dickenson, Anthony H
2009-01-01
Brainstem and midbrain areas engage descending facilitatory and inhibitory neurones to potentiate or suppress the passage of sensory inputs from spinal loci to the brain. The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states and can critically determine the efficacy of certain analgesic drugs. There is good evidence for a prominent α2 adrenoceptor-mediated inhibitory system and for 5-HT3 receptor-mediated excitatory control of spinal cord activity that originates in supraspinal areas. Given the multiple roles of these transmitters in pain and functions such as sleep, depression, and anxiety, the link between spinal and supraspinal processing of noxious inputs (via the monoamine transmitters) could be pivotal for linking the sensory and affective components of pain and their common co-morbidities, and also may potentially explain differences in pain scores and treatment outcomes in the patient population. PMID:20948695
DOE Office of Scientific and Technical Information (OSTI.GOV)
United States. Bonneville Power Administration, Portland, OR; Oregon Department of Agriculture Noxious Weed Control Program
During the 1996 season ODA executed the contract between BPA and ODA. Execution of this contract included the following activities: Survey for target noxious weeds, such as Gorse; collection and redistribution of biological control agents, for example, Apion seed weevils for Scotch broom, bioagents for diffuse and spotted knapweed, Gorse spider mite, and gall fly releases for control of Canada thistle and bull thistle; and control of isolated infestations of Gorse on BPA rights-of-way. Training was provided for line crews at the Chemawa, Alevy and North Bend districts. The purpose of the program is to assist BPA in the integratedmore » prevention and control of noxious weed species on BPA transmission line maintenance right-of-ways.« less
Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats
Tsujimura, Takanori; Kondo, Masahiro; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Saito, Kimiko; Tohara, Haruka; Ueda, Koichiro; Sessle, Barry J; Iwata, Koichi
2009-01-01
In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and γ-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABAA receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABAA receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin–NTS, lingual muscle–NTS and lingual muscle–Pa5–NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures. PMID:19124539
Martel, Marc O; Wasan, Ajay D; Edwards, Robert R
2013-11-01
To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls, among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. In this test-retest study, patients underwent a series of standardized psychophysical pain-testing procedures designed to assess CPM on two separate occasions (i.e., baseline and follow up). Patients also completed self-report measures of catastrophizing (Pain Catastrophizing Scale [PCS] and negative affect [NA]). Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher's Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychological factors (PCS and NA). Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men's endogenous pain-inhibitory function. Wiley Periodicals, Inc.
Martel, MO; Wasan, AD; Edwards, RR
2013-01-01
Objectives To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls (DNIC), among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. Design & subjects, and methods In this test-retest study, patients underwent a series of standardized psychophysical pain testing procedures designed to assess CPM on two separate occasions (i.e., baseline, follow-up). Patients also completed self-report measures of catastrophizing (PCS) and negative affect (NA). Results Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher’s Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychologic factors (PCS, NA). Conclusions Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men’s endogenous pain-inhibitory function. PMID:23924369
Nonpainful wide-area compression inhibits experimental pain.
Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena
2016-09-01
Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.
Xenon inhibits excitatory but not inhibitory transmission in rat spinal cord dorsal horn neurons
2010-01-01
Background The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method. Results In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist. Conclusions Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon. PMID:20444263
Aversive learning shapes neuronal orientation tuning in human visual cortex.
McTeague, Lisa M; Gruss, L Forest; Keil, Andreas
2015-07-28
The responses of sensory cortical neurons are shaped by experience. As a result perceptual biases evolve, selectively facilitating the detection and identification of sensory events that are relevant for adaptive behaviour. Here we examine the involvement of human visual cortex in the formation of learned perceptual biases. We use classical aversive conditioning to associate one out of a series of oriented gratings with a noxious sound stimulus. After as few as two grating-sound pairings, visual cortical responses to the sound-paired grating show selective amplification. Furthermore, as learning progresses, responses to the orientations with greatest similarity to the sound-paired grating are increasingly suppressed, suggesting inhibitory interactions between orientation-selective neuronal populations. Changes in cortical connectivity between occipital and fronto-temporal regions mirror the changes in visuo-cortical response amplitudes. These findings suggest that short-term behaviourally driven retuning of human visual cortical neurons involves distal top-down projections as well as local inhibitory interactions.
Nonpainful wide-area compression inhibits experimental pain
Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena
2016-01-01
Abstract Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM. PMID:27152691
Bee, L A; Dickenson, A H
2007-07-13
Complex networks of pathways project from various structures in the brain to modulate spinal processing of sensory input in a top-down fashion. The rostral ventromedial medulla (RVM) in the brainstem is one major final common output of this endogenous modulatory system and is involved in the relay of sensory information between the spinal cord and brain. The net output of descending neurons that exert inhibitory and facilitatory effects will determine whether neuronal activity in the spinal cord is increased or decreased. By pharmacologically blocking RVM activity with the local anesthetic lignocaine, and then measuring evoked responses of dorsal horn neurons to a range of applied peripheral stimuli, our aim was to determine the prevailing descending influence operating in normal anesthetized animals and animals with experimental neuropathic pain. The injection of 0.8 microl 2% lignocaine into the RVM caused a reduction in deep dorsal horn neuronal responses to electrical and natural stimuli in 64% of normal animals and in 81% of spinal-nerve-ligated (SNL) animals. In normal animals, responses to noxious input were predominantly reduced, while in SNL animals, reductions in spinal cord activity induced by intra-RVM lignocaine further included responses to non-noxious stimuli. This suggests that in terms of activity at least, if not number, descending facilitations are the predominant RVM influence that impacts the spinal cord in normal animals. Moreover, the increase in the proportion of neurons showing a post-lignocaine reduction in dorsal horn activity in SNL rats suggests that the strength of these facilitatory influences increases after neuropathy. This predominant inhibitory spinal effect following the injection of lignocaine into the RVM may be due to blockade of facilitatory On cells.
Pain perception studies in tension-type headache.
Bezov, David; Ashina, Sait; Jensen, Rigmor; Bendtsen, Lars
2011-02-01
Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders. © 2010 American Headache Society.
An artificial nociceptor based on a diffusive memristor.
Yoon, Jung Ho; Wang, Zhongrui; Kim, Kyung Min; Wu, Huaqiang; Ravichandran, Vignesh; Xia, Qiangfei; Hwang, Cheol Seong; Yang, J Joshua
2018-01-29
A nociceptor is a critical and special receptor of a sensory neuron that is able to detect noxious stimulus and provide a rapid warning to the central nervous system to start the motor response in the human body and humanoid robotics. It differs from other common sensory receptors with its key features and functions, including the "no adaptation" and "sensitization" phenomena. In this study, we propose and experimentally demonstrate an artificial nociceptor based on a diffusive memristor with critical dynamics for the first time. Using this artificial nociceptor, we further built an artificial sensory alarm system to experimentally demonstrate the feasibility and simplicity of integrating such novel artificial nociceptor devices in artificial intelligence systems, such as humanoid robots.
2007-04-01
philoxeroides Alligatorweed Alabama Class C noxious weed Imperata cylindrica Cogongrass Alabama Class A noxious weed; Mississippi noxious weed Ipomoea...Invasive Species Alternanthera philoxeroides Phragmites australis Cuscuta spp. Imperata cylindrica ...weed Cuscuta spp. Dodder Alabama Class A noxious weed Imperata cylindrica Cogongrass Alabama Class A noxious weed; MS noxious weed Ipomoea
Choi, J C; Kim, J; Kang, E; Choi, J-H; Park, W Y; Choi, Y-S; Cha, J; Han, C; Park, S K; Kim, M H; Lee, G H; Do, H-J; Jung, S W; Lee, J-M
2016-01-01
We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Xiuwen, Yang; Hongchen, Liu; Ke, Li; Zhen, Jin; Gang, Liu
2014-12-01
We used functional magnetic resonance imaging (fMRI) to explore the effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water. Six male and female subjects were subjected to whole-brain fMRI during the phasic delivery of non-noxious hot (23 °C) and no- xious cold (4 °C) water intraoral stimulation. A block-design blood oxygenation level-dependent fMRI scan covering the entire brain was also carried out. The activated cortical areas were as follows: left pre-/post-central gyrus, insula/operculum, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), midbrain red nucleus, and thalamus. The activated cortical areas under cold condition were as follows: left occipital lobe, premotor cortex/Brodmann area (BA) 6, right motor language area BA44, lingual gyrus, parietal lobule (BA7, 40), and primary somatosensory cortex S I. Comparisons of the regional cerebral blood flow response magnitude were made among stereotactically concordant brain regions that showed significant responses under the two conditions of this study. Compared with non-noxious warmth, more regions were activated in noxious coldness, and the magnitude of activation in areas produced after non-noxious warm stimulation significantly increased. However, ACC only significantly increased the magnitude of activation under noxious coldness stimulation. Results suggested that a similar network of regions was activated common to the perception of pain and no-pain produced by either non-noxious warmth or noxious coldness stimulation. Non-noxious warmth also activated more brain regions and significantly increased the response magnitude of cerebral-cortex activation compared with noxious coldness. Noxious coldness stimulation further significantly increased the magnitude of activation in ACC areas compared with noxious warmth.
Qin, Chao; Chen, Jiande D Z; Zhang, Jing; Foreman, Robert D
2007-12-01
Clinically, the overlap of gastroduodenal symptoms, such as visceral pain or hypersensitivity, is often observed in functional gastrointestinal disorders. The underlying mechanism may be related to intraspinal neuronal processing of noxious convergent inputs from the stomach and the intestine. The purpose of this study was to examine whether single low thoracic (T9-T10) spinal neurons responded to both gastric and duodenal mechanical stimulation. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Graded gastric distensions (GD, 20, 40, 60 mm Hg, 20 s) were induced by air inflation of a latex balloon surgically placed in the stomach. Graded duodenal distensions (DD, 0.2, 0.4, 0.6 ml, 20 s) were produced by water inflation of a latex balloon placed into the duodenum. Of 70 deeper (depth from dorsal surface of spinal cord: 0.3-1.2 mm) spinal neurons responsive to noxious GD (> or =40 mm Hg), 44(63%) also responded to noxious DD (> or =0.4 ml). Similarly, 13/17 (76%) superficial neurons (depth <0.3 mm) responded to both GD and DD. Of 57 gastroduodenal convergent neurons, 41 (72%) had excitatory and 6 had inhibitory responses to both GD and DD; the remaining neurons exhibited multiple patterns of excitation and inhibition. 43/57 (75%) gastroduodenal convergent neurons had low-threshold (< or =20 mm Hg) responses to GD, whereas 42/57 (74%) of these neurons had high-threshold (> or =0.4 ml) responses to DD. In addition, 34/40 (85%) gastroduodenal convergent neurons had somatic receptive fields on the back, flank, and medial/lateral abdominal areas. These results suggested that superficial and deeper T9-T10 spinal neurons received innocuous and/or noxious convergent inputs from mechanical stimulation of the stomach and duodenum. Gastroduodenal convergent spinal neurons might contribute to intraspinal sensory transmission for cross-organ afferent-afferent communication between the stomach and duodenum and play a role in visceral nociception and reflexes.
A novel paradigm to evaluate conditioned pain modulation in fibromyalgia.
Schoen, Cynthia J; Ablin, Jacob N; Ichesco, Eric; Bhavsar, Rupal J; Kochlefl, Laura; Harris, Richard E; Clauw, Daniel J; Gracely, Richard H; Harte, Steven E
2016-01-01
Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning ( P =0.007 and P =0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect ( P >0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation ( P =0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus ( P =0.269). The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls.
A novel paradigm to evaluate conditioned pain modulation in fibromyalgia
Schoen, Cynthia J; Ablin, Jacob N; Ichesco, Eric; Bhavsar, Rupal J; Kochlefl, Laura; Harris, Richard E; Clauw, Daniel J; Gracely, Richard H; Harte, Steven E
2016-01-01
Introduction Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus. Methods Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus. Results In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect (P>0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269). Conclusion The current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls. PMID:27713648
Regulation of body temperature and nociception induced by non-noxious stress in rat.
Vidal, C; Suaudeau, C; Jacob, J
1984-04-09
The effects of 3 different non-noxious stressors on body temperature (Tb) were investigated in the rat: (1) loose restraint in cylinders, (2) removal of the rats from cylinders, exposure to a novel environment and replacement in cylinders, a stressor called here 'novelty', and (3) gentle holding of the rats by the nape of the neck. Loose restraint and 'novelty' produced hyperthermia. On the contrary, holding induced hypothermia. Hypophysectomy (HX) reduced basal Tb, abolished restraint hyperthermia and reduced both 'novelty' hyperthermia and holding hypothermia. Dexamethasone ( DEXA ) had no effect upon either restraint or novelty hyperthermia but reduced the hypothermia. Naloxone (Nx) produced a slight fall in basal Tb accounting for its reduction of restraint and 'novelty' hyperthermias ; it did not affect holding hypothermia. The inhibitory effects of HX suggest a participation of the pituitary in the hyperthermias ; the neurointermediate lobe would be involved as the hyperthermias were not affected by DEXA , which is known to block the stress-induced release of pituitary secretions from the anterior lobe but not from the neurointermediate lobe. In contrast, substances from the anterior lobe might participate in hypothermia due to holding since it is reduced by HX and DEXA . As to the effects of Nx, endogenous opioids would not be significantly involved in the thermic effects of the stressors used in this study; they might play, if any, only a minor role in the regulation of basal Tb. These results are compared with those previously obtained on nociception using the same non-noxious stressors. It emerges that, depending on the stressor, different types of association between thermoregulation and nociception may occur, i.e. hyperthermia with analgesia, hyperthermia with hyperalgesia and hypothermia with hyperalgesia.
Code of Federal Regulations, 2012 CFR
2012-01-01
... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...
Code of Federal Regulations, 2014 CFR
2014-01-01
... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...
Code of Federal Regulations, 2013 CFR
2013-01-01
... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...
7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 5 2011-01-01 2011-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...
7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 5 2011-01-01 2011-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...
7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 5 2014-01-01 2014-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...
7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 5 2014-01-01 2014-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...
7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 5 2013-01-01 2013-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...
7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 5 2012-01-01 2012-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...
7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 5 2013-01-01 2013-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...
7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 5 2012-01-01 2012-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...
Code of Federal Regulations, 2011 CFR
2011-01-01
... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...
Code of Federal Regulations, 2014 CFR
2014-01-01
... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...
Code of Federal Regulations, 2012 CFR
2012-01-01
... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...
Code of Federal Regulations, 2013 CFR
2013-01-01
... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...
Pronociceptive pain modulation in patients with painful chemotherapy-induced polyneuropathy.
Nahman-Averbuch, Hadas; Yarnitsky, David; Granovsky, Yelena; Sprecher, Elliot; Steiner, Mariana; Tzuk-Shina, Tzahala; Pud, Dorit
2011-08-01
Several chemotherapy agents induce polyneuropathy that is painful for some patients, but not for others. We assumed that these differences might be attributable to varying patterns of pain modulation. The aim of the present study was to evaluate pain modulation in such patients. Twenty-seven patients with chemotherapy-induced polyneuropathy were tested for detection thresholds (cold, warm, and mechanical) in both the forearm and foot, as well as for heat pain threshold, mechanical temporal summation (TS), and conditioned pain modulation (CPM; also known as the diffuse noxious inhibitory control-like effect), which were tested in the upper limbs. Positive correlations were found between clinical pain levels and both TS (r=0.52, P=0.005) and CPM (r=0.40, P=0.050) for all patients. In addition, higher TS was associated with less efficient CPM (r=0.56, P=0.004). The group of patients with painful polyneuropathy (n=12) showed a significantly higher warm detection threshold in the foot (P=0.03), higher TS (P<0.01), and less efficient CPM (P=0.03) in comparison to the group with nonpainful polyneuropathy. The painfulness of polyneuropathy is associated with a "pronociceptive" modulation pattern, which may be primary to the development of pain. The higher warm sensory thresholds in the painful polyneuropathy group suggest that the severity of polyneuropathy may be another factor in determining its painfulness. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana
2018-03-01
The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.
Ladouceur, Alexandra; Rustamov, Nabi; Dubois, Jean-Daniel; Tessier, Jessica; Lehmann, Alexandre; Descarreaux, Martin; Rainville, Pierre; Piché, Mathieu
2017-10-10
The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p's <0.001), while selective attention only decreased pain (p < 0.01) and the N100 (p<0.001). In contrast, the P260 was decreased by HNCS only when attention was directed toward the HNCS stimulus (p<0.01). This indicates that patients with the characteristics described above do not show altered pain inhibitory mechanisms involved in HNCS and selective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Brain Mechanisms Supporting Discrimination of Sensory Features of Pain: A New Model
Oshiro, Yoshitetsu; Quevedo, Alexandre S.; McHaffie, John G.; Kraft, Robert A.; Coghill, Robert C.
2010-01-01
Pain can be very intense or only mild, and can be well localized or diffuse. To date, little is known as to how such distinct sensory aspects of noxious stimuli are processed by the human brain. Using functional magnetic resonance imaging and a delayed match-to-sample task, we show that discrimination of pain intensity, a non-spatial aspect of pain, activates a ventrally directed pathway extending bilaterally from the insular cortex to the prefrontal cortex. This activation is distinct from the dorsally-directed activation of the posterior parietal cortex and right dorsolateral prefrontal cortex that occurs during spatial discrimination of pain. Both intensity and spatial discrimination tasks activate highly similar aspects of the anterior cingulate cortex, suggesting that this structure contributes to common elements of the discrimination task such as the monitoring of sensory comparisons and response selection. Taken together, these results provide the foundation for a new model of pain in which bidirectional dorsal and ventral streams preferentially amplify and process distinct sensory features of noxious stimuli according to top-down task demands. PMID:19940188
7 CFR 360.301 - Information required for applications for permits to move noxious weeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...
7 CFR 360.301 - Information required for applications for permits to move noxious weeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...
7 CFR 360.301 - Information required for applications for permits to move noxious weeds.
Code of Federal Regulations, 2011 CFR
2011-01-01
... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...
7 CFR 360.301 - Information required for applications for permits to move noxious weeds.
Code of Federal Regulations, 2014 CFR
2014-01-01
... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-01-25
... Collection; Plant Pest, Noxious Weed, and Garbage Regulations AGENCY: Animal and Plant Health Inspection... with plant pest, noxious weed, and garbage regulations. DATES: We will consider all comments that we... pest, noxious weed, and garbage regulations, contact Dr. Shirley Wager- Pag[eacute], Chief, Pest Permit...
7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...
7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.
Code of Federal Regulations, 2014 CFR
2014-01-01
... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...
7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...
7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.
Code of Federal Regulations, 2011 CFR
2011-01-01
... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...
7 CFR 360.300 - General prohibitions and restrictions on the movement of noxious weeds; permits.
Code of Federal Regulations, 2010 CFR
2010-01-01
... of noxious weeds; permits. 360.300 Section 360.300 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 General prohibitions and restrictions on the movement of noxious weeds; permits. (a) No...
Code of Federal Regulations, 2010 CFR
2010-07-01
... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...
Code of Federal Regulations, 2011 CFR
2011-07-01
... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...
Code of Federal Regulations, 2013 CFR
2013-07-01
... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...
Code of Federal Regulations, 2014 CFR
2014-07-01
... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...
Code of Federal Regulations, 2012 CFR
2012-07-01
... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...
7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 5 2013-01-01 2013-01-01 false Petitions to remove a taxon from the noxious weed...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501 Petitions to remove a taxon from the noxious weed lists. A person may petition the Administrator to remove a...
Fuchs, P C; Barry, A L; Thornsberry, C; Gavan, T L; Jones, R N
1983-01-01
Augmentin (Beecham Laboratories, Bristol, Tenn.), a combination drug consisting of two parts amoxicillin to one part clavulanic acid and a potent beta-lactamase inhibitor, was evaluated in vitro in comparison with ampicillin or amoxicillin or both for its inhibitory and bactericidal activities against selected clinical isolates. Regression analysis was performed and tentative disk diffusion susceptibility breakpoints were determined. A multicenter performance study of the disk diffusion test was conducted with three quality control organisms to determine tentative quality control limits. All methicillin-susceptible staphylococci and Haemophilus influenzae isolates were susceptible to Augmentin, although the minimal inhibitory concentrations for beta-lactamase-producing strains of both groups were, on the average, fourfold higher than those for enzyme-negative strains. Among the Enterobacteriaceae, Augmentin exhibited significantly greater activity than did ampicillin against Klebsiella pneumoniae, Citrobacter diversus, Proteus vulgaris, and about one-third of the Escherichia coli strains tested. Bactericidal activity usually occurred at the minimal inhibitory concentration. There was a slight inoculum concentration effect on the Augmentin minimal inhibitory concentrations. On the basis of regression and error rate-bounded analyses, the suggested interpretive disk diffusion susceptibility breakpoints for Augmentin are: susceptible, greater than or equal to 18 mm; resistant, less than or equal to 13 mm (gram-negative bacilli); and susceptible, greater than or equal to 20 mm (staphylococci and H. influenzae). The use of a beta-lactamase-producing organism, such as E. coli Beecham 1532, is recommended for quality assurance of Augmentin susceptibility testing. PMID:6625554
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 5 2011-01-01 2011-01-01 false Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a...
Patel, Dhaval D; Anderson, Bradley D
2014-05-05
This study quantitatively explores the mechanisms underpinning the effects of model pharmaceutical polymeric precipitation inhibitors (PPIs) on the crystal growth and, in turn, maintenance of supersaturation of indomethacin, a model poorly water-soluble drug. A recently developed second-derivative UV spectroscopy method and a first-order empirical crystal growth model were used to determine indomethacin crystal growth rates in the presence of model PPIs. All three model PPIs including HP-β-CD, PVP, and HPMC inhibited indomethacin crystal growth at both high and low degrees of supersaturation (S). The bulk viscosity changes in the presence of model PPIs could not explain their crystal growth inhibitory effects. At 0.05% w/w, PVP (133-fold) and HPMC (28-fold) were better crystal growth inhibitors than HP-β-CD at high S. The inhibitory effect of HP-β-CD on the bulk diffusion-controlled indomethacin crystal growth at high S was successfully modeled using reactive diffusion layer theory, which assumes reversible complexation in the diffusion layer. Although HP-β-CD only modestly inhibited indomethacin crystal growth at either high S (∼15%) or low S (∼2-fold), the crystal growth inhibitory effects of PVP and HPMC were more dramatic, particularly at high S (0.05% w/w). The superior crystal growth inhibitory effects of PVP and HPMC as compared with HP-β-CD at high S were attributed to a change in the indomethacin crystal growth rate-limiting step from bulk diffusion to surface integration. Indomethacin crystal growth inhibitory effects of all three model PPIs at low S were attributed to retardation of the rate of surface integration of indomethacin, a phenomenon that may reflect the adsorption of PPIs onto the growing crystal surface. The quantitative approaches outlined in this study should be useful in future studies to develop tools to predict supersaturation maintenance effects of PPIs.
Yamamoto, Naomi; Oshima, Masamitsu; Tanaka, Chie; Ogawa, Miho; Nakajima, Kei; Ishida, Kentaro; Moriyama, Keiji; Tsuji, Takashi
2015-01-01
The tooth is an ectodermal organ that arises from a tooth germ under the regulation of reciprocal epithelial-mesenchymal interactions. Tooth morphogenesis occurs in the tooth-forming field as a result of reaction-diffusion waves of specific gene expression patterns. Here, we developed a novel mechanical ligation method for splitting tooth germs to artificially regulate the molecules that control tooth morphology. The split tooth germs successfully developed into multiple correct teeth through the re-regionalisation of the tooth-forming field, which is regulated by reaction-diffusion waves in response to mechanical force. Furthermore, split teeth erupted into the oral cavity and restored physiological tooth function, including mastication, periodontal ligament function and responsiveness to noxious stimuli. Thus, this study presents a novel tooth regenerative technology based on split tooth germs and the re-regionalisation of the tooth-forming field by artificial mechanical force. PMID:26673152
Task Inhibition and Response Inhibition in Older vs. Younger Adults: A Diffusion Model Analysis
Schuch, Stefanie
2016-01-01
Differences in inhibitory ability between older (64–79 years, N = 24) and younger adults (18–26 years, N = 24) were investigated using a diffusion model analysis. Participants performed a task-switching paradigm that allows assessing n−2 task repetition costs, reflecting inhibitory control on the level of tasks, as well as n−1 response-repetition costs, reflecting inhibitory control on the level of responses. N−2 task repetition costs were of similar size in both age groups. Diffusion model analysis revealed that for both younger and older adults, drift rate parameters were smaller in the inhibition condition relative to the control condition, consistent with the idea that persisting task inhibition slows down response selection. Moreover, there was preliminary evidence for task inhibition effects in threshold separation and non-decision time in the older, but not the younger adults, suggesting that older adults might apply different strategies when dealing with persisting task inhibition. N−1 response-repetition costs in mean RT were larger in older than younger adults, but in mean error rates tended to be larger in younger than older adults. Diffusion-model analysis revealed longer non-decision times in response repetitions than response switches in both age groups, consistent with the idea that motor processes take longer in response repetitions than response switches due to persisting response inhibition of a previously executed response. The data also revealed age-related differences in overall performance: Older adults responded more slowly and more accurately than young adults, which was reflected by a higher threshold separation parameter in diffusion model analysis. Moreover, older adults showed larger non-decision times and higher variability in non-decision time than young adults, possibly reflecting slower and more variable motor processes. In contrast, overall drift rate did not differ between older and younger adults. Taken together, diffusion model analysis revealed differences in overall performance between the age groups, as well as preliminary evidence for age differences in dealing with task inhibition, but no evidence for an inhibitory deficit in older age. PMID:27895599
Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco
2011-02-01
Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.
Guidelines for management of noxious weeds at Hanford
DOE Office of Scientific and Technical Information (OSTI.GOV)
Roos, R.C.; Malady, M.B.
1995-10-27
Integrated Pest Management Services is responsible for management and control of noxious weeds on the Hanford Site. Weed species and populations are prioritized and objective defined, according to potential site and regional impact. Population controls are implemented according to priority. An integrated approach is planned for noxious weed control in which several management options are considered and implemented separately or in coordination to best meet management objectives. Noxious weeds are inventories and monitored to provide information for planning and program review.
Code of Federal Regulations, 2013 CFR
2013-01-01
..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.100 Definitions. As used in this part, words in the... in this definition. Noxious weed. Any plant or plant product that can directly or indirectly injure... Administrator to move plants, plant products, biological control organisms, plant pests, noxious weeds, or...
Code of Federal Regulations, 2014 CFR
2014-01-01
..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.100 Definitions. As used in this part, words in the... in this definition. Noxious weed. Any plant or plant product that can directly or indirectly injure... Administrator to move plants, plant products, biological control organisms, plant pests, noxious weeds, or...
Shryock, Thomas R; Staples, J Mitchell; DeRosa, David C
2002-09-01
Tilmicosin is a novel macrolide antibiotic developed for exclusive use in veterinary medicine. Tilmicosin has been approved as a feed premix to control porcine respiratory disease associated with Pasteurella multocida and Actinobacillus pleuropneumoniae. The development of antimicrobial susceptibility testing guidelines for tilmicosin was predicated on the relationship of clinical efficacy studies that demonstrated a favorable therapeutic outcome, on pharmacokinetic data, and on in vitro test data, as recommended by the National Committee for Clinical Laboratory Standards (NCCLS). The approved breakpoints for the minimum inhibitory concentration dilution testing for both species are resistant, > or = 32 microg/ml, and susceptible, < or = 16 microg/ml. The zone of inhibition interpretive criteria for disk diffusion testing with a 15-microg tilmicosin disk are resistant, < or = 10 mm, and susceptible, > or = 11 mm.
You, H-J; Lei, J; Niu, N; Yang, L; Fan, X-L; Tjølsen, A; Li, Q
2013-03-01
Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. We found that the MD nuclei participated in the descending facilitation of mechanical hyperalgesia, and that the VM nuclei were specifically involved in the descending inhibition of heat hypoalgesia. Neither descending facilitation nor descending inhibition was affected after electrolytic lesion of the thalamic CM, SM, and VPL nuclei. This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
Grau, James W; Huang, Yung-Jen; Turtle, Joel D; Strain, Misty M; Miranda, Rajesh C; Garraway, Sandra M; Hook, Michelle A
2017-05-15
Spinal cord injury (SCI) is often accompanied by other tissue damage (polytrauma) that provides a source of pain (nociceptive) input. Recent findings are reviewed that show SCI places the caudal tissue in a vulnerable state that exaggerates the effects nociceptive stimuli and promotes the development of nociceptive sensitization. Stimulation that is both unpredictable and uncontrollable induces a form of maladaptive plasticity that enhances nociceptive sensitization and impairs spinally mediated learning. In contrast, relational learning induces a form of adaptive plasticity that counters these adverse effects. SCI sets the stage for nociceptive sensitization by disrupting serotonergic (5HT) fibers that quell overexcitation. The loss of 5HT can enhance neural excitability by reducing membrane-bound K + -Cl - cotransporter 2, a cotransporter that regulates the outward flow of Cl - . This increases the intracellular concentration of Cl - , which reduces the hyperpolarizing (inhibitory) effect of gamma-aminobutyric acid. Uncontrollable noxious stimulation also undermines the recovery of locomotor function, and increases behavioral signs of chronic pain, after a contusion injury. Nociceptive stimulation has a greater effect if experienced soon after SCI. This adverse effect has been linked to a downregulation in brain-derived neurotrophic factor and an upregulation in the cytokine, tumor necrosis factor. Noxious input enhances tissue loss at the site of injury by increasing the extent of hemorrhage and apoptotic/pyroptotic cell death. Intrathecal lidocaine blocks nociception-induced hemorrhage, cellular indices of cell death, and its adverse effect on behavioral recovery. Clinical implications are discussed.
The economic cost of noxious weeds on Montana grazing lands
USDA-ARS?s Scientific Manuscript database
We distributed a 16-question survey concerning noxious weed abundances, impacts and management to livestock producers grazing on privately-owned or leased grazing lands in Montana. The noxious weeds most commonly reported as being present on respondents’ grazing units were Canada thistle (64% of gra...
7 CFR 352.3 - Enforcement and administration.
Code of Federal Regulations, 2013 CFR
2013-01-01
... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...
7 CFR 352.10 - Inspection; safeguards; disposal.
Code of Federal Regulations, 2013 CFR
2013-01-01
... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...
7 CFR 352.3 - Enforcement and administration.
Code of Federal Regulations, 2014 CFR
2014-01-01
... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...
7 CFR 352.3 - Enforcement and administration.
Code of Federal Regulations, 2011 CFR
2011-01-01
... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...
7 CFR 301.1 - Purpose and scope.
Code of Federal Regulations, 2014 CFR
2014-01-01
... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...
7 CFR 352.3 - Enforcement and administration.
Code of Federal Regulations, 2012 CFR
2012-01-01
... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...
7 CFR 352.10 - Inspection; safeguards; disposal.
Code of Federal Regulations, 2014 CFR
2014-01-01
... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...
7 CFR 301.1 - Purpose and scope.
Code of Federal Regulations, 2012 CFR
2012-01-01
... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...
7 CFR 352.10 - Inspection; safeguards; disposal.
Code of Federal Regulations, 2012 CFR
2012-01-01
... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...
7 CFR 301.1 - Purpose and scope.
Code of Federal Regulations, 2013 CFR
2013-01-01
... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...
7 CFR 352.10 - Inspection; safeguards; disposal.
Code of Federal Regulations, 2011 CFR
2011-01-01
... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...
Not in whose backyard? Minority population concentrations and noxious facility sites
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nieves, L.A.
1992-04-01
The NIMBY (not in may backyard) syndrome has become the nemesis of facility siting efforts in the USA. Given people`s reluctance to live near noxious facilities, in whose backyard are such facilities located? This study employs US county-level data to examine relative concentrations of minorities living near noxious facilities. Facility types analyzed include electric generating plants, manufacturing plants, Superfund sites, and radioactive waste disposal sites. While this study does not address which cam first, the minority population concentration or the noxious facilities, it documents their current degree of association.
Not in whose backyard Minority population concentrations and noxious facility sites
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nieves, L.A.
1992-01-01
The NIMBY (not in may backyard) syndrome has become the nemesis of facility siting efforts in the USA. Given people's reluctance to live near noxious facilities, in whose backyard are such facilities located This study employs US county-level data to examine relative concentrations of minorities living near noxious facilities. Facility types analyzed include electric generating plants, manufacturing plants, Superfund sites, and radioactive waste disposal sites. While this study does not address which cam first, the minority population concentration or the noxious facilities, it documents their current degree of association.
Astrocytic Ca2+ responses in the spinal dorsal horn by noxious stimuli to the skin.
Yoshihara, Kohei; Matsuda, Tsuyoshi; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto
2018-05-03
The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca 2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca 2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca 2+ responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Waning of "conditioned pain modulation": a novel expression of subtle pronociception in migraine.
Nahman-Averbuch, Hadas; Granovsky, Yelena; Coghill, Robert C; Yarnitsky, David; Sprecher, Elliot; Weissman-Fogel, Irit
2013-01-01
To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine. One of the most explored mechanisms underlying the pain modulation system is "diffuse noxious inhibitory controls," which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation. Migraineurs (n = 26) and healthy controls (n = 35), all females, underwent 3 stimulation series, consisting of repeated (1) "test-stimulus" (Ts) alone that was given first followed by (2) parallel CPM application (CPM-parallel), and (3) sequential CPM application (CPM-sequential), in which the Ts is delivered during or following the conditioning-stimulus, respectively. In all series, the Ts repeated 4 times (0-3). In the CPM series, repetition "0" consisted of the Ts-alone that was followed by 3 repetitions of the Ts with a conditioning-stimulus application. Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM-parallel efficiency along the series for migraineurs (P = .005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM-sequential series was correlated with less reported extent of pain reduction by episodic medication (r = 0.493, P = .028). Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine. © 2013 American Headache Society.
7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 5 2014-01-01 2014-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...
7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 5 2011-01-01 2011-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...
7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 5 2012-01-01 2012-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...
7 CFR 360.600 - Preemption of State and local laws.
Code of Federal Regulations, 2014 CFR
2014-01-01
... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...
Code of Federal Regulations, 2012 CFR
2012-01-01
... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...
7 CFR 360.600 - Preemption of State and local laws.
Code of Federal Regulations, 2013 CFR
2013-01-01
... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...
7 CFR 352.6 - Application for permit and approval or denial thereof.
Code of Federal Regulations, 2014 CFR
2014-01-01
... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...
Code of Federal Regulations, 2014 CFR
2014-01-01
... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...
7 CFR 352.6 - Application for permit and approval or denial thereof.
Code of Federal Regulations, 2012 CFR
2012-01-01
... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...
7 CFR 352.6 - Application for permit and approval or denial thereof.
Code of Federal Regulations, 2013 CFR
2013-01-01
... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...
7 CFR 360.600 - Preemption of State and local laws.
Code of Federal Regulations, 2011 CFR
2011-01-01
... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...
7 CFR 360.600 - Preemption of State and local laws.
Code of Federal Regulations, 2012 CFR
2012-01-01
... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...
Code of Federal Regulations, 2013 CFR
2013-01-01
... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...
7 CFR 360.400 - Preemption of State and local laws.
Code of Federal Regulations, 2010 CFR
2010-01-01
... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.400 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...
A network of autism linked genes stabilizes two pools of synaptic GABAA receptors
Tong, Xia-Jing; Hu, Zhitao; Liu, Yu; Anderson, Dorian; Kaplan, Joshua M
2015-01-01
Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABAA receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABAA receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD. DOI: http://dx.doi.org/10.7554/eLife.09648.001 PMID:26575289
Huang, W; Simpson, R K
1999-09-01
Sensitization of the second order neurons in the spinal dorsal horn after somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. These neurons also express c-Fos immunoreactivity in response to the somatic noxious stimuli. The present study assessed the influence of intrathecal pre-treatment with MK-801, a non-competitive antagonist of NMDA receptor, on thermal sensitization following peripheral noxious heat stimulation. In addition, the influence of MK-801 on c-Fos immunoreactivity in the rat lumbar spinal cord neurons after the peripheral noxious heat was examined. Sprague-Dawley rats were subject to intrathecal catheterization and administration of MK-801 or saline before and after noxious heat (52 degrees C) stimulation of rat hindpaws. Thermal sensitization was tested after MK-801 (0.1 mumol 10 microliters-1). Fos-like immunoreactivity was evaluated 2 h after noxious stimulation in a separate group of animals. MK-801 significantly increased the thermal withdrawal threshold by 60% following noxious heat stimulation and reduced c-Fos immunoreactivity in the second order neurons by 70% in the dorsal horn. The study suggests that glutamate plays a pivotal role in the thermal nociceptive pathway and indicates that the NMDA receptor is necessary to maintain normal thermal sensitization, possibly by regulating c-fos gene expression in second order neurons.
Madrid, Isabel Martins; Mattei, Antonella Souza; Santin, Rosema; dos Reis Gomes, Angelita; Cleff, Marlete Brum; Meireles, Mário Carlos Araújo
2012-05-01
The susceptibility of Sporothrix schenckii isolates from clinical cases of canine, feline and human sporotrichosis, and from the environment, was evaluated with 4% sodium hypochlorite and 6.6% chlorhexidine digluconate using the broth microdilution, agar diffusion and direct exposure techniques. The minimal inhibitory concentration was smaller than 0.8% for chlorhexidine digluconate and between 8% and 4% for sodium hypochlorite. Inhibition zones were not found in agar diffusion for sodium hypochlorite, and zones averaging 1.9 mm were found for chlorhexidine digluconate. In the direct exposure test, sodium hypochlorite demonstrated best performance at 20 min of contact, as chlorhexidine digluconate presented little antimicrobial activity. © 2011 Blackwell Verlag GmbH.
Barbara Goodrich Phillips; Debra Crisp
2001-01-01
Many noxious weed infestations are initiated or increased by soil disturbance. With the recent emphasis on reintroduction of fire into natural ecosystems there has been increased interest in the effects of noxious weeds following fires. This paper discusses the effects of fire on Flagstaff pennyroyal, a Forest Service Region 3 sensitive plant, and the subsequent...
Patel, Atit A.; Cox, Daniel N.
2017-01-01
To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural activity in response to noxious cold, we implemented a GCaMP6-based calcium imaging assay enabling in vivo studies of intracellular calcium dynamics in intact Drosophila larvae. We identified Drosophila class III multidendritic (md) sensory neurons as multimodal sensors of innocuous mechanical and noxious cold stimuli and to dissect the mechanistic bases of multimodal sensory processing we developed two independent functional assays. First, we developed an optogenetic dose response assay to assess whether levels of neural activation contributes to the multimodal aspects of cold sensitive sensory neurons. Second, we utilized CaMPARI, a photo-switchable calcium integrator that stably converts fluorescence from green to red in presence of high intracellular calcium and photo-converting light, to assess in vivo functional differences in neural activation levels between innocuous mechanical and noxious cold stimuli. These novel assays enable investigations of behavioral and functional roles of peripheral sensory neurons and multimodal sensory processing in Drosophila larvae. PMID:28835907
Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Hirata, Hiromi; Moorhouse, Andrew J.; Ishibashi, Hitoshi
2017-01-01
Abstract Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system. PMID:28197549
Nakahata, Yoshihisa; Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Kuriu, Toshihiko; Hirata, Hiromi; Moorhouse, Andrew J; Ishibashi, Hitoshi; Nabekura, Junichi
2017-01-01
Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo . While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca 2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system.
Vegeto, Elisabetta; Benedusi, Valeria; Maggi, Adriana
2008-01-01
Recent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer’s and Parkinson’s Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia. PMID:18522863
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hutchinson, Kenneth
To perform remedial vegetation management for keeping vegetation a safe distance away from electric power facilities and controlling noxious weeds within a section of BPA's Big Eddy-Ostrander Transmission Corridor. During a site review conducted in late fall of 2001, the inspector observed various species of hardwood trees resprouted from stumps. The new vegetative growth encroached on the required “Minimum Safe Distance” between the top of vegetation and the conductor cables. The management action is necessary to reduce the current and potential future hazards that tall-growing vegetation poses to transmission conductors. In addition, BPA will include weed control as part ofmore » their remedial vegetation management action. Noxious weeds occur within the corridor. Under a 1999 Executive Order, all federal agencies are required to detect and control noxious weeds. In addition, BPA is required under the 1990 amendment to the Noxious Weed Act (7 USC 2801-2814) to manage undesirable plants on federal land. Also, the Bonneville Power Administration (BPA) has responsibility to manage noxious weeds under the Transmission System Vegetation Management Program Final Environmental Impact Statement (FEIS).1 State statutes and regulations also mandate action by BPA and the USFS to control noxious weeds. The Oregon Department of Agriculture (ODA) has requested that agencies aggressively control these weeds before additional spread occurs.« less
Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria
2010-08-15
This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Piovesan, Elcio Juliato; Di Stani, Fabrizio; Kowacs, Pedro André; Mulinari, Rogério Andrade; Radunz, Victor Hugo; Utiumi, Marco; Muranka, Eder B; Giublin, Mario Luiz; Werneck, Lineu César
2007-09-01
Activation of the trigemino-cervical system constitutes one of the first steps in the genesis of migraine. The objective of this study was to confirm the presence of trigemino-cervical convergence mechanisms and to establish whether such mechanisms may also be of inhibitory origin. We describe a case of a 39-years-old woman suffering from episodic migraine who showed a significant improvement in her frontal headache during migraine attacks if the greater occipital nerve territory was massaged after the appearance of static mechanical allodynia (cortical sensitization). We review trigemino-cervical convergence and diffuse nociceptive inhibitory control (DNIC) mechanisms and suggest that the convergence mechanisms are not only excitatory but also inhibitory.
Integrating impairments in reaction time and executive function using a diffusion model framework
Karalunas, Sarah L.; Huang-Pollock, Cynthia L.
2013-01-01
Using Ratcliff’s diffusion model and ex-Gaussian decomposition, we directly evaluate the role individual differences in reaction time (RT) distribution components play in the prediction of inhibitory control and working memory (WM) capacity in children with and without ADHD. Children with (n=92, x̄ age= 10.2 years, 67% male) and without ADHD (n=62, x̄ age=10.6 years, 46% male) completed four tasks of WM and a stop signal reaction time (SSRT) task. Children with ADHD had smaller WM capacities and less efficient inhibitory control. Diffusion model analyses revealed that children with ADHD had slower drift rates (v) and faster non-decision times (Ter), but there were no group differences in boundary separations (a). Similarly, using an ex-Gaussian approach, children with ADHD had larger τ values than non-ADHD controls, but did not differ in µ or σ distribution components. Drift rate mediated the association between ADHD status and performance on both inhibitory control and WM capacity. τ also mediated the ADHD-executive function impairment associations; however, models were a poorer fit to the data. Impaired performance on RT and executive functioning tasks has long been associated with childhood ADHD. Both are believed to be important cognitive mechanisms to the disorder. We demonstrate here that drift rate, or the speed at which information accumulates towards a decision, is able to explain both. PMID:23334775
Irkin, Reyhan; Abay, Secil; Aydin, Fuat
2011-03-01
We investigated the inhibitory activity of commercially marketed essential oils of mint, rosemary, orange, sage, cinnamon, bay, clove, and cumin against Arcobacter butzleri and Arcobacter skirrowii and the effects of the essential oil of rosemary against A. butzleri in a cooked minced beef system. Using the disc diffusion method to determine the inhibitory activities of these plant essential oils against strains of Arcobacter, we found that those of rosemary, bay, cinnamon, and clove had strong inhibitory activity against these organisms, whereas the essential oils of cumin, mint, and sage failed to show inhibitory activity against most of the Arcobacter strains tested. The 0.5% (vol/wt) essential oil of rosemary was completely inhibitory against A. butzleri in the cooked minced beef system at 4°C. These essential oils may be further investigated as a natural solution to the food industry by creating an additional barrier (hurdle technology) to inhibit the growth of Arcobacter strains.
Leiras, Roberto; Martín-Cora, Francisco; Velo, Patricia; Liste, Tania
2015-01-01
Animals and human beings sense and react to real/potential dangerous stimuli. However, the supraspinal mechanisms relating noxious sensing and nocifensive behavior are mostly unknown. The collateralization and spatial organization of interrelated neurons are important determinants of coordinated network function. Here we electrophysiologically studied medial medullary reticulospinal neurons (mMRF-RSNs) antidromically identified from the cervical cord of anesthetized cats and found that 1) more than 40% (79/183) of the sampled mMRF-RSNs emitted bifurcating axons running within the dorsolateral (DLF) and ventromedial (VMF) ipsilateral fascicles; 2) more than 50% (78/151) of the tested mMRF-RSNs with axons running in the VMF collateralized to the subnucleus reticularis dorsalis (SRD) that also sent ipsilateral descending fibers bifurcating within the DLF and the VMF. This percentage of mMRF collateralization to the SRD increased to more than 81% (53/65) when considering the subpopulation of mMRF-RSNs responsive to noxiously heating the skin; 3) reciprocal monosynaptic excitatory relationships were electrophysiologically demonstrated between noxious sensitive mMRF-RSNs and SRD cells; and 4) injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin evidenced mMRF to SRD and SRD to mMRF projections contacting the soma and proximal dendrites. The data demonstrated a SRD-mMRF network interconnected mainly through collaterals of descending axons running within the VMF, with the subset of noxious sensitive cells forming a reverberating circuit probably amplifying mutual outputs simultaneously regulating motor activity and spinal noxious afferent input. The results provide evidence that noxious stimulation positively engages a reticular SRD-mMRF-SRD network involved in pain-sensory-to-motor transformation and modulation. PMID:26581870
Rahman, Wahida; Sikandar, Shafaq; Sikander, Shafaq; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H
2007-06-04
Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives facilitation.
Harper, Daniel E; Ichesco, Eric; Schrepf, Andrew; Hampson, Johnson P; Clauw, Daniel J; Schmidt-Wilcke, Tobias; Harris, Richard E; Harte, Steven E
2018-06-01
Conditioned pain modulation (CPM), a psychophysical paradigm that is commonly used to infer the integrity of endogenous pain-altering systems by observation of the effect of one noxious stimulus on another, has previously identified deficient endogenous analgesia in fibromyalgia (FM) and other chronic pain conditions. The mechanisms underlying this deficiency, be they insufficient inhibition and/or active facilitation, are largely unknown. The present cross-sectional study used a combination of behavioral CPM testing, voxel-based morphometry, and resting state functional connectivity to identify neural correlates of CPM in healthy controls (HC; n = 14) and FM patients (n = 15), and to probe for differences that could explain the pain-facilitative CPM that was observed in our patient sample. Voxel-based morphometry identified a cluster encompassing the periaqueductal gray (PAG) that contained significantly less gray matter volume in FM patients. Higher resting connectivity between this cluster and cortical pain processing regions was associated with more efficient inhibitory CPM in both groups, whereas PAG connectivity with the dorsal pons was associated with greater CPM inhibition only in HC. Greater PAG connectivity to the caudal pons/rostral medulla, which was pain-inhibitory in HC, was associated with pain facilitation in FM patients. These findings indicate that variation in the strength of the PAG resting functional connectivity can explain some of the normal variability in CPM. In addition, pain-facilitative CPM observed in FM patients likely involves attenuation of pain inhibitory as well as amplification of pain facilitative processes in the central nervous system. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.
Arenas, Oscar M.; Zaharieva, Emanuela E.; Para, Alessia; Vásquez-Doorman, Constanza; Petersen, Christian P.; Gallio, Marco
2017-01-01
All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant flies (Drosophila) are also defective in noxious heat responses. Unexpectedly, we find that either planarian or human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. PMID:29184198
Noxious heat and scratching decrease histamine-induced itch and skin blood flow.
Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D
2005-12-01
The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hutchinson, Kenneth
Vegetation Management on sections of the McNary-Ross, McNary-Horse Heaven, Horse Heaven-Harvarlum, Harvarlum-Big Eddy, and Hanford-John Day Transmission lines. The treatment areas are identified in Step 1 of the Planning Steps shown below. The work will involve the control of noxious weeds in the subject rights-of-ways (ROWs). BPA, in cooperation with the various County Noxious Weed Control Boards and associated landowners, will provide resources to assist landowners in controlling noxious weeds on the subject ROWs. The Weed Board will perform all activities on behalf of BPA.
Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain
Kanju, Patrick; Chen, Yong; Lee, Whasil; Yeo, Michele; Lee, Suk Hee; Romac, Joelle; Shahid, Rafiq; Fan, Ping; Gooden, David M.; Simon, Sidney A.; Spasojevic, Ivan; Mook, Robert A.; Liddle, Rodger A.; Guilak, Farshid; Liedtke, Wolfgang B.
2016-01-01
TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV4 are available. Here we developed TRPV4-inhibitory molecules based on modifications of a known TRPV4-selective tool-compound, GSK205. We not only increased TRPV4-inhibitory potency, but surprisingly also generated two compounds that potently co-inhibit TRPA1, known to function as chemical sensor of noxious and irritant signaling. We demonstrate TRPV4 inhibition by these compounds in primary cells with known TRPV4 expression - articular chondrocytes and astrocytes. Importantly, our novel compounds attenuate pain behavior in a trigeminal irritant pain model that is known to rely on TRPV4 and TRPA1. Furthermore, our novel dual-channel blocker inhibited inflammation and pain-associated behavior in a model of acute pancreatitis – known to also rely on TRPV4 and TRPA1. Our results illustrate proof of a novel concept inherent in our prototype compounds of a drug that targets two functionally-related TRP channels, and thus can be used to combat isoforms of pain and inflammation in-vivo that involve more than one TRP channel. This approach could provide a novel paradigm for treating other relevant health conditions. PMID:27247148
Fernández, B; Alberti, I; Kitchen, I; Paz Viveros, M
1999-01-29
To address the existence of possible functional interactions between delta- and mu- receptors in relation to the affective component of pain, we have studied the effects of functional blockade of delta-receptors by a chronic treatment with naltrindole (1 mg/kg, 8 consecutive days) on antinociceptive responses to morphine (2 and 5 mg/kg) in the tail electric stimulation test, in adult male rats. The thresholds for the motor response (tail withdrawal), vocalization during stimulus and vocalization afterdischarge were assessed. These responses are considered to be integrated at spinal, medulla oblongata and diencephalon-rhinencephalon levels, respectively. The results show that the vocalization during stimulus and the vocalization afterdischarge were significantly affected by morphine in a dose dependent manner, the latter response being the most sensitive to the effects of the mu-opioid agonist. However, no significant effect was observed on motor responses at the doses used in this study. Chronic naltrindole treatment did not modify the inhibitory effect of morphine on the vocalization responses. Since the vocalization afterdischarge is related to the affective component of pain, the data suggest that the delta-opioid receptor is not involved in the supraspinal mechanisms at which these responses are organized and that there is not a mu-delta interaction in the modulation of the affective responses to noxious electrical stimulation.
Spinal cord stimulation modulates intraspinal colorectal visceroreceptive transmission in rats
Qin, C.; Lehew, R.T.; Khan, K.A.; Wienecke, G.M.; Foreman, R.D.
2007-01-01
Previous studies have shown that spinal cord stimulation (SCS) of upper lumbar segments decreases visceromotor responses to mechanical stimuli in a sensitized rat colon and reduces symptoms of irritable bowel syndrome in patients. SCS applied to the upper cervical spinal dorsal column reduces pain of chronic refractory angina. Further, chemical stimulation of C1-C2 propriospinal neurons in rats modulates the responses of lumbosacral spinal neurons to colorectal distension. The present study was designed to compare the effects of upper cervical and lumbar SCS on activity of lumbosacral neurons receiving noxious colorectal input. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms) at low intensity (90% of motor threshold) was applied to the dorsal column of upper cervical (C1-C2) or upper lumbar (L2-L3) ipsilateral spinal segments. Colorectal distension (CRD, 20, 40, 60 mmHg, 20 s) was produced by air inflation of a latex balloon. Results showed that SCS applied to L2-L3 and C1-C2 segments significantly reduced the excitatory responses to noxious CRD from 417.6±68.0 imp to 296.3±53.6 imp (P<0.05, n=24) and from 336.2±64.5 imp to 225.0±73.3 imp (P<0.05, n= 18), respectively. Effects of L2-L3 and C1-C2 SCS lasted 10.2±1.9 min and 8.0±0.9 min after offset of CRD. Effects of SCS were observed on spinal neurons with either high or low threshold excitatory responses to CRD. However, L2-L3 or C1-C2 SCS did not significantly affect inhibitory neuronal responses to CRD. C1-C2 SCS-induced effects were abolished by cutting the C7-C8 dorsal column but not by spinal transection at cervicomedullary junction. These data demonstrated that upper cervical or lumbar SCS modulated responses of lumbosacral spinal neurons to noxious mechanical stimulation of the colon, thereby, proved two loci for a potential therapeutic effect of SCS in patients with irritable bowel syndrome and other colonic disorders. PMID:17324482
Asymmetric pain processing in Parkinson's disease.
Granovsky, Y; Schlesinger, I; Fadel, S; Erikh, I; Sprecher, E; Yarnitsky, D
2013-10-01
Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.
Noxious Weeds in the US and Canada
projects  Comments Agricultural Research Service United States Department of Agriculture Noxious weeds in supported by the USDA Agricultural Research Service. Principal investigators: Dr. Kerri Skinner, University
Synthesis and antibacterial activity of aromatic and heteroaromatic amino alcohols.
de Almeida, Camila G; Reis, Samira G; de Almeida, Angelina M; Diniz, Claudio G; da Silva, Vânia L; Le Hyaric, Mireille
2011-11-01
Two series of aromatic and heteroaromatic amino alcohols were synthesized from alcohols and aldehydes and evaluated for their antibacterial activities. All the octylated compounds displayed a better activity against the four bacteria tested when evaluated by the agar diffusion method and were selected for the evaluation of minimal inhibitory concentration. The best results were obtained for p-octyloxybenzyl derivatives against Staphylococcus epidermidis (minimal inhibitory concentrations = 32 μm). © 2011 John Wiley & Sons A/S.
Outer-membrane translocation of bulky small molecules by passive diffusion
van den Berg, Bert; Prathyusha Bhamidimarri, Satya; Dahyabhai Prajapati, Jigneshkumar; Kleinekathöfer, Ulrich; Winterhalter, Mathias
2015-01-01
The outer membrane (OM) of gram-negative bacteria forms a protective layer around the cell that serves as a permeability barrier to prevent unrestricted access of noxious substances. The permeability barrier of the OM results partly from the limited pore diameters of OM diffusion channels. As a consequence, there is an “OM size-exclusion limit,” and the uptake of bulky molecules with molecular masses of more than ∼600 Da is thought to be mediated by TonB-dependent, active transporters. Intriguingly, the OM protein CymA from Klebsiella oxytoca does not depend on TonB but nevertheless mediates efficient OM passage of cyclodextrins with diameters of up to ∼15 Å. Here we show, by using X-ray crystallography, molecular dynamics simulations, and single-channel electrophysiology, that CymA forms a monomeric 14-stranded β-barrel with a large pore that is occluded on the periplasmic side by the N-terminal 15 residues of the protein. Representing a previously unidentified paradigm in OM transport, CymA mediates the passive diffusion of bulky molecules via an elegant transport mechanism in which a mobile element formed by the N terminus acts as a ligand-expelled gate to preserve the permeability barrier of the OM. PMID:26015567
The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.
Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo
2006-04-01
Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.
Integrating impairments in reaction time and executive function using a diffusion model framework.
Karalunas, Sarah L; Huang-Pollock, Cynthia L
2013-07-01
Using Ratcliff's diffusion model and ex-Gaussian decomposition, we directly evaluate the role individual differences in reaction time (RT) distribution components play in the prediction of inhibitory control and working memory (WM) capacity in children with and without ADHD. Children with (n = 91, [Formula: see text] age = 10.2 years, 67 % male) and without ADHD (n = 62, [Formula: see text] age = 10.6 years, 46 % male) completed four tasks of WM and a stop signal reaction time (SSRT) task. Children with ADHD had smaller WM capacities and less efficient inhibitory control. Diffusion model analyses revealed that children with ADHD had slower drift rates (v) and faster non-decision times (Ter), but there were no group differences in boundary separations (a). Similarly, using an ex-Gaussian approach, children with ADHD had larger τ values than non-ADHD controls, but did not differ in μ or σ distribution components. Drift rate mediated the association between ADHD status and performance on both inhibitory control and WM capacity. τ also mediated the ADHD-executive function impairment associations; however, models were a poorer fit to the data. Impaired performance on RT and executive functioning tasks has long been associated with childhood ADHD. Both are believed to be important cognitive mechanisms to the disorder. We demonstrate here that drift rate, or the speed at which information accumulates towards a decision, is able to explain both.
Belasen, Abigail; Youn, Youngwon; Gee, Lucy; Prusik, Julia; Lai, Brant; Ramirez-Zamora, Adolfo; Rizvi, Khizer; Yeung, Philip; Shin, Damian S; Argoff, Charles; Pilitsis, Julie G
2016-10-01
Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits. © 2016 International Neuromodulation Society.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hermeston, Mark W.
Franklin County noxious weed management along BPA rights-of-ways, transmission structures, roads, and switches listed in Attachment 1. Attachment 1 identifies the ROW, ROW width, and ROW length of the proposed action. Includes all BPA 115kV, 230kV, and 500 kV ROWs in Franklin County, Washington. BPA proposes to clear noxious and/or unwanted low-growing vegetation in all BPA ROWs in Franklin County, Washington. In a cooperative effort, BPA, through landowners and the Franklin County Weed Control Board, plan to eradicate noxious plants and other unwanted, low-growing vegetation within the ROW width including all structures and access roads. BPA’s overall goal is tomore » eradicate all noxious and unwanted vegetation through chemical treatment and reseeding. Selective and nonselective chemical treatment using spot, local and broadcast methods. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hermeston, Mark W.
Benton County noxious weed management along BPA rights-of-ways, transmission structures, roads, and switches listed in Attachment 1. Attachment 1 identifies the ROW, ROW width, and ROW length of the proposed action. Includes all BPA 115kV, 230kV, 345kV and 500 kV ROWs in Benton County, Washington. BPA proposes to clear noxious and/or unwanted low-growing vegetation in all BPA ROWs in Benton County, Washington. In a cooperative effort, BPA, through landowners and the Benton County Weed Control Board, plan to eradicate noxious plants and other unwanted, low-growing vegetation within the ROW width including all structures and access roads. BPA’s overall goal ismore » to eradicate all noxious and unwanted vegetation through chemical treatment and reseeding. Selective and nonselective chemical treatment using spot, local and broadcast methods. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002.« less
Brain mediators of the effects of noxious heat on pain
Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.
2014-01-01
Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572
Nir, Rony-Reuven; Sinai, Alon; Moont, Ruth; Harari, Eyal; Yarnitsky, David
2012-03-01
Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-24
... pests, noxious weeds, and biological control agents, which may be used to control plant pests or noxious... detect, in collaboration with the National Plant Diagnostic Network and the U.S. Department of...
7 CFR 201.52 - Noxious-weed seeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... the bulk examined for noxious-weed seeds need not be noted: 1/2-gram purity working sample, 16 or more seeds; 1-gram purity working sample, 23 or more seeds; 2-gram purity working sample or larger, 30 or...
Tsuruoka, Masayoshi; Maeda, Masako; Hayashi, Bunsho; Liu, Limin; Inoue, Tomio
2008-01-01
The onset of the antinociceptive effect with loxoprofen sodium (LOX), a non-steroidal anti-inflammatory drug, was examined electrophysiologically during carrageenan-induced hindpaw inflammation in the rat. Extracellular recordings were made from either wide dynamic range (WDR) or high threshold (HT) neurons in the dorsal horn. Recordings from the same neuron were continued for at least 3 h after the injection of carrageenan. Three hours after the induction of inflammation, either a fresh solution of LOX (1 mg/kg) or distilled water was directly administered into the stomach through PE 50 tubing. LOX significantly reduced inflammation-increased background activity and noxious heat-evoked responses in both HT and WDR neurons, whereas distilled water did not produce any change. Asignificant difference in the onset of the inhibitory effect of LOX was observed between HT and WDR neurons. The results show that WDR neurons precede HT neurons regarding inhibition of nociceptive processing in the dorsal horn after administration of LOX.
NASA Astrophysics Data System (ADS)
Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Sleigh, J. W.
2013-04-01
Electrical recordings of brain activity during the transition from wake to anesthetic coma show temporal and spectral alterations that are correlated with gross changes in the underlying brain state. Entry into anesthetic unconsciousness is signposted by the emergence of large, slow oscillations of electrical activity (≲1Hz) similar to the slow waves observed in natural sleep. Here we present a two-dimensional mean-field model of the cortex in which slow spatiotemporal oscillations arise spontaneously through a Turing (spatial) symmetry-breaking bifurcation that is modulated by a Hopf (temporal) instability. In our model, populations of neurons are densely interlinked by chemical synapses, and by interneuronal gap junctions represented as an inhibitory diffusive coupling. To demonstrate cortical behavior over a wide range of distinct brain states, we explore model dynamics in the vicinity of a general-anesthetic-induced transition from “wake” to “coma.” In this region, the system is poised at a codimension-2 point where competing Turing and Hopf instabilities coexist. We model anesthesia as a moderate reduction in inhibitory diffusion, paired with an increase in inhibitory postsynaptic response, producing a coma state that is characterized by emergent low-frequency oscillations whose dynamics is chaotic in time and space. The effect of long-range axonal white-matter connectivity is probed with the inclusion of a single idealized point-to-point connection. We find that the additional excitation from the long-range connection can provoke seizurelike bursts of cortical activity when inhibitory diffusion is weak, but has little impact on an active cortex. Our proposed dynamic mechanism for the origin of anesthetic slow waves complements—and contrasts with—conventional explanations that require cyclic modulation of ion-channel conductances. We postulate that a similar bifurcation mechanism might underpin the slow waves of natural sleep and comment on the possible consequences of chaotic dynamics for memory processing and learning.
Hopes for the Future of Pain Control.
Bannister, Kirsty; Kucharczyk, Mateusz; Dickenson, Anthony H
2017-12-01
Here we aim to present an accessible review of the pharmacological targets for pain management, and succinctly discuss the newest trends in pain therapy. A key task for current pain pharmacotherapy is the identification of receptors and channels orchestrating nociception. Notwithstanding peripheral alterations in the receptors and channels following pathophysiological events, the modulatory mechanisms in the central nervous system are also fundamental to the regulation of pain perception. Bridging preclinical and clinical studies of peripheral and central components of pain modulation, we present the different types of pain and relate these to pharmacological interventions. We firstly highlight the roles of several peripheral nociceptors, such as NGF, CGRP, sodium channels, and TRP-family channels that may become novel targets for therapies. In the central nervous system, the roles of calcium channels and gabapentinoids as well as NMDA receptors in generating excitability are covered including ideas on central sensitization. We then turn to central modulatory systems and discuss opioids and monoamines. We aim to explain the importance of central sensitization and the dialogue of the spinal circuits with the brain descending modulatory controls before discussing a mechanism-based effectiveness of antidepressants in pain therapy and their potential to modulate the descending controls. Emphasizing the roles of conditioned pain modulation and its animal's equivalent, diffuse noxious inhibitory controls, we discuss these unique descending modulations as a potential tool for understanding mechanisms in patients suffering from pain. Mechanism-based therapy is the key to picking the correct treatments and recent clinical studies using sensory symptoms of patients as surrogates for underlying mechanisms can be used to subgroup patients and reveal actions of drugs that may be lost when studying heterogenous groups of patients. Key advances in the understanding of basic pain principles will impact our thinking about therapy targets. The complexity of pain syndromes will require tailored pharmacological drugs, often in combination or through drugs with more than one action, and often psychotherapy, to fully control pain.
33 CFR 151.30 - Applicability.
Code of Federal Regulations, 2014 CFR
2014-07-01
....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...
33 CFR 151.30 - Applicability.
Code of Federal Regulations, 2012 CFR
2012-07-01
....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...
33 CFR 151.30 - Applicability.
Code of Federal Regulations, 2011 CFR
2011-07-01
....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...
33 CFR 151.30 - Applicability.
Code of Federal Regulations, 2010 CFR
2010-07-01
....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...
Ünlü, Gülhan; Nielsen, Barbara; Ionita, Claudia
2015-12-01
One hundred and eight strains of lactic acid bacteria (LAB) were screened for bacteriocin production by the modified deferred antagonism and agar well diffusion methods. When the modified deferred antagonism method was employed, 82 LAB strains showed inhibitory action against Listeria monocytogenes v7 ½a, whereas 26 LAB strains expressed no inhibition. Only 12 LAB strains exhibited inhibitory activity when the agar well diffusion method was used, 11 of which had been previously recognized as bacteriocin production positive (Bac(+)). Lactobacillus viridescens NRRL B-1951 was determined, for the first time, to produce an inhibitory compound with a proteinaceous nature. The inhibitory activity was observed in the presence of lipase, α-chymotrypsin, and trypsin, but no inhibition zone could be detected in the presence of proteinase K, indicating the proteinaceous nature of the inhibitory compound. The inhibitory compound was active against Lact. sake ATCC 15521 and Lact. plantarum NCDO 995. Bacteriocin production by the Bac(+) LAB strains was assessed in Lactobacillus MRS Broth as well as in dairy-based media such as nonfat milk, demineralized whey powder, and cheddar cheese whey supplemented with complex nutrient sources that are rich in nitrogen. Lact. sake ATCC 15521 and L. monocytogenes CWD 1002, CWD 1092, CWD 1157, CWD 1198, and v7 ½a were used as indicators. The inhibitory activities of the bacteriocins varied depending on the indicator strains and the growth media used. The LAB indicator strains were found to be more sensitive to inhibition by bacteriocins when compared to the listerial indicator strains. Among the listerial indicators, L. monocytogenes CWD 1002 and CWD 1198 were the most sensitive strains to the bacteriocins investigated in this study. Media composition had a significant influence on bacteriocin production and activity. When compared to demineralized whey powder medium and cheddar cheese whey medium supplemented with whey protein concentrate, cheddar cheese whey medium supplemented with complex nutrient sources such as yeast extract, polypeptone, proteose peptone nr. 3, or soytone appeared to be more supportive of bacteriocin production.
33 CFR 151.15 - Reporting requirements.
Code of Federal Regulations, 2011 CFR
2011-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...
33 CFR 151.15 - Reporting requirements.
Code of Federal Regulations, 2014 CFR
2014-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...
33 CFR 151.15 - Reporting requirements.
Code of Federal Regulations, 2012 CFR
2012-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-03
... data on plant pests, noxious weeds, and biological control agents, which may be used to control plant..., eradicate, suppress, control, prevent, or retard the spread of plant pests and noxious weeds that are new to...
Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah
2014-11-01
More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1-12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n=12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n=39), where a subset (n=11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P=0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P=0.30). Experimental tactile (P=0.012) and noxious (P=0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah
2014-01-01
More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1–12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n = 12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n = 39), where a subset (n = 11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P = 0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P = 0.30). Experimental tactile (P = 0.012) and noxious (P = 0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. PMID:25218826
Granovsky, Yelena; Shor, Merav; Shifrin, Alla; Sprecher, Elliot; Yarnitsky, David; Bar-Shalita, Tami
2018-03-27
Migraineurs with aura (MWA) express higher interictal response to non-noxious and noxious experimental sensory stimuli compared with migraineurs without aura (MWoA), but whether these differences also prevail in response to everyday non-noxious stimuli is not yet explored. This is a cross-sectional study testing 53 female migraineurs (30 MWA; 23 MWoA) who underwent a wide battery of noxious psychophysical testing at a pain-free phase, and completed a Sensory Responsiveness Questionnaire and pain-related psychological questionnaires. The MWA group showed higher questionnaire-based sensory over-responsiveness (P = .030), higher magnitude of pain temporal summation (P = .031) as well as higher monthly attack frequency (P = .027) compared with the MWoA group. Overall, 45% of migraineurs described abnormal sensory (hyper- or hypo-) responsiveness; its incidence was higher among MWA (19 of 30, 63%) versus MWoA (6 of 23, 27%, P = .012), with an odds ratio of 3.58 for MWA. Sensory responsiveness scores were positively correlated with attack frequency (r = .361, P = .008) and temporal summation magnitude (r = .390, P = .004), both regardless of migraine type. MWA express higher everyday sensory responsiveness than MWoA, in line with higher response to experimental noxious stimuli. Abnormal scores of sensory responsiveness characterize people with sensory modulation dysfunction, suggesting possible underlying mechanisms overlap, and possibly high incidence of both clinical entities. This article presents findings distinguishing MWA, showing enhanced pain amplification, monthly attack frequency, and over-responsiveness to everyday sensations, compared with MWoA. Further, migraine is characterized by a high incidence of abnormal responsiveness to everyday sensation, specifically sensory over-responsiveness, that was also found related to pain. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.
Chatelle, Camille; Hauger, Solveig L; Martial, Charlotte; Becker, Frank; Eifert, Bernd; Boering, Dana; Giacino, Joseph T; Laureys, Steven; Løvstad, Marianne; Maurer-Karattup, Petra
2018-04-10
Investigate the relationship between consciousness and nociceptive responsiveness (i.e., Nociception Coma Scale-Revised [NCS-R]), examine the suitability of the NCS-R for assessing nociception in participants with disorders of consciousness (DoC) and replicate previous findings on psychometric properties of the scale. We prospectively assessed consciousness with the Coma Recovery Scale-Revised (CRS-R). Responses during baseline, non-noxious and noxious stimulations were scored with the NCS-R, CRS-R oromotor and motor subscales. Specialized DoC program and university hospitals. Eighty-five participants diagnosed with DoCs. Correlation between CRS-R total scores and CRS-R and NCS-R (sub)scores to noxious stimulation, proportion of grimace and/or cry in participants with minimally consciousness (MCS) and unresponsive wakefulness syndrome (UWS) during non-noxious and noxious conditions. Not applicable RESULTS: CRS-R total scores correlated with NCS-R total scores and subscores. CRS-R motor subscale correlated with NCS-R total scores and motor subscale and CRS-R oromotor subscale correlated with NCS-R total scores, as well as verbal and facial expression. There was a difference between participants with UWS and MCS in the proportion of grimace and/or crying during the noxious condition. We replicated previous findings on psychometric properties of the scale, but found a different score as the best threshold for nociception. We report a strong relationship between responsiveness to nociception and the level of consciousness. The NCS-R seems to offer a valuable tool to assess nociception in an efficient manner, but additional studies are needed to allow recommendations for clinical assessment of subjective pain experience. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Brain mediators of the effects of noxious heat on pain.
Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D
2014-08-01
Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada
2018-03-01
In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.
Tékus, Valéria; Horváth, Ádám; Hajna, Zsófia; Borbély, Éva; Bölcskei, Kata; Boros, Melinda; Pintér, Erika; Helyes, Zsuzsanna; Pethő, Gábor; Szolcsányi, János
2016-06-01
To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice. In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold. It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains. Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics. Copyright © 2016 Elsevier Inc. All rights reserved.
Triggering Descending Pain Inhibition by Observing Ourselves or a Loved-One in Pain.
Gougeon, Véronique; Gaumond, Isabelle; Goffaux, Philippe; Potvin, Stéphane; Marchand, Serge
2016-03-01
Recent studies demonstrate that empathy-evoked brain responses include the activation of brainstem structures responsible for triggering descending pain inhibition. Unfortunately, direct evidence linking empathy for pain and descending inhibitory controls (conditioned pain modulation) is lacking. This study, therefore, aimed to determine if the observation of ourselves or a loved-one in pain could activate descending pain inhibition without exposure to a noxious stimulation; which is otherwise required. Descending pain inhibition was triggered by immersing the right arm of participants (15 heterosexual couples; mean age±SE: 28.89±2.14) in a bath of cold water. The effects of empathy on descending pain inhibition were observed by immersing the right arm of participants in a bath of lukewarm water while having them watch a video of either themselves or their spouse during a previous nociceptive immersion. Immersion of the arm in a bath of lukewarm water without empathic (video) observation was also included as a control condition. A strong inhibitory response activated by the mere observation of the video of themselves or their spouse in pain without a nociceptive conditioning stimulus. Associative statistics also showed that strong pain catastrophizing responses while watching the video resulted in stronger pain inhibition. Moreover, high levels of empathy were associated with stronger pain inhibition, but only for women. This study showed that observing someone in pain triggers descending pain inhibition. Results also demonstrate how empathy and gender are affecting pain modulation mechanisms.
7 CFR 301.1 - Purpose and scope.
Code of Federal Regulations, 2011 CFR
2011-01-01
... articles, means of conveyance, plants, plant products, biological control organisms, plant pests, or... biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...
7 CFR 301.1 - Purpose and scope.
Code of Federal Regulations, 2010 CFR
2010-01-01
... articles, means of conveyance, plants, plant products, biological control organisms, plant pests, or... biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...
33 CFR 151.39 - Operating requirements: Category D NLS.
Code of Federal Regulations, 2014 CFR
2014-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.39 - Operating requirements: Category D NLS.
Code of Federal Regulations, 2013 CFR
2013-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.43 - Control of discharge of NLS residues.
Code of Federal Regulations, 2012 CFR
2012-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.43 - Control of discharge of NLS residues.
Code of Federal Regulations, 2014 CFR
2014-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.43 - Control of discharge of NLS residues.
Code of Federal Regulations, 2013 CFR
2013-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.43 - Control of discharge of NLS residues.
Code of Federal Regulations, 2011 CFR
2011-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.39 - Operating requirements: Category D NLS.
Code of Federal Regulations, 2011 CFR
2011-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.39 - Operating requirements: Category D NLS.
Code of Federal Regulations, 2012 CFR
2012-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.39 - Operating requirements: Category D NLS.
Code of Federal Regulations, 2010 CFR
2010-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.43 - Control of discharge of NLS residues.
Code of Federal Regulations, 2010 CFR
2010-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
A leptin-regulated circuit controls glucose mobilization during noxious stimuli.
Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G
2017-08-01
Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.
[Occupational digestive diseases in chemical industry workers of West Siberia].
Pomytkina, T E; Pershin, A N
2010-01-01
The high incidence of chronic digestive diseases is recorded in chemical industry workers exposed to the isolated action of noxious substances. The aim of the investigation was to make a hygienic assessment of the risk for occupational digestive diseases in chemical industry workers exposed to a combination of noxious drugs. The working conditions and the prevalence of digestive diseases were studied in 4120 workers engaged in chemical and auxiliary processes. Under the isolated action of noxious substances, the workers had an average of 35% increase in the incidence of digestive diseases than unexposed ones (p < 0.05). Under the combined action of hazardous substances, the incidence of digestive diseases was 1.7-fold greater (p < 0.05) than in the unexposed subjects and 1.2-fold greater in those under isolated action. The odd ratio and relative risk for digestive diseases in the workers exposed to a combination of noxious substances were 4.0-11.1 and 3.5-10.7 times higher, respectively (p < 0.05) than in the unexposed subjects.
Morrow, T J; Casey, K L
1983-01-01
The responses of 302 neurons in the medial medullary reticular formation (MRF) to a variety of noxious and innocuous somatic stimuli were studied in anesthetized and awake rats. In addition, the effects of analgesic electrical stimulation in the mesencephalon (MES) on unit responses were examined. Tail shock was the most effective stimulus, exciting more than 80% of all units recorded. This stimulus was considered separately during data analysis, since it could not be classified as noxious or innocuous. Noxious somatic stimuli (including pinch, firm pressure, pin prick, and radiant heating of the tail above 45 degrees C were especially effective in eliciting discharge in a significant fraction of all cells in both awake (123/205) and anesthetized (45/97) animals. Nociceptive neurons could be classified as nociceptive specific (NS) or wide dynamic range (WDR) depending on their responses to all somatic stimuli tested. Nociceptive neurons showed no preferential anatomical distribution. Most neurons, including those responsive to noxious inputs, exhibited large, often bilateral receptive fields which frequently covered the tail, one or more limbs, and extensive areas of the body or head. Electrical stimulation within or adjacent to the mesencephalic periaqueductal gray matter depressed the spontaneous and evoked discharge of MRF neurons in both acute and chronic preparations. This inhibition showed a significant preference (p less than 0.001, chi-square statistic) for units that were excited by somatic and especially noxious stimuli. No units were facilitated by MES stimulation. In the awake rat, unit suppression closely followed the time course and level of MES-induced analgesia. Excitability data from the acute experiments suggest that this response inhibition may be the result of a direct action on MRF neurons. Anesthesia severely depressed the spontaneous discharge of MRF neurons as well as the activity evoked by innocuous somatic stimulation. Our data suggest that analgesia produced by MES stimulation is at least in part due to the depression of MRF unit activity, and support the hypothesis that MRF neurons play a critical role in the mediation of behavioral responses to noxious stimuli.
Laing, Robyn J; Dhaka, Ajay
2015-01-01
The ability of the body to perceive noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors. The molecular receptors of noxious mechanical, temperature or chemical stimuli are expressed in these neurons and have drawn considerable attention as possible targets for analgesic development to improve treatment for the millions who suffer from chronic pain conditions. A number of thermoTRPs, a subset of the transient receptor potential family of ion channels, are activated by a wide range on noxious stimuli. In this review, we review the function of these channels and examine the evidence that thermoTRPs play a vital role in acute, inflammatory and neuropathic nociception. PMID:25608689
33 CFR 151.32 - Special areas for the purpose of Annex II.
Code of Federal Regulations, 2013 CFR
2013-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
7 CFR 201.16 - Noxious-weed seeds.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...
7 CFR 201.52 - Noxious-weed seeds.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...
7 CFR 201.52 - Noxious-weed seeds.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...
7 CFR 201.52 - Noxious-weed seeds.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...
7 CFR 201.16 - Noxious-weed seeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...
7 CFR 201.16 - Noxious-weed seeds.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...
7 CFR 201.16 - Noxious-weed seeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...
7 CFR 201.52 - Noxious-weed seeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...
33 CFR 151.32 - Special areas for the purpose of Annex II.
Code of Federal Regulations, 2012 CFR
2012-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.32 - Special areas for the purpose of Annex II.
Code of Federal Regulations, 2014 CFR
2014-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
33 CFR 151.32 - Special areas for the purpose of Annex II.
Code of Federal Regulations, 2011 CFR
2011-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
75 FR 23151 - Noxious Weeds; Old World Climbing Fern and Maidenhair Creeper
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-03
.... APHIS-2008-0097] Noxious Weeds; Old World Climbing Fern and Maidenhair Creeper AGENCY: Animal and Plant... adding Old World climbing fern (Lygodium microphyllum (Cavanilles) R. Brown) and maidenhair creeper... amended the regulations by adding Old World climbing fern (Lygodium microphyllum (Cavanilles) R. Brown...
33 CFR 151.32 - Special areas for the purpose of Annex II.
Code of Federal Regulations, 2010 CFR
2010-07-01
... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...
7 CFR 361.6 - Noxious weed seeds.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 5 2010-01-01 2010-01-01 false Noxious weed seeds. 361.6 Section 361.6 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE... measured from the base of the rachilla. (3) Seeds of legumes (Fabaceae) with the seed coats entirely...
7 CFR 201.65 - Noxious-weed seeds in interstate commerce.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.65 - Noxious weed seeds in interstate commerce.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.65 - Noxious-weed seeds in interstate commerce.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.65 - Noxious-weed seeds in interstate commerce.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.65 - Noxious weed seeds in interstate commerce.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
Code of Federal Regulations, 2011 CFR
2011-01-01
... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant... prevent the introduction or dissemination of a biological control organism, plant pest, or noxious weed...) The provisions in this part apply whether the controls over arrival, temporary stay, unloading...
ERIC Educational Resources Information Center
Mason, Maria J.; Watkins, Amanda J.; Wakabayashi, Jordann; Buechler, Jennifer; Pepino, Christine; Brown, Michelle; Wright, William G.
2014-01-01
Previous research on sensitization in "Aplysia" was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce…
43 CFR 4120.5-2 - Cooperation with Tribal, state, county, and Federal agencies.
Code of Federal Regulations, 2011 CFR
2011-10-01
... laws and regulations relating to livestock, livestock diseases, sanitation, and noxious weeds... 1971 (16 U.S.C. 1331 et seq.); (b) County or other local weed control districts in analyzing noxious weed problems and developing control programs for areas of the public lands and other lands...
7 CFR 623.13 - Wetlands reserve plan of operations.
Code of Federal Regulations, 2012 CFR
2012-01-01
... program, including, but not limited to: (i) measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...
7 CFR 623.13 - Wetlands reserve plan of operations.
Code of Federal Regulations, 2013 CFR
2013-01-01
... program, including, but not limited to: (i) Measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) Measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...
7 CFR 623.13 - Wetlands reserve plan of operations.
Code of Federal Regulations, 2014 CFR
2014-01-01
... program, including, but not limited to: (i) measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...
33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.
Code of Federal Regulations, 2012 CFR
2012-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.
Code of Federal Regulations, 2011 CFR
2011-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.
Code of Federal Regulations, 2014 CFR
2014-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.
Code of Federal Regulations, 2012 CFR
2012-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.
Code of Federal Regulations, 2014 CFR
2014-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.
Code of Federal Regulations, 2013 CFR
2013-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.
Code of Federal Regulations, 2011 CFR
2011-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.
Code of Federal Regulations, 2010 CFR
2010-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.
Code of Federal Regulations, 2010 CFR
2010-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...
Kent E. Houston; Walter J. Hartung; Carol J. Hartung
2001-01-01
This field guide was designed for people with minimal botanical training. It is an identification aid to plant species that have ecological indicator value, are on sensitive species lists, or are considered noxious weeds. It contains illustrations and simplified taxonomic descriptions.
Módenes, Aparecido N; Espinoza-Quiñones, Fernando R; Colombo, Andréia; Geraldi, Claudinéia L; Trigueros, Daniela E G
2015-05-01
The uptake of Cd(2+) and Pb(2+) ions by a soybean hull (SH) biosorbent in single and binary systems has been investigated. Sorption tests regarding SH in natura and chemically treated were carried out testing a suitable value range of solution pH, sorption temperature and shaking velocity. Sorption capacity is improved at pH 4, 30 °C temperature and 100 rpm. When a strong base is applied, a related-to-untreated SH increasing of 20% in the sorption capacity of Pb(2+) ions was observed, but with poor results for Cd(2+) uptake. Additionally, a relatively strong decreasing in both sorption capacities of Pb(2+) and Cd(2+) ions was evidenced for all acidic treatments. Regarding untreated SH, kinetic sorption data of both metals were well-interpreted by a pseudo second-order model and a rate-limiting step on the basis of an intra-particle diffusion model was suggested to occur. An inhibitory effect of Pb(2+) diffusion over Cd(2+) one was observed, limiting to reach the obtained maximum sorption capacity in single system. Maximum adsorption capacities of 0.49 and 0.67mequivg(-1) for Cd(2+) and Pb(2+), respectively, were predicted by the Langmuir isotherm model that reproduced well the equilibrium sorption data for single systems. The inhibitory effect of one metal over the other one was verified in equilibrium sorption data for binary systems interpreted on the basis of a modified extended Langmuir isotherm model, predicting changes in metal affinity onto the SH surface. Finally, SH is an alternative biosorbent with a great potential for the wastewater treatment containing cadmium and lead ions. Copyright © 2015 Elsevier Ltd. All rights reserved.
The Effects of Noxious Subliminal Suggestion upon Smoking Attitudes and Behavior.
ERIC Educational Resources Information Center
Dutto, Franklin N.; Galli, Nicholas
The efforts of smoking cessation programs have met with various degrees of success and fresh approaches to the problem are needed. An innovative technique that interrupts the psychogenic drives of smokers was employed to determine the effect of noxious subliminal suggestion on smoking attitudes and behavior. Adult smokers (N=60) were shown…
33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.35 Certificates needed to carry Category D NLS and Category D Oil-like... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID...
33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.33 Certificates needed to carry Category C Oil-like NLS. (a) A U.S. oceangoing ship may not... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL...
7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-12
... provide a safe environment for miners. Methane is liberated from the strata, and noxious gases and dusts from blasting and other mining activities may be present. The explosive and noxious gases and dusts... collection of information, including the validity of the methodology and assumptions used; Enhance the...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-21
... to use certified noxious-weed-free forage and straw. Restoration, rehabilitation, and stabilization... domestic ungulates, weaken rehabilitation and landscape restoration efforts, increase soil erosion and... consistent with and supportive of the statewide Conservation Plan for the Greater Sage- Grouse in Idaho...
33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.
Code of Federal Regulations, 2014 CFR
2014-07-01
... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...
Code of Federal Regulations, 2014 CFR
2014-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...
33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.
Code of Federal Regulations, 2012 CFR
2012-07-01
... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...
33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.
Code of Federal Regulations, 2011 CFR
2011-07-01
... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...
Code of Federal Regulations, 2012 CFR
2012-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...
Code of Federal Regulations, 2011 CFR
2011-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...
Code of Federal Regulations, 2012 CFR
2012-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...
Code of Federal Regulations, 2014 CFR
2014-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...
Code of Federal Regulations, 2012 CFR
2012-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...
Code of Federal Regulations, 2011 CFR
2011-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...
Code of Federal Regulations, 2014 CFR
2014-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...
Code of Federal Regulations, 2011 CFR
2011-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...
Code of Federal Regulations, 2013 CFR
2013-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...
Code of Federal Regulations, 2010 CFR
2010-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...
Code of Federal Regulations, 2010 CFR
2010-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...
Code of Federal Regulations, 2010 CFR
2010-07-01
... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...
33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.
Code of Federal Regulations, 2010 CFR
2010-07-01
... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...
2005-01-01
native groundcover vegetation. Specifically, natalgrass (Rhynchelytrum repens) and Cogan grass ( Imperata cylindrica ), both invasive exotics, have the...stability creates an environment conducive for noxious weeds. If noxious weeds establish, the EA acknowledges that they can be chemically treated
Rogers, R W; Mewborn, C R
1976-07-01
Three factorial experiments examined the persuasive effects of the noxiousness of threatened event, its probability of occurrence, and the efficacy of recommended protective measures. A total of 176 students participated in separate studies on the topics of cigarette smoking, driving safety, and venereal disease. The results disclosed that increments in the efficacy variable increased intentions to adopt the efficacy variable increased intentions to adopt the recommended practices. Interaction effects revealed that when the preventive practices were effective, increments in the noxiousness and probability variables facilitated attitude change; however, when the coping responses were the preventive practices were effective, increments in the noxiousness and probability either had no effect or a deleterious effect, respectively. These interaction effects were discussed in terms of a defensive avoidance hypothesis, the crucial component of which was an inability to ward off the danger. Furthermore, the effect of the emotion of fear upon intentions was found to be mediated by the cognitive appraisal of severity of the threat. Finally, similarities with and extensions of previous studies were reviewed.
Adasme, Tatiana; Paula-Lima, Andrea; Hidalgo, Cecilia
2015-02-27
Ryanodine is a cell permeant plant alkaloid that binds selectively and with high affinity to ryanodine receptor (RyR) Ca(2+) release channels. Sub-micromolar ryanodine concentrations activate RyR channels while micromolar concentrations are inhibitory. Several reports indicate that neuronal synaptic plasticity, learning and memory require RyR-mediated Ca(2+)-release, which is essential for muscle contraction. The use of micromolar (inhibitory) ryanodine represents a common strategy to suppress RyR activity in neuronal cells: however, micromolar ryanodine promotes RyR-mediated Ca(2+) release and endoplasmic reticulum Ca(2+) depletion in muscle cells. Information is lacking in this regard in neuronal cells; hence, we examined here if addition of inhibitory ryanodine elicited Ca(2+) release in primary hippocampal neurons, and if prolonged incubation of primary hippocampal cultures with inhibitory ryanodine affected neuronal ER calcium content. Our results indicate that inhibitory ryanodine does not cause Ca(2+) release from the ER in primary hippocampal neurons, even though ryanodine diffusion should produce initially low intracellular concentrations, within the RyR activation range. Moreover, neurons treated for 1 h with inhibitory ryanodine had comparable Ca(2+) levels as control neurons. These combined findings imply that prolonged incubation with inhibitory ryanodine, which effectively abolishes RyR-mediated Ca(2+) release, preserves ER Ca(2+) levels and thus constitutes a sound strategy to suppress neuronal RyR function. Copyright © 2015 Elsevier Inc. All rights reserved.
Lichtner, Gregor; Auksztulewicz, Ryszard; Kirilina, Evgeniya; Velten, Helena; Mavrodis, Dionysios; Scheel, Michael; Blankenburg, Felix; von Dincklage, Falk
2018-05-15
Drug-induced unconsciousness is an essential component of general anesthesia, commonly attributed to attenuation of higher-order processing of external stimuli and a resulting loss of information integration capabilities of the brain. In this study, we investigated how the hypnotic drug propofol at doses comparable to those in clinical practice influences the processing of somatosensory stimuli in the spinal cord and in primary and higher-order cortices. Using nociceptive reflexes, somatosensory evoked potentials and functional magnet resonance imaging (fMRI), we found that propofol abolishes the processing of innocuous and moderate noxious stimuli at low to medium concentration levels, but that intense noxious stimuli evoked spinal and cerebral responses even during deep propofol anesthesia that caused profound electroencephalogram (EEG) burst suppression. While nociceptive reflexes and somatosensory potentials were affected only in a minor way by further increasing doses of propofol after the loss of consciousness, fMRI showed that increasing propofol concentration abolished processing of intense noxious stimuli in the insula and secondary somatosensory cortex and vastly increased processing in the frontal cortex. As the fMRI functional connectivity showed congruent changes with increasing doses of propofol - namely the temporal brain areas decreasing their connectivity with the bilateral pre-/postcentral gyri and the supplementary motor area, while connectivity of the latter with frontal areas is increased - we conclude that the changes in processing of noxious stimuli during propofol anesthesia might be related to changes in functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.
Reduced local field potential power in the medial prefrontal cortex by noxious stimuli.
Li, Ai-Ling; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo
2016-10-01
Nociceptive signals produced by noxious stimuli at the periphery reach the brain through ascending pathways. These signals are processed by various brain areas and lead to activity changes in those areas. The medial prefrontal cortex (mPFC) is involved in higher cognitive functions and emotional processing. It receives projections from brain areas involved in nociception. In this study, we investigated how nociceptive input from the periphery changes the local field potential (LFP) activity in the mPFC. Three different types of noxious stimuli were applied to the hind paw contralateral to the LFP recording site. They were transcutaneous electrical stimulations, mechanical stimuli and a chemical stimulus (formalin injection). High intensity transcutaneous stimulations (10V to 50V) and noxious mechanical stimulus (pinch) significantly reduced the LFP power during the stimulating period (p<0.05), but not the low intensity subcutaneous stimulations (0.1V to 5V) and other innocuous mechanical stimuli (brush and pressure). More frequency bands were inhibited with increased intensity of transcutaneous electrical stimulation, and almost all frequency bands were inhibited by stimulations at or higher than 30v. Pinch significantly reduced the power for beta band and formalin injection significantly reduced the power of alpha and beta band. Our data demonstrated the noxious stimuli-induced reduction of LFP power in the mPFC, which indicates the active processing of nociceptive information by the mPFC. Copyright © 2016 Elsevier Inc. All rights reserved.
White, Corey N.; Congdon, Eliza; Mumford, Jeanette A.; Karlsgodt, Katherine H.; Sabb, Fred W.; Freimer, Nelson B.; London, Edythe D.; Cannon, Tyrone D.; Bilder, Robert M.; Poldrack, Russell A.
2014-01-01
The Stop-signal task (SST), in which participants must inhibit prepotent responses, has been used to identify neural systems that vary with individual differences in inhibitory control. To explore how these differences relate to other aspects of decision-making, a drift diffusion model of simple decisions was fitted to SST data from Go trials to extract measures of caution, motor execution time, and stimulus processing speed for each of 123 participants. These values were used to probe fMRI data to explore individual differences in neural activation. Faster processing of the Go stimulus correlated with greater activation in the right frontal pole for both Go and Stop trials. On Stop trials stimulus processing speed also correlated with regions implicated in inhibitory control, including the right inferior frontal gyrus, medial frontal gyrus, and basal ganglia. Individual differences in motor execution time correlated with activation of the right parietal cortex. These findings suggest a robust relationship between the speed of stimulus processing and inhibitory processing at the neural level. This model-based approach provides novel insight into the interrelationships among decision components involved in inhibitory control, and raises interesting questions about strategic adjustments in performance and inhibitory deficits associated with psychopathology. PMID:24405185
Cavassin, Emerson Danguy; de Figueiredo, Luiz Francisco Poli; Otoch, José Pinhata; Seckler, Marcelo Martins; de Oliveira, Roberto Angelo; Franco, Fabiane Fantinelli; Marangoni, Valeria Spolon; Zucolotto, Valtencir; Levin, Anna Sara Shafferman; Costa, Silvia Figueiredo
2015-10-05
Multidrug resistant microorganisms are a growing challenge and new substances that can be useful to treat infections due to these microorganisms are needed. Silver nanoparticle may be a future option for treatment of these infections, however, the methods described in vitro to evaluate the inhibitory effect are controversial. This study evaluated the in vitro activity of silver nanoparticles against 36 susceptible and 54 multidrug resistant Gram-positive and Gram-negative bacteria from clinical sources. The multidrug resistant bacteria were oxacilin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., carbapenem- and polymyxin B-resistant A. baumannii, carbapenem-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae. We analyzed silver nanoparticles stabilized with citrate, chitosan and polyvinyl alcohol and commercial silver nanoparticle. Silver sulfadiazine and silver nitrate were used as control. Different methods were used: agar diffusion, minimum inhibitory concentration, minimum bactericidal concentration and time-kill. The activity of AgNPs using diffusion in solid media and the MIC methods showed similar effect against MDR and antimicrobial-susceptible isolates, with a higher effect against Gram-negative isolates. The better results were achieved with citrate and chitosan silver nanoparticle, both with MIC90 of 6.75 μg mL(-1), which can be due the lower stability of these particles and, consequently, release of Ag(+) ions as revealed by X-ray diffraction (XRD). The bactericidal effect was higher against antimicrobial-susceptible bacteria. It seems that agar diffusion method can be used as screening test, minimum inhibitory concentration/minimum bactericidal concentration and time kill showed to be useful methods. The activity of commercial silver nanoparticle and silver controls did not exceed the activity of the citrate and chitosan silver nanoparticles. The in vitro inhibitory effect was stronger against Gram-negative than Gram-positive, and similar against multidrug resistant and susceptible bacteria, with best result achieved using citrate and chitosan silver nanoparticles. The bactericidal effect of silver nanoparticle may, in the future, be translated into important therapeutic and clinical options, especially considering the shortage of new antimicrobials against the emerging antimicrobial resistant microorganisms, in particular against Gram-negative bacteria.
Chapman, C Richard; Vierck, Charles J
2017-04-01
The nature of the transition from acute to chronic pain still eludes explanation, but chronic pain resulting from surgery provides a natural experiment that invites clinical epidemiological investigation and basic scientific inquiry into the mechanisms of this transition. The primary purpose of this article is to review current knowledge and hypotheses on the transition from acute to persistent postsurgical pain, summarizing literature on clinical epidemiological studies of persistent postsurgical pain development, as well as basic neurophysiological studies targeting mechanisms in the periphery, spinal cord, and brain. The second purpose of this article is to integrate theory, information, and causal reasoning in these areas. Conceptual mapping reveals 5 classes of hypotheses pertaining to pain. These propose that chronic pain results from: 1) persistent noxious signaling in the periphery; 2) enduring maladaptive neuroplastic changes at the spinal dorsal horn and/or higher central nervous system structures reflecting a multiplicity of factors, including peripherally released neurotrophic factors and interactions between neurons and microglia; 3) compromised inhibitory modulation of noxious signaling in medullary-spinal pathways; 4) descending facilitatory modulation; and 5) maladaptive brain remodeling in function, structure, and connectivity. The third purpose of this article is to identify barriers to progress and review opportunities for advancing the field. This review reveals a need for a concerted, strategic effort toward integrating clinical epidemiology, basic science research, and current theory about pain mechanisms to hasten progress toward understanding, managing, and preventing persistent postsurgical pain. The development of chronic pain after surgery is a major clinical problem that provides an opportunity to study the transition from acute to chronic pain at epidemiologic and basic science levels. Strategic, coordinated, multidisciplinary research efforts targeting mechanisms of pain chronification can to help minimize or eliminate persistent postsurgical pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.
Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State
ERIC Educational Resources Information Center
Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.
2015-01-01
Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…
The Role of Physical Contact and Association in Early Contamination Sensitivity.
ERIC Educational Resources Information Center
Springer, Ken; Belk, Amy
1994-01-01
Children were asked whether someone would get sick from drinking juice placed near a bug. Some preschoolers and most seven- and eight-year olds recognized the need for physical contact with the bug to make the juice noxious, whereas some believed the mere presence of a contaminant made it noxious. Thus, associational contamination sometimes plays…
Ohno-Shosaku, T; Maejima, T; Kano, M
2001-03-01
Endogenous cannabinoids are considered to function as diffusible and short-lived modulators that may transmit signals retrogradely from postsynaptic to presynaptic neurons. To evaluate this possibility, we have made a paired whole-cell recording from cultured hippocampal neurons with inhibitory synaptic connections. In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory neurotransmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca2+ concentration caused transient suppression of inhibitory synaptic currents, which is mainly due to reduction of GABA release. This depolarization-induced suppression was completely blocked by selective cannabinoid antagonists. Our results reveal that endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals to cause the reduction of transmitter release.
Orbitofrontal disinhibition of pain in migraine with aura: an interictal EEG-mapping study.
Lev, Rina; Granovsky, Yelena; Yarnitsky, David
2010-08-01
This study aimed to identify the cortical mechanisms underlying the processes of interictal dishabituation to experimental pain in subjects suffering from migraine with aura (MWA). In 21 subjects with MWA and 22 healthy controls, cortical responses to two successive trials of noxious contact-heat stimuli were analyzed using EEG-tomography software. When compared with controls, MWA patients showed significantly increased pain-evoked potential amplitudes accompanied by reduced activity in the orbitofrontal cortex (OFC) and increased activity in the pain matrix regions, including the primary somatosensory cortex (SI) (p < .05). Similarly to controls, MWA subjects displayed an inverse correlation between the OFC and SI activities, and positive interrelations between other pain-specific regions. The activity changes in the OFC negatively correlated with lifetime headache duration and longevity (p < .05). Reduced inhibitory functioning of the prefrontal cortex is a possible cause for disinhibition of the pain-related sensory cortices in migraine. The finding of OFC hypofunction over the disease course is in keeping with current concepts of migraine as a progressive brain disorder.
Rudrappa, Thimmaraju; Bonsall, Justin; Gallagher, John L; Seliskar, Denise M; Bais, Harsh P
2007-10-01
Phragmites australis is considered the most invasive plant in marsh and wetland communities in the eastern United States. Although allelopathy has been considered as a possible displacing mechanism in P. australis, there has been minimal success in characterizing the responsible allelochemical. We tested the occurrence of root-derived allelopathy in the invasiveness of P. australis. To this end, root exudates of two P. australis genotypes, BB (native) and P38 (an exotic) were tested for phytotoxicity on different plant species. The treatment of the susceptible plants with P. australis root exudates resulted in acute rhizotoxicity. It is interesting to note that the root exudates of P38 were more effective in causing root death in susceptible plants compared to the native BB exudates. The active ingredient in the P. australis exudates was identified as 3,4,5-trihydroxybenzoic acid (gallic acid). We tested the phytotoxic efficacy of gallic acid on various plant systems, including the model plant Arabidopsis thaliana. Most tested plants succumbed to the gallic acid treatment with the exception of P. australis itself. Mechanistically, gallic acid treatment generated elevated levels of reactive oxygen species (ROS) in the treated plant roots. Furthermore, the triggered ROS mediated the disruption of the root architecture of the susceptible plants by damaging the microtubule assembly. The study also highlights the persistence of the exuded gallic acid in P. australis's rhizosphere and its inhibitory effects against A. thaliana in the soil. In addition, gallic acid demonstrated an inhibitory effect on Spartina alterniflora, one of the salt marsh species it successfully invades.
Sharma, Nivedita; Gupta, Anupama; Gautam, Neha
2014-01-01
In the present study, a bacterium isolated from Marcha- a herbal cake used as traditional starter culture to ferment local wine in North East India, was evaluated for bacteriocin like inhibitory substance production and was tested against six food borne/spoilage causing pathogens viz. Listeria monocytogenes MTCC 839, Bacillus subtilis MTCC 121, Clostridium perfringens MTCC 450, Staphylococcus aureus, Lactobacillus plantarum and Leuconostoc mesenteroides MTCC 107 by using bit/disc method followed by well diffusion method. The bacterial isolate was identified as Brevibacillus borstelensis on the basis of phenotypic, biochemical and molecular characteristics using 16Sr RNA gene technique. Bacteriocin like inhibitory substance produced by Brevibacillus borstelensis AG1 was purified by gel exclusion chromatography. The molecular mass of the Brevibacillus borstelensis AG1 was found to be 12 kDa. Purified bacteriocin like inhibitory substance of Brevibacillus borstelensis was further characterized by studying the effect of temperature, pH, proteolytic enzyme and stability. Bacteriocin like inhibitory substance was found to be thermostable upto 100 °C, active at neutral pH, sensitive to trypsin, and partially stable till third week of storage thus showing a bright prospective to be used as a potential food biopreservative.
Panneton, W. Michael; Gan, Qi; Ariel, Michael
2015-01-01
Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300μl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions. PMID:26154308
Panneton, W Michael; Gan, Qi; Ariel, Michael
2015-01-01
Although musculoskeletal pain disorders are common clinically, the central processing of muscle pain is little understood. The present study reports on central neurons activated by injections of algesic solutions into the gastrocnemius muscle of the rat, and their subsequent localization by c-Fos immunohistochemistry in the spinal cord and brainstem. An injection (300 μl) of an algesic solution (6% hypertonic saline, pH 4.0 acetate buffer, or 0.05% capsaicin) was made into the gastrocnemius muscle and the distribution of immunolabeled neurons compared to that obtained after control injections of phosphate buffered saline [pH 7.0]. Most labeled neurons in the spinal cord were found in laminae IV-V, VI, VII and X, comparing favorably with other studies, with fewer labeled neurons in laminae I and II. This finding is consistent with the diffuse pain perception due to noxious stimuli to muscles mediated by sensory fibers to deep spinal neurons as compared to more restricted pain localization during noxious stimuli to skin mediated by sensory fibers to superficial laminae. Numerous neurons were immunolabeled in the brainstem, predominantly in the lateral reticular formation (LRF). Labeled neurons were found bilaterally in the caudalmost ventrolateral medulla, where neurons responsive to noxious stimulation of cutaneous and visceral structures lie. Immunolabeled neurons in the LRF continued rostrally and dorsally along the intermediate reticular nucleus in the medulla, including the subnucleus reticularis dorsalis caudally and the parvicellular reticular nucleus more rostrally, and through the pons medial and lateral to the motor trigeminal nucleus, including the subcoerulear network. Immunolabeled neurons, many of them catecholaminergic, were found bilaterally in the nucleus tractus solitarii, the gracile nucleus, the A1 area, the CVLM and RVLM, the superior salivatory nucleus, the nucleus locus coeruleus, the A5 area, and the nucleus raphe magnus in the pons. The external lateral and superior lateral subnuclei of the parabrachial nuclear complex were consistently labeled in experimental data, but they also were labeled in many control cases. The internal lateral subnucleus of the parabrachial complex was labeled moderately. Few immunolabeled neurons were found in the medial reticular formation, however, but the rostroventromedial medulla was labeled consistently. These data are discussed in terms of an interoceptive, multisynaptic spinoreticulothalamic path, with its large receptive fields and role in the motivational-affective components of pain perceptions.
Karuppiah, Ponmurugan; Mustaffa, Muhammed
2013-01-01
Objective To investigate different Musa sp. leave extracts of hexane, ethyl acetate and methanol were evaluated for antibacterial activity against multi-drug resistant pathogens causing nosocomial infection by agar well diffusion method and also antioxidant activities. Methods The four different Musa species leaves were extracted with hexane, ethyl acetate and methanol. Antibacterial susceptibility test, minimum inhibitory concentration and minimum inhibitory bacterial concentration were determined by agar well diffusion method. Total phenolic content and in vitro antioxidant activity was determined. Results All the Musa sp. extracts showed moderate antibacterial activities expect Musa paradisiaca with the inhibition zone ranging from 8.0 to 18.6 mm. Among four species ethyl acetate extracts of Musa paradisiaca showed highest activity against tested pathogens particularly E. coli, P. aeruginosa and Citrobacter sp. The minimum inhibitory concentrations were within the value of 15.63- 250 µg/mL and minimum bactericidal concentrations were ranging from 31.25- 250 µg/mL. Antioxidant activity of Musa acuminate exhibited maximum activity among other three Musa species. Conclusions The present study concluded that among the different Musa species, Musa paradisiaca displayed efficient antibacterial activity followed by Musa acuminata against multi-drug resistant nosocomial infection causing pathogens. Further, an extensive study is needed to identify the bioactive compounds, mode of action and toxic effect in vivo of Musa sp. PMID:23998016
Karuppiah, Ponmurugan; Mustaffa, Muhammed
2013-09-01
To investigate different Musa sp. leave extracts of hexane, ethyl acetate and methanol were evaluated for antibacterial activity against multi-drug resistant pathogens causing nosocomial infection by agar well diffusion method and also antioxidant activities. The four different Musa species leaves were extracted with hexane, ethyl acetate and methanol. Antibacterial susceptibility test, minimum inhibitory concentration and minimum inhibitory bacterial concentration were determined by agar well diffusion method. Total phenolic content and in vitro antioxidant activity was determined. All the Musa sp. extracts showed moderate antibacterial activities expect Musa paradisiaca with the inhibition zone ranging from 8.0 to 18.6 mm. Among four species ethyl acetate extracts of Musa paradisiaca showed highest activity against tested pathogens particularly E. coli, P. aeruginosa and Citrobacter sp. The minimum inhibitory concentrations were within the value of 15.63- 250 µg/mL and minimum bactericidal concentrations were ranging from 31.25- 250 µg/mL. Antioxidant activity of Musa acuminate exhibited maximum activity among other three Musa species. The present study concluded that among the different Musa species, Musa paradisiaca displayed efficient antibacterial activity followed by Musa acuminata against multi-drug resistant nosocomial infection causing pathogens. Further, an extensive study is needed to identify the bioactive compounds, mode of action and toxic effect in vivo of Musa sp.
Woller, Sarah A.; Huie, J. Russell; Hartman, John J.; Hook, Michelle A.; Miranda, Rajesh C.; Huang, Yung-Jen; Ferguson, Adam R.; Grau, James W.
2014-01-01
We previously showed that peripheral noxious input after spinal cord injury (SCI) inhibits beneficial spinal plasticity and impairs recovery of locomotor and bladder functions. These observations suggest that noxious input may similarly affect the development and maintenance of chronic neuropathic pain, an important consequence of SCI. In adult rats with a moderate contusion SCI, we investigated the effect of noxious tail stimulation, administered one day after SCI, on mechanical withdrawal responses to von Frey stimuli from 1 to 28 days, post-treatment. In addition, because the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is implicated in numerous injury-induced processes including pain hypersensitivity, we assessed the temporal and spatial expression of TNFα, TNF receptors, and several downstream signaling targets after stimulation. Our results showed that unlike sham surgery or SCI only, nociceptive stimulation following SCI induced mechanical sensitivity by 24 hours. These behavioral changes were accompanied by increased expression of TNFα. Cellular assessments of downstream targets of TNFα revealed that nociceptive stimulation increased the expression of caspase 8 and the active subunit (12 kDa) of caspase 3 at a time point consistent with the onset of mechanical allodynia, indicative of active apoptosis. In addition, immunohistochemical analysis revealed distinct morphological signs of apoptosis in neurons and microglia at 24 hours post-stimulation. Interestingly, expression of the inflammatory mediator NFκB was unaltered by nociceptive stimulation. These results suggest that noxious input caudal to the level of SCI can increase the onset and expression of behavioral responses indicative of pain, potentially involving TNFα signaling. PMID:25180012
Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R. Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S
2014-01-01
Objective Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. Aim To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p=0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. Conclusion A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE. PMID:24590688
Ahluwalia, Vishwadeep; Wade, James B; Heuman, Douglas M; Hammeke, Thomas A; Sanyal, Arun J; Sterling, Richard K; Stravitz, R Todd; Luketic, Velimir; Siddiqui, Mohammad S; Puri, Puneet; Fuchs, Michael; Lennon, Micheal J; Kraft, Kenneth A; Gilles, HoChong; White, Melanie B; Noble, Nicole A; Bajaj, Jasmohan S
2014-12-01
Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin. 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.
Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis
Andrade, Milene Aparecida; Cardoso, Maria das Graças; Gomes, Marcos de Souza; de Azeredo, Camila Maria Oliveira; Batista, Luís Roberto; Soares, Maurilio José; Rodrigues, Leonardo Milani Avelar; Figueiredo, Ana Cristina S.
2015-01-01
This study had analyzed the antibacterial, antifungal and trypanocidal activity of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons. Activity against the pathogenic bacteria Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , Salmonella choleraesuis and Staphylococcus aureus was evaluated with the agar cavity diffusion method, while activity on the filamentous fungi Aspergillus flavus , Aspergillus niger , Aspergillus carbonarius and Penicillium commune was evaluated by the disk diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both essential oils exhibited low inhibitory effect towards bacteria, showing high MIC values (125–500 μg mL −1 ), with Gram positive bacteria being more susceptible. Better inhibitory effect was obtained for the evaluated fungi, with lower MIC values (7.81–250 μg mL −1 ), being A. flavus the most susceptible species. Both essential oils presented low trypanocidal activity, with IC 50 /24 h values of 209.30 μg mL −1 for S. guianensis and 282.93 μg mL −1 for C. dinisii . Thus, the high values observed for the MIC of evaluated bacteria and for IC 50 /24 h of T. cruzi , suggest that the essential oils have a low inhibitory activity against these microorganisms. In addition, the low MIC values observed for the tested fungi species indicate good inhibitory activity on these microorganisms’s growth. PMID:26221107
The Tao of treating weeds: Reaching for restoration in the northern Rocky Mountains
Lisa-Natalie Anjozian
2008-01-01
Noxious weeds are a serious problem that is spreading across the West. Herbicides such as Picloram have proven to be powerful tools in reducing weed invaders, although use of this tool has often produced unintended consequences. Broadleaf herbicides kill forbs, such as the noxious knapweed, but also harm native forbs such as arrowleaf balsamroot. Removing weedy forbs...
Charting environmental pollution. [by noise measurements
NASA Technical Reports Server (NTRS)
Halpert, E.; Bizo, F.; Karacsonyi, Z.
1974-01-01
It is found that areas affected by different noxious agents are within the limits traced for high noise level areas; consequently, it is suggested that high noise pressure levels should be used as the primary indication of environmental pollution. A complex methodology is reported for charting environmental pollution due to physical, chemical and biological noxious agents on the scale of an industrial district.
Observations on the effects of odours on the homeopathic response.
McGuigan, Moira
2014-07-01
Samuel Hahnemann described incidences where the homeopathic response was disrupted by noxious smells in the environment. An earlier paper proposed that homeopathic medicines may be sensed by vomeronasal cells (VNCs) i.e. microvillus or brush cells in the vomeronasal organ (VNO), the taste buds and associated with the trigeminal nerve and nervus terminalis. This paper proposes an extension to the theory and suggests that a subset of solitary chemosensory cells (SCCs) in the diffuse chemosensory system (DCS) that is morphologically similar to VNCs might also be receptive to homeopathic medicines. The types of odours that may interfere with this process are described. Two clinical cases of disruption of the homeopathic response are given as examples, showing that successful re-establishment of remedy action can be produced by timely repetition of the medicine. The ramifications on clinical homeopathic practice are discussed. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.
Sherman, S E; Loomis, C W
1996-08-01
Touch-evoked allodynia, an important symptom of clinical neural injury pain, can be modelled acutely and reversibly in the urethane-anesthetized rat using intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms), is manifest as a significant enhancement of cardiovascular and motor responses evoked by normally innocuous brushing of the hair (hair deflection), as compared to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t. STR (40 micrograms) with no tactile stimulus. The present study investigated: (1) the pharmacology of afferent neural inputs involved in STR-dependent allodynia using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg, s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85) significantly attenuated the responses evoked by noxious mechanical, thermal or chemical stimuli, but had no effect on STR-dependent allodynia. All hair deflection-evoked, STR-dependent responses were dose-dependently inhibited by i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5-19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR neither reduced nor enhanced the responses elicited by noxious stimuli in capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent allodynia is initiated by primary afferents not normally involved in nociception (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is selective for non-noxious sensory input. The sensitivity of STR-dependent allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm the independence of nociceptive pathways and STR-sensitive afferent inputs in this model.
Duncan, G H; Bushnell, M C; Oliveras, J L; Bastrash, N; Tremblay, N
1993-11-01
1. The present study evaluates the necessity of the ventroposterior medial thalamic nucleus (VPM) for discrimination of the intensity of noxious heating, innocuous cooling, and innocuous tactile (airpuff) stimulation of the maxillary skin. 2. Two rhesus monkeys were trained to detect small differences (< 1.0 degrees C) in the intensity of noxious heat (near 46 degrees C) and innocuous cold (near 30 degrees C) as well as differences in the force of an airpuff applied to the skin over the maxilla. As a control the monkeys also detected small differences in the intensity of a white light. Lidocaine hydrochloride (2%) was microinjected into regions of thalamus where single-unit recordings had identified neuronal responses to the noxious heating and/or cooling stimuli. The effectiveness of the anesthetic blockade was monitored by multiunit recordings using microelectrodes positioned 1-3 mm from the orifice of the injection cannula. The monkey's ability to detect near-threshold changes in stimulus intensity was compared before and after each injection. 3. During six experimental sessions, single injections of 1-4 microliters lidocaine near the dorsomedial border of VPM did not significantly alter the monkey's ability to detect small changes in the intensity of noxious heat, cool, airpuff, or visual stimuli despite neurophysiological evidence that spontaneous neuronal activity was blocked within parts of VPM. 4. During three experiments, dual simultaneous microinjections of lidocaine (delivered through 2 microcannulae separated by approximately 1 mm) resulted in profound deficits in noxious heat discrimination, with lesser deficits in cool and airpuff discrimination; visual discrimination was never altered. Monitoring of adjacent microelectrodes revealed that although activity ventral to the injection sites was blocked, activity in medial thalamic nuclei, implicated in nociceptive processing, was probably not altered by these injections. 5. These data suggest that VPM is important for the perception of noxious and innocuous thermal stimuli as well as for the perception of tactile stimuli. However, considering the ineffectiveness of small single microinjections of lidocaine, it appears that some critical proportion of VPM must be inactivated to disrupt thermal or tactile discrimination, possibly because of overlapping receptive field properties of neurons in different areas of the nucleus.
Saito, Shigeru; Nakatsuka, Kazumasa; Takahashi, Kenji; Fukuta, Naomi; Imagawa, Toshiaki; Ohta, Toshio; Tominaga, Makoto
2012-08-31
Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1.
Saito, Shigeru; Nakatsuka, Kazumasa; Takahashi, Kenji; Fukuta, Naomi; Imagawa, Toshiaki; Ohta, Toshio; Tominaga, Makoto
2012-01-01
Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1. PMID:22791718
Gao, Yong-Jing; Ji, Ru-Rong
2009-01-01
c-Fos, the protein of the protooncogene c-fos, has been extensively used as a marker for the activation of nociceptive neurons in the spinal cord for more than twenty years since Hunt et al. first reported that peripheral noxious stimulation to a hind paw of rats leads to a marked induction of c-Fos in superficial and deep dorsal horn neurons in 1987. In 1999, Ji et al. reported that phosphorylated extracellular signal-regulated kinase (pERK) is specifically induced by noxious stimulation in superficial dorsal horn neurons. Accumulating evidence indicates that pERK induction or ERK activation in dorsal horn neurons is essential for the development of central sensitization, increased sensitivity of dorsal horn neurons that is responsible for the generation of persistent pain. Further, molecular mechanisms underlying ERK-mediated central sensitization have been revealed. In contrast, direct evidence for c-Fos-mediated central sensitization is not sufficient. After a noxious stimulus (e.g., capsaicin injection) or tissue injury, c-Fos begins to be induced after 30-60 minutes, whereas pERK can be induced within a minute, which can correlate well with the development of pain hypersensitivity. While c-Fos is often induced in the nuclei of neurons, pERK can be induced in different subcellular structures of neurons such as nuclei, cytoplasma, axons, and dendrites. pERK can even be induced in spinal cord microglia and astrocytes after nerve injury. In summary, both c-Fos and pERK can be used as markers for neuronal activation following noxious stimulation and tissue injury, but pERK is much more dynamic and appears to be a better marker for central sensitization. PMID:19898681
Gleerup, Karina B; Forkman, Björn; Lindegaard, Casper; Andersen, Pia H
2015-01-01
Objective The objective of this study was to investigate the existence of an equine pain face and to describe this in detail. Study design Semi-randomized, controlled, crossover trial. Animals Six adult horses. Methods Pain was induced with two noxious stimuli, a tourniquet on the antebrachium and topical application of capsaicin. All horses participated in two control trials and received both noxious stimuli twice, once with and once without an observer present. During all sessions their pain state was scored. The horses were filmed and the close-up video recordings of the faces were analysed for alterations in behaviour and facial expressions. Still images from the trials were evaluated for the presence of each of the specific pain face features identified from the video analysis. Results Both noxious challenges were effective in producing a pain response resulting in significantly increased pain scores. Alterations in facial expressions were observed in all horses during all noxious stimulations. The number of pain face features present on the still images from the noxious challenges were significantly higher than for the control trial (p = 0.0001). Facial expressions representative for control and pain trials were condensed into explanatory illustrations. During pain sessions with an observer present, the horses increased their contact-seeking behavior. Conclusions and clinical relevance An equine pain face comprising ‘low’ and/or ‘asymmetrical’ ears, an angled appearance of the eyes, a withdrawn and/or tense stare, mediolaterally dilated nostrils and tension of the lips, chin and certain facial muscles can be recognized in horses during induced acute pain. This description of an equine pain face may be useful for improving tools for pain recognition in horses with mild to moderate pain. PMID:25082060
Nir, Rony-Reuven; Sinai, Alon; Raz, Einat; Sprecher, Elliot; Yarnitsky, David
2010-07-16
Recordings of neurophysiological brain responses to noxious stimuli have been traditionally based on short stimuli, in the order of milliseconds, which induce distinct event-related potentials (ERPs). However, using such stimuli in the experimental setting is disadvantageous as they are too brief to faithfully simulate clinical pain. We aimed at utilizing continuous EEG to investigate the properties of peak alpha frequency (PAF) as an objective cortical measure associated with subjective perception of tonic pain. Five minute long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with peak frequencies of alpha power-curves derived from central, temporal and frontal electrodes. NPSs and PAFs remained stable throughout the recording conditions (RM-ANOVAs; Ps>0.51). In the noxious condition, PAFs obtained at the bilateral temporal scalp were correlated with NPSs (Ps<0.001). Moreover, resting-state PAFs recorded at the bilateral temporal scalp were correlated with NPSs reported during the noxious condition (Ps<0.01). These psychophysical-neurophysiological relations attest to the properties of PAF as a novel cortical objective measure of subjective perception of tonic pain. Moreover, resting-state PAFs might hold inherent pain modulation attributes, possibly enabling the prediction of individual responsiveness to prolonged pain. The relevance of PAF to the neural processing of tonic pain may indicate its potential to advance pain research as well as clinical pain characterization. Copyright (c) 2010 Elsevier B.V. All rights reserved.
Dysmenorrhoea is associated with central changes in otherwise healthy women.
Vincent, Katy; Warnaby, Catherine; Stagg, Charlotte J; Moore, Jane; Kennedy, Stephen; Tracey, Irene
2011-09-01
Patients with chronic pain conditions demonstrate altered central processing of experimental noxious stimuli, dysfunction of the hypothalamic-pituitary-adrenal axis, and reduced quality of life. Dysmenorrhoea is not considered a chronic pain condition, but is associated with enhanced behavioural responses to experimental noxious stimuli. We used behavioural measures, functional magnetic resonance imaging, and serum steroid hormone levels to investigate the response to experimental thermal stimuli in otherwise healthy women, with and without dysmenorrhoea. Women with dysmenorrhoea reported increased pain to noxious stimulation of the arm and abdomen throughout the menstrual cycle; no menstrual cycle effect was observed in either group. During menstruation, deactivation of brain regions in response to noxious stimulation was observed in control women but not in women with dysmenorrhoea. Without background pain (ie, in nonmenstrual phases), activity in the entorhinal cortex appeared to mediate the increased responses in women with dysmenorrhoea. Mean cortisol was significantly lower in women with dysmenorrhoea and was negatively correlated with the duration of the symptom. Additionally, women with dysmenorrhoea reported significantly lower physical but not mental quality of life. Thus, many features of chronic pain conditions are also seen in women with dysmenorrhoea: specifically a reduction in quality of life, suppression of the hypothalamic-pituitary-adrenal axis, and alterations in the central processing of experimental noxious stimuli. These alterations persist when there is no background pain and occur in response to stimuli at a site distant from that of the clinical pain. These findings indicate the potential importance of early and adequate treatment of dysmenorrhoea. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Biofilm inhibition mechanism from extract of Hymenocallis littoralis leaves.
Nadaf, Naiem H; Parulekar, Rishikesh S; Patil, Rahul S; Gade, Trupti K; Momin, Anjum A; Waghmare, Shailesh R; Dhanavade, Maruti J; Arvindekar, Akalpita U; Sonawane, Kailas D
2018-04-24
Hymenocallis littoralis (Jacq.) Salisb. has been referred as beach spider lily and commonly known for its rich phytochemical diversity. Phytochemicals such as alkaloids, volatile constituents, phenols, flavonoids, flavonols extracted from different parts of these plants like bulbs, flowers, leaf, stem and root had been used in folk medicines from ancient times because of their excellent antimicrobial and antioxidant properties. The leaf and bulb extract of H. littoralis plant was traditionally used for wound healing. Alkaloids extracted from bulb of this plant possess anti-viral, anti-neoplastic and cytotoxic properties. However, these phytochemicals have also shown antibiofilm activity, which is considered as one of the important factor accountable for the drug resistance in microorganisms. Thus, the investigation of medicinal properties of H. littoralis could be useful to control biofilm producing pathogens. Explore antimicrobial, antibiofilm and antioxidant potentials of H. littoralis against pathogenic microorganisms using experimental and computational biology approach. Phytochemical extraction from dried powder of H. littoralis leaves was done by solvent extraction using methanol. Antimicrobial and antibiofilm activities of leaves extract were carried out using agar well diffusion method, growth curve, minimum inhibitory concentration (MIC) and Scanning Electron Microscopy (SEM). Liquid Chromatography and Mass Spectroscopy (LCMS) technique was used for the identification of phytochemicals. Molecular docking studies of antibiofilm agents with adhesin proteins were performed using Autodock 4.2. Antioxidant activity of extract was carried out by FRAP assay. The noxious effect of extract was investigated by histological studies on rat skin. The preliminary phytochemical analysis of methanolic leaves extract revealed the presence of alkaloids, flavonoids, terpenoid, glycosides, terpene, terpenoids and phenolics. The various phytochemicals such as Apigenin 7-(4'', 6'' diacetylalloside)-4'- alloside, Catechin 7-O- apiofuranoside, Emodic acid, Epicatechin 3-O- β-D-glucopyranoside, 4 - Methylesculetin, Methylisoeugenol, Quercetin 5,7,3',4'-tetramethyl ether 3-rutinoside, 4 - Methylumbelliferyl β-D- glucuronide were extracted, characterized and recognized from the leaves extract of H. littoralis. The identification of these phytochemicals was performed using LC-MS. The antimicrobial property of H. littoralis leaf extract was investigated against different pathogenic microorganisms. Out of these tested microorganisms, promising antibiofilm and antimicrobial activities were confirmed against S. aureus NCIM 2654 and C. albicans NCIM 3466 by using growth curve and SEM analysis. MIC of this leaf extract was identified as 45 µg/ml and 70 µg/ml for S. aureus NCIM 2654 and C. albicans NCIM 3466 respectively. The leaves extract also showed good antioxidant activity due to presence of phenols and flavonoids. Molecular docking of these identified antibiofilm components interacts with the active site residues of adhesin proteins, Sortase A and Als3 from S. aureus and C. albicans respectively. Histological studies of extracted phytochemicals revealed non-noxious effects on rat skin. Thus, the present study revealed that the leaves extract of H. littoralis contains various phytochemicals having good extent of antimicrobial, antibiofilm and antioxidant properties. The in-vitro and in-silico results would be useful to design new lead compounds against biofilm producing pathogenic microorganisms. Copyright © 2018 Elsevier B.V. All rights reserved.
Jeong, Keun-Yeong; Seong, Jinsil
2014-06-15
The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1. Copyright © 2014 Elsevier B.V. All rights reserved.
Hoeger Bement, Marie K; Weyer, Andy D; Yoon, Tejin; Hunter, Sandra K
2014-02-01
The purposes of this study were to assess corticomotor excitability in people with fibromyalgia during a noxious stimulus before and after fatiguing exercise and examine associations with pain perception. Fifteen women with fibromyalgia completed three sessions: one familiarization and two experimental. The experimental sessions were randomized and involved measurement of pain perception and motor evoked potentials before and after (1) quiet rest and (2) isometric contraction of the elbow flexor muscles. Motor evoked potential amplitude of brachioradialis muscle was measured following transcranial magnetic stimulation delivered before, during, and after a noxious mechanical stimulus. After quiet rest, there was no change in pain perception. After the submaximal contraction, there was considerable variability in the pain response. Based on the changes in the experimental pain, subjects were divided into three groups (increase, decrease, and no change in pain). There was an interaction between pain response and the pain-induced change in motor evoked potentials. Those individuals who had an increase in motor evoked potentials during the pain test had an increase in pain after exercise. Thus, women with fibromyalgia were classified based on their pain response to exercise, and this response was associated with the change in corticomotor excitability during the application of a noxious stimulus.
Sharma, Nivedita; Gupta, Anupama; Gautam, Neha
2014-01-01
In the present study, a bacterium isolated from Marcha- a herbal cake used as traditional starter culture to ferment local wine in North East India, was evaluated for bacteriocin like inhibitory substance production and was tested against six food borne/spoilage causing pathogens viz. Listeria monocytogenes MTCC 839, Bacillus subtilis MTCC 121, Clostridium perfringens MTCC 450, Staphylococcus aureus, Lactobacillus plantarum and Leuconostoc mesenteroides MTCC 107 by using bit/disc method followed by well diffusion method. The bacterial isolate was identified as Brevibacillus borstelensis on the basis of phenotypic, biochemical and molecular characteristics using 16Sr RNA gene technique. Bacteriocin like inhibitory substance produced by Brevibacillus borstelensis AG1 was purified by gel exclusion chromatography. The molecular mass of the Brevibacillus borstelensis AG1 was found to be 12 kDa. Purified bacteriocin like inhibitory substance of Brevibacillus borstelensis was further characterized by studying the effect of temperature, pH, proteolytic enzyme and stability. Bacteriocin like inhibitory substance was found to be thermostable upto 100 °C, active at neutral pH, sensitive to trypsin, and partially stable till third week of storage thus showing a bright prospective to be used as a potential food biopreservative. PMID:25477937
Antimicrobial activity of lactobacillus strains against uropathogens.
Shim, Yoon Hee; Lee, Seung Joo; Lee, Jung Won
2016-10-01
The use of lactobacillus probiotics has been proposed as an alternative to prophylactic antibiotics for preventing urinary tract infection (UTI) in the era of antibiotic resistance. In this study, the antimicrobial activity of lactobacillus strains against uropathogens, was evaluated and compared with that of antibiotics. To evaluate inhibitory activities of lactobacilli against uropathogens, six lactobacillus strains (L. gasseri, L. rhamnosus, L. acidophilus, L. plantarum, L. paracasei, L. acidophilus) and four representative uropathogens of infantile UTI (extended-spectrum beta-lactamase [ESBL](-) Escherichia coli, ESBL(+) E. coli, Proteus vulgaris, Enterococcus fecalis) were selected. Lactobacillus strain in vitro inhibition of each uropathogen was evaluated on MRS agar well diffusion assay and compared with that of commercial antibiotic discs. Average inhibitory zone for each of the six lactobacillus strains against the four uropathogens showed slightly different but consistent inhibition (inhibitory zone diameter, 10.5-20.0 mm). This was different to that of the antibiotic discs, which had a wider range of inhibition (inhibitory zone diameter, <6.0-27.5 mm) depending on the uropathogen resistance pattern. The inhibitory zone of the six lactobacillus strains was between that of sensitive and resistant antibiotics (P < 0.05). Lactobacillus strains had similar moderate antimicrobial activities against uropathogens. Further research is needed to ascertain the strains with the best probiotic potential. © 2016 Japan Pediatric Society.
Smith, A; Pedler, A
2018-01-01
Various conditioned pain modulation (CPM) methodologies have been used to investigate diffuse noxious inhibitory control pain mechanisms in healthy and clinical populations. Occlusion cuff parameters have been poorly studied. We aimed to investigate whether occlusion cuff intensity and/or duration influenced CPM magnitudes. We also investigated the role of physical activity levels on CPM magnitude. Two studies were performed to investigate the role of intensity and duration of occlusion cuff conditioning stimulus on test stimulus (tibialis anterior pressure pain thresholds). In Study 1, conditioning stimulus intensity of 2/10 or 5/10 (duration <20 s) was evaluated using a paired-samples t-test. In Study 2, duration of 2/10 conditioning stimulus was 3 min. One-way repeated-measures ANOVA was used to investigate the effect of time (0, 1, 2 and 3 min) on CPM magnitude. In Study 1, 27 healthy volunteers (mean ± SD: 24.9 years (±4.5); eight female) demonstrated that an occlusion cuff applied to the upper arm eliciting 5/10 local pain resulted in a significant (mean ± SD: 17% ± 46%) increase in CPM magnitude, when compared to 2/10 intensity (-3% ± 38%, p = 0.026), whereas in Study 2, 25 healthy volunteers (22.5 years (±2.7); 13 female) demonstrated that 3 min of 2/10 CS intensity did not result in a significant change in CPM (p = 0.21). There was no significant relationship between physical activity levels and CPM in either study (p > 0.22). This study demonstrated that an occlusion cuff of 5/10 conditioning stimulus intensity, when compared to 2/10, significantly increased CPM magnitude. Maintaining 2/10 conditioning stimulus for 3 min did not increase CPM magnitude. Dysfunctional conditioned pain modulation (CPM) has been associated with poor health outcomes. Various factors can influence CPM outcomes. The role of occlusion cuff conditioning stimulus intensity and duration has not been previously investigated. Intensity (5/10), but not duration of lower intensity (2/10) conditioning stimulus, affects CPM magnitude. © 2017 European Pain Federation - EFIC®.
Gerhardt, Andreas; Hartmann, Mechthild; Tesarz, Jonas; Janke, Susanne; Leisner, Sabine; Seidler, Günter; Eich, Wolfgang
2012-08-03
Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated.The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1) identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients. We will examine a population-based chronic pain sample (n = 100), a clinical tertiary care sample (n = 100) and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively). The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma), perceptual and central sensitisation (quantitative sensory testing), descending inhibition (conditioned pain modulation, the diffuse noxious inhibitory control-like effect), as well as measurement of the plasma levels of nerve growth factor and endocannabinoids. The identification of the underlying pathophysiologic mechanisms in different subgroups of chronic musculoskeletal pain patients will contribute to a mechanism-based subgroup classification. This will foster the development of mechanism-based treatments and holds promise to treat patients more sufficient.
Inhibitory effects of terpene alcohols and aldehydes on growth of green alga Chlorella pyrenoidosa
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ikawa, Miyoshi; Mosley, S.P.; Barbero, L.J.
1992-10-01
The growth of the green alga Chlorella pyrenoidosa was inhibited by terpene alcohols and the terpene aldehyde citral. The strongest activity was shown by citral. Nerol, geraniol, and citronellol also showed pronounced activity. Strong inhibition was linked to acyclic terpenes containing a primary alcohol or aldehyde function. Inhibition appeared to be taking place through the vapor phase rather than by diffusion through the agar medium from the terpene-treated paper disks used in the system. Inhibition through agar diffusion was shown by certain aged samples of terpene hydrocarbons but not by recently purchased samples.
Shetty, Sapna B.; Mahin-Syed-Ismail, Prabu; Varghese, Shaji; Thomas-George, Bibin; Kandathil- Thajuraj, Pathinettam; Baby, Deepak; Haleem, Shaista; Sreedhar, Sreeja
2016-01-01
Background Ethnomedicine is gaining admiration since years but still there is abundant medicinal flora which is unrevealed through research. The study was conducted to assess the in vitro antimicrobial potential and also determine the minimum inhibitory concentration (MIC) of Citrus sinensis peel extracts with a view of searching a novel extract as a remedy for dental caries pathogens. Material and Methods Aqueous and ethanol (cold and hot) extracts prepared from peel of Citrus sinensis were screened for in vitro antimicrobial activity against Streptococcus mutans and Lactobacillus acidophilus, using agar well diffusion method. The lowest concentration of every extract considered as the minimal inhibitory concentration (MIC) values were determined for both test organisms. One way ANOVA with Post Hoc Bonferroni test was applied for statistical analysis. Confidence level and level of significance were set at 95% and 5% respectively. Results Dental caries pathogens were inhibited most by hot ethanolic extract of Citrus sinensispeel followed by cold ethanolic extract. Aqueous extracts were effective at very high concentrations. Minimum inhibitory concentration of hot and cold ethanolic extracts of Citrus sinensis peel ranged between 12-15 mg/ml against both the dental caries pathogens. Conclusions Citrus sinensispeels extract was found to be effective against dental caries pathogens and contain compounds with therapeutic potential. Nevertheless, clinical trials on the effect of these plants are essential before advocating large-scale therapy. Key words:Agar well diffusion, antimicrobial activity, dental caries, Streptococcus mutans, Lactobacillus acidophilus. PMID:26855710
Papadopoulos, Theofilos; Schemm, Rudolf; Grubmüller, Helmut; Brose, Nils
2015-01-01
Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects—or synaptopathies—are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the CbR290H mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans. PMID:25678704
Papadopoulos, Theofilos; Schemm, Rudolf; Grubmüller, Helmut; Brose, Nils
2015-03-27
Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects--or synaptopathies--are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the Cb(R290H) mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Blood parameters and electroencephalographic responses of goats to slaughter without stunning.
Sabow, A B; Goh, Y M; Zulkifli, I; Sazili, A Q; Kaka, U; Kadi, M Z A Ab; Ebrahimi, M; Nakyinsige, K; Adeyemi, K D
2016-11-01
The study compared changes in blood biochemistry, hormonal and electroencephalographic indices associated with possible noxious stimuli following neck cut slaughter in conscious, non-anaesthetized versus minimally-anaesthetized goats. Ten male Boer crossbreed goats were assigned into two groups and subjected to either slaughter conscious without stunning (SWS) or slaughter following minimal anaesthesia (SMA). Hormonal responses and changes in electroencephalographic (EEG) parameters were not influenced by slaughter method. The SWS goats had higher glucose and lactate than did SMA goats. It can be concluded that the noxious stimulus from the neck cut is present in both conscious and minimally anaesthetized goats. The application of slaughter without stunning causes changes in the EEG activities that are consistent with the presence of post slaughter noxious sensory input associated with tissue damage and would be expected to be experienced as pain in goats. Copyright © 2016. Published by Elsevier Ltd.
Bagawath-Singh, Sunitha; Staaf, Elina; Stoppelenburg, Arie Jan; Spielmann, Thiemo; Kambayashi, Taku; Widengren, Jerker; Johansson, Sofia
2016-01-01
Cytokines have the potential to drastically augment immune cell activity. Apart from altering the expression of a multitude of proteins, cytokines also affect immune cell dynamics. However, how cytokines affect the molecular dynamics within the cell membrane of immune cells has not been addressed previously. Molecular movement is a vital component of all biological processes, and the rate of motion is, thus, an inherent determining factor for the pace of such processes. Natural killer (NK) cells are cytotoxic lymphocytes, which belong to the innate immune system. By fluorescence correlation spectroscopy, we investigated the influence of cytokine stimulation on the membrane density and molecular dynamics of the inhibitory receptor Ly49A and its ligand, the major histocompatibility complex class I allele H-2Dd, in freshly isolated murine NK cells. H-2Dd was densely expressed and diffused slowly in resting NK cells. Ly49A was expressed at a lower density and diffused faster. The diffusion rate in resting cells was not altered by disrupting the actin cytoskeleton. A short-term stimulation with interleukin-2 or interferon-α + β did not change the surface density of moving H-2Dd or Ly49A, despite a slight upregulation at the cellular level of H-2Dd by interferon-α + β, and of Ly49A by IL-2. However, the molecular diffusion rates of both H-2Dd and Ly49A increased significantly. A multivariate analysis revealed that the increased diffusion was especially marked in a subpopulation of NK cells, where the diffusion rate was increased around fourfold compared to resting NK cells. After IL-2 stimulation, this subpopulation of NK cells also displayed lower density of Ly49A and higher brightness per entity, indicating that Ly49A may homo-cluster to a larger extent in these cells. A faster diffusion of inhibitory receptors could enable a faster accumulation of these molecules at the immune synapse with a target cell, eventually leading to a more efficient NK cell response. It has previously been assumed that cytokines regulate immune cells primarily via alterations of protein expression levels or posttranslational modifications. These findings suggest that cytokines may also modulate immune cell efficiency by increasing the molecular dynamics early on in the response. PMID:26870035
Chakraborty, Saikat; Rebecchi, Mario; Kaczocha, Martin; Puopolo, Michelino
2016-03-15
The transient receptor potential vanilloid type 1 (TRPV1) receptor plays a key role in the modulation of nociceptor excitability. To address whether dopamine can modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamine receptor agonists were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons. Dopamine or SKF 81297 (an agonist at D1/D5 receptors), caused inhibition of both inward and outward currents by ∼60% and ∼48%, respectively. The effect of SKF 81297 was reversed by SCH 23390 (an antagonist at D1/D5 receptors), confirming that it was mediated by activation of D1/D5 dopamine receptors. In contrast, quinpirole (an agonist at D2 receptors) had no significant effect on the capsaicin-activated current. Inhibition of the capsaicin-activated current by SKF 81297 was mediated by G protein coupled receptors (GPCRs), and highly dependent on external calcium. The inhibitory effect of SKF 81297 on the capsaicin-activated current was not affected when the protein kinase A (PKA) activity was blocked with H89, or when the protein kinase C (PKC) activity was blocked with bisindolylmaleimide II (BIM). In contrast, when the calcium-calmodulin-dependent protein kinase II (CaMKII) was blocked with KN-93, the inhibitory effect of SKF 81297 on the capsaicin-activated current was greatly reduced, suggesting that activation of D1/D5 dopamine receptors may be preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to modulate incoming noxious stimuli. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
Analgesia induced by localized injection of opiate peptides into the brain of infant rats.
Barr, G A; Wang, S
2013-05-01
Stimulation of a variety of brain sites electrically or by opiates activates descending inhibitory pathways to attenuate noxious input to the spinal cord dorsal horn and produce analgesia. Analgesia induced by electrical stimulation of the periaqueductal grey (PAG) of the midbrain or medial rostral ventral medulla (RVM) matures late, towards the end or past the pre-weaning period. Descending facilitation takes precedence over inhibition. Yet opiates injected intracerebroventricularly or directly into the PAG induce analgesia relatively early in development. Our goal was to re-examine the role of opiates specific to individual receptor types in analgesia at several supraspinal sites. Antinociception was tested following microinjection of DAMGO (μ-opiate agonist), DPDPE (∂-opiate agonist) or U50,488 (κ-opiate agonist) into the PAG, RVM or dorsal lateral pons (DLP) in 3-, 10- and 14-day-old rats. DAMGO produced analgesia at 3 days of age at each brain area; the RVM was the most effective and the dorsal PAG was the least effective site. DPDPE produced modest analgesia at 10 and 14 days of age at the ventral PAG, RVM or DLP, but not the dorsal PAG. U50,488H was ineffective at all sites and all ages. Antinociception could be elicited at all three sites by DAMGO as early as 3 days of age and DPDPE at 10 and 14 days of age. The degree of analgesia increased gradually during the first 2 weeks of life, and likely reflects the maturation of connections within the brain and of descending inhibitory paths from these sites. © 2012 European Federation of International Association for the Study of Pain Chapters.
Enhanced pain expectation in migraine: EEG-based evidence for impaired prefrontal function.
Lev, Rina; Granovsky, Yelena; Yarnitsky, David
2013-01-01
Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9 μV) and unchanged ones in MOAs (1.1 μV) but not in controls (decrease of 5 μV). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5 μV and 4.4 μV, respectively) compared with controls (decrease of 0.2 μV). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P < .05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P < .05) and concern of upcoming migraine attacks (P < .05) in MWAs, and with frequency of migraine attacks in MOAs (P < .05). Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks. © 2012 American Headache Society.
Tan, Guak-Kim; Tabata, Yasuhiko
2014-06-01
Inflammation is a host protective response to noxious stimuli, and excessive production of pro-inflammatory mediators by macrophages (mφ) can lead to numerous pathological conditions. In this study, immunomodulatory effects of immobilized and soluble glycosaminoglycans (GAGs) on mouse-bone-marrow-derived mφ were compared by measuring nitric oxide (NO). We demonstrate here that all GAGs studied except for heparin were able to modulate interferon-γ/lipopolysaccharide (IFN-γ/LPS)-induced NO release by mφ to varying extents after 24h of incubation. In particular, the modulatory activities of soluble chondroitin-6-sulfate (C6S), hyaluronic acid and heparan sulfate altered markedly after covalent immobilization. Of these, soluble C6S exhibited the strongest NO inhibitory activity, and the inhibition was dose- and time-dependent. Moreover, C6S significantly reduced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α production by IFN-γ/LPS- or LPS-activated mφ. Specifically, the C6S-mediated suppression of mφ pro-inflammatory phenotype was accompanied by an increase in the IL-10 level, suggesting a possible switch towards anti-inflammatory/wound healing M2 state. In addition, the highest magnitude of inhibitory effects was obtained when cells were pre-treated with C6S prior to IFN-γ/LPS or LPS challenge, suggesting an additional role for C6S in protection against microbial infection. Further investigations reveal that the anti-inflammatory effects of C6S on activated mφ may be ascribed at least in part to suppression of NF-κB nuclear translocation. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Rahman, Wahida; Suzuki, Rie; Hunt, Stephen P; Dickenson, Anthony H
2008-06-01
Activity in descending systems from the brainstem modulates nociceptive transmission through the dorsal horn. Intrathecal injection of the neurotoxin saporin conjugated to SP (SP-SAP) into the lumbar spinal cord results in the selective ablation of NK(1) receptor expressing (NK(1)+ve) neurones in the superficial dorsal horn (lamina I/III). Loss of these NK(1)+ve neurones attenuates excitability of deep dorsal horn neurones due to a disruption of both intrinsic spinal circuits and a spino-bulbo-spinal loop, which activates a descending excitatory drive, mediated through spinal 5HT(3) receptors. Descending inhibitory pathways also modulate spinal activity and hence control the level of nociceptive transmission relayed to higher centres. To ascertain the spinal origins of the major descending noradrenergic inhibitory pathway we studied the effects of a selective alpha2-adrenoceptor antagonist, atipamezole, on neuronal activity in animals pre-treated with SP-SAP. Intrathecal application of atipamezole dose dependently facilitated the mechanically evoked neuronal responses of deep dorsal horn neurones to low intensity von Frey hairs (5-15 g) and noxious thermal (45-50 degrees C) evoked responses in SAP control animals indicating a physiological alpha2-adrenoceptor control. This facilitatory effect of atipamezole was lost in the SP-SAP treated group. These data suggest that activity within noradrenergic pathways have a dependence on dorsal horn NK(1)+ve cells. Further, noradrenergic descending inhibition may in part be driven by lamina I/III (NK(1)+ve) cells, and mediated via spinal alpha2-adrenoceptor activation. Since the same neuronal population drives descending facilitation and inhibition, the reduced excitability of lamina V/VI WDR neurones seen after loss of these NK(1)+ve neurones indicates a dominant role of descending facilitation.
Ishnava, Kalpesh B.; Chauhan, Jenabhai B.; Garg, Akanksha A.; Thakkar, Arpit M.
2011-01-01
In vitro antibacterial potential of the chloroform, ethyl acetate, hexane, methanol and aqueous extracts of Calotropis gigantia (L.) R. Br. was evaluated by using five cariogenic bacteria, Actinomyces viscosus, Lactobacillus acidophilus, Lactobacillus casei, Streptococcus mitis and Streptococcus mutans. Agar well diffusion method and minimum inhibitory concentration (MIC) were used for this purpose. The chloroform extracted fraction of latex showed inhibitory effect against S. mutans and L. acidophilus with MIC value of 0.032 and 0.52 mg/mL, respectively. Qualitative investigation on structure elucidation of bioactive compound using IR, NMR and GC–MS techniques revealed the presence of methyl nonanoate, a saturated fatty acid. PMID:23961166
Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome
ERIC Educational Resources Information Center
Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.
2009-01-01
Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…
Aggarwal, P; Kashyap, B
2017-06-01
Rampant use of fluconazole in Candida infections has led to predominance of less susceptible non-albicans Candida over Candida albicans. The aim of the study was to determine if zone diameters around fluconazole disk can be used to estimate the minimum inhibitory concentration (MIC) for clinical isolates of Candida species and vice versa. Categorical agreement between the Clinical & Laboratory Standards Institute (CLSI) recommended disk diffusion and CLSI broth microdilution method was sought for. Antifungal susceptibility testing by disk diffusion and Broth microdilution was done as per CLSI document M44-S3 and CLSI document M27-S4 for Candida isolates respectively. Regression analysis correlating zone diameters to MIC value was done. Pearson's correlation coefficient was calculated to determine correlation between disk zone diameters and MICs. Candida albicans (33.3%) was clearly outnumbered by other non-albicans species predominantly Candida tropicalis (42.5%) and Candida glabrata (18.4%). Ten percent of the strains were resistant to fluconazole by disk diffusion and 13% by broth microdilution. MIC range for Candida albicans and Candida tropicalis ranged from≤0.25-64μg/ml while that of Candida glabrata ranged from≤0.25-128μg/ml. Categorical agreement between disk diffusion and broth microdilution was 86.8%. Pearson's coefficient of correlation was -0.5975 indicating moderate negative correlation between the two variables. Zone sizes can be used to estimate the MIC values, although with limited accuracy. There should be a constant effort to upgrade the guidelines in view of new clinical data, and laboratories should make an active effort to incorporate them. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Placing pain on the sensory map: classic papers by Ed Perl and colleagues.
Mason, Peggy
2007-03-01
This essay looks at two papers published by Ed Perl and co-workers that identified specifically nociceptive neurons in the periphery and superficial dorsal horn. Bessou P and Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025-1043 1969. Christensen BN and Perl ER. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol 33: 293-307 1970.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1985-12-01
MARPOL was developed to minimize accidental and operational pollution from ships carrying noxious liquid substances in bulk. Accidental pollution could result from a collision, a grounding, or an overflow of a cargo tank. Operational pollution results from the disposal of cargo tank washings. Major amendments were made to the original Annex II by the International Maritime Organization. The United States and other States party to MARPOL will implement Annex II, as amended, on April 7, 1987. Implementation will affect seagoing ships transporting noxious liquid substances to and from such ships. The attached documents contain internationally agreed requirements, interpretations, and guidelinesmore » necessary for the implementation of Annex II. The documents attached include: (1) MARPOL Annex II as amended by amendments adopted by the twenty-second session of the IMO Marine Environment Protection Committee; (2) Unified Interpretations of Annex II; (3) Standards for the Procedures and Arrangements for the Discharge of Noxious Liquid Substances; (4) Ammendments to the Bulk Chemical Code and the International Bulk Chemical Code to include marine pollution concerns; (5) Guidelines on the Provision of Adequate Reception Facilities in Ports, Part II (Noxious Liquid Substances). The contents of these documents are being placed in regulations. The purpose of this document is to give members of the interested public advance notification of impending regulations.« less
Nickel, Moritz M; May, Elisabeth S; Tiemann, Laura; Postorino, Martina; Ta Dinh, Son; Ploner, Markus
2017-11-01
Pain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences.
Huma, Zilli; Ireland, Kirsty; Maxwell, David J
2015-03-30
It is now well established that the cerebellum receives input from nociceptors which may serve to adjust motor programmes in response to pain and injury. In this study, we investigated the possibility that spinoreticular neurons (SRT) which project to a pre-cerebellar nucleus, the lateral reticular nucleus (LRt), respond to noxious mechanical stimulation. Seven adult male rats received stereotaxic injections of the b subunit of cholera toxin in the LRt. Following a 5 day interval, animals were anesthetised with urethane and a noxious mechanical stimulus was applied to the right hind paw. Animals were fixed by perfusion 5min following application of the stimulus. Retrogradely labelled SRT neurons of the lumbar spinal cord were examined for immunoreactivity for phosphorylated ERK (pERK) and the neurokinin-1 (NK-1) receptor. Approximately 15% of SRT cells in deep laminae (IV-VII and X) expressed pERK ipsilateral to the site of the stimulus. Around 60% of SRT cells with the NK-1 receptor expressed pERK but 5% of pERK expressing cells were negatively labelled for NK-1. It is concluded that a significant proportion of SRT cells projecting to the LRt respond to noxious mechanical stimuli and that one of the functions of this pathway may be to provide the cerebellum with nociceptive information. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Jafari, Jafar
2012-01-01
Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm. PMID:22323983
Sifrim, Daniel; Jafari, Jafar
2012-01-01
Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm.
Studies on the bioavailability of zinc in humans: intestinal interaction of tin and zinc.
Solomons, N W; Marchini, J S; Duarte-Favaro, R M; Vannuchi, H; Dutra de Oliveira, J E
1983-04-01
Mineral/mineral interactions at the intestinal level are important in animal nutrition and toxicology, but only limited understanding of their extent or importance in humans has been developed. An inhibitory interaction of dietary tin on zinc retention has been recently described from human metabolic studies. We have explored the tin/zinc interaction using the change-in-plasma-zinc-concentration method with a standard dosage of 12.5 mg of zinc as zinc sulfate in 100 ml of Coca-Cola. Sn/Zn ratios of 2:1, 4:1, and 8:1, constituted by addition of 25, 50, and 100 mg of tin as stannous chloride, had no significant overall effect on zinc uptake. The 100-mg dose of tin produced noxious gastrointestinal symptoms. Addition of iron as ferrous sulfate to form ratios of Sn/Fe/Zn of 1:1:1 and 2:2:1 with the standard zinc solution and the appropriate doses of tin produced a reduction of zinc absorption not dissimilar from that seen previously with zinc and iron alone, and addition of picolinic acid did not influence the uptake of zinc from the solution with the 2:2:1 Sn/Fe/Zn ratio.
Marics, Irène; Malapert, Pascale; Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz
2014-01-01
The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation.
Song, X J; Zhao, Z Q
1998-05-01
Interactions among antagonists acting at different regulatory sites within the N-methyl-D-aspartate (NMDA) receptor-channel complex on the evoked responses to noxious thermal stimuli of wide dynamic range (WDR) neurons in spinal dorsal horn were studied on 21 adult anesthetized and spinalized cats. The responses of nociceptive spinal dorsal horn neurons to noxious heating (45-55 degrees C) of the glabrous skin of the unilateral hind paw were reduced markedly by iontophoretically applied antagonists. The specific recognition site antagonist, DL-2-amino-5-phosphonovaleratic acid (APV), the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (7CKA), the polyamine site antagonist ifenprodil (IFEN), and the phencyclidine (PCP) site antagonists ketamine (KET) and MK-801 (40-100 nA) significantly reduced (t-tests, P < 0.01) the noxious thermal stimulus-evoked responses in about 70% of the neurons by (mean +/- SE) 54.1 +/- 5.8% (n = 19), 80.8 +/- 4.7% (n = 16), 51.1 +/- 6.4% (n = 10), 77 +/- 4.9% (n = 16) and 81.2 +/- 8.1% (n = 5), respectively. APV and IFEN were less effective in blocking noxious thermal stimuli-evoked responses than 7CKA, KET and MK-801 (ANOVA, P < 0.05). The responses were completely inhibited in some neurons. After co-administration of the antagonists, APV + 7CKA, APV + IFEN, 7CKA + IFEN, APV + KET and APV + MK-801, all at the subthreshold ejection current, the responses were reduced markedly in 13 of 16, 7 of 10, 5 of 10, 3 of 6 and 3 of 5 neurons, respectively. The present study suggests that blockage of any component of the NMDA receptor-channel complex antagonizes the NMDA receptor-mediated response, and that there are the cooperative interactions among the various regulatory sites within the NMDA receptor-channel complex in the transmission or modulation of spinal nociceptive thermal information.
Asghar, Mohammad Sohail; Pereira, Manuel Pedro; Werner, Mads Utke; Mårtensson, Johan; Larsson, Henrik B W; Dahl, Jørgen Berg
2015-01-01
Noxious stimulation of the skin with either chemical, electrical or heat stimuli leads to the development of primary hyperalgesia at the site of injury, and to secondary hyperalgesia in normal skin surrounding the injury. Secondary hyperalgesia is inducible in most individuals and is attributed to central neuronal sensitization. Some individuals develop large areas of secondary hyperalgesia (high-sensitization responders), while others develop small areas (low-sensitization responders). The magnitude of each area is reproducible within individuals, and can be regarded as a phenotypic characteristic. To study differences in the propensity to develop central sensitization we examined differences in brain activity and anatomy according to individual phenotypical expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy volunteers received a first-degree burn-injury (47 °C, 7 min, 9 cm(2)) on the non-dominant lower-leg. Areas of secondary hyperalgesia were assessed 100 min after the injury. We measured neuronal activation by recording blood-oxygen-level-dependent-signals (BOLD-signals) during mechanical noxious stimulation before burn injury and in both primary and secondary hyperalgesia areas after burn-injury. In addition, T1-weighted images were used to measure differences in gray-matter density in cortical and subcortical regions of the brain. We found significant differences in neuronal activity between high- and low-sensitization responders at baseline (before application of the burn-injury) (p < 0.05). After the burn-injury, we found significant differences between responders during noxious stimulation of both primary (p < 0.01) and secondary hyperalgesia (p ≤ 0.04) skin areas. A decreased volume of the right (p = 0.001) and left caudate nucleus (p = 0.01) was detected in high-sensitization responders in comparison to low-sensitization responders. These findings suggest that brain-structure and neuronal activation to noxious stimulation differs according to secondary hyperalgesia phenotype. This indicates differences in central sensitization according to phenotype, which may have predictive value on the susceptibility to development of high-intensity acute and persistent pain.
Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz
2014-01-01
The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation. PMID:24925072
Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.
Foscarin, Simona; Raha-Chowdhury, Ruma; Fawcett, James W; Kwok, Jessica C F
2017-06-28
Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.
Chen, Ling-Ju; Tsai, Hsiu-Ting; Chen, Wei-Jen; Hsieh, Chu-Yang; Wang, Pi-Chieh; Chen, Chung-Shih; Wang, Lina; Yang, Chi-Chiang
2012-10-01
As lactobacilli possess an antagonistic growth property, these bacteria may be beneficial as bioprotective agents for infection control. However, whether the antagonistic growth effects are attributed to the lactobacilli themselves or their fermentative broth remains unclear. The antagonistic growth effects of Lactobacillus salivarius and Lactobacillus fermentum as well as their fermentative broth were thus tested using both disc agar diffusion test and broth dilution method, and their effects on periodontal pathogens, including Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis in vitro at different concentrations and for different time periods were also compared. Both Lactobacillus salivarius and Lactobacillus fermentum and their concentrated fermentative broth were shown to inhibit significantly the growth of Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis, although different inhibitory effects were observed for different pathogens. The higher the counts of lactobacilli and the higher the folds of concentrated fermentative broth, the stronger the inhibitory effects are observed. The inhibitory effect is demonstrated to be dose-dependent. Moreover, for the lactobacilli themselves, Lactobacillus fermentum showed stronger inhibitory effects than Lactobacillus salivarius. However, the fermentative broth of Lactobacillus fermentum showed weaker inhibitory effects than that of Lactobacillus salivarius. These data suggested that lactobacilli and their fermentative broth exhibit antagonistic growth activity, and consumption of probiotics or their broth containing lactobacilli may benefit oral health.
[Stings, bites and other adventures...].
De Dobbeleer, G
2000-09-01
Most of us live in cities and nature seems beneficial. Unfortunately, invertebrates and vertebrates may be aggressive. We will try here a review of the diseases caused by arthropods and other noxious animals. Injuries caused by the following insects will be described: mosquitoes, flies, fleas, bees, wasps and ants, bugs, beetles, butterflies and caterpillars. In the class arachnida: spiders, scopions, ticks and mites. Among invertebrates: leeches, anemons, corals, sea urchins, sponges and mollusca. Noxious or venomous vertebrates will not be forgotten. Basic and practical attitudes are proposed.
1978-08-01
Acoustic, and Noxious Stimuli Thesis in the Superior Colliculus of the Golden 6. PERFORMING OG. REPORT NUMBER Hamster -. _ // 7. AUTHOR( a ) S. CONTRACT...OR GRANT NUMBER(s) James P. Dixon I - "JV 9. PERF 7 MING ORGANIZATION NAME A D10. PROGRAM ELEMENT, PROJECT, TASK AFIT Student at: Virginia...studied in the superior colliculus of the golden hamster. A laminar organiza- tion was observed with cells in the superficial layers responding exclusively
Yang, Shih-Chun; Yen, Feng-Lin; Wang, Pei-Wen; Aljuffali, Ibrahim A; Weng, Yi-Han; Tseng, Chih-Hua; Fang, Jia-You
2017-09-01
Naphtho[1,2-b]furan-4,5-dione (N12D) and naphtho[2,3-b]furan-4,9-dione (N23D) are furanonaphthoquinone derivatives from natural resources. We examined the antimicrobial activity of N12D and N23D against drug-resistant Staphylococcus aureus. Minimum inhibitory concentration, minimum bactericidal concentration, bacterial viability and agar diffusion assay were conducted against methicillin-resistant S. aureus (MRSA) and clinical isolates of vancomycin-resistant S. aureus. The minimum inhibitory concentration of N12D and N23D against MRSA was 4.9-9.8 and 39 μM, respectively. With regard to the agar diffusion test, the inhibition zone of the quinone compounds was threefold larger than that of oxacillin. N12D was found to inhibit MRSA biofilm thickness from 24 to 16 μm as observed by confocal microscopy. N12D showed a significant reduction of the intracellular MRSA burden without decreasing the macrophage viability. The antibacterial mechanisms of N12D may be bacterial wall/membrane damage and disturbance of gluconeogenesis and the tricarboxylic acid cycle.
Mohsenipour, Zeinab; Hassanshahian, Mehdi
2015-01-01
Objective: Microorganisms are responsible for many problems in industry and medicine because of biofilm formation. Therefore, this study was aimed to examine the effect of Thymus vulgaris (T. vulgaris) extracts on the planktonic form and biofilm structures of six pathogenic bacteria. Materials and methods: Antimicrobial activities of the plant extracts against the planktonic form of the bacteria were determined using the disc diffusion method. MIC and MBC values were evaluated using macrobroth dilution technique. Anti-biofilm effects were assessed by microtiter plate method. Results: According to disc diffusion test (MIC and MBC), the ability of Thymus vulgaris (T. vulgaris ) extracts for inhibition of bacteria in planktonic form was confirmed. In dealing with biofilm structures, the inhibitory effect of the extracts was directly correlated to their concentration. Except for the inhibition of biofilm formation, efficacy of each extract was independent from type of solvent. Conclusion: According to the potential of Thymus vulgaris (T. vulgaris) extracts to inhibit the test bacteria in planktonic and biofilm form, it can be suggested that Thymus vulgaris (T. vulgaris) extracts can be applied as antimicrobial agents against the pathogenic bacteria particularly in biofilm forms. PMID:26442753
Brain processing of pain in patients with unresponsive wakefulness syndrome
Markl, Alexandra; Yu, Tao; Vogel, Dominik; Müller, Friedemann; Kotchoubey, Boris; Lang, Simone
2013-01-01
By definition, patients with unresponsive wakefulness syndrome (UWS) do not experience pain, but it is still not completely understood how far their brain can process noxious stimuli. The few positron emission tomography studies that have examined pain processing did not yield a clear and consistent result. We performed an functional magnetic resonance imaging scan in 30 UWS patients of nontraumatic etiology and 15 age- and sex-matched healthy control participants (HC). In a block design, noxious electrical stimuli were presented at the patients' left index finger, alternating with a resting baseline condition. Sixteen of the UWS patients (53%) showed neural activation in at least one subsystem of the pain-processing network. More specifically, 15 UWS patients (50%) showed responses in the sensory-discriminative pain network, 30% in the affective pain network. The data indicate that some patients completely fulfilling the clinical UWS criteria have the neural substrates of noxious stimulation processing, which resemble that in control individuals. We therefore suppose that at least some of these patients can experience pain. PMID:23533065
Neurophysiological measures of nociceptive brain activity in the newborn infant--the next steps.
Hartley, Caroline; Slater, Rebeccah
2014-03-01
Infants within neonatal intensive care units can receive multiple medically essential painful procedures per day. How they respond to these events, how best to alleviate the negative effects, and the long-term consequences for the infant are all significant questions that have yet to be fully answered. In recent years, several studies have examined cortical responses to noxious stimuli in the neonate through the use of near-infrared spectroscopy (NIRS) and electroencephalography (EEG). These investigations dispel any notion that the newborn infant does not process noxious stimuli at a cortical level and open the way for future research. In this Viewpoint Article, we review these studies and discuss key clinical challenges which may be elucidated with the use of these techniques. Simultaneously measuring the changes that are evoked in behaviour, physiology and the cortex following noxious events will provide the best approach to understanding the neonate's experience of pain. © 2013 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Porter, Mark C.; Ketchum, Sarah
Noxious weeds threaten fish and wildlife habitat by contributing to increased sedimentation rates, diminishing riparian structure and function, and reducing forage quality and quantity. Wallowa Resources Wallowa Canyonlands Partnership (WCP) protects the unique ecological and economic values of the Hells Canyon grasslands along lower Joseph Creek, the lower Grande Ronde and Imnaha Rivers from invasion and degradation by noxious weeds using Integrated Weed Management techniques. Objectives of this grant were to inventory and map high priority weeds, coordinate treatment of those weeds, release and monitor bio-control agents, educate the public as to the dangers of noxious weeds and how tomore » deal with them, and restore lands to productive plant communities after treatment. With collaborative help from partners, WCP inventoried {approx} 215,000 upland acres and 52.2 miles of riparian habitat, released bio-controls at 23 sites, and educated the public through posters, weed profiles, newspaper articles, and radio advertisements. Additionally, WCP used other sources of funding to finance the treatment of 1,802 acres during the course of this grant.« less
Puri, Sakshi; Faulkes, Zen
2015-01-01
Nociceptors are sensory neurons that are tuned to tissue damage. In many species, nociceptors are often stimulated by noxious extreme temperatures and by chemical agonists that do not damage tissue (e.g., capsaicin and isothiocyanate). We test whether crustaceans have nociceptors by examining nociceptive behaviours and neurophysiological responses to extreme temperatures and potentially nocigenic chemicals. Crayfish (Procambarus clarkii) respond quickly and strongly to high temperatures, and neurons in the antenna show increased responses to transient high temperature stimuli. Crayfish showed no difference in behavioural response to low temperature stimuli. Crayfish also showed no significant changes in behaviour when stimulated with capsaicin or isothiocyanate compared to controls, and neurons in the antenna did not change their firing rate following application of capsaicin or isothiocyanate. Noxious high temperatures appear to be a potentially ecologically relevant noxious stimulus for crayfish that can be detected by sensory neurons, which may be specialized nociceptors. PMID:25819841
Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex.
Zhao, Ruohe; Zhou, Hang; Huang, Lianyan; Xie, Zhongcong; Wang, Jing; Gan, Wen-Biao; Yang, Guang
2018-01-01
The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5) pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.
Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E
2014-01-01
Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772
Postural stability is altered by the stimulation of pain but not warm receptors in humans.
Blouin, Jean-Sébastien; Corbeil, Philippe; Teasdale, Normand
2003-10-17
It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C) were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively). For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. The stimulation of the warm receptors (40 degrees C) did not induce any postural deterioration. With pain (45 degrees C), subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure). A non-noxious stimulation (40 degrees C) of the small diameter afferents is not a sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C) of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated) could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly) or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy).
Effect of aqueous and ethanolic extracts of Lippia citriodora on candida albicans
Ghasempour, Maryam; Omran, Saeid Mahdavi; Moghadamnia, Ali Akbar; Shafiee, Faranak
2016-01-01
Introduction Because of resistance and side effects to common antifungal drugs activity, the research on herbal substances with antifungal activity is frequent. Lemon verbena (Lippia citriodora) is a member of Verbenaceae family. The aim of this study was to determine the anti-candida activities of the ethanolic and aqueous extracts of the lemon verbena leaves and compare them with nystatin and fluconazole. Methods In this 2015 study, 15 clinical isolates and standard strain of candida albicans PTCC 5027 were used, and the inhibitory effects of the ethanolic and aqueous extracts, Nystatin and Fluconazole, were evaluated using disk and well diffusion methods. Also, the minimal inhibitory concentration (MIC) was determined. Five concentrations of aqueous and ethanolic extracts (156–2500 μg/ml), Nystatin (8–128 μg/ml) and Fluconazole (4–64 μg/ml) were used in disk and well diffusion methods, and nine concentrations of aqueous and ethanolic extracts (19–5000 μg/ml), Nystatin (0.5–128 μg/ml), and Fluconazole (0.25–64 μg/ml) were applied for MIC. Data were analyzed using Tukey’s post-hoc and one-way ANOVA tests. The significant level was considered p < 0.05 in the current study. Results In the well and disk diffusion techniques, limited growth inhibition halos were produced around some clinical isolates at different concentrations of ethanolic extract; however, no growth inhibitory halo was observed with any concentrations of the aqueous extract. The MIC values of ethanolic extract, aqueous extract, Nystatin and Fluconazole for clinical isolated and standard strain were 833 ± 78.5and 625μg/ml; 4156 ± 67.4 and 2500 μg/ml; 10.13 ± 1.91 and 4 μg/ml; and 1.97 ± 0.25 and 1 μg/ml, respectively. Conclusion The results showed that the ethanolic extract was stronger than the aqueous extract of this plant, which can be used as an alternative for drugs. It is recommended that the ethanolic extract of this plant be investigated in vivo for better evaluation of its efficacy and properties. PMID:27757185
Race, ethnicity, and noxious facilities: Environmental racism re- examined
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nieves, A.L.; Nieves, L.A.
1992-10-01
The charge has been made that hazardous facilities tend to be located in proximity to minority populations. This study uses a facility density measure for three categories of noxious facilities to examine the relationship between facilities and minority population concentrations. County-level data are used in a correlation analysis for African Americans, Hispanics, and Asians in the four major regions of the US. Even controlling for income and housing value, and limiting the data set to urban areas, consistent patterns of moderate to strong association of facility densities with minority population percentages are found.
Dahiya, Praveen; Purkayastha, Sharmishtha
2012-01-01
The in vitro antibacterial activity of various solvents and water extracts of aloe vera, neem, bryophyllum, lemongrass, tulsi, oregano, rosemary and thyme was assessed on 10 multi-drug resistant clinical isolates from both Gram-positive and Gram-negative bacteria and two standard strains including Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. The zone of inhibition as determined by agar well diffusion method varied with the plant extract, the solvent used for extraction, and the organism tested. Klebsiella pneumoniae 2, Escherichia coli 3 and Staphylococcus aureus 3 were resistant to the plant extracts tested. Moreover, water extracts did not restrain the growth of any tested bacteria. Ethanol and methanol extracts were found to be more potent being capable of exerting significant inhibitory activities against majority of the bacteria investigated. Staphylococcus aureus 1 was the most inhibited bacterial isolate with 24 extracts (60%) inhibiting its growth whereas Escherichia coli 2 exhibited strong resistance being inhibited by only 11 extracts (28%). The results obtained in the agar diffusion plates were in fair correlation with that obtained in the minimum inhibitory concentration tests. The minimum inhibitory concentration of tulsi, oregano, rosemary and aloe vera extracts was found in the range of 1.56-6.25 mg/ml for the multi-drug resistant Staphylococcus aureus isolates tested whereas higher values (6.25-25 mg/ml) were obtained against the multi-drug resistant isolates Klebsiella pneumoniae 1 and Escherichia coli 1 and 2. Qualitative phytochemical analysis demonstrated the presence of tannins and saponins in all plants tested. Thin layer chromatography and bioautography agar overlay assay of ethanol extracts of neem, tulsi and aloe vera indicated flavonoids and tannins as major active compounds against methicillin-resistant Staphylococcus aureus. PMID:23716873
A novel multivariate STeady-state index during general ANesthesia (STAN).
Castro, Ana; de Almeida, Fernando Gomes; Amorim, Pedro; Nunes, Catarina S
2017-08-01
The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.
Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi
2017-02-06
Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.
McIlhone, Amanda E; Beausoleil, Ngaio J; Kells, Nikki J; Mellor, David J; Johnson, Craig B
2018-01-01
The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species. The aim of the current study was to determine whether the MAM can be applied to the study of nociception in birds. Ten chickens were lightly anaesthetised with halothane and their EEG recorded using surface electrodes during the application of supramaximal mechanical, thermal and electrical noxious stimuli. Spectral analysis revealed no EEG responses to any of these stimuli. Given that birds possess the neural apparatus to detect and process pain, and that the applied noxious stimuli elicit behavioural signs of pain in conscious chickens, this lack of response probably relates to methodological limitations. Anatomical differences between the avian and mammalian brains, along with a paucity of knowledge regarding specific sites of pain processing in the avian brain, could mean that EEG recorded from the head surface is insensitive to changes in neural activity in the pain processing regions of the avian brain. Future investigations should examine alternative electrode placement sites, based on avian homologues of the mammalian brain regions involved in pain processing.
Kakita, Kaede; Tsubouchi, Hirona; Adachi, Mayu; Takehana, Shiori; Shimazu, Yoshihito; Takeda, Mamoru
2017-11-29
Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuronal activity elicited by non-noxious and noxious orofacial mechanical stimulation in pentobarbital anesthetized rats. The mean number of SpVc WDR neuronal firings responding to both non-noxious and noxious mechanical stimuli were significantly and dose-dependently inhibited by local subcutaneous administration of CGA (0.1-10mM), with the maximal inhibition of discharge frequency revealed within 10min and reversed after approximately 30min. The mean frequency of SpVc neuronal discharge inhibition by CGA was comparable to that by a local anesthetic, the sodium channel blocker, 1% lidocaine. These results suggest that local CGA injection into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via the activation of voltage-gated potassium channels and modulation of ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons. Therefore, local injection of CGA could contribute to local anesthetic agents for the treatment of trigeminal nociceptive pain. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
McIlhone, Amanda E.; Beausoleil, Ngaio J.; Mellor, David J.; Johnson, Craig B.
2018-01-01
The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species. The aim of the current study was to determine whether the MAM can be applied to the study of nociception in birds. Ten chickens were lightly anaesthetised with halothane and their EEG recorded using surface electrodes during the application of supramaximal mechanical, thermal and electrical noxious stimuli. Spectral analysis revealed no EEG responses to any of these stimuli. Given that birds possess the neural apparatus to detect and process pain, and that the applied noxious stimuli elicit behavioural signs of pain in conscious chickens, this lack of response probably relates to methodological limitations. Anatomical differences between the avian and mammalian brains, along with a paucity of knowledge regarding specific sites of pain processing in the avian brain, could mean that EEG recorded from the head surface is insensitive to changes in neural activity in the pain processing regions of the avian brain. Future investigations should examine alternative electrode placement sites, based on avian homologues of the mammalian brain regions involved in pain processing. PMID:29698446
Uchida, Sae; Hotta, Harumi; Hanada, Tomoko; Okuno, Yuka; Aikawa, Yoshihiro
2007-08-01
The effects of thermal stimulation, applied to the hindpaw via a hot bath set to either 40 degrees C (non-noxious) or 49 degrees C (noxious), upon ovarian blood flow were examined in nonpregnant anesthetized rats. Ovarian blood flow was measured using a laser Doppler flowmeter. Blood pressure was markedly increased following 49 degrees C stimulation. Ovarian blood flow, however, showed no obvious change during stimulation, although a small increase was observed after stimulation. Ovarian blood flow and blood pressure responses to 49 degrees C stimulation were abolished after hindlimb somatic nerves proximal to the stimuli were cut. Heat stimulation (49 degrees C) resulted in remarkable increases in both ovarian blood flow and blood pressure in rats in which the sympathetic nerves supplying the ovary were cut but the hindlimb somatic nerves remained intact. The efferent activity of the ovarian plexus nerve was increased during stimulation at 49 degrees C. Stimulation at 40 degrees C had no effect upon ovarian blood flow, blood pressure or ovarian plexus nerve activity. Electrical stimulation of the distal part of the severed ovarian plexus nerve resulted in a decrease in both the diameter of ovarian arterioles, observed using a digital video microscope, and ovarian blood flow.The present results demonstrate that noxious heat, but not non-noxious warm, stimulation of the hindpaw skin in anesthetized rats influences ovarian blood flow in a manner that is attributed to reflex responses in ovarian sympathetic nerve activity and blood pressure.
The inhibitory effect of natural bioactives on the growth of pathogenic bacteria
Kim, Ji-Sun
2007-01-01
The objective of this study was to evaluate the inhibitory activity of natural products, against growth of Escherichia coli (ATCC 25922) and Salmonella typhimurium (KCCM 11862). Chitosan, epigallocatechin gallate (EGCG), and garlic were used as natural bioactives for antibacterial activity. The testing method was carried out according to the disk diffusion method. All of chitosan, EGCG, and garlic showed inhibitory effect against the growth of E. coli and Salmonella typhi. To evaluate the antibacterial activity of natural products during storage, chicken skins were inoculated with 106 of E. coli or Salmonella typhi. The inoculated chicken skins, treated with 0.5, 1, or 2% natural bioactives, were stored during 8 day at 4℃. The numbers of microorganisms were measured at 8 day. Both chitosan and EGCG showed significant decrease in the number of E. coli and Salmonella typhi in dose dependent manner (P < 0.05). These results suggest that natural bioactives such as chitosan, EGCG may be possible to be used as antimicrobial agents for the improvement of food safety. PMID:20368950
Zoning, equity, and public health.
Maantay, J
2001-07-01
Zoning, the most prevalent land use planning tool in the United States, has substantial implications for equity and public health. Zoning determines where various categories of land use may go, thereby influencing the location of resulting environmental and health impacts. Industrially zoned areas permit noxious land uses and typically carry higher environmental burdens than other areas. Using New York City as a case study, the author shows that industrial zones have large residential populations within them or nearby. Noxious uses tend to be concentrated in poor and minority industrial neighborhoods because more affluent industrial areas and those with lower minority populations are rezoned for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning policies, therefore, can have adverse impacts on public health and equity. The location of noxious uses and the pollution they generate have ramifications for global public health and equity; these uses have been concentrated in the world's poorer places as well as in poorer places within more affluent countries. Planners, policymakers, and public health professionals must collaborate on a worldwide basis to address these equity, health, and land use planning problems.
Zoning, equity, and public health.
Maantay, J
2001-01-01
Zoning, the most prevalent land use planning tool in the United States, has substantial implications for equity and public health. Zoning determines where various categories of land use may go, thereby influencing the location of resulting environmental and health impacts. Industrially zoned areas permit noxious land uses and typically carry higher environmental burdens than other areas. Using New York City as a case study, the author shows that industrial zones have large residential populations within them or nearby. Noxious uses tend to be concentrated in poor and minority industrial neighborhoods because more affluent industrial areas and those with lower minority populations are rezoned for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning policies, therefore, can have adverse impacts on public health and equity. The location of noxious uses and the pollution they generate have ramifications for global public health and equity; these uses have been concentrated in the world's poorer places as well as in poorer places within more affluent countries. Planners, policymakers, and public health professionals must collaborate on a worldwide basis to address these equity, health, and land use planning problems. PMID:11441726
Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria.
Chomnawang, Mullika Traidej; Surassmo, Suvimol; Nukoolkarn, Veena S; Gritsanapan, Wandee
2005-10-03
Propionibacterium acnes and Staphylococcus epidermidis have been recognized as pus-forming bacteria triggering an inflammation in acne. The present study was conducted to evaluate antimicrobial activities of Thai medicinal plants against these etiologic agents of acne vulgaris. Crude extracts were tested for antimicrobial activities by disc diffusion and broth dilution methods. The results from the disc diffusion method showed that 13 medicinal plants could inhibit the growth of Propionibacterium acnes. Among those, Senna alata, Eupatorium odoratum, Garcinia mangostana, and Barleria lupulina had strong inhibitory effects. Based on a broth dilution method, the Garcinia mangostana extract had the greatest antimicrobial effect. The MIC values were the same (0.039 mg/ml) for both bacterial species and the MBC values were 0.039 and 0.156 mg/ml against Propionibacterium acnes and Staphylococcus epidermidis, respectively. In bioautography assay, the Garcinia mangostana extract produced strong inhibition zones against Propionibacterium acnes. Antimicrobial activity from fractions of column chromatography revealed one of the active compounds in Garcinia mangostana could be mangostin, a xanthone derivative. Taken together, our data indicated that Garcinia mangostana had a strong inhibitory effect on Propionibacterium acnes and Staphylococcus epidermidis. Therefore, this plant would be an interesting topic for further study and possibly for an alternative treatment for acne.
Bharti, Veni; Vasudeva, Neeru; Dhuhan, Joginder Singh
2013-01-01
Purpose: The study is aimed at finding new antibiotic therapy for aquaculture due to potential of bacteria to develop resistance to the existing therapies. Use of large quantities of synthetic antibiotics in aquaculture thus has the potential to be detrimental to fish health, to the environment and wildlife and to human health. Methods: Antimicrobial potential of volatile oil and fractions of chloroform extract of Oreganum vulgare was evaluated alone and in the presence of standard antimicrobials against common fish pathogens by disc-diffusion, agar well assay and two fold microdilution method by nanodrop spectrophotometric method. Results: The best results were represented by volatile oil followed by phenolic fraction by disc-diffusion, agar well and microdilution assays (Minimum inhibitory concentration). By the interaction studies, it was observed that the volatile oil and phenolic fraction were able to inhibit the pathogens at very low concentration compared to standard drugs. The fractional inhibitory concentration index (FICI) was calculated and volatile oil and phenolic fractions were found to be synergistic against Pseudomonas fluorescens and Candida albicans. Conclusion: The experimental data suggests the use of volatile oil and phenolic fraction in combination with standard antimicrobials to maintain healthy aquaculture with lesser adverse effects as compared to synthetic antibiotic therapy. PMID:24312842
Altered behavior in experimental cortical dysplasia.
Zhou, Fu-Wen; Rani, Asha; Martinez-Diaz, Hildabelis; Foster, Thomas C; Roper, Steven N
2011-12-01
Developmental delay and cognitive impairment are common comorbidities in people with epilepsy associated with malformations of cortical development (MCDs). We studied cognition and behavior in an animal model of diffuse cortical dysplasia (CD), in utero irradiation, using a battery of behavioral tests for neuromuscular and cognitive function. Fetal rats were exposed to 2.25 Gy external radiation on embryonic day 17 (E17). At 1 month of age they were tested using an open field task, a grip strength task, a grid walk task, inhibitory avoidance, an object recognition task, and the Morris water maze task. Rats with CD showed reduced nonlocomotor activity in the open field task and impaired motor coordination for grid walking but normal grip strength. They showed a reduced tendency to recognize novel objects and reduced retention in an inhibitory avoidance task. Water maze testing showed that learning and memory were impaired in irradiated rats for both cue discrimination and spatially oriented tasks. These results demonstrate significant deficits in cortex- and hippocampus-dependent cognitive functions associated with the diffuse abnormalities of cortical and hippocampal development that have been documented in this model. This study documents multimodal cognitive deficits associated with CD and can serve as the foundation for future investigations into the mechanisms of and possible therapeutic interventions for this problem. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.
Visceral and somatic pain modalities reveal NaV1.7‐independent visceral nociceptive pathways
Hockley, James R. F.; González‐Cano, Rafael; McMurray, Sheridan; Tejada‐Giraldez, Miguel A.; McGuire, Cian; Torres, Antonio; Wilbrey, Anna L.; Cibert‐Goton, Vincent; Nieto, Francisco R.; Pitcher, Thomas; Knowles, Charles H.; Baeyens, José Manuel; Wood, John N.; Winchester, Wendy J.; Bulmer, David C.; Cendán, Cruz Miguel
2017-01-01
Key points Voltage‐gated sodium channels play a fundamental role in determining neuronal excitability.Specifically, voltage‐gated sodium channel subtype NaV1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown.Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling.These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality‐specific manner and help to direct drug discovery efforts towards novel visceral analgesics. Abstract Voltage‐gated sodium channel NaV1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor‐specific NaV1.7 knockout mouse (NaV1.7Nav1.8) and selective small‐molecule NaV1.7 antagonist PF‐5198007. NaV1.7Nav1.8 mice showed normal nociceptive behaviours in response to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both NaV1.7Nav1.8 and littermate controls. Loss, or blockade, of NaV1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve–gut preparations in mouse, or following antagonism of NaV1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage‐gated sodium channel α subunits revealed NaV1.7 mRNA transcripts in nearly all retrogradely labelled colonic neurons, suggesting redundancy in function. By contrast, using comparative somatic behavioural models we identify that genetic deletion of NaV1.7 (in NaV1.8‐expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective NaV1.7 antagonist PF‐5198007. Our data demonstrate that NaV1.7 (in NaV1.8‐expressing neurons) contributes to defined pain pathways in a modality‐dependent manner, modulating somatic noxious heat pain, but is not required for visceral pain processing, and advocate that pharmacological block of NaV1.7 alone in the viscera may be insufficient in targeting chronic visceral pain. PMID:28105664
An inhibitor of TRPV1 channels isolated from funnel Web spider venom.
Kitaguchi, Tetsuya; Swartz, Kenton J
2005-11-29
Capsaicin receptor channels (TRPV1) are nonselective cation channels that integrate multiple noxious stimuli in sensory neurons. In an effort to identify new inhibitors of these channels we screened a venom library for activity against TRPV1 channels and found robust inhibitory activity in venom from Agelenopsis aperta, a north American funnel web spider. Fractionation of the venom using reversed-phase HPLC resulted in the purification of two acylpolyamine toxins, AG489 and AG505, which inhibit TRPV1 channels from the extracellular side of the membrane. The activity of AG489 was characterized further, and the toxin was found to inhibit TRPV1 channels with a K(i) of 0.3 microM at -40 mV. Inhibition of TRPV1 channels by AG489 is strongly voltage-dependent, with relief of inhibition at positive voltages, consistent with the toxin inhibiting the channel through a pore-blocking mechanism. We used scanning mutagenesis throughout the TM5-TM6 linker, a region thought to form the outer pore of TRPV1 channels, to identify pore mutations that alter toxin affinity. Four mutants dramatically decrease toxin affinity and several mutants increase toxin affinity, consistent with the notion that the TM5-TM6 linker forms the outer vestibule of TRPV1 channels and that AG489 is a pore blocker.
Futatsubashi, Genki; Sasada, Shusaku; Tazoe, Toshiki; Komiyama, Tomoyoshi
2013-07-01
To investigate the neural alteration of reflex pathways arising from cutaneous afferents in patients with chronic ankle instability. Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the sural nerve of subjects with chronic ankle instability (n=17) and control subjects (n=17) while sitting. Electromyographic (EMG) signals were recorded from each ankle and thigh muscle. The middle latency response (MLR; latency: 70-120 ms) component was analyzed. In the peroneus longus (PL) and vastus lateralis (VL) muscles, linear regression analyses between the magnitude of the inhibitory MLR and background EMG activity showed that, compared to the uninjured side and the control subjects, the gain of the suppressive MLR was increased in the injured side. This was also confirmed by the pooled data for both groups. The degree of MLR alteration was significantly correlated to that of chronic ankle instability in the PL. The excitability of middle latency cutaneous reflexes in the PL and VL is modulated in subjects with chronic ankle instability. Cutaneous reflexes may be potential tools to investigate the pathological state of the neural system that controls the lower limbs in subjects with chronic ankle instability. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Antifouling activities of marine bacteria associated with sponge ( Sigmadocia sp.)
NASA Astrophysics Data System (ADS)
Satheesh, S.; Soniamby, A. R.; Sunjaiy Shankar, C. V.; Mary Josephine Punitha, S.
2012-09-01
The present study aimed at assessing the antifouling activity of bacteria associated with marine sponges. A total of eight bacterial strains were isolated from the surface of sponge Sigmadocia sp., of them, SS02, SS05 and SS06 showed inhibitory activity against biofilm-forming bacteria. The extracts of these 3 strains considerably affected the extracellular polymeric substance producing ability and adhesion of biofilm-forming bacterial strains. In addition to disc diffusion assay, microalgal settlement assay was carried out with the extracts mixed with polyurethane wood polish and coated onto stainless steel coupons. The extract of strain SS05 showed strong microalgal settlement inhibitory activity. Strain SS05 was identified as Bacillus cereus based on its 16S rRNA gene. Metabolites of the bacterial strains associated with marine invertebrates promise to be developed into environment-friendly antifouling agents.
Adachi, K; Murray, G M; Lee, J-C; Sessle, B J
2008-09-01
The mechanisms whereby orofacial pain affects motor function are poorly understood. The aims were to determine whether 1) lingual algesic chemical stimulation affected face primary motor cerebral cortex (face MI) excitability defined by intracortical microstimulation (ICMS); and 2) any such effects were limited to the motor efferent MI zones driving muscles in the vicinity of the noxious stimulus. Ketamine-anesthetized Sprague-Dawley male rats were implanted with electromyographic (EMG) electrodes into anterior digastric, masseter, and genioglossus muscles. In 38 rats, three microelectrodes were located in left face MI at ICMS-defined sites for evoking digastric and/or genioglossus responses. ICMS thresholds for evoking EMG activity from each site were determined every 15 min for 1 h, then the right anterior tongue was infused (20 microl, 120 microl/h) with glutamate (1.0 M, n = 18) or isotonic saline (n = 7). Subsequently, ICMS thresholds were determined every 15 min for 4 h. In intact control rats (n = 13), ICMS thresholds were recorded over 5 h. Only left and right genioglossus ICMS thresholds were significantly increased (< or =350%) in the glutamate infusion group compared with intact and isotonic saline groups (P < 0.05). These dramatic effects of glutamate on ICMS-evoked genioglossus activity contrast with its weak effects only on right genioglossus activity evoked from the internal capsule or hypoglossal nucleus. This is the first documentation that intraoral noxious stimulation results in prolonged neuroplastic changes manifested as a decrease in face MI excitability. These changes appear to occur predominantly in those parts of face MI that provide motor output to the orofacial region receiving the noxious stimulation.
Johnson, Wayne A.; Carder, Justin W.
2012-01-01
A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719
Dickenson, Anthony H.
2016-01-01
Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. PMID:27098028
Patel, Ryan; Dickenson, Anthony H
2016-07-01
Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.
Franz, Marcel; Nickel, Moritz M; Ritter, Alexander; Miltner, Wolfgang H R; Weiss, Thomas
2015-04-01
Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention. Copyright © 2015 the American Physiological Society.
Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J
2017-09-01
Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan
2016-02-01
A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.
Bajic, Dusica; Commons, Kathryn G.
2010-01-01
It is poorly understood if and how pain may modify the effect of opioids on neural systems that contribute to reward and addictive behavior. We hypothesized that the activation of ascending dopaminergic and serotonergic nuclei by morphine is modified by the presence of noxious stimulation. Immunohistochemical double-labeling technique with Fos was used to examine if an intraplantar formalin injection, an acute noxious input, changed the effect of morphine on dopaminergic neurons of the ventral tegmental area (VTA), and serotonergic neurons of the dorsal raphe nucleus (DR). Four groups of rats were analyzed: (1) CONTROL injected with normal saline subcutaneously, (2) rats treated with FORMALIN into the hind paw 30 minutes after normal saline injection, (3) rats injected with MORPHINE sulfate subcutaneously, and (4) rats treated with formalin into the hind paw 30 minutes after morphine injection (MORPHINE/FORMALIN). Following morphine injection, there was an increase in the number of dopaminergic neurons in the VTA with Fos immunolabeling. However, noxious stimulation did not detectably change morphine's effect on Fos expression in VTA dopamine neurons. In contrast, the number of serotonergic neurons containing Fos was increased in the morphine/formalin group compared to all other groups and this effect was topographically selective for the dorsal area of the DR at mid rostro-caudal levels. Therefore, morphine's activation of the VTA, which is associated with motivated behavior and reward seeking, appears similar in the context of pain. However, activation of the ascending serotonin system, which influences mood and has the capacity to modify reward pathways, appears different. In addition, these findings reveal interactions between nociceptive signaling and opioids that contrasts with the notion that opioids simply block access of nociceptive signaling to supraspinal structures. PMID:20026253
Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade
Mills, Holly; Ortega, Amanda; Law, Wenjing; Hapiak, Vera; Summers, Philip; Clark, Tobias
2016-01-01
The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. In Caenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued in npr-17-null animals by the expression of npr-17 or a human κ opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by both nlp-3 and nlp-24, and either nlp-3 or nlp-24 overexpression mimics morphine and suppresses withdrawal. Peptides encoded by nlp-3 act differentially, with only NLP-3.3 mimicking morphine, whereas other nlp-3 peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception in Caenorhabditis elegans through a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals. SIGNIFICANCE STATEMENT Opiates are used extensively to treat chronic pain. In Caenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a α-adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human κ opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate signaling in mammals. PMID:27194330
Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats.
Matsushita, Yumi; Manabe, Miki; Kitamura, Naoki; Shibuya, Izumi
2018-01-01
Transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor channel that responds to multiple types of stimuli, such as heat, acid, mechanical pressure and some vanilloids. Capsaicin is the most commonly used vanilloid to stimulate TRPV1. TRPV1 channels are expressed in dorsal root ganglion neurons that extend to Aδ- and C-fibers and have a role in the transduction of noxious inputs to the skin into the electrical signals of the sensory nerve. Although noradrenergic nervous systems, including the descending antinociceptive system and the sympathetic nervous system, are known to modulate pain sensation, the functional association between TRPV1 and noradrenaline in primary sensory neurons has rarely been examined. In the present study, we examined the effects of noradrenaline on capsaicin-evoked currents in cultured dorsal root ganglion neurons of the rat by the whole-cell voltage clamp method. Noradrenaline at concentrations higher than 0.1 pM significantly reduced the amplitudes of the inward capsaicin currents recorded at -60 mV holding potential. This inhibitory action was reversed by either yohimbine (an α2 antagonist, 10 nM) or propranolol (a β antagonist, 10 nM). The α2 agonists, clonidine (1 pM) and dexmedetomidine (1 pM) inhibited capsaicin currents, and yohimbine (1 nM) reversed the effects of clonidine. The inhibitory action of noradrenaline was not seen in the neurons pretreated with pertussis toxin (100 μg/ml for 24 h) and the neurons dialyzed intracellularly with guanosine 5'- [β-thio] diphosphate (GDPβS, 200 μM), the catalytic subunit of protein kinase A (250 U/ml) or okadaic acid (1 μM). These results suggest that noradrenaline directly acts on dorsal root ganglion neurons to inhibit the activity of TRPV1 depending on the activation of α2-adrenoceptors followed by the inhibition of the adenylate cyclase/cAMP/protein kinase A pathway.
Soto, Cristina; Canedo, Antonio
2011-01-01
Abstract Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3–4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5–2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain. PMID:21746779
Soto, Cristina; Canedo, Antonio
2011-09-01
Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.
Prenylated flavonoids from Desmodium caudatum and evaluation of their anti-MRSA activity.
Sasaki, Hisako; Kashiwada, Yoshiki; Shibata, Hirofumi; Takaishi, Yoshihisa
2012-10-01
Seven prenylated flavonoids and a prenylated chromanochroman derivative, together with eight known flavonoids, were isolated from roots of Desmodium caudatum. The 15 structures were elucidated by extensive spectroscopic analyses. The antibacterial activity of many of other compounds was evaluated against methicillin-resistant Staphylococcus aureus (MRSA: COL and 5) by a disc diffusion method, and the minimum inhibitory concentrations (MICs) to MRSA were determined. Copyright © 2012 Elsevier Ltd. All rights reserved.
Revised Ciprofloxacin Breakpoints for Salmonella: Is it Time to Write an Obituary?
Girish, Revathy; Kumar, Anil; Khan, Sadia; Dinesh, Kavitha R; Karim, Shamsul
2013-11-01
To determine the minimum inhibitory concentration of ciprofloxacin among 50 blood stream isolates of Salmonella enterica. A total of 50 consecutive isolates of Salmonella enterica were tested for susceptibility to antimicrobials using the Kirby Bauer disk diffusion method. Minimum inhibitory concentrations were determined using Hi-Comb strips. All results were interpreted according to the CLSI guidelines. Of the 50 isolates 70%were Salmonella Typhi, 4% Salmonella paratyphi A, 2% Salmonella paratyphi B and the remaining 10% were identified only as Salmonella species. Using the CLSI 2011 breakpoints for disc diffusion, 86% (43/50) were resistant to nalidixic acid(NA), 22% (11/50) to ciprofloxacin, 12% to azithromycin, 6% to cotrimoxazole, 4% to ampicillin and 1% to chloramphenicol. The MIC50 and MIC90 of ciprofloxacin for S.Typhi were 0.181 μg/mL and 5.06 μg/mL respectively. While the same for S. paratyphi A was 0.212μg/mL and 0.228μg/mL respectively. None of the isolates were multi drug resistant and all were susceptible to ceftriaxone. Using the CLSI 2012 revised ciprofloxacin breakpoints for disc diffusion (>31mm) & MIC (<0.06 μg/mL), 90% (45/50) of these isolates were found to be resistant. MIC's of ciprofloxacin should be reported for all salmonella isolates and should be used to guide treatment. Blindly following western guidelines for a disease which is highly endemic in the subcontinent will spell the death knell of a cheap and effective drug in our armamentarium. Therefore it will be too premature to declare that "the concept of using ciprofloxacin in typhoid fever is dead!"
Biofouling: A critical consideration for evaluating in situ biotreatment feasibility
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kaufman, K.A.
1995-09-01
It is recognized by the EPA and many state and local regulatory agencies that in situ bioremedial treatment can be a technically sound and highly cost-effective method for the mitigation of soil and groundwater contamination, and numerous case histories corroborate this belief. Though not widely publicized (for understandable reasons), notable failures of similar treatment attempts can be traced to the consequences of biofouling, resultant from the inappropriate use of in situ treatment technologies. Such consequences can be related to the development of anaerobiosis due to inadequate diffusion of bioavailable oxygen to allow for aerobic metabolism within the contaminated soil matrix.more » Appropriate engineering and hydrogeological considerations of a site`s compatibility with in situ treatment requirements prior to process initiation can preclude the potential for the generation of noxious and/or toxic/explosive gases, as well as toxic endproducts of anaerobic microbial metabolism. Appropriate utilization of hydrogen peroxide, taking into account for the requirement for the enzyme catalase, and the biotoxic nature of hydrogen peroxide to many microorganisms, can minimize the deleterious effects of anaerobiosis and enhance oxidative bioremedial activity.« less
Marini, John J; Gattinoni, Luciano
2008-12-01
To describe the clinical implications of an often neglected mechanism through which localized acute lung injury may be propagated and intensified. Experimental and clinical evidence from the medical literature relevant to the airway propagation hypothesis and its consequences. The diffuse injury that characterizes acute respiratory distress syndrome is often considered a process that begins synchronously throughout the lung, mediated by inhaled or blood-borne noxious agents. Relatively little attention has been paid to possibility that inflammatory lung injury may also begin focally and propagate sequentially via the airway network, proceeding mouth-ward from distal to proximal. Were this true, modifications of ventilatory pattern and position aimed at geographic containment of the injury process could help prevent its generalization and limit disease severity. The purposes of this communication are to call attention to this seldom considered mechanism for extending lung injury that might further justify implementation of low tidal volume/high positive end-expiratory pressure ventilatory strategies for lung protection and to suggest additional therapeutic measures implied by this broadened conceptual paradigm.
Cao, Meng-Li; Meng, Qing-Hao; Zeng, Ming; Sun, Biao; Li, Wei; Ding, Cheng-Jun
2014-06-27
This paper investigates the problem of locating a continuous chemical source using the concentration measurements provided by a wireless sensor network (WSN). Such a problem exists in various applications: eliminating explosives or drugs, detecting the leakage of noxious chemicals, etc. The limited power and bandwidth of WSNs have motivated collaborative in-network processing which is the focus of this paper. We propose a novel distributed least-squares estimation (DLSE) method to solve the chemical source localization (CSL) problem using a WSN. The DLSE method is realized by iteratively conducting convex combination of the locally estimated chemical source locations in a distributed manner. Performance assessments of our method are conducted using both simulations and real experiments. In the experiments, we propose a fitting method to identify both the release rate and the eddy diffusivity. The results show that the proposed DLSE method can overcome the negative interference of local minima and saddle points of the objective function, which would hinder the convergence of local search methods, especially in the case of locating a remote chemical source.
The Postnatal Development of Spinal Sensory Processing
NASA Astrophysics Data System (ADS)
Fitzgerald, Maria; Jennings, Ernest
1999-07-01
The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.
Forecasting system predicts presence of sea nettles in Chesapeake Bay
NASA Astrophysics Data System (ADS)
Brown, Christopher W.; Hood, Raleigh R.; Li, Zhen; Decker, Mary Beth; Gross, Thomas F.; Purcell, Jennifer E.; Wang, Harry V.
Outbreaks of noxious biota, which occur in both aquatic and terrestrial systems, can have considerable negative economic impacts. For example, an increasing frequency of harmful algal blooms worldwide has negatively affected the tourism industry in many regions. Such impacts could be mitigated if the conditions that give rise to these outbreaks were known and could be monitored. Recent advances in technology and communications allow us to continuously measure and model many environmental factors that are responsible for outbreaks of certain noxious organisms. A new prototype ecological forecasting system predicts the likelihood of occurrence of the sea nettle (Chrysaora quinquecirrha), a stinging jellyfish, in the Chesapeake Bay.
Westbrooks, Randy G.
2011-01-01
The U.S. Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW) is a formal partnership between 16 federal agencies that have invasive plant management and regulatory responsibilities for the United States and its territories. Efforts to develop a national level federal interagency committee to coordinate federal activities were initiated by national weed program managers with the USDA Forest Service and the Bureau of Land Management in 1989. FICMNEW was formally established through a Memorandum of Understanding that was signed by agency administrators of member agencies in August, 1994.
Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige
2005-05-01
The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.
Vriens, Joris; Voets, Thomas
2018-05-01
Heat sensation, the ability to detect warm and noxious temperatures, is an ancient and indispensable sensory process. Noxious temperatures can have detrimental effects on the physiology and integrity of cells, and therefore, the detection of environmental hot temperatures is absolutely crucial for survival. Temperature-sensitive ion channels, which conduct ions in a highly temperature-dependent manner, have been put forward as molecular thermometers expressed at the endings of sensory neurons. In particular, several temperature-sensitive members of the transient receptor potential (TRP) superfamily of ion channels have been identified, and a multitude of in vivo studies have shown that the capsaicin-sensitive TRPV1 channel plays a key role as a noxious heat sensor. However, Trpv1-deficient mice display a residual heat sensitivity suggesting the existence of additional heat sensor(s). In this chapter, we provide evidence for the role of the non-selective calcium-permeable TRPM3 ion channel as an additional heat sensor that acts independently of TRPV1, and give an update of the modulation of this channel by various molecular mechanisms. Finally, we compare antagonists of TRPM3 to specific blockers of TRPV1 as potential analgesic drugs to treat pathological pain.
Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight.
Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W; Frye, Mark A
2012-08-15
Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously 'anti-track' the noxious source.
Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight
Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W.; Frye, Mark A.
2012-01-01
SUMMARY Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously ‘anti-track’ the noxious source. PMID:22837456
Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric
2009-04-01
The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals.
Multi-modal pain measurements in infants
Worley, A.; Fabrizi, L.; Boyd, S.; Slater, R.
2012-01-01
A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33 μs and 624 μs respectively) and accuracy (523 μs and 256 μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7 ± 15.7 ms (n = 6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions. PMID:22285660
Multi-modal pain measurements in infants.
Worley, A; Fabrizi, L; Boyd, S; Slater, R
2012-04-15
A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33 μs and 624 μs respectively) and accuracy (523 μs and 256 μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7 ± 15.7 ms (n=6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions. Copyright © 2012 Elsevier B.V. All rights reserved.
Functional neuroanatomy of the central noradrenergic system.
Szabadi, Elemer
2013-08-01
The central noradrenergic neurone, like the peripheral sympathetic neurone, is characterized by a diffusely arborizing terminal axonal network. The central neurones aggregate in distinct brainstem nuclei, of which the locus coeruleus (LC) is the most prominent. LC neurones project widely to most areas of the neuraxis, where they mediate dual effects: neuronal excitation by α₁-adrenoceptors and inhibition by α₂-adrenoceptors. The LC plays an important role in physiological regulatory networks. In the sleep/arousal network the LC promotes wakefulness, via excitatory projections to the cerebral cortex and other wakefulness-promoting nuclei, and inhibitory projections to sleep-promoting nuclei. The LC, together with other pontine noradrenergic nuclei, modulates autonomic functions by excitatory projections to preganglionic sympathetic, and inhibitory projections to preganglionic parasympathetic neurones. The LC also modulates the acute effects of light on physiological functions ('photomodulation'): stimulation of arousal and sympathetic activity by light via the LC opposes the inhibitory effects of light mediated by the ventrolateral preoptic nucleus on arousal and by the paraventricular nucleus on sympathetic activity. Photostimulation of arousal by light via the LC may enable diurnal animals to function during daytime. LC neurones degenerate early and progressively in Parkinson's disease and Alzheimer's disease, leading to cognitive impairment, depression and sleep disturbance.
Hussain, Khaja Amjad; Tarakji, Bassel; Kandy, Binu Purushothaman Panar; John, Jacob; Mathews, Jacob; Ramphul, Vandana; Divakar, Darshan Devang
2015-01-01
Use of plant extracts and phytochemicals with known antimicrobial properties may have great significance in therapeutic treatments. To assess the in vitro antimicrobial potential and also determine the minimum inhibitory concentration (MIC) of Citrus sinensis peel extracts with a view of searching a novel extract as a remedy for periodontal pathogens. Aqueous and ethanol (cold and hot) extracts prepared from peel of Citrus sinensis were screened for in vitro antimicrobial activity against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, using agar well diffusion method. The lowest concentration of every extract considered as the minimal inhibitory concentration (MIC) values were determined for both test organisms. Confidence level and level of significance were set at 95% and 5% respectively. Prevotella intermedia and Porphyromonas gingivalis were resistant to aqueous extracts while Aggregatibacter actinomycetemcomitans was inhibited at very high cncentrations. Hot ethanolic extracts showed significantly higher zone of inhibition than cold ethanolic extract. Minimum inhibitory concentration of hot and cold ethanolic extracts of Citrus sinensis peel ranged between 12-15 mg/ml against all three periodontal pathogens. Both extracts were found sensitive and contain compounds with therapeutic potential. Nevertheless, clinical trials on the effect of these plants are essential before advocating large-scale therapy.
Combined Excitatory and Inhibitory Coupling in a 1-D Array of Belousov-Zhabotinsky Droplets
2014-01-01
with numerical chemical models of the BZ reaction in which components that participate in the excitatory (bromine dioxide and bromous acid) and...verify the transport through the fluorinated oil of chlorine dioxide and several weak acids, including malonic acid. 1. Introduction Recent studies1...finite element model (COMSOLs) of the reaction - diffusion equation in 1-D, 2-D and 3-D, where each drop is modeled as a point, disk or sphere
Chaimanee, V; Thongtue, U; Sornmai, N; Songsri, S; Pettis, J S
2017-11-01
To explore alternative nonchemical control measures against two honeybee pathogens, Paenibacillus larvae and Ascosphaera apis, 37 plant species were screened for antimicrobial activity. The activity of selected plant extracts was screened using an in vitro disc diffusion assay and the minimal inhibitory concentration (MIC) was determined by the broth microdilution method. The results showed that 36 plant extracts had some antibacterial activity on P. larvae by disc diffusion assay. Chromolaena odorata showed the greatest antibacterial activity against P. larvae (MIC 16-64 μg ml -1 ). Of the 37 tested plants, only seven species, Amomum krervanh, Allium sativum, Cinnamomum sp., Piper betle, Piper ribesioides, Piper sarmentosum and Syzygium aromaticum had inhibitory effects on A. apis (MICs of 32-64 μg ml -1 ). The results demonstrated that promising plant extracts were not toxic to adult bees at the concentrations used in this study. The results demonstrate the potential antimicrobial activity of natural products against honeybee diseases caused by P. larvae and A. apis. Chromolaena odorata in particular showed high bioactivity against P. larvae. Further study is recommended to develop these nonchemical treatments against American foulbrood and chalkbrood in honeybees. This work proposes new natural products for the control of American foulbrood and chalkbrood in honeybees. © 2017 The Society for Applied Microbiology.
Cohen-Gilbert, JE; Killgore, WDS; White, CN; Schwab, ZJ; Crowley, DJ; Covell, MJ; Sneider, JT; Silveri, MM
2015-01-01
Social cognition matures dramatically during adolescence and into early adulthood, supported by continued improvements in inhibitory control. During this time, developmental changes in interpreting and responding to social signals such as facial expressions also occur. In the present study, subjects performed a Go No-Go task that required them to respond or inhibit responding based on threat or safety cues present in facial expressions. Subjects (N = 112) were divided into three age groups: adolescent (12–15 years), emerging adult (18–25 years) and adult (26–44 years). Analyses revealed a significant improvement in accuracy on No-Go trials, but not Go trials, during both safe and threat face conditions, with changes evident through early adulthood. In order to better identify the decision-making processes responsible for these changes in inhibitory control, a drift diffusion model (DDM) was fit to the accuracy and reaction time data, generating measures of caution, response bias, nondecision time (encoding + motor response), and drift rate (face processing efficiency). Caution and nondecision time both increased significantly with age while bias towards the Go response decreased. Drift rate analyses revealed significant age-related improvements in the ability to map threat faces to a No-Go response while drift rates on all other trial types were equivalent across age groups. These results suggest both stimulus-independent and stimulus-dependent processes contribute to improvements in inhibitory control in adolescence with processing of negative social cues being specifically impaired by self-regulatory demands. Findings from this novel investigation of emotional responsiveness integrated with inhibitory control may provide useful insights about healthy development that can be applied to better understanding adolescent risk taking behavior and the elevated incidence of related forms of psychopathology during this period of life. PMID:24387267
Inhibition of norsolorinic acid accumulation to Aspergillus parasiticus by marine actinomycetes
NASA Astrophysics Data System (ADS)
Yan, Peisheng; Shi, Cuijuan; Shen, Jihong; Wang, Kai; Gao, Xiujun; Li, Ping
2014-11-01
Thirty-six strains of marine actinomycetes were isolated from a sample of marine sediment collected from the Yellow Sea and evaluated in terms of their inhibitory activity on the growth of Aspergillus parasiticus and the production of norsolorinic acid using dual culture plate assay and agar diffusion methods. Among them, three strains showed strong antifungal activity and were subsequently identified as Streptomyces sp. by 16S rRNA gene sequencing analysis. The supernatant from the fermentation of the MA01 strain was extracted sequentially with chloroform and ethyl acetate, and the activities of the extracts were determined by tip culture assay. The assay results show that both extracts inhibited mycelium growth and toxin production, and the inhibitory activities of the extracts increased as their concentrations increased. The results of this study suggest that marine actinomycetes are biologically important for the control of mycotoxins, and that these bacteria could be used as novel biopesticides against mycotoxins.
Antimicrobial activity of chemically modified dextran derivatives.
Tuchilus, Cristina G; Nichifor, Marieta; Mocanu, Georgeta; Stanciu, Magdalena C
2017-04-01
Cationic amphiphilic dextran derivatives with a long alkyl group attached to the reductive end of the polysaccharide chain and quaternary ammonium groups attached as pendent groups to the main dextran backbone were synthesized and tested for their antimicrobial properties against several bacteria and fungi strains. Dependence of antimicrobial activity on both polymer chemical composition (dextran molar mass, length of end alkyl group and chemical structure of ammonium groups) and type of microbes was highlighted by disc-diffusion method (diameter of inhibition zone) and broth microdilution method (minimum inhibitory concentrations). Polymers had antimicrobial activity for all strains studied, except for Pseudomonas aeruginosa ATCC 27853. The best activity against Staphylococcus aureus (Minimun Inhibitory Concentration 60μg/mL) was provided by polymers obtained from dextran with lower molecular mass (Mn=4500), C 12 H 25 or C 18 H 37 end groups, and N,N-dimethyl-N-benzylammonium pendent groups. Copyright © 2017 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Özbek, Neslihan; Alyar, Saliha; Memmi, Burcu Koçak; Gündüzalp, Ayla Balaban; Bahçeci, Zafer; Alyar, Hamit
2017-01-01
2-Hydroxyacetophenone-N-methyl p-toluenesulfonylhydrazone (afptsmh) derived from p-toluenesulfonicacid-1-methylhydrazide (ptsmh) and its Co(II), Pd(II), Pt(II) complexes were synthesized for the first time. Synthesized compounds were characterized by spectroscopic methods (FT-IR, 1Hsbnd 13C NMR, LC-MS, UV-vis), magnetic susceptibility and conductivity measurements. 1H and 13C shielding tensors for crystal structure of ligand were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The vibrational band assignments were performed at B3LYP/6-311++G(d,p) theory level combined with scaled quantum mechanics force field (SQMFF) methodology. The antibacterial activities of synthesized compounds were studied against some Gram positive and Gram negative bacteria by using microdilution and disc diffusion methods. In vitro enzyme inhibitory effects of the compounds were measured by UV-vis spectrophotometer. The enzyme activities against human carbonic anhydrase II (hCA II) were evaluated as IC50 (the half maximal inhibitory concentration) values. It was found that afptsmh and its metal complexes have inhibitory effects on hCA II isoenzyme. General esterase activities were determined using alpha and beta naphtyl acetate substrates (α- and β-NAs) of Drosophila melanogaster (D. melanogaster). Activity results show that afptsmh does not strongly affect the bacteria strains and also shows poor inhibitory activity against hCAII isoenzyme whereas all complexes posses higher biological activities.
Inhibitory rTMS applied on somatosensory cortex in Wilson's disease patients with hand dystonia.
Lozeron, Pierre; Poujois, Aurélia; Meppiel, Elodie; Masmoudi, Sana; Magnan, Thierry Peron; Vicaut, Eric; Houdart, Emmanuel; Guichard, Jean-Pierre; Trocello, Jean-Marc; Woimant, France; Kubis, Nathalie
2017-10-01
Hand dystonia is a common complication of Wilson's disease (WD), responsible for handwriting difficulties and disability. Alteration of sensorimotor integration and overactivity of the somatosensory cortex have been demonstrated in dystonia. This study investigated the immediate after effect of an inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on the writing function in WD patients with hand dystonia. We performed a pilot prospective randomized double-blind sham-controlled crossover rTMS study. A 20-min 1-Hz rTMS session, stereotaxically guided, was applied over the left somatosensory cortex in 13 WD patients with right dystonic writer's cramp. After 3 days, each patient was crossed-over to the alternative treatment. Patients were clinically evaluated before and immediately after each rTMS session with the Unified Wilson's Disease rating scale (UWDRS), the Writers' Cramp Rating Scale (WCRS), a specifically designed scale for handwriting difficulties in Wilson's disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual analog scale (VAS) for handwriting discomfort. No significant change in UWDRS, WCRS, VAS, or FAR scores was observed in patients treated with somatosensory inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with UWDRS (r = -0.6; P = 0.02), but not with the WCRS score, disease duration, MRI diffusion lesions, or with atrophy scores. In our experimental conditions, a single inhibitory rTMS session applied over somatosensory cortex did not improve dystonic writer cramp in WD patients.
Anesthetic effects on fictive locomotion in the rat isolated spinal cord
Jinks, Steven L.; Andrada, Jason; Satter, Omar
2011-01-01
General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced vs noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion via a GABAA-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation. PMID:21817927
Responsibility modulates pain-matrix activation elicited by the expressions of others in pain
Cui, Fang; Abdelgabar, Abdel-Rahman; Keysers, Christian; Gazzola, Valeria
2015-01-01
Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured. PMID:25800210
Goldspink, Lauren K; Mollinger, Joanne L; Barnes, Tamsin S; Groves, Mitchell; Mahony, Timothy J; Gibson, Justine S
2015-02-01
This study investigated antimicrobial resistance traits, clonal relationships and epidemiology of Histophilus somni isolated from clinically affected cattle in Queensland and New South Wales, Australia. Isolates (n = 53) were subjected to antimicrobial susceptibility testing against six antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tetracycline, tilmicosin and tulathromycin) using disc diffusion and minimum inhibitory concentration (MIC) assays. Clonal relationships were assessed using repetitive sequence PCR and descriptive epidemiological analysis was performed. The H. somni isolates appeared to be geographically clonal, with 27/53 (47%) isolates grouping in one cluster from one Australian state. On the basis of disc diffusion, 34/53 (64%) isolates were susceptible to all antimicrobial agents tested; there was intermediate susceptibility to tulathromycin in 12 isolates, tilmicosin in seven isolates and resistance to tilmicosin in one isolate. Using MIC, all but one isolate was susceptible to all antimicrobial agents tested; the non-susceptible isolate was resistant to tetracycline, but this MIC result could not be compared to disc diffusion, since there are no interpretative guidelines for disc diffusion for H. somni against tetracycline. In this study, there was little evidence of antimicrobial resistance in H. somni isolates from Australian cattle. Disc diffusion susceptibility testing results were comparable to MIC results for most antimicrobial agents tested; however, results for isolates with intermediate susceptibility or resistance to tilmicosin and tulathromycin on disc diffusion should be interpreted with caution in the absence of MIC results. Copyright © 2014 Elsevier Ltd. All rights reserved.
Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees
Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela
2016-01-01
The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected. PMID:27534586
Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees.
Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela
2016-08-18
The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected.
Toda, Hiroko; Maruyama, Hitoshi; Budgell, Brian; Kurosawa, Mieko
2008-08-01
In urethane-anesthetized, artificially ventilated rats, alterations in dorsal spinal cord blood flow (SCBF) at the L4-6 level were measured with laser Doppler flowmetry in response to noxious mechanical cutaneous stimulation (pinching) of either a forepaw or a hindpaw. The stimulation was delivered ipsilaterally or contralaterally to the site of blood flow measurement. Pinching of the forepaw or the hindpaw on either side increased mean arterial pressure (MAP) to the same degree. However, the SCBF response to pinching of the ipsilateral hindpaw was significantly greater than that to other stimulations. These responses were not influenced by denervation of the baroreceptors. The responses of SCBF to pinching of the ipsilateral hindpaw persisted both after treatment with phenoxybenzamine and after spinalization at the C1-2 level, whereas the responses to pinching at other sites disappeared. The responses of MAP to stimulation at all four sites became negligible after treatment with phenoxybenzamine and after spinalization at the C1-2 level. These results indicate that noxious mechanical stimulation of the skin produces increases in SCBF via two mechanisms: one is via an elevation of systemic arterial pressure; the other is via a localized spinal mechanism evoked by ipsilateral, segmental inputs.
The noxious effects of electroimmobilization in adult Holstein cows: a pilot study.
Pascoe, P J; McDonell, W N
1986-01-01
Ten adult Holstein cows were used in an experiment to determine whether the induction of electroimmobilization was a noxious event. The cows were halter trained and accustomed to being led into a set of stocks. The time taken for the cattle to walk the last ten metres into the stocks was recorded. The heart rate of the cow was recorded for a three minute period prior to a ten second exposure to a high pitched sound (the conditioning stimulus). Measurements were collected for three repetitions and then the cows were assigned to two groups of five. One group was immobilized for 30 seconds using a commercial electroimmobilizer, the other group was not treated. This procedure was repeated ten times over a period of eight days. The cows were then exposed to the conditioning stimulus and their response observed. The treated group took significantly (P less than 0.05) longer to get into the stocks and the regression slopes for heart rate were significantly different from the control group. The treated cows responded to the conditioning stimulus at five and nine months after the end of the conditioning period. Adult Holstein cows regarded electroimmobilization as a noxious event and were very strongly conditioned to this stimulus. PMID:3756681
7 CFR 360.200 - Designation of noxious weeds.
Code of Federal Regulations, 2010 CFR
2010-01-01
... mantegazzianum Sommier & Levier (giant hogweed) Homeria spp. Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Raeuschel (cogongrass) Ischaemum rugosum Salisbury (murainograss) Leptochloa...
Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception
Lindstedt, Fredrik; Karshikoff, Bianka; Schalling, Martin; Olgart Höglund, Caroline; Ingvar, Martin; Lekander, Mats; Kosek, Eva
2012-01-01
Background Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities. Methods Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C–49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed. Results Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged. Conclusion/Significance To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a ‘hypo- to hyperalgesic’ response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted. PMID:22952650
Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.
Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H
2015-12-01
Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Hagman, Ragnvi; Stridsberg, Mats
2015-01-01
Objectives: Biomarkers representing sympathetic tone and the surgical stress response are measured to objectively evaluate surgical techniques and anaesthetic protocols. If a part of the intraoperative procedure is repeated on the contralateral organ, one animal may potentially serve as its own control and, if so, may minimize the problem of individual differences of the stress response to anaesthesia and surgery. This study aimed to investigate the use of chromogranin A for measurement of the intraoperative sympathetic tone. Additional aims were to investigate chromogranin A and cortisol as indicators of the intraoperative surgical stress response caused by repeated noxious stimuli in dogs subjected to ovariohysterectomy and thereby to investigate the possibility of one dog serving as its own control. Methods: Experiments were carried out on 10 dogs subjected to ovariohysterectomy. Perioperative blood samples (0–6) were collected after premedication, immediately before induction of anaesthesia (0), after induction of anaesthesia and before incision (1), before (2) and after (3) removal of the first ovary, after a 15-min pause before removal of the second ovary (4), after removal of the second ovary (5) and after closing the abdomen (6). Plasma chromogranin A and cortisol were analysed. Results: Plasma chromogranin A did not change. Plasma cortisol concentration did not change between before anaesthesia and opening of the abdomen. Plasma cortisol increased at removal of the first ovary. Cortisol did not change at removal of the second ovary but remained increased compared to initial sample. Conclusion: The results suggest chromogranin A is a poor indicator of intraoperative sympathetic tone during elective surgery in dogs. Cortisol measurement was useful for assessment of intraoperative noxious stimuli. However, at these test conditions, neither plasma chromogranin A nor plasma cortisol was useful for assessment of repeated intraoperative noxious stimuli where one dog served as its own control. PMID:26770773
Stockman, Jonathan; Weber, Ernest Scott P; Kass, Philip H; Pascoe, Peter J; Paul-Murphy, Joanne
2013-01-01
To evaluate the physiological effect and response to noxious stimulation at five concentrations of MS-222 in koi (Cyprinus carpio). Prospective experimental study. Twenty-one healthy adult unknown sex koi fish weighing mean 450±SD 120 g. Each fish was exposed to five different concentrations of MS-222 (50, 70, 110, 150 and 190 mg L(-1) ) in a random sequence during the same anaesthetic event. For each concentration of MS-222, vital functions such as heart rate (HR) (via Doppler) and opercular rate (OpR) were recorded after a standardized induction period. Response to two noxious stimuli in the form of haemostat clamp pressure applied on the tail and the lip was evaluated, and blood was drawn to measure biochemical and blood gas values. Decrease in response to noxious stimulation with an increase of MS-222 concentration both for the lip (p=0.0027) and the tail (p<0.0001) stimulus was observed. Biochemical values were unaffected by the concentration of MS-222 with the exception of lactate concentration which was weakly correlated with the duration of anaesthesia (r=0.31, p<0.001) and the number of times the fish was clamped or bled prior to sampling (r=0.23, p<0.001). Opercular rate decreased with the increase in anaesthetic concentration, and HR was not affected. Our results indicated a decrease in response to stimulus and a decrease in OpR that were associated with increased concentrations of MS-222. This may assist in establishing anaesthetic protocols using MS-222 in fish and supports the use of supramaximal pressure stimuli to teleost fish under variable MS-222 concentrations as a model for future studies. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.
Sucrose-induced analgesia during early life modulates adulthood learning and memory formation.
Nuseir, Khawla Q; Alzoubi, Karem H; Alabwaini, Jehad; Khabour, Omar F; Kassab, Manal I
2015-06-01
This study is aimed at examining the long-term effects of chronic pain during early life (postnatal day 0 to 8weeks), and intervention using sucrose, on cognitive functions during adulthood in rats. Pain was induced in rat pups via needle pricks of the paws. Sucrose solution or paracetamol was administered for analgesia before the paw prick. Control groups include tactile stimulation to account for handling and touching the paws, and sucrose alone was used. All treatments were started on day one of birth and continued for 8weeks. At the end of the treatments, behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM), as well as pain threshold via foot-withdrawal response to a hot plate apparatus. Additionally, the hippocampus was dissected, and blood was collected. Levels of neurotrophins (BDNF, IGF-1 and NT-3) and endorphins were assessed using ELISA. The results show that chronic noxious stimulation resulted in comparable foot-withdrawal latency between noxious and tactile groups. On the other hand, pretreatment with sucrose or paracetamol increased pain threshold significantly both in naive rats and noxiously stimulated rats (P<0.05). Chronic pain during early life impaired short-term memory, and sucrose treatment prevented such impairment (P<0.05). Sucrose significantly increased serum levels of endorphin and enkephalin. Chronic pain decreased levels of BDNF in the hippocampus and this decrease was prevented by sucrose and paracetamol treatments. Hippocampal levels of NT-3 and IGF-1 were not affected by any treatment. In conclusion, chronic pain induction during early life induced short memory impairment, and pretreatment with sucrose prevented this impairment via mechanisms that seem to involve BDNF. As evident in the results, sucrose, whether alone or in the presence of pre-noxious stimulation, increases pain threshold in such circumstances; most likely via a mechanism that involves an increase in endogenous opioids. Copyright © 2015 Elsevier Inc. All rights reserved.
Takechi, Kenichi; Carstens, Mirela Iodi; Klein, Amanda H.; Carstens, E.
2013-01-01
Background Propofol (2,6-diisopropylphenol) is an IV anesthetic used for general anesthesia. Recent evidence suggests that propofol-anesthetized patients experience less postoperative pain, and that propofol has analgesic properties when applied topically. We presently investigated the antinociceptive effects of topical propofol using behavioral and single-unit electrophysiological methods in rats. Methods In behavioral experiments with rats, we assessed the effect of topical hindpaw application of propofol (1–25%) on heat and mechanically evoked paw withdrawals. In electrophysiology experiments we recorded from lumbar dorsal horn wide dynamic range (WDR)-type neurons in pentobarbital-anesthetized rats. We assessed the effect of topical application of propofol to the ipsilateral hindpaw on neuronal responses elicited by noxious heat, cold and mechanical stimuli. We additionally tested if propofol blocks heat sensitization of paw withdrawals and WDR neuronal responses induced by topical application of allyl isothiocyanate (AITC; mustard oil). Results Topical application of propofol (1–25%) significantly increased the mean latency of the thermally evoked hindpaw withdrawal reflex on the treated (but not opposite) side in a concentration-dependent manner, with no effect on mechanically evoked hindpaw withdrawal thresholds. Propofol also prevented shortening of paw withdrawal latency induced by AITC. In electrophysiological experiments, topical application of 10 and 25% propofol, but not 1% propofol or vehicle (10% intralipid), to the ipsilateral hindpaw significantly attenuated the magnitude of responses of WDR neurons to noxious heating of glabrous hindpaw skin with no significant change in thermal thresholds. Maximal suppression of noxious heat-evoked responses was achieved 15-min after application followed by recovery to the pre-propofol baseline by 30 min. Responses to skin cooling or graded mechanical stimuli were not significantly affected by any concentration of propofol. Topical application of AITC enhanced the noxious heat-evoked response of dorsal horn neurons. This enhancement of heat-evoked responses was attenuated when 10% propofol was applied topically after application of AITC. Conclusions The results indicate that topical propofol inhibits responses of WDR neurons to noxious heat consistent with analgesia, and reduced AITC sensitization of WDR neurons consistent with an antihyperalgesic effect. These results are consistent with clinical studies demonstrating reduced postoperative pain in surgical patients anesthetized with propofol. The mechanism of analgesic action of topical propofol is not clear, but may involve desensitization of TRPV1 or TRPA1 receptors expressed in peripheral nociceptive nerve endings, engagement of endocannabinoids, or activation of peripheral gamma-aminobutyric acid A receptors. PMID:23337417
7 CFR 361.6 - Noxious weed seeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... & Levier Hydrilla verticillata (Linnaeus f.) Royle Hygrophila polysperma T. Anderson Imperata brasiliensis Trinius Imperata cylindrica (Linnaeus) Palisot de Beauvois Inula britannica Linnaeus Ipomoea aquatica...
7 CFR 360.200 - Designation of noxious weeds.
Code of Federal Regulations, 2014 CFR
2014-01-01
... mantegazzianum Sommier & Levier (giant hogweed) Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Palisot de Beauvois (cogongrass) Inula britannica Linnaeus (British elecampane, British...
7 CFR 361.6 - Noxious weed seeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... & Levier Hydrilla verticillata (Linnaeus f.) Royle Hygrophila polysperma T. Anderson Imperata brasiliensis Trinius Imperata cylindrica (Linnaeus) Palisot de Beauvois Inula britannica Linnaeus Ipomoea aquatica...
7 CFR 361.6 - Noxious weed seeds.
Code of Federal Regulations, 2014 CFR
2014-01-01
... & Levier Hydrilla verticillata (Linnaeus f.) Royle Hygrophila polysperma T. Anderson Imperata brasiliensis Trinius Imperata cylindrica (Linnaeus) Palisot de Beauvois Inula britannica Linnaeus Ipomoea aquatica...
7 CFR 360.200 - Designation of noxious weeds.
Code of Federal Regulations, 2013 CFR
2013-01-01
... mantegazzianum Sommier & Levier (giant hogweed) Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Palisot de Beauvois (cogongrass) Inula britannica Linnaeus (British elecampane, British...
7 CFR 360.200 - Designation of noxious weeds.
Code of Federal Regulations, 2012 CFR
2012-01-01
... mantegazzianum Sommier & Levier (giant hogweed) Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Palisot de Beauvois (cogongrass) Inula britannica Linnaeus (British elecampane, British...
Evaluation of the effectiveness of peracetic acid in the sterilization of dental equipment.
Ceretta, R; Paula, M M S; Angioletto, Ev; Méier, M M; Mitellstädt, F G; Pich, C T; Junior, S A; Angioletto, E
2008-01-01
To evaluate the effectiveness of peracetic acid in the microbiological sterilisation of dental materials. Peracetic acid solution was evaluated at concentrations of 800, 1500 and 2500 ppm. At these concentrations, it was determined whether peracetic acid caused corrosion to dental instruments and induced cellular mutagenicity and cytotoxicity. In addition, the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC), agar diffusion and diffusion by well method, were also verified. The corrosion rate, calculated from potentiodynamic assays was 10(-6) cm/year, indicating that the product does not damage equipment. The sterilisation capacity of peracetic acid at 2500 ppm was the best. The comet assay indicated genotoxic activity at 2500 ppm. This study demonstrated the effectiveness of peracetic acid for sterilizing dental equipment, providing another alternative for the prevention of infections in clinics.
An experimental design method leading to chemical Turing patterns.
Horváth, Judit; Szalai, István; De Kepper, Patrick
2009-05-08
Chemical reaction-diffusion patterns often serve as prototypes for pattern formation in living systems, but only two isothermal single-phase reaction systems have produced sustained stationary reaction-diffusion patterns so far. We designed an experimental method to search for additional systems on the basis of three steps: (i) generate spatial bistability by operating autoactivated reactions in open spatial reactors; (ii) use an independent negative-feedback species to produce spatiotemporal oscillations; and (iii) induce a space-scale separation of the activatory and inhibitory processes with a low-mobility complexing agent. We successfully applied this method to a hydrogen-ion autoactivated reaction, the thiourea-iodate-sulfite (TuIS) reaction, and noticeably produced stationary hexagonal arrays of spots and parallel stripes of pH patterns attributed to a Turing bifurcation. This method could be extended to biochemical reactions.
Lima, Edna T.; Andreatti Filho, Raphael L.; Okamoto, Adriano S.; Noujaim, José C.; Barros, Mércia R.; Crocci, Adalberto J.
2007-01-01
To determine the inhibitory capacity of lactic acid bacteria due to the action of antagonistic substances, we tested 474 isolates of Lactobacillus from the crop and cecum of chickens against gram-positive and gram-negative indicator microorganisms by the spot-on-the-lawn and well-diffusion antagonism methods. Of the 474 isolates, 265 demonstrated antimicrobial activity against the indicator microorganisms. Isolates identified as L. reuteri, L. salivarius, or Lactobacillus spp. inhibited Enterococcus faecalis, E. faecium, Listeria monocytogenes, and Salmonella spp. but not L. casei, L. delbrueckii, L. fermentum, or L. helveticus by the well-diffusion simultaneous antagonism method under anaerobic incubation conditions. The antagonistic substances produced by some of the Lactobacillus isolates were inactivated after treatment by proteolytic enzymes, which suggested that the substances could be antimicrobial peptides or bacteriocins. PMID:17479773
Gestal, J J
1987-01-01
Except for infectious diseases all the main occupational hazards affecting health workers are reviewed: accidents (explosions, fires, electrical accidents, and other sources of injury); radiation (stochastic and non-stochastic effects, protective measures, and personnel most at risk); exposure to noxious chemicals, whose effects may be either local (allergic eczema) or generalised (cancer, mutations), particular attention being paid to the hazards presented by formol, ethylene oxide, cytostatics, and anaesthetic gases; drug addiction (which is more common among health workers than the general population) and psychic problems associated with promotion, shift work, and emotional stress; and assault (various types of assault suffered by health workers, its causes, and the characterisation of the most aggressive patients). PMID:3307896
Hibbing, Michael E; Fuqua, Clay
2012-06-01
Environmental biofilms often contain mixed populations of different species. In these dense communities, competition between biofilm residents for limited nutrients such as iron can be fierce, leading to the evolution of competitive factors that affect the ability of competitors to grow or form biofilms. We have discovered a compound(s) present in the conditioned culture fluids of Pseudomonas aeruginosa that disperses and inhibits the formation of biofilms produced by the facultative plant pathogen Agrobacterium tumefaciens. The inhibitory activity is strongly induced when P. aeruginosa is cultivated in iron-limited conditions, but it does not function through iron sequestration. In addition, the production of the biofilm inhibitory activity is not regulated by the global iron regulatory protein Fur, the iron-responsive extracytoplasmic function σ factor PvdS, or three of the recognized P. aeruginosa quorum-sensing systems. In addition, the compound(s) responsible for the inhibition and dispersal of A. tumefaciens biofilm formation is likely distinct from the recently identified P. aeruginosa dispersal factor, cis-2-decenoic acid (CDA), as dialysis of the culture fluids showed that the inhibitory compound was larger than CDA and culture fluids that dispersed and inhibited biofilm formation by A. tumefaciens had no effect on biofilm formation by P. aeruginosa.
Hibbing, Michael E.; Fuqua, Clay
2013-01-01
Environmental biofilms often contain mixed populations of different species. In these dense communities, competition between biofilm residents for limited nutrients such as iron, can be fierce, leading to the evolution of competitive factors that affect the ability of competitors to grow or form biofilms. We have discovered a compound(s) present in the conditioned culture fluids of Pseudomonas aeruginosa that disperses and inhibits the formation of biofilms produced by the facultative plant pathogen Agrobacterium tumefaciens. The inhibitory activity is strongly induced when P. aeruginosa is cultivated in iron-limited conditions, but it does not function through iron sequestration. In addition, the production of the inhibitory activity is not regulated by the global iron regulatory protein Fur, the iron-responsive extra-cytoplasmic function (ECF) σ factor PvdS, or three of the recognized P. aeruginosa quorum sensing systems. In addition, the compound(s) responsible for the inhibition and dispersal of A. tumefaciens biofilm formation is likely distinct from the recently identified P. aeruginosa dispersal factor, cis-2-decenoic acid (CDA), as dialysis of the culture fluids showed that the inhibitory compound was larger than CDA and culture fluids that dispersed and inhibited biofilm formation by A. tumefaciens had no effect on biofilm formation by P. aeruginosa. PMID:22105093
Biphasic interactions between a cationic dendrimer and actin.
Ruenraroengsak, Pakatip; Florence, Alexander T
2010-12-01
Gene delivery systems face the problem not only of the route toward the cell and tissues in question, but also of the molecularly crowded environment of both the cytoplasm and the nucleus itself. One of the physical barriers in the cytoplasm for diffusing nanoparticles is an actin network. Here, we describe the finding that a self-fluorescent sixth generation cationic dendrimer (6 nm in diameter) interacts reversibly and possibly electrostatically with actin filaments in vitro. Not only does this interaction slow the diffusion of the dendrimer but it also affects actin polymerization in a biphasic manner. At low concentrations the dendrimer behaves like a G-binding actin protein, retarding actin polymerization, whereas at high concentrations the dendrimer acts as a nucleating protein accelerating the polymerization. Thus in vivo the diffusion of a dendrimer carrier such as this has both physical and chemical elements: by decreasing polymerization it might accelerate its own transport, and by enhancing actin polymerization retard it. This finding suggests that such a dendrimer may have a role as an anticancer agent through its inhibitory effect on actin polymerization.
The in-vitro antimicrobial activities of some medicinal plants from Cameroon.
Gangoué-Piéboji, J; Pegnyemb, D E; Niyitegeka, D; Nsangou, A; Eze, N; Minyem, C; Mbing, J Ngo; Ngassam, P; Tih, R Ghogomu; Sodengam, B L; Bodo, B
2006-04-01
The antimicrobial activities of 10 plant species (Voacanga africana, Crepis cameroonica, Plagiostyles africana, Crotalaria retusa, Mammea africana, Lophira lanceolata, Ochna afzelii, Ouratea elongata, Ou. flava and Ou. sulcata), each of which is currently used in the traditional medicine of Cameroon, were investigated in vitro. The activities of a methanol extract of each plant were tested, in disc-diffusion assays, against 37 reference or laboratory strains of seven species of microorganism (Staphylococcus aureus, S. epidermidis, Enterococcus hirae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans). The minimal inhibitory concentrations of each extract were then estimated, against each of the more susceptible microorganisms (i.e. those giving an inhibition zone measuring at least 9 mm in diameter in the disc-diffusion assays), by agar dilution. Although, in the disc-diffusion assays, each of the 10 methanol extracts investigated displayed some degree of antimicrobial activity against at least one species of microorganism, no activity against the Gram-negative bacteria (Es. coli, K. pneumoniae and Ps. aeruginosa) was observed. The extract with the greatest antimicrobial activity was that of Pl. africana (Euphorbiaceae).
Kaur, Gurinder J; Arora, Daljit S
2009-01-01
Background Anethum graveolens Linn., Foeniculum vulgare Mill. and Trachyspermum ammi L. are widely used traditional medicinal plants to treat various ailments. To provide a scientific basis to traditional uses of these plants, their aqueous and organic seed extracts, as well as isolated phytoconstituents were evaluated for their antibacterial potential. Methods Antibacterial activity of aqueous and organic seed extracts was assessed using agar diffusion assay, minimum inhibitory concentration and viable cell count studies; and their antibacterial effect was compared with some standard antibiotics. The presence of major phytoconstituents was detected qualitatively and quantitatively. The isolated phytoconstituents were subjected to disc diffusion assay to ascertain their antibacterial effect. Results Hot water and acetone seed extracts showed considerably good antibacterial activity against all the bacteria except Klebsiella pneumoniae and one strain of Pseudomonas aeruginosa. Minimum inhibitory concentration for aqueous and acetone seed extracts ranged from 20–80 mg/ml and 5–15 mg/ml respectively. Viable cell count studies revealed the bactericidal nature of the seed extracts. Statistical analysis proved the better/equal efficacy of some of these seed extracts as compared to standard antibiotics. Phytochemical analysis showed the presence of 2.80 – 4.23% alkaloids, 8.58 – 15.06% flavonoids, 19.71 – 27.77% tannins, 0.55–0.70% saponins and cardiac glycosides. Conclusion Antibacterial efficacy shown by these plants provides a scientific basis and thus, validates their traditional uses as homemade remedies. Isolation and purification of different phytochemicals may further yield significant antibacterial agents. PMID:19656417
Redwan, Elrashdy M; El-Baky, Nawal Abd; Al-Hejin, Ahmed M; Baeshen, Mohammed N; Almehdar, Hussein A; Elsaway, Abdulrahman; Gomaa, Abu-Bakr M; Al-Masaudi, Saad Berki; Al-Fassi, Fahad A; AbuZeid, Isam Eldin; Uversky, Vladimir N
2016-01-01
Methicillin-resistant Staphylococcus aureus (MRSA) causes major healthcare problems in many countries, as it is present as several hospital- and community-associated strains. Hospital-associated MRSA is one of the most prevalent nosocomial pathogens throughout the world and infections caused by community-acquired MRSA are rising. This emphasizes the need for new and efficient anti-MRSA agents. We evaluated the antibacterial effects of camel lactoferrin (cLf) and human lactoferrin (hLf) alone and in combination with several antibiotics against MRSA. Antimicrobials were tested against MRSA and an S. aureus control strain by the agar disc diffusion method. The minimum inhibitory concentration (MIC) was determined for antimicrobials by the broth microdilution method. Synergy between cLf or hLf and antibiotics was examined by checkerboard and time-kill assays. The agar disc diffusion assay showed that MRSA growth was inhibited by cLf at 0.25-3 mg/ml and hLf at 1-3 mg/ml. cLf demonstrated 3 times higher inhibitory activity against MRSA than hLf in terms of MIC values (250 vs. 750 μg/ml, respectively). Biotinylated cLf was recognized by two membrane proteins of MRSA, 66-67 KDa. Combinations of cLf or hLf and oxacillin or vancomycin at sub-MIC levels enhanced in vitro antibacterial activity against MRSA compared with each agent alone. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Ciclopirox delivery into the human nail plate using novel lipid diffusion enhancers.
Hafeez, Farhaan; Hui, Xiaoying; Selner, Marc; Rosenthal, Bert; Maibach, Howard
2014-06-01
Onychomycosis is a common fungal infection of the nail plate and bed that affects up to 14% of the population and can have a substantial impact on the quality of life of those affected. This study compared the onychopharmacokinetics, nail absorption, nail distribution, and nail penetration of [(14)C]-ciclopirox dissolved in novel lipid diffusion enhancers with that of a commercial ciclopirox nail lacquer using the in vitro finite dose model. The penetration rate of ciclopirox was determined by applying doses of topical formulation twice daily to human nail plates for 11 d. Drug absorption was then measured by monitoring its rate of appearance in each nail layer and in the cotton pad/nail supporting bed. After a multiple day treatment, cumulative concentrations of ciclopirox formulated with lipid enhancers in the deep nail layer and the nail bed were significantly greater than cumulative concentrations of the commercial ciclopirox lacquer (p < 0.001) as well as several orders of magnitude greater than the minimal inhibitory concentration (MIC) deemed necessary to inhibit the growth of the causative dermatophyte species. When formulated with lipid enhancers, the amount of ciclopirox in the ventral/intermediate layer and supporting bed dramatically exceed the inhibitory concentration of ciclopirox for the most common onychomycosis organisms. These results suggest that topical ciclopirox with lipid enhancers has the potential to be an effective topical treatment for onychomycosis, and the lipidic pathway of the nail can be utilized as a means of effective transungual delivery.
33 CFR 151.1003 - Applicability.
Code of Federal Regulations, 2014 CFR
2014-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1003 Applicability. (a) Except as...
33 CFR 151.1003 - Applicability.
Code of Federal Regulations, 2013 CFR
2013-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1003 Applicability. (a) Except as...
33 CFR 151.1003 - Applicability.
Code of Federal Regulations, 2012 CFR
2012-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1003 Applicability. (a) Except as...
33 CFR 151.1003 - Applicability.
Code of Federal Regulations, 2011 CFR
2011-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1003 Applicability. (a) Except as...
33 CFR 151.1003 - Applicability.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1003 Applicability. (a) Except as...
Inturri, R; Stivala, A; Furneri, P M; Blandino, G
2016-12-01
The aim of this study was to test the inhibitory effect of supernatants of broth cultures of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001, both individually and in combination, against Gram-negative strains (uropathogens, enteropathogens and a reference strain). Moreover, in vitro protection of B. longum BB536 and L. rhamnosus HN001, both individually and in combination, against pathogen adhesion to HT-29 cell line, was investigated. The inhibitory activity was performed by the agar diffusion test and in vitro antagonistic activity against pathogen adhesion to human epithelial intestinal HT-29 cells was performed using standardized culture techniques. The study showed that B. longum BB536 and L. rhamnosus HN001, individually and in combination have inhibitory activity against the majority of the Gram negative strains tested. Furthermore, the results showed that both probiotic strains have a good capacity to inhibit pathogenic adhesion to HT-29 cells. Moreover, the ability of B. longum BB536 and L. rhamnosus HN001 to inhibit pathogenic adhesion increased when they were used in combination. The combination of B. longum BB536 and L. rhamnosus HN001 showed inhibitory activity against Gram-negatives and an improved ability to reduce their adhesion properties and to compete with them. The simultaneous presence of the two-probiotic strains could promote competitive mechanisms able to reduce the adhesion properties of pathogen strains and have an important ecological role within the highly competitive environment of the human gut.
Das, Hiranmoy; Wang, Zhihui; Niazi, M Khalid Khan; Aggarwal, Reeva; Lu, Jingwei; Kanji, Suman; Das, Manjusri; Joseph, Matthew; Gurcan, Metin; Cristini, Vittorio
2013-01-01
Molecular-focused cancer therapies, e.g., molecularly targeted therapy and immunotherapy, so far demonstrate only limited efficacy in cancer patients. We hypothesize that underestimating the role of biophysical factors that impact the delivery of drugs or cytotoxic cells to the target sites (for associated preferential cytotoxicity or cell signaling modulation) may be responsible for the poor clinical outcome. Therefore, instead of focusing exclusively on the investigation of molecular mechanisms in cancer cells, convection-diffusion of cytotoxic molecules and migration of cancer-killing cells within tumor tissue should be taken into account to improve therapeutic effectiveness. To test this hypothesis, we have developed a mathematical model of the interstitial diffusion and uptake of small cytotoxic molecules secreted by T-cells, which is capable of predicting breast cancer growth inhibition as measured both in vitro and in vivo. Our analysis shows that diffusion barriers of cytotoxic molecules conspire with γδ T-cell scarcity in tissue to limit the inhibitory effects of γδ T-cells on cancer cells. This may increase the necessary ratios of γδ T-cells to cancer cells within tissue to unrealistic values for having an intended therapeutic effect, and decrease the effectiveness of the immunotherapeutic treatment.
33 CFR 151.1502 - Applicability.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in the Great Lakes and Hudson...
33 CFR 151.1502 - Applicability.
Code of Federal Regulations, 2011 CFR
2011-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in the Great Lakes and Hudson...
Inhibitory Effects of Pterodon emarginatus Bean Oil and Extract on Staphylococcus aureus
Mendes, V. S.; Sant'Anna, J. B.; Oliveira, S. C. C.; Maldonade, Iriani Rodrigues; Machado, Eleuza Rodrigues
2017-01-01
Background: Pterodon emarginatus is a tree of the Brazilian Savannah. The beans of this tree are used in folk medicine as anti-inflammatory preparations, especially for infections caused by Staphylococcus aureus. These bacteria can cause simple infections or serious illnesses such as pneumonia, meningitis, endocarditis, toxic shock syndrome, septicemia, and others. Objective: This study had the goal of verifying the effect of the essential oil (OE) from P. emarginatus on the inhibition of S. aureus in culture medium, i.e., “ in vitro” tests. Materials and Methods: The vegetable material was cut and crushed with a press. The OE was obtained by extraction using hexane, alcohol, and water. The P. emarginatus extracts obtained were used to evaluate the antimicrobial effect on S. aureus (ATCC 25923) by tests of well diffusion, disc diffusion, and microdilution. The strain used in the assays was maintained in brain heart infusion broth and nutrient agar until testing. Afterward, the bacteria were spread on agar plates with Mueller-Hinton agar medium. In the wells and on the paper discs, the OE suspensions were placed in the following volumes: 10, 15, 20, 25, 30, 40, and 80 μL and subsequently they were incubated at 35°C ± 2°C. After 24 h, the number of colony-forming unit was determined. Results: Pure OE and hydroalcoholic extract inhibited the growth of S. aureus, while aqueous extract had no effect on bacterial growth in all microbial methods used. Conclusion: Thus, the present study showed the potential of sucupira-based extracts against S. aureus growth, opening new perspectives for the evaluation of these bioactive compounds as phytopharmaceutical products. SUMMARY Plant extract act as antimicrobials to prevent and reduce bacterial contaminationBeans of Pterodon emarginatus has antibacterial propertiesExtraction with different solvents might implicate on the rate of bacterial deathThe effect of different microbiological methods (well diffusion, disc diffusion and microdilution) was evaluated on reducing CFUThe results showed by MBC that concentrations superior to 10% (v/v) using AC and 7.5% (v/v) using OE were necessary to eliminate colonies formedAccording to data of MIC, at 2.5% of AC and OE was enough to kill S. aureusThe well diffusion technique demonstrated better performance than disc diffusion test for OE and AC extractsHydroalcoholic and oil extracts of sucupira beans had highest effect against Staphylococcus aureusAqueous extract had no effect on bacterial growth in all microbial methods testedThe sucupira-based extracts is a promising source as herbal drug due to therapeutic value Abbreviations Used: OE: Essencial oil; AC: Hydroalcoholic oil extract; AQ: Aqueous extracts; MIC: Minimum inhibitory concentration; MBC: Minimum bactericidal concentration; CFU: Colony formed unit. PMID:29263627
Inhibitory Effects of Pterodon emarginatus Bean Oil and Extract on Staphylococcus aureus.
Mendes, V S; Sant'Anna, J B; Oliveira, S C C; Maldonade, Iriani Rodrigues; Machado, Eleuza Rodrigues
2017-01-01
Pterodon emarginatus is a tree of the Brazilian Savannah. The beans of this tree are used in folk medicine as anti-inflammatory preparations, especially for infections caused by Staphylococcus aureus . These bacteria can cause simple infections or serious illnesses such as pneumonia, meningitis, endocarditis, toxic shock syndrome, septicemia, and others. This study had the goal of verifying the effect of the essential oil (OE) from P. emarginatus on the inhibition of S. aureus in culture medium, i.e., " in vitro " tests. The vegetable material was cut and crushed with a press. The OE was obtained by extraction using hexane, alcohol, and water. The P. emarginatus extracts obtained were used to evaluate the antimicrobial effect on S. aureus (ATCC 25923) by tests of well diffusion, disc diffusion, and microdilution. The strain used in the assays was maintained in brain heart infusion broth and nutrient agar until testing. Afterward, the bacteria were spread on agar plates with Mueller-Hinton agar medium. In the wells and on the paper discs, the OE suspensions were placed in the following volumes: 10, 15, 20, 25, 30, 40, and 80 μL and subsequently they were incubated at 35°C ± 2°C. After 24 h, the number of colony-forming unit was determined. Pure OE and hydroalcoholic extract inhibited the growth of S. aureus , while aqueous extract had no effect on bacterial growth in all microbial methods used. Thus, the present study showed the potential of sucupira-based extracts against S. aureus growth, opening new perspectives for the evaluation of these bioactive compounds as phytopharmaceutical products. Plant extract act as antimicrobials to prevent and reduce bacterial contaminationBeans of Pterodon emarginatus has antibacterial propertiesExtraction with different solvents might implicate on the rate of bacterial deathThe effect of different microbiological methods (well diffusion, disc diffusion and microdilution) was evaluated on reducing CFUThe results showed by MBC that concentrations superior to 10% (v/v) using AC and 7.5% (v/v) using OE were necessary to eliminate colonies formedAccording to data of MIC, at 2.5% of AC and OE was enough to kill S. aureus The well diffusion technique demonstrated better performance than disc diffusion test for OE and AC extractsHydroalcoholic and oil extracts of sucupira beans had highest effect against Staphylococcus aureus Aqueous extract had no effect on bacterial growth in all microbial methods testedThe sucupira-based extracts is a promising source as herbal drug due to therapeutic value Abbreviations Used: OE: Essencial oil; AC: Hydroalcoholic oil extract; AQ: Aqueous extracts; MIC: Minimum inhibitory concentration; MBC: Minimum bactericidal concentration; CFU: Colony formed unit.
Science and Management of the Introduced Seagrass Zostera ...
Healthy seagrass is considered a prime indicator of estuarine ecosystem function. On the Pacific coast of North America, at least two congeners of Zostera occur: native Zostera marina, and introduced, Z. japonica. Z. japonica is considered “invasive” and therefore, ecologically and economically harmful by some, while others consider it benign or perhaps beneficial. Z. japonica does not appear on the Federal or the Oregon invasive species or noxious weed lists. However, the State of California lists it as both an invasive and noxious weed; Washington State recently listed it as a noxious weed. We describe the management dynamics in North America with respect to these congener species and highlight the science and policies behind these decisions. In recent years, management strategies at the state level have ranged from historical protection of Z. japonica as a priority habitat in Washington to eradication in California. In 2011, Washington State reversed its long standing policy to protect Z. japonica and is developing permits for chemical control of this plant. This fractured management approach contradicts efforts to conserve and protect seagrass in other regions of the US and around the world. Science must play a critical role in the assessment of Z. japonica ecology and the immediate and long-term effects of management actions. The information and recommendations provided here can serve as a basis for providing scientific data in order to develo
2012-01-01
Background Responding to noxious stimuli by invoking an appropriate escape response is critical for survival of an organism. The sensations of small and large changes in temperature in most organisms have been studied separately in the context of thermotaxis and nociception, respectively. Here we use the nematode C. elegans to address the neurogenetic basis of responses to thermal stimuli over a broad range of intensities. Results C. elegans responds to aversive temperature by eliciting a stereotypical behavioral sequence. Upon sensation of the noxious stimulus, it moves backwards, turns and resumes forward movement in a new direction. In order to study the response of C. elegans to a broad range of noxious thermal stimuli, we developed a novel assay that allows simultaneous characterization of multiple aspects of escape behavior elicited by thermal pulses of increasing amplitudes. We exposed the laboratory strain N2, as well as 47 strains with defects in various aspects of nervous system function, to thermal pulses ranging from ΔT = 0.4°C to 9.1°C and recorded the resulting behavioral profiles. Conclusions Through analysis of the multidimensional behavioral profiles, we found that the combinations of molecules shaping avoidance responses to a given thermal pulse are unique. At different intensities of aversive thermal stimuli, these distinct combinations of molecules converge onto qualitatively similar stereotyped behavioral sequences. PMID:23114012
Phaopongthai, Jatuporn; Wiyakrutta, Suthep; Meksuriyen, Duangdeun; Sriubolmas, Nongluksna; Suwanborirux, Khanit
2013-12-01
In this study, a tropical endophytic fungus, Alternaria alternata Tche-153 was isolated from a Thai medicinal plant Terminalia chebula Rezt. The ethyl acetate extract prepared from the fermentation broth exhibited significant ketoconazole-synergistic activity against Candida albicans. Bioassay-directed fractionation of the ethyl acetate extract led to the isolation of altenusin (1), isoochracinic acid (2), and altenuic acid (3) together with 2,5-dimethyl-7-hydroxychromone (4). Using the disc diffusion method and the microdilution chequerboard technique, only altenusin (1) in combination with each of three azole drugs, ketoconazole, fluconazole or itraconazole at their low sub-inhibitory concentrations exhibited potent synergistic activity against C. albicans with the fractional inhibitory concentration index range of 0.078 to 0.188. This first discovery of altenusin (1) as a new azole-synergistic prototype possessing a biphenyl structure is of significance for further development of new azole-synergists to treat invasive candidiasis.
Iseppi, Ramona; Sabia, Carla; de Niederhäusern, Simona; Pellati, Federica; Benvenuti, Stefania; Tardugno, Roberta; Bondi, Moreno; Messi, Patrizia
2018-06-06
The antibacterial activity of Rosmarinus officinalis L. and Thymus vulgaris L. essential oils (EOs), and their combination against food-borne and spoilage bacteria (Listeria monocytogenes, Salmonella enteritidis, Yersinia enterocolitica, Escherichia coli and Pseudomonas spp.) was determined. The EOs inhibitory effect was evaluated both in vitro by using the disk diffusion assay and the minimum inhibitory concentration (MIC) determination, and on food by using an artificially contaminated ready-to-eat (RTE) vegetables. The results showed that the lowest MIC values were obtained with R. officinalis and T. vulgaris EOs against E. coli (4 and 8 μL/mL, respectively). The incorporation of the EOs alone or their combination in RTE vegetables reduced the viable counts of all the tested strains. Lastly, in the on food study we simulated the worst hygienic conditions, obtaining results that can be considered a warranty of safety.
Ferrazzano, Lucia; Viola, Angelo; Lonati, Elena; Bulbarelli, Alessandra; Musumeci, Rosario; Cocuzza, Clementina; Lombardo, Marco; Tolomelli, Alessandra
2016-11-29
Among the different classes of antibiotics, oxazolidinone derivatives represent important drugs, since their unique mechanism of action overcomes commonly diffused multidrug-resistant bacteria. Anyway, the structural similarity of these molecules to monoamino oxidase (MAO) inhibitors, like toloxatone and blefoxatone, induces in many cases loss of selectivity as a major concern. A small library of compounds based on isoxazolidinone and dehydro-β-proline scaffold was designed with the aim to obtain antibacterial agents, evaluating at the same time the potential effects of structural features on MAO inhibitory behaviour. The structural modification introduced in the backbone, starting from Linezolid model, lead to a significant loss in antibiotic activity, while a promising inhibitory effect could be observed on monoamino oxidases. These interesting results are also in agreement with docking experiments suggesting a good binding pose of the synthesized compounds into the pocket of the oxidase enzymes, in particular of MAO-B. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Moon, Sun Hee; Lee, Jae Hoon; Kim, Kee-Tae; Park, Yong-Sun; Nah, Seung-Yeol; Ahn, Dong Uk; Paik, Hyun-Dong
2013-10-28
The antimicrobial effect of a novel flavonoid (7-O-butylnaringenin) on Helicobacter pylori 26695, 51, and SS1 strains and its inhibitory effect on the urease activity of the strains were evaluated and compared with those of several natural flavonoids. First, various flavonoids were screened for antimicrobial activities using the paper disc diffusion method. Hesperetin and naringenin showed the strongest antimicrobial effects among the natural flavonoids tested, and thus hesperetin and naringenin were selected for comparison with 7-O-butylnaringenin. The antimicrobial effect of 7-O-butylnaringenin was greater than that of the hesperetin and naringenin. H. pylori 51 was more sensitive to 7-O-butylnaringenin (2 log reduction of colony forming units, p < 0.05) than the other two strains at 200 μM. 7-O-Butylnaringenin also showed the highest inhibitory effect against urease activity of H. pylori. Morphological changes of H. pylori 26695 treated with these flavonoids indicated that both hesperetin and 7-O-butylnaringenin at 200 μM damaged the cell membranes.
Antimicrobial activity and safety evaluation of peptides isolated from the hemoglobin of chickens.
Hu, Fengjiao; Wu, Qiaoxing; Song, Shuang; She, Ruiping; Zhao, Yue; Yang, Yifei; Zhang, Meikun; Du, Fang; Soomro, Majid Hussain; Shi, Ruihan
2016-12-05
Hemoglobin is a rich source of biological peptides. As a byproduct and even wastewater of poultry-slaughtering facilities, chicken blood is one of the most abundant source of hemoglobin. In this study, the chicken hemoglobin antimicrobial peptides (CHAP) were isolated and the antimicrobial and bactericidal activities were tested by the agarose diffusion assay, minimum inhibitory concentration (MIC) analysis, minimal bactericidal concentration (MBC) analysis, and time-dependent inhibitory and bactericidal assays. The results demonstrated that CHAP had potent and rapid antimicrobial activity against 19 bacterial strains, including 9 multidrug-resistant bacterial strains. Bacterial biofilm and NaCl permeability assays, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were further performed to detect the mechanism of its antimicrobial effect. Additionally, CHAP showed low hemolytic activity, embryo toxicity, and high stability in different temperatures and animal plasma. CHAP may have great potential for expanding production and development value in animal medication, the breeding industry and environment protection.
Varsha, Kontham Kulangara; Nishant, Gopalan; Sneha, Srambikal Mohandas; Shilpa, Ganesan; Devendra, Leena; Priya, Sulochana; Nampoothiri, Kesavan Madhavan
2016-12-01
A bioactive compound was purified from the culture medium of a new strain of Lactococcus BSN307 by solvent extraction followed by chromatographic techniques. This bioactive compound was identified to belong to phenazine class of compounds by MS, NMR and FTIR. The phenazine compound showed antifungal activity against Aspergillus niger , Penicillium chrysogenum as well as Fusarium oxysporum by disc diffusion assay in addition to antioxidant potential as demonstrated by DPPH scavenging assay. The compound demonstrated selective cytotoxicity against cancer cell lines HeLa and MCF-7 where IC 50 was achieved with 20 and 24 µg/mL respectively. At the same time no cytotoxicity was occurred in normal H9c2 cells. The bioactive found to be inhibitory to both leucine and proline aminopeptidases and thus revealed its potential as metalloenzyme inhibitor. This study, for the first time reports the production of phenazine class of compounds by lactic acid bacteria.
Antagonistic activity of fungi of Olea europaea L. against Colletotrichum acutatum.
Landum, Miguel C; Félix, Maria do Rosário; Alho, Joana; Garcia, Raquel; Cabrita, Maria João; Rei, Fernando; Varanda, Carla M R
2016-02-01
Fungi naturally present in olive trees were identified and tested for their antagonistic potential against Colletotrichum acutatum. A total of 14 isolates were identified, 12 belonged to genera Alternaria, Epicoccum, Fusarium, Aspergillus, Anthrinium, Chaetomium, Diaporthe, Nigrospora, one to family Xylariaceae and one was unclassified. All fungal isolates showed some inhibitory action over the growth of C. acutatum during dual culture growth, however, when agar-diffusible tests were performed only five fungal isolates caused C. acutatum growth inhibition: Alternaria sp. isolate 2 (26.8%), the fungus from Xylariaceae family (14.3%), Alternaria sp. isolate 1 (10.7%); Diaporthe sp. (10.7%), Nigrospora oryzae (3.5%). Volatile substances produced by these isolates were identified through gas-chromatography techniques, as phenylethyl alcohol, 4-methylquinazoline, benzothiazole, benzyl alcohol, lilial, galaxolide, among others. These inhibitory volatiles could play a significant role in reduction of C. acutatum expansion in olive and their study as potential biocontrol agents should be further explored. Copyright © 2015 Elsevier GmbH. All rights reserved.
46 CFR 194.15-5 - Ventilation.
Code of Federal Regulations, 2011 CFR
2011-10-01
....15-5 Ventilation. (a) Operations, reactions or experiments which produce toxic, noxious or corrosive...) Ventilation of air conditioning systems serving the chemical laboratory shall be designed so that air cannot...
33 CFR 151.1508 - Revocation of clearance.
Code of Federal Regulations, 2011 CFR
2011-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in the Great Lakes and Hudson...
33 CFR 151.1508 - Revocation of clearance.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in the Great Lakes and Hudson...
33 CFR 151.1506 - Restriction of operation.
Code of Federal Regulations, 2011 CFR
2011-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in the Great Lakes and...
33 CFR 151.1506 - Restriction of operation.
Code of Federal Regulations, 2010 CFR
2010-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in the Great Lakes and...
Genovese, Giuseppa; Leitner, Sandra; Minicante, Simona A; Lass-Flörl, Cornelia
2013-09-01
The red algae Asparagopsis taxiformis collected from the Straits of Messina (Italy) were screened for antifungal activity against Aspergillus species. EUCAST methodology was applied and extracts showed antifungal activity against A. fumigatus, A. terreus and A. flavus. The lowest minimum inhibitory concentrations observed were <0.15 mg ml(-1) and the highest were >5 mg ml(-1) for Aspergillus spp. tested. Agar diffusion assays confirmed antifungal activity of A. taxiformis extracts in Aspergillus species. © 2013 Blackwell Verlag GmbH.
In-vitro Antimicrobial Activities of Some Iranian Conifers
Afsharzadeh, Maryam; Naderinasab, Mahboobe; Tayarani Najaran, Zahra; Barzin, Mohammad; Emami, Seyed Ahmad
2013-01-01
Male and female leaves and fruits of eleven different taxons of Iranian conifers (Cupressus sempervirens var. horizontalis, C. sempervirens var. sempervirens, C. sempervirens cv. Cereifeormis, Juniperus communis subsp. hemisphaerica, J. excelsa subsp. excelsa, J. excelsa subsp. polycarpos, J. foetidissima, J. oblonga, J. sabina, Platycladus orientalis and Taxus baccata) were collected from different localities of Iran, dried and extracted with methanol. The extracts were tested for their antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Candida albicans. The extracts were screened qualitatively using four different methods, the disc diffusion, hole plate, cylinder agar diffusion and agar dilution methods, whereas the minimum inhibitory concentrations (MIC) of each extract were determined by the agar dilution method. The best result was obtained by means of hole plate method in qualitative determination of antimicrobial activities of extracts and the greatest activity was found against S. aureus in all tested methods. PMID:24250573
Cherian, M A; Richmond, I
2000-10-01
The potential health hazards of handling industrial fish are well documented. Wet fish in storage consume oxygen and produce poisonous gases as they spoil. In addition to oxygen depletion, various noxious agents have been demonstrated in association with spoilage including carbon dioxide, sulphur dioxide, and ammonia. A fatal case of methane and cyanide poisoning among a group of deep sea trawler men is described. Subsequent independent investigation as a result of this case led to the discovery of cyanides as a further potential noxious agent. This is thus the first case in which cyanide poisoning has been recognised as a potentially fatal complication of handling spoiled fish. The previous literature is reviewed and the implications of the current case are discussed.
Azami, J; Green, D L; Roberts, M H; Monhemius, R
2001-05-01
We have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic activation of descending inhibition of the nociceptive response of spinal multireceptive cells occurs in the nucleus reticularis gigantocellularis pars alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are responsible for activating this inhibition via a pathway which runs in the contralateral dorsolateral funiculus. The effects of dynamically activating this system by noxious stimulation on behavioural responses to noxious stimuli have not been established. Here we demonstrate the effects of GiA on the behavioural response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is possible that chronic pain states may also activate GiA. We have therefore investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310 g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6 days. The responses of each animal during the formalin test (Pain 4 (1977) 161) and the tail flick test (Pain 12 (1982) 229) were recorded on different days. Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were performed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However microinjection of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4 +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection of GABA to GiA increased the behavioural response to formalin between 10 and 20 min post-injection, while microinjection of DLH reduced this response at all time points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioural response to contralaterally applied formalin from 15 min post-injection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA to GiA significantly increased the behavioural response to formalin from 20 to 50 min post-injection. The inactivation of GiA only causes behavioural effects in nociceptive tests of a long enough duration to activate the system (i.e. the formalin test but not the tail flick test). Chemical activation of the system affects both tests. These data strongly support the concept of an important analgesic system which is activated in response to noxious stimulation, and subsequently acts to reduce behavioural responses to noxious stimuli.
Folasire, Oladayo S; Chess-Williams, Russ; Sellers, Donna J
2017-09-01
The urethral uroepithelium has been implicated in urethral sensation and maintenance of continence. However, relatively little is known about the function of the urethral urothelium compared with that of the bladder. The aim of the study was to examine the role of the urothelium/lamina propria on contractility of the porcine urethra, along with the influence of nitric oxide, prostaglandins and ageing. Porcine urethral tissues, intact and denuded of urothelium/lamina propria, were mounted in tissue baths and contractions to noradrenaline, phenylephrine and carbachol obtained. Contractions in the presence of Nώ-nitro-l-arginine (100 μmol/L) and indomethacin (10 μmol/L) were examined, along with contractions of tissues from young (6 months) and older (3 years) animals. The urothelium/lamina propria of the urethra significantly inhibited contractions to carbachol, noradrenaline and phenylephrine. This inhibitory effect was not significantly different for the three agonists (58.7±10.3%, 60.4±12.6% and 39.4±12.2% inhibition; n=4-7), and was also observed when denuded tissues were co-incubated with a second tissue with intact urothelium/lamina propria (40.6±7.5% inhibition; n=6). Inhibition of nitric oxide and prostaglandin production did not attenuate the inhibitory effect of the urothelium/lamina propria on noradrenaline contractions. In addition, ageing did not alter the inhibitory effect for either phenylephrine contractions (33.9±2.2% vs 41.0±9.7%, young vs older urethral tissues) or noradrenaline contractions (32.9±11.1% vs 53.7±11.0%). In conclusion the urothelium/lamina propria of the urethra has an inhibitory effect on receptor-mediated urethral contraction. This inhibition is due to the release of a diffusible factor, and the effect is not mediated by nitric oxide or prostaglandins, or affected by age. © 2017 John Wiley & Sons Australia, Ltd.
Cohen-Gilbert, J E; Killgore, W D S; White, C N; Schwab, Z J; Crowley, D J; Covell, M J; Sneider, J T; Silveri, M M
2014-03-01
Social cognition matures dramatically during adolescence and into early adulthood, supported by continued improvements in inhibitory control. During this time, developmental changes in interpreting and responding to social signals such as facial expressions also occur. In the present study, subjects performed a Go No-Go task that required them to respond or inhibit responding based on threat or safety cues present in facial expressions. Subjects (N = 112) were divided into three age groups: adolescent (12-15 years), emerging adult (18-25 years) and adult (26-44 years). Analyses revealed a significant improvement in accuracy on No-Go trials, but not Go trials, during both safe and threat face conditions, with changes evident through early adulthood. In order to better identify the decision-making processes responsible for these changes in inhibitory control, a drift diffusion model (DDM) was fit to the accuracy and reaction time data, generating measures of caution, response bias, nondecision time (encoding + motor response), and drift rate (face processing efficiency). Caution and nondecision time both increased significantly with age while bias towards the Go response decreased. Drift rate analyses revealed significant age-related improvements in the ability to map threat faces to a No-Go response while drift rates on all other trial types were equivalent across age groups. These results suggest that both stimulus-independent and stimulus-dependent processes contribute to improvements in inhibitory control in adolescence with processing of negative social cues being specifically impaired by self-regulatory demands. Findings from this novel investigation of emotional responsiveness integrated with inhibitory control may provide useful insights about healthy development that can be applied to better understand adolescent risk-taking behavior and the elevated incidence of related forms of psychopathology during this period of life. © 2014 John Wiley & Sons Ltd.
2013-01-01
Background Dopaminergic fibers originating from area A11 of the hypothalamus project to different levels of the spinal cord and represent the major source of dopamine. In addition, tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of catecholamines, is expressed in 8-10% of dorsal root ganglia (DRG) neurons, suggesting that dopamine may be released in the dorsal root ganglia. Dopamine has been shown to modulate calcium current in DRG neurons, but the effects of dopamine on sodium current and on the firing properties of small DRG neurons are poorly understood. Results The effects of dopamine and dopamine receptor agonists were tested on the tetrodotoxin-resistant (TTX-R) sodium current recorded from acutely dissociated small (diameter ≤ 25 μm) DRG neurons. Dopamine (20 μM) and SKF 81297 (10 μM) caused inhibition of TTX-R sodium current in small DRG neurons by 23% and 37%, respectively. In contrast, quinpirole (20 μM) had no effects on the TTX-R sodium current. Inhibition by SKF 81297 of the TTX-R sodium current was not affected when the protein kinase A (PKA) activity was blocked with the PKA inhibitory peptide (6–22), but was greatly reduced when the protein kinase C (PKC) activity was blocked with the PKC inhibitory peptide (19–36), suggesting that activation of D1/D5 dopamine receptors is linked to PKC activity. Expression of D1and D5 dopamine receptors in small DRG neurons, but not D2 dopamine receptors, was confirmed by Western blotting and immunofluorescence analysis. In current clamp experiments, the number of action potentials elicited in small DRG neurons by current injection was reduced by ~ 30% by SKF 81297. Conclusions We conclude that activation of D1/D5 dopamine receptors inhibits TTX-R sodium current in unmyelinated nociceptive neurons and dampens their intrinsic excitability by reducing the number of action potentials in response to stimulus. Increasing or decreasing levels of dopamine in the dorsal root ganglia may serve to adjust the sensitivity of nociceptors to noxious stimuli. PMID:24283218
33 CFR 151.2005 - To which vessels does this subpart apply?
Code of Federal Regulations, 2011 CFR
2011-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species...
33 CFR 151.2005 - To which vessels does this subpart apply?
Code of Federal Regulations, 2010 CFR
2010-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species...
33 CFR 151.1024 - Display of number.
Code of Federal Regulations, 2013 CFR
2013-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1024 Display of number. (a) The owner...
33 CFR 151.1012 - Applying for a conditional permit.
Code of Federal Regulations, 2014 CFR
2014-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1012 Applying for a...
33 CFR 151.1009 - Transportation of municipal or commercial waste.
Code of Federal Regulations, 2014 CFR
2014-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1009...
33 CFR 151.1024 - Display of number.
Code of Federal Regulations, 2014 CFR
2014-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1024 Display of number. (a) The owner...
33 CFR 151.1012 - Applying for a conditional permit.
Code of Federal Regulations, 2012 CFR
2012-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1012 Applying for a...
33 CFR 151.1009 - Transportation of municipal or commercial waste.
Code of Federal Regulations, 2013 CFR
2013-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1009...
33 CFR 151.1009 - Transportation of municipal or commercial waste.
Code of Federal Regulations, 2012 CFR
2012-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1009...
33 CFR 151.1024 - Display of number.
Code of Federal Regulations, 2011 CFR
2011-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1024 Display of number. (a) The owner...
33 CFR 151.1012 - Applying for a conditional permit.
Code of Federal Regulations, 2011 CFR
2011-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1012 Applying for a...
33 CFR 151.1009 - Transportation of municipal or commercial waste.
Code of Federal Regulations, 2011 CFR
2011-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1009...
33 CFR 151.1012 - Applying for a conditional permit.
Code of Federal Regulations, 2013 CFR
2013-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1012 Applying for a...
33 CFR 151.1024 - Display of number.
Code of Federal Regulations, 2012 CFR
2012-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1024 Display of number. (a) The owner...
33 CFR 151.1024 - Display of number.
Code of Federal Regulations, 2010 CFR
2010-07-01
...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1024 Display of number. (a) The owner...
33 CFR 151.1012 - Applying for a conditional permit.
Code of Federal Regulations, 2010 CFR
2010-07-01
... (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1012 Applying for a...
33 CFR 151.1009 - Transportation of municipal or commercial waste.
Code of Federal Regulations, 2010 CFR
2010-07-01
... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste § 151.1009...
7 CFR 1412.61 - Contract violations.
Code of Federal Regulations, 2010 CFR
2010-01-01
... payments for each such acre. (2) Producers must protect land enrolled in DCP from weeds, including noxious weeds, and erosion, including providing sufficient cover if determined necessary by the county committee...
The Physiology of Bone Pain. How Much Do We Really Know?
Nencini, Sara; Ivanusic, Jason J.
2016-01-01
Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections. PMID:27199772
Gibson, William; Moss, Penny; Cheng, Tak Ho; Garnier, Alexandre; Wright, Anthony; Wand, Benedict M
2018-03-01
Many factors interact to influence threat perception and the subsequent experience of pain. This study investigated the effect of observing pain (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain threshold (PPT). Forty socially connected pairs of healthy volunteers were threat-primed and randomly allocated to experimental or control roles. An experimental pain modulation paradigm was applied, with non-nociceptive threat cues used as conditioning stimuli. In substudy 1, the extrinsic threat to the experimental participant was observation of the control partner in pain. The control participant underwent hand immersion in noxious and non-noxious water baths in randomized order. Change in the observing participant's PPT from baseline to mid- and postimmersion was calculated. A significant interaction was found for PPT between conditions and test time (F 2,78 = 24.9, P < .005). PPT increased by 23.6% ± 19.3% between baseline and during hand immersion (F 1,39 = 43.7, P < .005). Substudy 2 investigated threat of imminent pain to self. After a 15-minute break, the experimental participant's PPT was retested ("baseline 2"). Threat was primed by suggestion of whole arm immersion in an icier, larger water bath. PPT was tested immediately before anticipated arm immersion, after which the experiment ended. A significant increase in PPT between "baseline 2" and "pre-immersion" was seen (t = -7.6, P = .005), a pain modulatory effect of 25.8 ± 20.7%. Extrinsic and intrinsic threat of pain, in the absence of any afferent input therefore influences pain modulation. This may need to be considered in studies that use noxious afferent input with populations who show dysfunctional pain modulation. The effect on endogenous analgesia of observing another's pain and of threat of pain to oneself was investigated. Extrinsic as well as intrinsic threat cues, in the absence of any afferent input, increased pain thresholds, suggesting that mere threat of pain may initiate analgesic effects in traditional noxious experimental paradigms. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.
Weyer-Menkhoff, I; Thrun, M C; Lötsch, J
2018-05-01
Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background. Pain thresholds to noxious cold stimuli (range 32-0 °C, tonic: temperature decrease -1 °C/s, phasic: temperature decrease -8 °C/s) were acquired in 148 healthy volunteers. The probability density distribution was analysed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM), emergent self-organizing maps and self-organizing swarms of data agents. The probability density function of pain responses was trimodal (mean thresholds at 25.9, 18.4 and 8.0 °C for tonic and 24.5, 18.1 and 7.5 °C for phasic stimuli). Subjects' association with Gaussian modes was consistent between both types of stimuli (weighted Cohen's κ = 0.91). Patterns emerging in self-organizing neuronal maps and swarms could be associated with different trends towards decreasing cold pain sensitivity in different Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as particularly distinct. Thresholds at, roughly, 25 and 18 °C agree with known working temperatures of TRPM8 and TRPA1 ion channels, respectively, and hint at relative local dominance of either channel in respective subjects. Data patterns suggest involvement of further distinct mechanisms in cold pain perception at lower temperatures. Findings support data science approaches to identify biologically plausible hints at complex molecular mechanisms underlying human pain phenotypes. Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background. © 2018 European Pain Federation - EFIC®.
Pokes, Sunburn, and Hot Sauce: Drosophila as an Emerging Model for the Biology of Nociception
Im, Seol Hee; Galko, Michael J.
2012-01-01
The word “nociception” is derived from the Latin “nocere,” which means “to harm.” Nociception refers to the sensory perception of noxious stimuli that have the potential to cause tissue damage. Since the perception of such potentially harmful stimuli often results in behavioral escape responses, nociception provides a protective mechanism that allows an organism to avoid incipient (or further) damage to the tissue. It appears to be universal in metazoans as a variety of escape responses can be observed in both mammalian and non-mammalian vertebrates, as well as diverse invertebrates such as leeches, nematodes, and fruit flies (Sneddon [2004] Brain Research Review 46:123–130; Tobin and Bargmann [2004] Journal of Neurobiology 61:161–174; Smith and Lewin [2009] Journal of Comparative Physiology 195:1089–1106). Several types of stimuli can trigger nociceptive sensory transduction, including noxious heat, noxious chemicals, and harsh mechanical stimulation. Such high-threshold stimuli induce the firing of action potentials in peripheral nociceptors, the sensory neurons specialized for their detection (Basbaum et al. [2009] Cell 139:267–284). In vertebrates, these action potentials can either be relayed directly to a spinal motor neuron to provoke escape behavior (the so-called monosynaptic reflex) or can travel via spinal cord interneurons to higher-order processing centers in the brain. This review will cover the establishment of Drosophila as a system to study various aspects of nociceptive sensory perception. We will cover development of the neurons responsible for detecting noxious stimuli in larvae, the assays used to assess the function(s) of these neurons, and the genes that have been found to be required for both thermal and mechanical nociception. Along the way, we will highlight some of the genetic tools that make the fly such a powerful system for studies of nociception. Finally, we will cover recent studies that introduce new assays employing adult Drosophila to study both chemical and thermal nociception and provide an overview of important unanswered questions in the field. PMID:21932321
20 CFR 654.404 - Housing site.
Code of Federal Regulations, 2014 CFR
2014-04-01
... similar hazards. (c) Grounds within the housing site shall be free from debris, noxious plants (poison ivy, etc.) and uncontrolled weeds or brush. (d) The housing site shall provide a space for recreation...
20 CFR 654.404 - Housing site.
Code of Federal Regulations, 2013 CFR
2013-04-01
... similar hazards. (c) Grounds within the housing site shall be free from debris, noxious plants (poison ivy, etc.) and uncontrolled weeds or brush. (d) The housing site shall provide a space for recreation...
20 CFR 654.404 - Housing site.
Code of Federal Regulations, 2011 CFR
2011-04-01
... similar hazards. (c) Grounds within the housing site shall be free from debris, noxious plants (poison ivy, etc.) and uncontrolled weeds or brush. (d) The housing site shall provide a space for recreation...
20 CFR 654.404 - Housing site.
Code of Federal Regulations, 2012 CFR
2012-04-01
... similar hazards. (c) Grounds within the housing site shall be free from debris, noxious plants (poison ivy, etc.) and uncontrolled weeds or brush. (d) The housing site shall provide a space for recreation...
Code of Federal Regulations, 2010 CFR
2010-07-01
..., London, SE1 7SR, England. Medical waste means isolation wastes, infectious agents, human blood and blood... or facility which is a base of operations for ships serving the mineral and oil industry. Noxious...
Code of Federal Regulations, 2011 CFR
2011-07-01
..., London, SE1 7SR, England. Medical waste means isolation wastes, infectious agents, human blood and blood... or facility which is a base of operations for ships serving the mineral and oil industry. Noxious...
20 CFR 654.404 - Housing site.
Code of Federal Regulations, 2010 CFR
2010-04-01
... similar hazards. (c) Grounds within the housing site shall be free from debris, noxious plants (poison ivy, etc.) and uncontrolled weeds or brush. (d) The housing site shall provide a space for recreation...
33 CFR 151.1015 - Issuing or denying the issuance of a conditional permit.
Code of Federal Regulations, 2012 CFR
2012-07-01
..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste...
33 CFR 151.1015 - Issuing or denying the issuance of a conditional permit.
Code of Federal Regulations, 2011 CFR
2011-07-01
..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste...
33 CFR 151.1015 - Issuing or denying the issuance of a conditional permit.
Code of Federal Regulations, 2014 CFR
2014-07-01
..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste...
33 CFR 151.1015 - Issuing or denying the issuance of a conditional permit.
Code of Federal Regulations, 2013 CFR
2013-07-01
..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste...
33 CFR 151.1015 - Issuing or denying the issuance of a conditional permit.
Code of Federal Regulations, 2010 CFR
2010-07-01
..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Transportation of Municipal and Commercial Waste...
Inhibition of Listeria monocytogenes by Food-Borne Yeasts†
Goerges, Stefanie; Aigner, Ulrike; Silakowski, Barbara; Scherer, Siegfried
2006-01-01
Many bacteria are known to inhibit food pathogens, such as Listeria monocytogenes, by secreting a variety of bactericidal and bacteriostatic substances. In sharp contrast, it is unknown whether yeast has an inhibitory potential for the growth of pathogenic bacteria in food. A total of 404 yeasts were screened for inhibitory activity against five Listeria monocytogenes strains. Three hundred and four of these yeasts were isolated from smear-ripened cheeses. Most of the yeasts were identified by Fourier transform infrared spectroscopy. Using an agar-membrane screening assay, a fraction of approximately 4% of the 304 red smear cheese isolates clearly inhibited growth of L. monocytogenes. Furthermore, 14 out of these 304 cheese yeasts were cocultivated with L. monocytogenes WSLC 1364 on solid medium to test the antilisterial activity of yeast in direct cell contact with Listeria. All yeasts inhibited L. monocytogenes to a low degree, which is most probably due to competition for nutrients. However, one Candida intermedia strain was able to reduce the listerial cell count by 4 log units. Another four yeasts, assigned to C. intermedia (three strains) and Kluyveromyces marxianus (one strain), repressed growth of L. monocytogenes by 3 log units. Inhibition of L. monocytogenes was clearly pronounced in the cocultivation assay, which simulates the conditions and contamination rates present on smear cheese surfaces. We found no evidence that the unknown inhibitory molecule is able to diffuse through soft agar. PMID:16391059
In vitro inhibitory activity of probiotic products against oral Candida species.
Zhao, C; Lv, X; Fu, J; He, C; Hua, H; Yan, Z
2016-07-01
To evaluate the inhibitory activity of probiotics against oral Candida species. Four commercial probiotic products were screened. Bacillus subtilis R0179 was found to have a significant antifungal effect. Bacillus subtilis-Candida interactions were evaluated using disc diffusion tests, confocal laser scanning microscopy, scanning electron microscopy and interaction with engineered human oral mucosa tissue. Bacillus subtilis exhibited clear zones of inhibition for Candida albicans and Candida parapsilosis but not for Candida krusei. A remarkable reduction in the number of Candida cells and abundant Candida cell death were visualized with confocal laser scanning microscopy. Shrinkage and deformation of Candida cells was observed using scanning electron microscopy. Culture of C. albicans on engineered human oral mucosa tissues resulted in the presence of a large number of yeast cells on the tissue surface and the development of large-scale tissue damage. However, comparatively fewer Candida cells were observed on B. subtilis-treated tissues. We also use ultra performance liquid chromatography/time of flight mass spectrometry (UPLC/TOF MS) to explore the preliminary antifungal mechanism of B. subtilis R0179 and to detect that whether it can secrete an antifungal agent, Iturin A. Bacillus subtilis R0179 exhibits a significant inhibitory effect on the growth of Candida species. Bacillus subtilis has the potential to be used in the prevention or treatment of oral candidiasis. © 2016 The Society for Applied Microbiology.
Luo, W; Chen, M; Chen, A; Dong, W; Hou, X; Pu, B
2015-04-01
To isolate lactic acid bacteria (LAB) from pao cai, a Chinese traditional fermented vegetable, with outstanding inhibitory activity against Salmonella inoculated on fresh-cut apple, using a modelling method. Four kinds of pao cai were selected. A total of 122 isolates exhibited typical LAB characteristics: Gram-positive and catalase negative, among which 104 (85·24%) colonies showed antibacterial activity against Salmonella by the well diffusion assay. Four colonies showing maximum antibacterial radius against Salmonella were selected to co-inoculate with Salmonella on fresh-cut apple and stored at 10°C, further identified as three strains of Lactobacillus plantarum and one strain of Lactobacillus brevis by 16s rRNA gene sequence analysis. The modified Gompertz model was employed to analyse the growth of the micro-organisms on apple wedges. Two of the four selected strains showed antagonistic activity against Salmonella on fresh-cut apple, one of which, RD1, exhibited best inhibitory activity (Salmonella were greatly inhibited when co-inoculated with RD1 at 10°C at 168 h). No deterioration in odour or appearance of the apple piece was observed by the triangle test when fresh-cut apple was inoculated with RD1. The mathematical modelling method is essential to select LAB with outstanding inhibitory activity against Salmonella associated with fresh-cut apple. LAB RD1 holds promise for the preservation of fresh-cut apple. This study provided a new method on fresh-cut product preservation. Besides, to make the LAB isolating procedure a more correct one, this study first added the mathematical modelling method to the isolating procedure. © 2014 The Society for Applied Microbiology.
Structural and Functional Alterations in Neocortical Circuits after Mild Traumatic Brain Injury
NASA Astrophysics Data System (ADS)
Vascak, Michal
National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structuralfunctional alterations of excitatory and inhibitory systems in the neocortex.
Hosseinkhani, Faride; Jabalameli, Fereshteh; Banar, Maryam; Abdellahi, Nafiseh; Taherikalani, Morovat; Leeuwen, Willem B van; Emaneini, Mohammad
2016-04-01
The aim of this study was to determine whether an herbal extract containing monoterpene exhibited activity against multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa isolated from clinical infection samples. The essential oil of Trachyspermum ammi (L.) Sprague ex Turrill (Apiaceae) fruit was extracted by hydrodistillation. Fruit residues were treated with hydrochloric acid and re-hydrodistilled to obtain volatile compounds. Compounds in the distilled oil were identified using gas-chromatography (GC) and GC-mass spectrometry (MS). The antibiotic susceptibility of all bacterial isolates was analyzed using both the disc diffusion method and determination of the minimum inhibitory concentration (MIC). The sensitivity of antibiotic-resistant isolates to essential oil was also determined by using the disc diffusion method and MIC determination. Of 26 clinical isolates, 92% were multidrug-resistant (MDR). Aromatic monoterpenes (thymol, paracymene, and gamma-terpinene) were the major (90%) components of the oil. Growth of S. aureus strains was successfully inhibited by the oil, with an inhibitory zone diameter (IZD) between 30-60mm and MIC <0.02μL/mL. The oil had no antimicrobial activity against clinical isolates of P. aeruginosa; rather, it prevented pigment production in these isolates. This study revealed that the essential oil of Trachyspermum ammi, which contains monoterpene, has good antibacterial potency. Monoterpenes could thus be incorporated into antimicrobial ointment formulas in order to treat highly drug-resistant S. aureus infections. Our findings also underscore the utility of research on natural products in order to combat bacterial multidrug resistance.