Selley, Dana E; Welch, Sandra P; Sim-Selley, Laura J
A significant number of patients experience chronic pain and the intractable side effects of currently prescribed pain medications. Recent evidence indicates important pain-modulatory roles for two classes of G-protein-coupled receptors that are activated by endogenous lipid ligands, the endocannabinoid (eCB) and sphingosine-1-phosphate (S1P) receptors, which are widely expressed in both the immune and nervous systems. In the central nervous system (CNS), CB1 cannabinoid and S1P1 receptors are most abundantly expressed and exhibit overlapping anatomical distributions and similar signaling mechanisms. The eCB system has emerged as a potential target for treatment of chronic pain, but comparatively little is known about the roles of S1P in pain regulation. Both eCB and S1P systems modulate pain perception via the central and peripheral nervous systems. In most paradigms studied, the eCB system mainly inhibits pain perception. In contrast, S1P acting peripherally at S1P1 and S1P3 receptors can enhance sensitivity to various pain stimuli or elicit spontaneous pain. However, S1P acting at S1P1 receptors and possibly other targets in the CNS can attenuate sensitivity to various pain stimuli. Interestingly, other endogenous sphingolipid derivatives might play a role in central pain sensitization. Moreover, these sphingolipids can also act as CB1 cannabinoid receptor antagonists, but the physiological relevance of this interaction is unknown. Overall, both eCB and sphingolipid systems offer promising targets for the treatment of chronic pain. This review compares and contrasts the eCB and S1P systems with a focus on their roles in pain modulation, and considers possible points of interaction between these systems. Copyright © 2013 Elsevier Inc. All rights reserved.
Gagliardino Juan J
Full Text Available Abstract Background The possible participation of endogenous islet catecholamines (CAs in the control of insulin secretion was tested. Methods Glucose-induced insulin secretion was measured in the presence of 3-Iodo-L-Tyrosine (MIT, a specific inhibitor of tyrosine-hydroxylase activity, in fresh and precultured islets isolated from normal rats. Incubated islets were also used to measure CAs release in the presence of low and high glucose, and the effect of α2-(yohimbine [Y] and idazoxan [I] and α1-adrenergic antagonists (prazosin [P] and terazosin [T] upon insulin secretion elicited by high glucose. Results Fresh islets incubated with 16.7 mM glucose released significantly more insulin in the presence of 1 μM MIT (6.66 ± 0.39 vs 5.01 ± 0.43 ng/islet/h, p Conclusion Our results suggest that islet-originated CAs directly modulate insulin release in a paracrine manner.
Michael H. Ossipov
Full Text Available Pain is often perceived an unpleasant experience that includes sensory and emotional/motivational responses. Accordingly, pain serves as a powerful teaching signal enabling an organism to avoid injury, and is critical to survival. However, maladaptive pain, such as neuropathic or idiopathic pain, serves no survival function. Genomic studies of individuals with congenital insensitivity to pain or paroxysmal pain syndromes considerable increased our understanding of the function of peripheral nociceptors, and especially of the roles of voltage-gated sodium channels and of nerve growth factor (NGF/TrkA receptors in nociceptive transduction and transmission. Brain imaging studies revealed a “pain matrix,” consisting of cortical and subcortical regions that respond to noxious inputs and can positively or negatively modulate pain through activation of descending pain modulatory systems. Projections from the periaqueductal grey (PAG and the rostroventromedial medulla (RVM to the trigeminal and spinal dorsal horns can inhibit or promote further nociceptive inputs. The “pain matrix” can explain such varied phenomena as stress-induced analgesia, placebo effect and the role of expectation on pain perception. Disruptions in these systems may account for the existence idiopathic pan states such as fibromyalgia. Increased understanding of pain modulatory systems will lead to development of more effective therapeutics for chronic pain.
Full Text Available Abstract Background: High morbidity and limited therapies of hepatic fibro genesis are important factor for better understanding the molecular mechanisms of the disease. Advances in the understanding of the molecular behavior of hepatic stellate cells (HSC allow the progress of a field dedicated to anti-fibrotic therapy. Melanoma differentiation associated gene-7 (IL-24/mda-7 as a gene induced during terminal differentiation in human melanoma cells, but the inflammatory response of cells to IL-24/mda-7 is not entirely cleared. Materias and Methods: LX-2 cells (a human hepatic stellate cell were treated by leptin (positive control, media (control negative, or were transfected by empty plasmid and pcDNA3.1/mda-7. The inflammatory state was evaluated through measuring the mRNA expression level of inflammatory molecule, IL-1β. The role of IL-24/mda-7 modulation on inflammatory response was assayed using SOCS1 and SOCS3 gene expressions. Results: The expression levels of IL-1β, SOCS1 and SOCS3 were compared in LX-2 cell line groups. The expression of the IL-1β in the transfected cells was higher than the control cell, but it was not significant. The results indicated that the expressions of SOCS1 and SOCS3 were up-regulated following pcDNA 3.1/mda-7 transfection into LX-2 cells compared to control plasmids (p=0.0179, p=0.0428. Conclusion: The endogenous IL-24/mda-7 exhibited a significant modulatory effect on stellate cells. Therefore, IL-24/mda-7 and relevant signaling pathways could be employed as a target for fibrosis treatment.
Vaegter, Henrik Bjarke; Graven-Nielsen, Thomas
between subgroups. Cuff algometry was performed on lower legs in 400 chronic pain patients to assess pressure pain threshold (cPPT), pressure pain tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations), and conditioned pain modulation (CPM: increase in c......PPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain thresholds (HPT) at clinical painful and non-painful body areas were assessed. Based on TSP and CPM four distinct groups were formed: Group 1 (n=85) had impaired CPM and facilitated TSP. Group 2 (n=148) had...... impaired CPM and normal TSP. Group 3 (n=45) had normal CPM and facilitated TSP. Group 4 (n=122) had normal CPM and normal TSP. Group 1 showed more pain regions compared with the other three groups (PTSP plays an important role in widespread pain. Group 1...
Karlsson, L; Gerdle, B; Ghafouri, B; Bäckryd, E; Olausson, P; Ghafouri, N; Larsson, B
In peripheral tissue, several substances influence pain and pain modulation. Exercise has been found to decrease pain and improve function for chronic pain conditions, but how and why exercise produces beneficial effects remains unclear. This study investigates whether aspects of pain and concentrations of substances with algesic, analgesic and metabolic functions differ between women with chronic neck shoulder pain (CNSP) and healthy women (CON) and whether changes are found after an exercise intervention for CNSP. Forty-one women with CNSP and 24 CON subjects were included. The participants attended two microdialysis sessions with 4-6 months between the experiments. During this period, the CNSP subjects underwent an exercise intervention. Expression levels of substance P, beta-endorphin, cortisol, glutamate, lactate and pyruvate as well as pain intensity and pressure pain thresholds were analysed. At baseline, higher concentrations of glutamate and beta-endorphin and lower concentrations of cortisol in CNSP than CON were found. After exercise, decreased levels of substance P and possibly of glutamate, increased levels of beta-endorphin and cortisol as well as decreased pain intensity and increased pain pressure thresholds were found for CNSP. The findings at baseline indicated algesic and analgesic alterations in the painful trapezius muscles. The findings for CNSP after the exercise intervention, with changes in peripheral substances and decreased pain intensity and sensitivity, could reflect a long-term physiological effect of the exercise. © 2014 European Pain Federation - EFIC®
Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B
UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development...... of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P ... naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future...
Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H
Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...... hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r......TMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain...
Full Text Available In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB, an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.
treatment. Therefore, MO leaf extract has demonstrated some therapeutic effectiveness against APAP-induced nephrotoxicity through enhancement of the endogenous antioxidant system and a modulatory effect on specific inflammatory cytokines in kidney tissues.
Kamila Jankowiak Siuda
Full Text Available Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI, and the anterior cingulate cortex (ACC. High empathy may lead people to undertake pro-social behaviour. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behaviour and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male were studied using fMRI method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioural effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens’ faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain.
Endogenous pain inhibition is often deficient in adults with chronic pain conditions including irritable bowel syndrome (IBS). It is unclear whether deficiencies in pain inhibition are present in young children with IBS. The present study compared endogenous pain inhibition, somatic pain threshold, ...
Nijs, Jo; Kosek, Eva; Van Oosterwijck, Jessica; Meeus, Mira
Exercise is an effective treatment for various chronic pain disorders, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Although the clinical benefits of exercise therapy in these populations are well established (i.e. evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g. central pain modulation). Reviewing the available evidence addressing the effects of exercise on central pain modulation in patients with chronic pain. Narrative review. Exercise activates endogenous analgesia in healthy individuals. The increased pain threshold following exercise is due to the release of endogenous opioids and activation of (supra)spinal nociceptive inhibitory mechanisms orchestrated by the brain. Exercise triggers the release of beta-endorphins from the pituitary (peripherally) and the hypothalamus (centrally), which in turn enables analgesic effects by activating μ-opioid receptors peripherally and centrally, respectively. The hypothalamus, through its projections on the periaqueductal grey, has the capacity to activate descending nociceptive inhibitory mechanisms. However, several groups have shown dysfunctioning of endogenous analgesia in response to exercise in patients with chronic pain. Muscle contractions activate generalized endogenous analgesia in healthy, pain-free humans and patients with either osteoarthritis or rheumatoid arthritis, but result in increased generalised pain sensitivity in fibromyalgia patients. In patients having local muscular pain (e.g. shoulder myalgia), exercising non-painful muscles activates generalized endogenous analgesia. However, exercising painful muscles does not change pain sensitivity either in the exercising muscle or at distant locations. The reviewed studies examined acute effects of exercise rather than long-term effects of exercise therapy. A dysfunctional response of patients with chronic pain and
Van Oosterwijck, Jessica; Meeus, Mira; Paul, Lorna; De Schryver, Mieke; Pascal, Aurelie; Lambrecht, Luc; Nijs, Jo
There is evidence that education on pain physiology can have positive effects on pain, disability, and catastrophization in patients with chronic musculoskeletal pain disorders. A double-blind randomized controlled trial (RCT) was performed to examine whether intensive pain physiology education is also effective in fibromyalgia (FM) patients, and whether it is able to influence the impaired endogenous pain inhibition of these patients. Thirty FM patients were randomly allocated to either the experimental (receiving pain physiology education) or the control group (receiving pacing self-management education). The primary outcome was the efficacy of the pain inhibitory mechanisms, which was evaluated by spatially accumulating thermal nociceptive stimuli. Secondary outcome measures included pressure pain threshold measurements and questionnaires assessing pain cognitions, behavior, and health status. Assessments were performed at baseline, 2 weeks, and 3 months follow-up. Repeated measures ANOVAS were used to reveal possible therapy effects and effect sizes were calculated. After the intervention the experimental group had improved knowledge of pain neurophysiology (Pphysiology. Pain physiology education seems to be a useful component in the treatment of FM patients as it improves health status and endogenous pain inhibition in the long term.
Van Den Houte, Maaike; Van Oudenhove, Lukas; Bogaerts, Katleen; Van Diest, Ilse; Van den Bergh, Omer
Several chronic pain syndromes are characterized by deficient endogenous pain modulation as well as elevated negative affectivity and reduced resting heart rate variability. In order to elucidate the relationships between these characteristics, we investigated whether negative affectivity and heart rate variability are associated with endogenous pain modulation in a healthy population. An offset analgesia paradigm with noxious thermal stimulation calibrated to the individual's pain threshold was used to measure endogenous pain modulation magnitude in 63 healthy individuals. Pain ratings during constant noxious heat stimulation to the arm (15 seconds) were compared with ratings during noxious stimulation comprising a 1 °C rise and return of temperature to the initial level (offset trials, 15 seconds). Offset analgesia was defined as the reduction in pain following the 1 °C decrease relative to pain at the same time point during continuous heat stimulation. Evidence for an offset analgesia effect could only be found when noxious stimulation intensity (and, hence, the individual's pain threshold) was intermediate (46 °C or 47 °C). Offset analgesia magnitude was also moderated by resting heart rate variability: a small but significant offset effect was found in participants with high but not low heart rate variability. Negative affectivity was not related to offset analgesia magnitude. These results indicate that resting heart rate variability (HRV) is related to endogenous pain modulation (EPM) in a healthy population. Future research should focus on clarifying the causal relationship between HRV and EPM and chronic pain by using longitudinal study designs.
Fischer, Michael J; Stephan, Michael; Kielstein, Heike; Rahne, Henning; Nugraha, Boya; Gutenbrunner, Christoph; Ro, Jin Y; Svensson, Peter
Mastication may be able to activate endogenous pain inhibitory mechanisms and therefore lead to modulation of nociceptive processing. The purpose of this study was to examine the possible effect of food consistency on noxious input from the spinal system. Three groups of adult male Sprague-Dawley rats were given an injection of complete Freund adjuvant in a hind paw 10 days after eating soft or hard food (one group received a saline injection-the control group [C]; the other group (D) received no injection). Nocifensive behavior was assessed with the use of the hot plate and tail flick assays at 1, 3, 6, and 12 hours and at 6.5 days after injection for groups A/B, and c-Fos activity was assessed in the brain after testing. Groups C/D had hot plate testing at 1 hour and 6.5 days. The data were analyzed by general linear modeling and 1-way analysis of variance. There was a small increase in the hot plate percent maximum possible effect (MPE) from -45.7 to -61.1 in group A over the length of the experiment, but a very small decrease for group B over the same period (-33.5 to -28.8). For the saline control group, there was a small increase toward 0 %MPE over the same time frame (-15.0 to 1.7). The %MPE differences were significant between groups A and C (P test. c-Fos was mainly observed in the raphe pallidus area with significant differences between groups A and B at 3 and 6 hours after injection of CFA (P = .027 and .022, respectively). The results of this study indicate that food consistency (hardness) influences nocifensive behavior in this animal model via a descending pathway operating at the supraspinal level. Copyright © 2014 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.
Bruehl, Stephen; Burns, John W.; Gupta, Rajnish; Buvanendran, Asokumar; Chont, Melissa; Kinner, Ellen; Schuster, Erik; Passik, Steven; France, Christopher R.
Predictors of responsiveness to opioid analgesic medications are not well understood. This study tested whether individual differences in endogenous opioid (EO) function are associated with analgesic responsiveness to morphine. In randomized, counterbalanced order over three sessions, 45 chronic low back pain participants (CLBP) and 31 healthy controls received an opioid antagonist (8mg naloxone), morphine (0.08 mg/kg), or placebo. Participants then engaged in two laboratory evoked pain tasks (ischemic, thermal). Outcomes included pain threshold, pain tolerance, and pain ratings. Indexes of EO function and morphine analgesic responsiveness were derived for each measure as the difference in pain responses between the placebo condition, and naloxone or morphine conditions respectively. For all 7 pain measures across the two laboratory pain tasks, greater EO function was associated with significantly lower morphine analgesic responsiveness (p ≤ .001 − p=.02). Morphine reduced pain responses of low EO individuals to levels similar to high EO individuals under placebo. Higher placebo condition evoked pain sensitivity was associated with significantly greater morphine analgesic responsiveness for 5 of 7 pain measures (p<.001 − p=.02). These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes (p’s<.05). In the laboratory evoked pain context, opioid analgesic medications may supplement inadequate EO analgesia, with little incremental benefit in those with pre-existing high EO function. Implications for personalized medicine are discussed. PMID:23748117
Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam
Cognitive impairment is commonly associated with pain. The modulatory role of orexin 1 receptor (OX1R) in pain pathways as well as learning and memory processes is reported in several studies. The current study was designed to investigate the possible role of CA1-hippocampal OX1R on spatial learning and memory of rats following capsaicin-induced orofacial pain. Orofacial pain was induced by subcutaneous intra lip injection of capsaicin (100 μg). CA1 administration of orexin A and its selective antagonist (SB-334867-A) were performed 20 minutes prior to capsaicin injection. Learning and spatial memory performances were assessed by Morris Water Maze (MWM) task. Capsaicin treated rats showed impairment in spatial learning and memory. In addition, pretreatment with orexin A (20 and 40 nM/rat) significantly attenuated learning and memory impairment in capsaicin-treated rats. Conversely, blockage of OX1R via SB-334867-A (40 and 80 nM/rat) significantly exaggerated learning and memory loss in capsaicin-treated rats. The obtained results indicated that CA1 OX1R may be involved in modulation of capsaicin -induced spatial learning and memory impairment.
Takeda, Mamoru; Takehana, Shiori; Sekiguchi, Kenta; Kubota, Yoshiko; Shimazu, Yoshihito
...) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief...
Palit, Shreela; Bartley, Emily J; Kuhn, Bethany L; Kerr, Kara L; DelVentura, Jennifer L; Terry, Ellen L; Rhudy, Jamie L
Premenstrual dysphoric disorder (PMDD) is characterized by severe affective and physical symptoms, such as increased pain, during the late-luteal phase of the menstrual cycle. The mechanisms underlying hyperalgesia in women with PMDD have yet to be identified, and supraspinal pain modulation has yet to be examined in this population. The present study assessed endogenous pain inhibitory processing by examining conditioned pain modulation (CPM, a painful conditioning stimulus inhibiting pain evoked by a test stimulus at a distal body site) of pain and the nociceptive flexion reflex (NFR, a spinally-mediated withdrawal reflex) during the mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle. Participants were regularly-cycling women (14 without PMDD; 14 with PMDD). CPM was assessed by delivering electrocutaneous test stimuli to the sural nerve before, during, and after a painful conditioning ischemia task. Participants rated their pain to electrocutaneous stimuli, and NFR magnitudes were measured. A linear mixed model analysis was used to assess the influence of group and menstrual phase on CPM. Compared with controls, women with PMDD experienced greater pain during the late-luteal phase and enhanced spinal nociception during the ovulation phase, both of which were independent of CPM. Both groups showed CPM inhibition of pain that did not differ by menstrual phase. Only women with PMDD evidenced CPM inhibition of NFR. Endogenous modulation of pain and spinal nociception is not disrupted in women with PMDD. Additionally, greater NFR magnitudes during ovulation in PMDD may be due to tonically-engaged descending mechanisms that facilitate spinal nociception, leading to enhanced pain during the premenstrual phase.
Umar, A H; Suleiman, I; Muhammed, H
Lead (Pb) is cheap and there is a long tradition of its use, but its toxic effects have also been recognized. There is increased public health concern regarding the hazards of low dose Pb exposure to adults and children. Studies have shown the risks for hypertension, decrements in renal function, subtle decline in cognitive function, and adverse reproductive outcome at low blood Pb level. In this study, the possible modulatory role of cobalt (II) chloride (CoCl2) on low level Pb exposure on tail immersion test and formalin induced pain was investigated. Twenty adult Wistar rats of both sexes (weight 150g to 200g) were used. The animals were divided into four groups (n = 5) and administered Pb (5mg/kg), Pb (5mg/kg) + CoCl2 (50mg/kg) and CoCl2 (50mg/kg) orally for twenty-eight days. The last group served as control and were given distilled water only. In the tail immersion test, there was no significant change in reaction time for all three groups when compared to the control. In the formalin-induced pain, pain score after five and forty-five minutes also do not show significant change for all the three groups when compared to control. This work suggested that exposure to 5mg/kg Pb for twenty-eight days do not significantly impair reaction time in tail immersion test and pain score in formalin induced pain in Wistar rats. Also, administration of 50mg/kg CoCl2 do not improve performance of the animals in the experiments.
George Steven Z
Full Text Available Abstract Background Our purpose was to develop an induced musculoskeletal pain model of acute low back pain and examine the relationship among pain, disability and fear in this model. Methods Delayed onset muscle soreness was induced in 52 healthy volunteers (23 women, 17 men; average age 22.4 years; average BMI 24.3 using fatiguing trunk extension exercise. Measures of pain intensity, unpleasantness, and location, and disability, were tracked for one week after exercise. Results Pain intensity ranged from 0 to 68 with 57.5% of participants reporting peak pain at 24 hours and 32.5% reporting this at 48 hours. The majority of participants reported pain in the low back with 33% also reporting pain in the legs. The ratio of unpleasantness to intensity indicated that the sensation was considered more unpleasant than intense. Statistical differences were noted in levels of reported disability between participants with and without leg pain. Pain intensity at 24 hours was correlated with pain unpleasantness, pain area and disability. Also, fear of pain was associated with pain intensity and unpleasantness. Disability was predicted by sex, presence of leg pain, and pain intensity; however, the largest amount of variance was explained by pain intensity (27% of a total 40%. The second model, predicting pain intensity only included fear of pain and explained less than 10% of the variance in pain intensity. Conclusions Our results demonstrate a significant association between pain and disability in this model in young adults. However, the model is most applicable to patients with lower levels of pain and disability. Future work should include older adults to improve the external validity of this model.
Full Text Available Shreela Palit,1 Emily J Bartley,2 Bethany L Kuhn,1 Kara L Kerr,1 Jennifer L DelVentura,1 Ellen L Terry,1 Jamie L Rhudy1 1Department of Psychology, University of Tulsa, Tulsa, OK, USA; 2Department of Community Dentistry and Behavioral Science, Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA Purpose: Premenstrual dysphoric disorder (PMDD is characterized by severe affective and physical symptoms, such as increased pain, during the late-luteal phase of the menstrual cycle. The mechanisms underlying hyperalgesia in women with PMDD have yet to be identified, and supraspinal pain modulation has yet to be examined in this population. The present study assessed endogenous pain inhibitory processing by examining conditioned pain modulation (CPM, a painful conditioning stimulus inhibiting pain evoked by a test stimulus at a distal body site of pain and the nociceptive flexion reflex (NFR, a spinally-mediated withdrawal reflex during the mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle. Methods: Participants were regularly-cycling women (14 without PMDD; 14 with PMDD. CPM was assessed by delivering electrocutaneous test stimuli to the sural nerve before, during, and after a painful conditioning ischemia task. Participants rated their pain to electrocutaneous stimuli, and NFR magnitudes were measured. A linear mixed model analysis was used to assess the influence of group and menstrual phase on CPM. Results: Compared with controls, women with PMDD experienced greater pain during the late-luteal phase and enhanced spinal nociception during the ovulation phase, both of which were independent of CPM. Both groups showed CPM inhibition of pain that did not differ by menstrual phase. Only women with PMDD evidenced CPM inhibition of NFR. Conclusion: Endogenous modulation of pain and spinal nociception is not disrupted in women with PMDD. Additionally, greater NFR magnitudes during ovulation
Gwyn N Lewis
Full Text Available BACKGROUND: Conditioned pain modulation paradigms are often used to assess the diffuse noxious inhibitory control (DNIC system. DNICs provide one of the main supraspinal pain inhibitory pathways and are impaired in several chronic pain populations. Only one previous study has examined the psychometric properties of the conditioned pain modulation technique and this study did not evaluate intersession reliability.
Jarred W Younger
Full Text Available The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.
Laboureyras, Emilie; Aubrun, Frédéric; Monsaingeon, Maud; Corcuff, Jean-Benoît; Laulin, Jean-Paul; Simonnet, Guy
Opioid-induced hyperalgesia (OIH) is a recognized complication of opioid use that may facilitate the development of exaggerated postoperative pain. To examine the role of genetic factors on OIH by comparing four rat strains. Because the authors previously reported that the endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization, genetic and environmental factor interactions were also evaluated. First, the propensity of Sprague Dawley, Wistar, Lewis and Fischer rats to develop OIH following single or repeated fentanyl exposures was compared by measuring the nociceptive threshold using the paw pressure vocalization test. Second, Sprague Dawley and Fischer rats were exposed to a series of three non-nociceptive environmental stress sessions to evaluate the ability of endogenous opioids to enhance hyperalgesia associated with a carrageenan-induced hind-paw inflammation test performed two weeks later. Sprague Dawley, Wistar and Lewis rats exhibited OIH, although differences were observed. OIH was not observed in Fischer rats. Inflammatory hyperalgesia enhancement induced through previous stress in Sprague Dawley rats was not observed in Fischer rats. The pain level not only reflects nociceptive inputs but also depends on both the history and genetic factors of the individual. Genetic and environmental models may provide new insights into the mechanisms that underlie individual differences observed in postoperative pain.
Lannersten, Lisa; Kosek, Eva
The aim of this study was to investigate how exercise influenced endogenous pain modulation in healthy controls, shoulder myalgia patients and fibromyalgia (FM) patients. Twenty-one healthy subjects, 20 shoulder myalgia patients and 20 FM patients, all females, participated. They performed standardized static contractions, that is, outward shoulder rotation (m. infraspinatus) and knee extension (m. quadriceps). Pressure pain thresholds (PPTs) were determined bilaterally at m. infraspinatus and m. quadriceps. During contractions PPTs were assessed at the contracting muscle, the resting homologous contralateral muscle and contralaterally at a distant site (m. infraspinatus during contraction of m. quadriceps and vice versa). Myalgia patients had lower PPTs compared to healthy controls at m. infraspinatus bilaterally (ppain regulatory mechanisms in myalgia patients during contraction of the non-afflicted m. quadriceps, but a lack of pain inhibition during contraction of the painful m. infraspinatus. FM patients failed to activate their pain inhibitory mechanisms during all contractions. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Staikopoulos, Vasiliki; Gosnell, Martin E.; Anwer, Ayad G.; Mustafa, Sanam; Hutchinson, Mark R.; Goldys, Ewa M.
Fluorescence-based bio-imaging methods have been extensively used to identify molecular changes occurring in biological samples in various pathological adaptations. Auto-fluorescence generated by endogenous fluorescent molecules within these samples can interfere with signal to background noise making positive antibody based fluorescent staining difficult to resolve. Hyperspectral imaging uses spectral and spatial imaging information for target detection and classification, and can be used to resolve changes in endogenous fluorescent molecules such as flavins, bound and free NADH and retinoids that are involved in cell metabolism. Hyperspectral auto-fluorescence imaging of spinal cord slices was used in this study to detect metabolic differences within pain processing regions of non-pain versus sciatic chronic constriction injury (CCI) animals, an established animal model of peripheral neuropathy. By using an endogenous source of contrast, subtle metabolic variations were detected between tissue samples, making it possible to distinguish between animals from non-injured and injured groups. Tissue maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant tissue regions with compromised mitochondrial function. Taken together, our results demonstrate that hyperspectral imaging provides a new non-invasive method to investigate central changes of peripheral neuropathic injury and other neurodegenerative disease models, and paves the way for novel cellular characterisation in health, disease and during treatment, with proper account of intrinsic cellular heterogeneity.
Full Text Available BACKGROUND: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB, which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARgamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. CONCLUSION: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.
Co supplementation of rooibos and RPO significantly (P<0.05) increased plasma total polyphenol content, trolox equivalent antioxidant capacity (TEAC), as well as blood GSH and GSH/GSSG ratio. Plasma conjugated dienes (CD) and hepatic malondialdehyde (MDA) levels were reduced significantly by the combination ...
Mads U Werner
Full Text Available Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR antagonists in placebo-controlled, double-blind studies using 'inhibitory' or 'sensitizing', physiological test paradigms in healthy human subjects. The databases PubMed and Embase were searched according to predefined criteria. Out of a total of 2,142 records, 63 studies (1,477 subjects [male/female ratio = 1.5] were considered relevant. Twenty-five studies utilized 'inhibitory' test paradigms (ITP and 38 studies utilized 'sensitizing' test paradigms (STP. The ITP-studies were characterized as conditioning modulation models (22 studies and repetitive transcranial magnetic stimulation models (rTMS; 3 studies, and, the STP-studies as secondary hyperalgesia models (6 studies, 'pain' models (25 studies, summation models (2 studies, nociceptive reflex models (3 studies and miscellaneous models (2 studies. A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and rTMS. In the remaining 14 conditioning modulation studies either absence of effects or ambiguous effects by MOR-antagonists, were observed. In the STP-studies, no effect of the opioid-blockade could be demonstrated in 5 out of 6 secondary hyperalgesia studies. The direction of MOR-antagonist dependent effects upon pain ratings, threshold assessments and somatosensory evoked potentials (SSEP, did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect, presumably mediated by an EOS-dependent mechanisms of analgesia and hyperalgesia.
Bang, Sangsu; Yoo, Sungjae; Oh, Uhtaek; Hwang, Sun Wook
Environmental or internal noxious stimuli excite the primary sensory nerves in our body. The sensory nerves relay these signals by electrical discharges to the brain, leading to pain perception. Six transient receptor potential (TRP) ion channels are expressed in the sensory nerve terminals and play a crucial role in sensing diverse noxious stimuli. Cation influx through activated TRP ion channels depolarizes the plasma membrane, resulting in neuronal excitation and pain. Natural and synthetic compounds have been found to act on these sensory TRP channels to alter the nociception. Evidence is growing that lipidergic substances are also cable of modifying TRP ion channel activity by direct binding. Here, we focus on endogenously generated lipids that modulate the sensory TRP activities. Unsaturated fatty acids or their metabolites via lipoxygenase, cyclooxygenase or epoxygenase are able to modulate (activate, inhibit or potentiate) the function of specific TRPs. Isoprene lipids, diacylglycerol, resolvin, and lysophospholipids also show distinct activities on sensory TRP channels. Outcomes caused by the interactions between sensory TRPs and lipid ligands are also discussed. The knowledge we collected here implicates that information on lipidergic ligands may contribute to our understanding of peripheral pain mechanism and provide an opportunity to design novel therapeutic strategies.
Wilder-Smith, O.H.G.; Schreyer, T.; Scheffer, G.J.; Arendt-Nielsen, L.
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
Yang, Jun; Liang, Jin-Ying; Li, Peng; Pan, Yan-Juan; Qiu, Pei-Yong; Zhang, Jing; Hao, Fang; Wang, Da-Xin
Periaqueductal gray (PAG) plays a very important role in pain modulation through endogenous opiate peptides including leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), β-endorphin (β-Ep) and dynorphin A(1-13) (DynA(1-13)). Our pervious study has demonstrated that intra-PAG injection of oxytocin (OXT) increases the pain threshold, and local administration of OXT receptor antagonist decreases the pain threshold, in which the antinociceptive role of OXT can be reversed by pre-PAG administration of OXT receptor antagonist. The experiment was designed to investigate the effect of OXT on endogenous opiate peptides in the rat PAG during the pain process. The results showed that (1) the concentrations of OXT, L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased after the pain stimulation; (2) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were decreased by the OXT receptor antagonist; (3) the increased pain threshold induced by the OXT was attenuated by naloxone, an opiate receptor antagonist; and (4) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased by exogenous OXT administration. The data suggested that OXT in the PAG could influence the L-Ek, M-Ek and β-Ep rather than DynA(1-13) to participate in pain modulation, i.e. OXT in the PAG participate in pain modulation by influencing the L-Ek, M-Ek and β-Ep rather than DynA(1-13). Copyright © 2011 Elsevier Inc. All rights reserved.
Nijs, Jo; Kosek, Eva; Van Oosterwijck, Jessica; Meeus, Mira
Background: Exercise is an effective treatment for various chronic pain disorders, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Although the clinical benefits of exercise therapy in these populations are well established (i.e. evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g. central pain modulation). Objectives: Reviewing the available evidence addres...
Lautenschläger, Gothje; Habig, Kathrin; Best, Christoph; Kaps, Manfred; Elam, Mikael; Birklein, Frank; Krämer, Heidrun H
The interaction between sympathetic vasoconstrictor activity to muscles [muscle sympathetic nerve activity (MSNA), burst frequency (BF) and burst incidence (BI)] and different stress and somatosensory stimuli is still unclear. Eighteen healthy men (median age 28 years) underwent microneurography recordings from the peroneal nerve. MSNA was recorded during heat pain (HP) and cold pain (CP) alone as well as combined with different stress tasks (mental arithmetic, singing, giving a speech). An additional nine healthy men (median age 26 years) underwent the stimulation protocol with an additional control task (thermal pain combined with listening to music) to evaluate possible attentional confounders. MSNA was significantly increased by CP and HP. CP-evoked responses were smaller. The diastolic blood pressure followed the time course of MSNA while heart rate remained unchanged. The mental stress tasks further increased MSNA and were sufficient to reduce pain while the control task had no effect. MSNA activity correlated negatively with pain intensity and positively with analgesia. High blood pressure values were associated with lower pain intensity. Our study indicates an impact of central sympathetic drive on pain and pain control. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Full Text Available Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM paradigms. In this study we investigated (i the influence of age on CPM and (ii the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20-40 years, middle-aged = 41-60 years, old = 61-80 years were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS and immersion of the contralateral foot into ice water as the conditioning stimulus (CS. The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age.
Hsieh, Yueh-Ling; Hong, Chang-Zern; Liu, Szu-Yu; Chou, Li-Wei; Yang, Chen-Chia
Acupuncture applied at myofascial trigger points (MTrPs) of distant anatomical regions, to reduce pain in a patient's area of primary complaint, is one strategy that is available to manage myofascial pain. However, the endogenous opioid-mediated analgesic mechanism of distant acupuncture associated with pain control is still unclear. This aims of this study were to evaluate the changes in enkephalin and β-endorphin in serum, spinal cord, dorsal root ganglion (DRG) and muscle induced by acupuncture at distant myofascial trigger spots (MTrSs, similar to human MTrPs) in rabbits, to explore its underlying remote analgesic mechanism. Acupuncture at MTrSs of a distant muscle (gastrocnemius) was performed either for one session or five daily sessions in rabbits. The levels of enkephalin and β-endorphin in proximal muscle (biceps femoris), serum, DRGs and spinal cords (L5-S2) were then determined by immunoassay immediately and 5 days after treatment. Immediately after treatment, acupuncture comprising both one dose and five doses significantly enhanced spinal enkephalin expression and serum β-endorphin levels (pendorphin levels in the biceps femoris and DRGs (p0.05). Furthermore, 5 days after treatment, significantly increased levels of spinal enkephalin and serum β-endorphin persisted in animals that received 5-dose acupuncture (ppain management. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Winn, Shelley R; Emerich, Dwaine F
Spinal injections (intrathecal) of norepinephrine and/or opiod agonists are antinociceptive and when administered together may act in synergy. Spinal implants of adrenal chromaffin cells are an effective method for sustained delivery of the analgesic substances norepinephrine and enkephalin to the central nervous system (CNS). One method of packaging and implanting cell-loaded devices into the intrathecal space of recipients is by encapsulating the cell suspensions in a polymer membrane prior to implantation. Cells/tissue packaged within an encapsulating membrane obviate the need for immunosuppressive therapies in transplant recipients. In addition, device output can be quantified prior to implantation, and following the removal of the spinal implant. The ability to retrieve the devices with the present tubular configuration also confers an additional margin of safety over unencapsulated chromaffin cell implants. This paper reviews the research and clinical observations of cellular transplants containing adrenal chromaffin cells for relieving chronic pain. Encapsulated cell technology is discussed with an emphasis on our experiences developing pain-modulating clinical devices. The human-sized prototype devices were loaded with enzymatically isolated bovine chromaffin cells and maintained in vitro for 7 - 8 days in serum-free media. Two days prior to implantation, each device was assayed by static incubation to measure catecholamine and met-enkephalin output, and qualified devices (n = 6) were implanted into the sheep subarachnoid space for 6 weeks. Following a 6 week in life period, the retrieval forces of prototype devices were measured during removal from the subarachnoid space. Static incubation of the devices immediately following retrieval and after a 24 hour re-incubation period were used to quantify norepinephrine and met-enkephalin secretion profiles. This study demonstrated the safety, retrievability and maintenance of pharmacologically active encapsulated
Mazzardo-Martins, Leidiane; Martins, Daniel F; Marcon, Rodrigo; Dos Santos, Ubirajara D; Speckhann, Breno; Gadotti, Vinícius M; Sigwalt, André Roberto; Guglielmo, Luiz Guilherme A; Santos, Adair Roberto Soares
The present study examined the hyponociceptive effect of swimming exercise in a chemical behavioral model of nociception and the mechanisms involved in this effect. Male mice were submitted to swimming sessions (30 min/d for 5 days). Twenty-four hours after the last session, we noticed that swimming exercise decreased the number of abdominal constriction responses caused by acetic acid compared with the nonexercised group. The hyponociception caused by exercise in the acetic acid test was significantly attenuated by intraperitoneal (i.p.) pretreatment of mice with naloxone (a nonselective opioid receptor antagonist, 1 mg/kg), ρ-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days), and by bilateral adrenalectomy. Collectively, the present results provide experimental evidences indicating for the first time that high-intensity extended swimming exercise reduces pain-related behavior in mice. The mechanisms involve an interaction with opioid and serotonin systems. Furthermore, endogenous opioids released by adrenal glands probably are involved in this effect. Our results indicate that high-intensity extended exercise endogenously controls acute pain by activation of opioidergic and serotonergic pathways. Furthermore, these results support the use of exercise as a nonpharmacological approach for the management of acute pain. Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.
Flood, Andrew; Waddington, Gordon; Thompson, Kevin; Cathcart, Stuart
The potential relationship between physical activity and endogenous pain modulatory capacity remains unclear. Therefore, the aim of the current study was to compare the pain modulatory responses of athletes and non-athletes. Conditioned pain modulation (CPM) was assessed in 15 athletes and 15 non-athletes at rest. Participation was restricted to pain-free males between 18 and 40 years of age. To measure CPM capacity, a sequential CPM testing protocol was implemented, whereby a test stimulus (pressure pain threshold [PPT]) was presented before and immediately after a conditioning stimulus (4-min cold-pressor test). Pain intensity ratings were obtained at 15-s intervals throughout the cold-pressor task using a numerical rating scale. Athletes demonstrated higher baseline PPTs compared to non-athletes (P = .03). Athletes also gave lower mean (P athletes, showing enhanced CPM in athletes compared to non-athletes (P athletes helps clarify previous mixed findings. Potential implications for exercise performance and injury are discussed.
Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent
Full Text Available Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.
Takeda, Mamoru; Takehana, Shiori; Sekiguchi, Kenta; Kubota, Yoshiko; Shimazu, Yoshihito
Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.
Endogenous hypertriglyceridemia, which includes familial hypertriglyceridemia and idiopathic hypertriglyceridemia, is characterized by the increased level of VLDL-triglycerides in the blood. Increased production of VLDL from the liver and the decreased catabolism of VLDL-TG in the vessel, which are also the main metabolic features of insulin resistance, have been proposed to be the causes of endogenous hypertriglyceridemia. Genetic factors responsible for endogenous hypertriglyceridemia have been elucidated in several studies, however, these factors have so far not been clearly identified yet; thus the causes of endogenous hypertriglyceridemia would be polygenic. Recent advances in the genetic analytical methods like genome-wide association study would hopefully unveil the whole pictures of endogenous hypertriglyceridemia.
Kuzminskyte, Ruta; Kupers, Ron; Videbech, Poul; Gjedde, Albert; Fink, Per
Many patients in a variety of medical settings suffer from persistently painful bodily symptoms that are not explained by known pathophysiological mechanisms. In the most severe cases, these patients complain of multiple functional somatic symptoms (MFS). We tested the hypothesis of reduced pain threshold and pain tolerance levels in patients with MFS. Twenty-two patients with MFS and 27 age- and sex-matched healthy control subjects volunteered for this study. The subjects received innocuous and noxious thermal stimuli to the volar forearm by means of a Peltier contact heat probe. We assessed pain threshold and pain tolerance with an ascending staircase method. Anxiety levels and hemodynamic (blood pressure, pulse rate) and endocrine (cortisol and prolactin release) responses were measured before and after pain testing. We found no group differences for any of the physiological or self-rated subjective emotional responses to the pain stressor. Contrary to the hypothesis, the pain threshold was not lower in MFS; the data even showed a trend in the opposite direction. Pain tolerance scores were identical in the two groups but they correlated negatively with the number of functional somatic symptoms in MFS patients. Importantly, patients had a smaller temperature range between their pain threshold and pain tolerance scores, suggesting that they differentiate poorly within the noxious range. Minor increases in stimulus intensity of supra-threshold painful stimuli may lead to disproportionate increases in pain intensity in MFS patients, suggesting a defunct endogenous pain modulatory system. Copyright 2010 Elsevier Inc. All rights reserved.
Santos, Fabio Martinez; Grecco, Leandro Henrique; Pereira, Marcelo Gomes; Oliveira, Mara Evany; Rocha, Priscila Abreu; Silva, Joyce Teixeira; Martins, Daniel Oliveira; Miyabara, Elen Haruka; Chacur, Marucia
The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats. The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury. At the end of the sessions, the PAG was analyzed using Western blot assays for opioid receptors. Locomotion was analyzed by the Sciatic functional index (SFI), and muscle force was analyzed by the BIOPAC system. An improvement in locomotion was observed in animals treated with NM compared with injured animals. Animals treated with NM showed an increase in maximal tetanic force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR and KOR levels, respectively, after CCI injury compared to those from naive animals and an increase of 17% (p < 0.05) in KOR expression only after NM treatment compared to naive animals. There were no significant changes in MOR expression in the PAG. These data provide evidence that a non-pharmacological NM technique facilitates pain relief by endogenous analgesic modulation.
Malfliet, Anneleen; Leysen, Laurence; Pas, Roselien; Kuppens, Kevin; Nijs, Jo; Van Wilgen, Paul; Huysmans, Eva; Goudman, Lisa; Ickmans, Kelly
In the last decade, evidence regarding chronic pain has developed exponentially. Numerous studies show that many chronic pain populations show specific neuroplastic changes in the peripheral and central nervous system. These changes are reflected in clinical manifestations, like a generalized hypersensitivity of the somatosensory system. Besides a hypersensitivity of bottom-up nociceptive transmission, there is also evidence for top-down facilitation of pain due to malfunctioning of the endogenous descending nociceptive modulatory systems. These and other aspects of modern pain neuroscience are starting to be applied within daily clinical practice. However, currently the application of this knowledge is mostly limited to the general adult population with musculoskeletal problems, while evidence is getting stronger that also in other chronic pain populations these neuroplastic processes may contribute to the occurrence and persistence of the pain problem. Therefore, this masterclass article aims at giving an overview of the current modern pain neuroscience knowledge and its potential application in post-cancer, paediatric and sports-related pain problems. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.
... Grant Funding for Pain Initiatives Current Funding Opportunities Research on the Impact of Creative Arts in Military Populations More Health Professional Information Earn CME More Related Topics Chronic Pain ( NINDS ) NIH Pain Seminar Series Pain: You Can Get Help ( NIA ) NIH ...
Landburg, Precious P.; Teerlink, Tom; Muskiet, Frits A. J.; Duits, Ashley J.; Schnog, John-John B.
Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in the clinically asymptomatic state of sickle cell disease (SCD). However, the role of ADMA during vaso-occlusive complications has not been defined. ADMA concentrations were
modulatory effects of dezocine-propofol, and fentanyl-propofol combinations in colonoscopy. Methods: One hundred and thirty-four patients who received painless colonoscopy in Eastern Medical District of Linyi People's Hospital, Linyi City, ...
Stephan, Bradley C; Parsa, Fereydoun D
Prescribed opioids are routinely used for many postoperative patients. However, these medications have daunting adverse effects on the body's innate pain management system--the action of the beta-endorphins. The prescribed opioids not only severely impair the function of the mu-opioid receptors, but also inhibit the release of beta-endorphin. This is unfortunate, because beta-endorphin appears to be a much more potent agonist of the mu-opioid receptor than opioids. In addition, beta-endorphin indirectly elevates dopamine, a neurotransmitter related to feelings of euphoria. Therefore, by prescribing opioids, practitioners may inadvertently prolong and increase the overall intensity of the postoperative patients' pain as well as herald anhedonia. This article highlights the relationships between prescribed (exogenous) opioids, beta-endorphins, mu-opioid receptors, wellness, mood, and postoperative pain. The role of patient education, opioid alternatives, and additional recommendations regarding pain control in the postoperative patient are also discussed.
This thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain phenotypes are determined in patients with chronic pain. The ability of patients with acute pain after
Full Text Available The functional brain connectivity studies are generally based on the synchronization of the resting-state functional magnetic resonance imaging (fMRI signals. Functional connectivity measures usually assume a stable relationship over time; however, accumulating studies have reported time-varying properties of strength and spatial distribution of functional connectivity. The present study explored the modulation of functional connectivity between two regions by a third region using the physiophysiological interaction (PPI technique. We first identified eight brain networks and two regions of interest (ROIs representing each of the networks using a spatial independent component analysis. A voxel-wise analysis was conducted to identify regions that showed modulatory interactions (PPI with the two ROIs of each network. Mostly, positive modulatory interactions were observed within regions involved in the same system. For example, the two regions of the dorsal attention network revealed modulatory interactions with the regions related to attention, while the two regions of the extrastriate network revealed modulatory interactions with the regions in the visual cortex. In contrast, the two regions of the default mode network (DMN revealed negative modulatory interactions with the regions in the executive network, and vice versa, suggesting that the activities of one network may be associated with smaller within network connectivity of the competing network. These results validate the use of PPI analysis to study modulation of resting-state functional connectivity by a third region. The modulatory effects may provide a better understanding of complex brain functions.
Juul, A; Pedersen, A T
Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further...
neuropathic pain syndromes.10. Opioid analgesics. In response to severe or persistent pain, interneurons in the dorsal horn release endogenous opioids that work to reduce perceived pain. These endogenous substances. (enkephalins, endorphins and dynorphins) play a major role in the mechanism of pain reduction and ...
Hannan, Peer Abdul; Khan, Jamshaid Ali; Ullah, Irfan; Ullah, Safi
Hyperlipidemia, a major pathological condition associated with disrupted lipid levels and physiological redox homeostasis. The excessive release of reactive oxygen species (ROS) leads to enhanced lipid peroxidation, aggravated atherosclerosis and oxidative stress. Integration of natural antioxidant blends in alone or with conventional treatments can alleviate these issues synergistically contributing least side effects. Published literature reported the efficacy of natural antioxidants as individual and in combinations in various conditions but less data is available on their evaluation in low dose ratio blends particularly in hypercholesterolemic diet. Antihyperlipidemic effects of selected natural antioxidants; the phenolic oligomeric proanthocyanidins (OPC) and pterostilbene (PT) with niacin (NA) were investigated in current study. Their effects on lipid profile, lipid peroxidation and their aptitude to establish redox state between oxidants and antioxidants in body were evaluated in high cholesterol diet fed animal model. Male albino rabbits (n = 6) weighing 1.2-1.6 kg, supplemented with high cholesterol diet (400 mg/kg) for 12 weeks were used in the experiment. Antioxidants were administered individual high (100 mg/kg) and in low dose combinations (total dose = 100 mg/kg). Student's t test and one way analysis of variance (ANOVA) followed by Dunnet's test were used as statistical tools for evaluation. The results showed synergistic effects of low dose antioxidant blends. Therapies retarded elevation in blood lipid levels, lipid peroxidation and blood antioxidant depletion and consequently contributed in reestablishing redox homeostasis. The LDL/HDL ratio and atherogenic index were suppressed significantly in blend therapies with maximum effects of 59.3 and 25 % (p >0.001) observed in 50:30:20 ratios of OPC, NA and PT, compared to individual therapies 37 and 18 % max respectively. Moreover the results were also in close proximity with the statin therapy (52.66, 26.28 %). This study provides an evidence for natural antioxidants blends superiority over individual therapy in chronic diseases like hyperlipidemia. Such therapies in human equivalent doses can help in mitigating chronic illnesses in general populations.
Coppola, Jennifer J; Ward, Nicholas J; Jadi, Monika P; Disney, Anita A
Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states. Copyright © 2016 Elsevier Ltd. All rights reserved.
Stephan, Bradley C; Parsa, Fereydoun D
Prescribed opioids are routinely used for many postoperative patients. However, these medications have daunting adverse effects on the body's innate pain management system - the action of the beta-endorphins. The prescribed opioids not only severely impair the function of the mu-opioid receptors, but also inhibit the release of beta-endorphin. This is unfortunate, because beta-endorphin appears to be a much more potent agonist of the mu-opioid receptor than opioids. In addition, beta-endorphi...
Phelps, Elizabeth A; Lempert, Karolina M; Sokol-Hessner, Peter
Although the prevalent view of emotion and decision making is derived from the notion that there are dual systems of emotion and reason, a modulatory relationship more accurately reflects the current research in affective neuroscience and neuroeconomics. Studies show two potential mechanisms for affect's modulation of the computation of subjective value and decisions. Incidental affective states may carry over to the assessment of subjective value and the decision, and emotional reactions to the choice may be incorporated into the value calculation. In addition, this modulatory relationship is reciprocal: Changing emotion can change choices. This research suggests that the neural mechanisms mediating the relation between affect and choice vary depending on which affective component is engaged and which decision variables are assessed. We suggest that a detailed and nuanced understanding of emotion and decision making requires characterizing the multiple modulatory neural circuits underlying the different means by which emotion and affect can influence choices.
The work aim at investigating the channeling or modulatory effects of polyethylene glycol (PEG) (MW 4000 and 6000) on drug release from ibuprofen sustained release formulation. Different batches of ibuprofen matrix granules and tablet were prepared by melt granulation using different concentrations of carnauba wax and ...
This study examined the effects of short-term use of oral artesunate on testicular function in rats. Artesunate is an atermisinin derivative, now widely used to treat malaria. We also studied the modulatory effects of ascorbic acid (vitamin C) on any toxicity that might occur. We compared sperm parameters, serum testosterone, ...
Experiments were performed on adult local pigs with the aim of investigating the modulatory role of ascorbic acid (AA) on their behavioural responses to 4-h, road transportation during the harmattan season. Sixteen adult pigs administered with AA at the dose of 250 mg/kg dissolve in sterile water served as experimental ...
This study was carried out with the aim of investigating the modulatory effect of ascorbic acid (AA) on the physiological and behavioural parameters in confined West African dwarf goats during the rainy season. A total of fourteen adult West Africa Dwarf goats, male and non-pregnant, non-nursing female were used for the ...
Possible oxidative effects of isotretinoin and modulatory effects of vitamins A and C in Saccharomyces cerevisiae. Alaíde Silva Lemos, Vanessa Leopoldino Coelho Rodrigues, Marcus Vinícius Oliveira Barros de Alencar, Md. Torequl Islam, Raí Pablo Sousa de Aguiar, Ana Maria Oliveira Ferreira da Mata, Ricardo Melo de ...
)-y and tumor necrosis factor (TNF)-a are able to synergistically induce apoptosis in HaCaT keratinocyte cells. The present study aimed to elucidate modulatory effects of ethanolic extracts derived from Thai traditional medicinal plants on ...
Susu M. Zughaier
Full Text Available Protegrins are porcine antimicrobial peptides (AMPs that belong to the cathelicidin family of host defense peptides. Protegrin-1 (PG-1, the most investigated member of the protegrin family, is an arginine-rich peptide consisting of 18 amino acid residues, its main chain adopting a β-hairpin structure that is linked by two disulfide bridges. We report on the immune modulatory activity of PG-1 and its analogs in neutralizing bacterial endotoxin and capsular polysaccharides, consequently inhibiting inflammatory mediators’ release from macrophages. We demonstrate that the β-hairpin structure motif stabilized with at least one disulfide bridge is a prerequisite for the immune modulatory activity of this type of AMP.
Vægter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas
AND METHODS: On 2 days, manual pressure pain thresholds (PPTs) were recorded at the legs, arm, and shoulder in 61 chronic pain patients and they performed the cold pressor test, 2 exercise conditions (bicycling and isometric contraction), and a control condition in a randomized and counterbalanced order. PPTs...... implications as clinicians should evaluate pain sensitivity when considering treatment options utilizing the descending modulatory pain control.......OBJECTIVES: In chronic pain patients, impaired conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH) have been reported. No studies have compared CPM and EIH in chronic musculoskeletal pain patients with high pain sensitivity (HPS) and low pain sensitivity (LPS). MATERIALS...
Roesler, Rafael; Schröder, Nadja
Biological research has unraveled many of the molecular and cellular mechanisms involved in the formation of long-lasting memory, providing new opportunities for the development of cognitive-enhancing drugs. Studies of drug enhancement of cognition have benefited from the use of pharmacological treatments given after learning, allowing the investigation of mechanisms regulating the consolidation phase of memory. Modulatory systems influencing consolidation processes include stress hormones and several neurotransmitter and neuropeptide systems. Here, we review some of the findings on memory enhancement by drug administration in animal models, and discuss their implications for the development of cognitive enhancers. Copyright © 2011 Elsevier Inc. All rights reserved.
van Damme, E.E.C.; Hurkens, S.
We consider a linear price setting duopoly game with differentiated products and determine endogenously which of the players will lead and which will follow. While the follower role is most attractive for each firm, we show that waiting is more risky for the low cost firm so that, consequently, risk dominance considerations, as in Harsanyi and Selten (1988), allow the conclusion that only the high cost firm will choose to wait. Hence, the low cost firm will emerge as the endogenous price leader.
Atienza, Mercedes; Cantero, Jose L
Growing evidence suggests that declarative memory benefits from the modulatory effects of emotion and sleep. The primary goal of the present study was to determine whether these two factors interact to enhance memory or they act independently of each other. Twenty-eight volunteers participated in the study. Half of them were sleep deprived the night immediately following the exposure to emotional and non-emotional images, whereas the control group slept at home. Their memory for images was tested 1 week later along the valence and arousal dimension of emotion with the remember-know procedure. As emotional events appear to gain preference during encoding, via the modulatory effect of amygdala on prefrontal and medial temporal lobe regions, conscious retrieval of emotional pictures (relative to neutral ones) was expected to be less disrupted by sleep loss. Results indicated that emotional images were more richly experienced in memory than neutral, particularly those with high arousal and positive valence. Even though sleep deprivation resulted in behavioral impairment at retrieval of both emotional and neutral images, results revealed that remember-based recognition accuracy and its underlying process of recollection for emotional images were less influenced by the lack of sleep (the mean difference between control and sleep-deprived subjects was around 40% higher for neutral images than for emotional images). Familiarity, however, was affected by neither emotion nor sleep. Taken together, these results suggest that emotion and sleep influence differentially the subjective experience of remembering and knowing and the underlying processes of recollection and familiarity through brain mechanisms probably involving amygdala- and hippocampo-neocortical networks respectively.
van Schaik, A.B.T.M.; de Groot, H.L.F.
In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.
Augustenborg, Claudia Carrara
proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...
Huck, S; Rey Biel, P.
In this paper we study the mechanics of ``leading by example'' in teams. Leadership is beneficial for the entire team when agents are conformists, i.e., dislike effort differentials. We also show how leadership can arise endogenously and discuss what type of leader benefits a team most.
Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.
Withagen, C.A.A.M.; Vellinga, N.
This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found
Simpson, Norah S; Scott-Sutherland, Jennifer; Gautam, Shiva; Sethna, Navil; Haack, Monika
Chronic pain conditions are highly co-morbid with insufficient sleep. While the mechanistic relationships between the two are not understood, chronic insufficient sleep may be one pathway through which central pain-modulatory circuits deteriorate, thereby contributing to chronic pain vulnerability over time. To test this hypothesis, an in-laboratory model of three weeks of restricted sleep with limited recovery (five nights of 4-hour sleep/night followed by two nights of 8-hour sleep/night) was compared to three weeks of 8-hour sleep/night (control protocol). Seventeen healthy adults participated, with fourteen completing both three-week protocols. Measures of spontaneous pain, heat-pain thresholds, cold-pain tolerance (measuring habituation to cold over several weeks), and temporal summation of pain (examining the slope of pain ratings during cold water immersion) were assessed at multiple points during each protocol. Compared to the control protocol, participants in the sleep-restriction/recovery protocol experienced mild increases in spontaneous pain (ppain thresholds decreased following the first week of sleep restriction (pchronic exposure to restricted sleep was associated with decreased habituation to, and increased temporal summation in response to cold pain (both ppain-modulatory processes. Limited recovery sleep did not completely resolve these alterations in pain-modulatory processes, indicating that more extensive recovery sleep is required. Results suggest that exposure to chronic insufficient sleep may increase vulnerability to chronic pain by altering processes of pain habituation and sensitization.
Kirkham, T C; Williams, C M
Since pre-history, Cannabis sativa has been exploited for its potent and manifold pharmacological actions. Amongst the most renowned of these actions is a tendency to provoke ravenous eating. The characterization of the psychoactive principals in cannabis (exogenous cannabinoids) and, more recently, the discovery of specific brain cannabinoid receptors and their endogenous ligands (endocannabinoids) has stimulated research into the physiological roles of endocannabinoid systems. In this review, we critically discuss evidence from the literature that describe studies on animals and human subjects to support endocannabinoid involvement in the control of appetite. We describe the hyperphagic actions of the exogenous cannabinoid, Delta9-tetrahydrocannabinol, and the endogenous CB1 ligands, anandamide and 2-arachidonylglycerol, and present evidence to support a specific role of endocannabinoid systems in appetitive processes related to the incentive and reward properties of food. A case is made for more comprehensive and systematic analyses of cannabinoid actions on eating, in the anticipation of improved therapies for disorders of appetite and body weight, and a better understanding of the biopsychological processes underlying hunger.
Kim, B S; Kim, J Y; Lee, J G; Cho, Y; Huh, K H; Kim, M S; Kim, Y S
Thalidomide was originally used to alleviate morning sickness in pregnant women, but was banned due to severe adverse effects. Since the discovery of its anticancer and anti-inflammatory properties, it has regained research interest. However, its mechanism of action is still unknown. Therefore, we examined the effects of thalidomide on effector T (Teff) and regulatory T (Treg) cells in splenocytes of mice. Splenic CD4(+), CD44(low), and CD62L(high) T lymphocytes (Tnaives) isolated from C57BL/6 mice were cultured for T-cell proliferation and Treg conversion. For T-cell proliferation, naive T cells (Tnaives) were cultured for 72 hours with anti-CD3 and anti-CD28 antibodies, and carboxyfluorescein succinimidyl ester (CFSE) labeling method was used. For Treg conversion, Tnaives were cultured for 72 hours with transforming growth factor-β1 (TGF-β1) and interleukin-2 (IL-2). Naïve T cells were plated at 1.5 × 10(5) cells on 96-well plates with 0, 1, 10, 50, or 100 μmol/L thalidomide. All samples were analyzed by flow cytometry after staining with CFSE, APC-conjugated anti-mouse CD4, and FITC-conjugated anti-mouse FoxP3. Thalidomide significantly decreased the proliferation of CD4(+) Teffs in a dose-dependent manner (P thalidomide treatment, although the increase was not statistically significant. These findings suggest that thalidomide may have an immune modulatory effect by selectively suppressing CD4(+) Teff proliferation. Further studies will be needed to elucidate the underlying signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.
Andrew J Mitchell
Full Text Available Substance P (SP is a prototypical neuropeptide with roles in pain and inflammation. Numerous mechanisms regulate endogenous SP levels, including the differential expression of SP mRNA and the controlled secretion of SP from neurons. Proteolysis has long been suspected to regulate extracellular SP concentrations but data in support of this hypothesis is scarce. Here, we provide evidence that proteolysis controls SP levels in the spinal cord. Using peptidomics to detect and quantify endogenous SP fragments, we identify the primary SP cleavage site as the C-terminal side of the ninth residue of SP. If blocking this pathway increases SP levels, then proteolysis controls SP concentration. We performed a targeted chemical screen using spinal cord lysates as a proxy for the endogenous metabolic environment and identified GM6001 (galardin, ilomastat as a potent inhibitor of the SP(1-9-producing activity present in the tissue. Administration of GM6001 to mice results in a greater-than-three-fold increase in the spinal cord levels of SP, which validates the hypothesis that proteolysis controls physiological SP levels.
The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles . The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions
Kovac, Jasna; Gavaric, Neda; Bucar, Franz; Mozina, Sonja Smole
.... We investigated antimicrobial and resistance modulatory activity of the phenolic extract, essential oil and post-distillation extract of Alpinia katsumadai seeds against Campylobacter jejuni and Staphylococcus aureus...
Full Text Available We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004 and Bunzel and Qiao (2005 to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.
that of fentanyl-propofol combination. Pain is associated with the activation of inflammatory reactions which are mediated by cytokines. Activation of inflammatory response results in release CRP, HSP70, IL-1β and other cytokines into the blood circulation. CRP is a liver-synthesized reactive protein released in the.
Martins, I; de Vries, M G; Teixeira-Pinto, A; Fadel, J; Wilson, S P; Westerink, B H C; Tavares, I
Antidepressants that inhibit the recapture of noradrenaline have variable effects in chronic pain which may be related to the complex role of noradrenaline in pain modulation. Whereas at the spinal cord noradrenaline blocks nociceptive transmission, both antinociception and pronociception were reported after noradrenaline release in the brain. To study the role of noradrenaline in pain modulatory areas of the brain, we elected the dorsal reticular nucleus (DRt), a key pain facilitatory area located at the medulla oblongata. Three studies were performed. First, we show that the infusion in the DRt of nomifensine, which increases local extracellular levels of noradrenaline as shown by in vivo microdialysis, also enhances pain behavioral responses during both phases of the formalin test, a classic inflammatory pain model. Then, we demonstrate that the formalin test triggers the release of noradrenaline in the DRt in a biphasic pattern that matches the two phases of the test. Finally, we show that reducing noradrenaline release into the DRt, using an HSV-1 vector which decreases the expression of tyrosine hydroxylase in noradrenergic DRt-projecting neurons, attenuates pain behavioral responses in both phases of the formalin test. The increased noradrenaline levels induced by the infusion of nomifensine at the DRt, along with the hyperalgesic effects of noradrenaline released at the DRt upon noxious stimulation, indicates that noradrenaline may enhance pain facilitation from the brain. It is important to evaluate if antidepressants that inhibit noradrenaline recapture enhance pain facilitation from the brain herein attenuating their analgesic effects. Copyright © 2013 Elsevier Ltd. All rights reserved.
Graffi, Shmuel; Peretz, Avi; Naftali, Modi
To report an unusual case of a patient with endogenous endophthalmitis caused by Actinomyces neuii. A 69-year-old woman in an immunosuppressed state and who had a previous history of periappendicular abscess presented with bilateral red painful eyes. The diagnosis was confirmed by culture and pan-bacterial polymerase chain reaction drawn from anterior chamber sample. On admission, the patient underwent an intravitreal injection of vancomycin combined with ceftazidime. Following a 3-week treatment of intravenous penicillin and topical sulfacetamide sodium, the patient recovered fully. Actinomyces neuii can cause endogenous endophthalmitis. Intravenous penicillin G is an effective treatment leading to favorable prognosis.
Full Text Available Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent pain-related behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear.In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain.These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight the importance of treatment of chronic pain at an early stage.
Mamoru Takeda; Shiori Takehana; Kenta Sekiguchi; Yoshiko Kubota; Yoshihito Shimazu
Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a com...
Pedro Alvarez; Xiaojie Chen; Oliver Bogen; Paul G. Green; Jon D. Levine
...), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain...
David M. Niddam
Full Text Available Neuroimaging has provided important information on how acute and chronic pain is processed in the human brain. The pain experience is now known to be the final product of activity in distributed networks consisting of multiple cortical and subcortical areas. Due to the complex nature of the pain experience, a single cerebral representation of pain does not exist. Instead, pain depends on the context in which it is experienced and is generated through variable expression of the different aspects of pain in conjunction with modulatory influences. While considerable data have been generated about the supraspinal organization of cutaneous pain, little is known about how nociceptive information from musculoskeletal tissue is processed in the brain. This is in spite of the fact that pain from musculoskeletal tissue is more frequently encountered in clinical practice, poses a bigger diagnostic problem and is insufficiently treated. Differences are known to exist between acute pain from cutaneous and muscular tissue in both psychophysical responses as well as in physiological characteristics. The 2 tissue types also differ in pain sensitivity to the same stimuli and in their response to analgesic substances. In this review, characteristics of acute and chronic muscle pain will be presented together with a brief overview of the methods of induction and psychophysical assessment of muscle pain. Results from the neuroimaging literature concerned with phasic and tonic muscle pain will be reviewed.
Whitta-Jacobsen, Hans Jørgen
We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized...
Sturgeon, John A.; Johnson, Kevin A.
Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain. PMID:28348505
Vani A Mathur
Full Text Available Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful, we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds and pre-scan pain ratings to mildly painful thermal stimuli, patients had aberrant suprathreshold nociceptive processing. Compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain versus mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS; bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula cortex, associated with indices of
Full Text Available Pain is a homeostatic mechanism that intervenes to protect the organism from harmful stimuli that could damage its integrity. It is made up of two components: the sensory-discriminative component, which identifies the provenance and characteristics of the type of pain; and the affective-motivational component, on which emotional reflexes, following the painful sensation, depend.There is a system for pain control at an encephalic and spinal level, principally made up of the periaqueductal grey matter, the periventricular area, the nucleus raphe magnus, and the pain-inhibition complex situated in the posterior horns of the spinal cord. Through the activation of these pain-control systems, the nervous system suppresses the afference of pain signals. Endogenous opioids represent another analgesic system.In the course of various studies on pain transmission in Down patients, the reduced tolerance of pain and the incapacity to give a qualitative and quantitative description emerged in a powerful way. All of these aspects cause difficulty in evaluating pain. This is linked to several learning difficulties. However, it cannot be excluded that in these anomalies of pain perception, both the anatomical and the neurotransmitter alteration, typical of this syndrome, may hold a certain importance.This fact may have important clinical repercussions that could affect the choice of therapeutic and rehabilitative schemes for treatment of pathologies in which pain is the dominant symptom, such as postoperative pain. It could influence research on analgesics that are more suitable for these patients, the evaluation of the depth of analgesia during surgical operation, and ultimately, absence of obvious pain manifestations. In conclusion, alterations of the central nervous system, neurotransmitters, pain transmission, and all related problems should be considered in the management of pain in patients with Down's syndrome, especially by algologists and
Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.
Derler, Isabella; Fahrner, Marc; Muik, Martin; Lackner, Barbara; Schindl, Rainer; Groschner, Klaus; Romanin, Christoph
STIM1 and ORAI1, the two limiting components in the Ca(2+) release-activated Ca(2+) (CRAC) signaling cascade, have been reported to interact upon store depletion, culminating in CRAC current activation. We have recently identified a modulatory domain between amino acids 474 and 485 in the cytosolic part of STIM1 that comprises 7 negatively charged residues. A STIM1 C-terminal fragment lacking this domain exhibits enhanced interaction with ORAI1 and 2-3-fold higher ORAI1/CRAC current densities. Here we focused on the role of this CRAC modulatory domain (CMD) in the fast inactivation of ORAI1/CRAC channels, utilizing the whole-cell patch clamp technique. STIM1 mutants either with C-terminal deletions including CMD or with 7 alanines replacing the negative amino acids within CMD gave rise to ORAI1 currents that displayed significantly reduced or even abolished inactivation when compared with STIM1 mutants with preserved CMD. Consistent results were obtained with cytosolic C-terminal fragments of STIM1, both in ORAI1-expressing HEK 293 cells and in RBL-2H3 mast cells containing endogenous CRAC channels. Inactivation of the latter, however, was much more pronounced than that of ORAI1. The extent of inactivation of ORAI3 channels, which is also considerably more prominent than that of ORAI1, was also substantially reduced by co-expression of STIM1 constructs missing CMD. Regarding the dependence of inactivation on Ca(2+), a decrease in intracellular Ca(2+) chelator concentrations promoted ORAI1 current fast inactivation, whereas Ba(2+) substitution for extracellular Ca(2+) completely abrogated it. In summary, CMD within the STIM1 cytosolic part provides a negative feedback signal to Ca(2+) entry by triggering fast Ca(2+)-dependent inactivation of ORAI/CRAC channels.
Steeples, L R; Jones, N P
PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.
Wang, Dawei; Yu, Weiqing; Liu, Yuntao; Zhong, Guofu; Zhao, Zhen; Yan, Xia; Liu, Qing
Autophagy is an evolutionarily conserved degradation process which eliminates dysfunctional proteins and cytoplasmic components to maintain homeostasis for cell survival. Increasing evidence has demonstrated the modulatory role of autophagy in ischemic heart diseases (IHDs). Traditionally, this process has been recognized as having protective functions, such as inhibiting atherosclerosis progression and reducing cell death during the ischemic phase. However, recent studies have suggested its dual roles in myocardial ischemia/reperfusion (MIR) injury. Excessive autophagy may play a deleterious role in cardiac function, due to overwhelming clearance of cellular constituents and proteins. Hence modulation of autophagy to increase cardiomyocyte survival and improve cardiac function is meaningful for the treatment of IHD. Chinese herbal medicine, including extractive compounds and patented drugs, has shown its potential role in treating IHD by addressing autophagy-related mechanisms. This review summarizes the updated knowledge on the molecular basis and modulatory role of autophagy in IHD and the recent progress of Chinese herbal medicine in its treatment.
S. Brakman (Steven); J.G.M. van Marrewijk (Charles)
textabstractIn a competitive and Walrasian stable world with two goods transfer paradoxes are very robust to endogenization (relating the size of the transfer to either the donor's or the recipient's GNP). Donor enrichment and/or recipient impoverishment occur in very general formulations of
Lagerlöf, Johan N. M.; Schottmüller, Christoph
We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...
Awodele,Olufunsho; Akintonwa,Alade; Osunkalu,Vincent O.; Coker,Herbert A.B.
The World Health Organization (WHO) has shown concern about the burden of tuberculosis in the developing countries. Even though rifampicin is an effective drug in the management of tuberculosis, it has been documented to have some toxic effects in humans. Therefore, this study intends to investigate the modulatory effect of vitamins C and E on the hepatotoxicity, sperm quality and brain toxicity of Rifampicin. Forty Wistar albino rats were used, 10 animals per group. Group 1 animals received ...
... over. There are two types: acute pain and chronic pain. Acute pain lets you know that you may ... have problem you need to take care of. Chronic pain is different. The pain may last for weeks, ...
Fosgerau, Mogens; Small, Kenneth
We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...
Di Marzo, V.; Bisogno, T.; Melck, D. [CNR, Arco Felice, Naples (Italy). Ist. per la Chimica di Molecole di Interesse Biologico; De Petrocellis, L. [CNR, Arco Felice, Naples (Italy). Ist. di Cibernetica
Only a few discoveries in the fields of pharmacology and physiology have benefited from the work of organic and synthetic chemists like the identification of the existence and possible physiological function of the `endogenous cannabinoid system`. The review emphasizes the key role played by chemists in this area of pharmacological research, and highlights the possible industrial implications of the discovery of cannabimimetic metabolites and of their mechanism of action.
Landau, R; Bollag, L; Ortner, C
With over four million deliveries annually in the United States alone and a constant increase in cesarean delivery rate, childbirth is likely to have a huge impact on the occurrence of acute and possibly chronic postpartum pain. Recent awareness that chronic pain may occur after childbirth has prompted clinicians and researchers to investigate this topic. Current evidence points towards a relatively low incidence of chronic pain after cesarean delivery, with rates ranging between 1% and 18%. To provide a potential mechanistic explanation for the relatively low occurrence of chronic pain after cesarean delivery compared with that after other types of surgery, it has been proposed that endogenous secretion of oxytocin may confer specific protection. Clinical interventions to reduce the incidence and severity of chronic post-surgical pain have not been consistently effective. Likely explanations are that the drugs that have been investigated were truly ineffective or that the effect was too modest because with a low incidence of chronic pain, studies were likely to be underpowered and failed to demonstrate an effect. In addition, since not all women require preventive therapies, preoperative testing that may identify women vulnerable to pain may be highly beneficial. Further research is needed to identify valid models that predict persistent pain to allow targeted interventions to women most likely to benefit from more tailored anti-hyperalgesic therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available The balance between glutamate- and GABA-mediated neurotransmission in the brain is fundamental in the nervous system, but it is regulated by the ‘tonic’ release of a variety of endogenous factors. One such important group of molecules are the neurosteroids (NSs which, similarly to benzodiazepines (BDZs, enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in-vivo physiologically relevant concentrations, the effects of NSs and BDZs as GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA recording technique and a novel analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect drug-induced network up-states (burst. We found that the NSs tetrahydrodeoxycorticosterone (THDOC and allopregnanolone (ALLO applied at low nM concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 µM, both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after washout, the excitability of inhibitory neurons continued to be depressed, leading to a network long term depression (LTD. The BDZs clonazepam (CLZ and midazolam (MDZ also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN, an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex-vivo networks show a sensitivity to NSs and BDZs comparable to that expressed in vivo, but also provide a new global in-vitro description that can help in understanding their activity in more complex
Full Text Available We report a case of a 74-year-old female, with a mitral heart valve, who presented with pain and blurred vision in the right eye for 2 days. Her visual acuity was light perception (LP in the right eye and 20/40 in the left eye. Slit lamp examination showed corneal edema and hypopyon, and a view of the right fundus was impossible. Echography showed vitreous condensation. One day after presentation, the patient developed acute lung edema requiring hospitalization, so she was not submitted to vitreous tap and intravitreal treatment. The cardiac and systemic evaluations revealed a mitral endocarditis secondary to Enterococcus faecalis. The patient improved systemically with treatment with gentamicin, vancomycin, and linezolid. Her visual acuity remained as no LP, and her intraocular pressure (IOP has been controlled with brimonidine bid despite developing a total cataract with 360° posterior synechia. A cardiac source for endogenous endophthalmitis should be considered in the presence of a prosthetic cardiac valve. The treatment and followup must be made in cooperation with a cardiologist specialist, but the ophthalmologist can play a key role in the diagnosis.
Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.
Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.
Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber
Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).
Garcia-Etxebarria, Koldo; Sistiaga-Poveda, Maialen; Jugo, Begoña Marina
Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates. Although the study of ERVs has been carried out mainly in humans and model organisms, recently, domestic animals have become important, and some species have begun to be analyzed to gain further insight into ERVs. Due to the availability of complete genomes and the development of new computer tools, ERVs can now be analyzed from a genome-wide viewpoint. In addition, more experimental work is being carried out to analyze the distribution, expression and interplay of ERVs within a host genome. Cats, cattle, chicken, dogs, horses, pigs and sheep have been scrutinized in this manner, all of which are interesting species in health and economic terms. Furthermore, several studies have noted differences in the number of endogenous retroviruses and in the variability of these elements among different breeds, as well as their expression in different tissues and the effects of their locations, which, in some cases, are near genes. These findings suggest a complex, intriguing relationship between ERVs and host genomes. In this review, we summarize the most important in silico and experimental findings, discuss their implications and attempt to predict future directions for the study of these genomic elements. PMID:25132796
... Conditions Living Well with Rheumatic Disease Neck Pain Neck Pain Fast Facts Whiplash from motor vehicle accidents is ... more frequently in women than men. What causes neck pain? Most episodes of neck pain are caused by ...
Tumors have developed different strategies to escape immune recognition. This could be due to altered expression of classical and non-classical human leukocyte antigens (HLA), co-inhibitory or co-stimulatory molecules as well as components of the interferon signaling pathway. Furthermore, changes in the tumor microenvironment negatively interfere with anti-tumor immune responses and the frequency and activity of immune effector cells and professional antigen presenting cells (APC), while the number of immune suppressive cells is increased. Recently, microRNAs (miRNA) identified known as important players in the posttranscriptional regulation of gene expression have been demonstrated to be differentially expressed in tumors of distinct origin and present in nanovesicles secreted by tumors. They not only exhibit tumor suppressive and oncogenic potential, but also immune modulatory functions. This review focusses on the role of miRNA in posttranscriptional control of immune modulatory molecules in tumors and in exosomes, which might represent prognostic biomarkers and novel therapeutic targets. Copyright © 2017. Published by Elsevier Ltd.
Full Text Available Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC. Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo.
Bhattacharya, Palash; Thiruppathi, Muthusamy; Elshabrawy, Hatem A.; Alharshawi, Khaled; Kumar, Prabhakaran; Prabhakar, Bellur S.
GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases like Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance. PMID:26113402
Lei, Jing; You, Hao-Jun
In conscious rats, intramuscular injection of 2.5% formalin into the gastrocnemius muscle, at volumes between 25 and 200 μl, evoked dose-dependent biphasic persistent flinching activities: phase 1 (0-10 min) and phase 2 (10-60 min). During this intramuscular formalin-induced ipsilateral muscle nociception, bilateral secondary mechanical hyperalgesia and heat hypoalgesia assessed by measuring thresholds of paw withdrawal reflex to noxious mechanical and heat stimuli were observed (Pnociception, and the occurrence of bilateral secondary mechanical hyperalgesia was significantly delayed (Pnociceptive behavior in the late part (30-60 min) of phase 2, and the bilateral secondary heat hypoalgesia was temporarily prevented (Pnociception, and that bilateral secondary mechanical hyperalgesia and heat hypoalgesia are differentially controlled by endogenous descending facilitation and inhibition respectively. It is further suggested that thalamic MD nucleus and VM nucleus constitute an endogenous discriminative, modulatory system that exerts, via pathways in the DF and DLF, descending facilitatory and inhibitory actions on responses to peripheral afferent activity evoked by noxious mechanical and heat stimulation. Copyright © 2013 Elsevier Inc. All rights reserved.
Andersen, Hjalte H; van Laarhoven, Antoinette I M; Elberling, Jesper; Arendt-Nielsen, Lars
Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.
Haefeli, Mathias; Elfering, Achim
Pain usually is the major complaint of patients with problems of the back, thus making pain evaluation a fundamental requisite in the outcome assessment in spinal surgery. Pain intensity, pain-related disability, pain duration and pain affect are the aspects that define pain and its effects. For each of these aspects, different assessment instruments exist and are discussed in terms of advantages and disadvantages. Risk factors for the development of chronic pain have been a major topic in pain research in the past two decades. Now, it has been realised that psychological and psychosocial factors may substantially influence pain perception in patients with chronic pain and thus may influence the surgical outcome. With this background, pain acceptance, pain tolerance and pain-related anxiety as factors influencing coping strategies are discussed. Finally, a recommendation for a minimum as well as for a more comprehensive pain assessment is given.
Karthivashan, Govindarajan; Kura, Aminu Umar; Arulselvan, Palanisamy; Md Isa, Norhaszalina; Fakurazi, Sharida
...; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO...
Govers, Coen; Tomassen, Monic M.M.; Rieder, Anne; Ballance, Simon; Knutsen, Svein H.; Mes, Jurriaan J.
The correct identification of immune-modulatory activity of polysaccharides is often hampered by immune-stimulatory contaminants, with pyrogens such as lipopolysaccharide (LPS) as a very potent example. In order to avoid false positive immuno-stimulatory properties to be attributed to
Johansson, Helle Wulf; Hay-Schmidt, Anders; Poulsen, Asser Nyander
(Ca) channel protein was visualized by western blotting and histochemistry. The presence of the modulatory beta1-beta 4 subunit mRNAs was investigated using RT-PCR. beta1-, beta2- and beta 4-subunit mRNAs were expressed in rat TG whereas beta2- and beta 4-subunits were detected in porcine TG. Western blotting...
Umland, Oliver; Heine, Holger; Miehe, Michaela
Lipopolysaccharide (LPS) has been shown to induce proliferation of human T-lymphocytes only in the presence of monocytes and CD34(+) hematopoietic cells (HCs) from peripheral blood. This finding provided evidence of an active role of CD34(+) HCs during inflammation and immunological events....... To investigate mechanisms by which CD34(+) HCs become activated and exert their immune-modulatory function, we used the human CD34(+) acute myeloid leukemia cell line KG-1a and CD34(+) bone marrow cells (BMCs). We showed that culture supernatants of LPS-stimulated mononuclear cells (SUP(LPS)) as well as tumor...... in stimulated KG-1a cells and CD34(+) BMCs. Although monokine induced by IFN-gamma, IFN-inducible protein 10, and IFN-gamma were exclusively up-regulated in KG-1a cells, differential expression of monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine, myeloid progenitor inhibitory factor-2...
Ajeet Pratap Singh
Full Text Available Olfactory sensory neurons connect to the antennal lobe of the fly to create the primary units for processing odor cues, the glomeruli. Unique amongst antennal-lobe neurons is an identified wide-field serotonergic neuron, the contralaterally-projecting, serotonin-immunoreactive deutocerebral neuron (CSDn. The CSDn spreads its termini all over the contralateral antennal lobe, suggesting a diffuse neuromodulatory role. A closer examination, however, reveals a restricted pattern of the CSDn arborization in some glomeruli. We show that sensory neuron-derived Eph interacts with Ephrin in the CSDn, to regulate these arborizations. Behavioural analysis of animals with altered Eph-ephrin signaling and with consequent arborization defects suggests that neuromodulation requires local glomerular-specific patterning of the CSDn termini. Our results show the importance of developmental regulation of terminal arborization of even the diffuse modulatory neurons to allow them to route sensory-inputs according to the behavioural contexts.
Yeung, Ryan; Nguyen-Hoang, Phuong
The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…
Eichmüller, Stefan B; Osen, Wolfram; Mandelboim, Ofer; Seliger, Barbara
Current therapies against cancer utilize the patient's immune system for tumor eradication. However, tumor cells can evade immune surveillance of CD8+ T and/or natural killer (NK) cells by various strategies. These include the aberrant expression of human leukocyte antigen (HLA) class I antigens, co-inhibitory or costimulatory molecules, and components of the interferon (IFN) signal transduction pathway. In addition, alterations of the tumor microenvironment could interfere with efficient antitumor immune responses by downregulating or inhibiting the frequency and/or functional activity of immune effector cells and professional antigen-presenting cells. Recently, microRNAs (miRNAs) have been identified as major players in the post-transcriptional regulation of gene expression, thereby controlling many physiological and also pathophysiological processes including neoplastic transformation. Indeed, the cellular miRNA expression pattern is frequently altered in many tumors of distinct origin, demonstrating the tumor suppressive or oncogenic potential of miRNAs. Furthermore, there is increasing evidence that miRNAs could also influence antitumor immune responses by affecting the expression of immune modulatory molecules in tumor and immune cells. Apart from their important role in tumor immune escape and altered tumor-host interaction, immune modulatory miRNAs often exert neoplastic properties, thus representing promising targets for future combined immunotherapy approaches. This review focuses on the characterization of miRNAs involved in the regulation of immune surveillance or immune escape of tumors and their potential use as diagnostic and prognostic biomarkers or as therapeutic targets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)
Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.
Banerjee, Meenal; Kanitkar, Meghana; Bhonde, Ramesh R
The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its beta-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in beta-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, beta-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing beta-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration.
Pradeep Kumar Panigrahi
Full Text Available We report a rare case of Aspergillus terreus endogenous endophthalmitis in an immunocompetent patient with subretinal abscess and also review the reported cases. A 50-year-old healthy male presented with sudden painful loss of vision in right eye. He was diagnosed with endogenous endophthalmitis and underwent urgent vitrectomy. Aspergillus terreus growth was obtained in culture. At final follow-up, there was complete resolution of the infection but visual acuity was poor due to macular scar. Aspergillus terreus is a rare cause of endophthalmitis with usually poor outcomes. Newer antifungals like Voriconazole can be sometimes associated with better prognosis.
J Michael Walker
Full Text Available Cannabinoids have been used to treat pain for many centuries. However, only during the past several decades have rigorous scientific methods been applied to understand the mechanisms of cannabinoid action. Cannabinoid receptors were discovered in the late 1980s and have been found to mediate the effects of cannabinoids on the nervous system. Several endocannabinoids were subsequently identified. Many studies of cannabinoid analgesia in animals during the past century showed that cannabinoids block all types of pain studied. These effects were found to be due to the suppression of spinal and thalamic nociceptive neurons, independent of any actions on the motor systems. Spinal, supraspinal and peripheral sites of cannabinoid analgesia have been identified. Endocannabinoids are released upon electrical stimulation of the periaqueductal gray, and in response to inflammation in the extremities. These observations and others thus suggest that a natural function of cannabinoid receptors and their endogenous ligands is to regulate pain sensitivity. The therapeutic potential of cannabinoids remains an important topic for future investigations, with previous work suggesting utility in clinical studies of cancer and surgical pain. New modes of delivery and/or new compounds lacking the psychotropic properties of the standard cannabinoid ligands offer promise for cannabinoid therapeutics for pain.
... Accessed May 29, 2015. Adult acute and subacute low back pain. Bloomington, Minn.: Institute for Clinical Systems Improvement. http://www.icsi.org/low_back_pain/adult_low_back_pain__8.html. Accessed June ...
Kehlet, H; Dahl, J B
Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...... also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree...
Yoo, Sungjae; Lim, Ji Yeon; Hwang, Sun Wook
The efficacy of many of pain-relieving drugs is based on mechanisms by which the drugs interfere with the body's natural pain-mediating pathways. By contrast, although it is less popular, other drugs including opioids exert more powerful analgesic actions by augmenting endogenous inhibitory neural circuits for pain mediation. Recently, a novel endogenous pain-inhibitory principle was suggested and is now attracting both scientific and clinical attentions. The central players for the actions are particular body lipids: resolvins. Although research is in the preclinical phase, multiple hypotheses have actively been matured regarding the potency and molecular and neural processes of the analgesic effects of these substances. Consistently, accumulating experimental evidence has been demonstrating that treatment with these lipid substances is strongly effective at controlling diverse types of pain. Treatment of resolvins does not appear to disturb the body homeostasis as severely as many other therapeutic agents that interrupt the body's natural signaling flow, which enables us to predict their fewer adverse effects. This paper serves as a review of currently documented painkilling actions of resolvins, summarizes the potential cellular and receptor-mediated mechanisms to date, and discusses the many clinical uses for these therapeutic lipids that have not yet been tested. Future scientific efforts will more concentrate to unveil such aspects of the substances and to construct clear proofs of concept for pain relief.
Li, Run; Vasquez, Kevin; Xu, M.
Endogenous fluorescence is a powerful technique for probing both structure and function of tissue. We show that enabling wide-field fluorescence microscopy with chemometrics can significantly enhance the performance of tissue diagnosis with endogenous fluorescence. The spatial distribution and absolute concentration of fluorophores is uncovered with non-negative factorization aided by the spatial diversity from microscopic autofluorescence color images. Fluorescence quantification in terms of its absolute concentration map avoids issues dependent on specific measurement approach or systems and yields biologically meaningful data. The standardization of endogenous fluorescence in terms of absolute concentration will facilitate its translation to the clinics and simplifies the assessment of competing methods relating to tissue fluorescence.
Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell
Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
Flower Rod J
Full Text Available Abstract Background Autoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system. We have reported novel biological functions for Annexin A1, an effector of endogenous anti-inflammation, to produce positive actions on the adaptive immune system by reducing the threshold of T cell activation. In this study, we investigated the potential modulatory role of Annexin A1 in the development of experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Methods Male control C57/BL6 and AnxA1 null mice were immunized subcutaneously with an emulsion consisting of 300 μg of MOG35-55 in PBS combined with an equal volume of CFA. Lymph node cells obtained from mice immunized with MOG33-55 for 14 days were re-stimulated in vitro with MOG33-55 (100 μg/ml for 4 days and the Th1/Th17 cytokine profile measured by ELISA. Spinal cords were processed either to isolate the infiltrated T cells or fixed and stained with haematoxylin and eosin. Statistical analyses were performed using two-tailed, unpaired Student's t tests or ANOVA. Results Our results show a direct correlation between Annexin A1 expression and severity of EAE. Analysis of MOG35-55-induced EAE development in Annexin A1 null mice showed decreased signs of the disease compared to wild type mice. This defect was significant at the peak of the disease and accompanied by reduced infiltration of T cells in the spinal cord. Finally, analysis of the T cell recall response in vitro following stimulation with MOG35-55 showed a decrease proliferation of Annexin A1 null T cells, with a significantly reduced Th1/Th17 phenotype, compared to wild type cells. Conclusion Together these findings suggest that Annexin A1 null mice have an impaired capacity to develop EAE. Furthermore strategies aiming at reducing Annexin A1 functions or expression in T cells might represent a
Ruscheweyh, Ruth; Kühnel, Maria; Filippopulos, Filipp; Blum, Bernhard; Eggert, Thomas; Straube, Andreas
Animal studies have suggested that the cerebellum, in addition to its motor functions, also has a role in pain processing and modulation, possibly because of its extensive connections with the prefrontal cortex and with brainstem regions involved in descending pain control. Consistently, human imaging studies have shown cerebellar activation in response to painful stimulation. However, it is presently not clear whether cerebellar lesions affect pain perception in humans. In the present study, we used experimental pain testing to compare acute pain perception and endogenous pain inhibition in 30 patients 1 to 11 years after cerebellar infarction and in 30 sex- and age-matched healthy control subjects. Compared to controls, patients exhibited a significantly increased pain perception in response to acute heat stimuli (44 °C-48 °C, average pain intensity rating for patients 3.4±2.8 and for controls 1.5±1.7 [on a numeric rating scale of 0-10], Ppain intensity rating: 0.0%±15.8% vs. -16.9%±36.3%, Ppain intensity rating: -1.0±1.1 vs. -1.8±1.3 [0-10], Pcontrols. In contrast, heat and pressure pain thresholds were not significantly different between groups. These results show that, after cerebellar infarction, patients perceive heat and repeated mechanical stimuli as more painful than do healthy control subjects and have deficient activation of endogenous pain inhibitory mechanisms (offset and placebo analgesia). This suggests that the cerebellum has a previously underestimated role in human pain perception and modulation. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
pain is not at all clear and this can be attributed to the fact that terminology defining the disease is very uncertain. ... This is also classified as chronic pain. In these ... CRPS Type II (Complete regional pain syndrome). * Phantom limb pain. * Spinal cord injury. * Post surgery. - laminectorny. - spinal fusion. - general surgery.
Nijs, Jo; Crombez, Geert; Meeus, Mira; Knoop, Hans; Damme, Stefaan Van; Cauwenbergh, Vandeborah; Bleijenberg, Gijs
Besides chronic fatigue, patients with chronic fatigue syndrome (CFS) have debilitating widespread pain. Yet pain from CFS is often ignored by clinicians and researchers. To examine whether pain is a unique feature of CFS, or does it share the same underlying mechanisms as other CFS symptoms? Second, it is examined whether effective treatments for pain from CFS are currently available. Narrative review covering the scientific literature up through December 2011. Several universities. From the available literature, it is concluded that musculoskeletal factors are unlikely to account for pain from CFS. Pain seems to be one out of many symptoms related to central sensitization from CFS. This idea is supported by the findings of generalized hyperalgesia (including widespread increased responsiveness to painful stimuli) and dysfunctional endogenous analgesia in response to noxious thermal stimuli. Pain catastrophizing and depression partly account for pain from CFS. Pain increases during exercise is probably due to the lack of endogenous analgesia and activation of several genes in response to exercise in CFS. There is currently no evidence in support for the efficacy of complementary medicine in the treatment of pain from CFS. Intensive education about the biology of pain from CFS (within the framework of central sensitization) has positive short-term effects for patients with CFS, and fatigue-targeting cognitive behavioral therapy appears to be effective for pain from CFS as well. The role of the deficient hypothalamus-pituitary-adrenal axis in relation to pain from CFS, as well as the interactions with immune (dys)functioning require further study. Recent research has increased our understanding of pain from CFS, including its treatment. It is advocated to optimize current CFS treatment protocols by targeting the underlying mechanism for those patients having severe pain.
Sep 17, 2008 ... INTRODUCTION. Aging and its degenerative diseases appear to be due in good part to oxidative damage to DNA and other macro- molecules. Four endogenous sources appear to account for most of the oxidants produced by cells: 1) As a consequence of normal aerobic respiration in the mito- chondria ...
Yakunchikov, Dmitry Y; Olechowski, Camille J; Simmonds, Mark K; Verrier, Michelle J; Rashiq, Saifudin; McWilliams, Lachlan A; Sobolev, Igor A; Dick, Bruce D
In this study, we were interested in determining whether we could alter a pain response in a chronic pain patient population by exposing participants to different videos prior to inducing acute pain. This observational case series study required participants to report their pain level during the cold pressor task after viewing an instruction video. Recruitment and testing took place in a tertiary care multidisciplinary pain center. Forty adults with chronic pain participated in the study and completed the cold pressor test. Prior to testing, questionnaires measuring pain, empathy, and catastrophic thinking were completed and participants were randomized to view an instructional video where an actress either demonstrated pain behavior or a stoic response during the cold pressor test. Participants with higher levels of catastrophizing reported higher pain levels during the cold pressor test. Personal Distress Empathy measures of participants who viewed the pain catastrophizing video were significantly correlated with their final pain reports. Following the cold pressor task, participants' pain reports for their primary chronic pain sites were significantly reduced. These results support previous findings that people with chronic pain show the tendency toward increased acute pain experience if levels of catastrophizing and Personal Distress Empathy measures are higher. Participants reported attenuated chronic pain following induced pain, also in line with previous research suggesting a central endogenous inhibitory effect. Our findings shed light on the role of emotional and social components affecting the experience of pain in individuals with chronic pain.
Arulmozhi, D K; Veeranjaneyulu, A; Bodhankar, S L; Arora, S K
The effect of the aqueous extract of Sapindus trifoliatus (ST) on chemical, thermal-induced pain, nitroglycerin-induced hyperalgesia and pain on inflamed tissue was investigated. The extract (20 and 100 mg x kg(-1), i.p.) significantly inhibited acetic-acid-induced abdominal constrictions, formalin-induced pain licking and hotplate-induced pain in mice. Furthermore, the extract significantly increased the response latencies of nitroglycerin-induced hyperalgesia by the tail-flick method and mechanical pain on carrageenan-induced inflamed paw in rats. The data suggest that ST has an inhibitory activity on both peripheral and central pain mechanisms and has a modulatory role in NO-mediated nociceptive transmission.
Memon, Muhammad; Raman, Vasant
A systemically well 66-year-old white Caucasian man presented to the urgent care department with a short history of progressive pain and blurring of vision in his left eye. He denied a history of trauma, intraocular surgery or use of illicit drugs. He was diagnosed with endogenous endophthalmitis. Vitreous biopsy grew Serratia marcescens, a Gram negative bacteria. In spite of extensive investigation, there was no obvious source of infection. He had an indwelling urine catheter for prostate hypertrophy, but urine culture was negative. There was no evidence of immunocompromise. He was treated with systemic as well as intravitreal antibiotics. In spite of appropriate treatment, the patient lost vision. S. marcescens endophthalmitis, seen even in immunocompetent people, carries a poor visual prognosis. 2016 BMJ Publishing Group Ltd.
Hassan, Memy H; El-Beshbishy, Hesham A; Aly, Hamdy; Attia, Sabry M; Bahashwan, Saleh A; Ghobara, Mohamed M
This study was undertaken to assess the possible modulatory effects and mechanisms of meloxicam, a cyclooxygenase-2 inhibitor, on the antitumor activity and cardiotoxicity of doxorubicin in a mice model of mammary carcinoma. Solid tumor mass was developed in female albino mice using Ehrlich carcinoma cells. Forty mice-bearing tumor were divided randomly into four groups for treatment: with saline, meloxicam 10 mg/kg, doxorubicin 5 mg/kg and meloxicam 1 h ahead of doxorubicin, twice weekly for 2 weeks. Tumor volume was followed up and cardiac protective utility was estimated via measuring heart and serum parameters. Meloxicam expressed a non-significant increase in doxorubicin antitumor activity. Conversely, meloxicam significantly (p Meloxicam significantly abrogated doxorubicin-induced disturbance in heart histology and relative heart weight to body weight. Meloxicam normalized doxorubicin-induced suppression in heart antioxidant enzymes activities and gene expressions [superoxide dismutase, glutathione peroxidase (GSH-Px) and catalase], and heart GSH content. In addition, meloxicam ameliorated doxorubicin-induced disturbance in phase II metabolizing enzyme, cardiac quinone reductase (QR), at activity level and mRNA expression. Meloxicam protects heart against doxorubicin toxicity without affecting its antitumor activity against solid mammary cancer model in mice. This protective effect is attributed to antioxidant effect, antiradical effect, antiinflammatory action, antiapoptotic effect and induction of QR enzyme.
Henry Hungtao Jerng
Full Text Available Auxiliary subunits are non-conducting, modulatory components of the multi-protein ion channel complexes that underlie normal neuronal signaling. They interact with the pore-forming α-subunits to modulate surface distribution, ion conductance, and channel gating properties. For the somatodendritic subthreshold A-type potassium (ISA channel based on Kv4 α-subunits, two types of auxiliary subunits have been extensively studied: Kv channel-interacting proteins (KChIPs and dipeptidyl peptidase-like proteins (DPLPs. KChIPs are cytoplasmic calcium-binding proteins that interact with intracellular portions of the Kv4 subunits, whereas DPLPs are type II transmembrane proteins that associate with the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites that are used by various neuronal populations to drive the differential expression of functionally distinct N-terminal variants. In turn, these N-terminal variants generate tremendous functional diversity across the nervous system. Here, we focus our review on (1 the molecular mechanism underlying the unique properties of different N-terminal variants, (2 the shaping of native ISA properties by the concerted actions of KChIPs and DPLP variants, and (3 the surprising ways that KChIPs and DPLPs coordinate the activity of multiple channels to fine-tune neuronal excitability. Unlocking the unique contributions of different auxiliary subunit N-terminal variants may provide an important opportunity to develop novel targeted therapeutics to treat numerous neurological disorders.
Gut microbiota play an important role in human immunological processes, potentially affecting allergic diseases such as eczema. The diversity and structure of gut microbiota in infants with eczema have been previously documented. This study aims to evaluate by comparative metagenomics differences in genetic content in gut microbiota of infants with eczema and their matched controls. Stools were collected at the age of one month old from twelve infants from an at risk birth cohort in a case control manner. Clinical follow up for atopic outcomes were carried out at the age of 12 and 24 months. Microbial genomic DNA were extracted from stool samples and used for shotgun sequencing. Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs were significantly enriched in the six healthy controls (C) communities compared to the six eczema subjects (E), with many encoded by Bifidobacterium (38% of the total motifs in the C communities). Draft genomes of five Bifidobacterium species populations (B. longum, B. bifidum, B. breve, B. dentium, and B. pseudocatenulatum) were recovered from metagenomic datasets. The B. longum BFN-121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per one million genome sequence) than other Bifidobacterium genomes. Additionally, the communities in the stool of controls (C) were also significantly enriched in functions associated with tetrapyrrole biosynthesis compared to those of eczema (E). Our results show distinct immune-modulatory genomic properties of gut microbiota in infants associated with eczema and provide new insights into potential role of gut microbiota in affecting human immune homeostasis.
Abdo, Safaa E; El-Kassas, Seham; El-Nahas, Abeer F; Mahmoud, Shawky
In a novel approach, monochromatic blue light was used to investigate its modulatory effect on heat stress biomarkers in two commercial broiler strains (Ross 308 and Cobb 500). At 21 days old, birds were divided into four groups including one group housed in white light, a second group exposed to blue light, a 3rd group exposed to white light + heat stress, and a 4th group exposed to blue light + heat stress. Heat treatment at 33°C lasted for five h for four successive days. Exposure to blue light during heat stress reduced MDA concentration and enhanced SOD and CAT enzyme activities as well as modulated their gene expression. Blue light also reduced the degenerative changes that occurred in the liver tissue as a result of heat stress. It regulated, though variably, liver HSP70, HSP90, HSF1, and HSF3 gene expression among Ross and Cobb chickens. Moreover, the Cobb strain showed better performance than Ross manifested by a significant reduction of rectal temperature in the case of H + B. Furthermore, a significant linear relationship was found between the lowered rectal temperature and the expression of all HSP genes. Generally, the performance of both strains by most assessed parameters under heat stress is improved when using blue light.
Full Text Available Objectives: Much evidence exists that herbs have effective immunomodulatory activities. Chrysanthemi Flos (CF is effective in clearing heat, reducing inflammation, dropping blood pressure and treating headache and is used as a pharmaceutical raw material for an immune enhancer. The purpose of this study was to investigate the modulatory effect of Chrysanthemi Flos pharmacopuncture on nitric-oxide (NO production in activating macrophages. Methods: After a murine macrophage cell line, RAW 264.7, was cultured in the presence of lipopolysaccharide (LPS, immune-modulating abilities of CF were evaluated by using NO, interleukin-6 (IL-6 and tumor necrosis factor-alpha (TNF-α production and phagocytic activity of macrophages. Results: CF enhanced the activities of macrophages by increasing the phagocytic activity and decreasing NO production. Especially, both LPS and CF, 200 ㎍/ml, treatment could significantly reduce the NO production, but did not change the production of IL-6 and TNF-α. Conclusion: The results of this study indicate that CF may be of immunomodulatory value, especially for adverse diseases due to increased NO production. It may have potential for use as immunoenhancing pharmacopuncture.
Full Text Available This study investigated the modulatory role of emotion in the effect of time delay on recognition memory for pictures. Participants viewed neutral, positive and negative pictures, and took a recognition memory test 5 minutes, 24 hours, or 1 week after learning. The findings are: 1 For neutral, positive and negative pictures, overall recognition accuracy in the 5-min delay did not significantly differ from that in the 24-h delay. For neutral and positive pictures, overall recognition accuracy in the 1-week delay was lower than in the 24-h delay; for negative pictures, overall recognition in the 24-h and 1-week delay did not significantly differ. Therefore negative emotion modulates the effect of time delay on recognition memory, maintaining retention of overall recognition accuracy only within a certain frame of time. 2 For the three types of pictures, recollection and familiarity in the 5-min delay did not significantly differ from that in the 24-h and the 1-week delay. Thus emotion does not appear to modulate the effect of time delay on recollection and familiarity. However, recollection in the 24-h delay was higher than in the 1-week delay, whereas familiarity in the 24-h delay was lower than in the 1-week delay.
Full Text Available Early embryonic loss and adverse birth outcomes are the major reproductive disorders that affect both human and animals. The LPS induces inflammation by interacting with robust cellular mechanism which was considered as a plethora of numerous reproductive disorders such as fetal resorption, preterm birth, teratogenicity, intrauterine growth restriction, abortion, neural tube defects, fetal demise, and skeletal development retardation. LPS-triggered overproduction of free radicals leads to oxidative stress which mediates inflammation via stimulation of NF-κB and PPARγ transcription factors. Flavonoids, which exist in copious amounts in nature, possess a wide array of functions; their supplementation during pregnancy activates Nrf2 signaling pathway which encounters pregnancy disorders. It was further presumed that the development of strong antioxidant uterine environment during gestation can alleviate diseases which appear at adult stages. The purpose of this review is to focus on modulatory properties of flavonoids on oxidative stress-mediated pregnancy insult and abnormal outcomes and role of Nrf2 activation in pregnancy disorders. These findings would be helpful for providing new insights in ameliorating oxidative stress-induced pregnancy disorders.
Full Text Available IL-22 is a Th17/Th22 cytokine that is increased in asthma. However, recent animal studies showed controversial findings in the effects of IL-22 in allergic asthma. To determine the role of IL-22 in ovalbumin-induced allergic inflammation we generated inducible lung-specific IL-22 transgenic mice. Transgenic IL-22 expression and signaling activity in the lung were determined. Ovalbumin (OVA-induced pulmonary inflammation, immune responses, and airway hyperresponsiveness (AHR were examined and compared between IL-22 transgenic mice and wild type controls. Following doxycycline (Dox induction, IL-22 protein was readily detected in the large (CC10 promoter and small (SPC promoter airway epithelial cells. IL-22 signaling was evidenced by phosphorylated STAT3. After OVA sensitization and challenge, compared to wild type littermates, IL-22 transgenic mice showed decreased eosinophils in the bronchoalveolar lavage (BAL, and in lung tissue, decreased mucus metaplasia in the airways, and reduced AHR. Among the cytokines and chemokines examined, IL-13 levels were reduced in the BAL fluid as well as in lymphocytes from local draining lymph nodes of IL-22 transgenic mice. No effect was seen on the levels of serum total or OVA-specific IgE or IgG. These findings indicate that IL-22 has immune modulatory effects on pulmonary inflammatory responses in allergen-induced asthma.
Safaa E. Abdo
Full Text Available In a novel approach, monochromatic blue light was used to investigate its modulatory effect on heat stress biomarkers in two commercial broiler strains (Ross 308 and Cobb 500. At 21 days old, birds were divided into four groups including one group housed in white light, a second group exposed to blue light, a 3rd group exposed to white light + heat stress, and a 4th group exposed to blue light + heat stress. Heat treatment at 33°C lasted for five h for four successive days. Exposure to blue light during heat stress reduced MDA concentration and enhanced SOD and CAT enzyme activities as well as modulated their gene expression. Blue light also reduced the degenerative changes that occurred in the liver tissue as a result of heat stress. It regulated, though variably, liver HSP70, HSP90, HSF1, and HSF3 gene expression among Ross and Cobb chickens. Moreover, the Cobb strain showed better performance than Ross manifested by a significant reduction of rectal temperature in the case of H + B. Furthermore, a significant linear relationship was found between the lowered rectal temperature and the expression of all HSP genes. Generally, the performance of both strains by most assessed parameters under heat stress is improved when using blue light.
Full Text Available Amylase is one of the important digestive enzymes involved in hydrolysis of starch. In this paper, we describe a novel approach to study the interaction of amylase enzyme with gold nanoparticles (AuNPs and silver nanoparticles (AgNPs and checked its catalytic function. AuNPs are synthesized using citrate reduction method and AgNPs were synthesized using biological route employing Ficus benghalensis and Ficus religiosa leaf extract as a reducing and stabilizing agent to reduce silver nitrate to silver atoms. A modulatory effect of nanoparticles on amylase activity was observed. Gold nanoparticles are excellent biocompatible surfaces for the immobilization of enzymes. Immobilized amylase showed 1- to 2-fold increase of activity compared to free enzyme. The biocatalytic activity of amylase in the bioconjugate was marginally enhanced relative to the free enzyme in solution. The bioconjugate material also showed significantly enhanced pH and temperature stability. The results indicate that the present study paves way for the modulator degradation of starch by the enzyme with AuNPs and biogenic AgNPs, which is a promising application in the medical and food industry.
Mehmet Bilgehan Pektas
Full Text Available The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling including IR, IRS-1, IRS-2, Akt, PI3K, eNOS, mTOR, and PPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well as iNOS, Nrf2, and PI3K mRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes.
This study investigated the modulatory role of emotion in the effect of time delay on recognition memory for pictures. Participants viewed neutral, positive and negative pictures, and took a recognition memory test 5 minutes, 24 hours, or 1 week after learning. The findings are: 1) For neutral, positive and negative pictures, overall recognition accuracy in the 5-min delay did not significantly differ from that in the 24-h delay. For neutral and positive pictures, overall recognition accuracy in the 1-week delay was lower than in the 24-h delay; for negative pictures, overall recognition in the 24-h and 1-week delay did not significantly differ. Therefore negative emotion modulates the effect of time delay on recognition memory, maintaining retention of overall recognition accuracy only within a certain frame of time. 2) For the three types of pictures, recollection and familiarity in the 5-min delay did not significantly differ from that in the 24-h and the 1-week delay. Thus emotion does not appear to modulate the effect of time delay on recollection and familiarity. However, recollection in the 24-h delay was higher than in the 1-week delay, whereas familiarity in the 24-h delay was lower than in the 1-week delay. PMID:24971457
Paul, Katharina; Walentowska, Wioleta; Bakic, Jasmina; Dondaine, Thibaut; Pourtois, Gilles
Goal-adaptive behavior requires the rapid detection of conflicts between actions and intentions or goals. Although many studies have focused in the past on the influence of negative affect on this cognitive control process (and more specifically, on error monitoring), little is known about the possible modulatory effects of positive affect on it. To address this question, we used a standard (positive) mood induction procedure (based on guided imagery) and asked participants to carry out a speeded go/no-go task while high-density electroencephalography was recorded concurrently. As a control condition, we used a group with neutral mood. Event-related potential results showed that the error-related negativity (ERN) component, reflecting early error detection within the dorsal anterior cingulate cortex, was not influenced by happy mood. In contrast, the subsequent error positivity (Pe) component, related to the appraisal of the motivational significance of errors, was reliably smaller in the happy than in the neutral mood group. Complementing source localization analyses showed that this effect was explained by decreased activation within the posterior cingulate and insular cortices. These results were obtained in the absence of group differences regarding behavioral performance and tonic arousal. These findings suggest that happy mood likely decreases and changes the motivational significance of worse-than-expected events (Pe), while leaving their earlier automatic detection (ERN) unaltered. We discuss these new results in terms of dynamic changes in the complex interplay of performance monitoring with motivation.
Kufner, Marco; Brückner, Sabrina; Kammer, Thomas
Recently, it was reported that the application of a static magnetic field by placing a strong permanent magnet over the scalp for 10 min led to an inhibition of motor cortex excitability for at least 6 min after removing the magnet. When placing the magnet over the somatosensory cortex, a similar inhibitory after effect could be observed as well. Our aim was to replicate the inhibitory effects of transcranial static magnetic field stimulation in the motor and somatosensory system. The modulatory effect of static magnetic field stimulation was investigated in three experiments. In two experiments motor cortex excitability was measured before and after 10 or 15 min of magnet application, respectively. The second experiment included a sham condition and was designed in a double-blinded manner. In a third experiment, paired-pulse SSEPs were measured pre and four times post positioning the magnet over the somatosensory cortex for 10 min on both hemispheres, respectively. The SSEPs of the non stimulated hemisphere served as control condition. We did not observe any systematic effect of the static magnetic field neither on motor cortex excitability nor on SSEPs. Moreover, no SSEP paired-pulse suppression was found. We provide a detailed analysis of possible confounding factors and differences to previous studies on tSMS. After all, our results could not confirm the static magnetic field effect. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
Benoy, Amrita; Dasgupta, Ananya; Sajikumar, Sreedharan
The hippocampus is a critical brain region for the formation of declarative memories. While social memory had long been attributed to be a function of the hippocampus, it is only of late that the area CA2 of the hippocampus was demarcated as essential for social memory formation. In addition to this distinct role, CA2 possesses unique molecular, structural and physiological characteristics compared to the other CA regions-CA1 and CA3, and the dentate gyrus (DG). CA2 pyramidal neurons are positioned at a location between CA1 and CA3, receiving inputs from CA3 and DG, in addition to forming a powerful disynaptic circuit with direct input from the entorhinal cortical layer II neurons. CA2 also receives direct inputs from the hypothalamic regions and displays a unique expression pattern for receptors for neuromodulators. The location, inputs, and molecular signatures of the area CA2 point to the possibility that CA2 serves as a modulatory gateway that processes information from the entorhinal cortex and CA3, before relaying them onto CA1, the major output of the hippocampus. This review discusses recent findings regarding plasticity and neuromodulation in the CA2 region of the hippocampus, and how this may have the potential to influence plasticity in connecting circuits, and thereby memory and behaviour.
This study investigated the modulatory role of emotion in the effect of time delay on recognition memory for pictures. Participants viewed neutral, positive and negative pictures, and took a recognition memory test 5 minutes, 24 hours, or 1 week after learning. The findings are: 1) For neutral, positive and negative pictures, overall recognition accuracy in the 5-min delay did not significantly differ from that in the 24-h delay. For neutral and positive pictures, overall recognition accuracy in the 1-week delay was lower than in the 24-h delay; for negative pictures, overall recognition in the 24-h and 1-week delay did not significantly differ. Therefore negative emotion modulates the effect of time delay on recognition memory, maintaining retention of overall recognition accuracy only within a certain frame of time. 2) For the three types of pictures, recollection and familiarity in the 5-min delay did not significantly differ from that in the 24-h and the 1-week delay. Thus emotion does not appear to modulate the effect of time delay on recollection and familiarity. However, recollection in the 24-h delay was higher than in the 1-week delay, whereas familiarity in the 24-h delay was lower than in the 1-week delay.
Verweij, Frederik Johannes; Bebelman, Maarten P; Jimenez, Connie R; Garcia-Vallejo, Juan J; Janssen, Hans; Neefjes, Jacques; Knol, Jaco C; de Goeij-de Haas, Richard; Piersma, Sander R; Baglio, S Rubina; Verhage, Matthijs; Middeldorp, Jaap M; Zomer, Anoek; van Rheenen, Jacco; Coppolino, Marc G; Hurbain, Ilse; Raposo, Graça; Smit, Martine J; Toonen, Ruud F G; van Niel, Guillaume; Pegtel, D Michiel
Exosomes are small endosome-derived extracellular vesicles implicated in cell-cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB-PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB-PM fusion using live total internal reflection fluorescence and dynamic correlative light-electron microscopy. Quantitative analysis demonstrates that MVB-PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB-PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies. © 2018 Verweij et al.
Boardman, Lori A; Stockdale, Colleen K
Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.
Terzian, C; Pélisson, A; Bucheton, A
The genome of invertebrates is rich in retroelements which are structurally reminiscent of the retroviruses of vertebrates. Those containing three open reading frames (ORFs), including an env-like gene, may well be considered as endogenous retroviruses. Further support to this similarity has been provided by the ability of the env-like gene of DmeGypV (the Gypsy endogenous retrovirus of Drosophila melanogaster) to promote infection of Drosophila cells by a pseudotyped vertebrate retrovirus vector. To gain insights into their evolutionary story, a sample of thirteen insect endogenous retroviruses, which represents the largest sample analysed until now, was studied by computer-assisted comparison of the translated products of their gag, pol and env genes, as well as their LTR structural features. We found that the three phylogenetic trees based respectively on Gag, Pol and Env common motifs are congruent, which suggest a monophyletic origin for these elements. We showed that most of the insect endogenous retroviruses belong to a major clade group which can be further divided into two main subgroups which also differ by the sequence of their primer binding sites (PBS). We propose to name IERV-K and IERV-S these two major subgroups of Insect Endogenous Retro Viruses (or Insect ERrantiVirus, according to the ICTV nomenclature) which respectively use Lys and Ser tRNAs to prime reverse transcription.
loosdrecht, Marc C. M. Van; Henze, Mogens
mechanism is microbiologically correct. The lysis/decay model mechanism is a strongly simplified representation of reality. This paper tries to review the processes grouped under endogenous respiration in activated sludge models. Mechanisms and processes such as maintenance, lysis, internal and external...... and maintenance processes. This conversion will in general be denoted as endogenous respiration. Based on the literature review the phenomena are discussed and organised, in order to create a working platform for discussing more detailed activated sludge models, one of which is being sketched. (C) 1999 IAWQ......In activated sludge processes an increased sludge age is associated with a decreased sludge production. This phenomenon is generally interpreted as a result of endogenous respiration processes. In the activated sludge models cell lysis (or decay) is incorporated. The lysis is modelled...
Rocha, Vera; Van Praag, Mirjam; B. Folta, Timothy
Managers engage in a variety of strategies, not randomly, but having in mind their performance implications. Therefore, strategic choices are endogenous in performance equations. Despite increasing efforts by various scholars in solving endogeneity bias, prior attempts have almost exclusively......, such as employees, strategic partners, customers, or investors, whose choices and preferences also affect the final decision. We discuss how endogeneity can plague the measurement of the performance effects of these two-sided strategic decisions—which are more complex, but more realistic, than prior representations...... of organizational decision making. We provide an empirical demonstration of possible methods to deal with three different sources of bias, by analyzing the performance effects of two human capital choices made by founders at startup: the size and average quality of the initial workforce....
... Scrotal pain. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2016. Jan. 11, 2018 Original article: http://www.mayoclinic.org/symptoms/testicle-pain/basics/definition/SYM-20050942 . Mayo Clinic Footer Legal Conditions and ...
... triggers muscle strains. Even minor things, such as reading in bed or gritting your teeth, can strain ... determine the cause of your pain. Other tests Electromyography (EMG). If your doctor suspects your neck pain ...
Ma, Qianting; He, Jianmin; Li, Shouwei
We construct an endogenous network characterized by commercial credit relationships connecting the upstream and downstream firms. Simulation results indicate that the endogenous network model displays a scale-free property which exists in real-world firm systems. In terms of the network structure, with the expansion of the scale of network nodes, the systemic risk increases significantly, while the heterogeneities of network nodes have no effect on systemic risk. As for firm micro-behaviors, including the selection range of trading partners, actual output, labor requirement, price of intermediate products and employee salaries, increase of all these parameters will lead to higher systemic risk.
He, Jianmin; Sui, Xin; Li, Shouwei
In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.
Full Text Available Gut microbiota play an important role in human immunological processes, potentially affecting allergic diseases such as eczema. The diversity and structure of gut microbiota in infants with eczema have been previously documented. This study aims to evaluate by comparative metagenomics differences in genetic content in gut microbiota of infants with eczema and their matched controls. Stools were collected at the age of one month old from twelve infants from an at risk birth cohort in a case control manner. Clinical follow up for atopic outcomes were carried out at the age of 12 and 24 months. Microbial genomic DNA were extracted from stool samples and used for shotgun sequencing. Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs were significantly enriched in the six healthy controls (C communities compared to the six eczema subjects (E, with many encoded by Bifidobacterium (38% of the total motifs in the C communities. Draft genomes of five Bifidobacterium species populations (B. longum, B. bifidum, B. breve, B. dentium, and B. pseudocatenulatum were recovered from metagenomic datasets. The B. longum BFN-121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per one million genome sequence than other Bifidobacterium genomes. Additionally, the communities in the stool of controls (C were also significantly enriched in functions associated with tetrapyrrole biosynthesis compared to those of eczema (E. Our results show distinct immune-modulatory genomic properties of gut microbiota in infants associated with eczema and provide new insights into potential role of gut microbiota in affecting human immune homeostasis.
Kumar, Anil; Garg, Ruchika; Gaur, Vaibhav; Kumar, Puneet
Present study has been designed to elucidate the nitric oxide modulatory mechanism of venlafaxine in experimental model of chronic behavior despair in mice. Animals (male albino laca mice) were forced to swim daily for 6 min test session for 7 days and immobility period of each animal was measured on every alternate days. Six minutes forced swimming test session for 7 days caused anxiety-like behavior (as assessed by mirror chamber and plus maze tests) and impairment in locomotor activity followed by oxidative damage (increased lipid peroxidation, nitrite concentration, depleted reduced glutathione and catalase activity) as compared to naïve animals. Seven days venlafaxine (5 and 10 mg/kg) treatment significantly caused anti-anxiety-like effect, improved locomotor activity and attenuated oxidative damage (reduced lipid peroxidation, nitrite concentration and caused restoration of reduce glutathione and catalase activity) as compared to control. Caffeine (10 mg/kg) pretreatment with venlfaxine (5 mg/kg) did not produce any significant effect on locomotor activity, immobility period and oxidative damage as compared to their effect per se. Further, L-NAME (5 mg/kg) and methylene blue (10 mg/kg) pretreatment with sub effective dose of venlafaxine (5 mg/kg) potentiated its protective effect which was significant as compared to their effect per se. However, L-arginine (100 mg/kg) pretreatment with venlafaxine (5 mg/kg) significantly reversed the protective effect of venlafaxine (P<0.05). Present study suggests that nitric oxide modulation might be involved in the protective effects of venlafaxine. Copyright 2009 Elsevier B.V. All rights reserved.
Full Text Available Reduced neural processing of a tone is observed when it is presented after a sound whose spectral range closely frames the frequency of the tone. This observation might be explained by the mechanism of lateral inhibition (LI due to inhibitory interneurons in the auditory system. So far, several characteristics of bottom up influences on LI have been identified, while the influence of top-down processes such as directed attention on LI has not been investigated. Hence, the study at hand aims at investigating the modulatory effects of focused attention on LI in the human auditory cortex. In the magnetoencephalograph, we present two types of masking sounds (white noise vs. withe noise passing through a notch filter centered at a specific frequency, followed by a test tone with a frequency corresponding to the center-frequency of the notch filter. Simultaneously, subjects were presented with visual input on a screen. To modulate the focus of attention, subjects were instructed to concentrate either on the auditory input or the visual stimuli. More specific, on one half of the trials, subjects were instructed to detect small deviations in loudness in the masking sounds while on the other half of the trials subjects were asked to detect target stimuli on the screen. The results revealed a reduction in neural activation due to LI, which was larger during auditory compared to visual focused attention. Attentional modulations of LI were observed in two post-N1m time intervals. These findings underline the robustness of reduced neural activation due to LI in the auditory cortex and point towards the important role of attention on the modulation of this mechanism in more evaluative processing stages.
Engell, Alva; Junghöfer, Markus; Stein, Alwina; Lau, Pia; Wunderlich, Robert; Wollbrink, Andreas; Pantev, Christo
Reduced neural processing of a tone is observed when it is presented after a sound whose spectral range closely frames the frequency of the tone. This observation might be explained by the mechanism of lateral inhibition (LI) due to inhibitory interneurons in the auditory system. So far, several characteristics of bottom up influences on LI have been identified, while the influence of top-down processes such as directed attention on LI has not been investigated. Hence, the study at hand aims at investigating the modulatory effects of focused attention on LI in the human auditory cortex. In the magnetoencephalograph, we present two types of masking sounds (white noise vs. withe noise passing through a notch filter centered at a specific frequency), followed by a test tone with a frequency corresponding to the center-frequency of the notch filter. Simultaneously, subjects were presented with visual input on a screen. To modulate the focus of attention, subjects were instructed to concentrate either on the auditory input or the visual stimuli. More specific, on one half of the trials, subjects were instructed to detect small deviations in loudness in the masking sounds while on the other half of the trials subjects were asked to detect target stimuli on the screen. The results revealed a reduction in neural activation due to LI, which was larger during auditory compared to visual focused attention. Attentional modulations of LI were observed in two post-N1m time intervals. These findings underline the robustness of reduced neural activation due to LI in the auditory cortex and point towards the important role of attention on the modulation of this mechanism in more evaluative processing stages.
Full Text Available Although acoustic frequency is not a spatial property of physical objects, in common language, pitch, i.e., the psychological correlated of frequency, is often labeled spatially (i.e., high in pitch or low in pitch. Pitch-height is known to modulate (and interact with the response of participants when they are asked to judge spatial properties of non-auditory stimuli (e.g., visual in a variety of behavioral tasks. In the current study we investigated whether the modulatory action of pitch-height extended to the haptic estimation of height of a virtual step.We implemented a HW/SW setup which is able to render virtual 3D objects (stair-steps haptically through a PHANTOM device, and to provide real-time continuous auditory feedback depending on the user interaction with the object. The haptic exploration was associated with a sinusoidal tone whose pitch varied as a function of the interaction point’s height within (i a narrower and (ii a wider pitch range, or (iii a random pitch variation acting as a control audio condition. Explorations were also performed with no sound (haptic only. Participants were instructed to explore the virtual step freely, and to communicate height estimation by opening their thumb and index finger to mimic the step riser height, or verbally by reporting the height in centimeters of the step riser. We analyzed the role of musical expertise by dividing participants into non musicians and musicians. Results showed no effects of musical pitch on high-realistic haptic feedback. Overall there is no difference between the two groups in the proposed multimodal conditions. Additionally, we observed a different haptic response distribution between musicians and non musicians when estimations of the auditory conditions are matched with estimations in the no sound condition.
Escrich, Eduard; Solanas, Montserrat; Moral, Raquel; Escrich, Raquel
Breast cancer is the most common cancer among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically dietary habits, plays a key role in the aetiology of this malignancy. Epidemiological and, especially, experimental studies have shown a relationship between dietary lipids and breast cancer although there are conflicting results concerning their potential to modify cancer risk in humans. Abundant data have attributed a potential chemopreventive effect to extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from cardiovascular disease and some cancers, including that of the breast. It is well-established that the healthy effects of EVOO can be attributed both to its particular fatty acid composition (a high content in oleic acid (OA), a suitable quantity of essential polyunsaturated fatty acids (PUFA) and a relatively low n-6 PUFA/n-3 PUFA ratio) and its richness in minor bioactive compounds such as squalene and phenolic antioxidants. The specific mechanisms by which EVOO and other dietary lipids may exert their modulatory effects on cancer are not fully understood although abundant research has proposed the following: They influence in the stages of the carcinogenesis process, oxidative stress, alteration of the hormonal status, modification of the structure and function of cell membranes, modulation of cell signalling transduction pathways, regulation of gene expression and influence in the immune system. This article will explore the current knowledge of these mechanisms, including our own results in the context of the international literature.
Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza E Silva, Alair Pedro
One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson's disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer's disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies.
Dutta, Dipanwita; Devi, S Saravana; Krishnamurthi, K; Kumar, Koel; Vyas, Priyanka; Muthal, P L; Naoghare, P; Chakrabarti, T
To study the modulatory effect of distillate of Ocimum sanctum (traditionally known as Tulsi) leaf extract (DTLE) on genotoxicants. In the present investigation, we studied the antigenotoxic and anticlastogenic effect of distillate of Tulsi leaf extract on (i) human polymorphonuclear leukocytes by evaluating the DNA strand break without metabolic activation against mitomycin C (MMC) and hexavalent chromium (Cr+6) and (ii) human peripheral lymphocytes (in vitro) with or without metabolic activation against mitomycin C (MMC), hexavalent chromium (Cr+6) and B[a]P by evaluating chromosomal aberration (CA) and micronucleus assay (MN). Three different doses of DTLE, 50 microL/mL, 100 microL/mL, and 200 microL/mL were selected on the basis of cytotoxicity assay and used for studying DNA strand break, chromosomal aberration and micronucleus emergence. The following positive controls were used for inducing genotoxicity and clastogenicity: MMC (0.29 micromol/L) for DNA strand break, chromosomal aberration and 0.51 micromol/L for micronucleus assay; Potassium dichromate (Cr+6) 600 micromol/L for DNA strand break and 5 micromol/L for chromosomal aberration and micronucleus assay; Benzo[a]pyrene (30 micromol/L) for chromosomal aberration and 40 micromol/L for micronucleus assay. The active ingredients present in the distillate of Tulsi leaf extract were identified by HPLC and LC-MS. Mitomycin C (MMC) and hexavalent chromium (Cr+6) induced statistically significant DNA strand break of respectively 69% and 71% (PTulsi leaf extract possesses antioxidants contributed mainly by eugenol, luteolin and apigenin as identified by LC-MS. These active ingredients may have the protective effect against genotoxicants.
... or tightness in your chest Crushing or searing pain that radiates to your back, neck, jaw, shoulders, and one or both arms Pain that lasts ... com. Accessed Sept. 6, 2017. Yelland MJ. Outpatient evaluation of the adult with chest pain. https://www.uptodate.com/contents/search. Accessed Sept. ...
... arms or hands or if you have shooting pain into your shoulder or down your arm. Symptoms Signs and symptoms ... org/search/Pages/results.aspx?k=Chronic neck pain. Accessed June 11, 2015. Isaac Z. Evaluation of the patient with neck pain and cervical ...
... the level of of hormones during menstruation or pregnancy often cause breast pain. Some swelling and tenderness just before your period is normal. Some women who have pain in one or both breasts may fear breast cancer . However, breast pain is not a common symptom ...
Izzo, R., E-mail: email@example.com [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: firstname.lastname@example.org [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: email@example.com [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: firstname.lastname@example.org [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)
Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide . LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic
Thomas H. Fritz
Full Text Available Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm.Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency.Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test.Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity.Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful.
Leknes, Siri; Berna, Chantal; Lee, Michael C; Snyder, Gregory D; Biele, Guido; Tracey, Irene
Context can influence the experience of any event. For instance, the thought that "it could be worse" can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the "relative relief context," moderate pain represented the best outcome, since the alternative outcome was intense pain. However, in the control context, moderate pain represented the worst outcome and elicited negative hedonic feelings. The context manipulation resulted in a "hedonic flip," such that moderate pain elicited positive hedonics in the relative relief context. Somewhat surprisingly, moderate pain was even rated as pleasant in this context, despite being reported as painful in the control context. This "hedonic flip" was corroborated by physiological and functional neuroimaging data. When moderate pain was perceived as pleasant, skin conductance and activity in insula and dorsal anterior cingulate were significantly attenuated relative to the control moderate stimulus. "Pleasant pain" also increased activity in reward and valuation circuitry, including the medial orbitofrontal and ventromedial prefrontal cortices. Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced "hedonic flip" of pain. Copyright © 2012 International Association for the Study of Pain. All rights reserved.
de Bont, L.G.
Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either
Donner, Mechthild; Horlings, Lummina; Fort, Fatiha; Vellema, Sietze
This article deals with place branding on the regional scale, in the rural context of food and tourism networks in Europe. Place branding is linked to the concepts of endogenous rural development, territory and embeddedness, by analysing how the valorisation of specific rural assets takes shape.
In this treatise, a quick look is taken at the spectrum (range) of research from pure basic, strategic basic, applied, experimental development or research and development (R&D) to endogenous research and innovation (ER&I). It also defines development, innovation, food security, poverty; and discusses some contemporary ...
DesRochers, David W; Reed, J Michael; Awerman, Jessica; Kluge, Jonathan A; Wilkinson, Julia; van Griethuijsen, Linnea I; Aman, Joseph; Romero, L Michael
We investigated how exogenous and endogenous glucocorticoids affect feather replacement in European starlings (Sturnus vulgaris) after approximately 56% of flight feathers were removed. We hypothesized that corticosterone would retard feather regrowth and decrease feather quality. After feather regrowth began, birds were treated with exogenous corticosterone or sham implants, or endogenous corticosterone by applying psychological or physical (food restriction) stressors. Exogenous corticosterone had no impact on feather length and vane area, but rectrices were lighter than controls. Exogenous corticosterone also decreased inter-barb distance for all feathers and increased barbule number for secondaries and rectrices. Although exogenous corticosterone had no affect on rachis tensile strength and stiffness, barbicel hooking strength was reduced. Finally, exogenous corticosterone did not alter the ability of Bacillus licheniformis to degrade feathers or affect the number of feathers that failed to regrow. In contrast, endogenous corticosterone via food restriction resulted in greater inter-barb distances in primaries and secondaries, and acute and chronic stress resulted in greater inter-barb distances in rectrices. Food-restricted birds had significantly fewer barbules in primaries than chronic stress birds and weaker feathers compared to controls. We conclude that, although exogenous and endogenous corticosterone had slightly different effects, some flight feathers grown in the presence of high circulating corticosterone are lighter, potentially weaker, and with altered feather micro-structure.
Purpose: To use endogenous myrosinase in Carica papaya seed to convert benzyl glucosinolate (BG) to benzyl isothiocyanate (BITC) and then extract it for further studies. Methods: Process variables including seed powder particle size, sample-to-solvent ratio, pH of buffer solution, enzymolysis temperature, enzymolysis ...
Jan 2, 2002 ... demonstrated in New Zealand Black mice, where the reproductive tract of males were shown to contain C-type retrovirus(35). Also endogenous mouse mammary tumour virus (MMTV) proteins (p28 and gp47) have been identiﬁed in the epididymis and seminal vesicles of adult Swiss. Albino mice devoid of ...
Senyuta, Olena; Žigić, Krešimir
Roč. 35, June (2016), s. 45-64 ISSN 0167-6245 R&D Projects: GA ČR(CZ) GAP402/12/0961 Institutional support: PRVOUK-P23 Keywords : endogenous sunk costs * innovations * knowledge spillovers Subject RIV: AH - Economics Impact factor: 0.739, year: 2016
van der Kuyl, A. C.; Dekker, J. T.; Goudsmit, J.
Cross-species transmission of retroviruses among primates has recently been recognized as the source of the current epidemics of HIV-1, HIV-2 and human T cell leukemia virus type 1 (HTLV-1). The distribution of baboon endogenous virus among non-human primates resembles that of exogenous viruses and
Ray Chaudhuri, A.; Pandey, Manish
We document that immigration to U.S. states has increased the mass of workers at the lower range of the skill distribution. We use this change in skill distribution of workers to analyze the effect of immigration on wages. Our model allows firms to endogenously respond to the immigration-induced
Mazza, I.; van Winden, F.
Endogenous policy models usually neglect that government policies are frequently the result of decisions taken at different tiers by different agents, each enjoying some degree of autonomy. In this paper, policies are the outcome of the choices made by two agents within a hierarchy. A legislator
P.A.G. van Bergeijk (Peter); G.H.A. van Hagen; R.A. de Mooij (Ruud); J. van Sinderen (Jarig)
textabstractThis paper endogenizes technology and human capital formation in the MESEM model that was developed by van Sinderen (Economic Modelling, 1993, 13, 285-300). Tax allowances for private R&D expenditures and public expenditures on both education and R& D are effective instruments to
In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...
sufficient feed. In the TME procedure, as publishecl by. Sibbald ( 1976), endogenous energy excretion is deter- mined with fasted animals, a situation which can be re- garded as being physiologically undesirable since birds would be in an energy-deficient state and to an extent also in a protein deficient state. When in a ...
This requires not only an understanding of what endogenous knowledge is, but also an alignment of personal values, innovative strategies and an attitude of activism. An integral part of an extensive skills set to implement ... competence of dispute resolution practitioners in Africa. AFRICA INSIGHT Vol 42 (1) – June 2012 ...
... systematically gathered for consumption and marketing. Few studies have been done on the ethnobotany and endogenous practices determining its conservation of the species in Benin. This study aims to produce a database on those aspects in Benin. Two hundred and sixty-three people from the six major socio-cultural ...
Aziz, Mubeena; Sidelmann, Johannes J; Wissing, Marie Louise Muff
OBJECTIVES: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria. DESIGN: Multicenter...
Full Text Available Endomorphin-1 (EM1 and endomorphin-2 (EM2 are two endogenous ligands that belong to the opioid peptide family and have the highest affinity and selectivity for the µ-opioid receptor (MOR. The neuroanatomical distribution, ultrastructural features and neural circuitry of EM-containing neuronal structures have been morphologically demonstrated. In addition, the modulation effects of the EMs in different areas reflect their potential endogenous roles in many major physiological processes, including their remarkable roles in the transmission and modulation of noxious information. The distinguished antinociceptive property of the EMs in acute and chronic pain, including neuropathic pain, cancer pain and inflammatory pain, has been revealed and investigated for therapeutic purposes. However, EMs exert adverse effects in the gastrointestinal, urinary, cardiovascular, and respiratory systems, which impede the development of EMs as new analgesics. Numerous studies have synthesized and investigated EM analogues and demonstrated that these EM derivatives had improved pharmacological properties, supporting their therapeutic perspectives. In the present review, the results of previous studies, particularly morphological and pharmacological studies, were summarized. Finally, EM modifications and their potential clinical implications were described. Applying this knowledge about EMs may provide information for further investigations in clinical application.
Locke, David; Gibson, William; Moss, Penny; Munyard, Kylie; Mamotte, Cyril; Wright, Anthony
Conditioned pain modulation (CPM) encompasses the effects of inhibitory and facilitatory pain modulatory systems and is inefficient in some chronic pain states. A proportion of healthy subjects also exhibit little or no CPM, perhaps suggesting that inherent factors such as gender or genetics may be influential. However, there is no consensus on how best to determine a meaningful CPM effect. This study aimed to determine the proportion of pain-free subjects exhibiting a meaningful CPM effect. Analyses of associations between 5HTTLPR (serotonin transporter-linked polymorphic region) polymorphisms on the serotonin transporter gene (SLC6A4), gender, and CPM effect were also carried out. A total of 125 healthy subjects (47 male; 78 female) underwent pressure pain threshold testing before, during, and after a cold pressor conditioning stimulus. A buccal cell sample was collected for analysis of 5HTTLPR genotype. Meaningful CPM effect was determined as an increase in pressure pain threshold values from baseline greater than the inherent error of measurement, calculated as 5.3%. During the conditioning stimulus, 116 subjects (92.8%) exhibited a CPM effect whereas 9 did not. CPM effect did not differ significantly between genders or between 5HTTLPR genotypes. This provides a clear basis on which to determine the proportion of patients with a chronic pain disorder that exhibit a meaningful CPM effect. This study proposes a method for calculating meaningful CPM effect and reports the proportion and magnitude of effect elicited in a large sample. Associations between CPM, gender, and genotype were also analyzed. Clarification of normal CPM response may help to elucidate the mechanisms driving CPM inefficiency in chronic pain. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.
Full Text Available INTRODUCTI ON: Endogenous or metastatic endophthalmitis is a very rare sever form of ocular disease which is uncommon now - a - days. Prevalence of endogenous bacterial endophthalmitis is 2 - 8% of all cases of endophthalmitis 1 . Mostly it is associated with chronic disease like diabetes mellitus, renal failure, liver abscesses, prolong placement of catheter, IV line or central venous line, drug abusers and immunocompromise d patients. Gram +bacteria are the most common causative organism of the endogenous bacterial endophthalmitis . 1 A few cases of endogenous bacterial endophthalmitis due to klebsiella pneumonias, a gram - ve organism have been documented and majority of them were in Taiwan . 2, 3,4,5,6, 7 K. pneumonia endophthalmitis is associated with diabetes mellitus and hepatic abscesses can be bilateral and resulted into poor visual outcome . 2,3,4,5,6, 7 K. pneumonia pneumonia has been reported most frequently from patients with alcoholic liver diseases and one of the common cause of acute osteomyelitis and septic arthritis . 8,9 In this scenario we report the case of a Malawian in African Continent who developed bilateral endogenous bacterial endophthalmitis after suffering from pneumonia in immunocompromise state. PURPOSE : to report a case bilateral endogenous endophthalmitis secondary to pneumonia in an AIDS patient . DESIGN : Observational case report . METHODS : A patient with bilateral pain full red eye with diminution of vision was seen in c onsultation by ophthalmology. RESULT : with clinical characteristic and laboratory diagnosis of sputum and blood conf i rmed the causative agent for pneumonia and endophthalmitis is K.pneumonia. CONCLUSION : it is unusual disease, required early detection and prompt treatment.
Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.
Yap, Gaik Chin
TCAAGCTTGA motifs (4.2 copies per 1 million genome sequence) than other Bifidobacterium genomes and was significantly overrepresented (P < 0.05) in the healthy communities. Conclusions: Our results report distinct immune-modulatory genomic properties of gut microbiotas in healthy infants as compared to children with eczema and provide new insights into potential roles of gut microbiotas in affecting human immune homeostasis.
Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie
Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....
Aasvang, Eske K; Møhl, Bo; Kehlet, Henrik
BACKGROUND: Sexual dysfunction due to ejaculatory and genital pain after groin hernia surgery may occur in approximately 2.5% of patients. However, the specific psychosexological and neurophysiologic characteristics have not been described, thereby precluding assessment of pathogenic mechanisms...... and treatment strategies. METHODS: Ten patients with severe pain-related sexual dysfunction and ejaculatory pain were assessed in detail by quantitative sensory testing and interviewed by a psychologist specialized in evaluating sexual functional disorders and were compared with a control group of 20 patients...... with chronic pain after groin hernia repair but without sexual dysfunction, to identify sensory changes associated with ejaculatory pain. RESULTS: Quantitative sensory testing showed significantly higher thermal and mechanical detection thresholds and lowered mechanical pain detection thresholds in both groups...
of pain , particularly beta- endorphins , has been the subject of increasing research, and is explicated below. Endogenous Pain Control System The... Endorphins have been found to play an important role in the perception of pain , including that resulting from coronary ischemia. Sheps et al. (1987) and...nonpregnant women, and 18 men. Although no statistical association between subjective pain levels and beta- endorphin levels was found, Cahill noted a
Colciago, Andrea; Rossi, Lorenza
We propose a model characterized by strategic interactions among an endogenous number of producers and search and matching frictions in the labor market. In line with U.S. data: (i) new firms account for a relatively small share of overall employment, but they create a relevant fraction of new jobs; (ii) firms entry is procyclical; (iii) price mark ups are countercyclical, while aggregate profits are procyclical. In response to a technology shock the labor share decreases on impact and overs...
Andersen, Torben M.; Bhattacharya, Joydeep
A classic result in dynamic public economics, dating back to Aaron (1966) and Samuelson (1975), states that there is no welfare rationale for PAYG pensions in a dynamically-efficient neoclassical economy with exogenous labor supply. This paper argues that this result, under the fairly......-mild restriction that the old be no less risk-averse than the young, extends to a neoclassical economy with endogenous labor supply....
Public procurement used as an innovation policy instrument has attracted attention the last decade. It has been argued that public procurement can be used to stimulate innovation from the demand-side. This paper problematizes ‘demand’ understood as a problem defined by a public procurer given...... underlying mechanisms critical for success. Instead the paper views public procurement of innovation as an instrument of endogenous- exogenous knowledge conversion....
Bhattacharyya, Chandril; Gupta, Manash Ranjan
In this paper, a model of endogenous economic growth is developed with special focus on the interaction between unionized labour market and environmental pollution. We introduce a trade union; and use both ‘Efficient Bargaining’ model and ‘Right to Manage’ model to solve the negotiation problem. Environmental pollution is the result of production; and the labour union bargains not only for wage and employment but also for the protection of environment. We derive properties of optimum income t...
Bennett T. McCallum
This paper begins with an exposition of neoclassical growth theory, including several analytical results such as the distinction between golden-rule and optimal steady states. Next it emphasizes that the neoclassical approach fails to provide any explanation of steady-state growth in per capita values of output and consumption, and also cannot plausibly explain actual growth differences by reference to transitional episodes. Three types of endogenous growth models, which attempt to provide ex...
Buyer search costs for price are changing in many markets. Through a model of buyer and seller behavior, I consider the effects of changing search costs on prices both when product differentiation is fixed and when it is endogenously determined in equilibrium. If firms cannot change product design, lower buyer search costs for price lead to increased price competition. However, if product design is a decision variable, lower search costs for price may also lead to higher product differentiati...
Storrøsten, Halvor Briseid
Authorities often lack information for efficient regulation of the commons. This paper derives a criterion comparing prices versus tradable quantities in terms of expected welfare, given uncertainty, optimal policy and endogenous cost structure. I show that one cannot determine which regulatory instrument that induces the highest expected welfare based on the relative curvatures of the cost and benefit functions alone. Furthermore, optimal policy involves different production (or price) targe...
Hirano, Tomohiro; Yanagawa, Noriyuki
This paper analyzes the effects of bubbles in an infinitely-lived agent model of endogenous growth with financial frictions and heterogeneous agents. We provide a complete characterization on the relationship between financial frictions and the existence of bubbles. Our model predicts that if the degree of pledgeability is sufficiently high or sufficiently low, bubbles can not exist. They can only arise at an intermediate degree. This suggests that improving the financial market condition mig...
Loggia, Marco L; Berna, Chantal; Kim, Jieun; Cahalan, Christine M; Gollub, Randy L; Wasan, Ajay D; Harris, Richard E; Edwards, Robert R; Napadow, Vitaly
While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief. Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of ~50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation). Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and pain-modulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished. FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/γ-aminobutyric acid-releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients. Copyright © 2014 by the American
de Oliveira, Allan Demetrius Leite; Galvao Rodrigue, Fabiola Fernandes; Douglas Melo Coutinho, Henrique; da Costa, Jose Galberto Martins; de Menezes, Irwin Rose Alencar
Several studies have shown that species of the genus Hyptis, have promising antimicrobial and antifungal effects. Identify of chemical constituents of essential oil from leaves of Hyptis martiusii and evaluate its effect against bacterial strains by direct and gaseous contact. Essential oil was extracted from leaves of Hyptis martiusii Benth using hydro-distillation, and its composition was determined using gas chromatography-mass spectrometry (GC-MS). Chemical analysis showed that there was a predominance of sesquiterpenes. The leaf essential oil was screened for its minimal inhibitory concentration and modulatory effect of aminoglycoside by the direct (MIC) and gaseous (MID) micro-dilution assays for various pathogenic microorganisms. The essential oil remarkably inhibited the growth of all of the tested bacteria (MIC essential oil of leaves were characterized; δ -3-carene (6.88%), 1, 8-cineole (7.01%), trans-caryophyllene (9.21%), Cariophyllene oxide (7.47%) and bicyclogermacrene (10.61%) were found as the major components. Modulatory aminoglycoside effect, by direct contact, was showed antagonistic relationship with antimicrobial activity. The gaseous component of the oil inhibited the bacterial growth of all of the tested bacteria in 50% and 25% of oil concentration and demonstrated synergistic interactions can be attributed to the constituting the oil compounds. These results show that this oil influences the activity of the antibiotic and may be used as an adjuvant in the antibiotic therapy of respiratory tract bacterial pathogens.
Piccinno, M; Rizzo, A; Maselli, M A; Derosa, M; Sciorsci, R L
This in vitro study investigates the modulatory effect of three antibiotics (amoxicillin, enrofloxacin, and rifaximin) on contractility of the bovine uterine tissue in follicular and luteal phases. The effects of these antibiotics at three single doses (10(-6), 10(-5), and 10(-4) M) on their basal contractility were evaluated in isolated organ bath. The functionality of the strip throughout the experiment was evaluated by a dose of carbachol (10(-5) M); the obtained effect had to be repeatable (difference of ≤20%) that is comparable to that induced by the previous administration of the same substance. The results demonstrate the different modulatory activities of these antibiotics on uterine contractility in follicular and luteal phases. The effects induced by amoxicillin and enrofloxacin are opposite: the first relaxes and the second increases the uterine contractility in both cycle phases. Instead, the activity of rifaximin varies depending on the phase of estrous cycle: it increases in the follicular phase and relaxes in the luteal phase. The obtained data provide the hypothesis of possible implications of these drugs in the pharmacologic modulation of uterine contractions. Their action at this level, associated with their specific antimicrobial effects, could suggest using these antibiotics for the treatment of diseases related to postpartum or infections that may occur in pregnant cattle, by virtue of their effects on myometrial contractility too. Copyright © 2014 Elsevier Inc. All rights reserved.
Yan, Xiaodong; Tian, He; Xie, Yujun; Kostelec, Andrew; Zhao, Huan; Cha, Judy J.; Tice, Jesse; Wang, Han
Modulatory input-dependent plasticity is a well-known type of hetero-synaptic response where the release of neuromodulators can alter the efficacy of neurotransmission in a nearby chemical synapse. Solid-state devices that can mimic such phenomenon are desirable for enhancing the functionality and reconfigurability of neuromorphic electronics. In this work, we demonstrated a tunable artificial synaptic device concept based on the properties of graphene and tin oxide that can mimic the modulatory input-dependent plasticity. By using graphene as the contact electrode, a third electrode terminal can be used to modulate the conductive filament formation in the vertical tin oxide based resistive memory device. The resulting synaptic characteristics of this device, in terms of the profile of synaptic weight change and the spike-timing-dependent-plasticity, is tunable with the bias at the modulating terminal. Furthermore, the synaptic response can be reconfigured between excitatory and inhibitory modes by this modulating bias. The operation mechanism of the device is studied with combined experimental and theoretical analysis. The device is attractive for application in neuromorphic electronics. This work is supported by ARO and NG-ION2 at USC.
Seyedeh Maryam Hosseini
Conclusion: Burn patients treated with broad-spectrum antibiotics are at risk of candidemia and its complications, including endogenous endophthalmitis. Early diagnosis of endogenous endophthalmitis in high risk patients could prevent visual loss.
Agrell, Per J.; Bogetoft, Peter
Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest of the ev......-priced out- puts is relevant. The results show that sector wide weighting schemes favor input/output combinations that are less variable than would individual units......Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest...... of the evaluated industry calls for attention. We offer endogenous general prices based on a reformulation of DEA where the units collectively propose the set of weights that maximize their efficiency. Thus, the sector-wide efficiency is then a result of compromising the scores of more specialized smaller units...
Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)
Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.
Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.
Full Text Available The numerous versions of endogenous explanations of economic growth emphasize the importance of technological change driving forces, as well as the existence of appropriate institutional arrangements. Endogenous growth theory contributes to a better understanding of various experiences with long-term growth of countries and regions. It changes the key assumptions of the Neoclassical growth theory and participates in the modern regional development physiology explanation. Based on these conclusions, the paper: a explicates the most important theoretical postulates of the theory, b explains the most important factors of economic growth in the regions in light of the Endogenous growth theory messages and c emphasizes the key determinants of regional competitiveness which in our view is conceptually between the phenomena of micro- and macro-competitiveness and represents their necessary and unique connection. First of all, micro-competitiveness is transformed into a regional competitiveness; then regional competitiveness is transformed into a macro-competitiveness. In turn, macro - influences the microeconomic competitiveness, and the circle is closed. After that, the process starts over again.
Bruce, W Robert; Lee, Owen; Liu, Zhen; Marcon, Norman; Minkin, Salomon; O'Brien, Peter J
We observed an unexpectedly strong association of three different endogenous aldehydes and noted that the association could be explained by multiple reactions in which oxidative stress increased the formation of endogenous aldehydes and endogenous aldehydes increased oxidative stress. These interactions make it reasonable to assess multiple exposures to endogenous oxidative and aldehyde stress with less specific measures such as advanced glycation end-products or protein carbonyls.
Alfonso Miranda; Massimiliano Bratti
In this presentation we define two qualitatitive response models: 1) Selection Endogenous Dummy Ordered Probit model (SED-OP); 2) a Selection Endogenous Dummy Dynamic Selection Ordered Probit model (SED- DOP). The SED-OP model is a three-equation model constituted of an endogenous dummy equation, a selection equation, and a main equation which has an ordinal response form. The main feature of the model is that the endogenous dummy enters both the selection equation and the main equation. The ...
Chest pain in ambulatory setting is predominantly not heart-associated. Most patients suffer from muskuloskeletal or functional (psychogenic) chest pain. Differential diagnosis covers aortic dissection, rib-fracture, shingles, GERD, Tietze-Syndrome, pulmonary embolism, pleuritis, pneumothorax, pleurodynia and metastatic disease. In most cases history, symptoms and signs allow a clinical diagnosis of high pretest-probability.
... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...
of muscle or tendons.4,14. Management of muscle pain. Non-Pharmacological Management. The non-pharmacological treatments for muscle pain are illustrated in Figure 1. Treatment modalities include the following. Transcutaneous electrical stimulation (TENS). TENS is a non-invasive procedure used in rehabilitation to.
... weight loss slowed growth rate lots of vomiting chronic severe diarrhea gastrointestinal blood loss persistent pain on the right ... or Spanish)—from The North American Society for Pediatric Gastroenterology, Hepatology and ... Chronic Abdominal Pain in Children , a clinical report from ...
Full Text Available Many factors can be involved in the painful shoulder. Beyond articularcauses other pathologies such as artrosis, periarticular diseases as rotadorcuff tears, long head of the biceps tendinitis, adhesive capsulitis, calcifyingtendinitis, degenerative arthritis of the acromioclavicular joint, cervicalradiculopathy and nervous injuries can cause pain in the shoulder.
... and ligaments inside the shoulder become stiff, making movement difficult and painful Overuse or injury of nearby tendons, such as the bicep muscles of the arms Tears of the rotator cuff tendons Watch this video about: Shoulder joint dislocation Sometimes, shoulder pain may ...
Benno Ejnismann; Gustavo Cará Monteiro; Luis Fernando Uyeda
Many factors can be involved in the painful shoulder. Beyond articularcauses other pathologies such as artrosis, periarticular diseases as rotadorcuff tears, long head of the biceps tendinitis, adhesive capsulitis, calcifyingtendinitis, degenerative arthritis of the acromioclavicular joint, cervicalradiculopathy and nervous injuries can cause pain in the shoulder.
Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.
... pain. The pain may spread to the arm, shoulder, jaw, or back. A tear in the wall of the aorta, the large blood vessel that takes blood from the heart to the rest of the body ( aortic dissection ) causes sudden, severe ...
Chu, Constance J; Huang, Susan M; De Petrocellis, Luciano; Bisogno, Tiziana; Ewing, Scott A; Miller, Jeffrey D; Zipkin, Robert E; Daddario, Nives; Appendino, Giovanni; Di Marzo, Vincenzo; Walker, J Michael
N-Arachidonoyldopamine (NADA) was recently identified as an endogenous ligand for the vanilloid type 1 receptor (VR1). Further analysis of the bovine striatal extract from which NADA was isolated indicated the existence of substances corresponding in molecular mass to N-oleoyldopamine (OLDA), N-palmitoyldopamine (PALDA), and N-stearoyldopamine (STEARDA). Quadrupole time-of-flight mass spectrometric analysis of bovine striatal extracts revealed the existence of OLDA, PALDA, and STEARDA as endogenous compounds in the mammalian brain. PALDA and STEARDA failed to affect calcium influx in VR1-transfected human embryonic kidney (HEK) 293 cells or paw withdrawal latencies from a radiant heat source, and there was no evidence of spontaneous pain behavior. By contrast, OLDA induced calcium influx (EC(50) = 36 nm), reduced the latency of paw withdrawal from a radiant heat source in a dose-dependent manner (EC(50) = 0.72 microg), and produced nocifensive behavior. These effects were blocked by co-administration of the VR1 antagonist iodo-resiniferatoxin (10 nm for HEK cells and 1 microg/50 micro;l for pain behavior). These findings demonstrate the existence of an endogenous compound in the brain that is similar to capsaicin and NADA in its chemical structure and activity on VR1. Unlike NADA, OLDA was only a weak ligand for rat CB1 receptors; but like NADA, it was recognized by the anandamide membrane transporter while being a poor substrate for fatty-acid amide hydrolase. Analysis of the activity of six additional synthetic and potentially endogenous N-acyldopamine indicated the requirement of a long unsaturated fatty acid chain for an optimal functional interaction with VR1 receptors.
Segall, S K; Maixner, W; Belfer, I; Wiltshire, T; Seltzer, Z; Diatchenko, L
The enzyme catechol-O-methyltransferase (COMT) has been shown to play a critical role in pain perception by regulating levels of epinephrine (Epi) and norepinephrine (NE). Although the key contribution of catecholamines to the perception of pain has been recognized for a long time, there is a clear dichotomy of observations. More than a century of research has demonstrated that increasing adrenergic transmission in the spinal cord decreases pain sensitivity in animals. Equally abundant evidence demonstrates the opposite effect of adrenergic signaling in the peripheral nervous system, where adrenergic signaling increases pain sensitivity. Viewing pain processing within spinal and peripheral compartments and determining the directionality of adrenergic signaling helps clarify the seemingly contradictory findings of the pain modulatory properties of adrenergic receptor agonists and antagonists presented in other reviews. Available evidence suggests that adrenergic signaling contributes to pain phenotypes through α(1/2) and β(2/3) receptors. While stimulation of α(2) adrenergic receptors seems to uniformly produce analgesia, stimulation of α(1) or β receptors produces either analgesic or hyperalgesic effects. Establishing the directionality of adrenergic receptor modulation of pain processing, and related COMT activity in different pain models are needed to bring meaning to recent human molecular genetic findings. This will enable the translation of current findings into meaningful clinical applications such as diagnostic markers and novel therapeutic targets for complex human pain conditions.
Segall, S.K.; Maixner, W.; Belfer, I.; Wiltshire, T.; Seltzer, Z.; Diatchenko, L.
The enzyme catechol-O-methyltransferase (COMT) has been shown to play a critical role in pain perception by regulating levels of epinephrine (Epi) and norepinephrine (NE). Although the key contribution of catecholamines to the perception of pain has been recognized for a long time, there is a clear dichotomy of observations. More than a century of research has demonstrated that increasing adrenergic transmission in the spinal cord decreases pain sensitivity in animals. Equally abundant evidence demonstrates the opposite effect of adrenergic signaling in the peripheral nervous system, where adrenergic signaling increases pain sensitivity. Viewing pain processing within spinal and peripheral compartments and determining the directionality of adrenergic signaling helps clarify the seemingly contradictory findings of the pain modulatory properties of adrenergic receptor agonists and antagonists presented in other reviews. Available evidence suggests that adrenergic signaling contributes to pain phenotypes through α 1/2 and β 2/3 receptors. While stimulation of α 2 adrenergic receptors seems to uniformly produce analgesia, stimulation of α 1 or β receptors produces either analgesic or hyperalgesic effects. Establishing the directionality of adrenergic receptor modulation of pain processing, and related COMT activity in different pain models are needed to bring meaning to recent human molecular genetic findings. This will enable the translation of current findings into meaningful clinical applications such as diagnostic markers and novel therapeutic targets for complex human pain conditions. PMID:22483297
Nir, Rony-Reuven; Yarnitsky, David; Honigman, Liat; Granot, Michal
Although painfulness of the conditioning stimulus (CS) is required for the activation of conditioned pain modulation (CPM), it is still unclear whether CPM expression depends on the objective physical intensity of the CS or the subjective perception of its pain. Accordingly, we cognitively manipulated the perceived CS pain, rendering the physical aspects of the CPM paradigm untouched. Baseline CPM was measured among 48 young healthy male subjects using the parallel paradigm with contact heat as test pain and hand immersion in hot water as CS. Subjects were then randomized into 4 groups, all of which were cognitively manipulated as to the CS-induced pain: group 1, placebo (CS less painful); group 2, nocebo (CS more painful); and groups 3 and 4, the informed control groups for groups 1 and 2, respectively. CPM was reassessed after the manipulation. Comparing the groups by MANCOVA (multivariate analysis of covariance) revealed that placebo exerted decreased CS pain and consequent attenuation of CPM magnitudes, while nocebo elicited increased CS pain, but without CPM elevation (Ppain was associated with diminished CPM responses (r=0.767; P=.001); however, no such relationship characterized the nocebo group. Pain inhibition under CPM seems to depend on the perceived level of the CS pain rather than solely its physical intensity. Cognitively decreasing the perceived CS pain attenuates CPM magnitude, although a ceiling effect may limit CPM enhancement after cognitively increased CS pain. These findings emphasize the relevance of cognitive mechanisms in determining endogenous analgesia processes in humans. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Baddack-Werncke, Uta; Busch-Dienstfertig, Melanie; González-Rodríguez, Sara; Maddila, Santhosh Chandar; Grobe, Jenny; Lipp, Martin; Stein, Christoph; Müller, Gerd
This study examined the development of chronic pain, a cardinal symptom of rheumatoid arthritis (RA), in mice with antigen- and collagen-induced arthritis (ACIA). Since the role of CD8(+) T cells in arthritis is controversial, we investigated the consequences of CD8-depletion on arthritis development and opioid modulation of pain in this novel model of chronic autoimmune arthritis. Disease severity in control and CD8-depleted animals was determined by histological assessment of knee-joint sections and measurement of autoantibody formation. Pain was evaluated by measuring mechanical allodynia and thermal hyperalgesia in von Frey and Hargreaves tests, respectively. The production and release of endogenous opioids and inflammatory cytokines was assessed in immunoassays. In ACIA, mice display persistent mechanical allodynia and thermal hyperalgesia for more than 2 months after induction of arthritis. The blockade of peripheral opioid receptors with naloxone-methiodide (NLXM) transiently increased thermal hyperalgesia, indicating that endogenous opioid peptides were released in the arthritic joint to inhibit pain. CD8(+) T cell depletion did not affect autoantibody formation or severity of joint inflammation, but serum levels of the pro-inflammatory cytokines TNFα and IL-17 were increased. The release of opioid peptides from explanted arthritic knee cells and the NLXM effect were significantly reduced in the absence of CD8(+) T cells. We have successfully modeled the development of chronic pain, a hallmark of RA, in ACIA. Furthermore, we detected a yet unknown protective role of CD8(+) T cells in chronic ACIA since pro-inflammatory cytokines rose and opioid peptide release decreased in the absence of these cells.
Delavierre, D; Sibert, L; Rigaud, J; Labat, J-J
To clarify definition, epidemiology, diagnosis, evaluation, etiologies and treatment of painful ejaculation (PE). Review of the literature performed by searching the Medline database using keywords ejaculation, orgasm, pain, pelvic pain, sexual behavior. PE is a pelviperineal pain caused by ejaculation or orgasm. Its prevalence rate is between 1 and 4% amongst the general population. Mainly located in the penis, pain usually lasts less than 5 minutes. Assessment is clinical and there is no level of evidence about the strategy of complementary investigations. Benign prostatic hyperplasia, chronic pelvic pain syndrome, radical prostatectomy, prostate brachytherapy and some antidepressant medications are the best estimated etiologies found in the literature. A link between urogenital infections and PE is likely but not clearly established. Alpha-blockers had good therapeutic results in few low level of evidence studies. The assessment of PE is not clearly defined. Some etiologies are known but PE may be a functionnal pain. Only high level of evidence studies would validate the use of the alpha-blockers as an efficient therapeutic option. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Damiano, Joël; Bouysset, Maurice
The hindfoot is the part of the foot which is proximal to the midtarsal joint. The obvious causes of pain are not considered (post-traumatic etiologies, sprains and fractures but also cutaneous lesions). The main etiologies on the subject are successively exposed by following the localization of the pain. Diffuse pains (ankle arthritis tarsal osteoarthritis, algodystrophy, calcaneo-navicular synostosis but also bone diseases like stress fractures, Paget disease or tumors). Plantar talalgia (Sever's disease, plantar fasciitis and entrapment neuropathies such as (esions of the medial calcaneal nerve, of the first branch of the plantar lateral nerve, medial plantar nerve and lateral plantar nerve). Posterior pains: calcaneal tendinopathy including peritendinitis, tendinosis, retro-calcaneal bursitis and pathology of the postero-lateral talar tuberosity. Medial pains: tendinopathies of the posterior tibial tendon and tendinopathy of the flexor hallucis longus tendon and tarsal tunnel syndrome. Lateral pains: fibularis tendinopathies including split lesions of the fibularis brevis tendon, displacement of the fibularis iongus tendon, sinus tarsi syndrome and finally thickenings of capsules and ligaments and ossifications localized under the tibial malleoli. Anterior pains: antero-inferior tibio-fibular ligament, anterior tibial tendinopathy and anterior impingment syndrome.
Full Text Available Pain disorder is a psychiatric disorder diagnosed when the pain becomes the predominant focus of the clinical presentation and causes significant distress or impairment. Besides the high economic impact, there is a reciprocal relationship with the affective state. Pain is a subjective sensation and its severity and quality of experience in an individual is dependent on a complex mix of factors. In the treatment of acute pain, the primary purpose is pain relief, while chronic pain typically requires a combination of psychotropic drugs. In this context, it is also important to recognize and treat depression. Psychological treatments aimed at providing mechanisms to allow patients to "control and live with the pain" rather than aspire to eliminate it completely. A growing group of researchers proposes the elimination of the chapter of Somatoform Disorders and the modification of the category "psychological factors affecting a medical condition" to "psychological factors affecting an identified or feared medical condition" with clinical entities as ubchapters, largely based upon Diagnostics for Psychosomatic Research criteria.
James David Adams
Full Text Available The most effective and safe treatment site for pain is in the skin. This chapter discusses the reasons to treat pain in the skin. Pain is sensed in the skin through transient receptor potential cation channels and other receptors. These receptors have endogenous agonists (yang and antagonists (yin that help the body control pain. Acupuncture works through modulation of these receptor activities (qi in the skin; as do moxibustion and liniments. The treatment of pain in the skin has the potential to save many lives and improve pain therapy in most patients.
Abatayo, Anna Lou; Lynham, John
It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... levels among CPR users in a laboratory experiment. We also observe no differences between weak external regulations and no regulations, after controlling for a potential confound. However, when we add communication to our endogenous treatment, we observe significant behavioral differences between...
Henriksen, J H; Schwartz, Tania; Bülow, J B
The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had...... concentration (r = 0.70, P less than 0.01). Hepatic venous PP was significantly higher than systemic PP in both controls and patients with kidney disease (P less than 0.001, n = 15). The values were positively correlated (r = 0.98, P less than 0.001; slope = 1.37 +/- 0.05, P less than 0.001), indicating...
Full Text Available The rationale for early psychotherapeutic intervention in combination with psychopharmatherapy in patients with endogenous disorders is provided. The mechanisms of psychological defenses to deal with traumatic experience, used by personalities functioning on a psychotic level, are also described here. Characteristic behavior patterns of extended family members in terms of emotional codependence are provided. Individual pathopsychology is considered as a symptom of abnormal functioning of the family. Emphasis is placed on the importance of inclusion of family members in psychotherapeutic interaction in order to correct interpersonal relations.
I. V. Aleksandrova
Full Text Available RELEVANCE. Sepsis is always accompanied by endogenous intoxication (EI. It is very important to study EI in the patients with severe sepsis and septic shock.MATERIAL AND METHODS. Twenty seven patients with severe sepsis and thirteen with septic shock in the postoperative period were enrolled into the study. EI was assessed using the measurements of total and effective albumin concentrations (EAC, middle-molecular-weight proteins (MMWP and EI index (Kei=MMWP/ EACx1000.RESULTS. The use of the EI index in patients with severe sepsis and septic shock leads to improvement of diagnostic and therapy monitoring.
Pedersen, Lars Haagen; Nielsen, Søren Bo; Sørensen, Peter Birch
The paper develops a model of endogenous economic growth with pollution externalities and a labor market distorted by union monopoly power and by taxes and transfers. We study the optimal second-best pollution tax and abatement policy and find that a shift toward greener preferences will tend...... to reduce unemployment, although it will hamper growth. We also find that greater labor-market distortions call for higher pollution tax rates. Finally, we show that a switch from quantity control of pollution combined with grandfathering of pollution rights to regulation via emission charges has...
Full Text Available ... Learned Going to the ER Communication Tools Pain Management Programs Videos Resources FAQs Glossary Surveys Resource Guide to Chronic Pain Treatments The Art of Pain Management Partners for Understanding Pain Pain Awareness Toolkits September ...
... Management Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Chronic Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...
Mensah-Nyagan, Ayikoe G; Meyer, Laurence; Schaeffer, Véronique; Kibaly, Cherkaouia; Patte-Mensah, Christine
Neurotransmitters such as glutamate, substance P, serotonin and gamma-aminobutyric acid pivotally control pain mechanisms. It is also well known that inflammatory and/or neuropathic pain may depend on the action of diverse cytokines and other molecules including eicosanoids, endorphins, calcitonin-gene related peptide, free radicals and transcription factors. Because steroids control the development, activities and plasticity of the nervous system, these compounds are of particular interest in the modulation of pain. The paper discusses various data supporting the existence of key regulatory effects of steroids in the control of pain. In particular, we analyzed three categories of observations which historically contributed to demonstrate that endogenous and synthetic steroids play a crucial role in the regulation of neurobiological processes involved in pain sensation. The first series of data, which present the chemical characteristics enabling steroids to act on several tissues, also summarize pertinent results supporting the modulation of pain sensation by steroidal compounds. The second category of data evokes psychosocial, fundamental and clinical results suggesting the existence of sex steroid-based differences in pain perception. Finally, we discuss recent evidence showing the endogenous production of neurosteroids and their effects in the spinal cord which crucially controls pain transmission. Taken together, the data reviewed herein suggest that future investigations aiming to develop effective steroid-based strategies against chronic pain must integrate in a complementary manner anti-inflammatory properties of steroids, sex steroid-induced dimorphism in pain perception and regulatory effects exerted by endogenous neurosteroids in pain neural circuits.
Joo Hyun Nam
Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.
Wulf-Johansson, Helle; Hay-Schmidt, Anders; Poulsen, Asser Nyander
(Ca) channel protein was visualized by western blotting and histochemistry. The presence of the modulatory beta1-beta 4 subunit mRNAs was investigated using RT-PCR. beta1-, beta2- and beta 4-subunit mRNAs were expressed in rat TG whereas beta2- and beta 4-subunits were detected in porcine TG. Western blotting...
... 16, 2014. Phantom pain Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...
... have shown that there are higher levels of endorphins in cerebrospinal fluid following acupuncture. Investigators are studying the effect of stress on the experience of chronic pain. Chemists are synthesizing new analgesics and discovering painkilling ...
Pain - penis ... Bites, either human or insect Cancer of the penis Erection that does not go away (priapism) Genital herpes Infected hair follicles Infected prosthesis of the penis Infection under the foreskin of uncircumcised men ( balanitis ) ...
... or conditions. It may be linked to arthritis , bursitis , and muscle pain . No matter what causes it, ... Autoimmune diseases such as rheumatoid arthritis and lupus Bursitis Chondromalacia patellae Crystals in the joint: Gout (especially ...
... chap 62. Kane SF, Lynch JH, Taylor JC. Evaluation of elbow pain in adults. Am Fam Physician . ... Chief, Sports Medicine and Shoulder Service, UCSF Department of Orthopaedic Surgery, San Francisco, ...
Ajslev, Jeppe Zielinski Nguyen; Lund, Henrik Lambrecht; Møller, Jeppe Lykke
In this article, we investigate the relations between discursive practices within the Danish construction industry and the perceived pain, physical deterioration, and strain affecting the construction workers. Of central importance is the widely accepted hegemonic discourse on physical strain...... and pain as unavoidable conditions in construction work. Based on 32 semi-structured interviews performed in eight case studies within four different construction professions, workers’ descriptions of physical strain and its relation to the organizational and social context are analyzed through concepts...... the industry reproduce physical strain and the habituation of pain as unquestioned conditions in construction work. The understanding of this mutual reinforcement of the necessity of physically straining, painful, high-paced construction work provides fruitful perspectives on the overrepresentation...
... improperly fitted or excessively worn shoes, or obesity. Plantar Fasciitis: Both heel pain and heel spurs are frequently associated with plantar fasciitis, an inflammation of the band of fibrous connective ...
... emotional stress. Sometimes the cause is unknown. Common risk factors for back pain include being overweight, poor physical conditioning, smoking, whole body vibration, and improper lifting technique and body mechanics, including poor posture. Repeated activities (lifting, carrying, bending, ...
... feels, and how much it hurts. This graphic representation provides a lot of important information in an ... can learn about the different parts of the body where nerve pain can manifest. Online Tool Back ...
... your uterus or other reproductive organs, such as endometriosis and uterine fibroids. This kind of pain often ... Taking a hot bath Doing relaxation techniques, including yoga and meditation You might also try taking over- ...
Nogueira, Lavouisier F B; Morais, Edson C; Brito, Maria A D; Santos, Beatriz S; Vale, Doanny L; Lucena, Bruno F F; Figueredo, Fernando G; Guedes, Glaucia M M; Tintino, Saulo R; Souza, Celestina E S; Nogueira, Raquel B S S; Matias, Edinardo F F; Morais-Braga, Maria Fb; Cunha, Emídio V L; Lima, Micheline A; Coutinho, Henrique D M
Multi-resistantmicroorganisms such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida tropicalis e Candida krusei are the main causes of microbial infections. Padina sanctae-crucis is a seaweed often used to check the contamination of ecosystems by materials such as heavy metals, but studies of the antimicrobial activity of the same seaweed were not found. The tests for the minimum inhibitory concentration and modulation of microbial resistance, with the use of ethanolic and methanolic extracts of Padina Sanctae-cruces combined with drugs of the class of aminoglycosides and antifungal were used to evaluate the activity against the cited microorganisms. Was observed a modulation of antibiotic activity between the natural products and the E. coli and S. aureus strains, indicating a synergism and antagonism respectively. The results showed a moderate modulatory effect against some microorganisms studied.
Klauber, Thomas Christopher Bogh
In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect on the dis......In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect...... immunotherapy (Project II). Transfer into the clinic of therapies based on gene silencing by siRNA delivered by synthetic vectors has yet to happen. A major reason is the lack of efficiency in the delivery process, partly due to insufficient understanding of cellular uptake and processing of the si...... to the conventional PEIs. However, lipid conjugation did not sufficiently reduce the inherent toxicity associated with high molecular weight PEI, and lipid conjugation of bPEI did also not change the ability of bPEI to affect lysosomal pH as a function of time. In contrast to gene silencing therapy, cancer...
Parent, Alexandre J; Beaudet, Nicolas; Daigle, Kathya; Sabbagh, Robert; Sansoucy, Yanick; Marchand, Serge; Sarret, Philippe; Goffaux, Philippe
Descending pain inhibition is an endogenous pain control system thought to depend partially on the activation of bulbospinal monoaminergic pathways. Deficits in descending pain inhibition have been reported in numerous human chronic pain conditions, but there is currently no consensus regarding the neurochemical correlates responsible for this deficit. The aims of this study were to 1) assess the efficacy of descending pain inhibition in pain-free and chronic pain subjects, 2) screen for changes in centrally (ie, cerebrospinal fluid) and peripherally (ie, plasma) acting monoamine concentrations, and 3) explore the relationship between descending pain inhibition and monoamine neurotransmitter concentrations. Our results clearly show a deficit in pain inhibition, along with lower plasma norepinephrine and metanephrine concentrations in chronic pain subjects, compared to pain-free subjects. No differences were found in cerebrospinal fluid neurotransmitter concentrations. Finally, our results revealed a positive relationship between blood-bound norepinephrine and metanephrine concentrations and the efficacy of descending pain inhibition. Thus, basal monoamine levels in blood were related to descending pain inhibition. This finding supports the emerging idea that individual differences in descending pain inhibition may be linked to individual differences in peripheral processes, such as monoamines release in blood, which are possibly related to cardiovascular control. This article presents psychophysical and neurochemical findings that indicate that the latent potential of descending pain inhibitory responses is associated with differential activity in peripheral processes governed by monoamine neurotransmitter release, bringing insights into the relationship between descending pain inhibition and cardiovascular control in humans. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M
The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive
George, Steven Z; Wu, Samuel S; Wallace, Margaret R; Moser, Michael W; Wright, Thomas W; Farmer, Kevin W; Greenfield, Warren H; Dai, Yunfeng; Li, Hua; Fillingim, Roger B
To identify novel combinations of genetic and psychological factors that predicted 12-month postoperative pain and disability outcomes following arthroscopic shoulder surgery. A prospective presurgical cohort (n = 150) was recruited to complete validated psychological questionnaires and have their DNA collected from saliva. DNA was genotyped for a priori selected genes involved with pain modulation (ADRB2, OPRM1, AVPR1A, GCH1, and KCNS1) and inflammation (IL1B, TNF/LTA, and IL6). The outcome measures of interest were the Brief Pain Inventory and Disabilities of the Arm, Shoulder, and Hand questionnaire. Followup for the cohort was at 3, 6, and 12 months postoperatively. After controlling for age, sex, race, and preoperative status, genetic and psychological factors were entered as main effects and interaction terms in separate general linear models for predicting postoperative pain and disability outcomes. Seven interactions involving pain-modulatory genes were identified. Three provided strong statistical evidence for different outcomes, including KCNS1 and kinesiophobia for preoperative pain intensity, ADRB2 and depressive symptoms for postoperative course, and GCH1 and anxiety symptoms for 12-month pain-intensity outcome. Ten interactions involving inflammatory genes were identified. Three provided strong statistical evidence for the 12-month postoperative course outcome, including 2 different IL6 single-nucleotide polymorphism and pain catastrophizing, and IL6 and depressive symptoms. The current study identified novel genetic and psychological interactions that can be used in future studies to further understand the development of persistent postoperative pain and investigate the effectiveness of tailored treatment. © 2016, American College of Rheumatology.
Full Text Available This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract (GIT. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals.
P.A. de Hek (Paul)
textabstractThis paper examines the effects of taxation on long-run growth in a two-sector endogenous growth model with (i) physical capital as an input in the education sector and (ii) leisure as an additional argument in the utility function. The analysis of the effects of taxation - including
Fortin, Dale A; Tillo, Shane E; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V; Guo, Caiying; Mao, Tianyi; Zhong, Haining
Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. Copyright © 2014 the authors 0270-6474/14/3416698-15$15.00/0.
Quang, Phuong N; Schmidt, Brian L
Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Full Text Available Mandibular nerve block is periodically used procedure used to treat neuralgic pain in the distribution of trigeminal nerve. It is a commonly performed block in outpatient settings at our institute. We present a case of an elderly edentulous patient with trigeminal neuralgia who suffered recurrent temporomandibular joint (TMJ dislocation following mandibular nerve block. The patient presented with complaints of severe pain, inability to close mouth, and eat food since 2 days. Anterior closed reduction of TMJ resulted in reduction of joint and immediate pain relief. However, the maneuver failed due to recurrent dislocation of the joint. A Barton dressing was applied to prevent another dislocation. This was followed by autologous blood injection into the joint. This case focuses on the preponderance of clinical evaluation and accentuates the need for additional forethought to be taken during pain procedures, particularly in the geriatric population.
Auerswald, Günter; Dolan, Gerry; Duffy, Anne; Hermans, Cédric; Jiménez-Yuste, Victor; Ljung, Rolf; Morfini, Massimo; Lambert, Thierry; Šalek, Silva Zupančić
Joint pain is common in haemophilia and may be acute or chronic. Effective pain management in haemophilia is essential to reduce the burden that pain imposes on patients. However, the choice of appropriate pain-relieving measures is challenging, as there is a complex interplay of factors affecting pain perception. This can manifest as differences in patients? experiences and response to pain, which require an individualized approach to pain management. Prophylaxis with factor replacement redu...
Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...
Full Text Available Preliminary evidence from studies using quantitative sensory testing suggests the presence of central mechanisms in patients with carpal tunnel syndrome (CTS as apparent by widespread hyperalgesia. Hallmarks of central mechanisms after nerve injuries include nociceptive facilitation and reduced endogenous pain inhibition. Methods to study nociceptive facilitation in CTS so far have been limited to quantitative sensory testing and the integrity of endogenous inhibition remains unexamined. The aim of this study was therefore to investigate changes in facilitatory and inhibitory processing in patients with CTS by studying hypersensitivity following experimentally induced pain (facilitatory mechanisms and the efficacy of conditioned pain modulation (CPM, inhibitory mechanisms. Twenty-five patients with mild to moderate CTS and 25 age and sex matched control participants without CTS were recruited. Increased pain facilitation was evaluated via injection of hypertonic saline into the upper trapezius. Altered pain inhibition through CPM was investigated through cold water immersion of the foot as the conditioning stimulus and pressure pain threshold over the thenar and hypothenar eminence bilaterally as the test stimulus. The results demonstrated that patients with CTS showed a greater duration (p = 0.047, intensity (p = 0.044 and area (p = 0.012 of pain in response to experimentally induced pain in the upper trapezius and impaired CPM compared to the control participants (p = 0.006. Although typically considered to be driven by peripheral mechanisms, these findings indicate that CTS demonstrates characteristics of altered central processing with increased pain facilitation and reduced endogenous pain inhibition.
Full Text Available Purpose. This study quantified the expression of substance P (SP, calcitonin gene-related peptide (CGRP, β-endorphins (β-End, and methionine-enkephalin (Met-Enk in human dental pulp following orthodontic intrusion. Methods. Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg, which would undergo controlled intrusive force for seven days, and the control group (CTRg, which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA. Results. All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg. Conclusions. SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain.
Balázs István Tóth
Full Text Available The aim of this research is to analyze territorial capital as a new paradigm to make best use of endogenous assets. The study is dealing with the preconditions, meaning and possible theoretical taxonomies of territorial capital. In this study I emphasize that the cumulative effects of regional potentials are more important than economies of scale and location factors. I present different approaches and interpretations of territorial capital, then make an attempt to create an own model. I try to find answers for questions, such as why territorial capital shows a new perspective of urban and regional development; how cognitive elements of territorial capital provide increasing return; how territorial capital influences competitiveness and what kind of relation it has with cohesion.
Petraglia, F; Facchinetti, F; M'Futa, K; Ruspa, M; Bonavera, J J; Gandolfi, F; Genazzani, A R
The present study demonstrates the presence of the endogenous opioid peptides beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), in the uterine fluid of fertile women and normally cycling and superovulated cows. The two peptides are undetectable in the uterine fluid of untreated postmenopausal women, whereas they are present following estrogen-progesterone treatment. Immunoreactive (IR) MET-ENK concentrations were higher in the secretory than in the proliferative phase of the menstrual cycle. IR beta-EP and IR MET-ENK are present also in the follicular, oviductal, and uterine fluid of cows, and in the uterine fluid, concentrations of IR MET-ENK are higher in the superovulated than in the control animals. Because opioids play important roles on endocrine and immune functions, the present data support the potential physiologic role of endometrial secretions.
Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper
Congenital heart defects are a major cause of perinatal mortality and morbidity, affecting >1% of all live births in the Western world, yet a large fraction of such defects have an unknown etiology. Recent studies demonstrated surprising dual roles for immune-related molecules and their effector...... protease (MASP)-3/collectin-L1/K1 hetero-oligomer, which impacts cardiac neural crest cell migration. We used knockdown and rescue strategies in zebrafish, a model allowing visualization and assessment of heart function, even in the presence of severe functional defects. Knockdown of embryonic expression...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...
Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina; Fablet, Marie
Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species.
Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.
Komarova, Tatiana V.; Petrunia, Igor V.; Shindyapina, Anastasia V.; Silachev, Denis N.; Sheshukova, Ekaterina V.; Kiryanov, Gleb I.; Dorokhov, Yuri L.
We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis. PMID:24587296
Full Text Available The involvement of the reticular formation (RF in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control. The RF contains centers that belong to the pain modulatory system, namely areas involved in bidirectional balance (decrease or enhancement of pain responses. It is currently accepted that the imbalance of pain modulation towards pain facilitation accounts for chronic pain. The medullary RF has the peculiarity of harboring areas involved in bidirectional pain control namely by the existence of specific neuronal populations involved in antinociceptive or pronociceptive behavioral responses, namely at the rostroventromedial medulla (RVM and the caudal ventrolateral medulla (VLM. Furthermore the dorsal reticular nucleus (also known as subnucleus reticularis dorsalis; DRt may enhance nociceptive responses, through a reverberative circuit established with spinal lamina I neurons and inhibit wide-dynamic range (WDR neurons of the deep dorsal horn. The components of the triad RVM-VLM-DRt are reciprocally connected and represent a key gateway for top-down pain modulation. The RVM-VLM-DRt triad also represents the neurobiological substrate for the emotional and cognitive modulation of pain, through pathways that involve the periaqueductal gray (PAG-RVM connection. Collectively, we propose that the RVM-VLM-DRt triad represents a key component of the “dynamic pain connectome” with special features to provide integrated and rapid responses in situations which are life
Rodriguez, Pau; Cucurull, Guillem; Gonzàlez, Jordi
appearance versus taking into account the whole image: As a result, we outperform current state- of-the-art AUC performance in the UNBC-McMaster Shoulder Pain Expression Archive Database. In addition, to evaluate the generalization properties of our proposed methodology on facial motion recognition, we also......Pain is an unpleasant feeling that has been shown to be an important factor for the recovery of patients. Since this is costly in human resources and difficult to do objectively, there is the need for automatic systems to measure it. In this paper, con- trary to current state-of-the-art techniques...... in pain assessment, which are based on facial features only, we suggest that the performance can be enhanced by feeding the raw frames to deep learning models, outperforming the latest state-of-the-art results while also directly facing the problem of imbalanced data. As a baseline, our approach first...
Ricardo Evangelista Marrocos de Aragão
Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.
Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... a few days during each menstrual cycle. Painful menstruation is the leading cause of lost time from ...
Ramponi, Denise R
Shoulder pain is a frequent complaint encountered in the emergency setting. A brief review of shoulder anatomy and physical examination sets the foundation for evaluation of shoulder pain. Considerations of patient's age are helpful to predict injuries. Fractured clavicles are often seen in traumatic injuries in children and young adults, whereas fractures of the humeral head are more often seen in the elderly from traumatic injuries. Shoulder dislocations are more common in teens to fourth decade. This article reviews specific acute injuries, chronic conditions, and radiologic considerations of patients with shoulder complaints encountered in emergency settings.
Zhang, Shuzhuo; Jin, Xu; You, Zerong; Wang, Shuxing; Lim, Grewo; Yang, Jinsheng; McCabe, Michael; Li, Na; Marota, John; Chen, Lucy; Mao, Jianren
Anxiety disorder is a comorbid condition of chronic pain. Analgesics and anxiolytics, subject to addiction and abuse, are currently used to manage pain and anxiety symptoms. However, the cellular mechanism underlying chronic pain and anxiety interaction remains to be elucidated. We report that persistent nociception following peripheral nerve injury induced anxiety-like behavior in rodents. Brain expression and release of neuropeptide S (NPS), a proposed endogenous anxiolytic peptide, was diminished in rodents with co-existing nociceptive and anxiety-like behaviors. Intracerebroventricular administration of exogenous NPS concurrently improved both nociceptive and anxiety-like behaviors. At the cellular level, NPS enhanced intra-amygdaloidal inhibitory transmission by increasing presynaptic GABA release from interneurons. These findings indicate that the interaction between nociceptive and anxiety-like behaviors in rodents may be regulated by the altered NPS-mediated intra-amygdaloidal GABAergic inhibition. The data suggest that enhancing the brain NPS function may be a new strategy to manage comorbid pain and anxiety. PMID:24793908
Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.
Riva, Paolo; Romero Lauro, Leonor J; Vergallito, Alessandra; DeWall, C Nathan; Bushman, Brad J
Social exclusion, ostracism, and rejection can be emotionally painful because they thwart the need to belong. Building on studies suggesting that the right ventrolateral prefrontal cortex (rVLPFC) is associated with regulation of negative emotions, the present experiment tests the hypothesis that decreasing the cortical excitability of the rVLPFC may increase negative emotional reactions to social exclusion. Specifically, we applied cathodal transcranial direct current stimulation (tDCS) over the rVLPFC and predicted an increment of negative emotional reactions to social exclusion. In Study 1, participants were either socially excluded or included, while cathodal tDCS or sham stimulation was applied over the rVLPFC. Cathodal stimulation of rVLPFC boosted the typical negative emotional reaction caused by social exclusion. No effects emerged from participants in the inclusion condition. To test the specificity of tDCS effects over rVLPFC, in Study 2, participants were socially excluded and received cathodal tDCS or sham stimulation over a control region (i.e., the right posterior parietal cortex). No effects of tDCS stimulation were found. Our results showed that the rVLPFC is specifically involved in emotion regulation and suggest that cathodal stimulation can increase negative emotional responses to social exclusion.
Anna Maria Haarmann
Full Text Available Introduction: Spreading depression (SD is a propagating wave of depolarization followed by depression of the neuroglial activities and can modulate extracellular dopamine concentrations in the neocortex. It has been shown that the dopaminergic system plays a role in migraine. SD has been suggested as a critical phenomenon in the pathophysiology of migraine. The aim of this study was to investigate the effect of dopamine D2 receptors on the characteristic features of SD in rat neocortical tissues. Methods: The effect of dopamine D2 receptor agonist quinpirole and D2 receptor antagonist sulpiride was tested on different characteristic features (amplitude, duration and velocity of KCl-induced SD in somatosensory neocortical slices of adult rats. The effect of above-mentioned substances on production of long-term potentiation (LTP in the neocortex was also evaluated. Results: The present data revealed a dose-dependent suppression of the amplitude and duration of SD in the presence of the dopamine D2 receptor antagonist sulpiride in the neocortex. D2 dopamine receptor agonist quinpirole dose-dependently enhanced the amplitude and duration of the neocortical SD. Furthermore, application of D2 receptor antagonist significantly suppressed induction of LTP. Discussion: These results indicate that D2 receptors modulate the initiation of SD in the neocortex. This finding refers to the potential role of D2 receptor antagonist in treatment of migraine pain.
Bogachus, Lindsey D; Oseid, Elizabeth; Bellin, Melena; Vella, Adrian; Robertson, R Paul
Total pancreatectomy followed by intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe, unrelenting abdominal pain caused by chronic pancreatitis, to improve quality of life, and to prevent diabetes. To determine the cause of exercise-induced hypoglycemia that is a common complaint in TP/IAT recipients. Participants completed 1 hour of steady-state exercise. Hospital research unit. We studied 14 TP/IAT recipients and 10 age- and body mass index-matched control subjects. Peak oxygen uptake (VO2) was determined via a symptom-limited maximal cycle ergometer test. Fasted subjects then returned for a primed [6,6-2H2]-glucose infusion to measure endogenous glucose production while completing 1 hour of bicycle exercise at either 40% or 70% peak VO2. Blood samples were obtained to measure glucose metabolism and counterregulatory hormones before, during, and after exercise. Although the Borg Rating of Perceived Exertion did not differ between recipients and control subjects, aerobic capacity was significantly higher in controls than in recipients (40.4 ± 2.0 vs 27.2 ± 1.4 mL/kg per minute; P < 0.001). This difference resulted in workload differences between control subjects and recipients to reach steady-state exercise at 40% peak VO2 (P = 0.003). Control subjects significantly increased their endogenous glucose production from 12.0 ± 1.0 to 15.2 ± 1.0 µmol/kg per minute during moderate exercise (P = 0.01). Recipients did not increase endogenous glucose production during moderate exercise (40% peak VO2) but succeeded during heavy exercise, from 10.1 ± 0.4 to 14.8 ± 2.0 µmol/kg per minute (70% peak VO2; P = 0.001). Failure to increase endogenous glucose production during moderate exercise may be a key contributor to the hypoglycemia TP/IAT recipients experience.
Morey, Kevin J; Antunes, Mauricio S; Barrow, Matt J; Solorzano, Fernando A; Havens, Keira L; Smith, J Jeff; Medford, June
Synthetic biology uses biological components to engineer new functionality in living organisms. We have used the tools of synthetic biology to engineer detector plants that can sense man-made chemicals, such as the explosive trinitrotoluene, and induce a response detectable by eye or instrumentation. A goal of this type of work is to make the designed system orthogonal, that is, able to function independently of systems in the host. In this review, the design and function of two partially synthetic signaling pathways for use in plants is discussed. We describe observed interactions (crosstalk) with endogenous signaling components. This crosstalk can be beneficial, allowing the creation of hybrid synthetic/endogenous signaling pathways, or detrimental, resulting in system noise and/or false positives. Current approaches in the field of synthetic biology applicable to the design of orthogonal signaling systems, including the design of synthetic components, partially synthetic systems that utilize crosstalk to signal through endogenous components, computational redesign of proteins, and the use of heterologous components, are discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Straneva, Patricia A; Maixner, William; Light, Kathleen C; Pedersen, Cort A; Costello, Nancy L; Girdler, Susan S
This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n = 27) and healthy controls (n = 27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD.
diabetes, viral illness or drugs. Nausea, bloating and fullness. Oesophageal spasm. Substernal chest pain, with or without dysphagia for liquids and solids. Gastro-oesophageal reflux disease. • Heartburn. • Occasional reflux of acid or the stomach contents into the mouth. • Symptoms occasionally triggered by lying down.
Connors, G. Patrick
Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…
... With Your Health Insurance Plan Federal Government Programs Patient Safety Informed Consent Children's Assent Scientific Review Ending Trials ... losing support once their care moves from their oncology team back to their primary ... Each patient needs a personal plan to control cancer pain. ...
Full Text Available In the primary care sector, diagnosis and initial management of orofacial pain are often performed by familydoctors and dentists. Knowledge of the different types of orofacial pain and headache disorders is therefor of great importance. The International Classification of Headache Disorders (ICHD-3 provides an overview of the different types of orofacial pain and will be discussed in this lecture. The main focus will be on trigeminal neuralgia and cluster headache and the current research in this field. Trigeminal Neuralgia (TN is defined as a disorder characterized by recurrent, unilateral, brief, electricshock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of thetrigeminal nerve and triggered by innocuous stimuli. Unfortunately, most TN is idiopathic, and the aetiology isnot clear. The guidelines on pharmaceutical TN management published by the American Academy of Neurology (AAN and the European Federation of Neurological Societies (EFNS recommend carbamazepine (CBZ; 200–1200 mg/day or oxcarbazepine (OXC; 600–1800 mg/day as first-line therapy. Both are antiepileptics with well known interactions with other drugs and safety problems. An overview of the currently available literature on the pharmaceutical management of TN patients is discussed. Cluster headache (CH is one of the most painful primary headache disorders. It is characterized by daily or almost daily attacks of unilateral excruciating periorbital pain associated with ipsilateral cranial autonomic symptoms, typically lasting between 15 and 180 minutes if untreated. Cluster headache is caused by the relaesement of neurotransmitters and vasodilators from the sphenopalatine ganglion (SPH. The SPG is a large extracranial parasympathetic ganglion located in the pterygopalatine fossa (PPF. The current treatments for CH attacks are injectable sumatriptan and oxygen inhalation. Both treatments have well known side effects and
Colín-González, Ana Laura; Maya-López, Marisol; Pedraza-Chaverrí, José; Ali, Syed F; Chavarría, Anahí; Santamaría, Abel
glutathione reductase (GR) and GST activities. However, these changes were likely to be merely compensatory as 3-HK-infused animals did not display behavioral (rotation) alterations or morphological changes in their injected striata. Altogether, these findings suggest that, despite 3-HK might exert pro-oxidant actions under certain conditions, these changes serve to evoke a redox modulatory activity that, in turn, could decrease the risk of cell damage. In light of this evidence, 3-HK seems to be more a redox modulatory molecule than a neurotoxic metabolite. Copyright © 2014 Elsevier B.V. All rights reserved.
... AQ FREQUENTLY ASKED QUESTIONS GYNECOLOGIC PROBLEMS FAQ020 When Sex Is Painful • How common is painful sex? • What causes pain during sex? • Where is pain during sex felt? • When should ...
Full Text Available Already a member? Log In or Sign Up Home About Us Support the ACPA Contact Us Shop ... Pain Awareness Toolkits September is Pain Awareness Month Home Pain Management Tools Videos What Is Chronic Pain? ...
Forssell, Heli; Alstergren, Per; Bakke, Merete
TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence...
Full Text Available ... Covington, MD, director of the Cleveland Clinic Pain Management Program, explains some of the physiology of pain. Narrator: Most pain is temporary and manageable, but chronic pain is different. And because it is different, we need to ...
al'Absi, Mustafa; Wittmers, Lorentz E; Ellestad, Deanna; Nordehn, Glenn; Kim, Suck Won; Kirschbaum, Clemens; Grant, Jon E
Sex differences in pain sensitivity and stress reactivity have been well documented. Little is known about the role of the endogenous opioid system in these differences. This study was conducted to compare adrenocortical, pain sensitivity, and blood pressure responses to opioid blockade using naltrexone in men and women. Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered, using a double-blind, counterbalanced design. Thermal pain threshold and heat tolerance were assessed. Participants also rated pain during a 90-second cold pressor test (CPT) and completed the McGill Pain Questionnaire (MPQ) after each pain challenge. Blood and saliva samples and cardiovascular and mood measures were obtained throughout the sessions. Plasma cortisol, adrenocorticotropin, beta endorphin, prolactin, and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo. Women reported more pain during both pain procedures and had lower thermal pain tolerance. In response to naltrexone, women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT. No effects of naltrexone on these measures were found in men. Although men and women exhibited similar hormonal responses to opioid receptor blockade, women reported less pain and showed smaller blood pressure responses during CPT. Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women.
Kuehn, S.; Veen, van A.P. (Tom); Muysken, J.
Standard New Keynesian models cannot generate the widely observed result that private consumption is crowded in by government spending. We use a New Keynesian endogenous growth model with endogenous labour supply to analyse this phenomenon. The presence of small direct productivity effects of
Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus
Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…
Lin, Xinzi; Qi, Lin; Li, Zhiguo; Chi, Hao; Lin, Wanjun; Wang, Yan; Jiang, Zesheng; Pan, Mingxin; Gao, Yi
The risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. Porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. We investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. The supernatant from a porcine kidney cell line was added to human liver cells, including a normal hepatocyte cell line (HL-7702 cells), primary hepatocytes (Phh cells), and a liver stellate cell line (Lx-2 cells), and to human embryonic kidney cells as a reference control. Expression of the porcine endogenous retrovirus antigen p15E in the human cells was evaluated with polymerase chain reaction, reverse transcription-polymerase chain reaction, and Western blot. The porcine endogenous retrovirus antigen p15E was not expressed in any human liver cells (HL-7702, Phh, or Lx-2 cells) that had been exposed to supernatants from porcine kidney cell lines. Porcine endogenous retrovirus-specific fragments were amplified in human kidney cells. Human liver cells tested were not susceptible to infection by porcine endogenous retrovirus. Therefore, not all human cells are susceptible to porcine endogenous retrovirus.
Paul L. Patterson
An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...
Pande, S.; Ertsen, M.W.
We propose and test the theory of endogenous change based on historical reconstructions of two ancient civilizations, Indus and Hohokam, in two water scarce basins, the Indus basin in the Indian subcontinent and the Lower Colorado basin in Southwestern United States. The endogenous institutional
Kruglanski, Arie W.
Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)
Cadet, Patrick; Rasmussen, Mads; Zhu, Wei
signaling molecule in neural, immune and vascular systems. In addition to their use in the treatment of pain, opioid peptides appear to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of opiate alkaloids, e.g., morphine, on tumor growth......The mu3 opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (e.g. morphine) and opioid peptide (e.g. methionine enkephalin) insensitive. This opiate receptor subtype has been found on human, including cancer cell lines, and invertebrate tissues...
Mohn, Christine; Vassend, Olav; Knardahl, Stein
Chronic pain may result both from a generalized hypersensitivity to acute pain, suggestive of central sensitization processes, and dysfunction of the endogenous pain regulatory system. One purpose of this study was to compare experimental pain sensitivity at several anatomic sites in temporomandibular disorder (TMD) patients and pain-free controls during baseline and after standardized mechanical load of the orofacial region. A second purpose was to compare the pain-modulating effects of cardiovascular responses in TMD patients and pain-free controls. Experimental pain was induced by electrocutaneous stimulation of the dorsal left hand and pressure algometry at the right masseter muscle and the sternum. The pain sensitivity of the orofacial region was manipulated by isometric contraction of the masseter muscles. Elevations of mean arterial pressure and heart rate were induced by a simulated job interview. At baseline, the TMD patients exhibited a significantly higher electrocutaneous pain threshold. Relative to the healthy controls, the TMD patients reported increased electrocutaneous and pressure pain sensitivity after isometric contraction of the orofacial region. In addition, there were correlations between mean arterial pressure and pain sensitivity in the TMD group only. Significant increases in generalized pain sensitivity occurred in the TMD group, but not in the control group, after isometric contraction of the orofacial muscles, suggestive of a central sensitization process in TMD. Moreover, only in the TMD group there were significant associations between cardiovascular responsesand pain sensitivity, challenging previous assumptions of this relationship occurring mainly in pain-free individuals.
Gilbert, C; Meik, J M; Dashevsky, D; Card, D C; Castoe, T A; Schaack, S
We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
Wielgus, Albert R; Roberts, Joan E
The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm and therefore light absorbed by the eye must be benign. However, exposure to the very intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age. There are age-related changes in the endogenous (natural) chromophores (lipofuscin, A2E and all-trans-retinal derivatives) in the human retina that makes it more susceptible to visible light damage. Intense visible light sources that do not filter short blue visible light (400-440 nm) used for phototherapy of circadian imbalance (i.e. seasonal affective disorder) increase the risk for age-related light damage to the retina. Moreover, many drugs, dietary supplements, nanoparticles and diagnostic dyes (xenobiotics) absorb ocular light and have the potential to induce photodamage to the retina, leading to transient or permanent blinding disorders. This article will review the underlying reasons why visible light in general and short blue visible light in particular dramatically raises the risk of photodamage to the human retina. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.
Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.
Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.
Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.
Mohr, C; Leyendecker, S; Petersen, D; Helmchen, C
Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex. © 2011 European Federation of International Association for the Study of Pain Chapters.
Michael Oluwole Osungunna
Full Text Available Context: The in vivo use of grapefruit seed in the treatment of urinary tract infections (UTIs has been reported but the mechanism of action is yet to be explained. Aims: Evaluate the anti-adhesion and antibiotic modulatory activities of grapefruit seed extract and juice as their possible mechanisms of action. Methods: Sub-inhibitory concentrations of 2.5 and 5 mg/mL as well as 10.3 and 5.15 mg/mL of grapefruit seed extract and juice respectively were evaluated for modulatory activity of ciprofloxacin, streptomycin and nalidixic acid against one hundred and twenty seven bacterial isolates from mid-stream urine (MSU (100, catheter-stream urine (CSU (14 and catheter tips (CT (13 using the agar dilution method. Anti-adhesion activity of grapefruit seed extract and juice at sub-inhibitory concentrations of 2.5 and 1.03 mg/mL respectively was evaluated against twenty three (23 moderately adherent bacterial isolates from MSU (10, CSU (7 and CT (6 using the tissue culture plate method. Results: The results revealed that grapefruit juice (5.15 mg/mL showed more effect on nalidixic acid activity than seed extract (2.5 mg/mL. Grapefruit juice showed more anti-adhesion activity than grapefruit seed extract at the concentration tested. Conclusions: The study concluded that grapefruit seed extract and juice had anti-adhesion and antibiotic modulatory effects on bacteria associated with UTIs.
Ignacchiti, M D C; Sesti-Costa, R; Marchi, L F; Chedraoui-Silva, S; Mantovani, B
Experimental and clinical evidence shows that neutrophils play an important role in the mechanism of tissue injury in immune complex diseases through the generation of reactive oxygen species. In this study, we examined the influence of academic psychological stress in post-graduate students on the capacity of their blood neutrophils to release superoxide when stimulated by immune complexes bound to nonphagocytosable surfaces and investigated the modulatory effect of cortisol on this immune function. The tests were performed on the day before the final examination. The state-trait anxiety inventory questionnaire was used to examine whether this stressful event caused emotional distress. In our study, the psychological stress not only increased plasma cortisol concentration, but it also provoked a reduction in superoxide release by neutrophils. This decrease in superoxide release was accompanied by diminished mRNA expression for subunit p47(phox) of the phagocyte superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase. These inhibitory effects were also observed by in vitro exposure of neutrophils from control volunteers to 10(- 7) M hydrocortisone, and could be prevented by the glucocorticoid receptor antagonist RU-486. These results show that in a situation of psychological stress, the increased levels of cortisol could inhibit superoxide release by neutrophils stimulated by IgG immune complexes bound to nonphagocytosable surfaces, which could attenuate the inflammatory state.
Wongrattanakamon, Pathomwat; Lee, Vannajan Sanghiran; Nimmanpipug, Piyarat; Jiranusornkul, Supat
The data is obtained from exploring the modulatory activities of bioflavonoids on P-glycoprotein function by ligand-based approaches. Multivariate Linear-QSAR models for predicting the induced/inhibitory activities of the flavonoids were created. Molecular descriptors were initially used as independent variables and a dependent variable was expressed as pFAR. The variables were then used in MLR analysis by stepwise regression calculation to build the linear QSAR data. The entire dataset consisted of 23 bioflavonoids was used as a training set. Regarding the obtained MLR QSAR model, R of 0.963, R (2)=0.927, [Formula: see text], SEE=0.197, F=33.849 and q (2)=0.927 were achieved. The true predictabilities of QSAR model were justified by evaluation with the external dataset (Table 4). The pFARs of representative flavonoids were predicted by MLR QSAR modelling. The data showed that internal and external validations may generate the same conclusion.
Conti, Bruno J; Santiago, Karina B; Búfalo, Michelle C; Herrera, Yahima F; Alday, Efrain; Velazquez, Carlos; Hernandez, Javier; Sforcin, José M
Propolis has been used in folk medicine in different regions of the world including Latin America. Propolis is a resinous mixture of substances collected by honey bees from several botanical sources, and its composition contains a rich chemical variety, depending on the geographical area and plant sources. Our aim was to compare the modulatory effect of propolis samples from three different countries of Latin America (Brazil, Cuba and Mexico) on pro- and anti-inflammatory cytokine production (tumor necrosis factor (TNF)-α and interleukin (IL)-10, respectively) by human monocytes. Cells were incubated with propolis for 18 h at 37°C. Cell viability was assessed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and cytokine production was determined by ELISA. All samples did not affect monocyte viability. Brazilian propolis stimulated both TNF-α and IL-10 production by monocytes. Cuban propolis stimulated TNF-α and inhibited IL-10 production, while Mexican sample exerted the opposite effect, inhibiting TNF-α and stimulating IL-10 production. The major compounds found in Brazilian, Cuban and Mexican propolis samples were artepillin C, isoflavonoids and pinocembrin, respectively. Brazilian, Cuban and Mexican propolis contained different components that may exert pro- and anti-inflammatory activity depending on concentration, what may provide a novel approach to the development of immunomodulatory drugs containing propolis. © 2015 Royal Pharmaceutical Society.
Smith, David S; Jones, Benedict C; Feinberg, David R; Allan, Kevin
From a functionalist perspective, human memory should be attuned to information of adaptive value for one's survival and reproductive fitness. While evidence of sensitivity to survival-related information is growing, specific links between memory and information that could impact upon reproductive fitness have remained elusive. Here, in two experiments, we showed that memory in women is sensitive to male voice pitch, a sexually dimorphic cue important for mate choice because it not only serves as an indicator of genetic quality, but may also signal behavioural traits undesirable in a long-term partner. In Experiment 1, we report that women's visual object memory is significantly enhanced when an object's name is spoken during encoding in a masculinised (i.e., lower-pitch) versus feminised (i.e., higher-pitch) male voice, but that no analogous effect occurs when women listen to other women's voices. Experiment 2 replicated this pattern of results, additionally showing that lowering and raising male voice pitch enhanced and impaired women's memory, respectively, relative to a baseline (i.e., unmanipulated) voice condition. The modulatory effect of sexual dimorphism cues in the male voice may reveal a mate-choice adaptation within women's memory, sculpted by evolution in response to the dilemma posed by the double-edged qualities of male masculinity.
Full Text Available The data is obtained from exploring the modulatory activities of bioflavonoids on P-glycoprotein function by ligand-based approaches. Multivariate Linear-QSAR models for predicting the induced/inhibitory activities of the flavonoids were created. Molecular descriptors were initially used as independent variables and a dependent variable was expressed as pFAR. The variables were then used in MLR analysis by stepwise regression calculation to build the linear QSAR data. The entire dataset consisted of 23 bioflavonoids was used as a training set. Regarding the obtained MLR QSAR model, R of 0.963, R2=0.927, Radj2=0.900, SEE=0.197, F=33.849 and q2=0.927 were achieved. The true predictabilities of QSAR model were justified by evaluation with the external dataset (Table 4. The pFARs of representative flavonoids were predicted by MLR QSAR modelling. The data showed that internal and external validations may generate the same conclusion.
Catherine E Hueston
Full Text Available During development, sensory neurons must choose identities that allow them to detect specific signals and connect with appropriate target neurons. Ultimately, these sensory neurons will successfully integrate into appropriate neural circuits to generate defined motor outputs, or behavior. This integration requires a developmental coordination between the identity of the neuron and the identity of the circuit. The mechanisms that underlie this coordination are currently unknown. Here, we describe two modes of regulation that coordinate the sensory identities of Drosophila melanogaster olfactory receptor neurons (ORNs involved in sex-specific behaviors with the sex-specific behavioral circuit identity marker fruitless (fru. The first mode involves a developmental program that coordinately restricts to appropriate ORNs the expression of fru and two olfactory receptors (Or47b and Ir84a involved in sex-specific behaviors. This regulation requires the chromatin modulatory protein Alhambra (Alh. The second mode relies on the signaling from the olfactory receptors through CamK and histone acetyl transferase p300/CBP to maintain ORN-specific fru expression. Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs. Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.
Pera-Guardiola, Vanessa; Batalla, Iolanda; Bosque, Javier; Kosson, David; Pifarré, Josep; Hernández-Ribas, Rosa; Goldberg, Ximena; Contreras-Rodríguez, Oren; Menchón, José M; Soriano-Mas, Carles; Cardoner, Narcís
Neuropsychological deficits in executive functions (EF) have been linked to antisocial behavior and considered to be cardinal to the onset and persistence of severe antisocial and aggressive behavior. However, when psychopathy is present, prior evidence suggests that the dorsolateral prefrontal cortex is unaffected leading to intact EF. Ninety-one male offenders with Antisocial Personality Disorder (ASPD) and 24 controls completed the Wisconsin Card Sorting Test (WCST). ASPD individuals were grouped in three categories according to Psychopathy Checklist-Revised (PCL-R) scores (low, medium and high). We hypothesized that ASPD offenders with high PCL-R scores will not differ from healthy controls in EF and will show better EF performance in comparison with subjects with low PCL-R scores. Results showed that ASPD offenders with low PCL-R scores committed more perseverative errors and responses than controls and offenders with high PCL-R scores, which did not differ from healthy controls. Moreover, scores on Factor 1 and the interpersonal facet of the PCL-R were predictors of better WCST performance. Our results suggest a modulatory role of psychopathy in the cognitive performance of ASPD offenders, and provide further evidence supporting that offenders with ASPD and psychopathy are characterized by a cognitive profile different from those with ASPD without psychopathy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Li, Xin; Wu, Wen-Qing; Ding, Li; Liu, Yuan-Lin; Mao, Ning; Zhang, Yi; Zhu, Heng; Ning, Shou-Bin
To investigate the modulatory effect of the MSC derived from low attaching culture systems (suspending MSC) on T lymphocytes and the related mechanisms. The suspending MSC were generated from mouse compact bones by using low attaching plates and adherent cell culture flasks, respectively. The morphology of suspending MSC was observed under the inverted microscope and the cells were induced to differentiate into osteoblasts and adipocytes. Further, the surface antigen profile of MSC was analyzed with flow cytometry. In addition, the culture medium (CM) of suspending MSC and adherent MSC was collected and added into the activated T cell cultures before detection of the proliferation by CFSE assay. Moreover, the modulaory effects of the CM on the T cell-derived cytokines were detected by quantitative PCR. Also, the mRNA expression of cytokines of MSC was detected. The suspending MSC grew in floating cell spheres and differentiated into osteoblasts and adipocytes in the induction medium. Furthermore, the suspending MSC shared the typical immuno-phenotype with their adherent counterparts. In addition, the results of CFSE assay demonstrated that suspending MSC derived CM suppressed ConA induced T cell proliferation. The results of quantitative PCR revealed that suspending MSC expressed transforming factor β1 and interleukin-6 at a higher level and suppressed the T cell expressing interferon γ and interleukine-17A. The suspending MSC exerted an unique modulatoy effect on T cells, which is quite different to adherent MSC.
Nwani, C D; Nagpure, N S; Kumar, Ravindra; Kushwaha, Basdeo; Lakra, W S
The present study was undertaken to evaluate the genotoxic and oxidative stress modulatory effects of commercial formulation of glyphosate-based herbicide (Roundup(®)) in freshwater fish Channa punctatus. Three sublethal test concentrations of the herbicide viz., SL-I (1/10th of LC50=∼3.25mgL(-1)), SL-II (1/8th of LC50=∼4.07mgL(-1)) and SL-III (1/5th of LC50=∼6.51mgL(-1)) were calculated using 96-LC50 value and the test specimens were exposed to these concentrations. Blood and gill cells of the exposed specimens were sampled on day 1, 7, 14, 21, 28 and 35 to examine the DNA damage using comet assay and to assess the alteration in lipid peroxidation and antioxidant enzymes activities. The highest DNA damage was observed on day 14 at all test concentrations followed by gradual non-linear decline. Induction of oxidative stress in the blood and gill cells were evidenced by increased lipid peroxidation level, while antioxidants namely superoxide dismutase, catalase and glutathione reductase responded in a concentration-dependent manner. The results supported the integrated use of comet and antioxidant assays in determining the toxicity of water pollutants which could be used as part of monitoring programs. Copyright © 2013 Elsevier B.V. All rights reserved.
Andre, Christelle M; Larsen, Lesley; Burgess, Elaine J; Jensen, Dwayne J; Cooney, Janine M; Evers, Danièle; Zhang, Jingli; Perry, Nigel B; Laing, William A
Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar "Merton Russet" and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar "Cox's Orange Pippin" and were not detected in the waxy apple cultivar "Royal Gala". High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both "Merton Russet" and "Royal Gala" trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-κB activation with IC50's of 6-9 μM. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 μM in the in vitro and ex vivo bioassays, boosting production of the pro-inflammatory cytokine TNFα in cells stimulated with bacterial lipopolysaccharides.
Mang, R.; Goudsmit, J.; van der Kuyl, A. C.
A complete endogenous type C viral genome has been isolated from a baboon genomic library. The provirus, Papio cynocephalus endogenous retrovirus (PcEV), is 8,572 nucleotides long, and 38 to 59 proviral copies per baboon genome are found. The PcEV provirus possesses the typical simple retroviral
Full Text Available BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC synthase, cytochrome P450(c21. METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21 was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG was demonstrated by metabolism analysis of (3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21, P450(2D4, P450(11β1 and 3β-hydroxysteroid dehydrogenase (3β-HSD were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21 and P450(2D4 can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.
Rita J. Valentino
Full Text Available Our dynamic environment regularly exposes us to potentially life-threatening challenges or stressors. To answer these challenges and maintain homeostasis, the stress response, an innate coordinated engagement of central and peripheral neural systems is initiated. Although essential for survival, the inappropriate initiation of the stress response or its continuation after the stressor is terminated has pathological consequences that have been linked to diverse neuropsychiatric and medical diseases. Substantial individual variability exists in the pathological consequences of stressors. A theme of this Special Issue is that elucidating the basis of individual differences in resilience or its flipside, vulnerability, will greatly advance our ability to prevent and treat stress-related diseases. This can be approached by studying individual differences in “pro-stress” mediators such as corticosteroids or the hypothalamic orchestrator of the stress response, corticotropin-releasing factor. More recently, the recognition of endogenous neuromodulators with “anti-stress” activity that have opposing actions or that restrain stress-response systems suggests additional bases for individual differences in stress pathology. These “anti-stress” neuromodulators offer alternative strategies for manipulating the stress response and its pathological consequences. This review uses the major brain norepinephrine system as a model stress-response system to demonstrate how co-regulation by opposing pro-stress (corticotropin-releasing factor and anti-stress (enkephalin neuromodulators must be fine-tuned to produce an adaptive response to stress. The clinical consequences of tipping this fine-tuned balance in the direction of either the pro- or anti-stress systems are emphasized. Finally, that each system provides multiple points at which individual differences could confer stress vulnerability or resilience is discussed.
SAIFELDIN A.F. EL-NAGERABI
Full Text Available El-Nagerabi SAF, Elshafie AE, AlKhanjari SS. 2014. Endophytic fungi associated with endogenous Boswellia sacra. Biodiversitas 15: 22-28. Endophytic fungi associated with leaves and stem tissues of Boswellia sacra growing in Dhofar Mountains of Oman were investigated from May 2008 through October 2011. The biological diversity, tissue-preference and seasonal variations of fungi were evaluated. Forty-three species and 3 varieties of fungi were recovered as new records from this plant. Of these isolates, 35 species are new reports to the mycoflora of Oman, whereas 12 species were added to the list of fungal flora of the Arabian Peninsula. The genus Alternaria (12 species is the most prevalent genus recovered from 12.5-83.3% of the screened leaves and stem samples, followed by Aspergillus (5 species, 3 varieties, 6.9-86.1%, Mycelia sterilia (76.4%, Rhizopus stolonifer (62.5%, Drechslera (3 species, 40.3-54.2%, Cladosporium (3 species, 20.8-52.8%, Curvularia lunata (38.8%, Chaetomium (2 species, 15.3-26.3%, Penicillim spp. (9.8-27.8%, Fusarium (9 species, 6.9-27.8%, Ulocladium consortiale (27.8%, Mucor hiemalis (19.5%, and the remaining species (Scytalidium thermophilum, Phoma solani, Taeniolella exilis, and Botryodiplodia theobromae exhibited very low levels of incidence (4.2-11.1%. Endophytic colonization of the leaf tissues was greater (43 species, 3 varieties comparable to stem tissues (25 species. This indicates heterogeneity and tissue-preference, with no evidence of seasonal variation. Therefore, the isolation of many fungal species and sterile mycelia supports the biodiversity of the endophytic fungi invading B. sacra and the high possibility of isolating more fungal species using advanced molecular techniques.
Full Text Available Assume a labor supply consisting of two types of workers, 1 and 2. Both workers are equally productive and exhibit supply functions with the same elasticity. We consider a firm (entrepreneur or shareholders that is competitive in the output market and monopsonistic in input markets. The firm uses the services of a manager who has a high human capital and whose wage is given by the market. It is supposed that the manager does not like to work with one type of worker, say type 1. If we allow the manager's effort to be an additional input without any extra (in addition to his salary cost for the firm, then the firm's pricing decision will be different for both workers. That is, there will be a wage differential and therefore endogenous economic discrimination2 in the labor markets.Vamos assumir que a oferta de trabalho consiste de dois tipos de trabalhadores, 1 e 2. Ambos os trabalhadores são igualmente produtivos e exibem funções de oferta com a mesma elasticidade. Consideramos uma firma (empresário ou acionistas, a qual é competitiva no mercado de produtos e monopsonista nos mercados de insumos. A firma usa os serviços de um gerente quem tem um alto capital humano e cujo salário é dado pelo mercado. Suponhamos que o gerente não gosta de trabalhar com um tipo de trabalhador, digamos o tipo 1. Se permitirmos que o esforço do gerente seja um insumo adicional sem nenhum custo extra (além de seu salário, a decisão de salários será diferente para ambos os trabalhadores. Isto é, haverá um diferencial de salários e, em conseqüência, uma discriminação econômica1 endógena nos mercados de trabalho.
Sornette, D.; Helmstetter, A.
Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).
Full Text Available Debbie L Morton, Javin S Sandhu, Anthony KP Jones Human Pain Research Group, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK Abstract: Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain’s role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained. Keywords: fMRI, PET, EEG, arthritis, fibromyalgia
Full Text Available Miguel Gorenberg,1,2 Kobi Schwartz31Department of Nuclear Medicine, B'nai Zion Medical Center, Haifa, Israel; 2The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; 3Department of Physical Therapy, B'nai Zion Medical Center, Haifa, IsraelAbstract: Low back pain in patients with myofascial pain syndrome is characterized by painful active myofascial trigger points (ATPs in muscles. This article reviews a novel, noninvasive modality that combines simultaneous imaging and treatment, thus taking advantage of the electrodermal information available from imaged ATPs to deliver localized neurostimulation, to stimulate peripheral nerve endings (Aδ fibers and in turn, to release endogenous endorphins. "Hyperstimulation analgesia" with localized, intense, low-rate electrical pulses applied to painful ATPs was found to be effective in 95% patients with chronic nonspecific low back pain, in a clinical validation study.Keywords: myofascial, noninvasive, electrical, impedance
Paulev, P E; Thorbøll, J E; Nielsen, U
The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of beta-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were...... significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of 19.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle...... pain was enhanced with naloxone. The increased perception of pain did not decrease the athletes ability to perform in terms of the distance run. We conclude that endogenous opiates are involved in the perception of pain associated with exhaustive exercise and may subserve psychological rather than...
Transcutaneous electrical nerve stimulation (TENS) is one of the therapies for painful neuropathy. Its analgesic mechanisms probably involve the gate control theory, the physiological block and the endogenous pain inhibitory system. The aim of the study was to determine whether TENS improves small fibre function diminished because of painful…
Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O' Brien, S.J.
Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked.
Miller, B.E.; Lipman, J.J.; Byrne, W.L.
Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.
Sunil Sharma; Sunil Pareek; Narashans Alok Sagar; Daniel Valero; Maria Serrano
Polyamines (PAs) are natural compounds involved in many growth and developmental processes in plants, and, specifically in fruits, play a vital role regulating its development, ripening and senescence processes. Putrescine (PUT), spermine (SPE), and spermidine (SPD) are prominent PAs applied exogenously to extend shelf life of fruits. They also originate endogenously during developmental phases of horticultural crops and simultaneously affect the quality attributes and shelf life. Their anti-...
Ruscheweyh, R; Becker, T; Born, Y; Çolak-Ekici, R; Marziniak, M; Evers, S; Gerlach, A L; Wolowski, A
The significance of occlusal disharmony for the development of painful temporomandibular disorder (TMD) is controversial. The ongoing biomechanical strain caused by occlusal disharmony might lead to sensitization processes in the nociceptive system. Understanding these processes might be an important step toward understanding the possible relationship between occlusal disharmony and TMD. In this study, we therefore investigated whether subjects with occlusal disharmony (n = 22) differ from healthy controls (n = 26) in their pain perception and pain modulation by stress and relaxation. Trigeminal and extratrigeminal experimental pain perception (pinprick, heat, and pressure pain) was assessed before and after stress (mental arithmetic) and relaxation (viewing of low-arousal pictures). There were no group differences in pain perception at baseline or during the stress task. Compared with controls, the occlusal disharmony group exhibited an inadequate reduction in pain perception during relaxation, which was significant for the extratrigeminal site (P < 0.01) and reached a trend for significance at the trigeminal site (P = 0.1). These results suggest that subjects with occlusal disharmony show signs of disturbed endogenous pain inhibition during relaxation. There is evidence for the presence of sensitization of the nociceptive system in subjects with occlusal disharmony. Possibly, deficient inhibition of extratrigeminal and trigeminal pain perception by relaxation might contribute to the development of TMD or other chronic pain disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Johnson, Katerina V-A; Dunbar, Robin I M
Personal social network size exhibits considerable variation in the human population and is associated with both physical and mental health status. Much of this inter-individual variation in human sociality remains unexplained from a biological perspective. According to the brain opioid theory of social attachment, binding of the neuropeptide β-endorphin to μ-opioid receptors in the central nervous system (CNS) is a key neurochemical mechanism involved in social bonding, particularly amongst primates. We hypothesise that a positive association exists between activity of the μ-opioid system and the number of social relationships that an individual maintains. Given the powerful analgesic properties of β-endorphin, we tested this hypothesis using pain tolerance as an assay for activation of the endogenous μ-opioid system. We show that a simple measure of pain tolerance correlates with social network size in humans. Our results are in line with previous studies suggesting that μ-opioid receptor signalling has been elaborated beyond its basic function of pain modulation to play an important role in managing our social encounters. The neuroplasticity of the μ-opioid system is of future research interest, especially with respect to psychiatric disorders associated with symptoms of social withdrawal and anhedonia, both of which are strongly modulated by endogenous opioids.
Falk, Sarah; Dickenson, Anthony H
but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved......Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional...... therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain...
Zhao, Jiubo; Zhao, Jingbo; Xiao, Rong; Yang, Xueling; Zhang, Xiaoyuan
To explore the incidence of suicide exposure and its association with suicide risk in Chinese college students, and study the modulatory effects of suicide exposure on the relations between life events and suicide risks. A total of 8202 college students from 12 Chinese colleges and universities in mainland China completed a cross-sectional survey that included suicidal behaviors questionnaire-revised (SBQ-R), Adolescent Self-Rating Life Events Check List (ASLEC), suicide exposure questionnaire, social and demographic characteristics questionnaire. The incidence of exposure to suicide events involving close relatives and acquaintances were 3.9% and 11.8% among sampled Chinese college students, respectively. Students exposed to suicide events involving close relatives had significantly higher total SBQ-R scores than those who did not (5.51∓2.44 vs 4.68∓2.11, Psuicide events of acquaintances were also associated with significantly increased total SBQ-R scores (5.51∓2.44 vs 4.68∓2.11, Psuicides events all contributed to significantly increased rates of suicidal ideation, suicide plans and suicide attempts in the college students (Psuicide risks (0.11≤r≤0.26, Psuicide events involving close relatives and acquaintances and the interactions of life events and suicide of close relatives for suicide risk were not significant (P>0.05), but exposure to acquaintance suicide events moderated the effects of life events on suicide risk (Pcollege students with a high level of life events and history of acquaintance suicide had the highest risk for suicide. In Chinese college students, the risk of suicide is closely associated with exposure to suicide events and life events, and exposure to suicide events involving acquaintances can modulate the effects of life events on suicide risk.
Full Text Available The Cerebral Giant Cells (CGCs are a pair of identified modulatory interneurons in the Central Nervous System of the pond snail Lymnaea stagnalis with an important role in the expression of both unconditioned and conditioned feeding behavior. Following single-trial food-reward classical conditioning, the membrane potential of the CGCs becomes persistently depolarized. This depolarization contributes to the conditioned response by facilitating sensory cell to command neuron synapses, which results in the activation of the feeding network by the conditioned stimulus. Despite the depolarization of the membrane potential, which enables the CGGs to play a key role in learning-induced network plasticity, there is no persistent change in the tonic firing rate or shape of the action potentials, allowing these neurons to retain their normal network function in feeding. In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs. We then used this model to elucidate how learning-induced changes in a somal persistent sodium and a delayed rectifier potassium current lead to a persistent depolarization of the CGCs whilst maintaining their firing rate. Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning. We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.
Wright, Nicholas J D; Sides, Lynda J; Walling, Kerry
The generation of the novel messenger molecule nitric oxide (NO) has been demonstrated in many tissues across phyla including nervous systems. It is produced on demand by the enzyme nitric oxide synthase often stimulated by intracellular calcium and typically affecting guanylate cyclase thought to be its principal target in an auto and/or paracrine fashion. This results in the generation of the secondary messenger cyclic guanosine monophosphate (cGMP). Nitric oxide synthase has been demonstrated in various mollusk brains and manipulation of NO levels has been shown to affect behavior in mollusks. Apart from modulation of the effect of the peptide GSPYFVamide, there appears little published on direct or modulatory effects of NO on Helix aspersa central neurons. We present here initial results to show that NO can be generated in the region around F1 in the right parietal ganglion and that NO and cGMP directly hyperpolarize this neuron. For example, application of the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP; 200 µM) can cause a mean hyperpolarization of 41.7 mV, while 2 mM 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) produced a mean hyperpolarization of 33.4 mV. Additionally, pre-exposure to NO-donors or cGMP appears to significantly reduce or even eliminates the normal hyperpolarizing K(+)-mediated response to dopamine (DA) by this neuron; 200 µM SNAP abolishes a standard response to 0.5 µM DA while 1 mM 8-bromo-cGMP reduces it 62%.
Yang, Wen-Kai; Kang, Chao-Kai; Hsu, An-Di; Lin, Chia-Hao; Lee, Tsung-Han
Upon salinity challenge, the Na(+)-K(+)-ATPase (NKA) of fish kidney plays a crucial role in maintaining ion and water balance. Moreover, the FXYD protein family was found to be a regulator of NKA. Our preliminary results revealed that fxyd12 was highly expressed in the kidneys of the two closely related euryhaline medaka species (Oryzias dancena and O. latipes) from different natural habitats (brackish water and fresh water). In this study, we investigated the expression and association of renal FXYD12 and NKA α-subunit as well as potential functions of FXYD12 in the two medakas. These findings illustrated and compared the regulatory roles of FXYD12 for NKA in kidneys of the two medakas in response to salinity changes. In this study, at the mRNA and/or protein level, the expression patterns were similar for renal FXYD12 and NKA in the two medakas. However, different patterns of NKA activities and different interaction levels between FXYD12 and NKA were found in the kidneys of these two medakas. The results revealed that different strategies were used in the kidneys of the two medaka species upon salinity challenge. On the other hand, gene knockdown experiments demonstrated that the function of O. dancena FXYD12 allowed maintenance of a high level of NKA activity. The results of the present study indicated that the kidneys of the examined euryhaline medakas originating from brackish water and fresh water exhibited different modulatory mechanisms through which renal FXYD12 enhanced NKA activity to maintain internal homeostasis. Our findings broadened the knowledge of expression and functions of FXYD proteins, the modulators of NKA, in vertebrates.
Booker, Sam A; Althof, Daniel; Degro, Claudius E; Watanabe, Masahiko; Kulik, Ákos; Vida, Imre
The perisomatic domain of cortical neurons is under the control of two major GABAergic inhibitory interneuron types: regular-spiking cholecystokinin (CCK) basket cells (BCs) and fast-spiking parvalbumin (PV) BCs. CCK and PV BCs are different not only in their intrinsic physiological, anatomical and molecular characteristics, but also in their presynaptic modulation of their synaptic output. Most GABAergic terminals are known to contain GABAB receptors (GABABR), but their role in presynaptic inhibition and surface expression have not been comparatively characterized in the two BC types. To address this, we performed whole-cell recordings from CCK and PV BCs and postsynaptic pyramidal cells (PCs), as well as freeze-fracture replica-based quantitative immunogold electron microscopy of their synapses in the rat hippocampal CA1 area. Our results demonstrate that while both CCK and PV BCs contain functional presynaptic GABABRs, their modulatory effects and relative abundance are markedly different at these two synapses: GABA release is dramatically inhibited by the agonist baclofen at CCK BC synapses, whereas a moderate reduction in inhibitory transmission is observed at PV BC synapses. Furthermore, GABABR activation has divergent effects on synaptic dynamics: paired-pulse depression (PPD) is enhanced at CCK BC synapses, but abolished at PV BC synapses. Consistent with the quantitative differences in presynaptic inhibition, virtually all CCK BC terminals were found to contain GABABRs at high densities, but only 40% of PV BC axon terminals contain GABABRs at detectable levels. These findings add to an increasing list of differences between these two interneuron types, with implications for their network functions.
Types of pain. There are three types of pain, namely acute pain, chronic non- cancer (non-malignant) pain and cancer pain (chronic malignant pain). These types are explained in more detail below. Acute pain. This is defined as pain of recent onset and of short or limited duration. The pain is related to an identifiable cause.
ANDERSEN, A.,. HUTCHINSON, W.M. & SlIM, J. Chr. 1977b. Ultrastructural studies on the endogenous development of. Eimeria brunetti IV. Formation and structure of the oocyst wall. Acta path. microbiol. scand. Sect. B 85: 201-211.
J.J. van Hilten (Jacobus)
textabstractUsing resident peritoneal macrophages, this study was focussed on the activating role of endogenous leukotrienes in the regulation of macrophage antitumor cytostatic activity in response to inflammatory stimuli. Inhibitors and inducers of leukotrienes synthesis were used to modulate
Gorog, Diana A.
The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions. PMID:28841147
The search for endogenous digitalis has led to the isolation of ouabain as well as several additional cardiotonic steroids of the cardenolide and bufadienolide type from blood, adrenals, and hypothalamus...
Conclusion: The results demonstrate that, with the achievable sensitivity of current analytical technology, physiological concentrations of endogenous steroids, such as hydrocortisone and cortisone, can be found in the SC of some individuals.
Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K
Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...
Vrinten, Dorien Henriëtte
Neuropathic pain (pain initiated by a lesion or dysfunction of the nervous system) is characterised by symptoms such as allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (an increased response to a stimulus that is normally painful). It constitutes a major
Dijk, J.F.M. van
Many patients experience pain after surgery. Adequate pain treatment begins with a reliable pain assessment. The Numeric Rating Scale (NRS) is often used for this purpose; patients are asked to score their pain on a scale from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable
Rafael Selbach Scheffel
Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.
This paper analyzes a two-phase endogenous growth model in which the adoption of a backstop technology (e.g., solar) yields a sustained supply of essential energy inputs previously obtained from exhaustible resources (e.g., oil). Growth is knowledge-driven and the optimal timing of technology switching is determined by welfare maximization. The optimal path exhibits discrete jumps in endogenous variables: technology switching implies sudden reductions in consumption and output, an increase in...
Vanden Berg-Foels, Wendy S
Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.
Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Jimenez-Vargas, Nestor N; Lopez-Lopez, Cintya; Jaramillo-Polanco, Josue; Okamoto, Takanobu; Nasser, Yasmin; Bunnett, Nigel W; Lomax, Alan E; Vanner, Stephen J
Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca2+ imaging techniques. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Full Text Available Topical research efforts on attention to pain often take a critical look at the modulatory role of top-down factors. For instance, it has been shown that the fearful expectation of pain at a location of the body directs attention towards that body part. In addition, motivated attempts to control this pain were found to modulate this prioritization effect. Such studies have often used a temporal order judgment task, requiring participants to judge the order in which two stimuli are presented by indicating which one they perceived first. As this constitutes a forced-choice response format, such studies may be subject to response bias. The aim of the current study was to address this concern. We used a ternary synchrony judgment paradigm, in which participants judged the order in which two somatosensory stimuli occurred. Critically, participants now also had the option to give a 'simultaneous' response when they did not perceive a difference. This way we eliminated the need for guessing, and thus reduced the risk of response bias. One location was threatened with the possibility of pain in half of the trials, as predicted by an auditory cue. Additionally, half of the participants (pain control group were encouraged to avoid pain stimuli by executing a quick button press. The other half (comparison group performed a similar action, albeit unrelated to the occurrence of pain. Our data did not support threat-induced spatial prioritization, nor did we find evidence that pain control attempts influenced attention in any way.
... Disease-Related Pain: Various cancers, ALS (Lou Gehrig's Disease), tuberculosis, HIV-AIDs, and others Head/Neck: Migraine, headaches, jaw pain (TMJ), earache, toothache, sore throat, sinus pain, facial numbness ...
Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.
Full Text Available ... Going to the ER Communication Tools Pain Management Programs Videos Resources FAQs Glossary Surveys Resource Guide to ... MD, director of the Cleveland Clinic Pain Management Program, explains some of the physiology of pain. Narrator: ...
Full Text Available ... the pain will go away. Part of the problem with chronic pain is that when we start ... is that the presence of a severe pain problem which exists for some period of time can ...
Buprenorphine (Belbuca) is used to relieve severe pain in people who are expected to need pain medication ... and who cannot be treated with other medications. Buprenorphine (Belbuca) should not be used to treat pain ...
Amandine E Rey; George A Michael; Corina Dondas; Marvin Thar; Luis Garcia-Larrea; Stéphanie Mazza
.... We show that being in pain leads to an expansion of subjective time whereby a stronger increase in pain perception relative to non-painful stimulation leads to a stronger time-estimate distortion...
Levashova, A I; Morozova, V S; Petrochenko, S N; Myagkova, М А; Moseikin, I A
To compare immunochemical and clinical parameters in patients with chronic radicular and myofascial back pain. A study included 92 patients (55 men and 37 women) with radicular pain syndrome and 97 patients (33 men and 64 women) with myofascial pain syndrome. Pain status was assessed with the differential visual analogous scale (at rest, on movement, at night and during spontaneous pain). Tensor algometry was used to measure pain intolerance thresholds at day and night. Levels of natural antibodies (nAB) to endogenous pain regulators (β-endorphin, orphanin, serotonin, dopamine, histamine and angiotensin) were determined in the blood serum by ELISA. Patients were examined at admission to the hospital, on 10th and 21st days of treatment. There was a significant decrease in pain syndrome in all patients to the 21st day. Pain intensity was higher in patients with radicular pain syndrome (рPain intolerance thresholds were initially reduced in both groups. No significant between-group differences in the dynamics were not found either in men or women. Women had lower pain intolerance thresholds compared to men. An analysis of nAB profiles to pain regulators showed that they were correlated with higher and high indices, with the predominance of nAB to β-endorphin, orphanin and histamine in both groups. The increased levels of antibodies circulate in the blood serum of patients with dorsalgia for a long time can further be a factor of pain chronification.
Sarah L. Jirek
Full Text Available This study extends prior research on vicarious traumatization and emotion management by exploring a deeper, more life-altering effect of working with traumatized clients—namely, “soul pain.” Analyses of in-depth interviews with 29 advocates working with survivors of physical and sexual violence reveal that, as a direct consequence of hearing countless stories of human brutality, some staff members experience a profound wounding of their spirit. This finding expands our understanding of the occupational hazards of the helping professions by revealing another dimension of advocates’ lives—that of the soul or spirit—that may be affected by their work with trauma survivors.
Hagiwara, Satoshi; Iwasaka, Hideo; Hasegawa, Akira; Noguchi, Takayuki
Low-level laser therapy (LLLT) has been reported to relieve pain, free of side effects. However, the mechanisms underlying LLLT are not well understood. Recent studies have also demonstrated that opioid-containing immune cells migrate to inflamed sites and release beta-endorphins to inhibit pain as a mode of peripheral endogenous opioid analgesia. We investigated whether pre-irradiation of blood by LLLT enhances peripheral endogenous opioid analgesia. The effect of LLLT pretreatment of blood on peripheral endogenous opioid analgesia was evaluated in a rat model of inflammation. Additionally, the effect of LLLT on opioid production was also investigated in vitro in rat blood cells. The expression of the beta-endorphin precursors, proopiomelanocortin and corticotrophin releasing factor, were investigated by reverse transcription polymerase chain reaction. LLLT pretreatment produced an analgesic effect in inflamed peripheral tissue, which was transiently antagonized by naloxone. Correspondingly, beta-endorphin precursor mRNA expression increased with LLLT, both in vivo and in vitro. These findings suggest that that LLLT pretreatment of blood induces analgesia in rats by enhancing peripheral endogenous opioid production, in addition to previously reported mechanisms.
Yang, Fei; Han, Ying; Li, Hui; Luo, Hongjun; Duan, Bo; Xu, Tianle; Maoying, Qiliang; Tan, Huangying; Wang, Jun; Zhao, Hongmei; Liu, Fengyu; Wan, You
Background There is current interest in understanding the molecular mechanisms of tumor-induced bone pain. Accumulated evidence shows that endogenous formaldehyde concentrations are elevated in the blood or urine of patients with breast, prostate or bladder cancer. These cancers are frequently associated with cancer pain especially after bone metastasis. It is well known that transient receptor potential vanilloid receptor 1 (TRPV1) participates in cancer pain. The present study aims to demonstrate that the tumor tissue-derived endogenous formaldehyde induces bone cancer pain via TRPV1 activation under tumor acidic environment. Methodology/Principal Findings Endogenous formaldehyde concentration increased significantly in the cultured breast cancer cell lines in vitro, in the bone marrow of breast MRMT-1 bone cancer pain model in rats and in tissues from breast cancer and lung cancer patients in vivo. Low concentrations (1∼5 mM) of formaldehyde induced pain responses in rat via TRPV1 and this pain response could be significantly enhanced by pH 6.0 (mimicking the acidic tumor microenvironment). Formaldehyde at low concentrations (1 mM to 100 mM) induced a concentration-dependent increase of [Ca2+]i in the freshly isolated rat dorsal root ganglion neurons and TRPV1-transfected CHO cells. Furthermore, electrophysiological experiments showed that low concentration formaldehyde-elicited TRPV1 currents could be significantly potentiated by low pH (6.0). TRPV1 antagonists and formaldehyde scavengers attenuated bone cancer pain responses. Conclusions/Significance Our data suggest that cancer tissues directly secrete endogenous formaldehyde, and this formaldehyde at low concentration induces metastatic bone cancer pain through TRPV1 activation especially under tumor acidic environment. PMID:20422007
Serrie, A; Thurel, C
Recent data indicate that 25 to 30% of the population in industrialized countries suffers from benign chronic pain. Among these patients, 50 to 75% are professionally incapable for varied lengths of time, from a few days to some weeks or months, or even definitively. The aetiology and clinical presentation of chronic benign pain are enormously varied because this definition includes such different pathologies as headache, pain of rheumatologic, postsurgical, organic, and post-zoster origin, lombalgia, radiculalgia, post-amputation pain, neuropathologic pain, causalgia, algoneurodystrophic pain, psychosomatic and idiopathic pain. Since these syndromes and causes of pain could not be discussed individually, they have been grouped according to their neurophysiology and pathophysiology.
Wirth, Brigitte; Humphreys, B Kim
Background Although adolescent spinal pain increases the risk for chronic back pain in adulthood, most adolescents can be regarded as healthy. The aim of the present study was to provide data on localization, intensity and frequency of adolescent spinal pain and to investigate which physical and psycho-social parameters predict these pain characteristics. Method On the occasion of Spine Day, an annual event where children and adolescents are examined by chiropractors on a voluntary basis for ...
Wirth, Brigitte; Humphreys, B Kim
Although adolescent spinal pain increases the risk for chronic back pain in adulthood, most adolescents can be regarded as healthy. The aim of the present study was to provide data on localization, intensity and frequency of adolescent spinal pain and to investigate which physical and psycho-social parameters predict these pain characteristics. On the occasion of Spine Day, an annual event where children and adolescents are examined by chiropractors on a voluntary basis for back problems, 412 adolescents (10 to 16 years) were tested (by questionnaire and physical examination). Pain characteristics (localization, intensity, and frequency) were identified and evaluated using descriptive statistics. Regression analyses were performed to investigate possible influencing psycho-social and physical influence factors. Adolescents who suffered from pain in more than one spinal area reported higher pain intensity and frequency than those with pain in only one spinal area. Sleep disorders were a significant predictor for pain in more than one spinal area (p report data on pain frequency, intensity and localization. Adolescents who present with pain in more than one spinal area or report frequent pain should be followed carefully. Reduced balance with visual deprivation might be a physical indicator of a serious back problem.
Zapata, Aura Ligia; Moraes, Ana Julia Pantoja; Leone, Claudio; Doria-Filho, Ulysses; Silva, Clovis Artur Almeida
The presence of musculoskeletal pain was evaluated in adolescents. Pain was reported by 40% of respondents, benign joint hypermobility syndrome by 10%, myofascial syndrome by 5%, tendonitis by 2%, and fibromialgia by 1%. Logistical regression analysis indicated that sex and age were predictive of pain.
Brown, Christopher A; Matthews, Julian; Fairclough, Michael; McMahon, Adam; Barnett, Elizabeth; Al-Kaysi, Ali; El-Deredy, Wael; Jones, Anthony K P
The experience of pain in humans is modulated by endogenous opioids, but it is largely unknown how the opioid system adapts to chronic pain states. Animal models of chronic pain point to upregulation of opioid receptors (OpR) in the brain, with unknown functional significance. We sought evidence for a similar relationship between chronic pain and OpR availability in humans. Using positron emission tomography and the radiotracer (11)C-diprenorphine, patients with arthritis pain (n = 17) and healthy controls (n = 9) underwent whole-brain positron emission tomography scanning to calculate parametric maps of OpR availability. Consistent with the upregulation hypothesis, within the arthritis group, greater OpR availability was found in the striatum (including the caudate) of patients reporting higher levels of recent chronic pain, as well as regions of interest in the descending opioidergic pathway including the anterior cingulate cortex, thalamus, and periaqueductal gray. The functional significance of striatal changes were clarified with respect to acute pain thresholds: data across patients and controls revealed that striatal OpR availability was related to reduced pain perception. These findings are consistent with the view that chronic pain may upregulate OpR availability to dampen pain. Finally, patients with arthritis pain, compared with healthy controls, had overall less OpR availability within the striatum specifically, consistent with the greater endogenous opioid binding that would be expected in chronic pain states. Our observational evidence points to the need for further studies to establish the causal relationship between chronic pain states and OpR adaptation.
Ali Jahan; Abolfazl Danaei; Mohammad Saeidfar
During the past few years, there have been growing competition in banking industry in Iran and there is a growing trend on emerge of new banks, which makes it difficult for existing banks to keep market share. In this paper, we study the effect of advertisements on customers’ willingness to accept banking services based on modulatory role of brand. The proposed study has been performed among 440 randomly selected customers in city of Tehran, Iran who were doing banking business with one of Ir...
Plasticity of Signaling by Spinal Estrogen Receptor α, κ-Opioid Receptor, and Metabotropic Glutamate Receptors over the Rat Reproductive Cycle Regulates Spinal Endomorphin 2 Antinociception: Relevance of Endogenous-Biased Agonism.
Liu, Nai-Jiang; Murugaiyan, Vijaya; Storman, Emiliya M; Schnell, Stephen A; Kumar, Arjun; Wessendorf, Martin W; Gintzler, Alan R
We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous μ-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle: minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and κ-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated metabotropic glutamate receptor 1 (mGluR1) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus). Differential signaling by mGluR1, depending on its activation by membrane estrogen receptor α (mERα; during diestrus) versus glutamate (during proestrus), concomitant with the ebb and flow of spinal dynorphin/KOR signaling, functions as a switch, preventing or promoting, respectively, spinal EM2 antinociception. Importantly, EM2 and glutamate-containing varicosities appose spinal neurons that express MOR along with mGluRs and mERα, suggesting that signaling mechanisms regulating analgesic effectiveness of intrathecally applied EM2 also pertain to endogenous EM2. Regulation of spinal EM2 antinociception by both the nature of the endogenous mGluR1 activator (i.e., endogenous biased agonism at mGluR1) and changes in spinal dynorphin/KOR signaling represent a novel mechanism for modulating analgesic responsiveness to endogenous EM2 (and perhaps other opioids). This points the way for developing noncanonical pharmacological approaches to pain management by harnessing endogenous opioids for pain relief.SIGNIFICANCE STATEMENT The current prescription opioid abuse epidemic underscores the urgency to develop alternative pharmacotherapies for managing pain. We find that the magnitude of spinal endomorphin 2 (EM2) antinociception not only varies
Full Text Available Anti-retroviral (ARV -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on
Adriani, Walter; Travaglini, Domenica; Lacivita, Enza; Saso, Luciano; Leopoldo, Marcello; Laviola, Giovanni
Serotonin receptor 7, i.e. 5-HT(7) protein coded by Htr7 gene, was discovered in supra-chiasmatic nucleus (SCN) of the hypothalamus but is widespread in the forebrain. Studies have shown that this receptor is involved in learning/memory, regulation of mood and circadian rhythms. The modulatory effects of two novel agonists, LP-211 and LP-378, were assessed in male adult CD-1 mice with a battery of behavioral tests. Exp. 1 (Black/White Boxes, BWB: Adriani et al., 2009) and Exp. 2 (Dark/Light, D/L; Novelty-seeking, N-S) show: a) that LP-211 administration (acutely, at a 0.25 mg/kg dose i.p.) increases locomotion and BWB exploration; b) that the time spent away from an aversive, lit chamber (i.e., stress-induced anxiety) and in a new environment (i.e., novelty-induced curiosity) are both reduced. Sub-chronic LP-211 (at a 2.5 mg/kg dose i.p.) reveals a sensitization of locomotor-stimulant properties over 4-5 days. In Exp. 3 (BWB), a three- to four-fold dosage (acutely, at 0.83 mg/kg i.p.) is needed with LP-378 to increase locomotion and BWB exploration. In Exp. 4, mice under constant-light conditions reveal the expected spontaneous lengthening (1.5 h per day) of circadian rhythms. A significant phase advance is induced by LP-211 (at a 0.25 mg/kg dose i.p., administered around activity offset), with onset of activity taking place 6 h earlier than in controls. In summary, LP-211 is able to act consistently onto exploratory motivation, anxiety-related profiles, and spontaneous circadian rhythm. In the next future, agonist modulation of 5-HT(7) receptors might turn out to be beneficial for sleep and/or anxiety disorders. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Mario Bernaba, Kevin A Johnson, Jiang-Ti Kong, Sean MackeyStanford Systems Neuroscience and Pain Laboratory, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USAPurpose: Conditioned pain modulation (CPM is an experimental approach for probing endogenous analgesia by which one painful stimulus (the conditioning stimulus may inhibit the perceived pain of a subsequent stimulus (the test stimulus. Animal studies suggest that CPM is mediated by a spino–bulbo–spinal loop using objective measures such as neuronal firing. In humans, pain ratings are often used as the end point. Because pain self-reports are subject to cognitive influences, we tested whether cognitive factors would impact on CPM results in healthy humans.Methods: We conducted a within-subject, crossover study of healthy adults to determine the extent to which CPM is affected by 1 threatening and reassuring evaluation and 2 imagery alone of a cold conditioning stimulus. We used a heat stimulus individualized to 5/10 on a visual analog scale as the testing stimulus and computed the magnitude of CPM by subtracting the postconditioning rating from the baseline pain rating of the heat stimulus.Results: We found that although evaluation can increase the pain rating of the conditioning stimulus, it did not significantly alter the magnitude of CPM. We also found that imagery of cold pain alone did not result in statistically significant CPM effect.Conclusion: Our results suggest that CPM is primarily dependent on sensory input, and that the cortical processes of evaluation and imagery have little impact on CPM. These findings lend support for CPM as a useful tool for probing endogenous analgesia through subcortical mechanisms.Keywords: conditioned pain modulation, endogenous analgesia, evaluation, imagery, cold presser test, CHEPS, contact heat-evoked potential stimulator
Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.
Diaz-delCastillo, Marta; Woldbye, David P D; Heegaard, Anne Marie
Chronic pain is a serious condition that significantly impairs the quality of life, affecting an estimate of 1.5 billion people worldwide. Despite the physiological, emotional and financial burden of chronic pain, there is still a lack of efficient treatments. Neuropeptide Y (NPY) is a highly conserved endogenous peptide in the central and peripheral nervous systems of all mammals, which has been implicated in both pro- and antinociceptive effects. NPY is expressed in the superficial laminae of the dorsal horn of the spinal cord, where it appears to mediate its antinociceptive actions via the Y1 and Y2 receptors. Intrathecal administration of NPY in animal models of neuropathic, inflammatory or postoperative pain has been shown to cause analgesia, even though its exact mechanisms are still unclear. It remains to be seen whether these promising central antinociceptive effects of NPY can be transferred into a future treatment for chronic pain. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Price, Rebecca C; Christou, Nicolas V; Backman, Steven B; Stone, Laura; Schweinhardt, Petra
Endogenous opioids inhibit nociceptive processing and promote the experience of pleasure. It has been proposed that pain and pleasure lie at opposite ends of an affective spectrum, but the relationship between pain and pleasure and the role of opioids in mediating this relationship has not been tested. Here, we used obese individuals as a model of a dysfunctional opioid system to assess the role of the endogenous opioid peptide, beta-endorphin, on pain and pleasure sensitivity. Obese (10M/10F) and age- and gender-matched non-obese (10M/10F) controls were included in the study. Pain sensitivity using threshold, tolerance, and subjective rating assessments and perceived sweet pleasantness using sucrose solutions were assessed in two testing sessions with placebo or the opioid antagonist, naltrexone (0.7 mg/kg body weight). Beta-endorphin levels were assessed in both sessions. Despite having higher levels of baseline beta-endorphin and altered beta-endorphin-reactivity to naltrexone, obese individuals reported a similar increase in pain and decrease in pleasantness following naltrexone compared to non-obese individuals. Beta-endorphin levels did not correlate with pain or pleasantness in either group, but naltrexone-induced changes in pain and pleasantness were mildly correlated. Moreover, naltrexone-induced changes in pain were related to depression scores, while naltrexone-induced changes in sweet pleasantness were related to anxiety scores, indicating that pain and pleasantness are related, but influenced by different processes.
... are good exercises to improve your overall fitness. Low back pain treatment Most people who have low back pain can ... sitting, standing, sleeping, or lifting.Severe cases of low back pain may require medical treatment. This could include prescription pain relievers or injections. ...
Wilson, Richard D; Chae, John
Hemiplegic shoulder pain is a common complaint for stroke survivors. Many pathologies are included in the diagnosis of hemiplegic shoulder pain, and many with shoulder pain have a multifactorial cause. This article provides rehabilitation specialists with an approach to evaluation and management of those with hemiplegic shoulder pain. Copyright © 2015 Elsevier Inc. All rights reserved.
cultural attitudes about pain, and the cognitive component of pain control.3 All of these ... applied to any patient, regardless of his/her age; however, paediatric pain expression is dependent on the child's level of cognitive development and .... pain.5 This approach involves the participation of the parent and the child during ...
Wąsik, D; Wąsik, N; Sygit, B; Dubiel, M
The subject matter of this publication is the legal assessment of endogenous infection - the specific type of hospital infections. The main aim of the publication is to answer the question of whether medical and legal grounds exist for civil liability for endogenous infections and for treating those infections as cases of medical malpractice or medical events. The research method adopted is a case study. The authors have analysed a civil lawsuit for compensation instituted by an infected patient against a Polish hospital, adjudicated in 2013. The main conclusion of the publication is to postulate distinguishing medical malpractice from complications resulting from the reactions of the human body to treatment. The authors argue that endogenous infections should be treated as the latter-mentioned of these two cases.
Hjaltadóttir, Rannveig Edda
This article sets out to explore endogenous institutions as the rules that govern the interaction between users and producers in public procurement of innovation in a regional context. It further aims to study how this interaction influences the results of the procurement process by investigating...... possible institutional barriers and what can be done to fence against them. The article addresses the question: How do endogenous institutions in the context of user-producer interaction affect performance in public procurement of innovation? Innovation is an interactive learning process...... and the participants in this interaction need a common code of communication to efficiently work together. The institutions that govern user-producer interaction have therefore been seen as a possible explanation for success or failure in public procurement of innovation. Endogenous institutions were found...
BACKGROUND Assessment of the bioequivalence of generic versions of certain reference drugs is complicated by the presence of endogenous levels of said compounds which cannot be distinguished from externally derived compound levels following drug administration. If unaccounted for, the presence of endogenous compound biases towards equivalence in bioequivalence studies of these drugs. Bioequivalence assessments may be complicated further as disposition of the exogenous analogue can be subject to various endogenous processes resulting in nonlinear pharmacokinetics. To overcome these inherent biases a number of different strategies have been employed. AIMS To critically review methods used to overcome confounding biases in bioequivalence studies of ‘endogenous’ drugs. METHODS A literature search of the EMBASE and PubMed databases was performed. RESULTS The following strategies were identified: ablation/modulation of baseline endogenous substance levels; recruitment of ‘substance-deficient’ populations; restriction of dietary intake of the relevant substance; standardization of conditions with the potential to affect relevant homeostatic mechanisms; correction for baseline substance levels; and administration of supra-therapeutic drug doses. CONCLUSIONS On the basis of this review key study design concepts, intended to optimize the design of future bioequivalence studies of these so-called ‘endogenous drugs’, are described. The dual stable isotope method, which could be used in a specific context, is also discussed. PMID:20233194
Falk, Sarah; Bannister, Kirsty; Dickenson, Anthony
Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells....... This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined...... to the mouse femur. This model prompted related approaches and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer induced bone pain results in progressive bone destruction, elevated osteoclast activity...
Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.
Chanana, Priyanka; Kumar, Anil
Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. Copyright © 2016 John Wiley & Sons, Ltd.
Antonia Eliene Duarte
Full Text Available Background: Rhaphiodon echinus is a weed plant used in the Brazilian folk medicinal for the treatment of infectious diseases. In this study, the essential oil of R. echinus leaf was investigated for its antimicrobial properties. Methods: The chemical constituents of the essential oil were characterized by GC-MS. The antimicrobial properties were determined by studying by the microdilution method the effect of the oil alone, and in combination with antifungal or antibiotic drugs against the fungi Candida albicans, Candida krusei and Candida tropicalis and the microbes Escherichia coli, Staphylococcus aureus and Pseudomonas. In addition, the iron (II chelation potential of the oil was determined. Results: The results showed the presence of β-caryophyllene and bicyclogermacrene in major compounds, and revealed a low antifungal and antibacterial activity of the essential oil, but a strong modulatory effect on antimicrobial drugs when associated with the oil. The essential oil showed iron (II chelation activity. Conclusions: The GC-MS characterization revealed the presence of monoterpenes and sesquiterpenes in the essential oil and metal chelation potential, which may be responsible in part for the modulatory effect of the oil. These findings suggest that essential oil of R. echinus is a natural product capable of enhancing the antibacterial and antifungal activity of antimicrobial drugs.
Full Text Available During the past few years, there have been growing competition in banking industry in Iran and there is a growing trend on emerge of new banks, which makes it difficult for existing banks to keep market share. In this paper, we study the effect of advertisements on customers’ willingness to accept banking services based on modulatory role of brand. The proposed study has been performed among 440 randomly selected customers in city of Tehran, Iran who were doing banking business with one of Iranian banks called Parsian. The results of survey have been analyzed using structural equation modeling and the preliminary results indicate that there was a positive and meaningful relationship between brand advertisement and associate name and brand identification. However, there was no meaningful relationship between brand advertisement and customer loyalty towards to brand. In addition, the results of survey indicate there was a meaningful relationship between brand equity components including perception quality on brand name, customer awareness from brand, loyalty to brand and customers’ willingness to accept banking services on modulatory role of brand.
Full Text Available The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC, which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a "behavioral control" paradigm, which involves the ability to terminate a noxious stimulus, and a "safety signaling" paradigm, which involves visual cues that signal the threat (or absence of threat that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.
Niesters, M; Proto, P L; Aarts, L; Sarton, E Y; Drewes, A M; Dahan, A
Tapentadol is an analgesic agent for treatment of acute and chronic pain that activates the µ-opioid receptor combined with inhibition of neuronal norepinephrine reuptake. Both mechanisms are implicated in activation of descending inhibitory pain pathways. In this study, we investigated the influence of tapentadol on conditioned pain modulation (CPM, an experimental measure of endogenous pain inhibition that gates incoming pain signals as a consequence of a preceding tonic painful stimulus) and offset analgesia (OA, a test in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation). Twenty-four patients with diabetic polyneuropathy (DPN) were randomized to receive daily treatment with tapentadol sustained-release (SR) [average daily dose 433 (31) mg] or placebo for 4 weeks. CPM and OA were measured before and on the last day of treatment. Before treatment, none of the patients had significant CPM or OA responses. At week 4 of treatment, CPM was significantly activated by tapentadol SR and coincided with significant analgesic responses. CPM increased from 9.1 (5.4)% (baseline) to 14.3 (7.2)% (placebo) and 24.2 (7.7)% (tapentadol SR, Ptapentadol than placebo (P=0.028). Neither placebo nor tapentadol SR treatment had an effect on the magnitude of the OA responses (P=0.78). Tapentadol's analgesic effect in chronic pain patients with DPN is dependent on activation of descending inhibitory pain pathways as observed by CPM responses. The study was registered at trialregister.nl under number NTR2716. © The Author . Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: email@example.com.
Li, Yingxue; Lefever, Mark R; Muthu, Dhanasekaran; Bidlack, Jean M; Bilsky, Edward J; Polt, Robin
Over the past two decades, potent and selective analgesics have been developed from endogenous opioid peptides. Glycosylation provides an important means of modulating interaction with biological membranes, which greatly affects the pharmacodynamics and pharmacokinetics of the resulting glycopeptide analogues. Furthermore, manipulation of the membrane affinity allows penetration of cellular barriers that block efficient drug distribution, including the blood–brain barrier. Extremely potent and selective opiate agonists have been developed from endogenous peptides, some of which show great promise as drug candidates. PMID:22300099
Fam Xeng Inn
Full Text Available Ureteroscopy (URS is commonly used by urologists to treat ureteral stones. It is a relatively low-risk procedure. Both urinary tract obstruction and contamination of instrument can cause candiduria post-URS, and this infection can be treated with an antifungal medication. Candidemia is known as hematogenous dissemination, and ocular tissue is a common invasion. However, endogenous endophthalmitis, due to postureteroscope candiduria, has not been reported up to date. This is a devastating complication that may lead to visual loss. Here, we describe a case of endogenous endophthalmitis as a consequence of candiduria after URS.
Pain assessment has taken a predominant role in nursing practice. In day-to-day care, the way a patient in pain is approached and the assessment of their pain are sometimes subject to extensive questioning. The subjective part of pain is still often emphasised when the quantified assessment and the nurse's clinical observation are contradictory. The exhaustive gathering of information is key to an effective assessment of a patient's pain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Brandsborg, B.; Nikolajsen, L.; Kehlet, H.
BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...
Brandsborg, B; Nikolajsen, L; Kehlet, Henrik
BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies. Udgivelsesdato: 2008-Mar...
Full Text Available Megumi Sumizono,1,2 Harutoshi Sakakima,1 Shotaro Otsuka,1 Takuto Terashi,1 Kazuki Nakanishi,1,2 Koki Ueda,1,2 Seiya Takada,1,2 Kiyoshi Kikuchi3 1Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan; 2Kirishima Orthopedics, Kirishima, Japan; 3Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Japan Background: Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI model. Materials and methods: Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group, CCI and low-frequency exercise (LFE group, CCI and no exercise (No-Ex group, and naive animals (control group. Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE or 3 (LFE days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes, expression of brain-derived neurotrophic factor (BDNF and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone were administered using intraperitoneal injection. Results: The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of
Christ, M; Dormann, H; Enk, R; Popp, S; Singler, K; Müller, C; Mang, H
A large number of patients present to the emergency department (ED) for evaluation of acute chest pain. About 10-15% are caused by acute myocardial infarction (MI), and over 50% of cases are due to noncardiac reasons. Further improvement for chest pain evaluation appears necessary. What are current options to improve chest pain evaluation in Germany? A selective literature search was performed using the following terms: "chest pain", "emergency department", "acute coronary syndrome" and "chest pain evaluation". A working group of the German Society of Cardiology published recommendations for infrastructure, equipment and organisation of chest pain units in Germany, which should be separated from the ED of hospitals and be under the leadership of a cardiologist. A symptom-based decision for acute care would be preferable if all differential diagnoses of diseases could be managed by one medical specialty: However, all four main symptoms of patients with acute MI (chest pain, acute dyspnea, abdominal pain, dizziness) are also caused by diseases of different specialties. Evaluation and treatment of acute chest pain by representatives of one specialty would lead to over- or undertreatment of affected patients. Therefore we suggest a multidisciplinary evaluation of patients with acute chest pain including representatives of emergency and critical care physicians, cardiologists, internists, geriatricians, family physicians, premedics and emergency nurses. Definition of key indicators of performance and institutionalized feedback will help to further improve quality of care.
Perry G. Fine
Full Text Available The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB1 receptors and in the periphery (primarily but not exclusively CB2 receptors are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking, as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.
Groysman, Maya; Shoval, Irit; Kalcheim, Chaya
Background Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion. PMID:18945340
Zhang, Suyi; Mano, Hiroaki; Ganesh, Gowrishankar; Robbins, Trevor; Seymour, Ben
Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection , escape and avoidance learning , and endogenous analgesia . Although a central role for the amygdala is well established , both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum . It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific "preparatory" system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals-the learned associability and prediction error-were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns "consummatory" limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Morell, María; Camprubí-Robles, María; Culler, Michael D; de Lecea, Luis; Delgado, Mario
Clinical pain, as a consequence of inflammation or injury of peripheral organs (inflammatory pain) or nerve injury (neuropathic pain), represents a serious public health issue. Treatment of pain-related suffering requires knowledge of how pain signals are initially interpreted and subsequently transmitted and perpetuated. To limit duration and intensity of pain, inhibitory signals participate in pain perception. Cortistatin is a cyclic-neuropeptide that exerts potent inhibitory actions on cortical neurons and immune cells. Here, we found that cortistatin is a natural analgesic component of the peripheral nociceptive system produced by peptidergic nociceptive neurons of the dorsal root ganglia in response to inflammatory and noxious stimuli. Moreover, cortistatin is produced by GABAergic interneurons of deep layers of dorsal horn of spinal cord. By using cortistatin-deficient mice, we demonstrated that endogenous cortistatin critically tunes pain perception in physiological and pathological states. Furthermore, peripheral and spinal injection of cortistatin potently reduced nocifensive behavior, heat hyperalgesia and tactile allodynia in experimental models of clinical pain evoked by chronic inflammation, surgery and arthritis. The analgesic effects of cortistatin were independent of its anti-inflammatory activity and directly exerted on peripheral and central nociceptive terminals via Gαi-coupled somatostatin-receptors (mainly sstr2) and blocking intracellular signaling that drives neuronal plasticity including protein kinase A-, calcium- and Akt/ERK-mediated release of nociceptive peptides. Moreover, cortistatin could modulate, through its binding to ghrelin-receptor (GHSR1), pain-induced sensitization of secondary neurons in spinal cord. Therefore, cortistatin emerges as an anti-inflammatory factor with potent analgesic effects that offers a new approach to clinical pain therapy, especially in inflammatory states. Copyright © 2013 Elsevier Inc. All rights
Full Text Available Abstract This review summarizes functional magnetic resonance imaging (fMRI findings that have informed our current understanding of pain, analgesia and related phenomena, and discusses the potential role of fMRI in improved therapeutic approaches to pain. It is divided into 3 main sections: (1 fMRI studies of acute and chronic pain. Physiological studies of pain have found numerous regions of the brain to be involved in the interpretation of the 'pain experience'; studies in chronic pain conditions have identified a significant CNS component; and fMRI studies of surrogate models of chronic pain are also being used to further this understanding. (2 fMRI studies of endogenous pain processing including placebo, empathy, attention or cognitive modulation of pain. (3 The use of fMRI to evaluate the effects of analgesics on brain function in acute and chronic pain. fMRI has already provided novel insights into the neurobiology of pain. These insights should significantly advance therapeutic approaches to chronic pain.
Gorczyca, Rafał; Filip, Rafał; Walczak, Ewa
Pain is defined "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". Pain is a sensation of the body, and is always an unpleasant emotional experience. The role of psychology is auxiliary and supplemental to medicine. This is an aid addressed to the patient, physician and patient's caregivers: professional caregivers, family members and significant others. At each stage of the diagnostic and therapeutic process, psychology offers help, both from the cognitive and practical aspects. The objective of the article is to present important psychological aspects of studies concerning pain, and the psychological methods and techniques of pain treatment. Pain is the leading reason for patients seeking medical care and is one of the most disabling, burdensome, and costly conditions. Pain accompanies many diseases, each one of which generates unique/separate diagnostic, therapeutic and research problems. DEPRESSION AND RELATED PSYCHICAL DISORDERS: There is a significant relationship between depression and pain symptoms, as well as between pain and suicidal thoughts. Patients with a long history of pain disorders also have increased depression and anxiety symptoms, as well as suicidal thoughts. Patients with more severe depression and anxiety symptoms also have an increase in pain problems. The intensity of pain correlates with the intensity of psychopathological symptoms - both with mood lowering and with anxiety symptoms and worry. Active pain coping strategies strive to function in spite of pain, or to distract oneself from pain, are associated with adaptive functioning. Passive strategies involve withdrawal or relinquishing control to an external force or agent and are related to greater pain and depression. Pain catastrophizing is a negatively distorted perception of pain as awful, horrible and unbearable. Catastrophizing is strongly associated with depression and pain. Studies in which
Donner, Mechthild; Horlings, Lummina; Fort, Fatiha; Vellema, Sietze
This article deals with place branding on the regional scale, in the rural context of food and tourism networks in Europe. Place branding is linked to the concepts of endogenous rural development, territory and embeddedness, by analysing how the valorisation of specific rural assets takes shape. The
The classic models of staggered adjustment of Taylor and Blanchard takes the frequency of price or wage adjustment as exogenous. This paper develops a model in which the frequency of price changes in endogenous. It then uses the model to analyze the effects of changes in the parameters of the economy on the frequency of adjustment and the real effects of monetary shocks.
The values obtained enabled calculation of nitrogen requirement of the sheep for maintenance, as well as the value of the experimental rations in the nutrition of the sheep. Values of MFN obtained by two methods were 3.31 and 3.10 g/kg Dry matter (DM) intake. Endogenous urinary nitrogen value was 0.024 g/day per ...
The aim in this research was to determine how endogenous factors such as gender, intelligence, self-concept, and personality relate to the eating habits of adolescents. An empirical investigation was conducted using 340 secondary school learners, 162 boys and 178 girls. From the results it appeared that girls tend to have ...
Abegaz, Dereje Fentie; Fosgerau, Mogens
and congestion. In: Kuhmo Nectar Conference and Summer School on Transportation Economics, 8–9 Jully 2010. Valencia, Spain: ITEA. Fosgerau, Mogens, Engelson, Leonid, & Franklin, Joel. 2012 (Dec.). Endogenous scheduling preferences and random travel time. Unpublished. Lam, Terence C., & Small, Kenneth A. 2001...
Kim, Jung-Sik; Bonifant, Challice; Bunz, Fred; Lane, William S; Waldman, Todd
Epitope tagging is a powerful and commonly used approach for studying the physical properties of proteins and their functions and localization in eukaryotic cells. In the case of Saccharomyces cerevisiae, it has been possible to exploit the high efficiency of homologous recombination to tag proteins by modifying their endogenous genes, making it possible to tag virtually every endogenous gene and perform genome-wide proteomics experiments. However, due to the relative inefficiency of homologous recombination in cultured human cells, epitope-tagging approaches have been limited to ectopically expressed transgenes, with the attendant limitations of their nonphysiological transcriptional regulation and levels of expression. To overcome this limitation, a modification and extension of adeno-associated virus-mediated human somatic cell gene targeting technology is described that makes it possible to simply and easily create an endogenous epitope tag in the same way that it is possible to knock out a gene. Using this approach, we have created and validated human cell lines with epitope-tagged alleles of two cancer-related genes in a variety of untransformed and transformed human cell lines. This straightforward approach makes it possible to study the physical and biological properties of endogenous proteins in human cells without the need for specialized antibodies for individual proteins of interest.
Alstonia boonei is a well-known plant of medicinal value but its effect on endogenous plasma antioxidant in diabetes remains unknown. Thus, need to investigate the effects of the methanolic extract of the plant on plasma bilirubin and uric acid level in alloxan induced diabetes rabbits. Twenty five rabbits divided into five ...
Klynge, Alice Heegaard
I develop a selection model in which the individual’s supply of ability is endogenous and subject to selection along with occupation. Additionally, I identify and estimate the returns to creative and innovative ability, communication ability, and reading and math ability for white-collar and blue...
Dastidar, K.G.; Furth, D.
In the present paper we study endogenous price leadership in the context of a homogeneous product Bertrand duopoly model in which the firms have different, strictly convex cost functions. In such a framework it is well known that a simultaneous move price choice game does not have an equilibrium in
Dec 8, 2010 ... organising principle of the society that this a distinct venture in endogeneity. 3.1. Ifi Amadiume: An ... Put simply, “gender was not an organizing principle in Yoruba society prior to colonization by the .... The consensus-focused public decision-making process also made disregarding the women's voice near ...
The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins. A unique way that B ...
Foss, Nicolai Juul; Felin, Teppo
several, endogeneity-related concerns, namely: (1) the problem of origins and causation, (2) the problem of extremes, (3) the problem of intentionality, (4) the problem of new knowledge, and (5) the problem of the environment. We introduce the ‘poverty of stimulus’ argument and discuss how an internalist...
Vigani, Mauro; Raimondi, V; Olper, A.
This paper quantifies the effect of GMO regulation on bilateral trade flows of agricultural products. We develop a composite index of GMO regulations and using a gravity model we show that bilateral differences in GMO regulation negatively affect trade flows. This effect is especially driven by labeling, approval process and traceability. Our results are robust to the endogeneity of GMO standards to trade flows.
Whyte, Jemima L; Smith, Andrew A; Liu, Bo; Manzano, Wilfred R; Evans, Nick D; Dhamdhere, Girija R; Fang, Mark Y; Chang, Howard Y; Oro, Anthony E; Helms, Jill A
.... Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2(LacZ/LacZ) mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing...
Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk
The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids…
Motivated by several empirical studies showing a positive relationship between residential density and vehicle fuel efficiency chosen by the residents, this paper presents a modified monocentric city model with endogenous vehicle-typechoices. Consumers are assumed to explicitly consider driving i...
the hypothesis that asthmatic patients have lower levels of circulating endogenous heparin than healthy ... of stimuli in guinea pig and rat models of allergic asthma, as well as in asthmatic patients.3 .... 2008; 585: 375-384. 4. Ceyhan B, Celikel T. Effect of inhaled heparin on methacholine-induced bronchial hyperreactivity.
Eigler, A; Greten, T F; Sinha, B; Haslberger, C; Sullivan, G W; Endres, S
Recent studies have demonstrated the inhibitory effect of exogenous adenosine on TNF production. During inflammation endogenous adenosine levels are elevated and may be one of several anti-inflammatory mediators that reduce TNF synthesis. In the present study the authors investigated this role of
Lejour, A.M.; Verbon, H.A.A.
This paper examines the effects of policy coordination in a two-country world with endogenous growth and imperfect capital mobility.Public investment and a public consumption good are financed by a source-based capital-income tax. By comparing the cases in which countries do and do not coordinate
Jun 29, 2011 ... Scientia Agricultura Sinica, 40(10): 2361-2367. Luo Q, Hu YY, Zhou KD (1998). Role of endogenous hormones in tissue culture of mature rice embryo. Chin. J. Rice Sci. 12(4): 238-240. Murashige T, Skoog F (1962). A revised medium for rapid growth and bioassays with tobacco tissue culture. Physiol. Plant ...
We extend the citizen candidate framework by allowing for endogenous party formation. When a party is formed, any member of that party that wants to be a candidate in the election, first has to run in the primary election of her party. We show that in equilibrium one left-wing and one right-wing
This paper argues for a middle-inclusive ground within multiple feminist perspectives from which the potential for the endogenous learning approach to gender and development studies can be grounded. There is a challenge of developing context-specific approaches to learn from Rwanda's achievements in gender and ...
Guillet, Marie; Boiteux, Serge
Abasic (AP) sites are among the most frequent endogenous lesions in DNA and present a strong block to replication. In Saccharomyces cerevisiae, an apn1 apn2 rad1 triple mutant is inviable because of its incapacity to repair AP sites and related 3'-blocked single-strand breaks (M. Guillet and S. Boiteux, EMBO J. 21:2833, 2002). Here, we investigated the origin of endogenous AP sites in yeast. Our results show that the deletion of the UNG1 gene encoding the uracil DNA glycosylase suppresses the lethality of the apn1 apn2 rad1 mutant. In contrast, inactivation of the MAG1, OGG1, or NTG1 and NTG2 genes encoding DNA glycosylases involved in the repair of alkylation or oxidation damages does not suppress lethality. Although viable, the apn1 apn2 rad1 ung1 mutant presents growth delay due to a G(2)/M checkpoint. These results point to uracil as a critical source of the formation of endogenous AP sites in DNA. Uracil can arise in DNA by cytosine deamination or by the incorporation of dUMP during replication. Here, we show that the overexpression of the DUT1 gene encoding the dUTP pyrophosphatase (Dut1) suppresses the lethality of the apn1 apn2 rad1 mutant. Therefore, this result points to the dUTP pool as an important source of the formation of endogenous AP sites in eukaryotes.
The painful events associated with the treatment of a severe burn can, because of their long-lasting and repetitive characteristics, be one of the most excruciating experiences in clinical practice. Moreover, burn pain has been shown to be detrimental to burn patients. Although nociception and peripheral hyperalgesia are considered the major causes of burn pain, the study of more hypothetical mechanisms like central hyperalgesia and neuropathic pain may lead to a better understanding of burn pain symptoms and to new therapeutic approaches. Continuous pain and intermittent pain due to therapeutic procedures are two distinct components of burn pain. They have to be evaluated and managed separately. Although continuous pain is by far less severe than intermittent pain, the treatment is, in both cases, essentially pharmacological relying basically on opioids. Because of wide intra- and inter-individual variations, protocols will have to leave large possibilities of adaptation for each case, systematic pain evaluation being mandatory to achieve the best risk/benefit ratio. Surprisingly, the dose of medication decreases only slowly with time, a burn often remaining painful for long periods after healing. Non pharmacological treatments are often useful and sometimes indispensable adjuncts; but their rationale and their feasibility depends entirely on previous optimal pharmacological control of burn pain. Several recent studies show that burn pain management is inadequate in most burn centres.
Goldberg, Daniel S
The primary claim of this paper is that understanding the stigma so commonly endured by chronic pain sufferers today in the USA and the UK is unlikely without proper appreciation of the history of pain. Ameliorating such stigma is an ethical imperative, and yet most approaches eschew even an attempt to trace connections between historical attitudes, practices and beliefs towards pain and the stigmatisation so many pain sufferers currently endure. The manuscript aims to help fill this gap by framing pain in the modern era in context of two crucial intellectual schemes that waxed in the 19th and 20th centuries: mechanical objectivity and somaticism. The analysis explains these frameworks and applies them to exploration of primary sources connected to contested pain conditions such as railway spine. By properly situating the historical roots of what it means to cite the 'subjectivity' of pain as a problem, the modern roots of stigmatising attitudes and practices towards chronic pain sufferers become much clearer. The manuscript concludes by suggesting that interventions expressly intended to target the root causes of such stigma are much more likely to be successful than approaches that proceed in ignorance of the historical forces shaping and driving pain stigma in the present. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Schlumbohm, C; Harmeyer, J
In previous experiments it has been shown that hyperketonemia lowered plasma glucose concentration in sheep and depressed endogenous glucose production by approximately 30%. This facilitates the onset of pregnancy toxemia. In the last trimester of gestation, hyperketonemia in sheep is often associated with hypocalcemia. There is an indication that hypocalcemia exerts an additional depressive effect on endogenous glucose production. The present study was undertaken to examine the effect in sheep of hypocalcemia on endogenous glucose production in the presence of normo- and hyperketonemia. The experiments were carried out with seven multiparous sheep during three different reproductive states, i.e., during pregnancy (10 +/- 8 d prepartum), during lactation (21 +/- 8 d postpartum), and 4 wk after weaning of the lambs. Concentration of glucose in plasma, turnover of glucose and the rate constant of glucose turnover were measured by isotope dilution during normo- and hypocalcemia and in the presence of normal and elevated beta-hydroxybutyrate (BHB) concentrations. Hypocalcemia was induced by i.v. infusions of Na2EDTA. Hyperketonemia was maintained by i.v. infusion of DL-beta-hydroxybutyrate. The experiments showed that induction of hypocalcemia: 1) induced a decline in plasma glucose concentration in all reproductive states during normo- and hyperketonemia and 2) significantly lowered endogenous production of glucose in nonpregnant hyperketonemic and in lactating normoketonemic ewes. Pregnant normoketonemic ewes were able to compensate for the hypoglycemic effect of hypocalcemia and to keep endogenous production at the normocalcemic level. We concluded that hypocalcemia does not promote the onset of pregnancy toxemia per se but will facilitate the development of the disease when it is present in combination with hyperketonemia.
It is now recognized that from the newborn period onwards, children are capable of experiencing pain. This includes the premature infant. The challenge for healthcare providers is to incorporate methods of pain assessment and treatment into their daily practices. The child's understanding of pain closely follows the cognitive and behavioral model developed by Jean Piaget. Based on these developmental stages, pain assessment measures have been developed. Pharmacologic advances have accompanied this improved understanding of infant, child, and adolescent psychology. While acute pain accounts for the majority of children's experiences, recurrent/chronic pain states do occur (e.g. sickle cell related and neuropathic) and can be effectively treated.
Niikura, Keiichi; Narita, Minoru; Butelman, Eduardo R; Kreek, Mary Jeanne; Suzuki, Tsutomu
Although morphine and other mu-opioid agonists are the main analgesics for severe pain, these compounds have potential for abuse and/or addiction. This has complicated the use of mu-agonists in the treatment of chronic pain. However, clinical studies show that when mu-agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur, although some risk factors that increase vulnerability need to be considered, including genetic variation. We review recent findings on molecular adaptations in sustained pain models, and propose how these adaptations (including sustained release of the endogenous mu-agonist beta-endorphin) can result in decreased abuse potential of mu-agonists in chronic pain states. We also review data on particular gene polymorphisms (e.g. in the mu-receptor gene) that could also influence the relative abuse potential of mu-agonists in clinical pain populations. Copyright 2010 Elsevier Ltd. All rights reserved.
Vaegter, Henrik Bjarke; Palsson, Thorvaldur Skuli; Graven-Nielsen, Thomas
Facilitated pain mechanisms and impaired pain inhibition are often found in chronic pain patients. This study compared clinical pain profiles, pain sensitivity, as well as pro-nociceptive and anti-nociceptive mechanisms in patients with localized low back pain (n=18), localized neck pain (n=17......), low back and radiating leg pain (n=18), or neck and radiating arm pain (n=17). It was hypothesized that patients with radiating pain had facilitated pain mechanisms and impaired pain inhibition compared with localized pain patients. Cuff algometry was performed on the non-painful lower leg to assess...... threshold (HPT) at the non-painful hand were also assessed. Clinical pain intensity, psychological distress, and disability were assessed with questionnaires. TSP was increased in patients with radiating back pain compared with localized back pain (Ppain or localized low...
Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won
Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Response to painful stimuli is susceptible to genetic variation. Numerous loci have been identified which contribute to this variation, one of which, MC1R, is better known as a gene involved in mammalian hair colour. MC1R is a G protein-coupled receptor expressed in melanocytes and elsewhere and mice lacking MC1R have yellow hair, whilst humans with variant MC1R protein have red hair. Previous work has found differences in acute pain perception, and response to analgesia in mice and humans with mutations or variants in MC1R.We have tested responses to noxious and non-noxious stimuli in mutant mice which lack MC1R, or which overexpress an endogenous antagonist of the receptor, as well as controls. We have also examined the response of these mice to inflammatory pain, assessing the hyperalgesia and allodynia associated with persistent inflammation, and their response to neuropathic pain. Finally we tested by a paired preference paradigm their aversion to oral administration of capsaicin, which activates the noxious heat receptor TRPV1. Female mice lacking MC1R showed increased tolerance to noxious heat and no alteration in their response to non-noxious mechanical stimuli. MC1R mutant females, and females overexpressing the endogenous MC1R antagonist, agouti signalling protein, had a reduced formalin-induced inflammatory pain response, and a delayed development of inflammation-induced hyperalgesia and allodynia. In addition they had a decreased aversion to capsaicin at moderate concentrations. Male mutant mice showed no difference from their respective controls. Mice of either sex did not show any effect of mutant genotype on neuropathic pain.We demonstrate a sex-specific role for MC1R in acute noxious thermal responses and pain of inflammatory origin.
... Steven Dowshen, MD Date reviewed: June 2015 For Teens For Kids For Parents MORE ON THIS TOPIC Why Do I Have Pain? How Do Pain Relievers Work? Growth Disorders I'm Growing Up - But Am I Normal? What Medicines Are and What They Do Feeling Too Tall or Too Short Contact Us Print Resources Send ...
... if I still have pain after finishing my medicine? Resources National Institutes of Health: MedlinePlus, Post Surgical Pain Treatment – Adults U.S. Food and Drug Administration, Opioid Medications Last Updated: July 2017 This article was contributed by: familydoctor.org editorial staff Categories: ...
... Nausea and Vomiting in Infants and Children Neck Pain Neck Swelling Shortness of Breath Shortness of Breath in Infants and Children Shoulder Problems Skin Rashes & Other Skin Problems Throat Problems Tooth Problems Urination Problems Back to Symptoms Step 2 Answering Questions Does your pain get ...
Sidebottom, Andrew J
Temporomandibular (TMJ) joint pain is a complex issue involving several factors in a spectrum including myofascial pain, internal derangement and degenerative disease, all of which are reciprocally affected by psychological factors.
Basbaum, A. I; Bushnell, M. Catherine
"The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage...
[b][/b][b]Introduction. [/b]Chronic pelvic pain (CPP) affects about 10–40% of women presenting to a physician, and is characterised by pain within the minor pelvis persisting for over 6 months. [b...
Full Text Available ... Support the ACPA Contact Us Shop What We Have Learned Going to the ER Communication Tools Pain ... are no longer ill or if your injuries have healed. In fact, many persons experience pain even ...
... angina with any of the following signs and symptoms, it may indicate a more serious condition, such as a heart attack: Pain in your arms, neck, jaw, shoulder or back accompanying chest pain Nausea Fatigue Shortness ...
... Psychological Flexibility Might Be the Key to Better Cognitive-Behavioral Interventions APS Presents 2016 Achievement Awards APS Honors ... with Pain Persistence After Pediatric Surgery Study Shows Cognitive Behavioral Therapy Improves Functioning for People with Chronic Pain ...
Full Text Available Chronic pain is a growing problem in children, with prevalence as high as 30.8%. Acupuncture has been found to be useful in many chronic pain conditions, and may be of clinical value in a multidisciplinary treatment program. The basic principles of acupuncture are reviewed, as well as studies exploring basic mechanisms of acupuncture and clinical efficacy. Conditions commonly treated in the pediatric pain clinic, including headache, abdominal pain, fibromyalgia, juvenile arthritis, complex regional pain syndrome, cancer pain, as well as perioperative pain studies are reviewed and discussed. Areas in need of further research are identified, and procedural aspects of acupuncture practice and safety studies are reviewed. Acupuncture can be an effective adjuvant in the care of pediatric patients with painful conditions, both in a chronic and an acute setting. Further studies, including randomized controlled trials, as well as trials of comparative effectiveness are needed.
... gel (Voltaren) is used to relieve pain from osteoarthritis (arthritis caused by a breakdown of the lining ... Diclofenac topical liquid (Pennsaid) is used to relieve osteoarthritis pain in the knees. Diclofenac is in a ...
Full Text Available ... chronic pain there may be no apparent physical injury or illness to explain it. The physician and ... expected period of healing for an illness or injury. You can experience pain even if you are ...
A. S. Salim
Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.
... or "heaviness" or “misery.” Look for behavior or body language that looks like a response to pain. An ... to communicate about pain in words. Behaviors or body language to look for include facial expressions such as ...
Brown, Matthew Rd; Ramirez, Juan D; Farquhar-Smith, Paul
Cancer and its treatment exert a heavy psychological and physical toll. Of the myriad symptoms which result, pain is common, encountered in between 30% and 60% of cancer survivors. Pain in cancer survivors is a major and growing problem, impeding the recovery and rehabilitation of patients who have beaten cancer and negatively impacting on cancer patients' quality of life, work prospects and mental health. Persistent pain in cancer survivors remains challenging to treat successfully. Pain can arise both due to the underlying disease and the various treatments the patient has been subjected to. Chemotherapy causes painful chemotherapy-induced peripheral neuropathy (CIPN), radiotherapy can produce late effect radiation toxicity and surgery may lead to the development of persistent post-surgical pain syndromes. This review explores a selection of the common causes of persistent pain in cancer survivors, detailing our current understanding of the pathophysiology and outlining both the clinical manifestations of individual pain states and the treatment options available.
... breast pain is from hormonal fluctuations from menstruation, pregnancy, puberty, menopause, and breastfeeding. Breast pain can also be associated with fibrocystic breast disease, but it is a very unusual symptom of breast cancer.
... Prevent Back Pain Print This Topic En español Prevent Back Pain Browse Sections The Basics Overview Am ... at Risk? 3 of 5 sections Take Action: Prevent Injuries Focus on good posture. Good posture can ...
... 3, 2017. Related Vagina Endometriosis: Reduce pain during sex Painful intercourse (dyspareunia) Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. Advertising & ...
McEwen, Bruce S; Kalia, Madhu
The relationship between corticosteroids (endogenous and exogenous) and stress is well known, as is the use of steroids as concomitant treatment in pain management during acute inflammation. In the past, steroids have not been considered the first line of treatment in pain management. In this review, we examine new scientific and clinical evidence that demonstrates the direct role that steroids play in the generation and clinical management of chronic pain. We will discuss the new findings demonstrating the fact that steroids and related mediators produce paradoxical effects on pain such as analgesia, hyperalgesia, and even placebo analgesia. In addition, we will examine the physiologic effect of stress, high allostatic load, and idiopathic disease states such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and burnout. The recently observed positive relationship between glutaminergic activity in the insula and clinical pain will be examined in the context of understanding the central role of steroids in chronic pain. The complex role of the hypothalamic-pituitary-adrenal axis in pain will be discussed as well as other heterogeneous forms of chronic pain that involve many components of the central nervous system. Components of the hypothalamic-pituitary-adrenal axis have paradoxical effects on certain types of pain that are dependent on dose and on site (whether peripheral or central) and mode of application. Recent studies on glia have shown that they prolong a state of neuronal hypersensitization in the dorsal root ganglia by releasing growth factors and other substances that act on the immune system. We will discuss the implication of these new findings directly linking pain to steroids, stress, and key higher brain regions in the context of future therapeutic targets. Copyright © 2010 Elsevier Inc. All rights reserved.
Full Text Available Jay Chhablani,1 Aditya Sudhalkar,1 Animesh Jindal,2 Taraprasad Das,1 Swapna R Motukupally,3 Savitri Sharma,3 Avinash Pathengay,2 Harry W Flynn Jr4 1Srimati Kannuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Kallam Anji Reddy Campus, Hyderabad, India; 2L V Prasad Eye Institute, GMR Varalakshmi Campus, Visakhapatnam, India; 3Jhaveri Microbiology Centre, L V Prasad Eye Institute, Kallam Anji Reddy Campus, Hyderabad, India; 4Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, Miami, FL, USA Objective: To describe clinical presentation, antibiotic susceptibility, and outcomes in patients with Stenotrophomonas maltophilia endogenous endophthalmitis.Design: Retrospective case series.Participants: Four eyes of four patients with S. maltophilia endogenous endophthalmitis.Methods: Retrospective chart review of culture-positive S. maltophilia endogenous endophthalmitis treated at L V Prasad Eye Institute, Hyderabad, India, between January 2007 and December 2012, was done. Collected information included demographic, clinical, and microbiology data.Results: These four patients with S. maltophilia endogenous endophthalmitis cases accounted for 0.47% (4/836 of total bacterial endophthalmitis cases treated in this period. All patients were from a rural setting and younger than 40 years. Two of the four patients had a history of immune compromise or hospitalization. The visual acuity at presentation was less than 20/320 in all patients. Common presenting features were severe anterior and posterior segment inflammation and hypopyon. All patients underwent vitrectomy with injection of intravitreal antibiotics and dexamethasone. Direct microscopy of the vitreous sample was positive in all cases. All isolates were sensitive to fluoroquinolones and chloramphenicol; sensitivity to aminoglycosides and third-generation cephalosporins was highly variable. The final visual acuity was 20
Alappattu, Meryl J; George, Steven Z; Robinson, Michael E; Fillingim, Roger B; Moawad, Nashat; LeBrun, Emily Weber; Bishop, Mark D
Introduction Evidence suggests that painful intercourse, pain-related psychosocial factors, and altered pain processing magnify the pain experience, but it is not clear how these factors are related to each other. Aim The aims were to (i) characterize differences between women with pelvic pain and pain-free women using a battery of pain-related psychosocial measures, clinical pain ratings, and evoked local and remote pain sensitivity; and (ii) examine the relationship between intercourse pain, clinical pain, and local and remote evoked pain sensitivity. Methods Women with pelvic pain lasting at least 3 months and pain-free women completed questionnaires and underwent pain sensitivity testing. Self-report measures included clinical pain intensity, pain catastrophizing, pain-related fear, pain anxiety, depression, sexual function, and self-efficacy. Pain sensitivity measures included threshold and tolerance and temporal summation of pain. Separate analyses of variance (anova) were used to test group differences in self-report and pain sensitivity measures. Correlations were calculated among dyspareunia, psychosocial factors, and evoked pain. Main Outcome Measures Self-reported pain and pain sensitivity measures. Results Twenty-eight pain-free women and 14 women with pelvic pain participated in this study. Women with pelvic pain reported greater pain intensity and greater psychosocial involvement compared with pain-free women. No differences existed between groups for thermal or pressure measures, but women with pelvic pain rated their pain with pain testing significantly higher than pain-free women. Intercourse pain was significantly associated with affective and sensory pain and pressure pain ratings at the puborectalis, vulvar vestibule, adductor longus tendons, and tibialis anterior muscle. Conclusions Differences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of
Carter, Brian S; Brunkhorst, Jessica
Pain management in the neonatal ICU remains challenging for many clinicians and in many complex care circumstances. The authors review general pain management principles and address the use of pain scales, non-pharmacologic management, and various agents that may be useful in general neonatal practice, procedurally, or at the end of life. Chronic pain and neonatal abstinence are also noted. Copyright © 2017 Elsevier Inc. All rights reserved.
Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequentl...
Masino, Susan A.; Ruskin, David N.
Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain. PMID:23680946
Masino, Susan A.; Ruskin, David N.
Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.
Rafael, Benoliel; Sorin, Teich; Eli, Eliav
This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions. Copyright © 2016 Elsevier Inc. All rights reserved.
Singh, Namrata; Savanur, Mohammed Azharuddin; Srivastava, Shubhi; D'Silva, Patrick; Mugesh, Govindasamy
Nanomaterials with enzyme-like activities (nanozymes) attracts significant interest due to their therapeutic potential for the treatment of various diseases. Herein, we report that a Mn3 O4 nanozyme functionally mimics three major antioxidant enzymes, that is, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the multienzyme activity is size as well as morphology-dependent. The redox modulatory effect of Mn3 O4 plays a crucial role in protecting the cells from MPP+ induced cytotoxicity in a Parkinson disease (PD)-like cellular model, indicating that manganese-based nanomaterials having multi-enzyme activity can robustly rescue the cells from oxidative damage and thereby possess therapeutic potential to prevent ROS-mediated neurological disorders. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nonspecific back pain - work; Backache - work; Lumbar pain - work; Pain - back - chronic; Low back pain - work; Lumbago - work ... strong. If walking is too hard for you, work with a physical therapist to develop an exercise ...
... it: “atypical chest pain, chest pain of undetermined origin, unexplained chest pain, functional chest pain, soldier’s heart, ... Return to Top GI Health Centers Colorectal Cancer Hepatitis C Inflammatory Bowel Disease Irritable Bowel Syndrome Obesity ...
Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. It may happen ... move the affected body part The cause of CRPS is unknown. There is no specific diagnostic test. ...
music therapy, physiotherapy, and cognitive behavioural therapy, the pain team should consider surgery. The techniques available in the surgical management of pain are summarised in Table 1.[5-12]. Surgery can help in the management of pain in the following ways: • by modulating neural function:[5-8] TENS, spinal cord ...
Treating chronic musculoskeletal pain, and chronic joint pain (osteoarthritis (OA)) in particular, is challenging as the peripheral and central pain mechanisms are not fully discovered, and safe and as efficient analgesic drugs are not available. In general, the preclinical models of OA are limited...
Wolff, A.P.; Vanduynhoven, E.; Kleef, M. van; Huygen, F.; Pope, J.E.; Mekhail, N.
Phantom pain is pain caused by elimination or interruption of sensory nerve impulses by destroying or injuring the sensory nerve fibers after amputation or deafferentation. The reported incidence of phantom limb pain after trauma, injury or peripheral vascular diseases is 60% to 80%. Over half the
subsequently, to poor pain management. Objective. To investigate the pain knowledge of sports and orthopaedic manipulative physiotherapists in South Africa (SA). Methods. Data were collected online by means of a demographic questionnaire and Unruh's Revised Pain Knowledge and Attitudes. Questionnaire (RPKAQ).
human right, and therefore the aim of acute pain management is adequate pain control to achieve ... the intervention causes unacceptable side-effects, it can lead to suboptimal pain relief and potentially dire outcomes. Knowledge .... it was found in a systematic review that music therapy reduces anxiety and analgesia ...
Objective: The objective of this study was to identify possible differences between chronic pain patients (consumers) and persons with chronic pain lasting >1 year who had not consulted a doctor because of the pain during the last year (nonconsumers). Group differences were studied from the
Vanelderen, P.; Szadek, K.M.; Cohen, S.P.; Witte, J.; Lataster, A.; Patijn, J.; Mekhail, N.; van Kleef, M.; van Zundert, J.
The sacroiliac joint accounts for approximately 16% to 30% of cases of chronic mechanical low back pain. Pain originating in the sacroiliac joint is predominantly perceived in the gluteal region, although pain is often referred into the lower and upper lumbar region, groin, abdomen, and/ or lower
Baat, C. de
In daily social life, orofacial pain is strongly associated with teeth. However, edentulousness is no lifetime guarantee of being pain-free in the orofacial region. Common oral pains in edentulous people are caused by denture misfits or occlusal errors, by alveolar ridge atrophy, by (sharp)
Pain is a complex interaction of sensory, emotional and behavioral factors. There are no pain pathways, ... of Pain as an “unpleasant sensory and emotional experience, associated with actual or potential tissue ..... to interact and sleep deprivation all contribute to psychological disturbances, which can increase the risk of ...
Diwakar, Bastihalli Tukaramrao; Lokesh, Belur Ramaswamy; Naidu, Kamatham Akhilender
Vegetable oils containing α-linolenic acid (ALA; 18 : 3n-3) have been shown to modulate the functions of immunocompetent cells. The aim of the present study was to understand the modulatory effect of ALA-rich garden cress (Lepidium sativum L.) seed oil (GCO) on lipid composition, spleen lymphocyte (SL) proliferation and inflammatory mediator production by peritoneal macrophages (PMΦ) in rats. Female Wistar rats were fed diets containing either GCO (2·5, 5·0 and 10 %, w/w) or sunflower oil (SFO, 10 % w/w) for 8 weeks. Ex vivo proliferation of SL was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. IL-2 and TNF-α in SL and PMΦ were analysed by ELISA. Inflammatory mediators such as NO, leukotriene B(4) (LTB(4)) and H(2)O(2) were measured in mitogen-activated PMΦ. GCO significantly increased the levels of ALA, EPA and DHA, but reduced linoleic acid and arachidonic acid in SL and PMΦ lipids. GCO (10 %) significantly decreased the concanavalin A (Con-A)- and phytohaemagglutinin-mediated proliferation of SL by 54 and 38 %, respectively, in comparison with SFO. A marginal decrease in IL-2 and TNF-α was observed in Con-A-stimulated SL and lipopolysaccharide-stimulated PMΦ. LTB(4) levels in Ca ionophore-stimulated PMΦ were reduced by 40 % in GCO-fed rats. NO release in response to various stimuli was significantly decreased in PMΦ of GCO-fed rats. The present study is the first report on the modulatory efficacy of GCO on immunomediators in rats. GCO modulated inflammatory mediators such as NO and LTB(4), and thus may play a role in alleviating inflammatory conditions favourably.
Selleck, Ryan A; Baldo, Brian A
Whereas reward-modulatory opioid actions have been intensively studied in subcortical sites such as the nucleus accumbens (Acb), the role of cortical opioid transmission has received comparatively little attention. The objective of this study is to describe recent findings on the motivational actions of opioids in the prefrontal cortex (PFC), emphasizing studies of food motivation and ingestion. PFC-based opioid effects will be compared/contrasted to those elicited from the Acb, to glean possible common functional principles. Finally, the motivational effects of opioids will be placed within a network context involving the PFC, Acb, and hypothalamus. Mu-opioid receptor (μ-OR) stimulation in both the Acb and PFC induces eating and enhances food-seeking instrumental behaviors; μ-OR signaling also enhances taste reactivity within a highly circumscribed zone of medial Acb shell. In both the Acb and PFC, opioid-sensitive zones are aligned topographically with the sectors that project to feeding-modulatory zones of the hypothalamus and intact glutamate transmission in the lateral/perifornical (LH-PeF) hypothalamic areas is required for both Acb- and PFC-driven feeding. Conversely, opioid-mediated feeding responses elicited from the PFC are negatively modulated by AMPA signaling in the Acb shell. Opioid signaling in the PFC engages functionally opposed PFC➔hypothalamus and PFC➔Acb circuits, which, respectively, drive and limit non-homeostatic feeding, producing a disorganized and "fragmented" pattern of impulsive food-seeking behaviors and hyperactivity. In addition, opioids act directly in the Acb to facilitate food motivation and taste hedonics. Further study of this cortico-striato-hypothalamic circuit, and incorporation of additional opioid-responsive telencephalic structures, could yield insights with translational relevance for eating disorders and obesity.
Meryl J. Alappattu, DPT, PhD
Conclusions: Differences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of stimuli does not differ. Alappattu MJ, George SZ, Robinson ME, Fillingim RB, Moawad N, LeBrun EW, and Bishop MD. Painful intercourse is significantly associated with evoked pain perception and cognitive aspects of pain in women with pelvic pain. Sex Med 2015;3:14–23.
Bujedo, Borja Mugabure
Opioids have been used for spinal analgesia for more than a century, and their injection epidurally and intrathecally has a key role in the control of postoperative pain. Since the discovery of the endogenous opioid system, 3 decades ago, their use has become more generalized in obstetric analgesia, the management of chronic pain, and acute postoperative pain. To use opioids effectively for this type of analgesia, it is important to understand the pharmacokinetics and clinical pharmacology of these drugs, specifically those that produce analgesia by an intrinsic spinal mechanism. Evidence from animal and human experiments indicates that hydrophilic opioids (such as hydromorphone and morphine) bind more strongly to specific receptors within the dorsal horn of the spinal cord than lipophilic opioids (such as alfentanil, fentanyl, and sufentanil). This can be understood by considering the spinal cord selectivity and bioavailability of these opioids. This difference is attributable to differences in the pharmacokinetic and pharmacodynamic properties of the 2 groups. It is more difficult for lipophilic opioids to reach and remain at sufficiently high concentrations at the site of action due to their sequestration in epidural fat and rapid plasma clearance from both epidural and intrathecal spaces, resulting in analgesia with a limited spread and duration, as well as the appearance of early supraspinal side effects. In contrast, morphine has very different properties, including greater spinal bioavailability and therefore administered neuraxially, it is suitable choice for the treatment of acute postoperative pain. However, when using morphine, a greater incidence of adverse effects can be expected, and it requires careful patient selection. © 2013 World Institute of Pain.
Trigo, José Manuel; Martin-García, Elena; Berrendero, Fernando; Robledo, Patricia; Maldonado, Rafael
Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.
van Oorschot, Joep W M; Gho, Johannes M I H; van Hout, Gerardus P J; Froeling, Martijn; Jansen Of Lorkeers, Sanne J; Hoefer, Imo E; Doevendans, Pieter A; Luijten, Peter R; Chamuleau, Steven A J; Zwanenburg, Jaco J M
The aim of this review is to provide an overview of detection of cardiac fibrosis with MRI using current standards and novel endogenous MRI techniques. Assessment of cardiac fibrosis is important for diagnosis, prediction of prognosis and follow-up after therapy. During the past years, progress has been made in fibrosis detection using MRI. Cardiac infarct size can be assessed noninvasively with late gadolinium enhancement. Several methods for fibrosis detection using endogenous contrast have been developed, such as native T1 -mapping, T1ρ -mapping, Magnetization transfer imaging, and T2 *-mapping. Each of these methods will be described, providing the basic methodology, showing potential applications from applied studies, and discussing the potential and challenges or pitfalls. We will also identify future steps and developments that are needed for bringing these methods to the clinical practice. © 2014 Wiley Periodicals, Inc.
Zhang, Jing; Lodish, Harvey F
K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.
Full Text Available Hydroponic experiments were performed to exam the dynamic change of endogenous proline in rice seedlings exposed to potassium chromate chromium (VI or chromium nitrate chromium (III. Although accumulation of both chromium species in rice seedlings was obvious, more chromium was detected in plant tissues of rice seedlings exposed to chromium (III than those in chromium (VI, majority being in roots rather than shoots. Results also showed that the accumulation capacity of chromium by rice seedlings was positively correlated to chromium concentrations supplied in both chromium variants and the accumulation curve depicted an exponential trend in both chromium treatments over the entire period of exposure. Proline assays showed that both chromium variants induced the change of endogenous proline in shoots and roots of rice seedlings. Chromium (VI of 12.8 mg/L increased proline content significantly (p
T S Melnikova
Full Text Available A trend in EEG interhemispheric asymmetry was studied in patients with endogenous depressions in morning and evening hours. In the morning, the spectral power of alpha rhythm particularly in the occipital cortical regions, proved to be higher than that in the evening. In the morning, the interhemispheric differences in the power of occipital alpha rhythm were leveled off while in the evening there was normalization of interhemispheric balance with the higher power of alpha rhythm in the right occipital region. Analysis of the mean coherence (mean Coh of alpha rhythm in individual cortical regions revealed that the patients with endogenous depression had higher readings mainly in the parietal and central regions of both hemispheres and in the right temporal regions in the morning than in the evening. The occipital and posttemporal regions showed an inverse trend in the mean Coh - it was lower in the morning than in the evening
Tarlinton, R; Meers, J; Young, P
Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).
Regnault, Thomas; Davière, Jean-Michel; Achard, Patrick
Gibberellins (GAs) are phytohormones controlling major aspects of plant growth and development. Although previous studies suggested the existence of a transport of GAs in plants, the nature and properties associated with this transport were unknown. We recently showed through micrografting and biochemical approaches that the GA12 precursor is the chemical form of GA undergoing long-distance transport across plant organs in Arabidopsis. Endogenous GA12 moves through the plant vascular system from production sites to recipient tissues, in which GA12 can be converted to bioactive forms to support growth via the activation of GA-dependent processes. GAs are also essential to promote seed germination; hence GA biosynthesis mutants do not germinate without exogenous GA treatment. Our results suggest that endogenous GAs are not (or not sufficiently) transmitted to the offspring to successfully complete the germination under permissive conditions.
Kouznetsov, Andrian I.; Stepanov, Eugene V.; Shulagin, Yurii A.; Skrupskii, Vladimir A.
High sensitive CO gas analyzer based on tunable diode laser (TDL) was used as a real time monitor of endogenous carbon monoxide in a set of breath physiology experiments. The measurements of the CO content dynamics in exhaled air with 10 ppb sensitivity were attended with detection of carbon dioxide and O2 in breath, lung ventilation parameters, heart rate and blood analysis using conventional techniques. Variations of endogenous CO in human breath caused by hyperoxia, hypoxia, hyperventilation as well as sport loading were studied in real time. Scattering of the CO variation time constants was observed for different tested persons. Possible reasons for this scattering related with the organisms' physiology peculiarities are discussed.
Ji, Jiantao; Peng, Yongzhen; Wang, Bo; Wang, Shuying
This study proposed a novel strategy for achievement of partial denitrification driven by endogenous carbon sources in an anaerobic/anoxic/aerobic activated sludge system. Results showed that in the steady-stage, the nitrate-to-nitrite transformation ratio (NTR) was kept at around 87% without nitrate in the effluent. During the anaerobic period, exogenous carbon sources was completely taken up, accompanied by the consumption of glycogen and production of polyhydroxyalkanoates (PHAs). During the anoxic period, nitrate was reduced to nitrite by using PHAs as carbon sources, followed by the replenishment of glycogen. Thus, the phenotype of denitrifying GAOs was clearly observed and endogenous partial denitrification (EPD) occurred. Furthermore, results showed the nitrate reduction was prior to the nitrite reduction in the presence of nitrate, which led to the high nitrite accumulation. Copyright © 2016 Elsevier Ltd. All rights reserved.
Chatterji, Bijon; Pich, Andreas
In recent years, MALDI imaging mass spectrometry (MALDI-IMS) has developed as a promising tool to investigate the spatial distribution of biomolecules in intact tissue specimens. Ion densities of various molecules can be displayed as heat maps while preserving anatomical structures. In this short review, an overview of different biomolecules that can be analyzed by MALDI-IMS is given. Many reviews have covered imaging of lipids, small metabolites, whole proteins and enzymatically digested proteins in the past. However, little is known about imaging of endogenous peptides, for example, in the rat brain, and this will therefore be highlighted in this review. Furthermore, sample preparation of frozen or formalin-fixed, paraffin-embedded (FFPE) tissue is crucial for imaging experiments. Therefore, some aspects of sample preparation will be addressed, including washing and desalting, the choice of MALDI matrix and its deposition. Apart from mapping endogenous peptides, their reliable identification in situ still remains challenging and will be discussed as well.
Esteve, R; Marquina-Aponte, V
Previous studies on children's pain perspectives remain limited to English-speaking populations. An exploratory cross-sectional descriptive design was used to investigate the developmental progression of children's pain perspectives, including their pain experience, its definition and attributes, causality and coping. The Children's Pain Perspectives Inventory was applied to 180 healthy Spanish children. A coding system was developed following the content analysis method. Three age groups were compared: 4-6 years, corresponding to the Piagetian pre-operational stage of cognitive development; 7-11 years, corresponding to stage of concrete operations; and 12-14 years, corresponding to the period of early formal operations. In children between 4 and 6, the predominant narratives related to physical injuries, the notion of causality and the definition of pain. In children between 7 and 11, the predominant narratives were those in which pain was described as a sensation in one part of the body. The view of pain as having an emotional basis significantly increased with age and was more frequent in adolescents. In contrast, children between 4-6 and 7-11 indicated that pain occurs spontaneously. The denial of any positive aspects of pain significantly decreased with age; some children between 7 and 11 referred to the 'possibility of relief', while the view that pain is a 'learning experience' was significantly more frequent among adolescents aged between 12 and 14 years. The use of cognitive strategies to control pain significantly increased with age. Between 12 and 14 years of age, adolescents communicate pain by non-verbal behaviour and reported that they do not express demands for relief. There was a progression from concrete to more complex notions of pain as age increased. These results may be of use to health professionals and parents to understand how children at various developmental stages express and cope with pain and to develop tools that effectively assess and
Full Text Available The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC, leading to tolerance to cerebral ischemia. Here we studied the role of thrombin’s endogenous potent inhibitor, protease nexin-1 (PN-1, in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI exposed to oxygen and glucose deprivation (OGD. We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1−/− mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection.
Pomerleau, O F
The present report examines efforts to elucidate the role of opioid mechanisms in the reinforcement of smoking. A number of approaches have been used to evaluate nicotine-opioid interactions. Opiate agonists such as heroin or methadone have been found to increase cigarette smoking reliably in humans, and morphine has been shown to increase the potency and efficacy of nicotine in rats. There is also an extensive literature documenting the nicotine-stimulated release of endogenous opioids in various brain regions involved in the mediation of opiate reinforcement. Blockade studies using opioid antagonists have not been as conclusive. Although animal models have demonstrated commonalities between nicotine withdrawal and the opiate abstinence syndrome, including reversibility by morphine, and although the impact of nicotine on certain response systems such as respiratory reflexes has clearly been shown to involve opioid mediation, attempts to demonstrate opioid modulation for the key indicators of smoking reinforcement--cigarette consumption and nicotine self-administration--have been fraught with difficulty. Resolution of the apparent contradictions will require taking into account: (a) the biphasic properties of nicotine-opioid effects at higher doses and anti-opioid effects at lower doses; (b) the contributions of the opioid receptor populations--mu, kappa, sigma--stimulated at various dose levels; (c) the possibility that endogenous-opioid activity is entrained primarily during the acquisition or re-acquisition of nicotine self-administration; (d) the possibility that the endogenous opioid response does contribute to nicotine reinforcement but only as a delimited component of the neuroregulatory cascade of nicotine; and (e) the possibility that opioids contribute primarily to nicotine reinforcement under special conditions such as stress. Taking these considerations into account should allow studies on endogenous opioid effects to begin to do justice to the