Science.gov

Sample records for alleviated mechanical allodynia

  1. Huperzine A Alleviates Mechanical Allodynia but Not Spontaneous Pain via Muscarinic Acetylcholine Receptors in Mice.

    PubMed

    Zuo, Zhen-Xing; Wang, Yong-Jie; Liu, Li; Wang, Yiner; Mei, Shu-Hao; Feng, Zhi-Hui; Wang, Maode; Li, Xiang-Yao

    2015-01-01

    Chronic pain is a major health issue and most patients suffer from spontaneous pain. Previous studies suggest that Huperzine A (Hup A), an alkaloid isolated from the Chinese herb Huperzia serrata, is a potent analgesic with few side effects. However, whether it alleviates spontaneous pain is unclear. We evaluated the effects of Hup A on spontaneous pain in mice using the conditioned place preference (CPP) behavioral assay and found that application of Hup A attenuated the mechanical allodynia induced by peripheral nerve injury or inflammation. This effect was blocked by atropine. However, clonidine but not Hup A induced preference for the drug-paired chamber in CPP. The same effects occurred when Hup A was infused into the anterior cingulate cortex. Furthermore, ambenonium chloride, a competitive inhibitor of acetylcholinesterase, also increased the paw-withdrawal threshold but failed to induce place preference in CPP. Therefore, our data suggest that acetylcholinesterase in both the peripheral and central nervous systems is involved in the regulation of mechanical allodynia but not the spontaneous pain. PMID:26697233

  2. Transplantation of human umbilical cord blood or amniotic epithelial stem cells alleviates mechanical allodynia after spinal cord injury in rats.

    PubMed

    Roh, Dae-Hyun; Seo, Min-Soo; Choi, Hoon-Seong; Park, Sang-Bum; Han, Ho-Jae; Beitz, Alvin J; Kang, Kyung-Sun; Lee, Jang-Hern

    2013-01-01

    Stem cell therapy is a potential treatment for spinal cord injury (SCI), and a variety of different stem cell types have been grafted into humans suffering from spinal cord trauma or into animal models of spinal injury. Although several studies have reported functional motor improvement after transplantation of stem cells into injured spinal cord, the benefit of these cells for treating SCI-induced neuropathic pain is not clear. In this study, we investigated the therapeutic effect of transplanting human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) or amniotic epithelial stem cells (hAESCs) on SCI-induced mechanical allodynia (MA) and thermal hyperalgesia (TH) in T13 spinal cord hemisected rats. Two weeks after SCI, hUCB-MSCs or hAESCs were transplanted around the spinal cord lesion site, and behavioral tests were performed to evaluate changes in SCI-induced MA and TH. Immunohistochemical and Western blot analyses were also performed to evaluate possible therapeutic effects on SCI-induced inflammation and the nociceptive-related phosphorylation of the NMDA NR1 receptor subunit. While transplantation of hUCB-MSCs showed a tendency to reduce MA, transplantation of hAESCs significantly reduced MA. Neither hUCB-MSC nor hAESC transplantation had any effect on SCI-induced TH. Transplantation of hAESCs also significantly reduced the SCI-induced increase in NMDA receptor NR1 subunit phosphorylation (pNR1) expression in the spinal cord. Both hUCB-MSCs and hAESCs reduced the SCI-induced increase in spinal cord expression of the microglial marker, F4/80, but not the increased expression of GFAP or iNOS. Taken together, these findings demonstrate that the transplantation of hAESCs into the injured spinal cord can suppress mechanical allodynia, and this effect seems to be closely associated with the modulation of spinal cord microglia activity and NR1 phosphorylation.

  3. Spinal mechanism of standard analgesics: evaluation using mouse models of allodynia.

    PubMed

    Tsukamoto, Mina; Kiso, Tetsuo; Shimoshige, Yukinori; Aoki, Toshiaki; Matsuoka, Nobuya

    2010-05-25

    Spinal neurotransmission plays an important role in the perception of pain signaling. In the present study, we investigated the spinal anti-nociceptive mechanism of current standard analgesics in mouse models of tactile allodynia induced by intrathecal administration of N-methyl-D-aspartic acid (NMDA), prostaglandin E2 (PGE2), and bicuculline. NMDA-induced allodynia is induced by postsynaptic NMDA receptor activation, while PGE2-induced allodynia is triggered by the enhancement of presynaptic glutamate release via EP1 receptor activation. In contrast, bicuculline induces allodynia by the blockade of gamma-aminobutyric acid (GABA)A receptor-mediated inhibitory system. As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models. Pregabalin almost completely alleviated NMDA-, PGE2-, and bicuculline-induced allodynia. Despite being classified as an agent with a similar molecular target mechanism, ziconotide could only alleviate PGE2-induced allodynia, but not NMDA- or bicuculline-induced allodynia, as did mexiletine and duloxetine. These results taken together suggest that ziconotide, mexiletine, and duloxetine suppress spinal hyperactivity via the presynaptic site mechanism. In contrast, pregabalin could suppress via the downstream step during spinal hyperactivation such as postsynaptic NMDA activation or dysfunction of GABAergic control in addition to presynaptic mechanism. In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade. PMID:20188724

  4. Isolation rearing reduces mechanical allodynia in a mouse model of chronic inflammatory pain.

    PubMed

    Horiguchi, Naotaka; Ago, Yukio; Hasebe, Shigeru; Higashino, Kosuke; Asada, Kazuki; Kita, Yuki; Takuma, Kazuhiro; Matsuda, Toshio

    2013-11-15

    Social isolation rearing in mice after weaning reduces pain sensitivity to acute pain, and this hypoalgesia is mediated by the descending serotonergic pain inhibitory system in which the spinal serotonin (5-HT)1A receptor is involved. However, it is not known whether isolation rearing affects pain sensitivity to neuropathic or inflammatory chronic pain. In this study, we examined the effects of isolation rearing on chronic pain induced by Freund's complete adjuvant (FCA) and partial sciatic nerve ligation using the von Frey test (to assess mechanical allodynia) and the plantar test (to assess thermal hyperalgesia). In the FCA model, isolation rearing reduced mechanical allodynia, but not thermal hyperalgesia. In contrast, isolation rearing had no effect on allodynia or hyperalgesia in the sciatic nerve ligation model. The isolation rearing-induced inhibition of allodynia was alleviated by intrathecal injection of WAY100635, a selective 5-HT1A receptor antagonist. FCA increased 5-HT turnover and decreased 5-HT1A receptor expression in the spinal cord of group-reared mice, while it did not have these effects in isolation-reared mice. These results suggest that FCA suppresses the serotonergic pain inhibitory system selectively in group-reared mice. Moreover, systemic administration of osemozotan, a selective 5-HT1A receptor agonist, inhibited FCA-induced mechanical allodynia in group-reared mice, and this effect of the drug was suppressed by intrathecal injection of WAY100635. Collectively, these findings suggest that isolation rearing selectively reduces FCA-induced mechanical allodynia in mice and that this effect is mediated by the activation of spinal 5-HT1A receptors.

  5. Differential pharmacological alleviation of oxaliplatin-induced hyperalgesia/allodynia at cephalic versus extra-cephalic level in rodents.

    PubMed

    Michot, Benoit; Kayser, Valérie; Bastian, Gérard; Bourgoin, Sylvie; Hamon, Michel

    2014-04-01

    Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves responds differently to alleviating drugs at cephalic versus extracephalic level. Because neuropathic pain evoked by anti-cancer drugs differs from that triggered by mechanical nerve lesion, we investigated whether differences between cephalic and extracephalic levels could also be characterized in rodents rendered neuropathic by treatment with the anti-cancer platinum derivative oxaliplatin. C57BL/6J mice received two injections and Sprague-Dawley rats three injections of oxaliplatin (10 mg/kg, i.p.) or its vehicle, with three days intervals. Supersensitivity to mechanical (von Frey filaments), cold (acetone drop) and chemical/inflammatory (formalin) stimulations was assessed in vibrissae and hindpaw territories. Transcripts of neuroinflammatory markers were quantified by real-time RT-qPCR in rat ganglia and central tissues. Oxaliplatin induced mechanical allodynia, cold hyperalgesia and chemical/inflammatory supersensitivity at both hindpaw and vibrissal levels in mice and rats. Acute treatment with gabapentin (30 mg/kg i.p.), morphine (3 mg/kg s.c.) or the 5-HT1A receptor agonist 8-OH-DPAT (0.16 mg/kg s.c.) significantly reduced oxaliplatin-induced supersensitivity in hindpaw but not vibrissal territory. In contrast, the antimigraine drugs naratriptan (0.1 mg/kg s.c.) and olcegepant (0.6 mg/kg i.v.) decreased oxaliplatin-induced supersensitivity in vibrissal territory only. Among the various markers investigated, only TRPA1 transcript was upregulated in ganglia of oxaliplatin-treated rats. These data showed that oxaliplatin induced supersensitivity to various stimuli in both cephalic and extra-cephalic territories in rodents. Regional differences in the efficacy of drugs to alleviate oxaliplatin-induced allodynia/hyperalgesia further support the idea that mechanisms underlying neuropathic pain have peculiarities at cephalic versus extra-cephalic level.

  6. Evaluation of milnacipran, in comparison with amitriptyline, on cold and mechanical allodynia in a rat model of neuropathic pain.

    PubMed

    Berrocoso, Esther; Mico, Juan-Antonio; Vitton, Olivier; Ladure, Philippe; Newman-Tancredi, Adrian; Depoortère, Ronan; Bardin, Laurent

    2011-03-25

    Milnacipran, a serotonin/norepinephrine reuptake inhibitor (SNRI), has shown efficacy against several chronic pain conditions, including fibromyalgia. Here, we evaluated, in rats, its anti-allodynic effects following acute or sub-chronic treatment in a model of neuropathic pain (chronic constriction injury, CCI, of the sciatic nerve). Amitriptyline, a tricyclic antidepressant active pre-clinically and clinically against neuropathic pains, was added as a comparison compound. Upon acute i.p. administration, milnacipran was potently efficacious in the CCI model. It significantly reduced thermal allodynia in the cold (4°C) plate test (MED=2.5mg/kg), and attenuated mechanical allodynia in the von Frey filaments test (MED=10mg/kg). Given sub-chronically (7day, b.i.d.), milnacipran was effective at 10mg/kgi.p. in both tests. Acute amitriptyline (10mg/kgi.p.) was efficacious against mechanical, but less so against cold allodynia; under sub-chronic conditions, it was only active against mechanical allodynia. These data show that milnacipran is as efficacious as the reference compound amitriptyline in a pre-clinical model of injury-induced neuropathy, and demonstrate for the first time that it is active acutely and sub-chronically against cold allodynia. They also suggest that milnacipran has the potential to alleviate allodynia associated with nerve compression-induced neuropathic pain in the clinic (for example following discal hernia, avulsion or cancer-induced tissue damage). PMID:21277295

  7. Maternal Separation Induces Orofacial Mechanical Allodynia in Adulthood.

    PubMed

    Yasuda, M; Shinoda, M; Honda, K; Fujita, M; Kawata, A; Nagashima, H; Watanabe, M; Shoji, N; Takahashi, O; Kimoto, S; Iwata, K

    2016-09-01

    It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood.

  8. Maternal Separation Induces Orofacial Mechanical Allodynia in Adulthood.

    PubMed

    Yasuda, M; Shinoda, M; Honda, K; Fujita, M; Kawata, A; Nagashima, H; Watanabe, M; Shoji, N; Takahashi, O; Kimoto, S; Iwata, K

    2016-09-01

    It is well known that exposure to maternal separation (MS) in early life causes plastic changes in the nervous system in adulthood, occasionally resulting in ubiquitous chronic pain. However, the pathogenic mechanisms of pain hypersensitivity remain unclear. Here, the authors examined the involvement of corticosterone in orofacial mechanical hypersensitivity induced by MS. To establish a rat model of MS, pups were placed in isolated cages 180 min/d and kept in a temperature-controlled environment at 22 ± 2 °C for 14 d. Mechanical allodynia in the whisker pad skin in adulthood was induced by MS and was significantly suppressed by successive postnatal subcutaneous administration of the glucocorticoid receptor antagonist mifepristone. Corticosterone levels were increased in the serum of MS rats, and successive postnatal administration of subcutaneous corticosterone to naive rats induced mechanical allodynia in the whisker pad skin. The number of P2X3 receptor-immunoreactive (P2X3R-IR) trigeminal ganglion (TG) neurons innervating the whisker pad skin was significantly increased in MS rats and decreased following subcutaneous administration of mifepristone. The number of P2X3R-IR TG neurons innervating the whisker pad skin was also significantly increased following successive postnatal administration of subcutaneous corticosterone in naive rats. Moreover, the mechanical allodynia was suppressed 30 min after administration of the P2X3R antagonist A317491 to the whisker pad skin in MS rats. These findings suggest that the increase in P2X3R-IR TG neurons innervating the whisker pad skin via enhanced neonatal corticosterone signaling by MS plays an important role in orofacial mechanical allodynia in adulthood. PMID:27474258

  9. Milnacipran inhibits oxaliplatin-induced mechanical allodynia through spinal action in mice.

    PubMed

    Andoh, Tsugunobu; Kitamura, Ryo; Kuraishi, Yasushi

    2015-01-01

    We investigated whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, would have therapeutic effect on oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin (3 mg/kg) induced mechanical allodynia, which peaked on day 10 after injection and almost completely subsided by day 20. Ten days post-oxaliplatin injection, the intraperitoneal administration of milnacipran (3-30 mg/kg) significantly and dose-dependently inhibited the established mechanical allodynia. Intrathecal injections of milnacipran (2.1-21 µg/site) also significantly and dose-dependently inhibited mechanical allodynia, but intracisternal and intracereboventricular injections at the same doses did not. The present results suggest that milnacipran is effective against oxaliplatin-induced mechanical allodynia and that the antiallodynic effect is mainly mediated by actions on the spinal cord. PMID:25744472

  10. Prokineticin 2 facilitates mechanical allodynia induced by α,β-methylene ATP in rats.

    PubMed

    Ren, Cuixia; Qiu, Chun-Yu; Gan, Xiong; Liu, Ting-Ting; Qu, Zu-Wei; Rao, Zhiguo; Hu, Wang-Ping

    2015-11-15

    Prokineticin 2 (PK2), a new chemokine, causes mechanical hypersensitivity in the rat hind paw, but little is known about the molecular mechanism. Here, we have found that ionotropic P2X receptor is essential to mechanical allodynia induced by PK2. First, intraplantar injection of high dose (3 or 10 pmol) of PK2 significantly increased paw withdrawal response frequency (%) to innocuous mechanical stimuli (mechanical allodynia). And the mechanical allodynia induced by PK2 was prevented by co-administration of TNP-ATP, a selective P2X receptor antagonist. Second, although low dose (0.3 or 1 pmol) of PK2 itself did not produce an allodynic response, it significantly facilitated the mechanical allodynia evoked by intraplantar injection of α,β-methylene ATP (α,β-meATP). Third, PK2 concentration-dependently potentiated α,β-meATP-activated currents in rat dorsal root ganglion (DRG) neurons. Finally, PK2 receptors and intracellular signal transduction were involved in PK2 potentiation of α,β-meATP-induced mechanical allodynia and α,β-meATP-activated currents, since the potentiation were blocked by PK2 receptor antagonist PKRA and selective PKC inhibitor GF 109203X. These results suggested that PK2 facilitated mechanical allodynia induced by α,β-meATP through a mechanism involved in sensitization of cutaneous P2X receptors expressed by nociceptive nerve endings.

  11. Differential regulation of peripheral IL-1β-induced mechanical allodynia and thermal hyperalgesia in rats.

    PubMed

    Kim, Min J; Lee, Sang Y; Yang, Kui Y; Nam, Soon H; Kim, Hyun J; Kim, Young J; Bae, Yong C; Ahn, Dong K

    2014-04-01

    This study examined the differential mechanisms of mechanical allodynia and thermal hyperalgesia after injection of interleukin (IL) 1β into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1β produced both mechanical allodynia and thermal hyperalgesia. Although a pretreatment with iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1β-induced mechanical allodynia, it significantly abolished IL-1β-induced thermal hyperalgesia. On the other hand, a pretreatment with D-AP5, an N-methyl-d-aspartate (NMDA) receptor antagonist, and NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, blocked IL-1β-induced mechanical allodynia. Pretreatment with H89, a protein kinase A (PKA) inhibitor, blocked IL-1β-induced mechanical allodynia but not thermal hyperalgesia. In contrast, pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor, inhibited IL-1β-induced thermal hyperalgesia. Subcutaneous injections of 2% lidocaine, a local anesthetic agent, blocked IL-1β-induced thermal hyperalgesia but not IL-1β-induced mechanical allodynia. In the resiniferatoxin (RTX)-pretreated rats, a subcutaneous injection of IL-1β did not produce thermal hyperalgesia due to the depletion of TRPV1 in the primary afferent fibers. Double immunofluorescence revealed the colocalization of PKA with neurofilament 200 (NF200) and of PKC with the calcitonin gene-related peptide (CGRP) in the trigeminal ganglion. Furthermore, NMDA receptor 1 (NR1) and TRPV1 predominantly colocalize with PKA and PKC, respectively, in the trigeminal ganglion. These results suggest that IL-1β-induced mechanical allodynia is mediated by sensitized peripheral NMDA/AMPA receptors through PKA-mediated signaling in the large-diameter primary afferent nerve fibers, whereas IL-1β-induced thermal hyperalgesia is mediated by sensitized peripheral TRPV1 receptors through PKC

  12. Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia.

    PubMed

    Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo

    2016-01-01

    Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain. PMID:27150152

  13. Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine.

    PubMed

    Dieb, W; Hafidi, A

    2013-09-01

    Trigeminal neuropathic pain affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying enhanced pain states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor-dependent changes play a critical role in triggering central sensitization in neuropathic pain. These receptors are regulated at the glycine site through a mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes. Therefore, the present study was carried out to determine whether astrocytes are involved, through D-serine secretion, in dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats. Two weeks after CCI-IoN, an important reaction of astrocytes was present in the medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine synthesis, which co-localized with its synthesis enzyme serine racemase, was strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D-amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O-sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain behavior in allodynic rats. These results demonstrate that astrocytes are involved in the modulation of orofacial post-traumatic neuropathic pain via the release of the gliotransmitter D-serine.

  14. Clonidine, an alpha-2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin-induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension.

    PubMed

    Yeo, Ji-Hee; Yoon, Seo-Yeon; Kim, Sol-Ji; Oh, Seog-Bae; Lee, Jang-Hern; Beitz, Alvin J; Roh, Dae-Hyun

    2016-05-15

    Cancer chemotherapy with platinum-based antineoplastic agents including oxaliplatin frequently results in a debilitating and painful peripheral neuropathy. We evaluated the antinociceptive effects of the alpha-2 adrenoceptor agonist, clonidine on oxaliplatin-induced neuropathic pain. Specifically, we determined if (i) the intraperitoneal (i.p.) injection of clonidine reduces mechanical allodynia in mice with an oxaliplatin-induced neuropathy and (ii) concurrent inhibition of p38 mitogen-activated protein kinase (MAPK) activity by the p38 MAPK inhibitor SB203580 enhances clonidine's antiallodynic effect. Clonidine (0.01-0.1 mg kg(-1), i.p.), with or without SB203580(1-10 nmol, intrathecal) was administered two weeks after oxaliplatin injection(10 mg kg(-1), i.p.) to mice. Mechanical withdrawal threshold, motor coordination and blood pressure were measured. Postmortem expression of p38 MAPK and ERK as well as their phosphorylated forms(p-p38 and p-ERK) were quantified 30 min or 4 hr after drug injection in the spinal cord dorsal horn of treated and control mice. Clonidine dose-dependently reduced oxaliplatin-induced mechanical allodynia and spinal p-p38 MAPK expression, but not p-ERK. At 0.1 mg kg(-1), clonidine also impaired motor coordination and decreased blood pressure. A 10 nmol dose of SB203580 alone significantly reduced mechanical allodynia and p-p38 MAPK expression, while a subeffective dose(3 nmol) potentiated the antiallodynic effect of 0.03 mg kg(-1) clonidine and reduced the increased p-p38 MAPK. Coadministration of SB203580 and 0.03 mg kg(-1) clonidine decreased allodynia similar to that of 0.10 mg kg(-1) clonidine, but without significant motor or vascular effects. These findings demonstrate that clonidine treatment reduces oxaliplatin-induced mechanical allodynia. The concurrent administration of SB203580 reduces the dosage requirements for clonidine, thereby alleviating allodynia without producing undesirable motor or cardiovascular effects.

  15. Mechanical and cold allodynia in a rat spinal cord contusion model.

    PubMed

    Yoon, Young Wook; Dong, Hongxin; Arends, Joop J A; Jacquin, Mark F

    2004-03-01

    This study examined the time course of mechanical and cold allodynia in rat hindpaw after spinal cord contusion. Hindpaw withdrawal threshold to graded von Frey hair stimulation and withdrawal frequency to acetone application were measured in rats subjected to contusions of varying severity, produced by a MASCIS impactor device with a 10 g weight dropped from 6.25, 12.5, or 25 mm. Mechanical and cold allodynia developed following the injury, and differences in the incidence of allodynia and in withdrawal threshold were significant among these groups. The least severe injury (6.25 mm) most consistently caused a decreased hindpaw threshold to mechanical stimulation and an increased withdrawal frequency to cold. PMID:15203971

  16. Comparison of mechanical allodynia and the affective component of inflammatory pain in rats.

    PubMed

    Boyce-Rustay, Janel M; Zhong, Chengmin; Kohnken, Rebecca; Baker, Scott J; Simler, Gricelda H; Wensink, Erica J; Decker, Michael W; Honore, Prisca

    2010-02-01

    Most animal models of pain cannot separate the sensory and affective components of pain. One model that has been used to assess affective pain is the place escape avoidance paradigm (PEAP). The aim of the current study is two-fold. First, validate PEAP with Complete Freund's Adjuvant (CFA)-induced inflammation for the assessment of the affective component of pain using the reference analgesics celecoxib, diclofenac and duloxetine; fluoxetine and scopolamine were tested as negative controls. Secondly, determine if there is a difference in efficacy in PEAP in comparison to the effects of the same compounds on von Frey-evoked mechanical allodynia in CFA animals. All compounds were tested in mechanical allodynia, place escape/avoidance, and for potentially confounding side effects in locomotor activity. Results show that celecoxib, diclofenac, and duloxetine significantly increased the time spent on the side associated with stimulation of the injured paw, whereas fluoxetine and scopolamine had no effect. Higher doses of celecoxib, diclofenac, duloxetine, and fluoxetine were required to attenuate von Frey-evoked mechanical allodynia. In the side effect assays, only fluoxetine decreased locomotor activity at doses used in PEAP. These results show that in inflammatory pain induced by CFA injection, PEAP is more sensitive to the effects of pain relieving compounds than mechanical allodynia. Fluoxetine showed efficacy in the mechanical allodynia test, but not PEAP, whereas duloxetine showed efficacy in mechanical allodynia and PEAP. These studies show that methods other than reflex based measures of pain such as affective pain models could be more predictive of efficacy/potency in the clinic.

  17. Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia

    PubMed Central

    Dieb, Wisam; Ouachikh, Omar; Durif, Franck; Hafidi, Aziz

    2014-01-01

    Background Pain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it. Aims We investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway. Results and discussion Lesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom. PMID:24944866

  18. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents.

  19. Involvement of mast cells and proteinase-activated receptor 2 in oxaliplatin-induced mechanical allodynia in mice.

    PubMed

    Sakamoto, Ayumi; Andoh, Tsugunobu; Kuraishi, Yasushi

    2016-03-01

    The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents. PMID:26804251

  20. Effects of repeated milnacipran and fluvoxamine treatment on mechanical allodynia in a mouse paclitaxel-induced neuropathic pain model.

    PubMed

    Katsuyama, Soh; Sato, Kazuma; Yagi, Tomomi; Kishikawa, Yukinaga; Nakamura, Hitoshi

    2013-04-01

    Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it frequently causes peripheral neuropathy. Milnacipran, a serotonin/noradrenaline reuptake inhibitor and fluvoxamine, a selective serotonin reuptake inhibitor, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of paclitaxel-induced mechanical allodynia in mice by milnacipran and fluvoxamine. Paclitaxel was administered once per day (2 mg/kg, intraperitoneally (i.p.)) for 5 days to mice. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In paclitaxel-treated mice, mechanical allodynia was observed on days 3-15 of paclitaxel administration. A single administration of milnacipran (20 mg/kg, i.p.) or fluvoxamine (40 mg/kg, i.p.) had no effect on paclitaxel- induced mechanical allodynia. However, repeated administration of milnacipran (10, 20 mg/kg, once per day, i.p.) for 5 days significantly reduced paclitaxel-induced mechanical allodynia. In contrast, repeated fluvoxamine administration (40 mg/kg, once per day, i.p.) for 5 days resulted in a weak attenuation of paclitaxel-induced mechanical allodynia. These results suggest that chronic paclitaxel administration induces mechanical allodynia, and that repeated milnacipran administration may be an effective therapeutic approach for the treatment of neuropathic pain caused by paclitaxel treatment for cancer.

  1. Peripherally injected linalool and bergamot essential oil attenuate mechanical allodynia via inhibiting spinal ERK phosphorylation.

    PubMed

    Kuwahata, Hikari; Komatsu, Takaaki; Katsuyama, Soh; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Sakurada, Shinobu; Sakurada, Tsukasa; Takahama, Kazuo

    2013-02-01

    Bergamot essential oil (BEO) is one of the most common essential oil containing linalool and linalyl acetate as major volatile components. This study investigated the effect of intraplantar (i.pl.) bergamot essential oil (BEO) or linalool on neuropathic hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. The i.pl. injection of BEO or linalool into the ipsilateral hindpaw to PSNL reduced PSNL-induced mechanical allodynia in a dose-dependent manner. Peripheral (i.pl.) injection of BEO or linalool into the contralateral hindpaw did not yield anti-allodynic effects, suggesting a local anti-mechanical allodynic effect of BEO or linalool in PSNL mice. Anti-mechanical hypersensitivity of morphine was enhanced by the combined injection of BEO or linalool at an ineffective dose when injected alone. We also examined the possible involvement of spinal extracellular signal-regulated protein kinase (ERK) in BEO or linalool-induced anti-mechanical allodynia. In western blotting analysis, i.pl. injection of BEO or linalool resulted in a significant blockade of spinal ERK activation induced by PSNL. These results suggest that i.pl. injection of BEO or linalool may reduce PSNL-induced mechanical allodynia followed by decreasing spinal ERK activation.

  2. Insular cortex representation of dynamic mechanical allodynia in trigeminal neuropathic rats.

    PubMed

    Alvarez, Pedro; Dieb, Wisam; Hafidi, Aziz; Voisin, Daniel L; Dallel, Radhouane

    2009-01-01

    Dynamic mechanical allodynia is a widespread symptom of neuropathic pain for which mechanisms are still poorly understood. The present study investigated the organization of dynamic mechanical allodynia processing in the rat insular cortex after chronic constriction injury to the infraorbital nerve (IoN-CCI). Two weeks after unilateral IoN-CCI, rats showed a dramatic bilateral trigeminal dynamic mechanical allodynia. Light, moving stroking of the infraorbital skin resulted in strong, bilateral upregulation of extracellular-signal regulated kinase phosphorylation (pERK-1/2) in the insular cortex of IoN-CCI animals but not sham rats, in whose levels were similar to those of unstimulated IoN-CCI rats. pERK-1/2 was located in neuronal cells only. Stimulus-evoked pERK-1/2 immunopositive cell bodies displayed rostrocaudal gradient and layer selective distribution in the insula, being predominant in the rostral insula and in layers II-III of the dysgranular and to a lesser extent, of the agranular insular cortex. In layers II-III of the rostral dysgranular insular cortex, intense pERK also extended into distal dendrites, up to layer I. These results demonstrate that trigeminal nerve injury induces a significant alteration in the insular cortex processing of tactile stimuli and suggest that ERK phosphorylation contributes to the mechanisms underlying abnormal pain perception under this condition.

  3. Intact cutaneous C fibre afferent properties in mechanical and cold neuropathic allodynia

    PubMed Central

    Hulse, Richard; Wynick, David; Donaldson, Lucy F.

    2010-01-01

    Patients with neuropathy, report changes in sensory perception, particularly mechanical and thermal allodynia, and spontaneous pain. Similar sensory changes are seen in experimental neuropathies, in which alteration in primary afferent properties can also be determined. The neural correlate of spontaneous pain is ongoing activity in sensory afferents. Mechanical and heat allodynia are thought to result from lowered activation thresholds in primary afferent and/or central neurones, but the mechanisms underlying cold allodynia are very poorly understood. We investigated nociceptive behaviours and the properties of C and A fibre intact afferents running adjacent to damaged afferents following a partial ligation injury of the saphenous nerve (PSNI). Animals developed mechanical and cold allodynia by 3 days after PSNI. Intact mechanosensitive C fibre afferents developed ongoing activity, and had slower conduction velocities 3 and 7 days following nerve injury, with no change in mechanical threshold. There was a large increase (∼46-fold) in calculated afferent input 3 days after nerve injury, as a result of the ongoing activity in these fibres. Mechano-cooling-sensitive C fibre afferents showed both enhanced cooling-evoked firing, and increased ongoing activity. The afferent barrage associated with mechano-cooling-sensitive afferents was increased 26-fold 7 days after nerve injury. We observed no differences in the properties of intact A fibre mechanosensitive afferents. These studies demonstrate for the first time that the altered nociception seen after PSNI is associated with ongoing activity and enhanced cooling-evoked activity in intact C fibre afferents in the saphenous nerve, with no concurrent alteration in A fibre afferents. PMID:19942464

  4. Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade

    PubMed Central

    Xu, Zhen-Zhong; Kim, Yong Ho; Bang, Sangsu; Zhang, Yi; Berta, Temugin; Wang, Fan; Oh, Seog Bae; Ji, Ru-Rong

    2016-01-01

    SUMMARY Mechanical allodynia, induced by normally innocuous low-threshold mechanical stimulation, represents a cardinal feature of neuropathic pain. Blockade or ablation of high-threshold small-diameter unmyelinated C-fibers has limited effects on mechanical allodynia1–4. While large myelinated A-fibers, in particular Aβ-fibers, have previously been implicated in mechanical allodynia5–7, an A-fiber-selective pharmacological blocker is still lacking. Here we report a new method for targeted silencing of A-fibers in neuropathic pain. We found that Toll-like receptor 5 (TLR5) is co-expressed with neurofilament-200 in large-diameter A-fiber neurons in the dorsal root ganglion (DRG). Activation of TLR5 with its ligand flagellin results in neuronal entry of the membrane impermeable lidocaine derivative QX-314, leading to TLR5-dependent blockade of sodium currents predominantly in A-fiber neurons of mouse DRGs. Intraplantar co-application of flagellin and QX-314 (flagellin/QX-314) dose-dependently suppressed mechanical allodynia following chemotherapy, nerve injury, and diabetic neuropathy, but this blockade is abrogated in Tlr5-deficient mice. In vivo electrophysiology demonstrated that flagellin/QX-314 co-application selectively suppressed Aβ-fiber conduction in naive and chemotherapy-treated mice. TLR5-mediated Aβ blockade but not capsaicin-mediated C-fiber blockade also reduced chemotherapy-induced ongoing pain without impairing motor function. Finally, flagellin/QX-314 co-application suppressed sodium currents in large-diameter human DRG neurons. Thus, our findings provide a new tool for targeted silencing of Aβ-fibers and neuropathic pain treatment. PMID:26479925

  5. Unique action mechanisms of tramadol in global cerebral ischemia-induced mechanical allodynia.

    PubMed

    Matsuura, Wataru; Kageyama, Erika; Harada, Shinichi; Tokuyama, Shogo

    2016-06-15

    Central poststroke pain is associated with specific somatosensory abnormalities, such as neuropathic pain syndrome. Although central poststroke pain is a serious condition, details pertaining to underlying mechanisms are not well established, making current standard treatments only partially effective. Here, we assessed the effects of tramadol, an analgesic drug mediated by opioid receptors, using a mouse model of global cerebral ischemia. Ischemia was induced by bilateral carotid artery occlusion (30 min) in male ddY mice. Development of hind-paw mechanical allodynia was measured 3 days after bilateral carotid artery occlusion using the von Frey test. Mechanical allodynia was significantly and dose dependently suppressed by intraperitoneal tramadol (10 or 20 mg/kg). These effects, which peaked at 10 min and continued for at least 60 min, were inhibited by naloxone (nonselective opioid receptor antagonist, 1 mg/kg, intraperitoneal). Tramadol antinociception was significantly negated by β-funaltrexamine (selective μ-opioid receptor antagonist, 20 mg/kg, intraperitoneal), but not naltrindole (selective δ-opioid receptor antagonist, 5 mg/kg, intraperitoneal) or nor-binaltorphimine (selective κ-opioid receptor antagonist, 10 mg/kg, intraperitoneal) after 5 min, by β-funaltrexamine and nor-binaltorphimine but not naltrindole after 10 min, and by all selective opioid receptor antagonists at 15 and 30 min after tramadol treatment. These results suggested that antinociception induced by tramadol through various opioid receptors was time dependent. Furthermore, it is possible that the opioid receptors involved in tramadol-induced antinociception change over time with the metabolism of this drug.

  6. Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation.

    PubMed

    Nassini, Romina; Gees, Maarten; Harrison, Selena; De Siena, Gaetano; Materazzi, Serena; Moretto, Nadia; Failli, Paola; Preti, Delia; Marchetti, Nicola; Cavazzini, Alberto; Mancini, Francesca; Pedretti, Pamela; Nilius, Bernd; Patacchini, Riccardo; Geppetti, Pierangelo

    2011-07-01

    Platinum-based anticancer drugs cause neurotoxicity. In particular, oxaliplatin produces early-developing, painful, and cold-exacerbated paresthesias. However, the mechanism underlying these bothersome and dose-limiting adverse effects is unknown. We hypothesized that the transient receptor potential ankyrin 1 (TRPA1), a cation channel activated by oxidative stress and cold temperature, contributes to mechanical and cold hypersensitivity caused by oxaliplatin and cisplatin. Oxaliplatin and cisplatin evoked glutathione-sensitive relaxation, mediated by TRPA1 stimulation and the release of calcitonin gene-related peptide from sensory nerve terminals in isolated guinea pig pulmonary arteries. No calcium response was observed in cultured mouse dorsal root ganglion neurons or in naïve Chinese hamster ovary (CHO) cells exposed to oxaliplatin or cisplatin. However, oxaliplatin, and with lower potency, cisplatin, evoked a glutathione-sensitive calcium response in CHO cells expressing mouse TRPA1. One single administration of oxaliplatin produced mechanical and cold hyperalgesia in rats, an effect selectively abated by the TRPA1 antagonist HC-030031. Oxaliplatin administration caused mechanical and cold allodynia in mice. Both responses were absent in TRPA1-deficient mice. Administration of cisplatin evoked mechanical allodynia, an effect that was reduced in TRPA1-deficient mice. TRPA1 is therefore required for oxaliplatin-evoked mechanical and cold hypersensitivity, and contributes to cisplatin-evoked mechanical allodynia. Channel activation is most likely caused by glutathione-sensitive molecules, including reactive oxygen species and their byproducts, which are generated after tissue exposure to platinum-based drugs from cells surrounding nociceptive nerve terminals.

  7. Central or peripheral delivery of an adenosine A1 receptor agonist improves mechanical allodynia in a mouse model of painful diabetic neuropathy.

    PubMed

    Katz, N K; Ryals, J M; Wright, D E

    2015-01-29

    Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8 weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N(6)-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of

  8. Ethnocultural allodynia.

    PubMed

    Comas-Díaz, L; Jacobsen, F M

    2001-01-01

    The authors introduce and define ethnocultural allodynia as an abnormally increased sensitivity to relatively innocuous or neutral stimuli resulting from previous exposure to painful culturally based situations. Ethnocultural, gender-specific, and cognitive-behavioral techniques are used in clinical vignettes to illustrate the pervasive ethnic, racial, and gender effects of ethnocultural allodynia in the lives of people of color. Therapy components for the treatment of ethnocultural allodynia are described, including psychoeducation regarding racism and its sequelae, racial socialization, inoculation, and racial stress management.

  9. Goshajinkigan reduces bortezomib-induced mechanical allodynia in rats: Possible involvement of kappa opioid receptor.

    PubMed

    Higuchi, Hitomi; Yamamoto, Shota; Ushio, Soichiro; Kawashiri, Takehiro; Egashira, Nobuaki

    2015-11-01

    In the present study, we investigated the effect of a Kampo medicine Goshajinkigan (GJG) on the bortezomib-induced mechanical allodynia in von Frey test in rats. The single administration of tramadol (10 mg/kg), GJG (1.0 g/kg) and its component processed Aconiti tuber (0.1 g/kg) significantly reversed the reduction in withdrawal threshold by bortezomib. These effects were abolished by the intrathecal injection of nor-binaltorphimine (10 μg/body), kappa opioid receptor antagonist. These findings suggest that kappa opioid receptor is involved in the effect of GJG on the bortezomib-induced mechanical allodynia.

  10. Lowering barometric pressure aggravates mechanical allodynia and hyperalgesia in a rat model of neuropathic pain.

    PubMed

    Sato, J; Morimae, H; Seino, Y; Kobayashi, T; Suzuki, N; Mizumura, K

    1999-04-30

    To examine the effects of meteorological change on the pain-related behaviors of neuropathic rats, animals with a chronic constriction injury (CCI) to the sciatic nerve were exposed to low barometric pressure (LP), 20 mmHg below the natural atmospheric pressure in a climate-controlled room. CCI caused a decreased hindpaw withdrawal threshold to von Frey hair (VFH) stimulation (mechanical allodynia) and prolonged duration of hindpaw withdrawal in response to pinprick stimulation (mechanical hyperalgesia). When the CCI rats were exposed to LP, both these pain-related behaviors were aggravated, whereas no change was seen in a group of controls. In the CCI rats sympathectomy inhibited this LP-induced augmentation of pain-related behaviors. These results show that LP intensifies the abnormalities in the pain-related behaviors of neuropathic rats, and that sympathetic activity contributes to the LP effect.

  11. Intraplantar PGE2 causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases

    PubMed Central

    Kassuya, C A L; Ferreira, J; Claudino, R F; Calixto, J B

    2007-01-01

    Background and purpose: Receptor subtypes involved in PGE2-induced nociception are still controversial. The present study investigated the prostanoid E receptor (EP) subtypes and the protein kinase (PK) pathways involved in the nociception induced by PGE2 injection in the mouse paw. Experimental approach: Paw-licking and mechanical allodynia were measured in vivo and protein kinase activation ex vivo by Western blots of extracts of paw skin. Key results: Intraplantar (i.pl.) injection of PGE2 into the mouse paw caused nociceptive behaviour of short duration with mean ED50 of 1.43 nmol. PGE2 produced a longer-lasting mechanical allodynia, with an ED50 of 0.05 nmol. Intraplantar injection of antagonists at EP3 or EP4, but not at EP1 or EP2 receptors inhibited PGE2-induced paw-licking. Paw-licking caused by PGE2 was blocked by an inhibitor of PKA but only partially decreased by inhibition of the extracellular-regulated kinase (ERK). Selective inhibitors of PKC, c-Jun N-terminal kinase (JNK) or p38, all failed to affect PGE2-induced paw-licking. An EP3 antagonist inhibited PGE2-induced mechanical allodynia. However, inhibitors of PKA, PKC or ERK, but not p38 or JNK, also partially inhibited PGE2-induced mechanical allodynia. Western blot analyses confirmed that i.pl. injection of PGE2 activated PKA, PKCα, and mitogen activated kinases (MAPKs) in the paw. Co-treatment with EP3 or EP4 receptor antagonists reduced PGE2-induced PKA and ERK, but not PKCα activation. Conclusions and Implications: The present results indicate that the nociceptive behaviour and mechanical allodynia caused by i.pl. PGE2 are mediated through activation of distinct EP receptors and PK-dependent mechanisms. PMID:17310141

  12. Spatio-Temporal Expression and Functional Involvement of Transient Receptor Potential Vanilloid 1 in Diabetic Mechanical Allodynia in Rats

    PubMed Central

    Wu, Huang-Hui; Qi, Jian; Shi, Juan; Li, Yun-Qing

    2014-01-01

    Diabetic neuropathic pain (DNP) is one of the most common clinical manifestations of diabetes mellitus (DM), which is characterized by prominent mechanical allodynia (DMA). However, the molecular mechanism underlying it has not fully been elucidated. In this study, we examined the spatio-temporal expression of a major nociceptive channel protein transient receptor potential vanilloid 1 (TRPV1) and analyzed its functional involvement by intrathecal (i.t.) application of TRPV1 antagonists in streptozocin (STZ)-induced DMA rat models. Western blot and immunofluorescent staining results showed that TRPV1 protein level was significantly increased in the soma of the dorsal root ganglion (DRG) neurons on 14 days after STZ treatment (DMA 14 d), whereas those in spinal cord and skin (mainly from the central and peripheral processes of DRG neurons) had already been enhanced on DMA 7 d to peak on DMA 14 d. qRT-PCR experiments confirmed that TRPV1 mRNA level was significantly up-regulated in the DRG on DMA 7 d, indicating a preceding translation of TRPV1 protein in the soma but preferential distribution of this protein to the processes under the DMA conditions. Cell counting assay based on double immunostaining suggested that increased TRPV1-immunoreactive neurons were likely to be small-sized and CGRP-ergic. Finally, single or multiple intrathecal applications of non-specific or specific TRPV1 antagonists, ruthenium red and capsazepine, at varying doses, effectively alleviated DMA, although the effect of the former was more prominent and long-lasting. These results collectively indicate that TRPV1 expression dynamically changes during the development of DMA and this protein may play important roles in mechanical nociception in DRG neurons, presumably through facilitating the release of CGRP. PMID:25020137

  13. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    PubMed

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.

  14. Berberine Ameliorates Allodynia Induced by Chronic Constriction Injury of the Sciatic Nerve in Rats.

    PubMed

    Kim, Hyun Jee

    2015-08-01

    The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model. PMID:25674823

  15. Burn injury-induced mechanical allodynia is maintained by Rac1-regulated dendritic spine dysgenesis.

    PubMed

    Tan, Andrew M; Samad, Omar A; Liu, Shujun; Bandaru, Samira; Zhao, Peng; Waxman, Stephen G

    2013-10-01

    Although nearly 11 million individuals yearly require medical treatment due to burn injuries and develop clinically intractable pain, burn injury-induced pain is poorly understood, with relatively few studies in preclinical models. To elucidate mechanisms of burn injury-induced chronic pain, we utilized a second-degree burn model, which produces a persistent neuropathic pain phenotype. Rats with burn injury exhibited reduced mechanical pain thresholds ipsilateral to the burn injury. Ipsilateral WDR neurons in the spinal cord dorsal horn exhibited hyperexcitability in response to a range of stimuli applied to their hindpaw receptive fields. Because dendritic spine morphology is strongly associated with synaptic function and transmission, we profiled dendritic spine shape, density, and distribution of WDR neurons. Dendritic spine dysgenesis was observed on ipsilateral WDR neurons in burn-injured animals exhibiting behavioral and electrophysiological evidence of neuropathic pain. Heat hyperalgesia testing produced variable results, as expected from previous studies of this model of second-degree burn injury in rats. Administration of Rac1-inhibitor, NSC23766, attenuated dendritic spine dysgenesis, decreased mechanical allodynia and electrophysiological signs of burn-induced neuropathic pain. These results support two related implications: that the presence of abnormal dendritic spines contributes to the maintenance of neuropathic pain, and that therapeutic targeting of Rac1 signaling merits further investigation as a novel strategy for pain management after burn injury.

  16. Tetrodotoxin suppresses thermal hyperalgesia and mechanical allodynia in a rat full thickness thermal injury pain model.

    PubMed

    Salas, Margaux M; McIntyre, Matthew K; Petz, Lawrence N; Korz, Walter; Wong, Donald; Clifford, John L

    2015-10-21

    Burn injuries have been identified as the primary cause of injury in 5% of U.S. military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom. Severe burn-associated pain is typically treated with opioids such as fentanyl, morphine, and methadone. Side effects of opioids include respiratory depression, cardiac depression, decrease in motor and cognitive function, as well as the development of hyperalgesia, tolerance and dependence. These effects have led us to search for novel analgesics for the treatment of burn-associated pain in wounded combat service members. Tetrodotoxin (TTX) is a selective voltage-gated sodium channel blocker currently in clinical trials as an analgesic. A phase 3 clinical trial for cancer-related pain has been completed and phase 3 clinical trials on chemotherapy-induced neuropathic pain are planned. It has also been shown in mice to inhibit the development of chemotherapy-induced neuropathic pain. TTX was originally identified as a neurotoxin in marine animals but has now been shown to be safe in humans at therapeutic doses. The antinociceptive effects of TTX are thought to be due to inhibition of Na(+) ion influx required for initiation and conduction of nociceptive impulses. One TTX sensitive sodium channel, Nav1.7, has been shown to be essential in lowering the heat pain threshold after burn injuries. To date, the analgesic effect of TTX has not been tested in burn-associated pain. Male Sprague-Dawley rats were subjected to a full thickness thermal injury on the right hind paw. TTX (8 μg/kg) was administered once a day systemically by subcutaneous injection beginning 3 days post thermal injury and continued through 7 days post thermal injury. Thermal hyperalgesia and mechanical allodynia were assessed 60 and 120 min post injection on each day of TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested and had a less robust, but statistically significant suppressive effect on mechanical

  17. Tetrodotoxin suppresses thermal hyperalgesia and mechanical allodynia in a rat full thickness thermal injury pain model.

    PubMed

    Salas, Margaux M; McIntyre, Matthew K; Petz, Lawrence N; Korz, Walter; Wong, Donald; Clifford, John L

    2015-10-21

    Burn injuries have been identified as the primary cause of injury in 5% of U.S. military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom. Severe burn-associated pain is typically treated with opioids such as fentanyl, morphine, and methadone. Side effects of opioids include respiratory depression, cardiac depression, decrease in motor and cognitive function, as well as the development of hyperalgesia, tolerance and dependence. These effects have led us to search for novel analgesics for the treatment of burn-associated pain in wounded combat service members. Tetrodotoxin (TTX) is a selective voltage-gated sodium channel blocker currently in clinical trials as an analgesic. A phase 3 clinical trial for cancer-related pain has been completed and phase 3 clinical trials on chemotherapy-induced neuropathic pain are planned. It has also been shown in mice to inhibit the development of chemotherapy-induced neuropathic pain. TTX was originally identified as a neurotoxin in marine animals but has now been shown to be safe in humans at therapeutic doses. The antinociceptive effects of TTX are thought to be due to inhibition of Na(+) ion influx required for initiation and conduction of nociceptive impulses. One TTX sensitive sodium channel, Nav1.7, has been shown to be essential in lowering the heat pain threshold after burn injuries. To date, the analgesic effect of TTX has not been tested in burn-associated pain. Male Sprague-Dawley rats were subjected to a full thickness thermal injury on the right hind paw. TTX (8 μg/kg) was administered once a day systemically by subcutaneous injection beginning 3 days post thermal injury and continued through 7 days post thermal injury. Thermal hyperalgesia and mechanical allodynia were assessed 60 and 120 min post injection on each day of TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested and had a less robust, but statistically significant suppressive effect on mechanical

  18. Bilateral mechanical and thermal hyperalgesia and tactile allodynia after chronic compression of dorsal root ganglion in mice.

    PubMed

    Chen, Rong-Gui; Kong, Wei-Wei; Ge, Da-Long; Luo, Ceng; Hu, San-Jue

    2011-08-01

    OBJECTIVE Low back pain is one of the most inextricable problems encountered in clinics. Animal models that imitate symptoms in humans are valuable tools for investigating low back pain mechanisms and the possible therapeutic applications. With the development of genetic technology in pain field, the possibility of mutating specific genes in mice has provided a potent tool for investigating the specific mechanisms of pain. The aim of the present study was to develop a mouse model of chronic compression of dorsal root ganglion (CCD), in which gene mutation can be applied to facilitate the studies of chronic pain. METHODS Chronic compression of L4 and L5 dorsal root ganglia was conducted in mice by inserting fine stainless steel rods into the intervertebral foramina, one at L4 and the other at L5. Mechanical allodynia and thermal hyperalgesia were examined with von Frey filaments and radiating heat stimulator, respectively. RESULTS The CCD mice displayed dramatic mechanical and thermal hyperalgesia as well as tactile allodynia in the hindpaw ipsilateral to CCD. In addition, this mechanical and thermal hyperalgesia as well as tactile allodynia was also found to spread to the contralateral hindpaw. CONCLUSION This model, combined with the possible genetic modification, will strengthen our knowledge of the underlying mechanisms of low back pain. It also favors the development of new treatment strategies for pain and hyperalgesia after spinal injury and other disorders which affect the dorsal root ganglion in humans. PMID:21788994

  19. Systemic Administration of Propentofylline, Ibudilast, and (+)-Naltrexone Each Reverses Mechanical Allodynia in a Novel Rat Model of Central Neuropathic Pain

    PubMed Central

    Ellis, Amanda; Wieseler, Julie; Favret, Jacob; Johnson, Kirk W.; Rice, Kenner C.; Maier, Steven F.; Falci, Scott; Watkins, Linda R.

    2014-01-01

    Central neuropathic pain (CNP) is a debilitating consequence of central nervous system (CNS) damage for which current treatments are ineffective. To explore mechanisms underlying CNP, we developed a rat model involving T13/L1 dorsal root avulsion. The resultant dorsal horn damage creates bilateral below-level (L4-6) mechanical allodynia. This allodynia, termed spinal neuropathic avulsion pain (SNAP), occurs in the absence of confounding paralysis. To characterize this model, we undertook a series of studies aimed at defining whether SNAP could be reversed by any of 3 putative glial activation inhibitors, each with distinct mechanisms of action. Indeed, the phosphodiesterase inhibitor propentofylline, the macrophage migration inhibitory factor (MIF) inhibitor ibudilast, and the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone each reversed below-level allodynia bilaterally. Strikingly, none of these impacted SNAP upon first administration but required 1–2 wk of daily administration before pain reversal was obtained. Given reversal of CNP by each of these glial modulatory agents, these results suggest that glia contribute to the maintenance of such pain and enduring release of MIF and endogenous agonists of TLR4 is important for sustaining CNP. The markedly delayed efficacy of all 3 glial modulatory drugs may prove instructive for interpretation of apparent drug failures after shorter dosing regimens. PMID:24412802

  20. Unity vs. diversity of neuropathic pain mechanisms: Allodynia and hyperalgesia in rats selected for heritable predisposition to spontaneous pain.

    PubMed

    Ziv-Sefer, Sagit; Raber, Pnina; Barbash, Shahar; Devor, Marshall

    2009-11-01

    Do contrasting neuropathic pain diagnoses share common pathophysiological mechanisms? Selective breeding was used to derive rat lines with a common genetic background but a striking difference in the degree of spontaneous pain behavior expressed in the neuroma model of neuropathic pain (HA rats (high autotomy) and LA rats (low autotomy)). The contrasting pain phenotype in these lines is attributable to allelic differences at a small number of genetic loci. Here we show that HA and LA rats also differ in their nocifensive response to applied stimuli in the Chung (spinal nerve ligation, SNL) model of neuropathic pain. This includes tactile allodynia and hyperalgesia, and heat allodynia. The degree of hypersensibility varied with sex, age at the time of nerve injury, and the extent of the nerve lesion. F1 crosses of HA and LA rats and inbred Lewis rats showed low levels of autotomy but variable levels of hypersensibility to applied stimuli. Results indicate that alleles which predispose to spontaneous neuropathic pain also predispose to stimulus-evoked pain (allodynia and hyperalgesia). This, in turn, suggests that despite contrasting etiology and behavioral endpoints, pain phenotype in the neuroma and the SNL models shares common pathophysiological mechanisms. PMID:19683390

  1. Activation of medullary dorsal horn γ isoform of protein kinase C interneurons is essential to the development of both static and dynamic facial mechanical allodynia.

    PubMed

    Pham-Dang, Nathalie; Descheemaeker, Amélie; Dallel, Radhouane; Artola, Alain

    2016-03-01

    The γ isoform of protein kinase C (PKCγ), which is concentrated in a specific class of interneurons within inner lamina II (IIi ) of the spinal dorsal horn and medullary dorsal horn (MDH), is known to be involved in the development of mechanical allodynia, a widespread and intractable symptom of inflammatory or neuropathic pain. However, although genetic and pharmacological impairment of PKCγ were shown to prevent mechanical allodynia in animal models of pain, after nerve injury or reduced inhibition, the functional consequences of PKCγ activation alone on mechanical sensitivity are still unknown. Using behavioural and anatomical approaches in the rat MDH, we tested whether PKCγ activation in naive animals is sufficient for the establishment of mechanical allodynia. Intracisternal injection of the phorbol ester, 12,13-dibutyrate concomitantly induced static as well as dynamic facial mechanical allodynia. Monitoring neuronal activity within the MDH with phospho-extracellular signal-regulated kinases 1 and 2 immunoreactivity revealed that activation of both lamina I-outer lamina II and IIi -outer lamina III neurons, including lamina IIi PKCγ-expressing interneurons, was associated with the manifestation of mechanical allodynia. Phorbol ester, 12,13-dibutyrate-induced mechanical allodynia and associated neuronal activations were all prevented by inhibiting selectively segmental PKCγ with KIG31-1. Our findings suggest that PKCγ activation, without any other experimental manipulation, is sufficient for the development of static and dynamic mechanical allodynia. Lamina IIi PKCγ interneurons have been shown to be directly activated by low-threshold mechanical inputs carried by myelinated afferents. Thus, the level of PKCγ activation within PKCγ interneurons might gate the transmission of innocuous mechanical inputs to lamina I, nociceptive output neurons, thus turning touch into pain.

  2. Effect of omega-3 polyunsaturated fatty acid treatment over mechanical allodynia and depressive-like behavior associated with experimental diabetes.

    PubMed

    Redivo, Daiany D B; Schreiber, Anne K; Adami, Eliana R; Ribeiro, Deidiane E; Joca, Samia R L; Zanoveli, Janaína M; Cunha, Joice M

    2016-02-01

    Neuropathic pain and depression are very common comorbidities in diabetic patients. As the pathophysiological mechanisms are very complex and multifactorial, current treatments are only symptomatic and often worsen the glucose control. Thus, the search for more effective treatments are extremely urgent. In this way, we aimed to investigate the effect of chronic treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, over the mechanical allodynia and in depressive-like behaviors in streptozotocin-diabetic rats. It was observed that the diabetic (DBT) animals, when compared to normoglycemic (NGL) animals, developed a significant mechanical allodynia since the second week after diabetes induction, peaking at fourth week which is completely prevented by FO treatment (0.5, 1 or 3g/kg). Moreover, DBT animals showed an increase of immobility frequency and a decrease of swimming and climbing frequencies in modified forced swimming test (MFST) since the second week after diabetes injection, lasting up at the 4th week. FO treatment (only at a dose of 3g/kg) significantly decreased the immobility frequency and increased the swimming frequency, but did not induce significant changes in the climbing frequency in DBT rats. Moreover, it was observed that DBT animals had significantly lower levels of BDNF in both hippocampus and pre frontal cortex when compared to NGL rats, which is completely prevented by FO treatment. In conclusion, our study demonstrates that FO treatment was able to prevent the mechanical allodynia and the depressive-like behaviors in DBT rats, which seems to be related to its capacity of BDNF level restoration.

  3. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    SciTech Connect

    Tong, Wei; Wang, Wei; Huang, Jing; Ren, Ning; Wu, Sheng-Xi; Li, Yong-Qi

    2010-05-14

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1{beta} was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1{beta} was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1{beta}. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1{beta} expression and thus modulating spinal excitatory synaptic transmission and pain response.

  4. Glycemia-dependent Nuclear Factor κB Activation Contributes to Mechanical Allodynia in Rats with Chronic Postischemia Pain

    PubMed Central

    Ross-Huot, Marie-Christine; Laferrière, André; Khorashadi, Mina; Coderre, Terence J.

    2015-01-01

    Background Ischemia-reperfusion injury causes chronic postischemia pain (CPIP), and rats with higher glycemia during ischemia-reperfusion injury exhibit increased allodynia. Glycemia-induced elevation of nuclear factor kappa-B (NFκB) may contribute to increased allodynia. Methods Glycemia during a 3 h ischemia-reperfusion injury was manipulated by: normal feeding; or normal feeding with administration of insulin; dextrose; or insulin/dextrose. In these groups, NFκB was measured in ipsilateral hind paw muscle and spinal dorsal horn by ELISA, and SN50, an NFκB inhibitor, was administered to determine its differential anti-allodynic effects depending on glycemia. Results CPIP fed/insulin rats (12.03 ± 4.9, N = 6) had less allodynia than fed, fed/insulin/dextrose and fed/dextrose rats (6.29 ± 3.37 N = 7, 4.57 ± 3.03 g, N = 6, 2.95 ± 1.10, N = 9), respectively. Compared to fed rats (0.209 ± 0.022, N = 7), NFκB in ipsilateral plantar muscles was significantly lower for fed/insulin rats and significantly higher for fed/dextrose rats (0.152 ± 0.053, N = 6; 0.240 ± 0.057, N = 7, respectively). Furthermore, NFκB in the dorsal horn of fed, fed/insulin/dextrose and fed/dextrose rats (0.293 ± 0.049, N = 6) was significantly higher than in fed/insulin animals (0.267 ± 0.037, N = 6). The anti-allodynic SN50 dose-response curves of CPIP rats in the fed/insulin/dextrose, fed/dextrose and fed conditions exhibited a rightward shift compared to the fed/insulin group. The threshold SN50 dose of CPIP fed/dextrose, fed/insulin/dextrose and fed rats (328.94 ± 92.4, 77.80 ± 44.50 and 24.89 ± 17.20, respectively) was higher than that for fed/insulin rats (4.06 ± 7.04). Conclusions NFκB was activated in a glycemia-dependent manner in CPIP rats. Hypoglycemic rats were more sensitive to SN50 than rats with higher glycemia. The finding that SN50 reduces mechanical allodynia suggests that NFκB inhibitors might be useful for treating postischemia pain. PMID:23695173

  5. Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity

    PubMed Central

    Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

    2016-01-01

    Background The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R−/−) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. Results At baseline, CB1R−/− mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R−/− mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R−/− mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/−) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R−/− mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different

  6. A streptozotocin-induced diabetic neuropathic pain model for static or dynamic mechanical allodynia and vulvodynia: validation using topical and systemic gabapentin.

    PubMed

    Ali, Gowhar; Subhan, Fazal; Abbas, Muzaffar; Zeb, Jehan; Shahid, Muhammad; Sewell, Robert D E

    2015-11-01

    Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5-29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin.

  7. Acute single dose of ketamine relieves mechanical allodynia and consequent depression-like behaviors in a rat model.

    PubMed

    Zhang, Guang-Fen; Wang, Jing; Han, Jin-Feng; Guo, Jie; Xie, Ze-Min; Pan, Wei; Yang, Jian-Jun; Sun, Kang-Jian

    2016-09-19

    Both chronic pain and depression are debilitating diseases, which often coexist in clinic. However, current analgesics and antidepressants exhibit limited efficacy for this comorbidity. The present study aimed to investigate the effect of ketamine on the comorbidity of inflammatory pain and consequent depression-like behaviors in a rat model established by intraplantar administration of complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal withdrawal latency, open field test, forced swimming test, and sucrose preference test were evaluated after the CFA injection and ketamine treatment. The hippocampus was harvested to determine the levels of interleukin (IL)-6, IL-1β, indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), 5-hydroxytryptamine (5-HT), and tryptophan (TRP). The inflammatory pain-induced depression-like behaviors presented on 7days and lasted to at least 14days after the CFA injection. Single dose of ketamine at 20mg/kg relieved both the mechanical allodynia and the associated depression-like behaviors as demonstrated by the attenuated mechanical withdrawal threshold, reduced immobility time in the forced swim test, and increased sucrose preference after ketamine treatment. The total distance had no significant change after the CFA injection or ketamine treatment in the open field test. Simultaneously, ketamine reduced the levels of IL-6, IL-1β, IDO, and KYN/TRP ratio and increased the 5-HT/TRP ratio in the hippocampus. In conclusion, acute single dose of ketamine can rapidly attenuate mechanical allodynia and consequent depression-like behaviors and down-regulate hippocampal proinflammatory responses and IDO/KYN signal pathway in rats. PMID:27497920

  8. A partial L5 spinal nerve ligation induces a limited prolongation of mechanical allodynia in rats: an efficient model for studying mechanisms of neuropathic pain.

    PubMed

    Guan, Yun; Yuan, Frank; Carteret, Alene F; Raja, Srinivasa N

    2010-02-26

    The relationship between pain severity and the extent of injury to a peripheral nerve remains elusive. In this study, we compared the pain behavior resulting from partial (1/3-1/2 thickness) and full L5 spinal nerve ligation (SNL) in rats. The decrease in paw withdrawal threshold (PWT) to mechanical stimuli in the hindpaw ipsilateral to the injury was comparable in the two groups on days 3-21 post-injury. However, the decreased PWT recovered earlier in the partial SNL group than in the full SNL group. These observations suggest that the duration of neuropathic pain behavior, but not the early development of mechanical allodynia, is dependent on the extent of nerve injury. On days 6 and 15 post-injury, when the mechanical allodynia was similar in the two groups, systemic morphine induced a greater reduction of mechanical allodynia in the partial SNL group than in the full SNL group. Furthermore, in partial SNL rats, at post-injury time points when they had largely recovered from the neuropathic pain state, systemic administration of naloxone hydrochloride (day 53) or naloxone methiodide (a non-selective peripherally acting opioid receptor antagonist; day 64) or intra-plantar injection of naloxone methiodide rekindled mechanical pain hypersensitivity in the ipsilateral hindpaw, suggesting a prolonged activation of endogenous opioidergic pain-inhibition. Therefore, partial SNL in rats may represent an efficient model for studying the mechanisms of neuropathic pain, testing effects of analgesic/antihyperalgesic drugs, and understanding endogenous pain-inhibitory mechanisms that lead to reversal of the pain behavior with time.

  9. Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

    PubMed

    Hewitt, Ellen; Pitcher, Thomas; Rizoska, Biljana; Tunblad, Karin; Henderson, Ian; Sahlberg, Britt-Louise; Grabowska, Urszula; Classon, Björn; Edenius, Charlotte; Malcangio, Marzia; Lindström, Erik

    2016-09-01

    Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beam walking. MIV-247, gabapentin, and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 µmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 µmol/kg) and pregabalin (63-377 µmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 µmol/kg) in combination with the minimum effective dose of pregabalin (75 µmol/kg) or gabapentin (146 µmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 µmol/kg) in combination with a subeffective dose of pregabalin (38 µmol/kg) or gabapentin (73 µmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions.

  10. Antibody directed against GD(2) produces mechanical allodynia, but not thermal hyperalgesia when administered systemically or intrathecally despite its dependence on capsaicin sensitive afferents.

    PubMed

    Sorkin, L S; Yu, A L; Junger, H; Doom, C M

    2002-03-15

    Anti-GD(2) antibodies have been shown to be effective for immunotherapy of neuroblastoma and other GD(2) enriched malignancies. Infusion of anti-GD(2) antibodies frequently causes spontaneous pain and allodynia for the duration of the immunotherapy and occasionally longer lasting neuropathic pain. Bolus intravenous injection of anti-GD(2) in rats initiates mechanical allodynia as measured by withdrawal threshold of the hindpaws. In this study, thermal thresholds were measured prior to and for up to 6 h following systemic anti-GD(2) administration in adult rats. In addition, both thermal and mechanical thresholds were tested following intrathecal administration of anti-GD(2) and IgG(2a). Murine anti-GD(2) elicited mechanical allodynia when administered into either the vasculature or the intrathecal space. Effective systemic doses were 1--3 mg/kg as previously shown. Intrathecally, optimal doses ranged from 0.01 to 0.1 ng; a higher dose was ineffective. Thermal hyperalgesia was not observed via either route of administration. Intrathecal pretreatment 48--72 h prior to the experiment with capsaicin at doses sufficient to cause a 50% depletion of dorsal horn CGRP, caused a total blockade of the mechanical allodynia indicating an involvement of peptidergic fine afferent fibers. It is likely that the antibody reacts with an antigen on peripheral nerve and/or myelin to initiate its effect. The lack of observed thermal hyperalgesia is surprising especially in light of the capsaicin-associated blockade, however, it is consistent with several other immune system related models of pain.

  11. Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

    PubMed

    Hewitt, Ellen; Pitcher, Thomas; Rizoska, Biljana; Tunblad, Karin; Henderson, Ian; Sahlberg, Britt-Louise; Grabowska, Urszula; Classon, Björn; Edenius, Charlotte; Malcangio, Marzia; Lindström, Erik

    2016-09-01

    Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beam walking. MIV-247, gabapentin, and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 µmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 µmol/kg) and pregabalin (63-377 µmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 µmol/kg) in combination with the minimum effective dose of pregabalin (75 µmol/kg) or gabapentin (146 µmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 µmol/kg) in combination with a subeffective dose of pregabalin (38 µmol/kg) or gabapentin (73 µmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions. PMID:27335437

  12. Co- transplantation of Bone Marrow Stromal Cells with Schwann Cells Evokes Mechanical Allodynia in the Contusion Model of Spinal Cord Injury in Rats

    PubMed Central

    Pourheydar, Bagher; Joghataei, Mohammad Taghi; Bakhtiari, Mehrdad; Mehdizadeh, Mehdi; Yekta, Zahra; Najafzadeh, Norooz

    2012-01-01

    functioning but greater Allodynia compared to the other experimental groups. Conclusion: The present study has shown that, although transplantation of BMSCs, SCs and a combination of these cells into the injured rat spinal cord can improve functional recovery, it leads to the development of mechanical Allodynia. This finding indicates that strategies to reduce Allodynia in cell transplantation studies are required. PMID:23508042

  13. Etodolac, a cyclooxygenase-2 inhibitor, attenuates paclitaxel-induced peripheral neuropathy in a mouse model of mechanical allodynia.

    PubMed

    Ito, Sunao; Tajima, Koyuki; Nogawa, Masaki; Inoue, Naoki; Kyoi, Takashi; Takahashi, Yosuke; Sasagawa, Takahiro; Nakamura, Akio; Kotera, Takashi; Ueda, Makoto; Yamashita, Yasuhiro; Banno, Kouji

    2012-07-01

    The effect of the cyclooxygenase-2 (COX-2) inhibitor etodolac on the mechanical allodynia induced by paclitaxel was investigated in mice and compared with the effects of the nonselective COX inhibitors indomethacin and diclofenac, the selective COX-2 inhibitor celecoxib, the calcium channel α(2)δ subunit inhibitor pregabalin, the sodium channel blocker mexiletine, and the serotonin-norepinephrine reuptake inhibitor duloxetine. The decrease in the paw-withdrawal threshold induced by paclitaxel was reversed by oral administration of etodolac at 10 mg/kg but was not affected by indomethacin, diclofenac, or celecoxib. The antiallodynic effect of etodolac gradually increased during repeated administration, and after 2 weeks the paw-withdrawal threshold at the preadministration point was significantly increased. Pregabalin, duloxetine, and mexiletine also showed an antiallodynic effect in this model. Whereas pregabalin had a preadministration effect similar to that of etodolac during repeated administration, mexiletine or duloxetine had no such effect. There was almost no difference in the distribution of etodolac and diclofenac in nervous tissue, indicating that COX inhibition is unlikely to be involved in the antiallodynic effect of etodolac. Etodolac did not show a neuroprotective effect against morphological transformations such as the axonal degeneration induced by paclitaxel. Instead, etodolac probably acts at the level of functional changes accompanying paclitaxel treatment, such as alterations in the activation state of components of the pain transmission pathway. Our findings suggest that etodolac attenuates paclitaxel-induced peripheral neuropathy by a COX-independent pathway and that it might be useful for the treatment of paclitaxel-induced peripheral neuropathy. PMID:22460833

  14. Human Adipose Stem Cells Improve Mechanical Allodynia and Enhance Functional Recovery in a Rat Model of Neuropathic Pain.

    PubMed

    Lee, Hye Yeong; Lee, Hye-Lan; Yun, Yeomin; Kim, Jin-Su; Ha, Yoon; Yoon, Do Heum; Lee, Soo-Hong; Shin, Dong Ah

    2015-07-01

    Stem cells are a promising source of tissue engineering due to their differentiation potential. Today, direct transplantation of stem cells for cell therapy is commonly performed. However, in cases of nerve injury, direct transplantation of cells could lead to secondary nerve damage. Male Sprague-Dawley rats were randomized into four groups: the phosphate-buffered saline epineural transplantation (PBS-ENT) group, the PBS intraneural transplantation (PBS-INT) group, the human adipose-derived stem cells epineural transplantation (hASCs-ENT) group, and human adipose-derived stem cells intraneural transplantation (hASCs-INT) group. Transplantation was conducted 1 week later after inflicting a crush injury with subsequent observation for 5 weeks. To evaluate pain, each group was examined with regard to paw withdrawal latency and evoked potentials. The sciatic functional index (SFI) was calculated to estimate functional recovery. The sciatic nerve was also examined histologically. The hASCs-ENT group showed a more rapid paw withdrawal threshold and SFI recovery than the other groups (p<0.05). The hASCs-ENT group also showed shorter initial latencies in both somatosensory evoked potential (SSEP) and motor evoked potential (MEP) than the PBS-INT group (p<0.05). In addition, the N1 latency of the MEP and the N1 and P1 latencies of the SSEP were significantly shorter than those of the PBS-INT group (p<0.05). Histological examination revealed that the transplanted groups showed better neural recovery and remyelination than the groups injected with PBS. These results show that the transplantation of hASCs into the injured sciatic nerve improved mechanical allodynia and functional recovery as determined by the paw withdrawal test, SFI analysis, and electrophysiological studies. ENT is superior to INT in terms of invasiveness and better outcomes.

  15. Human Adipose Stem Cells Improve Mechanical Allodynia and Enhance Functional Recovery in a Rat Model of Neuropathic Pain.

    PubMed

    Lee, Hye Yeong; Lee, Hye-Lan; Yun, Yeomin; Kim, Jin-Su; Ha, Yoon; Yoon, Do Heum; Lee, Soo-Hong; Shin, Dong Ah

    2015-07-01

    Stem cells are a promising source of tissue engineering due to their differentiation potential. Today, direct transplantation of stem cells for cell therapy is commonly performed. However, in cases of nerve injury, direct transplantation of cells could lead to secondary nerve damage. Male Sprague-Dawley rats were randomized into four groups: the phosphate-buffered saline epineural transplantation (PBS-ENT) group, the PBS intraneural transplantation (PBS-INT) group, the human adipose-derived stem cells epineural transplantation (hASCs-ENT) group, and human adipose-derived stem cells intraneural transplantation (hASCs-INT) group. Transplantation was conducted 1 week later after inflicting a crush injury with subsequent observation for 5 weeks. To evaluate pain, each group was examined with regard to paw withdrawal latency and evoked potentials. The sciatic functional index (SFI) was calculated to estimate functional recovery. The sciatic nerve was also examined histologically. The hASCs-ENT group showed a more rapid paw withdrawal threshold and SFI recovery than the other groups (p<0.05). The hASCs-ENT group also showed shorter initial latencies in both somatosensory evoked potential (SSEP) and motor evoked potential (MEP) than the PBS-INT group (p<0.05). In addition, the N1 latency of the MEP and the N1 and P1 latencies of the SSEP were significantly shorter than those of the PBS-INT group (p<0.05). Histological examination revealed that the transplanted groups showed better neural recovery and remyelination than the groups injected with PBS. These results show that the transplantation of hASCs into the injured sciatic nerve improved mechanical allodynia and functional recovery as determined by the paw withdrawal test, SFI analysis, and electrophysiological studies. ENT is superior to INT in terms of invasiveness and better outcomes. PMID:25857679

  16. Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia

    PubMed Central

    Koyanagi, Satoru; Kusunose, Naoki; Taniguchi, Marie; Akamine, Takahiro; Kanado, Yuki; Ozono, Yui; Masuda, Takahiro; Kohro, Yuta; Matsunaga, Naoya; Tsuda, Makoto; Salter, Michael W.; Inoue, Kazuhide; Ohdo, Shigehiro

    2016-01-01

    Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn. We identify serum- and glucocorticoid-inducible kinase-1 (SGK-1) as the key molecule responsible for the glucocorticoid-enhanced release of ATP from astrocytes. SGK-1 protein levels in spinal astrocytes are increased in response to glucocorticoid stimuli and enhanced ATP release by opening the pannexin-1 hemichannels. Our findings reveal an unappreciated circadian machinery affecting pain hypersensitivity caused by peripheral nerve injury, thus opening up novel approaches to the management of chronic pain. PMID:27739425

  17. Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats

    PubMed Central

    2013-01-01

    Background We have previously shown a sprouting of sympathetic fibers into the upper dermis of the skin following subcutaneous injection of complete Freund’s adjuvant (CFA) into the hindpaw. This sprouting correlated with an increase in pain-related sensitivity. We hypothesized that this sprouting and pain-related behavior were caused by an increase in nerve growth factor (NGF) levels. In this study, we investigated whether the inhibition of mature NGF degradation, using a matrix metalloproteinase 2 and 9 (MMP-2/9) inhibitor, was sufficient to reproduce a similar phenotype. Results Behavioral tests performed on male Sprague–Dawley rats at 1, 3, 7 and 14 days after intra-plantar MMP-2/9 inhibitor administration demonstrated that acute and chronic injections of the MMP-2/9 inhibitor induced sensitization, in a dose dependent manner, to mechanical, hot and cold stimuli as measured by von Frey filaments, Hargreaves and acetone tests, respectively. Moreover, the protein levels of mature NGF (mNGF) were increased, whereas the levels and enzymatic activity of matrix metalloproteinase 9 were reduced in the glabrous skin of the hind paw. MMP-2/9 inhibition also led to a robust sprouting of sympathetic fibers into the upper dermis but there were no changes in the density of peptidergic nociceptive afferents. Conclusions These findings indicate that localized MMP-2/9 inhibition provokes a pattern of sensitization and fiber sprouting comparable to that previously obtained following CFA injection. Accordingly, the modulation of endogenous NGF levels should be considered as a potential therapeutic target for the management of inflammatory pain associated with arthritis. PMID:23889761

  18. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury.

    PubMed

    Green, Dustin; Ruparel, Shivani; Gao, Xiaoli; Ruparel, Nikita; Patil, Mayur; Akopian, Armen; Hargreaves, Kenneth

    2016-01-01

    The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in the spinal cord. Accordingly, we evaluated whether burn injury evoked the central release of oxidized lipids . Analysis of lipid extracts of spinal cord tissue with HPLC-MS revealed a significant increase in levels of the epoxide and diol metabolites of linoleic acid: 9,10-DiHOME, 12,13-DiHOME, 9(10)-EpOME, and 12(13)-EpOME, that was reduced after intrathecal (i.t.) injection of the oxidative enzyme inhibitor ketoconazole. Moreover, we found that these four lipid metabolites were capable of specifically activating both TRPV1 and TRPA1. Intrathecal injection of specific antagonists to TRPV1 (AMG-517) or TRPA1 (HC-030031) significantly reduced post-burn mechanical and thermal allodynia. Finally, i.t. injection of ketoconazole significantly reversed post-burn mechanical and thermal allodynia. Our data indicate that spinal cord TRPV1 and TRPA1 contributes to pain after burn and identifies a novel class of oxidized lipids elevated in the spinal cord after burn injury. Since the management of burn pain is problematic, these findings point to a novel approach for treating post-burn pain.

  19. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical and thermal allodynia after burn injury

    PubMed Central

    Green, Dustin P; Ruparel, Shivani; Gao, Xiaoli; Ruparel, Nikita; Patil, Mayur; Akopian, Armen

    2016-01-01

    The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in the spinal cord. Accordingly, we evaluated whether burn injury evoked the central release of oxidized lipids. Analysis of lipid extracts of spinal cord tissue with HPLC-MS revealed a significant increase in levels of the epoxide and diol metabolites of linoleic acid: 9,10-DiHOME, 12,13-DiHOME, 9(10)-EpOME, and 12(13)-EpOME, that was reduced after intrathecal (i.t.) injection of the oxidative enzyme inhibitor ketoconazole. Moreover, we found that these four lipid metabolites were capable of specifically activating both TRPV1 and TRPA1. Intrathecal injection of specific antagonists to TRPV1 (AMG-517) or TRPA1 (HC-030031) significantly reduced post-burn mechanical and thermal allodynia. Finally, i.t. injection of ketoconazole significantly reversed post-burn mechanical and thermal allodynia. Our data indicate that spinal cord TRPV1 and TRPA1 contributes to pain after burn and identifies a novel class of oxidized lipids elevated in the spinal cord after burn injury. Since the management of burn pain is problematic, these findings point to a novel approach for treating post-burn pain. PMID:27411353

  20. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury.

    PubMed

    Green, Dustin; Ruparel, Shivani; Gao, Xiaoli; Ruparel, Nikita; Patil, Mayur; Akopian, Armen; Hargreaves, Kenneth

    2016-01-01

    The primary complaint of burn victims is an intense, often devastating spontaneous pain, with persistence of mechanical and thermal allodynia. The transient receptor potential channels, TRPV1 and TRPA1, are expressed by a subset of nociceptive sensory neurons and contribute to inflammatory hypersensitivity. Although their function in the periphery is well known, a role for these TRP channels in central pain mechanisms is less well defined. Lipid agonists of TRPV1 are released from peripheral tissues via enzymatic oxidation after burn injury; however, it is not known if burn injury triggers the release of oxidized lipids in the spinal cord. Accordingly, we evaluated whether burn injury evoked the central release of oxidized lipids . Analysis of lipid extracts of spinal cord tissue with HPLC-MS revealed a significant increase in levels of the epoxide and diol metabolites of linoleic acid: 9,10-DiHOME, 12,13-DiHOME, 9(10)-EpOME, and 12(13)-EpOME, that was reduced after intrathecal (i.t.) injection of the oxidative enzyme inhibitor ketoconazole. Moreover, we found that these four lipid metabolites were capable of specifically activating both TRPV1 and TRPA1. Intrathecal injection of specific antagonists to TRPV1 (AMG-517) or TRPA1 (HC-030031) significantly reduced post-burn mechanical and thermal allodynia. Finally, i.t. injection of ketoconazole significantly reversed post-burn mechanical and thermal allodynia. Our data indicate that spinal cord TRPV1 and TRPA1 contributes to pain after burn and identifies a novel class of oxidized lipids elevated in the spinal cord after burn injury. Since the management of burn pain is problematic, these findings point to a novel approach for treating post-burn pain. PMID:27411353

  1. Intrastriatal grafts of fetal ventral mesencephalon improve allodynia-like withdrawal response to mechanical stimulation in a rat model of Parkinson's disease.

    PubMed

    Takeda, Ryuichiro; Ishida, Yasushi; Ebihara, Kosuke; Abe, Hiroshi; Matsuo, Hisae; Ikeda, Tetsuya; Koganemaru, Go; Kuramashi, Aki; Funahashi, Hideki; Magata, Yasuhiro; Kawai, Keiichi; Nishimori, Toshikazu

    2014-06-24

    We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments. In the ipsilateral side of the 6-OHDA lesions, the withdrawal threshold in response to mechanical stimulation significantly increased in 6-OHDA rats with VM grafts compared with those with sham grafts, but did not change in the contralateral side at 5 weeks after transplantation. The present results suggest that the intrastriatal grafts of fetal VM may relieve pain sensation induced by mechanical stimulation in 6-OHDA rats. PMID:24831182

  2. The kainate receptor antagonist 2S,4R-4-methylglutamate attenuates mechanical allodynia and thermal hyperalgesia in a rat model of nerve injury.

    PubMed

    Sutton, J L; Maccecchini, M L; Kajander, K C

    1999-01-01

    Opioids and receptor antagonists of excitatory amino acids attenuate mechanical allodynia and thermal hyperalgesia in animal models of neuropathic pain. Recently, a kainate receptor antagonist, 2S,4R-4-methylglutamate, has been developed but has not been tested for antinociceptive effects in animal models of neuropathic pain. We evaluated whether 2S,4R-4-methylglutamate attenuated responses to mechanical and thermal stimuli in uninjured (control) rats and increased responsiveness in rats with chronic constriction injury. Rats were tested for a number of withdrawal responses using a calibrated von Frey filament (mechanical stimulus) and withdrawal latencies from a radiant heat source (thermal stimulus). In control rats, 2S,4R-4-methylglutamate produced a small but significant decrease in responses from the mechanical stimulus (25 mg/kg) and significantly increased withdrawal latencies from the thermal stimulus at the highest dose administered (100 mg/kg). In addition, 2S,4R-4-methylglutamate greatly attenuated increased responsiveness in rats with chronic constriction injury. At four to eight days following chronic constriction injury, animals that displayed increased responsiveness to mechanical and thermal stimuli were injected intraperitoneally with either dizocilpine maleate (0.1 mg/kg), morphine (4 mg/kg), vehicle as controls, or 2S,4R-4-methylglutamate (25, 50, 75 or 100 mg/kg). 2S,4R-4-Methylglutamate (25, 50, 75 and 100 mg/kg) significantly attenuated the frequency of responses to mechanical stimuli (Wilcoxon, P < 0.05) and the latency of responses to thermal stimuli (analysis of variance and Duncan's, P < 0.05). Dizocilpine maleate and morphine, as expected, also reduced these responses. These results suggest that, in addition to opioid and N-methyl-D-aspartate receptors, kainate receptors may play a role in the maintenance of mechanical allodynia and thermal hyperalgesia associated with peripheral nerve injury.

  3. Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin.

    PubMed

    Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2015-10-01

    Painful diabetic neuropathy is a common complication of diabetes mellitus, which often makes the patients suffer from severe hyperalgesia and allodynia. Thus far, the treatment of painful diabetic neuropathy remains unsatisfactory. Metformin, which is the first-line drug for type-2 diabetes, has been proved to attenuate hyperexcitability in sensory neurons linked to chemotherapy-induced neuropathic pain, highlighting its potential in alleviating pain related with painful diabetic neuropathy. The present study was designed to investigate the potential beneficial effect of metformin on hyperalgesia and allodynia in diabetic rats. The mechanical sensitivity, heat nociception, and cold allodynia were examined. The levels of malondialdehyde, superoxide dismutase, and advanced glycation end-products in the blood were measured. The expression of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and AMPK target genes were examined in the sciatic nerves of the animals. It was found that metformin was capable of attenuating diabetes-induced mechanical hyperalgesia, heat hyperalgesia and cold allodynia. In addition, metformin was capable of decreasing malondialdehyde and glycation end-products levels in blood, as well as increasing superoxide dismutas activity, indicating the inhibitory effect of metformin against diabetes-induced oxidative stress. Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats. In conclusion, metformin is able to attenuate diabetes-induced hyperalgesia and allodynia, which might be associated its anti-oxidative effect through AMPK pathway. Metformin might be used as an effective drug, especially with fewer side effects, for abnormal sensation in painful diabetic neuropathy. PMID:26054810

  4. Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin.

    PubMed

    Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2015-10-01

    Painful diabetic neuropathy is a common complication of diabetes mellitus, which often makes the patients suffer from severe hyperalgesia and allodynia. Thus far, the treatment of painful diabetic neuropathy remains unsatisfactory. Metformin, which is the first-line drug for type-2 diabetes, has been proved to attenuate hyperexcitability in sensory neurons linked to chemotherapy-induced neuropathic pain, highlighting its potential in alleviating pain related with painful diabetic neuropathy. The present study was designed to investigate the potential beneficial effect of metformin on hyperalgesia and allodynia in diabetic rats. The mechanical sensitivity, heat nociception, and cold allodynia were examined. The levels of malondialdehyde, superoxide dismutase, and advanced glycation end-products in the blood were measured. The expression of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and AMPK target genes were examined in the sciatic nerves of the animals. It was found that metformin was capable of attenuating diabetes-induced mechanical hyperalgesia, heat hyperalgesia and cold allodynia. In addition, metformin was capable of decreasing malondialdehyde and glycation end-products levels in blood, as well as increasing superoxide dismutas activity, indicating the inhibitory effect of metformin against diabetes-induced oxidative stress. Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats. In conclusion, metformin is able to attenuate diabetes-induced hyperalgesia and allodynia, which might be associated its anti-oxidative effect through AMPK pathway. Metformin might be used as an effective drug, especially with fewer side effects, for abnormal sensation in painful diabetic neuropathy.

  5. Small interfering RNA-mediated selective knockdown of Na(V)1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats.

    PubMed

    Dong, X-W; Goregoaker, S; Engler, H; Zhou, X; Mark, L; Crona, J; Terry, R; Hunter, J; Priestley, T

    2007-05-11

    The biophysical properties of a tetrodotoxin resistant (TTXr) sodium channel, Na(V)1.8, and its restricted expression to the peripheral sensory neurons suggest that blocking this channel might have therapeutic potential in various pain states and may offer improved tolerability compared with existing sodium channel blockers. However, the role of Na(V)1.8 in nociception cannot be tested using a traditional pharmacological approach with small molecules because currently available sodium channel blockers do not distinguish between sodium channel subtypes. We sought to determine whether small interfering RNAs (siRNAs) might be capable of achieving the desired selectivity. Using Northern blot analysis and membrane potential measurement, several siRNAs were identified that were capable of a highly-selective attenuation of Na(V)1.8 message as well as functional expression in clonal ND7/23 cells which were stably transfected with the rat Na(V)1.8 gene. Functional knockdown of the channel was confirmed using whole-cell voltage-clamp electrophysiology. One of the siRNA probes showing a robust knockdown of Na(V)1.8 current was evaluated for in vivo efficacy in reversing an established tactile allodynia in the rat chronic constriction nerve-injury (CCI) model. The siRNA, which was delivered to lumbar dorsal root ganglia (DRG) via an indwelling epidural cannula, caused a significant reduction of Na(V)1.8 mRNA expression in lumbar 4 and 5 (L4-L5) DRG neurons and consequently reversed mechanical allodynia in CCI rats. We conclude that silencing of Na(V)1.8 channel using a siRNA approach is capable of producing pain relief in the CCI model and further support a role for Na(V)1.8 in pathological sensory dysfunction. PMID:17367951

  6. Mas-related gene (Mrg) C receptors inhibit mechanical allodynia and spinal microglia activation in the early phase of neuropathic pain in rats.

    PubMed

    Wang, Dongmei; Xue, Yaping; Chen, Yajuan; Ruan, Liqin; Hong, Yanguo

    2016-04-01

    Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. Intrathecal (i.t.) administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) at 1 or 10nmol attenuated mechanical allodynia one day after L5 spinal nerve ligation (SNL) surgery. I.t. BAM8-22 (10 nmol) inhibited SNL-induced microglia activation in the spinal dorsal horn on day 2 post-SNL. The BAM8-22 treatment also abolished SNL-induced upregulation of neuronal nitric oxide synthesis (nNOS) in the dorsal root ganglia (DRG). On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.

  7. Stereotype threat and working memory: mechanisms, alleviation, and spillover.

    PubMed

    Beilock, Sian L; Rydell, Robert J; McConnell, Allen R

    2007-05-01

    Stereotype threat (ST) occurs when the awareness of a negative stereotype about a social group in a particular domain produces suboptimal performance by members of that group. Although ST has been repeatedly demonstrated, far less is known about how its effects are realized. Using mathematical problem solving as a test bed, the authors demonstrate in 5 experiments that ST harms math problems that rely heavily on working memory resources--especially phonological aspects of this system. Moreover, by capitalizing on an understanding of the cognitive mechanisms by which ST exerts its impact, the authors show (a) how ST can be alleviated (e.g., by heavily practicing once-susceptible math problems such that they are retrieved directly from long-term memory rather than computed via a working-memory-intensive algorithm) and (b) when it will spill over onto subsequent tasks unrelated to the stereotype in question but dependent on the same cognitive resources that stereotype threat also uses. The current work extends the knowledge of the causal mechanisms of stereotype threat and demonstrates how its effects can be attenuated and propagated.

  8. Comparison of Mechanical Allodynia and Recovery of Locomotion and Bladder Function by Different Parameters of Low Thoracic Spinal Contusion Injury in Rats

    PubMed Central

    Carter, Michael W.; Johnson, Kathia M.; Lee, Jun Yeon; Hulsebosch, Claire E.

    2016-01-01

    Background The present study was designed to examine the functional recovery following spinal cord injury (SCI) by adjusting the parameters of impact force and dwell-time using the Infinite Horizon (IH) impactor device. Methods Sprague-Dawley rats (225–240 g) were divided into eight injury groups based on force of injury (Kdyn) and dwell time (seconds), indicated as Force-Dwell time: 150-4, 150-3, 150-2, 150-1, 150-0, 200-0, 90-2 and sham controls, respectively. Results After T10 SCI, higher injury force produced greater spinal cord displacement (P < 0.05) and showed a significant correlation (r = 0.813) between the displacement and the force (P < 0.05). In neuropathic pain-like behavior, the percent of paw withdrawals scores in the hindpaw for the 150-4, 150-3, 150-2, 150-1 and the 200-0 injury groups were significantly lowered compared with sham controls (P < 0.05). The recovery of locomotion had a significant within-subjects effect of time (P < 0.05) and the 150-0 group had increased recovery compared to other groups (P < 0.05). In addition, the 200-0 and the 90-2 recovered significantly better than all the 150 kdyn impact groups that included a dwell-time (P < 0.05). In recovery of spontaneous bladder function, the 150-4 injury group took significantly longer recovery time whereas the 150-0 and the 90-2 groups had the shortest recovery times. Conclusions The present study demonstrates SCI parameters optimize development of mechanical allodynia and other pathological outcomes. PMID:27103963

  9. The 5-HT(1A) receptor agonist F 13640 attenuates mechanical allodynia in a rat model of trigeminal neuropathic pain.

    PubMed

    Deseure, Kristof; Koek, Wouter; Colpaert, Francis C; Adriaensen, Hugo

    2002-12-01

    The effects of acute intraperitoneal injections of the 5-HT(1A) receptor agonists F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl]piperidin-1-yl]-methadone] and F 13714 [3-chloro-4-fluorophenyl-(4-fluoro-4-[[(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl]-piperidin-1-yl-methanone] were studied in comparison with those of baclofen and morphine on responsiveness to von Frey hair stimulation after chronic constriction injury to the rat's infraorbital nerve (IoN-CCI). Following IoN-CCI, an ipsilateral hyperresponsiveness developed that remained stable in control rats throughout the period of drug testing. F 13640, F 13714, baclofen and morphine dose-dependently decreased the hyperresponsiveness; normalization of the response occurred at doses 0.63, 0.04, 5 and 10 mg/kg, respectively. Confirming earlier data, baclofen's effects further validate IoN-CCI as a model of trigeminal neuralgia. The effects of F 13640 and F 13714 are initial evidence that 5-HT(1A) receptor agonists produce profound analgesia in the IoN-CCI model. The present data extend recent evidence that high-efficacy 5-HT(1A) receptor activation constitutes a new mechanism of central analgesia the spectrum of which may also encompass trigeminal neuropathic pain. PMID:12450569

  10. Mu-opioid receptors are not necessary for nortriptyline treatment of neuropathic allodynia

    PubMed Central

    Tessier, Luc-Henri; Yalcin, Ipek; Gavériaux-Ruff, Claire; Kieffer, Brigitte L.; Freund-Mercier, Marie-José; Barrot, Michel

    2015-01-01

    Tricyclic antidepressants (TCAs) are among the first line treatments clinically recommended against neuropathic pain. However, the mechanism by which they alleviate pain is still unclear. Pharmacological and genetic approaches evidenced a critical role of delta-opioid receptors (DORs) in the therapeutic action of chronic TCA treatment. It is however unclear whether mu-opioid receptors (MORs) are also necessary to the pain-relieving action of TCAs. The lack of highly selective MOR antagonists makes difficult to conclude based on pharmacological studies. In the present work, we thus used a genetic approach and compared mutant mice lacking MORs and their wild-type littermates. The neuropathy was induced by unilateral sciatic nerve cuffing. The threshold for mechanical response was evaluated using von Frey filaments. MOR-deficient mice displayed the same baseline for mechanical sensitivity as their wild-type littermates. After sciatic nerve cuffing, both wild-type and MOR-deficient mice displayed an ipsilateral mechanical allodynia. After about 10 days of treatment, nortriptyline suppressed this allodynia in both wild-type and MOR-deficient mice. MORs are thus not critical for nortriptyline action against neuropathic pain. An acute injection of the DOR antagonist naltrindole induced a relapse of neuropathic allodynia in both wild-type and MOR-deficient mice, thus confirming the critical role of DORs in nortriptyline action. Moreover, morphine induced an acute analgesia in control and in neuropathic wild-type mice, but was without effect in MOR-deficient mice. While MORs are crucial for morphine action, they are not critical for nortriptyline action. Our results highlight the functional difference between DORs and MORs in mechanisms of pain relief. PMID:20056557

  11. Reduction in mechanical allodynia in complex regional pain syndrome patients with ultrasound-guided pulsed radiofrequency treatment of the superficial peroneal nerve

    PubMed Central

    Chae, Won Soek; Kim, Sang Hyun; Cho, Sung Hwan; Lee, Mi Sun

    2016-01-01

    The superficial peroneal nerve is vulnerable to damage from ankle sprain injuries and fractures as well as surgery to this region. And it is also one of the most commonly involved nerves in complex regional pain syndrome type II in the foot and ankle region. We report two cases of ultrasound-guided pulsed radiofrequency treatment of superficial peroneal nerve for reduction of allodynia in CRPS patients. PMID:27738506

  12. Contact lenses, migraine, and allodynia

    PubMed Central

    Timucin, Ozgur Bulent; Karadag, Mehmet Fatih; Mehmet, Baykara

    2016-01-01

    Clinical trials and electrophysiologic studies demonstrated increased perceptual sensitivity in patients suffering from migraines. At least, one triggering factor is described in 85% of migraine patients. The aim of this report was to investigate the relationship between contact lens (CL) usage and migraine attacks in two cases. Two patients who were diagnosed with migraine reported that the frequency of migraine attacks increased after they switched to using CL with different base curves (BCs). These two patients, who began using CL with different BCs experienced discomfort and dryness of the eye. The ocular complaints were followed by migraine attacks. CL intolerance was also developed during migraine attack in one of the cases. The frequency of migraine attacks decreased and allodynia relieved significantly when flatter BCs were selected. CL related stimulus could have triggered the migraine attack. CLs should be well fitted in migraine patients with allodynia. PMID:27433037

  13. Novel Alleviation Mechanisms of Aluminum Phytotoxicity via Released Biosilicon from Rice Straw-Derived Biochars

    NASA Astrophysics Data System (ADS)

    Qian, Linbo; Chen, Baoliang; Chen, Mengfang

    2016-07-01

    Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 °C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil.

  14. Novel Alleviation Mechanisms of Aluminum Phytotoxicity via Released Biosilicon from Rice Straw-Derived Biochars

    PubMed Central

    Qian, Linbo; Chen, Baoliang; Chen, Mengfang

    2016-01-01

    Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 °C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil. PMID:27385598

  15. Novel Alleviation Mechanisms of Aluminum Phytotoxicity via Released Biosilicon from Rice Straw-Derived Biochars.

    PubMed

    Qian, Linbo; Chen, Baoliang; Chen, Mengfang

    2016-01-01

    Replacing biosilicon and biocarbon in soil via biochar amendment is a novel approach for soil amelioration and pollution remediation. The unique roles of silicon (Si)-rich biochar in aluminum (Al) phytotoxicity alleviation have not been discovered. In this study, the alleviation of Al phytotoxicity to wheat plants (root tips cell death) by biochars fabricated from rice straw pyrolyzed at 400 and 700 °C (RS400 and RS700) and the feedstock (RS100) were studied using a slurry system containing typical acidic soils for a 15-day exposure experiment. The distributions of Al and Si in the slurry solution, soil and plant root tissue were monitored by staining methods, chemical extractions and SEM-EDS observations. We found that the biological sourced silicon in biochars served dual roles in Al phytotoxicity alleviation in acidic soil slurry. On one hand, the Si particles reduced the amount of soil exchangeable Al and prevented the migration of Al to the plant. More importantly, the Si released from biochars synchronously absorbed by the plants and coordinated with Al to form Al-Si compounds in the epidermis of wheat roots, which is a new mechanism for Al phytotoxicity alleviation in acidic soil slurry by biochar amendment. In addition, the steady release of Si from the rice straw-derived biochars was a sustainable Si source for aluminosilicate reconstruction in acidic soil. PMID:27385598

  16. Mechanisms of silicon-mediated alleviation of heavy metal toxicity in plants: A review.

    PubMed

    Adrees, Muhammad; Ali, Shafaqat; Rizwan, Muhammad; Zia-Ur-Rehman, Muhammad; Ibrahim, Muhammad; Abbas, Farhat; Farid, Mujahid; Qayyum, Muhammad Farooq; Irshad, Muhammad Kashif

    2015-09-01

    In present era, heavy metal pollution is rapidly increasing which present many environmental problems. These heavy metals are mainly accumulated in soil and are transferred to food chain through plants grown on these soils. Silicon (Si) is the second most abundant element in the soil. It has been widely reported that Si can stimulate plant growth and alleviate various biotic and abiotic stresses, including heavy metal stress. Research to date has explored a number of mechanisms through which Si can alleviate heavy metal toxicity in plants at both plant and soil levels. Here we reviewed the mechanisms through which Si can alleviate heavy metal toxicity in plants. The key mechanisms evoked include reducing active heavy metal ions in growth media, reduced metal uptake and root-to-shoot translocation, chelation and stimulation of antioxidant systems in plants, complexation and co-precipitation of toxic metals with Si in different plant parts, compartmentation and structural alterations in plants and regulation of the expression of metal transport genes. However, these mechanisms might be associated with plant species, genotypes, metal elements, growth conditions, duration of the stress imposed and so on. Further research orientation is also discussed.

  17. Spinally administered dynorphin A produces long-lasting allodynia: involvement of NMDA but not opioid receptors.

    PubMed

    Laughlin, T M; Vanderah, T W; Lashbrook, J; Nichols, M L; Ossipov, M; Porreca, F; Wilcox, G L

    1997-08-01

    The endogenous opioid peptide dynorphin A has non-opioid effects that can damage the spinal cord when given in high doses. Dynorphin has been shown to increase the receptive field size of spinal cord neurons and facilitate C-fiber-evoked reflexes. Furthermore, endogenous dynorphin levels increase following damage to the spinal cord, injury to peripheral nerves, or inflammation. In this study, sensory processing was characterized following a single, intrathecal injection of dynorphin A (1-17) in mice. A single intrathecal injection of dynorphin A (1-17) (3 nmol, i.t.) induced mechanical allodynia (hind paw, von Frey filaments) lasting 70 days, tactile allodynia (paint brush applied to flank) lasting 14 days, and cold allodynia (acetone applied to the dorsal hind paw) lasting 7 days. Similarly, dynorphin A (2-17) (3 nmol, i.t.), a non-opioid peptide, induced cold and tactile allodynia analogous to that induced by dynorphin A (1-17), indicating the importance of non-opioid receptors. Pretreatment with the NMDA antagonists, MK-801 and LY235959, but not the opioid antagonist, naloxone, blocked the induction of allodynia. Post-treatment with MK-801 only transiently blocked the dynorphin-induced allodynia, suggesting the NMDA receptors may be involved in the maintenance of allodynia as well as its induction. We have induced a long-lasting state of allodynia and hyperalgesia by a single intrathecal injection of dynorphin A (1-17) in mice. The allodynia induced by dynorphin required NMDA receptors rather than opioid receptors. This result is consistent with results in rats and with signs of clinically observed neuropathic pain. This effect of exogenously administered dynorphin raises the possibility that increased levels of endogenous dynorphins associated with spinal cord injuries may participate in the genesis and maintenance of neuropathic pain. PMID:9272810

  18. Mechanisms of body weight reduction and metabolic syndrome alleviation by tea.

    PubMed

    Yang, Chung S; Zhang, Jinsong; Zhang, Le; Huang, Jinbao; Wang, Yijun

    2016-01-01

    Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been shown to reduce body weight, alleviate metabolic syndrome, and prevent diabetes and cardiovascular diseases in animal models and humans. Such beneficial effects have generally been observed in most human studies when the level of tea consumption was three to four cups (600-900 mg tea catechins) or more per day. Green tea is more effective than black tea. In spite of numerous studies, the fundamental mechanisms for these actions still remain unclear. From a review of the literature, we propose that the two major mechanisms are: (i) decreasing absorption of lipids and proteins by tea constituents in the intestine, thus reducing calorie intake; and (ii) activating AMP-activated protein kinase by tea polyphenols that are bioavailable in the liver, skeletal muscle, and adipose tissues. The relative importance of these two mechanisms depends on the types of tea and diet consumed by individuals. The activated AMP-activated protein kinase would decrease gluconeogenesis and fatty acid synthesis and increase catabolism, leading to body weight reduction and metabolic syndrome alleviation. Other mechanisms and the health relevance of these beneficial effects of tea consumption remain to be further investigated.

  19. Mechanisms of silicon-mediated alleviation of drought and salt stress in plants: a review.

    PubMed

    Rizwan, Muhammad; Ali, Shafaqat; Ibrahim, Muhammad; Farid, Mujahid; Adrees, Muhammad; Bharwana, Saima Aslam; Zia-Ur-Rehman, Muhammad; Qayyum, Muhammad Farooq; Abbas, Farhat

    2015-10-01

    Drought and salinity are the main abiotic stresses limiting crop yield and quality worldwide. Improving food production in drought- and salt-prone areas is the key to meet the increasing food demands in near future. It has been widely reported that silicon (Si), a second most abundant element in soil, could reduce drought and salt stress in plants. Here, we reviewed the emerging role of Si in enhancing drought and salt tolerance in plants and highlighted the mechanisms through which Si could alleviate both drought and salt stress in plants. Silicon application increased plant growth, biomass, photosynthetic pigments, straw and grain yield, and quality under either drought or salt stress. Under both salt and drought stress, the key mechanisms evoked are nutrient elements homeostasis, modification of gas exchange attributes, osmotic adjustment, regulating the synthesis of compatible solutes, stimulation of antioxidant enzymes, and gene expression in plants. In addition, Si application decreased Na(+) uptake and translocation while increased K(+) uptake and translocation under salt stress. However, these mechanisms vary with plant species, genotype, growth conditions, duration of stress imposed, and so on. This review article highlights the potential for improving plant resistance to drought and salt stress by Si application and provides a theoretical basis for application of Si in saline soils and arid and semiarid regions worldwide. This review article also highlights the future research needs about the role of Si under drought stress and in saline soils.

  20. Mechanisms of silicon-mediated alleviation of drought and salt stress in plants: a review.

    PubMed

    Rizwan, Muhammad; Ali, Shafaqat; Ibrahim, Muhammad; Farid, Mujahid; Adrees, Muhammad; Bharwana, Saima Aslam; Zia-Ur-Rehman, Muhammad; Qayyum, Muhammad Farooq; Abbas, Farhat

    2015-10-01

    Drought and salinity are the main abiotic stresses limiting crop yield and quality worldwide. Improving food production in drought- and salt-prone areas is the key to meet the increasing food demands in near future. It has been widely reported that silicon (Si), a second most abundant element in soil, could reduce drought and salt stress in plants. Here, we reviewed the emerging role of Si in enhancing drought and salt tolerance in plants and highlighted the mechanisms through which Si could alleviate both drought and salt stress in plants. Silicon application increased plant growth, biomass, photosynthetic pigments, straw and grain yield, and quality under either drought or salt stress. Under both salt and drought stress, the key mechanisms evoked are nutrient elements homeostasis, modification of gas exchange attributes, osmotic adjustment, regulating the synthesis of compatible solutes, stimulation of antioxidant enzymes, and gene expression in plants. In addition, Si application decreased Na(+) uptake and translocation while increased K(+) uptake and translocation under salt stress. However, these mechanisms vary with plant species, genotype, growth conditions, duration of stress imposed, and so on. This review article highlights the potential for improving plant resistance to drought and salt stress by Si application and provides a theoretical basis for application of Si in saline soils and arid and semiarid regions worldwide. This review article also highlights the future research needs about the role of Si under drought stress and in saline soils. PMID:26335528

  1. siRNA-mediated downregulation of GluN2B in the rostral anterior cingulate cortex attenuates mechanical allodynia and thermal hyperalgesia in a rat model of pain associated with bone cancer

    PubMed Central

    XU, YONGGUANG; WANG, GONGMING; ZOU, XULI; YANG, ZAIQI; WANG, QIN; FENG, HAO; ZHANG, MENGYUAN

    2016-01-01

    It has previously been suggested that the upregulation of GluN2B-containing N-methyl D-aspartate receptors (GluN2B) within the rostral anterior cingulate cortex (rACC) may contribute to the development of chronic pain. The present study used a rat model of bone cancer pain in order to investigate whether lentiviral-mediated delivery of small interfering RNAs targeting GluN2B (LV-GluN2B) could attenuate pain associated with bone cancer, by selectively decreasing GluN2B expression within the rACC. Sprague Dawley rats were inoculated with osteosarcoma cells into the intramedullary space of the right tibia in order to induce persistent bone cancer-associated pain. Intra-rACC administration of the lentiviral siRNA was performed in the tumor bearing rats; and reverse transcription-quantitative polymerase chain reaction and western blotting were performed in order to detect the expression levels of GluN2B. Pain behavior changes were evaluated via paw withdrawal threshold and latency determinations. Marked and region-selective decreases in the mRNA and protein expression levels of GluN2B were detected in the rACC following the intra-rACC administration of LV-GluN2B. Furthermore, the rats also exhibited pain behavior changes corresponding to the decreased levels of GluN2B. By post-operative day 14, inoculation of osteosarcoma cells had significantly enhanced mechanical allodynia and thermal hyperalgesia in the rats, which were subsequently attenuated by the intra-rACC administration of LV-GluN2B. Notably, the paw withdrawal threshold and latency of the tumor-bearing rats had recovered to normal levels, by day 14 post-administration. The results of the present study suggest that GluN2B within the rACC may be a potential target for RNA interference therapy for the treatment of pain associated with bone cancer. Furthermore, the lentiviral vector delivery strategy may be a promising novel approach for the treatment of bone cancer pain. PMID:26889244

  2. Spinal activity of interleukin 6 mediates myelin basic protein-induced allodynia.

    PubMed

    Ko, Justin S; Eddinger, Kelly A; Angert, Mila; Chernov, Andrei V; Dolkas, Jennifer; Strongin, Alex Y; Yaksh, Tony L; Shubayev, Veronica I

    2016-08-01

    Mechanosensory fibers are enveloped by myelin, a unique multilamellar membrane permitting saltatory neuronal conduction. Damage to myelin is thought to contribute to severe pain evoked by innocuous tactile stimulation (i.e., mechanical allodynia). Our earlier (Liu et al., 2012) and present data demonstrate that a single injection of a myelin basic protein-derived peptide (MBP84-104) into an intact sciatic nerve produces a robust and long-lasting (>30days) mechanical allodynia in female rats. The MBP84-104 peptide represents the immunodominant epitope and requires T cells to maintain allodynia. Surprisingly, only systemic gabapentin (a ligand of voltage-gated calcium channel α2δ1), but not ketorolac (COX inhibitor), lidocaine (sodium channel blocker) or MK801 (NMDA antagonist) reverse allodynia induced by the intrasciatic MBP84-104. The genome-wide transcriptional profiling of the sciatic nerve followed by the bioinformatics analyses of the expression changes identified interleukin (IL)-6 as the major cytokine induced by MBP84-104 in both the control and athymic T cell-deficient nude rats. The intrasciatic MBP84-104 injection resulted in both unilateral allodynia and unilateral IL-6 increase the segmental spinal cord (neurons and astrocytes). An intrathecal delivery of a function-blocking IL-6 antibody reduced the allodynia in part by the transcriptional effects in large-diameter primary afferents in DRG. Our data suggest that MBP regulates IL-6 expression in the nervous system and that the spinal IL-6 activity mediates nociceptive processing stimulated by the MBP epitopes released after damage or disease of the somatosensory nervous system. PMID:26970355

  3. Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

    NASA Astrophysics Data System (ADS)

    Müller, M. N.; Ramos, J. Barcelos e.; Schulz, K. G.; Riebesell, U.; Kaźmierczak, J.; Gallo, F.; Mackinder, L.; Li, Y.; Nesterenko, P. N.; Trull, T. W.; Hallegraeff, G. M.

    2015-11-01

    Marine phytoplankton have developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L-1 in the presence of seawater Ca2+ concentrations of 10 mmol L-1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, phytoplankton taxonomic groups appear to have evolved different strategies, which may affect their ability to cope with changes in seawater Ca2+ concentrations in their environment on geological timescales. For example, the Cretaceous (145 to 66 Ma), an era known for the high abundance of coccolithophores and the production of enormous calcium carbonate deposits, exhibited seawater calcium concentrations up to 4 times present-day levels. We show that calcifying coccolithophore species (Emiliania huxleyi, Gephyrocapsa oceanica and Coccolithus braarudii) are able to maintain their relative fitness (in terms of growth rate and photosynthesis) at simulated Cretaceous seawater calcium concentrations, whereas these rates are severely reduced under these conditions in some non-calcareous phytoplankton species (Chaetoceros sp., Ceratoneis closterium and Heterosigma akashiwo). Most notably, this also applies to a non-calcifying strain of E. huxleyi which displays a calcium sensitivity similar to the non-calcareous species. We hypothesize that the process of calcification in coccolithophores provides an efficient mechanism to alleviate cellular calcium poisoning and thereby offered a potential key evolutionary advantage, responsible for the proliferation of coccolithophores during times of high seawater calcium concentrations. The exact function of calcification and the reason behind the highly ornate physical structures of coccoliths remain elusive.

  4. Non-Invasive Vagus Nerve Stimulation as Treatment for Trigeminal Allodynia

    PubMed Central

    Oshinsky, Michael L.; Murphy, Angela L.; Hekierski, Hugh; Cooper, Marnie; Simon, Bruce J.

    2014-01-01

    Implanted vagus nerve stimulation (VNS) has been used to treat seizures and depression. In this study, we explore the mechanism of action of non-invasive vagus nerve stimulation (nVNS) for the treatment of trigeminal allodynia. Rats were repeatedly infused with inflammatory mediators directly onto the dura, which leads to chronic trigeminal allodynia. nVNS for 2min decreases periorbital sensitivity in rats with periorbital trigeminal allodynia for up to 3.5hr after stimulation. Using microdialysis, we quantified levels of extracellular neurotransmitters in the trigeminal nucleus caudalis (TNC). Allodynic rats showed a 7.7±0.9 fold increase in extracellular glutamate in the TNC following i.p. administration of the chemical headache trigger, glyceryl trinitrate (GTN; 0.1mg/kg). Allodynic rats, which received nVNS, had only a 2.3±0.4 fold increase in extracellular glutamate following GTN similar to the response in control naive rats. When nVNS was delayed until 120min after GTN treatment, the high levels of glutamate in the TNC were reversed following nVNS. The nVNS stimulation parameters used in this study did not produce significant changes in blood pressure or heart rate. These data suggest that nVNS may be used to treat trigeminal allodynia. PMID:24530613

  5. An animal model of oxaliplatin-induced cold allodynia reveals a crucial role for Nav1.6 in peripheral pain pathways

    PubMed Central

    Deuis, Jennifer R; Zimmermann, Katharina; Romanovsky, Andrej A; Possani, Lourival D; Cabot, Peter J; Lewis, Richard J; Vetter, Irina

    2013-01-01

    Cold allodynia, pain in response to cooling, occurs during or within hours of oxaliplatin infusion and is thought to arise from a direct effect of oxaliplatin on peripheral sensory neurons. To characterize the pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia, we established a new intraplantar oxaliplatin mouse model that rapidly developed long-lasting cold allodynia mediated entirely through tetrodotoxin-sensitive Nav pathways. Using selective inhibitors and knockout animals, we found that Nav1.6 was the key isoform involved, while thermosensitive transient receptor potential channels were not involved. Consistent with a crucial role for delayed-rectifier potassium channels in excitability in response to cold, intraplantar administration of the K+-channel blocker 4-aminopyridine mimicked oxaliplatin-induced cold allodynia and was also inhibited by Navl.6 blockers. Intraplantar injection of the Nav1.6-activator Cn2 elicited spontaneous pain, mechanical allodynia and enhanced 4-aminopyridine-induced cold allodynia. These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple peripheral pain pathways including cold allodynia. PMID:23711479

  6. The mechanism by which NaCl treatment alleviates PSI photoinhibition under chilling-light treatment.

    PubMed

    Yang, Cheng; Zhang, Zi-shan; Gao, Hui-yuan; Fan, Xing-li; Liu, Mei-jun; Li, Xiang-dong

    2014-11-01

    The effects of chilling-light stress combined with additional stress on PSI and PSII photoinhibition and their interrelationship have not been known. To explore whether NaCl affects the PSI and PSII photoinhibition and their interrelationship under chilling-light treatment, the PSI and PSII activities were studied under chilling-light with or without NaCl treatment. The results showed that the extent of PSI and PSII photoinhibition both increased under chilling-light, while NaCl aggravated PSII photoinhibition and severely damaged cytochrome b₆/f complex but alleviated PSI photoinhibition. Moreover, DCMU had a similar effect as NaCl in this study, which indicates that NaCl alleviated PSI photoinhibition through reducing electrons transported to PSI. It was also showed that the increased damage to PSII by NaCl did not depend on the inhibition of PSII repair and PSI electron transportation. In conclusion, NaCl alleviated PSI photoinhibition by inhibiting electron transport from PSII under chilling-light conditions. In addition, PSII photoinhibition was not affected by PSI photoinhibition because of a full inhibition of PSII repair by chilling-light treatment. We also speculate that NaCl aggravates PSII photoinhibition by enhancing the damage instead of inhibiting the repair of it under chilling-light conditions.

  7. Spinal changes of a newly isolated neuropeptide endomorphin-2 concomitant with vincristine-induced allodynia.

    PubMed

    Yang, Yang; Zhang, Yong-Gang; Lin, Guo-An; Xie, He-Qiu; Pan, Hai-Tao; Huang, Ben-Qing; Liu, Ji-Dong; Liu, Hui; Zhang, Nan; Li, Li; Chen, Jian-Hua

    2014-01-01

    Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP. PMID:24586889

  8. The mechanism underlying alpinetin-mediated alleviation of pancreatitis-associated lung injury through upregulating aquaporin-1

    PubMed Central

    Liang, Xingsi; Zhang, Bin; Chen, Quan; Zhang, Jing; Lei, Biao; Li, Bo; Wei, Yangchao; Zhai, Run; Liang, Zhiqing; He, Songqing; Tang, Bo

    2016-01-01

    Characterized by its acute onset, critical condition, poor prognosis, and high mortality rate, severe acute pancreatitis (SAP) can cause multiple organ failure at its early stage, particularly acute lung injury (ALI). The pathogenesis of ALI is diffuse alveolar damage, including an increase in pulmonary microvascular permeability, a decrease in compliance, and invasion of many inflammatory cells. Corticosteroids are the main treatment method for ALI; however, the associated high toxicity and side effects induce pain in patients. Recent studies show that the effective components in many traditional Chinese medicines can effectively inhibit inflammation with few side effects, which can decrease the complications caused by steroid consumption. Based on these observations, the main objective of the current study is to investigate the effect of alpinetin, which is a flavonoid extracted from Alpinia katsumadai Hayata, on treating lung injury induced by SAP and to explore the mechanism underlying the alpinetin-mediated decrease in the extent of ALI. In this study, we have shown through in vitro experiments that a therapeutic dose of alpinetin can promote human pulmonary microvascular endothelial cell proliferation. We have also shown via in vitro and in vivo experiments that alpinetin upregulates aquaporin-1 and, thereby, inhibits tumor necrosis factor-α expression as well as reduces the degree of lung injury. Overall, our study shows that alpinetin alleviates SAP-induced ALI. The likely molecular mechanism includes upregulated aquaporin expression, which inhibits tumor necrosis factor-α and, thus, alleviates SAP-induced ALI. PMID:26966354

  9. HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

    PubMed Central

    Lin, Shenglan; Wang, Yana; Zhang, Xiaojin; Kong, Qiuyue; Li, Chuanfu; Li, Yuehua; Ding, Zhengnian

    2016-01-01

    Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation. PMID:27110324

  10. A novel mechanism of action for salidroside to alleviate diabetic albuminuria: effects on albumin transcytosis across glomerular endothelial cells.

    PubMed

    Wu, Dan; Yang, Xiaoyan; Zheng, Tao; Xing, Shasha; Wang, Jianghong; Chi, Jiangyang; Bian, Fang; Li, Wenjing; Xu, Gao; Bai, Xiangli; Wu, Guangjie; Jin, Si

    2016-02-01

    Salidroside (SAL) is a phenylethanoid glycoside isolated from the medicinal plant Rhodiola rosea. R. rosea has been reported to have beneficial effects on diabetic nephropathy (DN) and high-glucose (HG)-induced mesangial cell proliferation. Given the importance of caveolin-1 (Cav-1) in transcytosis of albumin across the endothelial barrier, the present study was designed to elucidate whether SAL could inhibit Cav-1 phosphorylation and reduce the albumin transcytosis across glomerular endothelial cells (GECs) to alleviate diabetic albuminuria as well as to explore its upstream signaling pathway. To assess the therapeutic potential of SAL and the mechanisms involved in DN albuminuria, we orally administered SAL to db/db mice, and the effect of SAL on the albuminuria was measured. The albumin transcytosis across GECs was explored in a newly established in vitro cellular model. The ratio of albumin to creatinine was significantly reduced upon SAL treatment in db/db mice. SAL decreased the albumin transcytosis across GECs in both normoglycemic and hyperglycemic conditions. SAL reversed the HG-induced downregulation of AMP-activated protein kinase and upregulation of Src kinase and blocked the upregulation Cav-1 phosphorylation. Meanwhile, SAL decreased mitochondrial superoxide anion production and moderately depolarized mitochondrial membrane potential. We conclude that SAL exerts its proteinuria-alleviating effects by downregulation of Cav-1 phosphorylation and inhibition of albumin transcytosis across GECs. These studies provide the first evidence of interference with albumin transcytosis across GECs as a novel approach to the treatment of diabetic albuminuria.

  11. Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats

    PubMed Central

    Wu, Wei; Luo, Ruijie; Lin, Ziqi; Xia, Qing

    2016-01-01

    To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID:27413385

  12. Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats.

    PubMed

    Wu, Wei; Luo, Ruijie; Lin, Ziqi; Xia, Qing; Xue, Ping

    2016-01-01

    To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID:27413385

  13. Role of glutamate receptors in the dorsal reticular nucleus in formalin-induced secondary allodynia.

    PubMed

    Ambriz-Tututi, Mónica; Palomero-Rivero, Marcela; Ramirez-López, Fernanda; Millán-Aldaco, Diana; Drucker-Colín, And René

    2013-10-01

    The role of glutamate receptors present in the medullary dorsal reticular nucleus (DRt) in the formalin test and formalin-induced secondary nociception was studied in rats. Secondary mechanical allodynia was assessed with von Frey filaments applied to the rat's hindpaw, and secondary thermal hyperalgesia was evaluated with the tail-immersion test. The selective glutamate receptor antagonists MK801 (N-methyl-D-aspartate receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA/KA receptor antagonist) and A841720 (metabotropic glutamate 1 receptor antagonist) were injected into the DRt before or 6 days after formalin injection in the rat. In the formalin test, the three antagonists significantly reduced the number of flinches in both phases of the test. DRt microinjection of MK801 or A841720, but not of CNQX, reduced both secondary nociceptive behaviors. Moreover, pre-treatment with the three antagonists injected into the DRt prevented the development of secondary mechanical allodynia and secondary thermal hyperalgesia. Similarly, in these rats, the number of c-Fos-like immunoreactive neurons were markedly reduced in both the superficial and deep lamina of the dorsal horn. Our findings support the role of DRt as a pain facilitator in acute and chronic pain states, and suggest a key role of glutamate receptors during the development and maintenance of formalin-induced secondary allodynia. PMID:23869620

  14. Intraneural dexamethasone applied simultaneously to rat sciatic nerve constriction delays the development of hyperalgesia and allodynia.

    PubMed

    Bastos, Leandro F S; Medeiros, Daniel C; Vieira, Rafael P; Watkins, Linda R; Coelho, Márcio M; Moraes, Márcio F D

    2012-02-21

    Although neuroimmune interactions associated with the development of pain sensitization in models of neuropathic pain have been widely studied, there are some aspects that require further investigation. Thus, we aimed to evaluate whether the local intraneural or perineural injections of dexamethasone, an efficacious anti-inflammatory and immunosuppressant drug, delays the development of both thermal hyperalgesia and mechanical allodynia in an experimental model of neuropathic pain in rats. Hargreaves and electronic von Frey tests were applied. The chronic constriction injury (CCI) of right sciatic nerve was performed. Single intraneural dexamethasone administration at the moment of constriction delayed the development of sensitization for thermal hyperalgesia and mechanical allodynia. However, perineural administration of dexamethasone, at the highest dose, did not delay experimental pain development. These results show that inflammation/immune response at the site of nerve lesion is an essential trigger for the pathological changes that lead to both hyperalgesia and allodynia. In conclusion, this approach opens new opportunities to study cellular and molecular neuroimmune interactions associated with the development of pain derived from peripheral neuropathies. PMID:22240103

  15. Selfish punishment with avoiding mechanism can alleviate both first-order and second-order social dilemma.

    PubMed

    Cui, Pengbi; Wu, Zhi-Xi

    2014-11-21

    Punishment, especially selfish punishment, has recently been identified as a potent promoter in sustaining or even enhancing the cooperation among unrelated individuals. However, without other key mechanisms, the first-order social dilemma and second-order social dilemma are still two enduring conundrums in biology and the social sciences even with the presence of punishment. In the present study, we investigate a spatial evolutionary four-strategy prisoner׳s dilemma game model with avoiding mechanism, where the four strategies are cooperation, defection, altruistic and selfish punishment. By introducing the low level of random mutation of strategies, we demonstrate that the presence of selfish punishment with avoiding mechanism can alleviate the two kinds of social dilemmas for various parametrizations. In addition, we propose an extended pair approximation method, whose solutions can essentially estimate the dynamical behaviors and final evolutionary frequencies of the four strategies. At last, considering the analogy between our model and the classical Lotka-Volterra system, we introduce interaction webs based on the spatial replicator dynamics and the transformed payoff matrix to qualitatively characterize the emergent co-exist strategy phases, and its validity are supported by extensive simulations. PMID:25088776

  16. Selfish punishment with avoiding mechanism can alleviate both first-order and second-order social dilemma.

    PubMed

    Cui, Pengbi; Wu, Zhi-Xi

    2014-11-21

    Punishment, especially selfish punishment, has recently been identified as a potent promoter in sustaining or even enhancing the cooperation among unrelated individuals. However, without other key mechanisms, the first-order social dilemma and second-order social dilemma are still two enduring conundrums in biology and the social sciences even with the presence of punishment. In the present study, we investigate a spatial evolutionary four-strategy prisoner׳s dilemma game model with avoiding mechanism, where the four strategies are cooperation, defection, altruistic and selfish punishment. By introducing the low level of random mutation of strategies, we demonstrate that the presence of selfish punishment with avoiding mechanism can alleviate the two kinds of social dilemmas for various parametrizations. In addition, we propose an extended pair approximation method, whose solutions can essentially estimate the dynamical behaviors and final evolutionary frequencies of the four strategies. At last, considering the analogy between our model and the classical Lotka-Volterra system, we introduce interaction webs based on the spatial replicator dynamics and the transformed payoff matrix to qualitatively characterize the emergent co-exist strategy phases, and its validity are supported by extensive simulations.

  17. Chondroitin sulfate attenuates formalin-induced persistent tactile allodynia.

    PubMed

    Nemoto, Wataru; Yamada, Kotaro; Ogata, Yoshiki; Nakagawasai, Osamu; Onodera, Katsuhito; Sakurai, Hidetomo; Tan-No, Koichi

    2016-08-01

    We examined the effect of chondroitin sulfate (CS), a compound used in the treatment of osteoarthritis and joint pain, on the formalin-induced tactile allodynia in mice. A repeated oral administration of CS (300 mg/kg, b.i.d.) significantly ameliorated the formalin-induced tactile allodynia from day 10 after formalin injection. On day 14, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons were attenuated by the repeated administration of CS. These findings suggest that CS attenuates formalin-induced tactile allodynia through the inhibition of p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the dorsal lumbar spinal cord. PMID:27567476

  18. Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms.

    PubMed

    Lim, L W; Prickaerts, J; Huguet, G; Kadar, E; Hartung, H; Sharp, T; Temel, Y

    2015-03-31

    Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.

  19. Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms

    PubMed Central

    Lim, L W; Prickaerts, J; Huguet, G; Kadar, E; Hartung, H; Sharp, T; Temel, Y

    2015-01-01

    Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN. PMID:25826110

  20. Mechanisms of biochar-mediated alleviation of toxicity of trace elements in plants: a critical review.

    PubMed

    Rizwan, Muhammad; Ali, Shafaqat; Qayyum, Muhammad Farooq; Ibrahim, Muhammad; Zia-ur-Rehman, Muhammad; Abbas, Tahir; Ok, Yong Sik

    2016-02-01

    Trace elements (TEs) contamination is one of the main abiotic stresses which limit plant growth and deteriorate the food quality by their entry into food chain. In recent, biochar (BC) soil amendment has been widely reported for the reduction of TE(s) uptake and toxicity in plants. This review summarizes the role of BC in enhancing TE(s) tolerance in plants. Under TE(s) stress, BC application increased plant growth, biomass, photosynthetic pigments, grain yield, and quality. The key mechanisms evoked are immobilization of TE(s) in the soil, increase in soil pH, alteration of TE(s) redox state in the soil, and improvement in soil physical and biological properties under TE(s) stress. However, these mechanisms vary with plant species, genotypes, growth conditions, duration of stress imposed, BC type, and preparation methods. This review highlights the potential for improving plant resistance to TE(s) stress by BC application and provides a theoretical basis for application of BC in TE(s) contaminated soils worldwide.

  1. Poverty alleviation and environmental restoration using the clean development mechanism: A case study from Humbo, Ethiopia.

    PubMed

    Brown, Douglas R; Dettmann, Paul; Rinaudo, Tony; Tefera, Hailu; Tofu, Assefa

    2011-08-01

    Poverty, hunger and demand for agricultural land have driven local communities to overexploit forest resources throughout Ethiopia. Forests surrounding the township of Humbo were largely destroyed by the late 1960s. In 2004, World Vision Australia and World Vision Ethiopia identified forestry-based carbon sequestration as a potential means to stimulate community development while engaging in environmental restoration. After two years of consultation, planning and negotiations, the Humbo Community-based Natural Regeneration Project began implementation--the Ethiopian organization's first carbon sequestration initiative. The Humbo Project assists communities affected by environmental degradation including loss of biodiversity, soil erosion and flooding with an opportunity to benefit from carbon markets while reducing poverty and restoring the local agroecosystem. Involving the regeneration of 2,728 ha of degraded native forests, it brings social, economic and ecological benefits--facilitating adaptation to a changing climate and generating temporary certified emissions reductions (tCERs) under the Clean Development Mechanism. A key feature of the project has been facilitating communities to embrace new techniques and take responsibility for large-scale environmental change, most importantly involving Farmer Managed Natural Regeneration (FMNR). This technique is low-cost, replicable, and provides direct benefits within a short time. Communities were able to harvest fodder and firewood within a year of project initiation and wild fruits and other non-timber forest products within three years. Farmers are using agroforestry for both environmental restoration and income generation. Establishment of user rights and local cooperatives has generated community ownership and enthusiasm for this project--empowering the community to more sustainably manage their communal lands.

  2. Poverty Alleviation and Environmental Restoration Using the Clean Development Mechanism: A Case Study from Humbo, Ethiopia

    NASA Astrophysics Data System (ADS)

    Brown, Douglas R.; Dettmann, Paul; Rinaudo, Tony; Tefera, Hailu; Tofu, Assefa

    2011-08-01

    Poverty, hunger and demand for agricultural land have driven local communities to overexploit forest resources throughout Ethiopia. Forests surrounding the township of Humbo were largely destroyed by the late 1960s. In 2004, World Vision Australia and World Vision Ethiopia identified forestry-based carbon sequestration as a potential means to stimulate community development while engaging in environmental restoration. After two years of consultation, planning and negotiations, the Humbo Community-based Natural Regeneration Project began implementation—the Ethiopian organization's first carbon sequestration initiative. The Humbo Project assists communities affected by environmental degradation including loss of biodiversity, soil erosion and flooding with an opportunity to benefit from carbon markets while reducing poverty and restoring the local agroecosystem. Involving the regeneration of 2,728 ha of degraded native forests, it brings social, economic and ecological benefits—facilitating adaptation to a changing climate and generating temporary certified emissions reductions (tCERs) under the Clean Development Mechanism. A key feature of the project has been facilitating communities to embrace new techniques and take responsibility for large-scale environmental change, most importantly involving Farmer Managed Natural Regeneration (FMNR). This technique is low-cost, replicable, and provides direct benefits within a short time. Communities were able to harvest fodder and firewood within a year of project initiation and wild fruits and other non-timber forest products within three years. Farmers are using agroforestry for both environmental restoration and income generation. Establishment of user rights and local cooperatives has generated community ownership and enthusiasm for this project—empowering the community to more sustainably manage their communal lands.

  3. Leaf cDNA-AFLP analysis reveals novel mechanisms for boron-induced alleviation of aluminum-toxicity in Citrus grandis seedlings.

    PubMed

    Wang, Liu-Qing; Yang, Lin-Tong; Guo, Peng; Zhou, Xin-Xing; Ye, Xin; Chen, En-Jun; Chen, Li-Song

    2015-10-01

    Little information is available on the molecular mechanisms of boron (B)-induced alleviation of aluminum (Al)-toxicity. 'Sour pummelo' (Citrus grandis) seedlings were irrigated for 18 weeks with nutrient solution containing different concentrations of B (2.5 or 20μM H3BO3) and Al (0 or 1.2mM AlCl3·6H2O). B alleviated Al-induced inhibition in plant growth accompanied by lower leaf Al. We used cDNA-AFLP to isolate 127 differentially expressed genes from leaves subjected to B and Al interactions. These genes were related to signal transduction, transport, cell wall modification, carbohydrate and energy metabolism, nucleic acid metabolism, amino acid and protein metabolism, lipid metabolism and stress responses. The ameliorative mechanisms of B on Al-toxicity might be related to: (a) triggering multiple signal transduction pathways; (b) improving the expression levels of genes related to transport; (c) activating genes involved in energy production; and (d) increasing amino acid accumulation and protein degradation. Also, genes involved in nucleic acid metabolism, cell wall modification and stress responses might play a role in B-induced alleviation of Al-toxicity. To conclude, our findings reveal some novel mechanisms on B-induced alleviation of Al-toxicity at the transcriptional level in C. grandis leaves.

  4. Toll-like receptor 4 knockout alleviates paraquat-induced cardiomyocyte contractile dysfunction through an autophagy-dependent mechanism.

    PubMed

    Wang, Shuyi; Zhu, Xiaoling; Xiong, Lize; Zhang, Yingmei; Ren, Jun

    2016-08-22

    Paraquat, a quarternary nitrogen herbicide, is a toxic prooxidant leading to multi-organ failure including the heart although the underlying mechanism remains poorly understood. This study was designed to examine the role of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in paraquat-induced cardiac contractile anomalies and the underlying mechanisms involved with a focus on autophagy, a conservative machinery governing protein and organelle degradation and recycling for cardiac homeostasis. Wild-type (WT) and TLR4 knockout (TLR4(-/-)) mice were challenged with paraquat (45mg/kg, i.p.) for 48h. Paraquat challenge did not affect mRNA levels of TLR2, TLR4 and TLR9 in WT mice nor did paraquat treatment alter TREM-1 levels. Paraquat challenge elicited cardiac mechanical defects including compromised cardiomyocyte contractile function, intracellular Ca(2+) handling, and overt autophagy as manifested by increased LC3BII-to-LC3BI ratio, Atg5, Atg7 and p62 levels. Interestingly, TLR4 knockout significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) derangement as well as alterations of autophagy markers. Paraquat-elicited changes in cardiac autophagy markers (LC3BII, LC3BII-to-LC3BI ratio and p62) were augmented by lysosomal inhibition using bafilomycin A1 in WT mice. TLR4 knockout significantly attenuated or negated paraquat-elicited increase in LC3BII, LC3BII-to-LC3BI ratio and p62 levels in the presence of lysosomal inhibition. In addition, paraquat challenge promoted phosphorylation of AMPK while suppressing the phosphorylation of mTOR and ULK1 (the autophagy inhibitory Ser(757)), the effects of which were significantly attenuated by TLR4 ablation. In vitro study revealed that AMPK activation using AICAR or mTOR inhibition using rapamycin effectively negated the beneficial cardiomyocyte mechanical effects of TLR4 inhibition (CLI-095) against paraquat toxicity, supporting a permissive role for AMPK-mTOR in TLR4 inhibition

  5. Toll-like receptor 4 knockout alleviates paraquat-induced cardiomyocyte contractile dysfunction through an autophagy-dependent mechanism.

    PubMed

    Wang, Shuyi; Zhu, Xiaoling; Xiong, Lize; Zhang, Yingmei; Ren, Jun

    2016-08-22

    Paraquat, a quarternary nitrogen herbicide, is a toxic prooxidant leading to multi-organ failure including the heart although the underlying mechanism remains poorly understood. This study was designed to examine the role of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in paraquat-induced cardiac contractile anomalies and the underlying mechanisms involved with a focus on autophagy, a conservative machinery governing protein and organelle degradation and recycling for cardiac homeostasis. Wild-type (WT) and TLR4 knockout (TLR4(-/-)) mice were challenged with paraquat (45mg/kg, i.p.) for 48h. Paraquat challenge did not affect mRNA levels of TLR2, TLR4 and TLR9 in WT mice nor did paraquat treatment alter TREM-1 levels. Paraquat challenge elicited cardiac mechanical defects including compromised cardiomyocyte contractile function, intracellular Ca(2+) handling, and overt autophagy as manifested by increased LC3BII-to-LC3BI ratio, Atg5, Atg7 and p62 levels. Interestingly, TLR4 knockout significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) derangement as well as alterations of autophagy markers. Paraquat-elicited changes in cardiac autophagy markers (LC3BII, LC3BII-to-LC3BI ratio and p62) were augmented by lysosomal inhibition using bafilomycin A1 in WT mice. TLR4 knockout significantly attenuated or negated paraquat-elicited increase in LC3BII, LC3BII-to-LC3BI ratio and p62 levels in the presence of lysosomal inhibition. In addition, paraquat challenge promoted phosphorylation of AMPK while suppressing the phosphorylation of mTOR and ULK1 (the autophagy inhibitory Ser(757)), the effects of which were significantly attenuated by TLR4 ablation. In vitro study revealed that AMPK activation using AICAR or mTOR inhibition using rapamycin effectively negated the beneficial cardiomyocyte mechanical effects of TLR4 inhibition (CLI-095) against paraquat toxicity, supporting a permissive role for AMPK-mTOR in TLR4 inhibition

  6. Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo

    PubMed Central

    Zhang, Wei Kevin; Tao, Shan-Shan; Li, Ting-Ting; Li, Yu-Sang; Li, Xiao-Jun; Tang, He-Bin; Cong, Ren-Huai; Ma, Fang-Li; Wan, Chu-Jun

    2016-01-01

    Background Chronic pain, or sometimes referred to as persistent pain, reduces the life quality of patients who are suffering from chronic diseases such as inflammatory diseases, cancer and diabetes. Hence, herbal medicines draw many attentions and have been shown effective in the treatment or relief of pain. Methods and Results Here in this study, we used the CFA-injected rats as a sustainable pain model to test the anti-inflammatory and analgesic effect of nutmeg oil, a spice flavor additive to beverages and baked goods produced from the seed of Myristica fragrans tree. Conclusions We have demonstrated that nutmeg oil could potentially alleviate the CFA-injection induced joint swelling, mechanical allodynia and heat hyperanalgesia of rats through inhibition of COX-2 expression and blood substance P level, which made it possible for nutmeg oil to be a potential chronic pain reliever. PMID:27121041

  7. Blockade of calcium channels can prevent the onset of secondary hyperalgesia and allodynia induced by intradermal injection of capsaicin in rats.

    PubMed

    Sluka, K A

    1997-06-01

    Intradermal capsaicin injection in humans results in primary hyperalgesia to heat and mechanical stimuli applied near the injection site, as well as secondary mechanical hyperalgesia (increased pain from noxious stimuli) and mechanical allodynia (pain from innocuous stimuli) in an area surrounding the site of primary hyperalgesia. This study in rats tested the hypothesis that the secondary hyperalgesia and allodynia observed following intradermal injection of capsaicin was dependent upon activation of voltage sensitive calcium channels in the spinal cord. Responses to application of von Frey filaments of 10 mN and 90 mN bending forces were tested in all rats before and after injection of capsaicin into the plantar surface of a hindpaw. Animals were pretreated with L-type (nifedipine), N-type (omega-conotoxin GVIA) or P-type (omega-agatoxin IVA) calcium channels blockers through a microdialysis fiber implanted in the spinal dorsal horn prior to the injection of capsaicin. None of the calcium channel blockers had any affect on normal sensory or motor responses. However, all three blockers dose dependently prevented the development of secondary mechanical hyperalgesia and allodynia. The threshold to mechanical stimulation with von Frey filaments was also increased significantly in animals treated with these calcium channel blockers when compared to articial cerebrospinal fluid control animals. These data suggest that calcium channels are important for the development of mechanical hyperalgesia and allodynia that occurs following capsaicin injection. PMID:9211477

  8. TRPV1 channel-mediated bilateral allodynia induced by unilateral masseter muscle inflammation in rats

    PubMed Central

    2013-01-01

    Pain in masticatory muscles is among the most prominent symptoms of temperomandibular disorders (TMDs) that have diverse and complex etiology. A common complaint of TMD is that unilateral pain of craniofacial muscle can cause a widespread of bilateral pain sensation, although the underlying mechanism remains unknown. To investigate whether unilateral inflammation of masseter muscle can cause a bilateral allodynia, we generated masseter muscle inflammation induced by unilateral injection of complete Freund’s adjuvant (CFA) in rats, and measured the bilateral head withdrawal threshold at different time points using a von Frey anesthesiometer. After behavioral assessment, both right and left trigeminal ganglia (TRG) were dissected and examined for histopathology and transient receptor potential vanilloid 1 (TRPV1) mRNA expression using quantitative real-time PCR analysis. A significant increase in TRPV1 mRNA expression occurred in TRG ipsilateral to CFA injected masseter muscle, whereas no significant alteration in TRPV1 occurred in the contralateral TRG. Interestingly, central injection of TRPV1 antagonist 5-iodoresiniferatoxin into the hippocampus significantly attenuated the head withdrawal response of both CFA injected and non-CFA injected contralateral masseter muscle. Our findings show that unilateral inflammation of masseter muscle is capable of inducing bilateral allodynia in rats. Upregulation of TRPV1 at the TRG level is due to nociception caused by inflammation, whereas contralateral nocifensive behavior in masticatory muscle nociception is likely mediated by central TRPV1, pointing to the involvement of altered information processing in higher centers. PMID:24377488

  9. Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

    PubMed

    Rodríguez-Angulo, H; Thomas, L E; Castillo, E; Cárdenas, E; Mogollón, F; Mijares, A

    2013-08-01

    Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase. PMID:23684908

  10. Complications of sodium hydroxide chemical matrixectomy: nail dystrophy, allodynia, hyperalgesia.

    PubMed

    Bostancı, Seher; Koçyiğit, Pelin; Güngör, Hilayda Karakök; Parlak, Nehir

    2014-11-01

    Ingrown toenails are seen most commonly in young adults, and they can seriously affect daily life. Partial nail avulsion with chemical matrixectomy, generally by using either sodium hydroxide or phenol, is one of the most effective treatment methods. Known complications of phenol matrixectomy are unpredictable tissue damage, prolonged postoperative drainage, increased secondary infection rates, periostitis, and poor cosmetic results. To our knowledge, there have been no reports about the complications related to sodium hydroxide matrixectomy. Herein, we describe three patients who developed nail dystrophy, allodynia, and hyperalgesia after sodium hydroxide matrixectomy.

  11. Mechanisms on Boron-Induced Alleviation of Aluminum-Toxicity in Citrus grandis Seedlings at a Transcriptional Level Revealed by cDNA-AFLP Analysis

    PubMed Central

    Zhou, Xin-Xing; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Chen, Li-Song

    2015-01-01

    The physiological and biochemical mechanisms on boron (B)-induced alleviation of aluminum (B)-toxicity in plants have been examined in some details, but our understanding of the molecular mechanisms underlying these processes is very limited. In this study, we first used the cDNA-AFLP to investigate the gene expression patterns in Citrus grandis roots responsive to B and Al interactions, and isolated 100 differentially expressed genes. Results showed that genes related to detoxification of reactive oxygen species (ROS) and aldehydes (i.e., glutathione S-transferase zeta class-like isoform X1, thioredoxin M-type 4, and 2-alkenal reductase (NADP+-dependent)-like), metabolism (i.e., carboxylesterases and lecithin-cholesterol acyltransferase-like 4-like, nicotianamine aminotransferase A-like isoform X3, thiosulfate sulfurtransferase 18-like isoform X1, and FNR, root isozyme 2), cell transport (i.e., non-specific lipid-transfer protein-like protein At2g13820-like and major facilitator superfamily protein), Ca signal and hormone (i.e., calcium-binding protein CML19-like and IAA-amino acid hydrolase ILR1-like 4-like), gene regulation (i.e., Gag-pol polyprotein) and cell wall modification (i.e., glycosyl hydrolase family 10 protein) might play a role in B-induced alleviation of Al-toxicity. Our results are useful not only for our understanding of molecular processes associated with B-induced alleviation of Al-toxicity, but also for obtaining key molecular genes to enhance Al-tolerance of plants in the future. PMID:25747450

  12. Mechanisms on boron-induced alleviation of aluminum-toxicity in Citrus grandis seedlings at a transcriptional level revealed by cDNA-AFLP analysis.

    PubMed

    Zhou, Xin-Xing; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Chen, Li-Song

    2015-01-01

    The physiological and biochemical mechanisms on boron (B)-induced alleviation of aluminum (B)-toxicity in plants have been examined in some details, but our understanding of the molecular mechanisms underlying these processes is very limited. In this study, we first used the cDNA-AFLP to investigate the gene expression patterns in Citrus grandis roots responsive to B and Al interactions, and isolated 100 differentially expressed genes. Results showed that genes related to detoxification of reactive oxygen species (ROS) and aldehydes (i.e., glutathione S-transferase zeta class-like isoform X1, thioredoxin M-type 4, and 2-alkenal reductase (NADP+-dependent)-like), metabolism (i.e., carboxylesterases and lecithin-cholesterol acyltransferase-like 4-like, nicotianamine aminotransferase A-like isoform X3, thiosulfate sulfurtransferase 18-like isoform X1, and FNR, root isozyme 2), cell transport (i.e., non-specific lipid-transfer protein-like protein At2g13820-like and major facilitator superfamily protein), Ca signal and hormone (i.e., calcium-binding protein CML19-like and IAA-amino acid hydrolase ILR1-like 4-like), gene regulation (i.e., Gag-pol polyprotein) and cell wall modification (i.e., glycosyl hydrolase family 10 protein) might play a role in B-induced alleviation of Al-toxicity. Our results are useful not only for our understanding of molecular processes associated with B-induced alleviation of Al-toxicity, but also for obtaining key molecular genes to enhance Al-tolerance of plants in the future. PMID:25747450

  13. Mechanisms on boron-induced alleviation of aluminum-toxicity in Citrus grandis seedlings at a transcriptional level revealed by cDNA-AFLP analysis.

    PubMed

    Zhou, Xin-Xing; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Chen, Li-Song

    2015-01-01

    The physiological and biochemical mechanisms on boron (B)-induced alleviation of aluminum (B)-toxicity in plants have been examined in some details, but our understanding of the molecular mechanisms underlying these processes is very limited. In this study, we first used the cDNA-AFLP to investigate the gene expression patterns in Citrus grandis roots responsive to B and Al interactions, and isolated 100 differentially expressed genes. Results showed that genes related to detoxification of reactive oxygen species (ROS) and aldehydes (i.e., glutathione S-transferase zeta class-like isoform X1, thioredoxin M-type 4, and 2-alkenal reductase (NADP+-dependent)-like), metabolism (i.e., carboxylesterases and lecithin-cholesterol acyltransferase-like 4-like, nicotianamine aminotransferase A-like isoform X3, thiosulfate sulfurtransferase 18-like isoform X1, and FNR, root isozyme 2), cell transport (i.e., non-specific lipid-transfer protein-like protein At2g13820-like and major facilitator superfamily protein), Ca signal and hormone (i.e., calcium-binding protein CML19-like and IAA-amino acid hydrolase ILR1-like 4-like), gene regulation (i.e., Gag-pol polyprotein) and cell wall modification (i.e., glycosyl hydrolase family 10 protein) might play a role in B-induced alleviation of Al-toxicity. Our results are useful not only for our understanding of molecular processes associated with B-induced alleviation of Al-toxicity, but also for obtaining key molecular genes to enhance Al-tolerance of plants in the future.

  14. Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain.

    PubMed

    Daou, Ihab; Beaudry, Hélène; Ase, Ariel R; Wieskopf, Jeffrey S; Ribeiro-da-Silva, Alfredo; Mogil, Jeffrey S; Séguéla, Philippe

    2016-01-01

    We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8(+) primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably blocked electrically induced action potentials in DRG neurons. Acute transdermal illumination of the hindpaws of Nav1.8-Arch(+) mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in double-transgenic Nav1.8-ChR2(+)-Arch(+) mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch(+) mice led to poststimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8(+) afferents in both inflammatory and neuropathic pain. Together, we present a selective analgesic approach in which genetically identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations. PMID:27022626

  15. Alleviating pain hypersensitivity through activation of type 4 metabotropic glutamate receptor.

    PubMed

    Vilar, Bruno; Busserolles, Jérôme; Ling, Bing; Laffray, Sophie; Ulmann, Lauriane; Malhaire, Fanny; Chapuy, Eric; Aissouni, Youssef; Etienne, Monique; Bourinet, Emmanuel; Acher, Francine; Pin, Jean-Philippe; Eschalier, Alain; Goudet, Cyril

    2013-11-27

    Hyperactivity of the glutamatergic system is involved in the development of central sensitization in the pain neuraxis, associated with allodynia and hyperalgesia observed in patients with chronic pain. Herein we study the ability of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate signaling and alleviate chronic pain. We show that mGlu4 are located both on unmyelinated C-fibers and spinal neurons terminals in the inner lamina II of the spinal cord where they inhibit glutamatergic transmission through coupling to Cav2.2 channels. Genetic deletion of mGlu4 in mice alters sensitivity to strong noxious mechanical compression and accelerates the onset of the nociceptive behavior in the inflammatory phase of the formalin test. However, responses to punctate mechanical stimulation and nocifensive responses to thermal noxious stimuli are not modified. Accordingly, pharmacological activation of mGlu4 inhibits mechanical hypersensitivity in animal models of inflammatory or neuropathic pain while leaving acute mechanical perception unchanged in naive animals. Together, these results reveal that mGlu4 is a promising new target for the treatment of chronic pain. PMID:24285900

  16. Demonstration of Cutaneous Allodynia in Association with Chronic Pelvic Pain

    PubMed Central

    Jarrell, John

    2009-01-01

    Pelvic pain is a common condition that is associated with dysmenorrhea and endometriosis. In some women the severe episodes of cyclic pain change and the resultant pain becomes continuous and this condition becomes known as Chronic Pelvic Pain. This state can be present even after the appropriate medical or surgical therapy has been instituted. It can be associated with pain and tenderness in the muscles of the abdomen wall and intra-pelvic muscles leading to severe dyspareunia. Additional symptoms of irritable bowel and interstitial cystitis are common. A common sign of the development of this state is the emergence of cutaneous allodynia which emerges from the so-called viscero-somatic reflex. A simple bedside test for the presence of cutaneous allodynia is presented that does not require excessive time or special equipment. This test builds on previous work associated with changes in sensation related to gall bladder function and the viscera-somatic reflex(1;2). The test is undertaken with the subject s permission after an explanation of how the test will be performed. Allodynia refers to a condition in which a stimulus that is not normally painful is interpreted by the subject as painful. In this instance the light touch associated with a cotton-tipped applicator would not be expected to be painful. A positive test is however noted by the woman as suddenly painful or suddenly sharp. The patterns of this sensation are usually in a discrete pattern of a dermatome of the nerves that innervate the pelvis. The underlying pathology is now interpreted as evidence of neuroplasticity as a consequence of severe and repeating pain with changes in the functions of the dorsal horns of the spinal cord that results in altered function of visceral tissues and resultant somatic symptoms(3). The importance of recognizing the condition lies in an awareness that this process may present coincidentally with the initiating condition or after it has been treated. It also permits the

  17. Exploratory tests of a simple aero-mechanical ride comfort system for lightly loaded aircraft. [evaluation of gust alleviating aircraft control surfaces

    NASA Technical Reports Server (NTRS)

    Hewes, D. E.; Stewart, E. C.

    1974-01-01

    Some exploratory wind tunnel and radio-controlled free-flight tests were made with a small high-wing airplane model (1.23m wing span) to study the concept of a simple aero mechanical system intended to alleviate gust loads and improve ride comfort of lightly loaded aircraft. The system consisted essentially of the outer portions of each wing being hinged in the chordwise direction and connected directly to the wing flaps using internal counter weights to provide neutral mass balance. When the wing experienced a change in velocity or angle of attack, the movable wing panels, acting as sensors and flap actuators, deflected in response to the changes in lift on the wing. The corresponding movements of the interconnected flaps tended to reduce the changes in the wing lift.

  18. Prior chronic stress induces persistent polyI:C-induced allodynia and depressive-like behavior in rats: Possible involvement of glucocorticoids and microglia.

    PubMed

    Chijiwa, Takeharu; Oka, Takakazu; Lkhagvasuren, Battuvshin; Yoshihara, Kazufumi; Sudo, Nobuyuki

    2015-08-01

    When animals suffer from viral infections, they develop a set of symptoms known as the "sickness response." Recent studies suggest that psychological stress can modulate the sickness response. However, it remains uncertain whether acute and chronic psychosocial stresses have the same effect on viral infection-induced sickness responses. To address this question, we compared changes in polyI:C-induced sickness responses, such as fever, change of body weight and food intake, mechanical allodynia, and depressive-like behavior, in rats that had been pre-exposed to single and repeated social defeat stresses. Intraperitoneal injection of polyI:C induced a maximal fever of 38.0°C 3h after injection. Rats exposed to prior social defeat stress exhibited blunted febrile responses, which were more pronounced in the repeated stress group. Furthermore, only the repeated stress group showed late-onset and prolonged mechanical allodynia lasting until 8days after injection in the von Frey test and prolonged immobility time in the forced swim test 9days post-injection. To assess the role of glucocorticoids and microglia in the delayed and persistent development of these sickness responses in rats exposed to repeated stress, we investigated the effect of pretreatment with RU486, a glucocorticoid receptor antagonist, and minocycline, an inhibitor of microglial activation, on polyI:C-induced allodynia and depressive-like behavior. Pretreatment with either drug inhibited both the delayed allodynia and depressive-like behavior. The present study demonstrates that repeated, but not single, social defeat stress followed by systemic polyI:C administration induced prolonged allodynia and depressive-like behavior in rats. Our results show that even though a single-event psychosocial stress does not have any effect by itself, animals may develop persistent allodynia and depressive-like behavior when they suffer from an infectious disease if they are pre-exposed to repeated or chronic

  19. Allodynia mediated by C-tactile afferents in human hairy skin

    PubMed Central

    Nagi, Saad S; Rubin, Troy K; Chelvanayagam, David K; Macefield, Vaughan G; Mahns, David A

    2011-01-01

    Abstract We recently showed a contribution of low-threshold cutaneous mechanoreceptors to vibration-evoked changes in the perception of muscle pain. Neutral-touch stimulation (vibration) of the hairy skin during underlying muscle pain evoked an overall increase in pain intensity, i.e. allodynia. This effect appeared to be dependent upon cutaneous afferents, as allodynia was abolished by intradermal anaesthesia. However, it remains unclear whether allodynia results from activation of a single class of cutaneous afferents or the convergence of inputs from multiple classes. Intriguingly, no existing human study has examined the contribution of C-tactile (CT) afferents to allodynia. Detailed psychophysical observations were made in 29 healthy subjects (18 males and 11 females). Sustained muscle pain was induced by infusing hypertonic saline (HS: 5%) into tibialis anterior muscle (TA). Sinusoidal vibration (200 Hz–200 μm) was applied to the hairy skin overlying TA. Pain ratings were recorded using a visual analogue scale (VAS). In order to evaluate the role of myelinated and unmyelinated cutaneous afferents in the expression of vibration-evoked allodynia, compression block of the sciatic nerve, and low-dose intradermal anaesthesia (Xylocaine 0.25%) were used, respectively. In addition, the modulation of muscle pain by gentle brushing (1.0 and 3.0 cm s−1) – known to excite CT fibres – was examined. Brushing stimuli were applied to the hairy skin with all fibres intact and following the blockade of myelinated afferents. During tonic muscle pain (VAS 4–6), vibration evoked a significant and reproducible increase in muscle pain (allodynia) that persisted following compression of myelinated afferents. During compression block, the sense of vibration was abolished, but the vibration-evoked allodynia persisted. In contrast, selective anaesthesia of unmyelinated cutaneous afferents abolished the allodynia, whereas the percept of vibration remained unaffected

  20. A novel model of combined neuropathic and inflammatory pain displaying long-lasting allodynia and spontaneous pain-like behaviour.

    PubMed

    Allchorne, Andrew J; Gooding, Hayley L; Mitchell, Rory; Fleetwood-Walker, Sue M

    2012-12-01

    Many clinical cases of chronic pain exhibit both neuropathic and inflammatory components. In contrast, most animal models of chronic pain focus on one type of injury alone. Here we present a novel combined model of both neuropathic and inflammatory pain and characterise its distinctive properties. This combined model of chronic constriction injury (CCI) and intraplantar Complete Freund's Adjuvant (CFA) injection results in enhanced mechanical allodynia, thermal hyperalgesia, a static weight bearing deficit, and notably pronounced spontaneous foot lifting (SFL) behaviour (which under our conditions was not seen in either individual model and may reflect ongoing/spontaneous pain). Dorsal root ganglion (DRG) expression of Activating Transcription Factor-3 (ATF-3), a marker of axonal injury, was no greater in the combined model than CCI alone. Initial pharmacological characterisation of the new model showed that the SFL was reversed by gabapentin or diclofenac, typical analgesics for neuropathic or inflammatory pain respectively, but not by mexiletine, a Na(+) channel blocker effective in both neuropathic and inflammatory pain models. Static weight bearing deficit was moderately reduced by gabapentin, whereas only diclofenac reversed mechanical allodynia. This novel animal model of chronic pain may prove a useful test-bed for further analysing the pharmacological susceptibility of complicated clinical pain states. PMID:23131427

  1. Fucoidan attenuates the existing allodynia and hyperalgesia in a rat model of neuropathic pain.

    PubMed

    Hu, Chuanyin; Zhang, Guoping; Zhao, Yun-Tao

    2014-06-13

    Fucoidan is an active constituent found in brown seaweeds, which have potential neuroprotection. The current study aimed to investigate the effects of fucoidan on the maintenance of neuropathic pain induced by L5 spinal nerve ligation (SNL) and the underlying mechanism related to the spinal neuroimmune responses. Animals were randomized into 5 groups: sham-operation with vehicle and SNL with vehicle or fucoidan (15, 50, and 100mg/kg). Different doses of fucoidan or vehicle were administered intrathecally once daily from postoperative day (POD) 11-20. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) was measured on 1 day before operation and days 10, 20, 22, 24, 26, 28, 30 after operation. Glial activation markers such as glial fibrillary acidic protein (GFAP) and macrophage antigen complex-1 (mac-1), inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 activation, and extracellular signalregulated protein kinase (ERK) activation in the lumbar spinal cord were determined on day 30 after operation. The results showed that fucoidan caused dose-dependently attenuation of mechanical allodynia and thermal hyperalgesia. Furthermore, fucoidan could markedly inhibit neuroimmune activation characterized by glial activation, production of cytokines as well as ERK activation. The analgesic effect of intrathecal fucoidan in rats receiving SNL might partly attribute to the inhibition of neuroimmune activation associated with the maintenance of neuropathic pain.

  2. Intrathecal [6]-gingerol administration alleviates peripherally induced neuropathic pain in male Sprague-Dawley rats.

    PubMed

    Gauthier, Marie-Lou; Beaudry, Francis; Vachon, Pascal

    2013-08-01

    [6]-Gingerol, a structural analog of capsaicin, is an agonist of the transient receptor potential vanilloid 1 channel, which is known to have therapeutic properties for the treatment of pain and inflammation. The main objective of this study was to determine the central effect of [6]-gingerol on neuropathic pain when injected intrathecally at the level of the lumbar spinal cord. [6]-Gingerol distribution was evaluated following a 40 mg/kg intraperitoneal injection, and the brain-to-plasma and spinal cord-to-plasma ratios (0.73 and 1.7, respectively) suggest that [6]-gingerol penetrates well the central nervous system of rats. Induction of pain was performed using the sciatic nerve ligation model on rats, and a 10-µg intrathecal injections of [6]-gingerol was performed to evaluate its central effect. The results suggest a significant decrease of secondary mechanical allodynia after 30 min, 2 h and 4 h (p < 0.05, p < 0.01 and p < 0.001) and thermal hyperalgesia after 30 min, 2 h and 4 h (p < 0.05, p < 0.01 and p < 0.01). These promising results illustrate that [6]-gingerol could alleviate neuropathic pain by acting centrally at the level of the spinal cord.

  3. Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response

    PubMed Central

    Dash, Srikanta; Chava, Srinivas; Aydin, Yucel; Chandra, Partha K.; Ferraris, Pauline; Chen, Weina; Balart, Luis A.; Wu, Tong; Garry, Robert F.

    2016-01-01

    Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, liver cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms by which HCV infection leads to chronic liver disease and HCC are not well understood. The infection cycle of HCV is initiated by the attachment and entry of virus particles into a hepatocyte. Replication of the HCV genome inside hepatocytes leads to accumulation of large amounts of viral proteins and RNA replication intermediates in the endoplasmic reticulum (ER), resulting in production of thousands of new virus particles. HCV-infected hepatocytes mount a substantial stress response. How the infected hepatocyte integrates the viral-induced stress response with chronic infection is unknown. The unfolded protein response (UPR), an ER-associated cellular transcriptional response, is activated in HCV infected hepatocytes. Over the past several years, research performed by a number of laboratories, including ours, has shown that HCV induced UPR robustly activates autophagy to sustain viral replication in the infected hepatocyte. Induction of the cellular autophagy response is required to improve survival of infected cells by inhibition of cellular apoptosis. The autophagy response also inhibits the cellular innate antiviral program that usually inhibits HCV replication. In this review, we discuss the physiological implications of the HCV-induced chronic ER-stress response in the liver disease progression. PMID:27223299

  4. Feasibility of Human Amniotic Fluid Derived Stem Cells in Alleviation of Neuropathic Pain in Chronic Constrictive Injury Nerve Model

    PubMed Central

    Chiang, Chien-Yi; Liu, Shih-An; Sheu, Meei-Ling; Chen, Fu-Chou; Chen, Chun-Jung; Su, Hong-Lin; Pan, Hung-Chuan

    2016-01-01

    Purpose The neurobehavior of neuropathic pain by chronic constriction injury (CCI) of sciatic nerve is very similar to that in humans, and it is accompanied by a profound local inflammation response. In this study, we assess the potentiality of human amniotic fluid derived mesenchymal stem cells (hAFMSCs) for alleviating the neuropathic pain in a chronic constriction nerve injury model. Methods and Methods This neuropathic pain animal model was conducted by four 3–0 chromic gut ligatures loosely ligated around the left sciatic nerve in Sprague—Dawley rats. The intravenous administration of hAFMSCs with 5x105 cells was conducted for three consecutive days. Results The expression IL-1β, TNF-α and synaptophysin in dorsal root ganglion cell culture was remarkably attenuated when co-cultured with hAFMSCs. The significant decrease of PGP 9.5 in the skin after CCI was restored by administration of hAFMSCs. Remarkably increased expression of CD 68 and TNF-α and decreased S-100 and neurofilament expression in injured nerve were rescued by hAFMSCs administration. Increases in synaptophysin and TNF-α over the dorsal root ganglion were attenuated by hAFMSCs. Significant expression of TNF-α and OX-42 over the dorsal spinal cord was substantially attenuated by hAFMSCs. The increased amplitude of sensory evoked potential as well as expression of synaptophysin and TNF-α expression was alleviated by hAFMSCs. Human AFMSCs significantly improved the threshold of mechanical allodynia and thermal hyperalgesia as well as various parameters of CatWalk XT gait analysis. Conclusion Human AFMSCs administration could alleviate the neuropathic pain demonstrated in histomorphological alteration and neurobehavior possibly through the modulation of the inflammatory response. PMID:27441756

  5. Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain123

    PubMed Central

    Daou, Ihab; Beaudry, Hélène; Ase, Ariel R.; Wieskopf, Jeffrey S.; Ribeiro-da-Silva, Alfredo; Mogil, Jeffrey S.

    2016-01-01

    Abstract We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8+ primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably blocked electrically induced action potentials in DRG neurons. Acute transdermal illumination of the hindpaws of Nav1.8-Arch+ mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in double-transgenic Nav1.8-ChR2+-Arch+mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch+ mice led to poststimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8+ afferents in both inflammatory and neuropathic pain. Together, we present a selective analgesic approach in which genetically identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations. PMID:27022626

  6. Intradermal glutamate and capsaicin injections: intra- and interindividual variability of provoked hyperalgesia and allodynia.

    PubMed

    Nilsson, Matias; Lassen, Dorte; Andresen, Trine; Nielsen, Anders K; Arendt-Nielsen, Lars; Drewes, Asbjørn M

    2014-06-01

    Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18-38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush-evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter- and intra-individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra-individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.

  7. Lipoxins and aspirin-triggered lipoxin alleviate bone cancer pain in association with suppressing expression of spinal proinflammatory cytokines

    PubMed Central

    2012-01-01

    Background The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. Methods The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t.) or intravenous (i.v.) injection. The protein level of LXA4 receptor (ALX) was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. Results Our results demonstrated that: 1) i.t. injection with the same dose (0.3 nmol) of lipoxin A4 (LXA4), lipoxin B4 (LXB4) or aspirin-triggered-15-epi-lipoxin A4 (ATL) could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2) The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3) Immunohistochemistry showed that the lipoxin receptor (ALX)-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4) Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly attenuate the

  8. The mechanisms involved in seed dormancy alleviation by hydrogen cyanide unravel the role of reactive oxygen species as key factors of cellular signaling during germination.

    PubMed

    Oracz, Krystyna; El-Maarouf-Bouteau, Hayat; Kranner, Ilse; Bogatek, Renata; Corbineau, Françoise; Bailly, Christophe

    2009-05-01

    The physiological dormancy of sunflower (Helianthus annuus) embryos can be overcome during dry storage (after-ripening) or by applying exogenous ethylene or hydrogen cyanide (HCN) during imbibition. The aim of this work was to provide a comprehensive model, based on oxidative signaling by reactive oxygen species (ROS), for explaining the cellular mode of action of HCN in dormancy alleviation. Beneficial HCN effect on germination of dormant embryos is associated with a marked increase in hydrogen peroxide and superoxide anion generation in the embryonic axes. It is mimicked by the ROS-generating compounds methylviologen and menadione but suppressed by ROS scavengers. This increase results from an inhibition of catalase and superoxide dismutase activities and also involves activation of NADPH oxidase. However, it is not related to lipid reserve degradation or gluconeogenesis and not associated with marked changes in the cellular redox status controlled by the glutathione/glutathione disulfide couple. The expression of genes related to ROS production (NADPHox, POX, AO1, and AO2) and signaling (MAPK6, Ser/ThrPK, CaM, and PTP) is differentially affected by dormancy alleviation either during after-ripening or by HCN treatment, and the effect of cyanide on gene expression is likely to be mediated by ROS. It is also demonstrated that HCN and ROS both activate similarly ERF1, a component of the ethylene signaling pathway. We propose that ROS play a key role in the control of sunflower seed germination and are second messengers of cyanide in seed dormancy release.

  9. Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury model mice via suppression of TNF-α expression in the spinal cord

    PubMed Central

    Nakanishi, Miho; Nakae, Aya; Kishida, Yuki; Baba, Kousuke; Sakashita, Noriko; Shibata, Masahiko; Yoshikawa, Hideki

    2016-01-01

    Background Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism of the analgesic effect of GJG in a chronic constriction injury model. Results GJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p < 0.0001; cold-plate test, p < 0.0001; hot-plate test p = 0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-α in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-α was co-expressed in Iba1-positive cells at day 3 post-operation. GJG decreased the phosphorylation of p38 in the ipsilateral dorsal horn. Moreover, intrathecal injection of tumor necrosis factor-α opposed the anti-allodynic effect of GJG in the cold-plate test. Conclusions Our data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-α expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation. PMID:27296622

  10. Tactile C fibers and their contributions to pleasant sensations and to tactile allodynia

    PubMed Central

    Liljencrantz, Jaquette; Olausson, Håkan

    2014-01-01

    In humans converging evidence indicates that affective aspects of touch are signaled by low threshold mechanoreceptive C tactile (CT) afferents. Analyses of electrophysiological recordings, psychophysical studies in denervated subjects, and functional brain imaging, all indicate that CT primary afferents contribute to pleasant touch and provide an important sensory underpinning of social behavior. Considering both these pleasant and social aspects of gentle skin-to-skin contact, we have put forward a framework within which to consider CT afferent coding properties and pathways—the CT affective touch hypothesis. Recent evidence from studies in mice suggests that CTs, when activated, may have analgesic or anxiolytic effects. However, in neuropathic pain conditions, light touch can elicit unpleasant sensations, so called tactile allodynia. In humans, tactile allodynia is associated with reduced CT mediated hedonic touch processing suggesting loss of the normally analgesic effect of CT signaling. We thus propose that the contribution of CT afferents to tactile allodynia is mainly through a loss of their normally pain inhibiting role. PMID:24639633

  11. Buffet Load Alleviation

    NASA Technical Reports Server (NTRS)

    Ryall, T. G.; Moses, R. W.; Hopkins, M. A.; Henderson, D.; Zimcik, D. G.; Nitzsche, F.

    2004-01-01

    High performance aircraft are, by their very nature, often required to undergo maneuvers involving high angles of attack. Under these conditions unsteady vortices emanating from the wing and the fuselage will impinge on the twin fins (required for directional stability) causing excessive buffet loads, in some circumstances, to be applied to the aircraft. These loads result in oscillatory stresses, which may cause significant amounts of fatigue damage. Active control is a possible solution to this important problem. A full-scale test was carried out on an F/A-18 fuselage and fins using piezoceramic actuators to control the vibrations. Buffet loads were simulated using very powerful electromagnetic shakers. The first phase of this test was concerned with the open loop system identification whereas the second stage involved implementing linear time invariant control laws. This paper looks at some of the problems encountered as well as the corresponding solutions and some results. It is expected that flight trials of a similar control system to alleviate buffet will occur as early as 2001.

  12. Anti-GD2 with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia

    PubMed Central

    Sorkin, Linda S.; Otto, Mario; Baldwin, William M.; Vail, Emily; Gillies, Stephen D.; Handgretinger, Rupert; Barfield, Raymond C.; Yu, Hui Ming; Yu, Alice L.

    2013-01-01

    Monoclonal antibodies against GD2 ganglioside, such as ch14.18, the human–mouse chimeric antibody, have been shown to be effective for the treatment of neuroblastoma. However, treatment is associated with generalized, relatively opiate-resistant pain. We investigated if a point mutation in ch14.18 antibody (hu14.18K332A) to limit complement-dependent cytotoxicity (CDC) would ameliorate the pain behavior, while preserving antibody-dependent cellular cytotoxicity (ADCC). In vitro, CDC and ADCC were measured using europium-TDA assay. In vivo, allodynia was evaluated by measuring thresholds to von Frey filaments applied to the hindpaws after injection of either ch14.18 or hu14.18K332 into wild type rats or rats with deficient complement factor 6. Other rats were pretreated with complement factor C5a receptor antagonist and tested following ch14.18 injection. The mutation reduces the antibody’s ability to activate complement, while maintaining its ADCC capabilities. Injection of hu14.18K322 (1 or 3 mg/kg) produced faster resolving allodynia than that engendered by ch14.18 (1 mg/kg). Injection of ch14.18 (1 mg/kg) into rats with C6 complement deficiency further reduced antibody-induced allodynia, while pre-treatment with complement factor C5a receptor antagonist completely abolished ch14.18-induced allodynia. These findings showed that mutant hu14.18 K322 elicited less allodynia than ch14.18 and that ch14.18-elicited allodynia is due to activation of the complement cascade: in part, to formation of membrane attack complex, but more importantly to release of complement factor C5a. Development of immunotherapeutic agents with decreased complement-dependent lysis while maintaining cellular cytotoxicity may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of therapeutic antibodies. PMID:20171010

  13. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation

    PubMed Central

    Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara; Lei, Jianxun; Gupta, Kalpna

    2016-01-01

    Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides ‘proof of principle’ for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia. PMID:26703965

  14. Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation.

    PubMed

    Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara; Lei, Jianxun; Gupta, Kalpna

    2016-05-01

    Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides 'proof of principle' for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia.

  15. Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury

    PubMed Central

    Davies, Jeannette E; Pröschel, Christoph; Zhang, Ningzhe; Noble, Mark; Mayer-Pröschel, Margot; Davies, Stephen JA

    2008-01-01

    Background Two critical challenges in developing cell-transplantation therapies for injured or diseased tissues are to identify optimal cells and harmful side effects. This is of particular concern in the case of spinal cord injury, where recent studies have shown that transplanted neuroepithelial stem cells can generate pain syndromes. Results We have previously shown that astrocytes derived from glial-restricted precursor cells (GRPs) treated with bone morphogenetic protein-4 (BMP-4) can promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, we now show that transplantation of GRP-derived astrocytes (GDAs) generated by exposure to the gp130 agonist ciliary neurotrophic factor (GDAsCNTF), the other major signaling pathway involved in astrogenesis, results in failure of axon regeneration and functional recovery. Moreover, transplantation of GDACNTF cells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2 weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. In contrast, rats transplanted with GDAsBMP did not exhibit pain syndromes. Conclusion Our results show that not all astrocytes derived from embryonic precursors are equally beneficial for spinal cord repair and they provide the first identification of a differentiated neural cell type that can cause pain syndromes on transplantation into the damaged spinal cord, emphasizing the importance of evaluating the capacity of candidate cells to cause allodynia before initiating clinical trials. They also confirm the particular promise of GDAs treated with bone morphogenetic protein for spinal cord injury repair. PMID:18803859

  16. Administration of N-acetylserotonin and melatonin alleviate chronic ketamine-induced behavioural phenotype accompanying BDNF-independent and dependent converging cytoprotective mechanisms in the hippocampus.

    PubMed

    Choudhury, Arnab; Singh, Seema; Palit, Gautam; Shukla, Shubha; Ganguly, Surajit

    2016-01-15

    Though growing evidence implicates both melatonin (MLT) and its immediate precursor N-acetylserotonin (NAS) in the regulation of hippocampal neurogenesis, their comparative mechanistic relationship with core behavioural correlates of psychiatric disorders is largely unknown. To address this issue, we investigated the ability of these indoleamines to mitigate the behavioral phenotypes associated with NMDA-receptor (NMDAR) hypofunction in mice. We demonstrated that exogenous MLT and NAS treatments attenuated the NMDAR antagonist (ketamine) induced immobility in the forced swim test (FST) but not the classical striatum-related hyperlocomotor activity phenotype. The MLT/NAS-mediated protection of the phenotype in FST could be correlated to the ability of these indoleamines to counteract the deleterious effects of chronic ketamine on pro-survival molecular events by restoring the activities in MEK-ERK and PI3K-AKT pathways in the hippocampus. MLT seems to modulate these pathways by promoting accumulation of the mature form of BDNF above the control (vehicle-treated) levels, perhaps via MLT receptor-dependent mechanisms and in the process overcoming the ketamine-induced down-regulation of BDNF. In contrast, NAS appears to partly restore the ketamine-induced decrease of BDNF to the control levels. In spite of this fundamental difference in modulating BDNF levels in the upstream events, both MLT and NAS seem to overlap in the TrkB-induced downstream pro-survival mechanisms in the hippocampus, providing protection against NMDAR-hypofunction related cellular events. Perhaps, this also signifies the physiological importance of robust MLT synthesizing machinery that converts serotonin to MLT, in ensuring positive impact on hippocampus-related symptoms in psychiatric disorders.

  17. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial.

    PubMed

    Nurmikko, Turo J; Serpell, Mick G; Hoggart, Barbara; Toomey, Peter J; Morlion, Bart J; Haines, Derek

    2007-12-15

    Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks. PMID:17997224

  18. N-hexane neuropathy with vertigo and cold allodynia in a silk screen printer: A case study.

    PubMed

    Pradhan, Sunil; Tandon, Ruchika

    2015-01-01

    N-hexane neuropathy is an occupational disease caused by exposure to n-hexane, which is used as a solvent in silk screen printing. Here, we describe a 35-year-old man, a silk screen printer by profession, who presented with dizziness, distal swelling of both lower limbs for 10 months and tingling and burning sensation in both feet for 9.5 months along with cold allodynia. The patient had normal results of a motor and sensory system examination, apart from an impaired temperature sense. Nerve conduction tests showed a conduction block in bilateral common peroneal nerves and absence of conduction in bilateral sural nerves. These symptoms resolved when further exposure to n-hexane was ceased but cold allodynia remained. Thus, cold allodynia and impaired temperature sense can be a manifestation of n-hexane neuropathy. Hence, abnormalities on nerve conduction studies can be detected in n-hexane neuropathy patients, even before clinical examination detects any such abnormalities. In the case of the patients presenting with sensory motor neuropathy, history of occupational exposure to n-hexane becomes important, as the sooner the disease is detected, the better the chances of recovery.

  19. The impact of allodynia on the efficacy of almotriptan when given early in migraine: data from the "Act when mild" study.

    PubMed

    Díaz-Insa, S; Goadsby, P J; Zanchin, G; Fortea, J; Falqués, M; Vila, C

    2011-12-01

    The objective of this study was to evaluate the impact of allodynia on treatment outcomes in the patients with acute migraine treated in the "Act when Mild" (AwM) study. AwM, a randomized placebo-controlled trial, studied almotriptan 12.5 mg in the early treatment (within 1 hr) of acute migraine when the pain was still mild, and investigated clinical outcomes in the presence or absence of allodynia, which was prospectively recorded using patient questionnaires. Of the total population, 39% (n = 404) reported allodynia that did not alter the efficacy of almotriptan administered for early/mild pain in terms of 2-hr pain-free rates (53.9% for allodynic patients vs. 52.5% for nonallodynic patients). Similarly, sustained pain-free rates were 47.2% versus 45.5%, and migraine duration 1.40 versus 1.54 hr, respectively. However, allodynia impaired the effectiveness of almotriptan in the patients with moderate/severe pain in terms of longer migraine duration, fewer patients achieving pain-free status, and more requiring rescue medication. In conclusion, the lack of effect of allodynia on the efficacy of almotriptan given for early/mild migraine pain might help explain the improved outcomes associated with the early-treatment strategy in AwM. Moreover, the data suggest that pain intensity is the main driver of triptan response, and not the presence or absence of allodynia. PMID:21777163

  20. Gust alleviation system to improve ride comfort of light airplanes

    NASA Technical Reports Server (NTRS)

    Stewart, E. C.; Phillips, W. H.; Hewes, D. E.

    1975-01-01

    System consists of movable auxiliary aerodynamic sensors mounted on fuselage and connected to trailing-edge flaps by rigid mechanical linkages. System achieves alleviation by reducing lift-curve slope of airplane to such a small value that gust-induced angles of attack will result in small changes in lift.

  1. [Relationship between cutaneous temperature and hand edema and allodynia after stroke--the etiology of shoulder-hand syndrome].

    PubMed

    Yamanaka, Hiroko; Yamanaka, Hidekata

    2015-01-01

    The etiology of shoulder-hand syndrome is as yet unknown. We hypothesized that it may be due to damaged unmyelinated fibers in front of the subscapular muscle. We examined the existence of edema and hypersensitivity to pain in the hands of stroke patients during the subacute stage and their relationships to cutaneous temperatures of the index fingertips in 75 hemiplegic patients (23 without edema, 32 with only edema, and 20 with edema plus allodynia). Patients were placed into two groups (comfortable and warm) depending on room temperature (22.2-25.6°C and 25.7-30°C, respectively). Of the patients with hand edema plus allodynia, 75% had a large lesion in the capsula, cortical white matter, and putamen. It was previously reported that the cutaneous temperature of the arm on the paralysis side of patients with lesions of the capsula or putamen was lower than that on the non-paralysis side. In the edema plus allodynia group, the temperature of the index fingertip on the affected side was higher than that of their contralateral fingers; the differences were smaller under warm conditions possibly due to blockade of the sympathetic nerves in the peripheral nerve. By contrast, in patients in the edema group, there were no differences in cutaneous temperatures of their two index fingers. Thus, it appears that patients with mild cases of shoulder-hand syndrome have conduction blocks in the posterior cord of the brachial plexus, while those with severe cases have both conduction blocks and neurogenic inflammation in both the lateral and posterior cords.

  2. Spinal microglial proliferation is evident in a rat model of painful disc herniation both in the presence of behavioral hypersensitivity and following minocycline treatment sufficient to attenuate allodynia.

    PubMed

    Rothman, Sarah M; Guarino, Benjamin B; Winkelstein, Beth A

    2009-09-01

    Although spinal glia acquire a reactive profile in radiculopathy, glial cell proliferation remains largely unstudied. This study investigated spinal glial proliferation in a model simulating painful disc herniation; the C7 nerve root underwent compression and chromic gut suture exposure or sham procedures. A subset of injured rats received minocycline injections prior to injury. Allodynia was assessed and bromodeoxyuridine (BrdU) was injected 2 hr before tissue harvest on day 1 or 3. Spinal cell proliferation and phenotype identification were assayed by fluorescent colabeling with antibodies to BrdU and either glial fibrillary acidic protein (astrocytes) or Iba1 (microglia). At day 1, ipsilateral allodynia was significantly increased (P < 0.001) for injury over sham. Minocycline treatment significantly decreased ipsilateral allodynia to sham levels at day 1 (P < 0.001). At day 3, ipsilateral allodynia remained and contralateral allodynia was also present for injury (P< 0.003) over sham. The number of BrdU-positive cells in the ipsilateral spinal dorsal horn at day 1 after injury was significantly elevated (P < 0.001) over sham. Approximately 70% of BrdU-positive cells labeled positively for Iba1; dividing microglia were significantly increased (P < 0.004) in the ipsilateral dorsal horn at day 1 following injury compared with sham. Spinal cellular proliferation after injury was not changed by minocycline injection. By day 3, the number of BrdU-positive cells had returned to sham levels bilaterally. Data indicate that spinal microglia proliferate after injury but that proliferation is not abolished by minocycline treatment that attenuates allodynia, indicating that spinal microglial proliferation may be related to injury and may not be linked to changes in sensory perception.

  3. Harnessing motivation to alleviate neglect.

    PubMed

    Russell, Charlotte; Li, Korina; Malhotra, Paresh A

    2013-01-01

    The syndrome of spatial neglect results from the combination of a number of deficits in attention, with patients demonstrating both spatially lateralized and non-lateralized impairments. Previous reports have hinted that there may be a motivational component to neglect and that modulating this might alleviate some of the debilitating symptoms. Additionally, recent work on the effects of reward on attention in healthy participants has revealed improvements across a number of paradigms. As the primary deficit in neglect has been associated with attention, this evidence for reward's effects is potentially important. However, until very recently there have been few empirical studies addressing this potential therapeutic avenue. Here we review the growing body of evidence that attentional impairments in neglect can be reduced by motivation, for example in the form of preferred music or anticipated monetary reward, and discuss the implications of this for treatments for these patients. Crucially these effects of positive motivation are not observed in all patients with neglect, suggesting that the consequences of motivation may relate to individual lesion anatomy. Given the key role of dopaminergic systems in motivational processes, we suggest that motivational stimulation might act as a surrogate for dopaminergic stimulation. In addition, we consider the relationship between clinical post stroke apathy and lack of response to motivation.

  4. Harnessing Motivation to Alleviate Neglect

    PubMed Central

    Russell, Charlotte; Li, Korina; Malhotra, Paresh A.

    2013-01-01

    The syndrome of spatial neglect results from the combination of a number of deficits in attention, with patients demonstrating both spatially lateralized and non-lateralized impairments. Previous reports have hinted that there may be a motivational component to neglect and that modulating this might alleviate some of the debilitating symptoms. Additionally, recent work on the effects of reward on attention in healthy participants has revealed improvements across a number of paradigms. As the primary deficit in neglect has been associated with attention, this evidence for reward’s effects is potentially important. However, until very recently there have been few empirical studies addressing this potential therapeutic avenue. Here we review the growing body of evidence that attentional impairments in neglect can be reduced by motivation, for example in the form of preferred music or anticipated monetary reward, and discuss the implications of this for treatments for these patients. Crucially these effects of positive motivation are not observed in all patients with neglect, suggesting that the consequences of motivation may relate to individual lesion anatomy. Given the key role of dopaminergic systems in motivational processes, we suggest that motivational stimulation might act as a surrogate for dopaminergic stimulation. In addition, we consider the relationship between clinical post stroke apathy and lack of response to motivation. PMID:23761744

  5. Alleviating α quenching by solar wind and meridional flows

    NASA Astrophysics Data System (ADS)

    Mitra, D.; Moss, D.; Tavakol, R.; Brandenburg, A.

    2011-02-01

    Aims: We study the ability of magnetic helicity expulsion to alleviate catastrophic α-quenching in mean field dynamos in two-dimensional spherical wedge domains. Methods: Motivated by the physical state of the outer regions of the Sun, we consider α^2Ω mean field models with a dynamical α quenching. We include two mechanisms which have the potential to facilitate helicity expulsion, namely advection by a mean flow ("solar wind") and meridional circulation. Results: We find that a wind alone can prevent catastrophic quenching, with the field saturating at finite amplitude. In certain parameter ranges, the presence of a large-scale meridional circulation can reinforce this alleviation. However, the saturated field strengths are typically below the equipartition field strength. We discuss possible mechanisms that might increase the saturated field.

  6. Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

    PubMed Central

    Watson, Jaime L.; Hala, Tamara J.; Putatunda, Rajarshi; Sannie, Daniel; Lepore, Angelo C.

    2014-01-01

    In humans, sensory abnormalities, including neuropathic pain, often result from traumatic spinal cord injury (SCI). SCI can induce cellular changes in the CNS, termed central sensitization, that alter excitability of spinal cord neurons, including those in the dorsal horn involved in pain transmission. Persistently elevated levels of neuronal activity, glial activation, and glutamatergic transmission are thought to contribute to the hyperexcitability of these dorsal horn neurons, which can lead to maladaptive circuitry, aberrant pain processing and, ultimately, chronic neuropathic pain. Here we present a mouse model of SCI-induced neuropathic pain that exhibits a persistent pain phenotype accompanied by chronic neuronal hyperexcitability and glial activation in the spinal cord dorsal horn. We generated a unilateral cervical contusion injury at the C5 or C6 level of the adult mouse spinal cord. Following injury, an increase in the number of neurons expressing ΔFosB (a marker of chronic neuronal activation), persistent astrocyte activation and proliferation (as measured by GFAP and Ki67 expression), and a decrease in the expression of the astrocyte glutamate transporter GLT1 are observed in the ipsilateral superficial dorsal horn of cervical spinal cord. These changes have previously been associated with neuronal hyperexcitability and may contribute to altered pain transmission and chronic neuropathic pain. In our model, they are accompanied by robust at-level hyperaglesia in the ipsilateral forepaw and allodynia in both forepaws that are evident within two weeks following injury and persist for at least six weeks. Furthermore, the pain phenotype occurs in the absence of alterations in forelimb grip strength, suggesting that it represents sensory and not motor abnormalities. Given the importance of transgenic mouse technology, this clinically-relevant model provides a resource that can be used to study the molecular mechanisms contributing to neuropathic pain

  7. A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4.

    PubMed

    Bastos, Leandro F S; Godin, Adriana M; Zhang, Yingning; Jarussophon, Suwatchai; Ferreira, Bruno C S; Machado, Renes R; Maier, Steven F; Konishi, Yasuo; de Freitas, Rossimiriam P; Fiebich, Bernd L; Watkins, Linda R; Coelho, Márcio M; Moraes, Márcio F D

    2013-05-24

    Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline's positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline's antibiotic actions and divalent cation (Ca(2+); Mg(2+)) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75 mg/kg, 47.50mg/kg or 95.00 mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca(2+) chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca(2+) chelating activities might confer greater safety over conventional tetracyclines. PMID:23523650

  8. Arbuscular mycorrhizal fungi in alleviation of salt stress: a review

    PubMed Central

    Evelin, Heikham; Kapoor, Rupam; Giri, Bhoopander

    2009-01-01

    Background Salt stress has become a major threat to plant growth and productivity. Arbuscular mycorrhizal fungi colonize plant root systems and modulate plant growth in various ways. Scope This review addresses the significance of arbuscular mycorrhiza in alleviation of salt stress and their beneficial effects on plant growth and productivity. It also focuses on recent progress in unravelling biochemical, physiological and molecular mechanisms in mycorrhizal plants to alleviate salt stress. Conclusions The role of arbuscular mycorrhizal fungi in alleviating salt stress is well documented. This paper reviews the mechanisms arbuscular mycorrhizal fungi employ to enhance the salt tolerance of host plants such as enhanced nutrient acquisition (P, N, Mg and Ca), maintenance of the K+ : Na+ ratio, biochemical changes (accumulation of proline, betaines, polyamines, carbohydrates and antioxidants), physiological changes (photosynthetic efficiency, relative permeability, water status, abscissic acid accumulation, nodulation and nitrogen fixation), molecular changes (the expression of genes: PIP, Na+/H+ antiporters, Lsnced, Lslea and LsP5CS) and ultra-structural changes. Theis review identifies certain lesser explored areas such as molecular and ultra-structural changes where further research is needed for better understanding of symbiosis with reference to salt stress for optimum usage of this technology in the field on a large scale. This review paper gives useful benchmark information for the development and prioritization of future research programmes. PMID:19815570

  9. Focused grooming networks and stress alleviation in wild female baboons.

    PubMed

    Wittig, Roman M; Crockford, Catherine; Lehmann, Julia; Whitten, Patricia L; Seyfarth, Robert M; Cheney, Dorothy L

    2008-06-01

    We examine the relationship between glucocorticoid (GC) levels and grooming behavior in wild female baboons during a period of instability in the alpha male rank position. All females' GC levels rose significantly at the onset of the unstable period, though levels in females who were at lower risk of infanticide began to decrease sooner in the following weeks. Three factors suggest that females relied on a focused grooming network as a coping mechanism to alleviate stress. First, all females' grooming networks became less diverse in the weeks following the initial upheaval. Second, females whose grooming had already focused on a few predictable partners showed a less dramatic rise in GC levels than females whose grooming network had been more diverse. Third, females who contracted their grooming network the most experienced a greater decrease in GC levels in the following week. We conclude that close bonds with a few preferred partners allow female baboons to alleviate the stress associated with social instability.

  10. Gust alleviation - Criteria and control laws

    NASA Technical Reports Server (NTRS)

    Rynaski, E. G.

    1979-01-01

    The relationships between criteria specified for aircraft gust alleviation and the form of the control laws that result from the criteria are considered. Open-loop gust alleviation based on the linearized, small perturbation equations of aircraft motion is discussed, and an approximate solution of the open-loop control law is presented for the case in which the number of degrees of freedom of the aircraft exceeds the rank of the control effectiveness matrix. Excessive actuator lag is compensated for by taking into account actuator dynamics in the equations of motion, resulting in the specification of a general load network. Criteria for gust alleviation when output motions are gust alleviated and the closed-loop control law derived from them are examined and linear optimal control law is derived. Comparisons of the control laws reveal that the effectiveness of an open-loop control law is greatest at low aircraft frequencies but deteriorates as the natural frequency of the actuators is approached, while closed-loop methods are found to be more effective at higher frequencies.

  11. Alleviation of Communication Apprehension: An Individualized Approach.

    ERIC Educational Resources Information Center

    Watson, Arden K.

    Communication apprehension (CA) affects from 15% to 20% of the college population, indicating inherent problems of negative cognitive appraisal, conditioned anxiety, or skills deficits. Use of an individualized approach to the alleviation of CA has been shown to increase students' class interaction and to improve their verbal skills. During an…

  12. Role of magnesium in alleviation of aluminium toxicity in plants.

    PubMed

    Bose, Jayakumar; Babourina, Olga; Rengel, Zed

    2011-04-01

    Magnesium is pivotal for activating a large number of enzymes; hence, magnesium plays an important role in numerous physiological and biochemical processes affecting plant growth and development. Magnesium can also ameliorate aluminium phytotoxicity, but literature reports on the dynamics of magnesium homeostasis upon exposure to aluminium are rare. Herein existing knowledge on the magnesium transport mechanisms and homeostasis maintenance in plant cells is critically reviewed. Even though overexpression of magnesium transporters can alleviate aluminium toxicity in plants, the mechanisms governing such alleviation remain obscure. Possible magnesium-dependent mechanisms include (i) better carbon partitioning from shoots to roots; (ii) increased synthesis and exudation of organic acid anions; (iii) enhanced acid phosphatase activity; (iv) maintenance of proton-ATPase activity and cytoplasmic pH regulation; (v) protection against an aluminium-induced cytosolic calcium increase; and (vi) protection against reactive oxygen species. Future research should concentrate on assessing aluminium toxicity and tolerance in plants with overexpressed or antisense magnesium transporters to increase understanding of the aluminium-magnesium interaction.

  13. Cav3.2-expressing low-threshold C fibres in human hairy skin contribute to cold allodynia--a non-TRPV1- and non-TRPM8-dependent phenomenon.

    PubMed

    Samour, Mohamad S; Nagi, Saad S; Mahns, David A

    2015-08-01

    It is generally agreed that cold allodynia is a consequence of impaired (Aδ-fibre-mediated) central inhibition of C-nociceptive inputs. However, it is also known that C polymodal nociceptors are not activated at innocuous low temperatures. Recently, we demonstrated the contribution of C-tactile fibres to tactile allodynia. In this study, we investigated whether this, or a related, C-fibre class contributes to cold allodynia. In 30 healthy and 3 chronic pain subjects, a series of normally innocuous localised thermal stimuli were applied to the skin overlying a painful tibialis anterior muscle (induced by infusion of hypertonic saline). The effects of thermal stimulation on muscle pain were observed before and after compression blockade of myelinated fibres. Furthermore, intradermal capsaicin, menthol and TTA-A2 were used for desensitisation of TRPV1, TRPM8, and T-type calcium (Cav3.2) channels, respectively. Before muscle pain, all thermal stimuli were reported as nonpainful regardless of whether myelinated fibres were conducting or not. During muscle pain, dynamic skin cooling (32°C → 20°C) evoked significant and reproducible increases in the overall pain intensity (allodynia). This increase was short lived and locked to the dynamic phase of cooling with pain levels returning to baseline during sustained cooling. Dynamic warming (32°C → 39°C) had no effect on pain levels. Cold allodynia persisted after nerve compression and TRPV1 and TRPM8 desensitisation but was abolished by localised Cav3.2 blockade. In clinical subjects, C-fibre-mediated allodynia was observed without the need for experimental pain-producing manipulations. In conclusion, cold allodynia represents a non-TRPV1- and non-TRPM8-dependent phenomenon, which is mediated by low-threshold Cav3.2-expressing C fibres. PMID:25932689

  14. Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia.

    PubMed

    Nagakura, Yukinori; Oe, Tomoya; Aoki, Toshiaki; Matsuoka, Nobuya

    2009-11-01

    Fibromyalgia is a prevalent and burdensome disorder characterized by chronic widespread pain and complex comorbid symptoms. To develop better treatments for pain-centered fibromyalgia symptoms, there is still a need for animal models which mimic the features of fibromyalgia patients. In the present study, we have established a fibromyalgia animal model by utilizing a never-before-published pharmacological effect of reserpine. Repeated administration of reserpine (1mg/kg s.c., once daily, for three consecutive days) causes a significant decrease in the muscle pressure threshold and tactile allodynia, which are sustained for 1week or more in both male and female rats. This treatment regimen decreases the amount of biogenic amines (dopamine, norepinephrine, and 5-hydroxytryptamine) in the spinal cord, thalamus, and prefrontal cortex, which are deeply involved in pain signal processing. It also significantly increases immobility time in the forced swim test, which is indicative of depression, a common comorbid symptom of fibromyalgia. Pregabalin, duloxetine, and pramipexole significantly attenuated the reserpine-induced decrease in muscle pressure threshold, but diclofenac did not. The validity of the use of this reserpinized animal as a fibromyalgia model is demonstrated from three different aspects, i.e., face validity (manifestation of chronic pain and comorbid symptoms), construct validity (dysfunction of biogenic amine-mediated central nervous system pain control is involved), and predictive validity (similar responses to treatments used in fibromyalgia patients). This animal model is expected to contribute to the better understanding of fibromyalgia pathophysiology and the evaluation of drugs, especially those which would activate biogenic amine system.

  15. Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia

    PubMed Central

    2011-01-01

    Background Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain. Results Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord. Conclusions These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive

  16. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    PubMed

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  17. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    PubMed

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  18. Aerodynamic side-force alleviator means

    NASA Technical Reports Server (NTRS)

    Rao, D. M. (Inventor)

    1980-01-01

    An apparatus for alleviating high angle of attack side force on slender pointed cylindrical forebodies such as fighter aircraft, missiles and the like is described. A symmetrical pair of helical separation trips was employed to disrupt the leeside vortices normally attained. The symmetrical pair of trips starts at either a common point or at space points on the upper surface of the forebody and extends along separate helical paths along the circumference of the forebody.

  19. Gust Alleviation Using Direct Gust Measurement

    NASA Technical Reports Server (NTRS)

    Hoppe, Sven Marco

    2000-01-01

    The increasing competition in the market of civil aircraft leads to operating efficiency and passenger comfort being very important sales arguments. Continuous developments in jet propulsion technology helped to reduce energy consumption, as well as noise and vibrations due to the engines. The main problem with respect to ride comfort is, however, the transmittance of accelerations and jerkiness imposed by atmospheric turbulence from the wings to the fuselage. This 'gust' is also a design constraint: Light airplane structures help to save, energy, but are more critical to resist the loads imposed by turbulence. For both reasons, efficient gust alleviation is necessary to improve the performance of modern aircraft. Gust can be seen as a change in the angle of attack or as an additional varying vertical component of the headwind. The effect of gust can be very strong, since the same aerodynamic forces that keep the airplane flying are involved. Event though the frequency range of those changes is quite low, it is impossible for the pilot to alleviate gust manually. Besides, most of the time during the flight, the, autopilot maintains course and the attitude of flight. Certainly, most autopilots should be capable of damping the roughest parts of turbulence, but they are unable to provide satisfactory results in that field. A promising extension should be the application of subsidiary, control, where the inner (faster) control loop alleviates turbulence and the outer (slower) loop controls the attitude of flight. Besides the mentioned ride comfort, another reason for gust alleviation with respect to the fuselage is the sensibility of electrical devices to vibration and high values of acceleration. Many modern airplane designs--especially inherently instable military aircraft--are highly dependent on avionics. The lifetime and the reliability of these systems is thus essential.

  20. A tarantula spider toxin, GsMTx4, reduces mechanical and neuropathic pain.

    PubMed

    Park, Seung Pyo; Kim, Byung Moon; Koo, Jae Yeon; Cho, Hawon; Lee, Chang Hoon; Kim, Misook; Na, Heung Sik; Oh, Uhtaek

    2008-07-01

    Mechanosensitive channels mediate various physiological functions including somatic sensation or pain. One of the peptide toxins isolated from the venom of the Chilean rose tarantula spider (Grammostola spatulata), mechanotoxin 4 (GsMTx4) is known to block stretch-activated cation channels. Since mechanosensitive channels in sensory neurons are thought to be molecular sensors for mechanotransduction, i.e., for touch, pressure, proprioception, and pain, we considered that the venom might block some types of mechanical pain. In order to prepare sufficiently large amounts of GsMTx4 for in vivo nociceptive behavioral tests, we constructed recombinant peptide of GsMTx4. Because the amino-acid sequence of the toxin, but not the nucleotide sequence, is known, we back-translated its amino-acid sequence to nucleotide sequence of yeast codons, constructed a template DNA, subcloned this into a Pichia pastoris expression vector, and purified the recombinant peptide. Intraperitoneal injection of the recombinant GsMTx4 to rats significantly increased the mechanical threshold for paw withdrawal in Randall Sellito test, eliciting significant analgesic responses to inflammation-induced mechanical hyperalgesia. GsMTx4 also reduced mechanical allodynia induced by inflammation and by sciatic nerve injury in Von Frey test. However, the venom was ineffective at changing withdrawal latency in hot plate and tail-flick tests. These results suggest that GsMTx4 selectively alleviates mechanical hyperalgesia, which it presumably achieves by blocking mechanosensitive channels. Because the peptide venom induces analgesia for some forms of mechanical pain, GsMTx4 appears to have potential clinical use as a pain treatment. PMID:18359568

  1. Microbial community dynamics alleviate stoichiometric constraints during litter decay.

    PubMed

    Kaiser, Christina; Franklin, Oskar; Dieckmann, Ulf; Richter, Andreas

    2014-06-01

    Under the current paradigm, organic matter decomposition and nutrient cycling rates are a function of the imbalance between substrate and microbial biomass stoichiometry. Challenging this view, we demonstrate that in an individual-based model, microbial community dynamics alter relative C and N limitation during litter decomposition, leading to a system behaviour not predictable from stoichiometric theory alone. Rather, the dynamics of interacting functional groups lead to an adaptation at the community level, which accelerates nitrogen recycling in litter with high initial C : N ratios and thus alleviates microbial N limitation. This mechanism allows microbial decomposers to overcome large imbalances between resource and biomass stoichiometry without the need to decrease carbon use efficiency (CUE), which is in contrast to predictions of traditional stoichiometric mass balance equations. We conclude that identifying and implementing microbial community-driven mechanisms in biogeochemical models are necessary for accurately predicting terrestrial C fluxes in response to changing environmental conditions. PMID:24628731

  2. Microbial community dynamics alleviate stoichiometric constraints during litter decay.

    PubMed

    Kaiser, Christina; Franklin, Oskar; Dieckmann, Ulf; Richter, Andreas

    2014-06-01

    Under the current paradigm, organic matter decomposition and nutrient cycling rates are a function of the imbalance between substrate and microbial biomass stoichiometry. Challenging this view, we demonstrate that in an individual-based model, microbial community dynamics alter relative C and N limitation during litter decomposition, leading to a system behaviour not predictable from stoichiometric theory alone. Rather, the dynamics of interacting functional groups lead to an adaptation at the community level, which accelerates nitrogen recycling in litter with high initial C : N ratios and thus alleviates microbial N limitation. This mechanism allows microbial decomposers to overcome large imbalances between resource and biomass stoichiometry without the need to decrease carbon use efficiency (CUE), which is in contrast to predictions of traditional stoichiometric mass balance equations. We conclude that identifying and implementing microbial community-driven mechanisms in biogeochemical models are necessary for accurately predicting terrestrial C fluxes in response to changing environmental conditions.

  3. Microbial community dynamics alleviate stoichiometric constraints during litter decay

    PubMed Central

    Kaiser, Christina; Franklin, Oskar; Dieckmann, Ulf; Richter, Andreas

    2014-01-01

    Under the current paradigm, organic matter decomposition and nutrient cycling rates are a function of the imbalance between substrate and microbial biomass stoichiometry. Challenging this view, we demonstrate that in an individual-based model, microbial community dynamics alter relative C and N limitation during litter decomposition, leading to a system behaviour not predictable from stoichiometric theory alone. Rather, the dynamics of interacting functional groups lead to an adaptation at the community level, which accelerates nitrogen recycling in litter with high initial C : N ratios and thus alleviates microbial N limitation. This mechanism allows microbial decomposers to overcome large imbalances between resource and biomass stoichiometry without the need to decrease carbon use efficiency (CUE), which is in contrast to predictions of traditional stoichiometric mass balance equations. We conclude that identifying and implementing microbial community-driven mechanisms in biogeochemical models are necessary for accurately predicting terrestrial C fluxes in response to changing environmental conditions. PMID:24628731

  4. [Pathophysiology of neuropathic pain: review of experimental models and proposed mechanisms].

    PubMed

    Garcia-Larrea, Luis; Magnin, Michel

    2008-02-01

    Neuropathic pain can be conceptualized as the result of an "aberrant learning" process, associated with maladaptive plasticity of the nervous system. A number of modifications of the peripheral nervous system have been described in animal models of neuropathic pain, but their relation with different symptoms in humans is far from fully understood. We note in particular ectopic discharges in damaged myelinated fibers, abnormal activity in undamaged fibers, overexpression of calcium channels increasing the release of excitatory neurotransmitters, and sympathetic sprouting towards the spinal ganglia. Spinal mechanisms involve central sensitization, kindling and potentiation phenomena. Underlying these phenomena may be connectivity changes--still controversial--of non-nociceptive terminals and variations in the sensitivity of postsynaptic receptors. Also contributing to these pathophysiologic modifications are attenuation of spinal inhibition by selective neuronal loss and the development of inflammatory phenomena, including cytokine secretion by macrophages and glial cells. Changes in the dorsal horn modify the activity of projections towards the brainstem and increase spinal hyperactivity still further by feedback loops. These effects are delayed, suggesting that maintenance of spinal sensitization requires the involvement of mechanisms of descending facilitation involving the brainstem. These phenomena induce changes in the activity of thalamocortical networks, which develop autonomous processes that maintain the pain. The cortical representation of body areas change after nervous lesions, and these changes may correlate with the emergence of pain. Neuropathic allodynia and hyperalgesia are supported by cortical modifications that experimental models reproduce very incompletely. Experimental allodynia and neuropathic allodynia share the activation of the cortical pain matrix as well as the bilateralization of insular activity. However, although experimental

  5. Dopamine alleviates salt-induced stress in Malus hupehensis.

    PubMed

    Li, Chao; Sun, Xiangkai; Chang, Cong; Jia, Dongfeng; Wei, Zhiwei; Li, Cuiying; Ma, Fengwang

    2015-04-01

    Dopamine mediates many physiological processes in plants. We investigated its role in regulating growth, ion homeostasis and the response to salinity in Malus hupehensis Rehd. Both hydroponics and field-pot experiments were conducted under saline conditions. Salt-stressed plants had reduced growth and a marked decline in their net photosynthetic rates, values for Fv /Fm and chlorophyll contents. However, pretreatment with 100 or 200 μM dopamine significantly alleviated this inhibition and enabled plants to maintain their photosynthetic capacity. In addition to changing stomatal behavior, supplementation with dopamine positively influenced the uptake of K, N, P, S, Cu and Mn ions but had an inhibitory effect on Na and Cl uptake, the balance of which is responsible for managing the response to salinity by Malus plants. Dopamine pretreatment also controlled the burst of hydrogen peroxide, possibly through direct scavenging and by enhancing the activities of antioxidative enzymes and the capacity of the ascorbate-glutathione cycle. We also investigated whether dopamine might regulate salt overly sensitive pathway genes under salinity. Here, MdHKT1, MdNHX1 and MdSOS1 were greatly upregulated in roots and leaves, which possibly contributed to the maintenance of ion homeostasis and, thus, improved salinity resistance in plants exposed earlier to exogenous dopamine. These results support our conclusion that dopamine alleviates salt-induced stress not only at the level of antioxidant defense but also by regulating other mechanisms of ion homeostasis.

  6. How cultivation alleviates soil water repellency

    NASA Astrophysics Data System (ADS)

    Orfanus, Tomas; Dlapa, Pavel; Fodor, Nandor; Rajkai, Kalman

    2010-05-01

    Prolonged droughts are still more frequent and last longer in Central Europe. Under high temperature and low water content, the wettability of organic substances, which cover soil particles, decreases and the infiltration process can be retarded or even entirely prevented. This phenomenon (usually called the soil water repellency - SWR) is very common in sandy soils, especially under natural-state vegetation (forests, grasslands). The objective of this study was to examine to what extent the SWR can be alleviated by sandy soil cultivation. Two study sites in Pannonian basin were selected; Sekule in south-western Slovakia and Őrbottyán in northern Hungary. Both have sandy soils with similar textural composition and elementary structure. They differ only by land use. The first is an untreated meadow while the other has been cultivated for decades and contains small after-fertilization residual amount of carbonates. As the reference material, pure aeolian sand with no organic matter from the Sekule study site was taken, since no SWR has been detected there. Infiltration tests under small positive pressure and comparative infiltration tests with water and ethanol under small negative pressure were performed on the three materials, after several prolonged dry seasons. The results show that, water infiltration is considerably retarded in both sandy soils, which contain organic matter (meadow and arable) when compared to the reference material. In arable soil the effect was partially alleviated by cultivation. One evident reason is the presence of residual after-fertilization carbonates in this soil. Carbonates on the one side enlarged the hydrophilic/hydrophobic surface ratio and on the other increased pH, which causes enhanced dissociation of carboxylic groups and by this way also overall hydrophilicity of soil organic matter. This assumption was proved by laboratory experiments with the meadow soil from Sekule, when after calcite addition into the soil the

  7. How to alleviate degradation of mangroves?

    PubMed

    Kathiresan, K

    2004-10-01

    This work has experimentally proved that hyper salinity, a major cause for degradation of coastal mangrove habitats, can be alleviated by flushing of hyper saline soil with tidal water and/or with rainwater. Over a period of three years after digging the creeks to flush hyper saline soil with tidal water, an appreciable reduction in soil salinity and a moderate increase in colonization of mangroves are observed. Soil analysis showed a significant reduction in salinity after 2 months of storage of rainwater with a significant and concomitant increase of heterotrophic bacterial counts and nutrients. This study raises the possibility of converting degrading mangrove habitats to luxuriant ones through man-made efforts.

  8. Neural predictive control for active buffet alleviation

    NASA Astrophysics Data System (ADS)

    Pado, Lawrence E.; Lichtenwalner, Peter F.; Liguore, Salvatore L.; Drouin, Donald

    1998-06-01

    The adaptive neural control of aeroelastic response (ANCAR) and the affordable loads and dynamics independent research and development (IRAD) programs at the Boeing Company jointly examined using neural network based active control technology for alleviating undesirable vibration and aeroelastic response in a scale model aircraft vertical tail. The potential benefits of adaptive control includes reducing aeroelastic response associated with buffet and atmospheric turbulence, increasing flutter margins, and reducing response associated with nonlinear phenomenon like limit cycle oscillations. By reducing vibration levels and thus loads, aircraft structures can have lower acquisition cost, reduced maintenance, and extended lifetimes. Wind tunnel tests were undertaken on a rigid 15% scale aircraft in Boeing's mini-speed wind tunnel, which is used for testing at very low air speeds up to 80 mph. The model included a dynamically scaled flexible fail consisting of an aluminum spar with balsa wood cross sections with a hydraulically powered rudder. Neural predictive control was used to actuate the vertical tail rudder in response to strain gauge feedback to alleviate buffeting effects. First mode RMS strain reduction of 50% was achieved. The neural predictive control system was developed and implemented by the Boeing Company to provide an intelligent, adaptive control architecture for smart structures applications with automated synthesis, self-optimization, real-time adaptation, nonlinear control, and fault tolerance capabilities. It is designed to solve complex control problems though a process of automated synthesis, eliminating costly control design and surpassing it in many instances by accounting for real world non-linearities.

  9. Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation

    NASA Astrophysics Data System (ADS)

    Cepeda-Humerez, Sarah A.; Rieckh, Georg; Tkačik, Gašper

    2015-12-01

    Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect regulatory crosstalk: the possibility that noncognate TFs could initiate transcription, with potentially disastrous effects for the cell. Here, we estimate the importance of crosstalk, suggest that its avoidance strongly constrains equilibrium models of TF binding, and propose an alternative nonequilibrium scheme that implements kinetic proofreading to suppress erroneous initiation. This proposal is consistent with the observed covalent modifications of the transcriptional apparatus and predicts increased noise in gene expression as a trade-off for improved specificity. Using information theory, we quantify this trade-off to find when optimal proofreading architectures are favored over their equilibrium counterparts. Such architectures exhibit significant super-Poisson noise at low expression in steady state.

  10. Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation.

    PubMed

    Cepeda-Humerez, Sarah A; Rieckh, Georg; Tkačik, Gašper

    2015-12-11

    Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect regulatory crosstalk: the possibility that noncognate TFs could initiate transcription, with potentially disastrous effects for the cell. Here, we estimate the importance of crosstalk, suggest that its avoidance strongly constrains equilibrium models of TF binding, and propose an alternative nonequilibrium scheme that implements kinetic proofreading to suppress erroneous initiation. This proposal is consistent with the observed covalent modifications of the transcriptional apparatus and predicts increased noise in gene expression as a trade-off for improved specificity. Using information theory, we quantify this trade-off to find when optimal proofreading architectures are favored over their equilibrium counterparts. Such architectures exhibit significant super-Poisson noise at low expression in steady state. PMID:26705657

  11. Stereotype Threat and Working Memory: Mechanisms, Alleviation, and Spillover

    ERIC Educational Resources Information Center

    Beilock, Sian L.; Rydell, Robert J.; McConnell, Allen R.

    2007-01-01

    Stereotype threat (ST) occurs when the awareness of a negative stereotype about a social group in a particular domain produces suboptimal performance by members of that group. Although ST has been repeatedly demonstrated, far less is known about how its effects are realized. Using mathematical problem solving as a test bed, the authors demonstrate…

  12. Central origin of secondary mechanical hyperalgesia.

    PubMed

    Klede, Monika; Handwerker, Hermann O; Schmelz, Martin

    2003-07-01

    The contribution for the development of secondary mechanical hyperalgesia by peripheral mechanisms has not been fully elucidated. We have reevaluated the effects of local anesthetics on electrically evoked flare reaction and mechanical hyperalgesia in human skin. We applied 2% lidocaine via intradermal microdialysis fibers at a length of 10 cm for 110 min to the volar forearm to establish a narrow and stable "anesthetic strip." After 60 min of lidocaine perfusion, transdermal electrical stimulation (1 Hz, 50 mA) was applied at a distance of 1 cm from the microdialysis fibers for 30 min. The areas of allodynia and punctate hyperalgesia were marked at the end of the stimulation period. The flare reaction was assessed by laser Doppler scanner and infrared thermography. Total protein content of the dialysate collected at the stimulating electrode was measured photometrically. We found no increase in protein content during electrical stimulation. Flare area (12.4 +/- 2.3 vs. 3.5 +/- 1.2 cm2) and intensity (426 +/- 24 vs. 257 +/- 21 PU) were significantly reduced beyond the lidocaine strip. The mean temperature increase in the area beyond the lidocaine strip was significantly reduced (1.1 +/- 0.1 vs. 0.2 +/- 0.1 degrees C) and did not differ from control areas. In contrast, allodynia (7.4 +/- 0.7 and 8.6 +/- 0.9 cm) and punctate hyperalgesia (7.6 +/- 0.7 and 8.6 +/- 0.9 cm) developed symmetrically on both sides of the anesthetic strip. Allodynia subsided 4 min after the end of the electrical stimulation. We conclude that the development of allodynia and punctate hyperalgesia in human skin is centrally mediated, whereas the axon reflex vasodilation is of peripheral origin. PMID:12843313

  13. Hypoxia inducible factor-1α inhibition produced anti-allodynia effect and suppressed inflammatory cytokine production in early stage of mouse complex regional pain syndrome model.

    PubMed

    Hsiao, Hung-Tsung; Lin, Ya-Chi; Wang, Jeffrey Chi-Fei; Tsai, Yu-Chuan; Liu, Yen-Chin

    2016-03-01

    Complex regional pain syndrome (CRPS) is related to microcirculation impairment associated with tissue hypoxia and peripheral cytokine overproduction in the affected limb. Previous studies suggest that the pathogenesis involves hypoxia inducible factor-1α (HIF-1α) and exaggerated regional inflammatory response. 1-methylpropyl 2-imidazolyl disulfide (PX-12) acts as the thioredoxin-1 (Trx-1) inhibitor and decreases the level of HIF-1α, and can rapidly be metabolized for Trx-1 redox inactivation. This study hypothesized that PX-12 can decrease the cytokine production for nociceptive sensitization in the hypoxia-induced pain model. CD1 mice weighing around 30 g were used. The animal CRPS model was developed via the chronic post-ischaemic pain (CPIP) model. The model was induced by using O-rings on the ankles of the mice hind limbs to produce 3-h ischaemia-reperfusion injury on the paw. PX-12 (25 mg/kg, 5 mg/kg) was given through tail vein injection immediately after ischaemia. Animal behaviour was tested using the von Frey method for 7 days. Local paw skin tissue was harvest from three groups (control, 5 mg/kg, 25 mg/kg) 2 h after injection of PX-12. The protein expression of interleukin-1β (IL-1β) and HIF-1α was analysed with the Western blotting method. Mice significantly present an anti-allodynia effect in a dose-related manner after the PX-12 administration. Furthermore, PX-12 not only decreased the expression of HIF-1α but also decreased the expression of IL-1β over the injured palm. This study, therefore, shows the first evidence of the anti-allodynia effect of PX-12 in a CPIP animal model for pain behaviour. The study concluded that inhibition of HIF-1α may produce an analgesic effect and the associated suppression of inflammatory cytokine IL-1β in a CPIP model. PMID:26711019

  14. Lactobacillus plantarum CCFM639 alleviates aluminium toxicity.

    PubMed

    Yu, Leilei; Zhai, Qixiao; Liu, Xiaoming; Wang, Gang; Zhang, Qiuxiang; Zhao, Jianxin; Narbad, Arjan; Zhang, Hao; Tian, Fengwei; Chen, Wei

    2016-02-01

    Aluminium (Al) is the most abundant metal in the earth's crust. Al exposure can cause a variety of adverse physiological effects in humans and animals. Our aim was to demonstrate that specific probiotic bacteria can play a special physiologically functional role in protection against Al toxicity in mice. Thirty strains of lactic acid bacteria (LAB) were tested for their aluminium-binding ability, aluminium tolerance, their antioxidative capacity, and their ability to survive the exposure to artificial gastrointestinal (GI) juices. Lactobacillus plantarum CCFM639 was selected for animal experiments because of its excellent performance in vitro. Forty mice were divided into four groups: control, Al only, Al plus CCFM639, and Al plus deferiprone (DFP). CCFM639 was administered at 10(9) CFU once daily for 10 days, followed by a single oral dose of aluminium chloride hexahydrate at 5.14 mg aluminium (LD50) for each mouse. The results showed that CCFM639 treatment led to a significant reduction in the mortality rates with corresponding decrease in intestinal aluminium absorption and in accumulation of aluminium in the tissues and amelioration of hepatic histopathological damage. This probiotic treatment also resulted in alleviation of hepatic, renal, and cerebral oxidative stress. The treatment of L. plantarum CCFM639 has potential as a therapeutic dietary strategy against acute aluminium toxicity.

  15. Wakeful rest alleviates interference-based forgetting.

    PubMed

    Mercer, Tom

    2015-01-01

    Retroactive interference (RI)--the disruptive influence of events occurring after the formation of a new memory--is one of the primary causes of forgetting. Placing individuals within an environment that postpones interference should, therefore, greatly reduce the likelihood of information being lost from memory. For example, a short period of wakeful rest should diminish interference-based forgetting. To test this hypothesis, participants took part in a foreign language learning activity and were shown English translations of 20 Icelandic words for immediate recall. Half of the participants were then given an 8-min rest before completing a similar or dissimilar interfering distractor task. The other half did not receive a rest until after the distractor task, at which point interference had already taken place. All participants were then asked to translate the Icelandic words for a second time. Results revealed that retention was significantly worse at the second recall test, but being allowed a brief rest before completing the distractor task helped reduce the amount of forgetting. Taking a short, passive break can shield new memories from RI and alleviate forgetting. PMID:24410154

  16. An Advanced Buffet Load Alleviation System

    NASA Technical Reports Server (NTRS)

    Burnham, Jay K.; Pitt, Dale M.; White, Edward V.; Henderson, Douglas A.; Moses, Robert W.

    2001-01-01

    This paper describes the development of an advanced buffet load alleviation (BLA) system that utilizes distributed piezoelectric actuators in conjunction with an active rudder to reduce the structural dynamic response of the F/A-18 aircraft vertical tails to buffet loads. The BLA system was defined analytically with a detailed finite-element-model of the tail structure and piezoelectric actuators. Oscillatory aerodynamics were included along with a buffet forcing function to complete the aeroservoelastic model of the tail with rudder control surface. Two single-input-single-output (SISO) controllers were designed, one for the active rudder and one for the active piezoelectric actuators. The results from the analytical open and closed loop simulations were used to predict the system performance. The objective of this BLA system is to extend the life of vertical tail structures and decrease their life-cycle costs. This system can be applied to other aircraft designs to address suppression of structural vibrations on military and commercial aircraft.

  17. The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia.

    PubMed

    Lolignier, Stéphane; Bonnet, Caroline; Gaudioso, Christelle; Noël, Jacques; Ruel, Jérôme; Amsalem, Muriel; Ferrier, Jérémy; Rodat-Despoix, Lise; Bouvier, Valentine; Aissouni, Youssef; Prival, Laetitia; Chapuy, Eric; Padilla, Françoise; Eschalier, Alain; Delmas, Patrick; Busserolles, Jérôme

    2015-05-19

    Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions.

  18. Comparison of piezoelectric systems and aerodynamic systems for aircraft vibration alleviation

    NASA Astrophysics Data System (ADS)

    Becker, Juergen; Luber, Wolfgang G.

    1998-06-01

    A comparison of active smart structure - piezoelectric control system and aerodynamic active systems for vibration alleviation and elastic mode damping of a military aircraft structure is presented. The vibration alleviation systems which are operative at flight in turbulence or during maneuvers at high incidence corresponding to severe buffeting conditions are under investigation by DASA as a part of research study on advanced aircraft structures. The active systems for elastic mode damping are designed as digital systems to provide vibration alleviation and have an interface to the flight control system (FCS) or are directly part of the FCS. The sensor concept of all different systems is the same as the sensor concept used for the FCS with the corresponding benefits of redundancy and safety. The design of systems and the comparisons of system properties are based on open and closed loop response calculations, performed with the dynamic model of the total aircraft including coupling of flight mechanics, structural dynamics, FCS dynamics and hydraulic actuator or piezo-actuator dynamics. Aerodynamic systems, like active foreplane and flap concepts, rudder and auxiliary rudder concepts, and piezoelectric systems, like piezo interface at the interconnection fin to rear fuselage and integrated piezo concepts are compared. Besides the essential effects on flexible aircraft mode stability and vibration alleviation factors system complexity and safety aspects are described.

  19. Agent Reward Shaping for Alleviating Traffic Congestion

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan; Agogino, Adrian

    2006-01-01

    Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.

  20. Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice

    PubMed Central

    Wu, Yu-er; Li, Ya-dong; Luo, Yan-jia; Wang, Tian-xiao; Wang, Hui-jing; Chen, Shuo-nan; Qu, Wei-min; Huang, Zhi-li

    2015-01-01

    Aim: Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. Methods: Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. Results: In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. Conclusion: Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine. PMID:26388157

  1. Can Earth Sciences Help Alleviate Global Poverty?

    NASA Astrophysics Data System (ADS)

    Mutter, J. C.

    2004-12-01

    essential and could hold the key to making gains toward alleviating the burden of global poverty.

  2. Crosstalk between exercise and galanin system alleviates insulin resistance.

    PubMed

    Fang, Penghua; He, Biao; Shi, Mingyi; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

    2015-12-01

    Studies have demonstrated that aerobic exercise can enhance insulin sensitivity, however, the precise mechanism for this outcome is not entirely identified. Emerging evidences point out that exercise can upregulate galanin protein and mRNA expression, resulting in improvement of insulin sensitivity via an increase in translocation of glucose transporter 4 and subsequent glucose uptake in myocytes and adipocytes of healthy and type 2 diabetic rats, which may be blocked by galanin antagonist. In return, galanin can exert the exercise-protective roles to prevent excessive movement of skeletal muscle and to accelerate exercise trauma repair in exercise-relative tissues. Studies also implicated that combination of aerobic exercise and activation of galanin system may make more significant improvement in insulin sensitivity than that of either one did. These suggest that galanin system is essential for physical activity to alleviate insulin resistance, namely, the beneficial effect of physical activity on glucose uptake is at least partly mediated by galanin system. Besides, co-treatment with galanin and exercise is an effective therapeutic strategy for reducing insulin resistance.

  3. MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice.

    PubMed

    Palazzo, Enza; Romano, Rosaria; Luongo, Livio; Boccella, Serena; De Gregorio, Danilo; Giordano, Maria Elvira; Rossi, Francesca; Marabese, Ida; Scafuro, Maria Antonietta; de Novellis, Vito; Maione, Sabatino

    2015-06-01

    This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to stimulation of the basolateral amygdala (BLA) with either excitation or inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical allodynia, reduced open-arm choice in the elevated plus-maze, increased time of immobility in the tail suspension, and increased digging and burying in the marble burying test. Cognitive performance was also significantly compromised in the SNI mice. Spared nerve injury induced phenotypic changes on pyramidal neurons of the PLC; excitatory responses increased, whereas inhibitory responses decreased after BLA stimulation. mGluR7 expression, mainly associated with vesicular glutamate transporter, increased in the hippocampus and decreased in the BLA, PLC, and dorsal raphe in SNI mice. MMPIP increased thermal and mechanical thresholds and open-arm choice. It reduced the immobility in the tail suspension test and the number of marbles buried and of digging events in the marble burying test. MMPIP also improved cognitive performance and restored the balance between excitatory and inhibitory responses of PLC neurons in SNI mice. 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one, XAP044, another selective mGluR7 NAM, reproduced the effects of MMPIP on thermal hyperalgesia, mechanical allodynia, tail suspension, and marble burying test. Altogether, these findings show that mGluR7 NAMs reduce pain responses and affective/cognitive impairments in neuropathic pain conditions.

  4. A-887826 is a structurally novel, potent and voltage-dependent Na(v)1.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats.

    PubMed

    Zhang, Xu-Feng; Shieh, Char-Chang; Chapman, Mark L; Matulenko, Mark A; Hakeem, Ahmed H; Atkinson, Robert N; Kort, Michael E; Marron, Brian E; Joshi, Shailen; Honore, Prisca; Faltynek, Connie R; Krafte, Douglas S; Jarvis, Michael F

    2010-09-01

    Activation of sodium channels is essential to action potential generation and propagation. Recent genetic and pharmacological evidence indicates that activation of Na(v)1.8 channels contributes to chronic pain. Herein, we describe the identification of a novel series of structurally related pyridine derivatives as potent Na(v)1.8 channel blockers. A-887826 exemplifies this series and potently (IC(50)=11nM) blocked recombinant human Na(v)1.8 channels. A-887826 was approximately 3 fold less potent to block Na(v)1.2, approximately 10 fold less potent to block tetrodotoxin-sensitive sodium (TTX-S Na(+)) currents and was >30 fold less potent to block Na(V)1.5 channels. A-887826 potently blocked tetrodotoxin-resistant sodium (TTX-R Na(+)) currents (IC(50)=8nM) from small diameter rat dorsal root ganglion (DRG) neurons in a voltage-dependent fashion. A-887826 effectively suppressed evoked action potential firing when DRG neurons were held at depolarized potentials and reversibly suppressed spontaneous firing in small diameter DRG neurons from complete Freund's adjuvant inflamed rats. Following oral administration, A-887826 significantly attenuated tactile allodynia in a rat neuropathic pain model. Further characterization of TTX-R current block in rat DRG neurons demonstrated that A-887826 (100nM) shifted the mid-point of voltage-dependent inactivation of TTX-R currents by approximately 4mV without affecting voltage-dependent activation and did not exhibit frequency-dependent inhibition. The present data demonstrate that A-887826 is a structurally novel and potent Na(v)1.8 blocker that inhibits rat DRG TTX-R currents in a voltage-, but not frequency-dependent fashion. The ability of this structurally novel Na(v)1.8 blocker to effectively reduce tactile allodynia in neuropathic rats further supports the role of Na(v)1.8 sodium channels in pathological pain states. PMID:20566409

  5. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    PubMed

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  6. Arsenic induced myocardial toxicity in rats: alleviative effect of Trichosanthes dioica fruit.

    PubMed

    Bhattacharya, Sanjib; Das, Sanjit Kumar; Haldar, Pallab Kanti

    2014-09-01

    The present study investigated the alleviative effect of aqueous extract of Trichosanthes dioica fruit (AQTD) against arsenic induced cardiotoxicity in Wistar albino rats. AQTD (50 and 100 mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10 mg/kg) for 8 days. Then the body weights, heart weights, hematological profile, serum biochemical profile; myocardial antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and DNA fragmentation were evaluated. Pretreatment with AQTD markedly and significantly normalized body weights, heart weights, hematological profile, serum biochemical profile and significantly modulated all the myocardial antioxidative parameters and reduced DNA fragmentation in arsenic intoxicated rats. Therefore, T. dioica fruit possessed remarkable alleviative effects against arsenic induced myocardial toxicity in Wistar albino rats mediated by amelioration of arsenic induced myocardial oxidative stress by several mechanisms.

  7. Calorie supply does not alleviate running-based taste aversion learning in rats.

    PubMed

    Nakajima, Sadahiko

    2011-12-01

    Voluntary running establishes aversion to the paired taste in rats. A proposed mechanism underlying this taste aversion learning is energy expenditure caused by the running. The energy expenditure hypothesis predicts that running-based taste aversion should be alleviated by a calorie supply since this would compensate for the energy expended by running. Accordingly, running-based taste aversion would be less readily established to a caloric substance (20% sucrose solution) than to a noncaloric substance (0.2% sodium saccharin solution). Because the sucrose and saccharin aversions were equivalent in Experiment 1, the validity of the energy expenditure hypothesis was questioned. Experiments 2 and 3 also pose a problem for this hypothesis, as post-session calorie supply by glucose tablets failed to alleviate running-based aversion to salty water. PMID:21843567

  8. Arsenic induced myocardial toxicity in rats: alleviative effect of Trichosanthes dioica fruit.

    PubMed

    Bhattacharya, Sanjib; Das, Sanjit Kumar; Haldar, Pallab Kanti

    2014-09-01

    The present study investigated the alleviative effect of aqueous extract of Trichosanthes dioica fruit (AQTD) against arsenic induced cardiotoxicity in Wistar albino rats. AQTD (50 and 100 mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10 mg/kg) for 8 days. Then the body weights, heart weights, hematological profile, serum biochemical profile; myocardial antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and DNA fragmentation were evaluated. Pretreatment with AQTD markedly and significantly normalized body weights, heart weights, hematological profile, serum biochemical profile and significantly modulated all the myocardial antioxidative parameters and reduced DNA fragmentation in arsenic intoxicated rats. Therefore, T. dioica fruit possessed remarkable alleviative effects against arsenic induced myocardial toxicity in Wistar albino rats mediated by amelioration of arsenic induced myocardial oxidative stress by several mechanisms. PMID:25057964

  9. Acute Morphine Treatments Alleviate Tremor in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Monkeys

    PubMed Central

    Yan, Ting; Rizak, Joshua Dominic; Yang, ShangChuan; Li, Hao; Huang, BaiHui; Ma, YuanYe; Hu, XinTian

    2014-01-01

    Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder associated with decreased striatal dopamine levels. Morphine has been found to elevate dopamine levels, which indicates a potential therapeutic effect in PD treatment that has not been investigated previously. To evaluate this hypothesis, an investigation of the acute effects of morphine on PD symptoms was carried out in male rhesus PD monkeys that had been induced with MPTP. All MPTP induced monkeys displayed progressive and irreversible PD motor symptoms. The behavioral response of these animals to morphine and L-Dopa were quantified with the Kurlan scale. It was found that L-Dopa alleviated bradykinesia, but did not significantly improve tremor. In contrast, acute morphine alleviated tremor significantly. These results suggested that, compared to L-Dopa, morphine has different therapeutic effects in PD therapy and may act through different biological mechanisms to alleviate PD symptoms. PMID:24520383

  10. Heat-rekindling in UVB-irradiated skin above NGF-sensitized muscle: experimental models of prolonged mechanical hypersensitivity.

    PubMed

    Vecchio, Silvia Lo; Finocchietti, Sara; Gazerani, Parisa; Petersen, Lars J; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

    2014-01-01

    Experimental models of prolonged pain hypersensitivity in humans are desirable for screening novel analgesic compounds. In this study, heat stimuli were applied in ultraviolet-B (UVB)-irradiated skin and in the UVB-irradiated skin combined with nerve growth factor (NGF)-injected muscle to investigate 1) whether the evoked mechanical hypersensitivity by UVB irradiation would be prolonged or enhanced following heat rekindling, and 2) whether the combination between cutaneous and muscle hypersensitivity may influence the rekindling effects. Skin sensitization was induced in 25 volunteers by UVB irradiation in areas above the upper-trapezius muscle, low-back or forearm. Muscle sensitization was induced in the low back by bilateral injections of NGF. The area of cutaneous hyperalgesia was evaluated 3 days after the irradiation by mechanical pin-prick stimulation whereas the areas of allodynia were evaluated 1, 2 and 3 days after irradiation by von Frey hair assessments. Cutaneous heat stimulation (40°C for 5 min) was performed on the 3(rd) day to investigate its effect on the areas of cutaneous allodynia and hyperalgesia. Findings revealed that 1) allodynia and hyperalgesia developed following UVB irradiation, 2) heat stimulation of the UVB-irradiated skin enlarged both hyperalgesic and allodynic areas (P < 0.01), and 3) muscle sensitization did not influence the effect of UVB on allodynia or the response to heat rekindling. These data suggest that heat rekindling applied to an UVB-sensitized skin can maintain or facilitate allodynia and hyperalgesia for a longer period offering a suitable model for testing analgesic compounds when sufficient duration of time is needed for investigation of drug efficacy. PMID:25349637

  11. [Seed dormancy alleviation and oxidative signaling].

    PubMed

    Bailly, Christophe; El Maarouf Bouteau, Hayat; Corbineau, Françoise

    2008-01-01

    Recent advances in plant physiology signaling pathways have led to consider reactive oxygen species (ROS) as being key actors in the regulation of germination and dormancy. ROS accumulation during seed dry storage or during their imbibition would trigger cellular events controlling the realization of germination. We show that ROS accumulation triggers specific carbonylation of proteins thus modifying the occurrence of enzyme-mediated reactions during germination or facilitating reserve protein degradation through the proteasome. This suggests that dormancy is in part controlled by protein oxidation. ROS can also act as a positive signal in seed dormancy release through their effect on other mechanisms such as the control of the cellular redox status and the activation of transcription factors. Their interaction with abscisic acid and gibberellins is also evoked and a new mechanism of dormancy regulation in which ROS crosstalk with hormonal pathways is proposed.

  12. Cellular Recycling of Proteins in Seed Dormancy Alleviation and Germination

    PubMed Central

    Oracz, Krystyna; Stawska, Marlena

    2016-01-01

    Each step of the seed-to-seed cycle of plant development including seed germination is characterized by a specific set of proteins. The continual renewal and/or replacement of these biomolecules are crucial for optimal plant adaptation. As proteins are the main effectors inside the cells, their levels need to be tightly regulated. This is partially achieved by specific proteolytic pathways via multicatalytic protease complexes defined as 20S and 26S proteasomes. In plants, the 20S proteasome is responsible for degradation of carbonylated proteins, while the 26S being a part of ubiquitin-proteasome pathway is known to be involved in proteolysis of phytohormone signaling regulators. On the other hand, the role of translational control of plant development is also well-documented, especially in the context of pollen tube growth and light signaling. Despite the current progress that has been made in seed biology, the sequence of cellular events that determine if the seed can germinate or not are still far from complete understanding. The role and mechanisms of regulation of proteome composition during processes occurring in the plant’s photosynthetic tissues have been well-characterized since many years, but in non-photosynthetic seeds it has emerged as a tempting research task only since the last decade. This review discusses the recent discoveries providing insights into the role of protein turnover in seed dormancy alleviation, and germination, with a focus on the control of translation and proteasomal proteolysis. The presented novel data of translatome profiling in seeds highlighted that post-transcriptional regulation of germination results from a timely regulated initiation of translation. In addition, the importance of 26S proteasome in the degradation of regulatory elements of cellular signaling and that of the 20S complex in proteolysis of specific carbonylated proteins in hormonal- and light-dependent processes occurring in seeds is discussed. Based on the

  13. Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model

    PubMed Central

    Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

    2015-01-01

    Objective: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Methods: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. Results: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Conclusions: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia. PMID:26617751

  14. Cellular Recycling of Proteins in Seed Dormancy Alleviation and Germination.

    PubMed

    Oracz, Krystyna; Stawska, Marlena

    2016-01-01

    Each step of the seed-to-seed cycle of plant development including seed germination is characterized by a specific set of proteins. The continual renewal and/or replacement of these biomolecules are crucial for optimal plant adaptation. As proteins are the main effectors inside the cells, their levels need to be tightly regulated. This is partially achieved by specific proteolytic pathways via multicatalytic protease complexes defined as 20S and 26S proteasomes. In plants, the 20S proteasome is responsible for degradation of carbonylated proteins, while the 26S being a part of ubiquitin-proteasome pathway is known to be involved in proteolysis of phytohormone signaling regulators. On the other hand, the role of translational control of plant development is also well-documented, especially in the context of pollen tube growth and light signaling. Despite the current progress that has been made in seed biology, the sequence of cellular events that determine if the seed can germinate or not are still far from complete understanding. The role and mechanisms of regulation of proteome composition during processes occurring in the plant's photosynthetic tissues have been well-characterized since many years, but in non-photosynthetic seeds it has emerged as a tempting research task only since the last decade. This review discusses the recent discoveries providing insights into the role of protein turnover in seed dormancy alleviation, and germination, with a focus on the control of translation and proteasomal proteolysis. The presented novel data of translatome profiling in seeds highlighted that post-transcriptional regulation of germination results from a timely regulated initiation of translation. In addition, the importance of 26S proteasome in the degradation of regulatory elements of cellular signaling and that of the 20S complex in proteolysis of specific carbonylated proteins in hormonal- and light-dependent processes occurring in seeds is discussed. Based on the

  15. Cellular Recycling of Proteins in Seed Dormancy Alleviation and Germination.

    PubMed

    Oracz, Krystyna; Stawska, Marlena

    2016-01-01

    Each step of the seed-to-seed cycle of plant development including seed germination is characterized by a specific set of proteins. The continual renewal and/or replacement of these biomolecules are crucial for optimal plant adaptation. As proteins are the main effectors inside the cells, their levels need to be tightly regulated. This is partially achieved by specific proteolytic pathways via multicatalytic protease complexes defined as 20S and 26S proteasomes. In plants, the 20S proteasome is responsible for degradation of carbonylated proteins, while the 26S being a part of ubiquitin-proteasome pathway is known to be involved in proteolysis of phytohormone signaling regulators. On the other hand, the role of translational control of plant development is also well-documented, especially in the context of pollen tube growth and light signaling. Despite the current progress that has been made in seed biology, the sequence of cellular events that determine if the seed can germinate or not are still far from complete understanding. The role and mechanisms of regulation of proteome composition during processes occurring in the plant's photosynthetic tissues have been well-characterized since many years, but in non-photosynthetic seeds it has emerged as a tempting research task only since the last decade. This review discusses the recent discoveries providing insights into the role of protein turnover in seed dormancy alleviation, and germination, with a focus on the control of translation and proteasomal proteolysis. The presented novel data of translatome profiling in seeds highlighted that post-transcriptional regulation of germination results from a timely regulated initiation of translation. In addition, the importance of 26S proteasome in the degradation of regulatory elements of cellular signaling and that of the 20S complex in proteolysis of specific carbonylated proteins in hormonal- and light-dependent processes occurring in seeds is discussed. Based on the

  16. Biomaterial strategies for alleviation of myocardial infarction

    PubMed Central

    Venugopal, Jayarama Reddy; Prabhakaran, Molamma P.; Mukherjee, Shayanti; Ravichandran, Rajeswari; Dan, Kai; Ramakrishna, Seeram

    2012-01-01

    World Health Organization estimated that heart failure initiated by coronary artery disease and myocardial infarction (MI) leads to 29 per cent of deaths worldwide. Heart failure is one of the leading causes of death in industrialized countries and is expected to become a global epidemic within the twenty-first century. MI, the main cause of heart failure, leads to a loss of cardiac tissue impairment of left ventricular function. The damaged left ventricle undergoes progressive ‘remodelling’ and chamber dilation, with myocyte slippage and fibroblast proliferation. Repair of diseased myocardium with in vitro-engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for heart failure patients. These events reflect an apparent lack of effective intrinsic mechanism for myocardial repair and regeneration. Motivated by the desire to develop minimally invasive procedures, the last 10 years observed growing efforts to develop injectable biomaterials with and without cells to treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen, chitosan, self-assembling peptides, biopolymers and a range of synthetic hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to generate biocompatible, non-immunogenic heart muscle with morphological and functional properties similar to natural myocardium to repair MI. This review summarizes the properties of biomaterial substrates having sufficient mechanical stability, which stimulates the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering. PMID:21900319

  17. Alleviating Contingency Violations through Visual Analytics and Suggested Actions

    SciTech Connect

    Rice, Mark J.; Huang, Zhenyu; Chen, Yousu; Allwardt, Craig H.; Mackey, Patrick S.

    2013-07-21

    Contingency analysis (CA) is essential in maintaining a stable and secure power grid. It is required by operating standards that contingency violations need to be alleviated within 30 minutes. In today’s practice, operators normally make decisions based on the information they have with limited support. This paper presents a new feature of user suggested actions integrated in the graphical contingency analysis (GCA) tool, developed by the authors to help the operator’s decision making process. This paper provides a few examples on showing how the decision support element of the GCA tool is further enhanced by this new feature to alleviate contingency violations for better grid reliability.

  18. Experimental investigations on wake vortices and their alleviation

    NASA Astrophysics Data System (ADS)

    Savaş, Ömer

    2005-05-01

    Recent wake vortex research in the laboratory has benefited considerably from concurrent analytical and numerical research on the instability of vortex systems. Tow tank, with dye flow visualization and particle image velocimetry is the most effective combination for laboratory research. Passive and active wake alleviation schemes have been successfully demonstrated in the laboratory. The passive alleviation systems exploit the natural evolution of vortex instabilities while the active systems rely on hastening selected instabilities by forcing the vortices individually or as a system. Their practical applicability, however, will have to meet further criteria beyond those dictated by fluid dynamics. To cite this article: Ö. Savaş, C. R. Physique 6 (2005).

  19. Duloxetine Inhibits Microglial P2X4 Receptor Function and Alleviates Neuropathic Pain after Peripheral Nerve Injury

    PubMed Central

    Yamashita, Tomohiro; Yamamoto, Shota; Zhang, Jiaming; Kometani, Miho; Tomiyama, Daisuke; Kohno, Keita; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R. In primary cultured microglial cells, duloxetine also inhibited P2X4R-, but not P2X7R-, mediated responses. Moreover, intrathecal administration of duloxetine in a model of neuropathic pain produced a reversal of nerve injury-induced mechanical allodynia, a cardinal symptom of neuropathic pain. In rats that were pretreated with a serotonin-depleting agent and a noradrenaline neurotoxin, the antiallodynic effect of duloxetine was reduced, but still remained. Based on these results, we suggest that, in addition to duloxetine’s primary inhibitory action on serotonin and noradrenaline transporters, an inhibitory effect on P2X4R may be involved at least in part in an antiallodynic effect of intrathecal duloxetine in a model of neuropathic pain. PMID:27768754

  20. Residual stress alleviation of aircraft metal structures reinforced with filamentary composites

    NASA Technical Reports Server (NTRS)

    Kelly, J. B.; June, R. R.

    1973-01-01

    Methods to eliminate or reduce residual stresses in aircraft metal structures reinforced by filamentary composites are discussed. Residual stress level reductions were achieved by modifying the manufacturing procedures used during adhesive bonding. The residual stress alleviation techniques involved various forms of mechanical constraint which were applied to the components during bonding. Nine methods were evaluated, covering a wide range in complexity. All methods investigated during the program affected the residual stress level. In general, residual stresses were reduced by 70 percent or more from the stress level produced by conventional adhesive bonding procedures.

  1. Fin-buffet alleviation via distributed piezoelectric actuators: materials qualification program

    NASA Astrophysics Data System (ADS)

    Zaglauer, Helmut W.; Duerr, Johannes K.; Floeth, Erik; Ihler, Elmar; Herold-Schmidt, Ursula; Dittrich, Kay W.; Simpson, John; Becker, Juergen

    1999-07-01

    One of the most innovative concepts for active fin-buffet alleviation in vertical tail aircraft is the use of piezoelectric patch actuators distributed across the tail surface to actively induce a counter-strain into the structure. This concept involves the development of a novel material compound structure consisting of a fiber-composite aircraft skin, a ceramic patch actuator and the bonding layer between both components. This actively controllable structure has to provide enough authority to dampen the fin- buffet vibrations. It also has to function reliably during long-term aircraft operation under severe mechanical and environmental load conditions.

  2. Causes and Alleviation of Occupational Stress in Child Care Work

    ERIC Educational Resources Information Center

    Dillenburger, Karola

    2004-01-01

    Occupational stress in not a new phenomenon in the working population. However, in the helping professions it has only recently attracted attention. The survey reported here was carried out in order to assess the extent of occupational stress, identify its causes, and suggest ways in which occupational stress can be alleviated. Field social…

  3. Training Teachers as Key Players in Poverty Alleviation

    ERIC Educational Resources Information Center

    Benavente, Ana; Ralambomanana, Stangeline; Mbanze, Jorge

    2008-01-01

    This article presents several questions, reflections and suggestions on pre-service and in-service teacher training that arose during the project "Curricular innovation and poverty alleviation in sub-Saharan Africa". While recognizing that the situation in the nine countries taking part in the project, and in many other countries in the southern…

  4. Helping Alleviate Statistical Anxiety with Computer Aided Statistical Classes

    ERIC Educational Resources Information Center

    Stickels, John W.; Dobbs, Rhonda R.

    2007-01-01

    This study, Helping Alleviate Statistical Anxiety with Computer Aided Statistics Classes, investigated whether undergraduate students' anxiety about statistics changed when statistics is taught using computers compared to the traditional method. Two groups of students were questioned concerning their anxiety about statistics. One group was taught…

  5. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    PubMed

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p < 0.01, respectively) in ATO-treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p < 0.01, respectively). The groups treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p < 0.01). Mice treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  6. Autophagy alleviates neurodegeneration caused by mild impairment of oxidative metabolism.

    PubMed

    Meng, Ya; Yong, Yue; Yang, Guang; Ding, Hanqing; Fan, Zhiqin; Tang, Yifen; Luo, Jia; Ke, Zun-Ji

    2013-09-01

    Thiamine deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the brain, which may be mediated by neuronal oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation. TD-induced brain damage is used to model neurodegenerative disorders, and the mechanism for the neuronal death is still unclear. We hypothesized that autophagy might be activated in the TD brain and play a protective role in TD-induced neuronal death. Our results demonstrated that TD induced the accumulation of autophagosomes in thalamic neurons measured by transmission electron microscopy, and the up-regulation of autophagic markers LC3-II, Atg5, and Beclin1 as measured with western blotting. TD also increased the expression of autophagic markers and induced LC3 puncta in SH-SY5Y neuroblastoma cells. TD-induced expression of autophagic markers was reversed once thiamine was re-administered. Both inhibition of autophagy by wortmannin and Beclin1 siRNA potentiated TD-induced death of SH-SY5Y cells. In contrast, activation of autophagy by rapamycin alleviated cell death induced by TD. Intraperitoneal injection of rapamycin stimulated neuronal autophagy and attenuated TD-induced neuronal death and microglia activation in the submedial thalamus nucleus (SmTN). TD inhibited the phosphorylation of p70S6 kinase, suggesting mTOR/p70S6 kinase pathway was involved in the TD-induced autophagy. These results suggest that autophagy is neuroprotective in response to TD-induced neuronal death in the central nervous system. This opens a potential therapeutic avenue for neurodegenerative diseases caused by mild impairment of oxidative metabolism. Autophagy is neuroprotective in response to thiamine deficiency (TD)-induced neuronal death. TD caused neuronal damage and induced the formation of autophagosome, and increased the expression of autophagy-related proteins. Autophagy sequestered damaged and dysfunctional organelles/protein, and transported them to

  7. Thymoquinone Alleviates the Experimental Diabetic Peripheral Neuropathy by Modulation of Inflammation

    PubMed Central

    Chen, Long; Li, Bing; Chen, Biqin; Shao, Yiye; Luo, Qiong; Shi, Xiaohong; Chen, Yinghui

    2016-01-01

    Thymoquinone has been reported to exhibit antioxidant and anti-inflammatory effects. Inflammation plays an important role in pathogenesis of diabetic peripheral neuropathy. This study investigated the effects of TQ on proliferation and apoptosis of Schwann cells exposed to high glucose conditions and electrophysiological and morphological changes of the sciatic nerve in a DPN rat model as well as relevant inflammatory mechanism. Cell proliferation and apoptosis of Schwann cells were measured using the Cell Counting Kit-8 and flow cytometry. DPN model was established in streptozotocin-induced diabetic rats. Nerve conduction velocity was measured before and after treatment. Morphologic changes were observed by H&E staining and transmission electron microscopy. COX-2, IL-1β, IL-6, and Caspase-3 expression was investigated by western blotting and Bio-Plex ProTM Assays. Finally, TQ alleviated the inhibition of Schwann cell proliferation and protected against Schwann cell apoptosis. It improved nerve conduction velocity, and alleviated the DPN-induced morphological changes and demyelination of the sciatic nerve. COX-2, IL-1β, IL-6 and Caspase-3 expression in sciatic nerve or isolated cultured Schwann cells, were also decreased by TQ. These results indicate TQ has a protective effect on peripheral nerves in a DPN rat model. The mechanism may be mediated partly by the modulation of the inflammatory reaction. PMID:27545310

  8. Thymoquinone Alleviates the Experimental Diabetic Peripheral Neuropathy by Modulation of Inflammation.

    PubMed

    Chen, Long; Li, Bing; Chen, Biqin; Shao, Yiye; Luo, Qiong; Shi, Xiaohong; Chen, Yinghui

    2016-01-01

    Thymoquinone has been reported to exhibit antioxidant and anti-inflammatory effects. Inflammation plays an important role in pathogenesis of diabetic peripheral neuropathy. This study investigated the effects of TQ on proliferation and apoptosis of Schwann cells exposed to high glucose conditions and electrophysiological and morphological changes of the sciatic nerve in a DPN rat model as well as relevant inflammatory mechanism. Cell proliferation and apoptosis of Schwann cells were measured using the Cell Counting Kit-8 and flow cytometry. DPN model was established in streptozotocin-induced diabetic rats. Nerve conduction velocity was measured before and after treatment. Morphologic changes were observed by H&E staining and transmission electron microscopy. COX-2, IL-1β, IL-6, and Caspase-3 expression was investigated by western blotting and Bio-Plex Pro(TM) Assays. Finally, TQ alleviated the inhibition of Schwann cell proliferation and protected against Schwann cell apoptosis. It improved nerve conduction velocity, and alleviated the DPN-induced morphological changes and demyelination of the sciatic nerve. COX-2, IL-1β, IL-6 and Caspase-3 expression in sciatic nerve or isolated cultured Schwann cells, were also decreased by TQ. These results indicate TQ has a protective effect on peripheral nerves in a DPN rat model. The mechanism may be mediated partly by the modulation of the inflammatory reaction. PMID:27545310

  9. Calcium alleviates cadmium-induced inhibition on root growth by maintaining auxin homeostasis in Arabidopsis seedlings.

    PubMed

    Li, Ping; Zhao, Chengzhou; Zhang, Yongqiang; Wang, Xiaomin; Wang, Xiaoyu; Wang, Jianfeng; Wang, Feng; Bi, Yurong

    2016-01-01

    Cadmium (Cd) toxicity has been widely studied in different plant species. However, the mechanism involved in its toxicity and the cell response to Cd has not been well established. In the present study, we investigated the possible mechanism of calcium (Ca) in protecting Arabidopsis from Cd toxicity. The results showed that 50 μM Cd significantly inhibited the seedling growth and decreased the chlorophyll content in Arabidopsis. Specifically, the primary root (PR) length was decreased but the lateral root (LR) number was increased under Cd stress. Furthermore, Cd enhanced the hydrogen peroxide (H2O2) content and lipid peroxidation as indicated by malondialdehyde (MDA) accumulation. Cd also altered the level and the distribution of auxin in PR tips (as evidenced by DR5::GUS and PIN:GFP reporter expression) and the expression of several putative auxin biosynthetic, catabolic, and transport pathway-related genes. Application of 3 mM Ca alleviated the inhibition of Cd on the root growth. Ca application not only led to reducing oxidative injuries but also restoring the normal auxin transport and distribution in Arabidopsis root under Cd stress. Taken together, these results suggest that Ca alleviates the root growth inhibition caused by Cd through maintaining auxin homeostasis in Arabidopsis seedlings.

  10. Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

    PubMed Central

    Wang, Lianmei; Zhang, Hongbing; Li, Chunying; Yi, Yan; Liu, Jing; Zhao, Yong; Tian, Jingzhuo; Zhang, Yushi; Wei, Xiaolu; Gao, Yue; Liang, Aihua

    2016-01-01

    Aristolochia manshuriensis Kom (AMK) is a member of the Aristolochiaceae family and is a well-known cause of aristolochic acid (AA) nephropathy. In this study, we investigated the potential of omeprazole (OM) to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in human renal tubular epithelial cells (HKCs). HKCs with ectopic CYP 1A1 expression were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK-mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the coadministration of OM might be beneficial for reducing of AA-induced nephrotoxicity. PMID:27716846

  11. Bending and Torsion Load Alleviator With Automatic Reset

    NASA Technical Reports Server (NTRS)

    delaFuente, Horacio M. (Inventor); Eubanks, Michael C. (Inventor); Dao, Anthony X. (Inventor)

    1996-01-01

    A force transmitting load alleviator apparatus and method are provided for rotatably and pivotally driving a member to be protected against overload torsional and bending (moment) forces. The load alleviator includes at least one bias spring to resiliently bias cam followers and cam surfaces together and to maintain them in locked engagement unless a predetermined load is exceeded whereupon a center housing is pivotal or rotational with respect to a crown assembly. This pivotal and rotational movement results in frictional dissipation of the overload force by an energy dissipator. The energy dissipator can be provided to dissipate substantially more energy from the overload force than from the bias force that automatically resets the center housing and crown assembly to the normally fixed centered alignment. The torsional and bending (moment) overload levels can designed independently of each other.

  12. Active control landing gear for ground loads alleviation

    NASA Technical Reports Server (NTRS)

    Mcgehee, J. R.

    1985-01-01

    An active landing gear has been created by connecting the hydraulic piston in an oleo strut to a hydraulic supply. A controller modulates the pressure in the oleo to achieve the desired dynamic characteristics. Tests on ground rigs (documented by a film) have demonstrated the successful alleviation of induced structural ground loads and the next step will be a flight test using a fighter aircraft.

  13. Damage in the dorsal striatum alleviates addictive behavior.

    PubMed

    Muskens, J B; Schellekens, A F A; de Leeuw, F E; Tendolkar, I; Hepark, S

    2012-01-01

    The ventral striatum has been assigned a major role in addictive behavior. In addition, clinical lesion studies have described involvement of the insula and globus pallidus. To the best of our knowledge, this is the first report of alleviation of alcohol and nicotine addiction after a cerebrovascular incident in the dorsal striatum. The patient was still abstinent from alcohol and nicotine at follow-up. This observation suggests that the dorsal striatum may play a critical role in addiction to alcohol and nicotine.

  14. A study of helicopter gust response alleviation by automatic control

    NASA Technical Reports Server (NTRS)

    Saito, S.

    1983-01-01

    Two control schemes designed to alleviate gust-induced vibration are analytically investigated for a helicopter with four articulated blades. One is an individual blade pitch control scheme. The other is an adaptive blade pitch control algorithm based on linear optimal control theory. In both controllers, control inputs to alleviate gust response are superimposed on the conventional control inputs required to maintain the trim condition. A sinusoidal vertical gust model and a step gust model are used. The individual blade pitch control, in this research, is composed of sensors and a pitch control actuator for each blade. Each sensor can detect flapwise (or lead-lag or torsionwise) deflection of the respective blade. The acturator controls the blade pitch angle for gust alleviation. Theoretical calculations to predict the performance of this feedback system have been conducted by means of the harmonic method. The adaptive blade pitch control system is composed of a set of measurements (oscillatory hub forces and moments), an identification system using a Kalman filter, and a control system based on the minimization of the quadratic performance function.

  15. Vortex wake alleviation studies with a variable twist wing

    NASA Technical Reports Server (NTRS)

    Holbrook, G. T.; Dunham, D. M.; Greene, G. C.

    1985-01-01

    Vortex wake alleviation studies were conducted in a wind tunnel and a water towing tank using a multisegmented wing model which provided controlled and measured variations in span load. Fourteen model configurations are tested at a Reynolds number of one million and a lift coefficient of 0.6 in the Langley 4- by 7-Meter Tunnel and the Hydronautics Ship Model Basin water tank at Hydronautics, Inc., Laurel, Md. Detailed measurements of span load and wake velocities at one semispan downstream correlate well with each other, with inviscid predictions of span load and wake roll up, and with peak trailing-wing rolling moments measured in the far wake. Average trailing-wing rolling moments are found to be an unreliable indicator of vortex wake intensity because vortex meander does not scale between test facilities and free-air conditions. A tapered-span-load configuration, which exhibits little or no drag penalty, is shown to offer significant downstream wake alleviation to a small trailing wing. The greater downstream wake alleviation achieved with the addition of spoilers to a flapped-wing configuration is shown to result directly from the high incremental drag and turbulence associated with the spoilers and not from the span load alteration they cause.

  16. Effective alleviation of aluminum phytotoxicity by manure-derived biochar.

    PubMed

    Qian, Linbo; Chen, Baoliang; Hu, Dingfei

    2013-03-19

    The alleviation of aluminum phytotoxicity to wheat plants in a hydroponic system through the amendment of biochar is investigated to explore the possibility of applying biochar in acidic soil amelioration. Biochar derived from cattle manure pyrolyzed at 400 °C (CM400) and the CM400 biochar washed with distilled-deionized water to remove alkalinity (WCM400) were prepared to determine the roles of the liming effect and adsorption during the alleviation of Al toxicity. Upon addition of 0.02% (W/V) CM400 to the exposure solution, the inhibition of plant growth by Al was significantly reduced while the toxic threshold was extended from 3 to 95 μmol/L Al(3+). Due to the biochar liming effect, the aluminum species were converted to Al(OH)(2+) and Al(OH)2(+) monomers, which were strongly adsorbed by biochar; furthermore, the highly toxic Al(3+) evolved to less toxic Al(OH)3 and Al(OH)4(-) species. Adsorption of Al by the biochar is dominated by surface complexation of the carboxyl groups with Al(OH)(2+)/Al(OH)2(+) rather than through electrostatic attraction of Al(3+) with negatively charged sites. Compared to the liming effect, the adsorption by biochar exhibited a sustainable effect on the alleviation of Al toxicity. Therefore, the biochar amendment appears to be a novel approach for aluminum detoxification in acidic soils. PMID:23398535

  17. Coherent Lidar Turbulence Measurement for Gust Load Alleviation

    NASA Technical Reports Server (NTRS)

    Bogue, Rodney K.; Ehernberger, L. J.; Soreide, David; Bagley, Hal

    1996-01-01

    Atmospheric turbulence adversely affects operation of commercial and military aircraft and is a design constraint. The airplane structure must be designed to survive the loads imposed by turbulence. Reducing these loads allows the airplane structure to be lighter, a substantial advantage for a commercial airplane. Gust alleviation systems based on accelerometers mounted in the airplane can reduce the maximum gust loads by a small fraction. These systems still represent an economic advantage. The ability to reduce the gust load increases tremendously if the turbulent gust can be measured before the airplane encounters it. A lidar system can make measurements of turbulent gusts ahead of the airplane, and the NASA Airborne Coherent Lidar for Advanced In-Flight Measurements (ACLAIM) program is developing such a lidar. The ACLAIM program is intended to develop a prototype lidar system for use in feasibility testing of gust load alleviation systems and other airborne lidar applications, to define applications of lidar with the potential for improving airplane performance, and to determine the feasibility and benefits of these applications. This paper gives an overview of the ACLAIM program, describes the lidar architecture for a gust alleviation system, and describes the prototype ACLAIM lidar system.

  18. Helicopter gust alleviation, attitude stabilization, and vibration alleviation using individual-blade-control through a conventional swash plate

    NASA Technical Reports Server (NTRS)

    Ham, N. D.

    1985-01-01

    The novel active control system presented for helicopter rotor aerodynamic and aeroelastic problems involves the individual control of each blade in the rotating frame over a wide range of frequencies (up to the sixth harmonic of rotor speed). This Individual Blade Control (IBC) system controls blade pitch by means of broadband electrohydraulic actuators attached to the swash plate (in the case of three blades) or individually to each blade, using acceleratometer signals to furnish control commands to the actuators. Attention is given to IBC's application to blade lag, flapping, and bending dynamics. It is shown that gust alleviation, attitude stabilization, vibration alleviation, and air/ground resonance suppression, are all achievable with a conventional helicopter swash plate.

  19. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants

    PubMed Central

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-01

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity. PMID:26744061

  20. Hydrogen Sulfide Alleviates Postharvest Senescence of Grape by Modulating the Antioxidant Defenses

    PubMed Central

    Ni, Zhi-Jing; Hu, Kang-Di; Song, Chang-Bing; Ma, Run-Hui; Li, Zhi-Rong; Zheng, Ji-Lian; Fu, Liu-Hui

    2016-01-01

    Hydrogen sulfide (H2S) has been identified as an important gaseous signal in plants. Here, we investigated the mechanism of H2S in alleviating postharvest senescence and rotting of Kyoho grape. Exogenous application of H2S released from 1.0 mM NaHS remarkably decreased the rotting and threshing rate of grape berries. H2S application also prevented the weight loss in grape clusters and inhibited the decreases in firmness, soluble solids, and titratable acidity in grape pulp during postharvest storage. The data of chlorophyll and carotenoid content suggested the role of H2S in preventing chlorophyll breakdown and carotenoid accumulation in both grape rachis and pulp. In comparison to water control, exogenous H2S application maintained significantly higher levels of ascorbic acid and flavonoid and total phenolics and reducing sugar and soluble protein in grape pulp. Meanwhile, H2S significantly reduced the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2∙−) in grape pulp. Further investigations showed that H2S enhanced the activities of antioxidant enzymes ascorbate peroxidase (APX) and catalase (CAT) and decreased those of lipoxygenase (LOX) in both grape peels and pulp. In all, we provided strong evidence that H2S effectively alleviated postharvest senescence and rotting of Kyoho grape by modulating antioxidant enzymes and attenuating lipid peroxidation. PMID:27594971

  1. Hydrogen Sulfide Alleviates Postharvest Senescence of Grape by Modulating the Antioxidant Defenses

    PubMed Central

    Ni, Zhi-Jing; Hu, Kang-Di; Song, Chang-Bing; Ma, Run-Hui; Li, Zhi-Rong; Zheng, Ji-Lian; Fu, Liu-Hui

    2016-01-01

    Hydrogen sulfide (H2S) has been identified as an important gaseous signal in plants. Here, we investigated the mechanism of H2S in alleviating postharvest senescence and rotting of Kyoho grape. Exogenous application of H2S released from 1.0 mM NaHS remarkably decreased the rotting and threshing rate of grape berries. H2S application also prevented the weight loss in grape clusters and inhibited the decreases in firmness, soluble solids, and titratable acidity in grape pulp during postharvest storage. The data of chlorophyll and carotenoid content suggested the role of H2S in preventing chlorophyll breakdown and carotenoid accumulation in both grape rachis and pulp. In comparison to water control, exogenous H2S application maintained significantly higher levels of ascorbic acid and flavonoid and total phenolics and reducing sugar and soluble protein in grape pulp. Meanwhile, H2S significantly reduced the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2∙−) in grape pulp. Further investigations showed that H2S enhanced the activities of antioxidant enzymes ascorbate peroxidase (APX) and catalase (CAT) and decreased those of lipoxygenase (LOX) in both grape peels and pulp. In all, we provided strong evidence that H2S effectively alleviated postharvest senescence and rotting of Kyoho grape by modulating antioxidant enzymes and attenuating lipid peroxidation.

  2. Elevated CO2 alleviates high PAR and UV stress in the unicellular chlorophyte Dunaliella tertiolecta.

    PubMed

    García-Gómez, Candela; Gordillo, Francisco J L; Palma, Armando; Lorenzo, M Rosario; Segovia, María

    2014-09-01

    The effects of increased CO2 and irradiance on the physiological performance of the chlorophyte Dunaliella tertiolecta were studied at different PAR and UVR (UVA + UVB) irradiances, simulating the solar radiation at different depths, at present (390 ppmv, LC) and predicted CO2 levels for the year 2100 (1000 ppmv, HC). Elevated CO2 resulted in higher optimum and effective quantum yields (F(v)/F(m) and ϕPSII, respectively), electron transport rates (ETR) and specific growth rates (μ). Cell stress was alleviated in HC with respect to LC as evidenced by a decrease in reactive oxygen species (ROS) accumulation. DNA damage showed a 42-fold increase in cyclobutane-pyrimidine dimer (CPD) formation under the highest irradiance (1100 μmol quanta m(-2) s(-1)) in LC with respect to the lowest irradiance (200 μmol quanta m(-2) s(-1)). Photolyase (CII-PCD-PL) gene expression was upregulated under HC resulting in a drastic decrease in CPD accumulation to only 25% with respect to LC. Proliferating cell nuclear antigen (PCNA) accumulation was always higher in HC and the accumulation pattern indicated its involvement in repair or growth depending on the irradiance dose. The repressor of silencing (ROS1) was only marginally involved in the response, suggesting that photoreactivation was the most relevant mechanism to overcome UVR damage. Our results demonstrate that future scenarios of global change result in alleviation of irradiance stress by CO2-induced photoprotection in D. tertiolecta.

  3. Selenium alleviates chromium toxicity by preventing oxidative stress in cabbage (Brassica campestris L. ssp. Pekinensis) leaves.

    PubMed

    Qing, Xuejiao; Zhao, Xiaohu; Hu, Chengxiao; Wang, Peng; Zhang, Ying; Zhang, Xuan; Wang, Pengcheng; Shi, Hanzhi; Jia, Fen; Qu, Chanjuan

    2015-04-01

    The beneficial role of selenium (Se) in alleviation of chromium (Cr)-induced oxidative stress is well established. However, little is known about the underlying mechanism. The impacts of exogenous Se (0.1mg/L) on Cr(1mg/L)-induced oxidative stress and antioxidant systems in leaves of cabbage (Brassica campestris L. ssp. Pekinensis) were investigated by using cellular and biochemical approaches. The results showed that supplementation of the medium with Se was effective in reducing Cr-induced increased levels of lipid peroxides and superoxide free radicals (O(-)2(·)), as well as increasing activities of superoxide dismutase (SOD) and peroxidase (POD). Meanwhile, 1mg/L Cr induced loss of plasma membrane integrity, growth inhibition, as well as ultrastructural changes of leaves were significantly reversed due to Se supplementation in the medium. In addition, Se application significantly altered the subcellular distribution of Cr which transported from mitochondria, nucleus and the cell-wall material to the soluble fraction and chloroplasts. However, Se application did no significant alteration of Cr effects on osmotic adjustment accumulating products. The study suggested that Se is able to protect leaves of cabbage against Cr toxicity by alleviation of Cr induced oxidative stress, and re-distribution of Cr in the subcellular of the leaf. Furthermore, free radicals, lipid peroxides, activity of SOD and POD, and subcellular distribution of Cr can be considered the efficient biomarkers to indicate the efficiency of Se to detoxification Cr.

  4. Hydrogen Sulfide Alleviates Postharvest Senescence of Grape by Modulating the Antioxidant Defenses.

    PubMed

    Ni, Zhi-Jing; Hu, Kang-Di; Song, Chang-Bing; Ma, Run-Hui; Li, Zhi-Rong; Zheng, Ji-Lian; Fu, Liu-Hui; Wei, Zhao-Jun; Zhang, Hua

    2016-01-01

    Hydrogen sulfide (H2S) has been identified as an important gaseous signal in plants. Here, we investigated the mechanism of H2S in alleviating postharvest senescence and rotting of Kyoho grape. Exogenous application of H2S released from 1.0 mM NaHS remarkably decreased the rotting and threshing rate of grape berries. H2S application also prevented the weight loss in grape clusters and inhibited the decreases in firmness, soluble solids, and titratable acidity in grape pulp during postharvest storage. The data of chlorophyll and carotenoid content suggested the role of H2S in preventing chlorophyll breakdown and carotenoid accumulation in both grape rachis and pulp. In comparison to water control, exogenous H2S application maintained significantly higher levels of ascorbic acid and flavonoid and total phenolics and reducing sugar and soluble protein in grape pulp. Meanwhile, H2S significantly reduced the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2 (∙-)) in grape pulp. Further investigations showed that H2S enhanced the activities of antioxidant enzymes ascorbate peroxidase (APX) and catalase (CAT) and decreased those of lipoxygenase (LOX) in both grape peels and pulp. In all, we provided strong evidence that H2S effectively alleviated postharvest senescence and rotting of Kyoho grape by modulating antioxidant enzymes and attenuating lipid peroxidation. PMID:27594971

  5. Parallel Mitogenome Sequencing Alleviates Random Rooting Effect in Phylogeography

    PubMed Central

    Hirase, Shotaro; Takeshima, Hirohiko; Nishida, Mutsumi; Iwasaki, Wataru

    2016-01-01

    Reliably rooted phylogenetic trees play irreplaceable roles in clarifying diversification in the patterns of species and populations. However, such trees are often unavailable in phylogeographic studies, particularly when the focus is on rapidly expanded populations that exhibit star-like trees. A fundamental bottleneck is known as the random rooting effect, where a distant outgroup tends to root an unrooted tree “randomly.” We investigated whether parallel mitochondrial genome (mitogenome) sequencing alleviates this effect in phylogeography using a case study on the Sea of Japan lineage of the intertidal goby Chaenogobius annularis. Eighty-three C. annularis individuals were collected and their mitogenomes were determined by high-throughput and low-cost parallel sequencing. Phylogenetic analysis of these mitogenome sequences was conducted to root the Sea of Japan lineage, which has a star-like phylogeny and had not been reliably rooted. The topologies of the bootstrap trees were investigated to determine whether the use of mitogenomes alleviated the random rooting effect. The mitogenome data successfully rooted the Sea of Japan lineage by alleviating the effect, which hindered phylogenetic analysis that used specific gene sequences. The reliable rooting of the lineage led to the discovery of a novel, northern lineage that expanded during an interglacial period with high bootstrap support. Furthermore, the finding of this lineage suggested the existence of additional glacial refugia and provided a new recent calibration point that revised the divergence time estimation between the Sea of Japan and Pacific Ocean lineages. This study illustrates the effectiveness of parallel mitogenome sequencing for solving the random rooting problem in phylogeographic studies. PMID:27016485

  6. Ganokendra: An Innovative Model for Poverty Alleviation In Bangladesh

    NASA Astrophysics Data System (ADS)

    Alam, Kazi Rafiqul

    2006-05-01

    Ganokendras (people's learning centers) employ a literacy-based approach to alleviating poverty in Bangladesh. They give special attention to empowering rural women, among whom poverty is widespread. The present study reviews the Ganokendra-approach to facilitating increased political and economic awareness and improving community conditions in line with government initiatives for poverty reduction. Many Ganokendras implement programmes geared towards income-generating activities and establish linkages with other service providers, both governmental and non-governmental. As is shown, one particularly successful strategy for facilitating women's economic empowerment involves co-ordinating micro-credit available through other agencies.

  7. A Comprehensive Robust Adaptive Controller for Gust Load Alleviation

    PubMed Central

    Quagliotti, Fulvia

    2014-01-01

    The objective of this paper is the implementation and validation of an adaptive controller for aircraft gust load alleviation. The contribution of this paper is the design of a robust controller that guarantees the reduction of the gust loads, even when the nominal conditions change. Some preliminary results are presented, considering the symmetric aileron deflection as control device. The proposed approach is validated on subsonic transport aircraft for different mass and flight conditions. Moreover, if the controller parameters are tuned for a specific gust model, even if the gust frequency changes, no parameter retuning is required. PMID:24688411

  8. A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation; Mitigation of NPY up-regulation in the touch sense pathway.

    PubMed

    Fukuoka, T; Noguchi, K

    2015-09-24

    Intrathecal delivery of glial cell line-derived neurotrophic factor (GDNF) reverses mechanical allodynia after 5th lumbar (L5) spinal nerve ligation (SNL). However, the molecular mechanism behind this process is not fully understood. Following sciatic nerve injury, primary afferent neurons in the injured dorsal root ganglion (DRG) begin to express neuropeptide Y (NPY) that is absent in normal DRG. The aim of the current study was to determine the relationship of this de novo expression of NPY and the anti-allodynic effect of GDNF. Following L5 SNL, 73% of neurons began to express NPY mRNA in the ipsilateral L5 DRG and robust NPY-immunoreactive fibers appeared in the ipsilateral GN where the touch-sense mediating A-fiber primary afferents from the hindpaw terminate. Seven-daylong intrathecal infusion of GDNF at the L5 DRG level, starting on day three when mechanical allodynia had fully developed, reversed once-established these changes. The GN neurons normally expressed NPY Y1 receptor, but not Y2, Y4, or Y5 receptors, and L5 SNL did not change the expression pattern. Bolus intracisternal injection of BIBP3226, a Y1 receptor antagonist, dose-dependently reversed mechanical allodynia. We demonstrated that GDNF reversed once-established mechanical allodynia as well as NPY induction in the touch-sense processing pathway. NPY could facilitate touch-sense processing by Y1 receptor in the gracile nucleus after peripheral nerve injury. GDNF may exert anti-allodynic effects through mitigation of this NPY up-regulation. The effectiveness of delayed treatment further indicates the therapeutic potential of GDNF on neuropathic pain.

  9. Short-term selective alleviation of glucotoxicity and lipotoxicity ameliorates the suppressed expression of key β-cell factors under diabetic conditions.

    PubMed

    Shimo, Naoki; Matsuoka, Taka-aki; Miyatsuka, Takeshi; Takebe, Satomi; Tochino, Yoshihiro; Takahara, Mitsuyoshi; Kaneto, Hideaki; Shimomura, Iichiro

    2015-11-27

    Alleviation of hyperglycaemia and hyperlipidemia improves pancreatic β-cell function in type 2 diabetes. However, the underlying molecular mechanisms are still not well clarified. In this study, we aimed to elucidate how the expression alterations of key β-cell factors are altered by the short-term selective alleviation of glucotoxicity or lipotoxicity. We treated db/db mice for one week with empagliflozin and/or bezafibrate to alleviate glucotoxicity and/or liptotoxicity, respectively. The gene expression levels of Pdx1 and Mafa, and their potential targets, insulin 1, Slc2a2, and Glp1r, were higher in the islets of empagliflozin-treated mice, and levels of insulin 2 were higher in mice treated with both reagents, than in untreated mice. Moreover, compared to the pretreatment levels, Mafa and insulin 1 expression increased in empagliflozin-treated mice, and Slc2a2 increased in combination-treated mice. In addition, empagliflozin treatment enhanced β-cell proliferation assessed by Ki-67 immunostaining. Our date clearly demonstrated that the one-week selective alleviation of glucotoxicity led to the better expression levels of the key β-cell factors critical for β-cell function over pretreatment levels, and that the alleviation of lipotoxicity along with glucotoxicity augmented the favorable effects under diabetic conditions. PMID:26471305

  10. Active smart material control system for buffet alleviation

    NASA Astrophysics Data System (ADS)

    Sheta, Essam F.; Moses, Robert W.; Huttsell, Lawrence J.

    2006-05-01

    Vertical tail buffeting is a serious multidisciplinary problem that limits the performance and maneuverability of twin-tail fighter aircraft. The buffet problem occurs at high angles of attack when the vortical flow breaks down ahead of the vertical tails resulting in unsteady and unbalanced loads on the tails leading to their premature fatigue failure. An active smart material control system, using distributed piezoelectric (PZT) actuators, is developed for buffet alleviation and is presented. The surfaces of the vertical tail are equipped with PZT actuators to control the buffet responses in the first bending and torsion modes. The electrodynamics of the PZT actuators are modeled using a finite-element model. A single-input/single-output controller is designed to drive the active PZT actuators. High-fidelity analysis modules for the fluid dynamics, structural dynamics, electrodynamics of the PZT actuators, control law, fluid-structure interfacing, and grid motion are integrated into a multidisciplinary computing environment that controls the temporal synchronization of the analysis modules. The results of this study indicate that the actively controlled PZT actuators are an effective tool for buffet alleviation over wide range of angels of attack. Peak values of power spectral density of tail-tip acceleration are reduced by as much as 22% in the first bending mode and by as much as 82% in the first torsion mode. The root mean square values of tail-tip acceleration are reduced by as much as 12%.

  11. Hypoxic Preconditioning Alleviates Ethanol Neurotoxicity: the Involvement of Autophagy

    PubMed Central

    Wang, Haiping; Bower, Kimberly A.; Frank, Jacqueline A.; Xu, Mei; Luo, Jia

    2013-01-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system (CNS) neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1% oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al., 2010). We therefore hypothesize that the modest hypoxic preconditioning may offer a protection against ethanol-induced neurotoxicity. We showed here that the modest hypoxic preconditioning (1% oxygen) for 8 hours significantly alleviated ethanol-induced death of SH-SY5Y neuroblastoma cells. Under the normoxia condition, cell viability in ethanol-exposed cultures (316 mg/dl for 48 hrs) was 49 ± 6% of untreated controls; however, with hypoxic preconditioning, cell viability in the ethanol-exposed group increased to 78 ± 7% of the controls (p < 0.05; n = 3). Bafilomycin A1, an inhibitor of autophagosome and lysosome fusion, blocked hypoxic preconditioning-mediated protection. Similarly, inhibition of autophagic initiation by wortmannin also eliminated hypoxic preconditioning-mediated protection. In contrast, activation of autophagy by rapamycin further enhanced neuroprotection caused by hypoxic preconditioning. Taken together, the results confirm that autophagy is a protective response against ethanol neurotoxicity and the modest hypoxic preconditioning can offer neuroprotection by activating autophagic pathways. PMID:23568540

  12. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes.

    PubMed

    Daverey, Amita; Agrawal, Sandeep K

    2016-10-01

    Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis.

  13. Resource Assessment for Afghanistan and Alleviation of Terrorism

    NASA Astrophysics Data System (ADS)

    Shroder, J. F.

    2002-05-01

    Mineral and water resources in Afghanistan may be the best means by which redevelopment of the country can be used to alleviate future terrorism. Remote-sensing analysis of snow, ice, resources, and topography in Afghanistan, and development of digital elevation models with ASTER imagery and previously classified, large scale topographic maps from the Department of Defense enable better assessment and forecasting resources in the country. Adequate resource assessment and planning is viewed as critical to alleviation of one cause of the problems associated with the fertilization of terrorism in Afghanistan. Long-term diminution of meltwater resources in Afghanistan is exemplified by the disastrous and famine-inducing droughts of the present time and three decades prior, as well as by the early Landsat assessment of glacier resources sponsored by USGS and now brought up-to-date with current imagery. Extensive cold-war projects undertaken by both the USSR and USA generated plentiful essential mineral, hydrocarbon, hydrogeological, and hydrological data, including an extensive stream gauging and vital irrigation network now adversly affected or destroyed entirely by decades of war. Analysis, measurement, prediction, rehabilitation, and reconstruction of critical resource projects are regarded as most critical elements in the war on terrorism in this portion of the world. The GLIMS (Global Land Ice Measurements from Space) Project, initially sponsored by USGS, has established our group as the Regional Center for Afghanistan and Pakistan, in which the above concepts serve as guiding research precepts.

  14. Gynura procumbens Extract Alleviates Postprandial Hyperglycemia in Diabetic Mice

    PubMed Central

    Choi, Sung-In; Park, Mi Hwa; Han, Ji-Sook

    2016-01-01

    This study was designed to investigate the inhibitory effect of Gynura procumbens extract against carbohydrate digesting enzymes and its ability to ameliorate postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. G. procumbens extract showed prominent α-glucosidase and α-amylase inhibitory effects. The half-maximal inhibitory concentration (IC50) of G. procumbens extract against α-glucosidase and α-amylase was 0.092±0.018 and 0.084±0.027 mg/mL, respectively, suggesting that the α-amylase inhibition activity of the G. procumbens extract was more effective than that of the positive control, acarbose (IC50=0.164 mg/mL). The increase in postprandial blood glucose levels was more significantly alleviated in the G. procumbens extract group than in the control group of STZ-induced diabetic mice. Moreover, the area under the curve significantly decreased with G. procumbens extract administration in STZ-induced diabetic mice. These results suggest that G. procumbens extract may help alleviate postprandial hyperglycemia by inhibiting carbohydrate digesting enzymes. PMID:27752493

  15. Low molecular weight fucoidan modulates P-selectin and alleviates diabetic nephropathy.

    PubMed

    Xu, Yingjie; Zhang, Quanbin; Luo, Dali; Wang, Jing; Duan, Delin

    2016-10-01

    Diabetic nephropathy (DN) is a serious microvascular complication that can lead to chronic and end-stage renal failure. It is understood that inflammation is associated with the onset and process of DN. Low molecular weight fucoidan (LMWF) isolated from Saccharina japonica has anti-inflammatory properties. Therefore, this study aimed to explore the mechanism of LMWF in DN model induced by streptozotocin. The biochemical indices levels showed LMWF reduced the DN diagnostic indices to protect renal function. The HE stained sections exhibited LMWF protected normal morphological structures and reduced inflammatory cell infiltration in the kidneys of DN rats. Furthermore, the levels of P-selectin and selectin-dependent inflammatory cytokines resulting from LMWF were obviously decreased at both the transcriptional and protein levels. Thus, our results found that LMWF protected the renal function in DN rats and alleviated inflammation through the modulation of P-selectin and inflammatory cytokines. LMWF may have therapeutic potential against DN. PMID:27234491

  16. Roles of meditation on alleviation of oxidative stress and improvement of antioxidant system.

    PubMed

    Mahagita, Chitrawina

    2010-11-01

    According to MEDLINE/Pubmed search to December 2009, the modulation effects of meditation on oxidative stress have been increasingly investigated for acute, short and long-term effects. Both invasive and noninvasive measurements have been utilized. Long-term transcendental and Zen meditators have been showed to diminish oxidative stress seen by a reduction of lipid peroxidation and biophoton emission. Glutathione level and activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase) have been facilitated in Yoga and Sudarshan Kriya practitioners. One year of Tai Chi training has been reported to promote superoxide dismutase activity and lessen lipid peroxidation. Performing diaphragmatic breathing after exhaustive exercise has attenuated oxidative stress faster than control. These data suggest possible roles of meditation and meditation-based techniques on the decrease of oxidative stress which may assist to prevent and/or alleviate deterioration of related diseases. However, further research needs to elucidate the cellular and molecular mechanisms which remain challenge to accomplish.

  17. Novel medical bathing with traditional Chinese herb formula alleviates paraplegia spasticity.

    PubMed

    Liu, Xin; Meng, Qingxi; Yu, Dapeng; Zhao, Xiwu; Zhao, Tingbao

    2014-06-01

    Paraplegia spasm is a kind of chronic disease which lacks effective treatment; the patients have to endure long-term pain, which is a tough problem for nursing practice. Lots of potential candidate medicines are under investigation, and a new Chinese herb formula is introduced in the current study. In the present study, we chose six different well-known Chinese herbs to form a formula, and boiled them into the water with an optimized ratio to make bath water; 80 paraplegic patients received this medicinal bath, and 80 patients received perfume water bath as placebo group. Compared with placebo control patients, the herb-treated patients have significant reduction in paraplegia spasm, visual analogue scale score, clinician global impression and sleep disorder. This novel six-combined formula traditional medicine could be beneficial for alleviating paraplegia spasm, but the underlying action mechanism deserves further study.

  18. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.

    PubMed

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-01-01

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches.

  19. Low molecular weight fucoidan modulates P-selectin and alleviates diabetic nephropathy.

    PubMed

    Xu, Yingjie; Zhang, Quanbin; Luo, Dali; Wang, Jing; Duan, Delin

    2016-10-01

    Diabetic nephropathy (DN) is a serious microvascular complication that can lead to chronic and end-stage renal failure. It is understood that inflammation is associated with the onset and process of DN. Low molecular weight fucoidan (LMWF) isolated from Saccharina japonica has anti-inflammatory properties. Therefore, this study aimed to explore the mechanism of LMWF in DN model induced by streptozotocin. The biochemical indices levels showed LMWF reduced the DN diagnostic indices to protect renal function. The HE stained sections exhibited LMWF protected normal morphological structures and reduced inflammatory cell infiltration in the kidneys of DN rats. Furthermore, the levels of P-selectin and selectin-dependent inflammatory cytokines resulting from LMWF were obviously decreased at both the transcriptional and protein levels. Thus, our results found that LMWF protected the renal function in DN rats and alleviated inflammation through the modulation of P-selectin and inflammatory cytokines. LMWF may have therapeutic potential against DN.

  20. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination

    PubMed Central

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-01-01

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches. PMID:27040771

  1. Naringenin Alleviates Cadmium-Induced Toxicity through the Abrogation of Oxidative Stress in Swiss Albino Mice.

    PubMed

    Das, Avratanu; Roy, Amrita; Das, Ruma; Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2016-01-01

    The present study evaluates the protective potential of the flavonoid naringenin (NRG) against experimentally induced cadmium (Cd) toxicity in Swiss albino mice. NRG (4 and 8 mg/kg) was orally administered to mice 30 min before oral administration of CdCl2 (12 mg/kg) for 11 consecutive days. On the 12th day, we evaluated body and organ weights, hematological profiles, serum biochemical profiles, and hepatic and renal tissue antioxidative parameters including lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase. Cotreatment with NRG markedly and significantly normalized body and organ weights, hematological profiles, and serum biochemical profiles and significantly modulated all of the hepatic and renal tissue biochemical parameters in Cd-intoxicated mice. The present findings show that NRG possesses a remarkable alleviative effect against Cd-induced toxicity in albino mice, mediated by abrogation of Cd-induced oxidative stress by multiple mechanisms. PMID:27481493

  2. Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction

    PubMed Central

    Chen, Fenqin; Zhang, Ning; Ma, Xiaoyu; Huang, Ting; Shao, Ying; Wu, Can; Wang, Qiuyue

    2015-01-01

    Naringin, a flavanone glycoside extracted from Citrus grandis Osbeck, has a wide range of pharmacological effects. In the present study we aimed at demonstrating the protective effect of naringin against diabetic kidney disease (DKD) and elucidating its possible molecular mechanism underlying. The beneficial effect of naringin was assessed in rats with streptozotocin (STZ)-induced diabetes and high glucose-induced HBZY-1 cells. According to our results, first we found that naringin relieved kidney injury, improved renal function and inhibited collagen formation and renal interstitial fibrosis. Second, we confirmed that naringin restrained oxidative stress by activating Nrf2 antioxidant pathway. Moreover, the results suggested that naringin significantly resisted inflammatory reaction by inhibiting NF- κ B signaling pathway. Taken together, our results demonstrate that naringin effectively alleviates DKD, which provide theoretical basis for naringin clinically used to treatment of DKD. PMID:26619044

  3. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.

    PubMed

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-01-01

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches. PMID:27040771

  4. Experimental evidence for alleviating nociceptive hypersensitivity by single application of capsaicin.

    PubMed

    Ma, Xiao-Li; Zhang, Fang-Xiong; Dong, Fei; Bao, Lan; Zhang, Xu

    2015-04-22

    The single application of high-concentration of capsaicin has been used as an analgesic therapy of persistent pain. However, its effectiveness and underlying mechanisms remain to be further evaluated with experimental approaches. The present study provided evidence showing that the single application of capsaicin dose-dependently alleviated nociceptive hypersensitivity, and reduced the action potential firing in small-diameter neurons of the dorsal root ganglia (DRG) in rats and mice. Pre-treatment with capsaicin reduced formalin-induced acute nocifensive behavior after a brief hyperalgesia in rats and mice. The inhibitory effects of capsaicin were calcium-dependent, and mediated by the capsaicin receptor (transient receptor potential vanilloid type-1). We further found that capsaicin exerted inhibitory effects on the persistent nociceptive hypersensitivity induced by peripheral inflammation and nerve injury. Thus, these results support the long-lasting and inhibitory effects of topical capsaicin on persistent pain, and the clinic use of capsaicin as a pain therapy.

  5. Novel medical bathing with traditional Chinese herb formula alleviates paraplegia spasticity.

    PubMed

    Liu, Xin; Meng, Qingxi; Yu, Dapeng; Zhao, Xiwu; Zhao, Tingbao

    2014-06-01

    Paraplegia spasm is a kind of chronic disease which lacks effective treatment; the patients have to endure long-term pain, which is a tough problem for nursing practice. Lots of potential candidate medicines are under investigation, and a new Chinese herb formula is introduced in the current study. In the present study, we chose six different well-known Chinese herbs to form a formula, and boiled them into the water with an optimized ratio to make bath water; 80 paraplegic patients received this medicinal bath, and 80 patients received perfume water bath as placebo group. Compared with placebo control patients, the herb-treated patients have significant reduction in paraplegia spasm, visual analogue scale score, clinician global impression and sleep disorder. This novel six-combined formula traditional medicine could be beneficial for alleviating paraplegia spasm, but the underlying action mechanism deserves further study. PMID:24621269

  6. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    SciTech Connect

    Cui, Ruibing; Yan, Lihui; Luo, Zheng; Guo, Xiaolan; Yan, Ming

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  7. Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway.

    PubMed

    Song, Young Mi; Lee, Yong-ho; Kim, Ji-Won; Ham, Dong-Sik; Kang, Eun-Seok; Cha, Bong Soo; Lee, Hyun Chul; Lee, Byung-Wan

    2015-01-01

    Metformin activates both PRKA and SIRT1. Furthermore, autophagy is induced by either the PRKA-MTOR-ULK1 or SIRT1-FOXO signaling pathways. We aimed to elucidate the mechanism by which metformin alleviates hepatosteatosis by examining the molecular interplay between SIRT1, PRKA, and autophagy. ob/ob mice were divided into 3 groups: one with ad libitum feeding of a standard chow diet, one with 300 mg/kg intraperitoneal metformin injections, and one with 3 g/d caloric restriction (CR) for a period of 4 wk. Primary hepatocytes or HepG2 cells were treated with oleic acid (OA) plus high glucose in the absence or presence of metformin. Both CR and metformin significantly improved body weight and glucose homeostasis, along with hepatic steatosis, in ob/ob mice. Furthermore, CR and metformin both upregulated SIRT1 expression and also stimulated autophagy induction and flux in vivo. Metformin also prevented OA with high glucose-induced suppression of both SIRT1 expression and SIRT1-dependent activation of autophagy machinery, thereby alleviating intracellular lipid accumulation in vitro. Interestingly, metformin treatment upregulated SIRT1 expression and activated PRKA even after siRNA-mediated knockdown of PRKAA1/2 and SIRT1, respectively. Taken together, these results suggest that metformin alleviates hepatic steatosis through PRKA-independent, SIRT1-mediated effects on the autophagy machinery.

  8. Silicon alleviates cadmium toxicity by enhanced photosynthetic rate and modified bundle sheath's cell chloroplasts ultrastructure in maize.

    PubMed

    Vaculík, Marek; Pavlovič, Andrej; Lux, Alexander

    2015-10-01

    Silicon was shown to alleviate the negative effects of various biotic and abiotic stresses on plant growth. Although the positive role of Si on toxic and heavy metal Cd has been already described, the mechanisms have been explained only partially and still remain unclear. In the present study we investigated the effect of Si on photosynthetic-related processes in maize exposed to two different levels of Cd via measurements of net photosynthetic rate (AN), chlorophyll a fluorescence and pigment analysis, as well as studies of leaf tissue anatomy and cell ultrastructure using bright-field and transmission electron microscopy. We found that Si actively alleviated the toxic syndromes of Cd by increasing AN, effective photochemical quantum yield of photosystem II (ϕPSII) and content of assimilation pigments, although did not decrease the concentration of Cd in leaf tissues. Cadmium did not affect the leaf anatomy and ultrastructure of leaf mesophyll's cell chloroplasts; however, Cd negatively affected thylakoid formation in chloroplasts of bundle sheath cells, and this was alleviated by Si. Improved thylakoid formation in bundle sheath's cell chloroplasts may contribute to Si-induced enhancement of photosynthesis and related increase in biomass production in C4 plant maize.

  9. Inhibition of Spinal Ca(2+)-Permeable AMPA Receptors with Dicationic Compounds Alleviates Persistent Inflammatory Pain without Adverse Effects.

    PubMed

    Kopach, Olga; Krotov, Volodymyr; Goncharenko, Julia; Voitenko, Nana

    2016-01-01

    Upregulation of Ca(2+)-permeable AMPA receptors (CP-AMPARs) in the dorsal horn (DH) neurons of the spinal cord has been causally linked to the maintenance of persistent inflammatory pain. Therefore, inhibition of CP-AMPARs could potentially alleviate an, otherwise, poorly treatable chronic pain. However, a loss of CP-AMPARs could produce considerable side effects because of the crucial role of CP-AMPARs in synaptic plasticity. Here we have tested whether the inhibition of spinal CP-AMPARs with dicationic compounds, the open-channel antagonists acting in an activity-dependent manner, can relieve inflammatory pain without adverse effects being developed. Dicationic compounds, N1-(1-phenylcyclohexyl)pentane-1,5-diaminium bromide (IEM-1925) and 1-trimethylammonio-5-1-adamantane-methyl-ammoniopentane dibromide (IEM-1460) were applied intrathecally (i.t.) as a post-treatment for inflammatory pain in the model of complete Freund's adjuvant (CFA)-induced long-lasting peripheral inflammation. The capability of dicationic compounds to ameliorate inflammatory pain was tested in rats in vivo using the Hargreaves, the von Frey and the open-field tests. Treatment with IEM-1460 or IEM-1925 resulted in profound alleviation of inflammatory pain. The pain relief appeared shortly after compound administration. The effects were concentration-dependent, displaying a high potency of dicationic compounds for alleviation of inflammatory hyperalgesia in the micromolar range, for both acute and long-lasting responses. The period of pain maintenance was shortened following treatment. Treatment with IEM-1460 or IEM-1925 changed neither thermal and mechanical basal sensitivities nor animal locomotion, suggesting that inhibition of CP-AMPARs with dicationic compounds does not give rise to detectable side effects. Thus, the ability of dicationic compounds to alleviate persistent inflammatory pain may provide new routes in the treatment of chronic pain. PMID:26973464

  10. Inhibition of Spinal Ca2+-Permeable AMPA Receptors with Dicationic Compounds Alleviates Persistent Inflammatory Pain without Adverse Effects

    PubMed Central

    Kopach, Olga; Krotov, Volodymyr; Goncharenko, Julia; Voitenko, Nana

    2016-01-01

    Upregulation of Ca2+-permeable AMPA receptors (CP-AMPARs) in the dorsal horn (DH) neurons of the spinal cord has been causally linked to the maintenance of persistent inflammatory pain. Therefore, inhibition of CP-AMPARs could potentially alleviate an, otherwise, poorly treatable chronic pain. However, a loss of CP-AMPARs could produce considerable side effects because of the crucial role of CP-AMPARs in synaptic plasticity. Here we have tested whether the inhibition of spinal CP-AMPARs with dicationic compounds, the open-channel antagonists acting in an activity-dependent manner, can relieve inflammatory pain without adverse effects being developed. Dicationic compounds, N1-(1-phenylcyclohexyl)pentane-1,5-diaminium bromide (IEM-1925) and 1-trimethylammonio-5-1-adamantane-methyl-ammoniopentane dibromide (IEM-1460) were applied intrathecally (i.t.) as a post-treatment for inflammatory pain in the model of complete Freund’s adjuvant (CFA)-induced long-lasting peripheral inflammation. The capability of dicationic compounds to ameliorate inflammatory pain was tested in rats in vivo using the Hargreaves, the von Frey and the open-field tests. Treatment with IEM-1460 or IEM-1925 resulted in profound alleviation of inflammatory pain. The pain relief appeared shortly after compound administration. The effects were concentration-dependent, displaying a high potency of dicationic compounds for alleviation of inflammatory hyperalgesia in the micromolar range, for both acute and long-lasting responses. The period of pain maintenance was shortened following treatment. Treatment with IEM-1460 or IEM-1925 changed neither thermal and mechanical basal sensitivities nor animal locomotion, suggesting that inhibition of CP-AMPARs with dicationic compounds does not give rise to detectable side effects. Thus, the ability of dicationic compounds to alleviate persistent inflammatory pain may provide new routes in the treatment of chronic pain. PMID:26973464

  11. Puerariae flos alleviates metabolic diseases in Western diet-loaded, spontaneously obese type 2 diabetic model mice.

    PubMed

    Kubo, Koshi; Shimada, Tsutomu; Onishi, Rei; Tsubata, Masahito; Kamiya, Tomoyasu; Nagamine, Rika; Iizuka, Seiichi; Sai, Yoshimichi; Amagaya, Sakae; Aburada, Masaki; Miyamoto, Ken-ichi

    2012-10-01

    Puerariae flos extract (PFE) has been reported to have many effects, including preventing the development of hangovers, liver protective effects, and an estrogenic effect. In addition, some papers reported that PFE is effective against metabolic diseases, with hypolipidemic and hypoglycemic effects. However, the mechanism underlying such effects remains unclear. For the purpose of clarifying the effect of PFE on metabolic diseases related to the accumulation of visceral fat and to determine the mechanism of such action, TSOD mice, a multifactorial genetic disease animal model that spontaneously develops various metabolic diseases such as obesity and type 2 diabetes, were given a Western diet (WTD) as an environmental factor to prepare a disease model (TSOD-WTD). When TSOD mice were loaded with WTD, it was confirmed that metabolic diseases such as obesity and abnormal glucose/lipid metabolism are aggravated. In contrast, PFE treatment to TSOD-WTD mice was shown to suppress body weight gain and visceral fat accumulation, alleviated the abnormal glucose tolerance and hyperinsulinemia, as well as causing an increase in blood adiponectin. Furthermore, the suppression of liver enlargement was observed in PFE-treated mice, with suppression of fatty degeneration and anti-inflammatory effect. In addition, to clarify the mechanism of the hyperlipidemia-alleviating effects in the liver, we investigated the effect of PFE on the expression of genes involved in cholesterol homeostasis. PFE was associated with a significant increase in gene expression for cholesterol synthesis rate-limiting enzyme HMG-CoA reductase, cholesterol catabolization enzyme Cyp7A1, bile salt export pump adenosine triphosphate-binding cassette transporter B11, and low-density lipoprotein receptor involved in cholesterol uptake. The above results suggest that PFE acts to alleviate the effects of various metabolic diseases based on the accumulation of visceral adipose tissue, including obesity, diabetes

  12. Non-pharmacological approaches to alleviate distress in dementia care.

    PubMed

    Mitchell, Gary; Agnelli, Joanne

    2015-11-25

    Distress is one of the most common clinical manifestations associated with dementia. Pharmacological intervention may be appropriate in managing distress in some people. However, best practice guidelines advocate non-pharmacological interventions as the preferred first-line treatment. The use of non-pharmacological interventions encourages healthcare professionals to be more person-centred in their approach, while considering the causes of distress. This article provides healthcare professionals with an overview of some of the non-pharmacological approaches that can assist in alleviating distress for people living with dementia including: reminiscence therapy, reality orientation, validation therapy, music therapy, horticultural therapy, doll therapy and pet therapy. It provides a summary of their use in clinical practice and links to the relevant literature. PMID:26602678

  13. Flight investigation of insect contamination and its alleviation

    NASA Technical Reports Server (NTRS)

    Peterson, J. B., Jr.; Fisher, D. F.

    1978-01-01

    An investigation of leading edge contamination by insects was conducted with a JetStar airplane instrumented to detect transition on the outboard leading edge flap and equipped with a system to spray the leading edge in flight. The results of airline type flights with the JetStar indicated that insects can contaminate the leading edge during takeoff and climbout. The results also showed that the insects collected on the leading edges at 180 knots did not erode at cruise conditions for a laminar flow control airplane and caused premature transition of the laminar boundary layer. None of the superslick and hydrophobic surfaces tested showed any significant advantages in alleviating the insect contamination problem. While there may be other solutions to the insect contamination problem, the results of these tests with a spray system showed that a continouous water spray while encountering the insects is effective in preventing insect contamination of the leading edges.

  14. Music-reading training alleviates crowding with musical notation.

    PubMed

    Wong, Yetta Kwailing; Wong, Alan C-N

    2016-06-01

    Crowding refers to the disrupted recognition of an object by nearby distractors. Prior work has shown that real-world music-reading experts experience reduced crowding specifically for musical stimuli. However, it is unclear whether music-reading training reduced the magnitude of crowding or whether individuals showing less crowding are more likely to learn and excel in music reading later. To examine the first possibility, we tested whether crowding can be alleviated by music-reading training in the laboratory. Intermediate-level music readers completed 8 hr of music-reading training within 2 weeks. Their threshold duration for reading musical notes dropped by 44.1% after training to a level comparable with that of extant expert music readers. Importantly, crowding was reduced with musical stimuli but not with the nonmusical stimuli Landolt Cs. In sum, the reduced crowding for musical stimuli in expert music readers can be explained by music-reading training.

  15. Optimal control alleviation of tilting proprotor gust response

    NASA Technical Reports Server (NTRS)

    Johnson, W.

    1975-01-01

    Optimal control theory is applied to the design of a control system for alleviation of the gust response of tilting proprotor aircraft. Using a proprotor and cantilever wing analytical model, the uncontrolled and controlled gust response is examined over the entire operating range of the aircraft except for hover: helicopter mode, conversion, and airplane mode flight. Substantial improvements in the loads, ride quality, and aeroelastic stability are possible with a properly designed controller. A single controller, nominally optimal only at the design point speed (160 knots here), operated efficiently over the entire speed range, with the possible exception of very low speed in helicopter mode. Kalman-Bucy filters were used as compensation networks to provide state estimates from various measurements in the wing motion, rotor speed perturbation, and tip-path-plane tilt.

  16. Wake vortex alleviation using rapidly actuated segmented Gurney flaps

    NASA Astrophysics Data System (ADS)

    Matalanis, Claude G.

    All bodies that generate lift also generate circulation. The circulation generated by large commercial aircraft remains in their wake in the form of trailing vortices. These vortices can be hazardous to following aircraft due to their strength and persistence. To account for this, airports abide by spacing rules which govern the frequency with which aircraft can use their runways when operating in instrument flight rules. These spacing rules are the limiting factor on increasing airport capacity. We conducted an experimental and computational study to assess the potential for using rapidly actuated segmented Gurney flaps, also known as Miniature Trailing Edge Effectors (MiTEs), for active wake vortex alleviation. Wind tunnel tests were performed on a half-span model NACA 0012 wing equipped with an array of 13 independent MITE pairs. The chord-based Reynolds number was around 350,000. Each MiTE could extend 0.015 chord lengths perpendicular to the freestream on the pressure side of the wing. Pressure profiles and a five-hole probe survey in the near wake were used to examine the influence that the MiTEs had upon the wing aerodynamics and the vortex rollup process. Particle image velocimetry was used to measure the static and time-dependent response of the vortex in the intermediate wake to various MiTE actuation schemes. These results were used to form complete initial conditions for vortex filament computations of the far wake evolution. Results from these computations showed that the perturbations created by MiTEs could be used to excite a variety of three-dimensional inviscid vortex instabilities. Finally, the research performed on MiTEs led to the invention of a more practical wake alleviation device: the spanwise actuating Gurney flap. Prototype tests showed that this device could produce similar perturbations to the MiTEs.

  17. Oral carbohydrate loading with 18% carbohydrate beverage alleviates insulin resistance.

    PubMed

    Tamura, Takahiko; Yatabe, Tomoaki; Kitagawa, Hiroyuki; Yamashita, Koichi; Hanazaki, Kazuhiro; Yokoyama, Masataka

    2013-01-01

    Preoperative 12.6% oral carbohydrate loading is an element of the Enhanced Recovery After Surgery (ERAS) protocol aimed at alleviating postoperative insulin resistance; however, in Japan, beverages with 18% carbohydrate content are generally used for preoperative carbohydrate loading. We investigated the effect of 18% carbohydrate loading on alleviating insulin resistance. Six healthy volunteers participated in this crossover-randomized study and were segregated into 2 groups: volunteers in the carbohydrate-loading group (group A) who fasted from after 9 pm and ingested 375 mL of a beverage containing 18% carbohydrate (ArginaidWaterTM; Nestle, Tokyo, Japan) between 9 pm and 12 pm, and 250 mL of the same liquid at 6:30 am. Volunteers in control group (group B) drank only water. At 8:30 am, a hyperinsulinemic normoglycemic clamp was initiated. Glucose infusion rate (GIR) and levels of ketone bodies and cytokines (IL-1β, IL-6, and TNF-α) before clamping were evaluated. p<0.05 was considered statistically significant. Levels of blood glucose, insulin, and cytokines at the start of the clamp were similar in both the groups. The GIR in group A was significantly higher than that in group B (11.5±2.4 vs 6.2±2.2 mg/kg/min, p=0.005), while blood ketone body levels were significantly lower in group A (22±4 vs 124±119 μmol/L, p=0.04). Preoperative 18% carbohydrate loading could prevent the decrease in insulin sensitivity and suppress catabolism in healthy volunteers. Thus, carbohydrate loading with a beverage with 18% carbohydrate content might contribute to improvements in perioperative management. PMID:23353610

  18. Nitrogen fertilizer improves boron phytoextraction by Brassica juncea grown in contaminated sediments and alleviates plant stress.

    PubMed

    Giansoldati, Virginia; Tassi, Eliana; Morelli, Elisabetta; Gabellieri, Edi; Pedron, Francesca; Barbafieri, Meri

    2012-06-01

    In this study we evaluated the effect of different fertilizer treatments on Brassica plants grown on boron-contaminated sediments. Experiments were conducted in the laboratory and on the lysimeter scale. At laboratory scale (microcosm), five different fertilizers were tested for a 35-d period. On the lysimeter scale, nitrogen fertilization was tested at three different doses and plants were allowed to grow until the end of the vegetative phase (70 d). Results showed that nitrogen application had effectively increased plant biomass production, while B uptake was not affected. Total B phytoextracted increased three-fold when the highest nitrogen dose was applied. Phytotoxicity on Brassica was evaluated by biochemical parameters. In plants grown in unfertilized B-contaminated sediments, the activity of antioxidant enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX) and pyrogallol peroxidase (PPX) increased, whereas catalase (CAT) decreased with respect to control plants. Addition of N progressively mitigated the alteration of enzymatic activity, thus suggesting that N can aid in alleviating B-induced oxidative stress. SOD activity was restored to control levels just at the lowest N treatment, whereas the CAT inhibition was partially restored only at the highest one. N application also lowered the B-induced increase in APX and PPX activities. Increased glutathione reductase activity indicated the need to restore the oxidative balance of glutathione. Data also suggest a role of glutathione and phytochelatins in B defense mechanisms. Results suggest that the nitrogen fertilizer was effective in improving B phytoextraction by increasing Brassica biomass and by alleviating B-induced oxidative stress. PMID:22382070

  19. Silicon alleviates deleterious effects of high salinity on the halophytic grass Spartina densiflora.

    PubMed

    Mateos-Naranjo, Enrique; Andrades-Moreno, Luis; Davy, Anthony J

    2013-02-01

    The non-essential element silicon is known to improve plant fitness by alleviating the effects of biotic and abiotic stresses, particularly in crops. However, its possible role in the exceptional tolerance of halophytes to salinity has not been investigated. This study reports the effect of Si supply on the salinity tolerance of the halophytic grass Spartina densiflora; plants were treated with NaCl (0-680 mM), with or without silicon addition of 500 μM, in a glasshouse experiment. Plant responses were examined using growth analysis, combined with measurements of gas exchange, chlorophyll fluorescence and photosynthetic pigment concentrations. In addition, tissue concentrations of aluminium, calcium, copper, iron, potassium, magnesium, sodium, phosphorus and silicon were determined. Although high salinity decreased growth, this effect was alleviated by treatment with Si. Improved growth was associated with higher net photosynthetic rate (A), and greater water-use efficiency (WUE). Enhanced A at high salinity could be explained by beneficial effects of Si on the photochemical apparatus, and on chlorophyll concentrations. Ameliorative effects of Si were correlated with reduced sodium uptake, which was unrelated to a reduction in the transpiration rate, since Si-supplemented plants had higher stomatal conductances (G(s)). These plants also had higher tissue concentrations of essential nutrients, suggesting that Si had a positive effect on the mineral nutrient balance in salt-stressed plants. Si appears to play a significant role in salinity tolerance even in a halophyte, which has other, specific salt-tolerance mechanisms, through diverse protective effects on the photosynthetic apparatus, water-use efficiency and mineral nutrient balance. PMID:23257076

  20. Arbuscular mycorrhizal symbiosis influences strigolactone production under salinity and alleviates salt stress in lettuce plants.

    PubMed

    Aroca, Ricardo; Ruiz-Lozano, Juan Manuel; Zamarreño, Angel María; Paz, José Antonio; García-Mina, José María; Pozo, María José; López-Ráez, Juan Antonio

    2013-01-01

    Arbuscular mycorrhizal (AM) symbiosis can alleviate salt stress in plants. However the intimate mechanisms involved, as well as the effect of salinity on the production of signalling molecules associated to the host plant-AM fungus interaction remains largely unknown. In the present work, we have investigated the effects of salinity on lettuce plant performance and production of strigolactones, and assessed its influence on mycorrhizal root colonization. Three different salt concentrations were applied to mycorrhizal and non-mycorrhizal plants, and their effects, over time, analyzed. Plant biomass, stomatal conductance, efficiency of photosystem II, as well as ABA content and strigolactone production were assessed. The expression of ABA biosynthesis genes was also analyzed. AM plants showed improved growth rates and a better performance of physiological parameters such as stomatal conductance and efficiency of photosystem II than non-mycorrhizal plants under salt stress since very early stages - 3 weeks - of plant colonization. Moreover, ABA levels were lower in those plants, suggesting that they were less stressed than non-colonized plants. On the other hand, we show that both AM symbiosis and salinity influence strigolactone production, although in a different way in AM and non-AM plants. The results suggest that AM symbiosis alleviates salt stress by altering the hormonal profiles and affecting plant physiology in the host plant. Moreover, a correlation between strigolactone production, ABA content, AM root colonization and salinity level is shown. We propose here that under these unfavourable conditions, plants increase strigolactone production in order to promote symbiosis establishment to cope with salt stress.

  1. Molecular hydrogen attenuates neuropathic pain in mice.

    PubMed

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

  2. Molecular Hydrogen Attenuates Neuropathic Pain in Mice

    PubMed Central

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

  3. Wake Vortex Alleviation Using Rapidly Actuated Segmented Gurney Flaps

    NASA Astrophysics Data System (ADS)

    Matalanis, Claude; Eaton, John

    2006-11-01

    A study to assess the potential for using rapidly actuated segmented Gurney flaps, also known as Miniature Trailing Edge Effectors (MiTEs), for active wake vortex alleviation is conducted using a half-span model wing with NACA 0012 shape and an aspect ratio of 4.1. All tests are performed with the wing at an 8.9 degree angle of attack and chord based Reynolds number around 350,000. The wing is equipped with an array of 13 MiTE pairs. Each MiTE has a flap that in the neutral position rests behind the blunt trailing edge of the wing, and in the down position extends 0.015 chord lengths perpendicular to the freestream on the pressure side of the wing. Dynamic PIV is used to measure the time dependent response of the vortex in the intermediate wake to various MiTE actuation schemes that deflect the vortex in both the spanwise and liftwise directions. A maximum spanwise deflection of 0.041 chord lengths is possible while nearly conserving lift. These intermediate wake results as well as pressure profile, five-hole probe, and static PIV measurements are used to form complete, experimentally-based initial conditions for vortex filament computations that are used to compute the far wake evolution. Results from these computations show that the perturbations created by MiTEs can be used to excite vortex instability.

  4. Cathepsin K knockout alleviates aging-induced cardiac dysfunction.

    PubMed

    Hua, Yinan; Robinson, Timothy J; Cao, Yongtao; Shi, Guo-Ping; Ren, Jun; Nair, Sreejayan

    2015-06-01

    Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects against pressure overload-induced cardiac hypertrophy and contractile dysfunction. Here we test the hypothesis that cathepsin K knockout alleviates age-dependent decline in cardiac function. Cardiac geometry, contractile function, intracellular Ca(2+) properties, and cardiomyocyte apoptosis were evaluated using echocardiography, fura-2 technique, immunohistochemistry, Western blot and TUNEL staining, respectively. Aged (24-month-old) mice exhibited significant cardiac remodeling (enlarged chamber size, wall thickness, myocyte cross-sectional area, and fibrosis), decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca(2+) release compared to young (6-month-old) mice, which were attenuated in the cathepsin K knockout mice. Cellular markers of senescence, including cardiac lipofuscin, p21 and p16, were lower in the aged-cathepsin K knockout mice compared to their wild-type counterpart. Mechanistically, cathepsin K knockout mice attenuated an age-induced increase in cardiomyocyte apoptosis and nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). In cultured H9c2 cells, doxorubicin stimulated premature senescence and apoptosis. Silencing of cathepsin K blocked the doxorubicin-induced translocation of AIF from the mitochondria to the nuclei. Collectively, these results suggest that cathepsin K knockout attenuates age-related decline in cardiac function via suppressing caspase-dependent and caspase-independent apoptosis. PMID:25692548

  5. Cathepsin K knockout alleviates aging-induced cardiac dysfunction

    PubMed Central

    Hua, Yinan; Robinson, Timothy J; Cao, Yongtao; Shi, Guo-Ping; Ren, Jun; Nair, Sreejayan

    2015-01-01

    Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects against pressure overload-induced cardiac hypertrophy and contractile dysfunction. Here we test the hypothesis that cathepsin K knockout alleviates age-dependent decline in cardiac function. Cardiac geometry, contractile function, intracellular Ca2+ properties, and cardiomyocyte apoptosis were evaluated using echocardiography, fura-2 technique, immunohistochemistry, Western blot and TUNEL staining, respectively. Aged (24-month-old) mice exhibited significant cardiac remodeling (enlarged chamber size, wall thickness, myocyte cross-sectional area, and fibrosis), decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca2+ release compared to young (6-month-old) mice, which were attenuated in the cathepsin K knockout mice. Cellular markers of senescence, including cardiac lipofuscin, p21 and p16, were lower in the aged-cathepsin K knockout mice compared to their wild-type counterpart. Mechanistically, cathepsin K knockout mice attenuated an age-induced increase in cardiomyocyte apoptosis and nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). In cultured H9c2 cells, doxorubicin stimulated premature senescence and apoptosis. Silencing of cathepsin K blocked the doxorubicin-induced translocation of AIF from the mitochondria to the nuclei. Collectively, these results suggest that cathepsin K knockout attenuates age-related decline in cardiac function via suppressing caspase-dependent and caspase-independent apoptosis. PMID:25692548

  6. Flutter suppression and gust alleviation using active controls

    NASA Technical Reports Server (NTRS)

    Nissim, E.

    1974-01-01

    The effects of active controls on the suppression of flutter and gust alleviation of two different types of subsonic aircraft (the Arava, twin turboprop STOL transport, and the Westwind twin-jet business transport) are investigated. The active controls are introduced in pairs which include, in any chosen wing strip, a leading-edge (LE) control and a trailing-edge (TE) control. Each control surface is allowed to be driven by a combined linear-rotational sensor system, located on the activated strip. The control law, which translates the sensor signals into control surface rotations, is based on the concept of aerodynamic energy. The results indicate the extreme effectiveness of the active systems in controlling flutter. A single system spanning 10% of the wing semispan made the Arava flutter-free, and a similar active system, for the Westwind aircraft, yielded a reduction of 75% in the maximum bending moment of the wing and a reduction of 90% in the acceleration of the cg of the aircraft. Results for simultaneous activation of several LE - TE systems are presented. Further work needed to bring the investigation to completion is also discussed.

  7. Gust alleviation of highly flexible UAVs with artificial hair sensors

    NASA Astrophysics Data System (ADS)

    Su, Weihua; Reich, Gregory W.

    2015-04-01

    Artificial hair sensors (AHS) have been recently developed in Air Force Research Laboratory (AFRL) using carbon nanotube (CNT). The deformation of CNT in air flow causes voltage and current changes in the circuit, which can be used to quantify the dynamic pressure and aerodynamic load along the wing surface. AFRL has done a lot of essential work in design, manufacturing, and measurement of AHSs. The work in this paper is to bridge the current AFRL's work on AHSs and their feasible applications in flight dynamics and control (e.g., the gust alleviation) of highly flexible aircraft. A highly flexible vehicle is modeled using a strain-based geometrically nonlinear beam formulation, coupled with finite-state inflow aerodynamics. A feedback control algorithm for the rejection of gust perturbations will be developed. A simplified Linear Quadratic Regulator (LQR) controller will be implemented based on the state-space representation of the linearized system. All AHS measurements will be used as the control input, i.e., wing sectional aerodynamic loads will be defined as the control output for designing the feedback gain. Once the controller is designed, closed-loop aeroelastic simulations will be performed to evaluate the performance of different controllers with the force feedback and be compared to traditional controller designs with the state feedback. From the study, the feasibility of AHSs in flight control will be assessed. The whole study will facilitate in building a fly-by-feel simulation environment for autonomous vehicles.

  8. ICAM-1 Targeted Nanogels Loaded with Dexamethasone Alleviate Pulmonary Inflammation

    PubMed Central

    Coll Ferrer, M. Carme; Shuvaev, Vladimir V.; Zern, Blaine J.; Composto, Russell J.; Muzykantov, Vladimir R.; Eckmann, David M.

    2014-01-01

    Lysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with “stealth” properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab) directed to Intercellular Adhesion Molecule-1(ICAM-NG), whereas IgG conjugated NG (IgG-NG) are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV) injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i) ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG); and, ii) DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation. PMID:25019304

  9. Cathepsin K knockout alleviates aging-induced cardiac dysfunction.

    PubMed

    Hua, Yinan; Robinson, Timothy J; Cao, Yongtao; Shi, Guo-Ping; Ren, Jun; Nair, Sreejayan

    2015-06-01

    Aging is a major risk factor for cardiovascular disease. It has previously been shown that protein levels of cathepsin K, a lysosomal cysteine protease, are elevated in the failing heart and that genetic ablation of cathepsin K protects against pressure overload-induced cardiac hypertrophy and contractile dysfunction. Here we test the hypothesis that cathepsin K knockout alleviates age-dependent decline in cardiac function. Cardiac geometry, contractile function, intracellular Ca(2+) properties, and cardiomyocyte apoptosis were evaluated using echocardiography, fura-2 technique, immunohistochemistry, Western blot and TUNEL staining, respectively. Aged (24-month-old) mice exhibited significant cardiac remodeling (enlarged chamber size, wall thickness, myocyte cross-sectional area, and fibrosis), decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca(2+) release compared to young (6-month-old) mice, which were attenuated in the cathepsin K knockout mice. Cellular markers of senescence, including cardiac lipofuscin, p21 and p16, were lower in the aged-cathepsin K knockout mice compared to their wild-type counterpart. Mechanistically, cathepsin K knockout mice attenuated an age-induced increase in cardiomyocyte apoptosis and nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). In cultured H9c2 cells, doxorubicin stimulated premature senescence and apoptosis. Silencing of cathepsin K blocked the doxorubicin-induced translocation of AIF from the mitochondria to the nuclei. Collectively, these results suggest that cathepsin K knockout attenuates age-related decline in cardiac function via suppressing caspase-dependent and caspase-independent apoptosis.

  10. Coumarin pretreatment alleviates salinity stress in wheat seedlings.

    PubMed

    Saleh, Ahmed Mahmoud; Madany, M M Y

    2015-03-01

    The potentiality of COU to improve plant tolerance to salinity was investigated. Wheat grains were primed with COU (50 ppm) and then grown under different levels of NaCl (50, 100, 150 mM) for two weeks. COU pretreatment improved the growth of wheat seedling under salinity, relative to COU-untreated seedlings, due to the accumulation of osmolytes such as soluble sugars and proline. Moreover, COU treatment significantly improved K(+)/Na(+) ratio in the shoots of both salt stressed and un-stressed seedlings. However, in the roots, this ratio increased only under non-salinity. In consistent with phenylalanine ammonia lyase (PAL), phenolics and flavonoids were accumulated in COU-pretreated seedlings under the higher doses of salinity, relative to COU-untreated seedlings. COU primed seedlings showed higher content of the coumarin derivative, scopoletin, and salicylic, chlorogenic, syringic, vanillic, gallic and ferulic acids, under both salinity and non-salinity conditions. Salinity stress significantly improved the activity of peroxidase (POD) in COU-pretreated seedlings. However, the effect of COU on the total antioxidant capacity (TAC) was only obtained at the highest dose of NaCl (150 mM). The present results suggest that COU pretreatment could alleviate the adverse effect of salinity on the growth of wheat seedlings through enhancing, at least partly, the osmoregulation process and antioxidant defense system.

  11. Rhizospheric bacteria alleviate salt-produced stress in sunflower.

    PubMed

    Shilev, Stefan; Sancho, Enrique D; Benlloch-González, María

    2012-03-01

    The effect of isolate Pseudomonas fluorescens biotype F and P. fluorescens CECT 378(T) inoculation on fresh weight and ions accumulation was studied in sunflower plants grown in sand:peat substrate with addition of 100mM NaCl. The inoculation resulted in an increase in fresh weight of more than 10% in salt treatments and in an accumulation of less Na(+) and more K(+) in plant tissues in all cases. The bacterial inoculants favoured the K(+)/Na(+) ratio in all plant parts and in the case of the isolate CECT 378(T) conducted to 66% increment in leaves, 34% in stems and 16% in roots, while the effect of isolate inoculation was (only) more evident in leaves and stems with 30% and 26%, respectively. Both strains were found to produce indoleacetic acid and siderophores in in-vitro tests, thus the production of indoles was highly dependent on the exogenous tryptophan in the medium. The results suggest that salt stress in sunflower plants was alleviated partially by the inoculation with strains that produce indoles and siderophores, having also a positive effect on the K(+)/Na(+) ratio in the shoot. Moreover, those plants were characterized with better-developed roots. PMID:20685030

  12. Synthesis of individual rotor blade control system for gust alleviation

    NASA Technical Reports Server (NTRS)

    Wang, Ji C.; Chu, Alphonse Y.; Talbot, Peter D.

    1990-01-01

    The utilization of rotor flapping in synthesizing an Individual Blade Control (IBC) system for gust alleviation is demonstrated. The objective is to illustrate and seek to improve Ham's IBC method. A sensor arrangement with two accelerometers mounted on the root and tip of a blade is proposed for estimating of flapping states for feedback control. Equivalent swash plate implementation of IBC is also deliberated. The study concludes by addressing the concept of general rotor states feedback, of which the IBC method is a special case. The blade flapping equation of motion is derived. Ham's original IBC method and a modified IBC scheme called Model Reference (MRIBC) are examined, followed by simulation study with ideal measurements and relative performances of the two methods. The practical aspects of IBC implementation are presented. Different configuration of sensors and their merits are considered. The realization of IBC using equivalent swash plate instead of direct actuator motion is discussed. It is shown that IBC is a particular case of rotor states feedback. The idea of general rotor states feedback is further elaborated. Finally, major conclusions are given.

  13. Visually induced motion sickness can be alleviated by pleasant odors.

    PubMed

    Keshavarz, Behrang; Stelzmann, Daniela; Paillard, Aurore; Hecht, Heiko

    2015-05-01

    Visually induced motion sickness (VIMS) is a common side effect in virtual environments and simulators. Several countermeasures against VIMS exist, but a reliable method to prevent or ease VIMS is unfortunately still missing. In the present study, we tested whether olfactory cues can alleviate VIMS. Sixty-two participants were exposed to a 15-min-long video showing a first-person-view bicycle ride that had successfully induced VIMS in previous studies. Participants were randomly assigned to one of three groups; the first group was exposed to a pleasant odor (rose) while watching the video, the second group was exposed to an unpleasant odor (leather), and the third group was not exposed to any odor. VIMS was measured using a verbal rating scale (0-20) and the Simulator Sickness Questionnaire. Results showed that only half of the participants who were exposed to the odor did notice it (n = 21), whereas the other half failed to detect the odor. However, among those participants who did notice the odor, the rose scent significantly reduced the severity of VIMS compared to the group that did not notice the odor. A moderate positive correlation between odor sensitivity and VIMS showed that participants with higher odor sensitivity also reported stronger VIMS. Our results demonstrate that olfaction can modulate VIMS and that a pleasant odor can potentially reduce VIMS. The relationship between olfactory perception, olfactory sensibility, and VIMS is discussed.

  14. Alleviating bias leads to accurate and personalized recommendation

    NASA Astrophysics Data System (ADS)

    Qiu, Tian; Wang, Tian-Tian; Zhang, Zi-Ke; Zhong, Li-Xin; Chen, Guang

    2013-11-01

    Recommendation bias towards objects has been found to have an impact on personalized recommendation, since objects present heterogeneous characteristics in some network-based recommender systems. In this article, based on a biased heat conduction recommendation algorithm (BHC) which considers the heterogeneity of the target objects, we propose a heterogeneous heat conduction algorithm (HHC), by further taking the heterogeneity of the source objects into account. Tested on three real datasets, the Netflix, RYM and MovieLens, the HHC algorithm is found to present better recommendation in both the accuracy and diversity than two benchmark algorithms, i.e., the original BHC and a hybrid algorithm of heat conduction and mass diffusion (HHM), while not requiring any other accessorial information or parameter. Moreover, the HHC algorithm also elevates the recommendation accuracy on cold objects, referring to the so-called cold-start problem. Eigenvalue analyses show that, the HHC algorithm effectively alleviates the recommendation bias towards objects with different level of popularity, which is beneficial to solving the accuracy-diversity dilemma.

  15. ATF3 deficiency in chondrocytes alleviates osteoarthritis development.

    PubMed

    Iezaki, Takashi; Ozaki, Kakeru; Fukasawa, Kazuya; Inoue, Makoto; Kitajima, Shigetaka; Muneta, Takeshi; Takeda, Shu; Fujita, Hiroyuki; Onishi, Yuki; Horie, Tetsuhiro; Yoneda, Yukio; Takarada, Takeshi; Hinoi, Eiichi

    2016-08-01

    Activating transcription factor 3 (Atf3) has been implicated in the pathogenesis of various diseases, including cancer and inflammation, as well as in the regulation of cell proliferation and differentiation. However, the involvement of Atf3 in developmental skeletogenesis and joint disease has not been well studied to date. Here, we show that Atf3 is a critical mediator of osteoarthritis (OA) development through its expression in chondrocytes. ATF3 expression was markedly up-regulated in the OA cartilage of both mice and humans. Conditional deletion of Atf3 in chondrocytes did not result in skeletal abnormalities or affect the chondrogenesis, but alleviated the development of OA generated by surgically inducing knee joint instability in mice. Inflammatory cytokines significantly up-regulated Atf3 expression through the nuclear factor-kB (NF-kB) pathway, while cytokine-induced interleukin-6 (Il6) expression was repressed, in ATF3-deleted murine and human chondrocytes. Mechanistically, Atf3 deficiency decreased cytokine-induced Il6 transcription in chondrocytes through repressing NF-kB signalling by the attenuation of the phosphorylation status of IkB and p65. These findings suggest that Atf3 is implicated in the pathogenesis of OA through modulation of inflammatory cytokine expression in chondrocytes, and the feed-forward loop of inflammatory cytokines/NF-kB/Atf3 in chondrocytes may be a novel therapeutic target for the treatment for OA. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Ergosterol Alleviates Kidney Injury in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Ang, Li; Yuguang, Liu; Liying, Wang; Shuying, Zhang; Liting, Xu; Shumin, Wang

    2015-01-01

    Ergosterol (ERG) has been widely used in the development of novel drugs due to its unique physiological function. However, little is known about the protective effects of ERG on diabetes. Hence, the current study was designed to evaluate the positive role of ergosterol on streptozotocin- (STZ-) induced diabetes in mice. Oral glucose tolerance test (OGTT) was carried out to assess blood glucose level. Biochemical parameters such as uric acid, creatinine, serum insulin, triglycerides (TG), and total cholesterol (TC) were also measured. Pathological condition of kidney was examined by hematoxylin-eosin (H&E) staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, NF-κBp65, p-NF-κBp65, IκBα, and p-IκBα were analyzed by western blot. ERG significantly reduced the concentrations of blood glucose, uric acid, creatinine, TG, and TC. Serum insulin was elevated with ERG treatment. In addition, renal pathologic changes of diabetes mice were also alleviated by ERG. Obtained data revealed that ERG restored the levels of PI3K/Akt/NF-κB signaling-related proteins in comparison with diabetes mice. Above all, it could be assumed that ERG might play a positive role in regulating STZ-induced diabetes through suppressing PI3K/Akt/NF-κB pathway. PMID:26664454

  17. Electroacupuncture Treatment Alleviates Central Poststroke Pain by Inhibiting Brain Neuronal Apoptosis and Aberrant Astrocyte Activation

    PubMed Central

    Tian, Gui-Hua; Tao, Shan-Shan; Chen, Man-Tang; Li, Yu-Sang; Shang, Hong-Cai; Tang, Xiao-Yi; Chen, Jian-Xin

    2016-01-01

    Electroacupuncture (EA) is reported to effectively relieve the central poststroke pain (CPSP). However, the underlying mechanism remains unclear. The present study investigated the detailed mechanisms of action of EA treatment at different frequencies for CPSP. A CPSP model was established with a single collagenase injection to the left ventral posterolateral nucleus of the thalamus. The EA-treated groups then received EA treatment at frequency of 2, 2/15, or 15 Hz for 30 min daily for five days. The pain-related behavioral responses, neuronal apoptosis, glial activation, and the expression of pain signal transmission-related factors (β-catenin, COX-2, and NK-1R) were assessed using behavioral tests, Nissl staining, TUNEL staining, and immunohistochemical staining, respectively. The low-frequency EA treatment significantly (1) reduced brain tissue damage and hematoma sizes and (2) inhibited neuronal apoptosis, thereby exerting abirritative effects. Meanwhile, the high-frequency EA treatment induced a greater inhibition of the aberrant astrocyte activation, accompanied by the downregulation of the expressions of COX-2, β-catenin, and subsequently NK-1R, thereby alleviating inflammation and producing strong analgesic effects. Together, these findings suggest that CPSP is closely related to pathological changes of the neocortex and hippocampus. EA treatments at different frequencies may exert abirritative effects by inhibiting brain neuronal apoptosis and aberrant astrocyte activation in the brain. PMID:27774321

  18. Tanshinone IIA Alleviates the AD Phenotypes in APP and PS1 Transgenic Mice

    PubMed Central

    Li, Fengling; Han, Guosheng; Wu, Kexiang

    2016-01-01

    Therapeutic approach for Alzheimer's disease (AD) is still deficient. To find active compounds from herbal medicine is of interest in the alleviation of AD symptoms. This study aimed to investigate the protective effects of Tanshinone IIA (TIIA) on memory performance and synaptic plasticity in a transgenic AD model at the early phase. 25–100 mg/kg TIIA (intraperitoneal injection, i.p.) was administered to the six-month-old APP and PS1 transgenic mice for 30 consecutive days. After treatment, spatial memory, synaptic plasticity, and related mechanisms were investigated. Our result showed that memory impairment in AD mice was mitigated by 50 and 100 mg/kg TIIA treatments. Hippocampal long-term potentiation was impaired in AD model but rescued by 100 mg/kg TIIA treatment. Mechanically, TIIA treatment reduced the accumulations of beta-amyloid 1–42, C-terminal fragments (CTFs), and p-Tau in the AD model. TIIA did not affect basal BDNF but promoted depolarization-induced BDNF synthesis in the AD mice. Taken together, TIIA repairs hippocampal LTP and memory, likely, through facilitating the clearance of AD-related proteins and activating synaptic BDNF synthesis. TIIA might be a candidate drug for AD treatment. PMID:27274990

  19. Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states.

    PubMed

    Little, Joshua W; Ford, Amanda; Symons-Liguori, Ashley M; Chen, Zhoumou; Janes, Kali; Doyle, Timothy; Xie, Jennifer; Luongo, Livio; Tosh, Dillip K; Maione, Sabatino; Bannister, Kirsty; Dickenson, Anthony H; Vanderah, Todd W; Porreca, Frank; Jacobson, Kenneth A; Salvemini, Daniela

    2015-01-01

    Chronic pain is a global burden that promotes disability and unnecessary suffering. To date, efficacious treatment of chronic pain has not been achieved. Thus, new therapeutic targets are needed. Here, we demonstrate that increasing endogenous adenosine levels through selective adenosine kinase inhibition produces powerful analgesic effects in rodent models of experimental neuropathic pain through the A3 adenosine receptor (A3AR, now known as ADORA3) signalling pathway. Similar results were obtained by the administration of a novel and highly selective A3AR agonist. These effects were prevented by blockade of spinal and supraspinal A3AR, lost in A3AR knock-out mice, and independent of opioid and endocannabinoid mechanisms. A3AR activation also relieved non-evoked spontaneous pain behaviours without promoting analgesic tolerance or inherent reward. Further examination revealed that A3AR activation reduced spinal cord pain processing by decreasing the excitability of spinal wide dynamic range neurons and producing supraspinal inhibition of spinal nociception through activation of serotonergic and noradrenergic bulbospinal circuits. Critically, engaging the A3AR mechanism did not alter nociceptive thresholds in non-neuropathy animals and therefore produced selective alleviation of persistent neuropathic pain states. These studies reveal A3AR activation by adenosine as an endogenous anti-nociceptive pathway and support the development of A3AR agonists as novel therapeutics to treat chronic pain. PMID:25414036

  20. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis.

    PubMed

    Cui, Ruibing; Yan, Lihui; Luo, Zheng; Guo, Xiaolan; Yan, Ming

    2015-08-15

    Extracellular Ca(2+) influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca(2+) entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague-Dawley rats. Our data demonstrated that ethanol (0-400mM) dose-dependently increased hepatocyte injury and 100mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca(2+) overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases.

  1. Hydrogen sulfide modulates cadmium-induced physiological and biochemical responses to alleviate cadmium toxicity in rice.

    PubMed

    Mostofa, Mohammad Golam; Rahman, Anisur; Ansary, Md Mesbah Uddin; Watanabe, Ayaka; Fujita, Masayuki; Tran, Lam-Son Phan

    2015-09-11

    We investigated the physiological and biochemical mechanisms by which H2S mitigates the cadmium stress in rice. Results revealed that cadmium exposure resulted in growth inhibition and biomass reduction, which is correlated with the increased uptake of cadmium and depletion of the photosynthetic pigments, leaf water contents, essential minerals, water-soluble proteins, and enzymatic and non-enzymatic antioxidants. Excessive cadmium also potentiated its toxicity by inducing oxidative stress, as evidenced by increased levels of superoxide, hydrogen peroxide, methylglyoxal and malondialdehyde. However, elevating endogenous H2S level improved physiological and biochemical attributes, which was clearly observed in the growth and phenotypes of H2S-treated rice plants under cadmium stress. H2S reduced cadmium-induced oxidative stress, particularly by enhancing redox status and the activities of reactive oxygen species and methylglyoxal detoxifying enzymes. Notably, H2S maintained cadmium and mineral homeostases in roots and leaves of cadmium-stressed plants. By contrast, adding H2S-scavenger hypotaurine abolished the beneficial effect of H2S, further strengthening the clear role of H2S in alleviating cadmium toxicity in rice. Collectively, our findings provide an insight into H2S-induced protective mechanisms of rice exposed to cadmium stress, thus proposing H2S as a potential candidate for managing toxicity of cadmium, and perhaps other heavy metals, in rice and other crops.

  2. Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice.

    PubMed

    Zhou, Xiaoyan; Zhang, Fang; Hu, Xiaotong; Chen, Jing; Wen, Xiangru; Sun, Ying; Liu, Yonghai; Tang, Renxian; Zheng, Kuiyang; Song, Yuanjian

    2015-11-01

    Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-κB) p65 and the expression of tumor necrosis factor-α (TNF-α) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-κB nuclear translocation and downregulate TNF-α expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-κB and down-regulating TNF-α. PMID:26272354

  3. Hydrogen sulfide modulates cadmium-induced physiological and biochemical responses to alleviate cadmium toxicity in rice

    PubMed Central

    Mostofa, Mohammad Golam; Rahman, Anisur; Ansary, Md. Mesbah Uddin; Watanabe, Ayaka; Fujita, Masayuki; Phan Tran, Lam-Son

    2015-01-01

    We investigated the physiological and biochemical mechanisms by which H2S mitigates the cadmium stress in rice. Results revealed that cadmium exposure resulted in growth inhibition and biomass reduction, which is correlated with the increased uptake of cadmium and depletion of the photosynthetic pigments, leaf water contents, essential minerals, water-soluble proteins, and enzymatic and non-enzymatic antioxidants. Excessive cadmium also potentiated its toxicity by inducing oxidative stress, as evidenced by increased levels of superoxide, hydrogen peroxide, methylglyoxal and malondialdehyde. However, elevating endogenous H2S level improved physiological and biochemical attributes, which was clearly observed in the growth and phenotypes of H2S-treated rice plants under cadmium stress. H2S reduced cadmium-induced oxidative stress, particularly by enhancing redox status and the activities of reactive oxygen species and methylglyoxal detoxifying enzymes. Notably, H2S maintained cadmium and mineral homeostases in roots and leaves of cadmium-stressed plants. By contrast, adding H2S-scavenger hypotaurine abolished the beneficial effect of H2S, further strengthening the clear role of H2S in alleviating cadmium toxicity in rice. Collectively, our findings provide an insight into H2S-induced protective mechanisms of rice exposed to cadmium stress, thus proposing H2S as a potential candidate for managing toxicity of cadmium, and perhaps other heavy metals, in rice and other crops. PMID:26361343

  4. Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate.

    PubMed

    Li, Ping; Luo, Shike; Pan, Chunji; Cheng, Xiaoshu

    2015-12-01

    Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)‑induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator‑activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO‑induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO‑induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

  5. Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet.

    PubMed

    Pan, Qing-Rong; Ren, Yan-Long; Zhu, Jia-Jia; Hu, Yan-Jin; Zheng, Jin-Su; Fan, Hui; Xu, Yuan; Wang, Guang; Liu, Wen-Xian

    2014-07-14

    Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

  6. Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate

    PubMed Central

    LI, PING; LUO, SHIKE; PAN, CHUNJI; CHENG, XIAOSHU

    2015-01-01

    Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)-induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator-activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO-induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO-induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

  7. Stratification Requirements for Seed Dormancy Alleviation in a Wetland Weed

    PubMed Central

    Boddy, Louis G.; Bradford, Kent J.; Fischer, Albert J.

    2013-01-01

    Echinochloaoryzicola(syn.E. phyllopogon) is an exotic weed of California rice paddies that has evolved resistance to multiple herbicides. Elimination of seedlingsthroughcertain weed control methods can limit the spread of this weed, but is contingent on accurate predictions of germination and emergence timing, which are influenced by seed dormancy levels.In summer annuals, dormancy can often be relieved through stratification, a period of prolonged exposure to cold and moist conditions.We used population-based threshold models to quantify the effects of stratification on seed germination of four E. Oryzicola populations at a range of water potential (Ψ) and oxygen levels. We also determined how stratification temperatures, moisture levels and durations contributed to dormancy release. Stratification released dormancy by decreasing base Ψ and hydrotimerequired for germination and by eliminating any germination sensitivity to oxygen. Stratification also increased average germination rates (GR), which were used as a proxy for relative dormancy levels. Alternating temperatures nearly doubled GR in all populations, indicating that seeds could be partially dormant despite achieving high final germination percentages. Stratification at Ψ = 0 MPa increased GR compared to stratification at lower water potentials, demonstrating that Ψ contributed to regulating dormancy release. Maximum GR occurred after 2-4 weeks of stratification at 0 MPa; GR were often more rapid for herbicide-resistant than for herbicide-susceptible seeds, implying greater dormancy in the latter. Manipulation of field conditions to promote dormancy alleviation of E. oryzicola seeds might improve the rate and uniformity of germination for seed bank depletion through seedling weed control. Our results suggest field soil saturation in winter would contribute towards E. oryzicola dormancy release and decrease the time to seedling emergence. PMID:24039714

  8. Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants.

    PubMed

    Baack, Michelle L; Puumala, Susan E; Messier, Stephen E; Pritchett, Deborah K; Harris, William S

    2016-04-01

    Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n = 31) or placebo supplemented (n = 29) preterm infants. Term peers (n = 30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p < 0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33 to 4.09 wt% or 2.88 to 3.55 mol%, p < 0.0001) while placebo-supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35 to 3.32 wt% or 2.91 to 2.87 mol%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97 wt% or 4.31 mol%) at discharge (p = 0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants. PMID:26846324

  9. Zinc supplementation alleviates heat stress in laying Japanese quail.

    PubMed

    Sahin, Kazim; Kucuk, Omer

    2003-09-01

    The study was conducted to determine whether zinc supplementation could alleviate the detrimental effects of high ambient temperature (34 degrees C) on egg production, digestibility of nutrients and antioxidant status in laying Japanese quail. Quail (n = 180; 52 d old) were divided into six groups (n = 30/group) and were fed a basal diet or the basal diet supplemented with 30 or 60 mg of zinc (ZnSO(4). H(2)O)/kg diet. Birds were kept at 22 degrees C and 58% relative humidity (RH). At 13 wk of age, the thermoneutral (TN) groups remained at the same temperature, whereas the heat-stress (HS) groups were kept in an environmentally controlled room at 34 degrees C and 42% RH for 3 wk. Heat exposure decreased egg production in birds fed the basal diet (P = 0.001). Linear increases in feed intake (P = 0.01) and egg production (P = 0.004) and improved feed efficiency (P = 0.01) and egg quality variables (P 0.05). Results of the present study suggest that supplementation with 60 mg zinc/kg diet protects quail by reducing the negative effects of heat stress.

  10. Predicting ice accretion and alleviating galloping on overhead power lines

    NASA Astrophysics Data System (ADS)

    Lu, Mingliang

    2002-04-01

    Both the static and dynamic effects of an ice storm on an overhead power line are investigated fairly comprehensively in this thesis. To determine the static, extreme ice load as well as the combined ice and wind load, a systematic procedure is established based on extensive freezing rain experiments and a Monte Carlo simulation. On the other hand, a dynamic effect---galloping---is examined quite extensively with the objective of better understanding its behavior. A novel add-on device---the hybrid nutation damper (HND)---is proposed to control galloping. Its effectiveness is assessed numerically by using a modified, 3DOF based, galloping software. The present investigations lead to the following findings. (i) Goodwin's simple theoretical model surprisingly predicts, quite accurately, the temporally changing weight of not only a dry ice growth but also a wet ice growth for a fixed, unheated conductor sample. (ii) The maximum ice loading may vary significantly over a power line's planned lifetime because of the randomness of an ice storm and its characteristics as well as the uncertainty involved in identifying the extreme probability distribution of the ice loading. Consequently, backup protection is presently essential for a power line in an ice prone area. (iii) A conductor's torsional flexibility does not appear to affect the growth of the accreted ice weight but it modifies the ice shape significantly. (iv) Three representative ice shapes (a crescent, D-like and icicle pendant) can initiate galloping so that galloping may occur in any icing condition. (v) A noticeable swingback or twist appears to develop only when their respective natural frequencies coincide with the plunge's natural frequency. (vi) A hydraulic jump is the major source of energy dissipation in a nutation damper. A properly induced rotation can significantly enhance a nutation damper's performance. (vii) A hybrid nutation damper has been demonstrated to be a promising means of alleviating

  11. Finite element code-based modeling of a multi-feature isolation system and passive alleviation of possible inner pounding

    NASA Astrophysics Data System (ADS)

    Ismail, Mohammed; López-Almansa, Francesc; Benavent-Climent, Amadeo; Pujades-Beneit, Luis G.

    2014-09-01

    The existing seismic isolation systems are based on well-known and accepted physical principles, but they are still having some functional drawbacks. As an attempt of improvement, the Roll-N-Cage (RNC) isolator has been recently proposed. It is designed to achieve a balance in controlling isolator displacement demands and structural accelerations. It provides in a single unit all the necessary functions of vertical rigid support, horizontal flexibility with enhanced stability, resistance to low service loads and minor vibration, and hysteretic energy dissipation characteristics. It is characterized by two unique features that are a self-braking (buffer) and a self-recentering mechanism. This paper presents an advanced representation of the main and unique features of the RNC isolator using an available finite element code called SAP2000. The validity of the obtained SAP2000 model is then checked using experimental, numerical and analytical results. Then, the paper investigates the merits and demerits of activating the built-in buffer mechanism on both structural pounding mitigation and isolation efficiency. The paper addresses the problem of passive alleviation of possible inner pounding within the RNC isolator, which may arise due to the activation of its self-braking mechanism under sever excitations such as near-fault earthquakes. The results show that the obtained finite element code-based model can closely match and accurately predict the overall behavior of the RNC isolator with effectively small errors. Moreover, the inherent buffer mechanism of the RNC isolator could mitigate or even eliminate direct structure-to-structure pounding under severe excitation considering limited septation gaps between adjacent structures. In addition, the increase of inherent hysteretic damping of the RNC isolator can efficiently limit its peak displacement together with the severity of the possibly developed inner pounding and, therefore, alleviate or even eliminate the

  12. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

  13. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

    PubMed

    Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

    2016-02-01

    Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain. PMID:26490459

  14. Melatonin directly interacts with cholesterol and alleviates cholesterol effects in dipalmitoylphosphatidylcholine monolayers.

    PubMed

    Choi, Youngjik; Attwood, Simon J; Hoopes, Matthew I; Drolle, Elizabeth; Karttunen, Mikko; Leonenko, Zoya

    2014-01-01

    Melatonin is a pineal hormone that has been shown to have protective effects in several diseases that are associated with cholesterol dysregulation, including cardiovascular disease, Alzheimer's disease, and certain types of cancers. Cholesterol is a major membrane constituent with both a structural and functional influence. It is also known that melatonin readily partitions into cellular membranes. We investigated the effects of melatonin and cholesterol on the structure and physical properties of a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayer as a simple membrane model using the Langmuir-Blodgett (L-B) monolayer technique and molecular dynamics (MD) simulations. We report that melatonin increases the area per lipid and elastic compressibility of the DPPC monolayer in a concentration dependent manner, while cholesterol has the opposite effect. When both melatonin and cholesterol were present in the monolayer, the compression isotherms showed normalization of the area per molecule towards that of the pure DPPC monolayer, thus indicating that melatonin counteracts and alleviates cholesterol's effects. Atomistic MD simulations of melatonin enriched DPPC systems correlate with our experimental findings and illustrate the structural effects of both cholesterol and melatonin. Our results suggest that melatonin is able to lessen the influence of cholesterol through two different mechanisms. Firstly, we have shown that melatonin has a fluidizing effect on monolayers comprising only lipid molecules. Secondly, we also observe that melatonin interacts directly with cholesterol. Our findings suggest a direct nonspecific interaction of melatonin may be a mechanism involved in reducing cholesterol associated membrane effects, thus suggesting the existence of a new mechanism of melatonin's action. This may have important biological relevance in addition to the well-known anti-oxidative and receptor binding effects. PMID:24651707

  15. Blended Buffet-Load-Alleviation System for Fighter Airplane

    NASA Technical Reports Server (NTRS)

    Moses, Robert W.

    2005-01-01

    The capability of modern fighter airplanes to sustain flight at high angles of attack and/or moderate angles of sideslip often results in immersion of part of such an airplane in unsteady, separated, vortical flow emanating from its forebody or wings. The flows from these surfaces become turbulent and separated during flight under these conditions. These flows contain significant levels of energy over a frequency band coincident with that of low-order structural vibration modes of wings, fins, and control surfaces. The unsteady pressures applied to these lifting surfaces as a result of the turbulent flows are commonly denoted buffet loads, and the resulting vibrations of the affected structures are known as buffeting. Prolonged exposure to buffet loads has resulted in fatigue of structures on several airplanes. Damage to airplanes caused by buffeting has led to redesigns of airplane structures and increased support costs for the United States Air Force and Navy as well as the armed forces of other countries. Time spent inspecting, repairing, and replacing structures adversely affects availability of aircraft for missions. A blend of rudder-control and piezoelectric- actuator engineering concepts was selected as a basis for the design of a vertical-tail buffet-load-alleviation system for the F/A-18 airplane. In this system, the rudder actuator is used to control the response of the first tail vibrational mode (bending at a frequency near 15 Hz), while directional patch piezoelectric actuators are used to control the second tail vibrational mode (tip torsion at a frequency near 45 Hz). This blend of two types of actuator utilizes the most effective features of each. An analytical model of the aeroservoelastic behavior of the airplane equipped with this system was validated by good agreement with measured results from a full-scale ground test, flight-test measurement of buffet response, and an in-flight commanded rudder frequency sweep. The overall performance of the

  16. Mesenchymal stem cells alleviate experimental rheumatoid arthritis through microRNA-regulated IκB expression

    PubMed Central

    Yan, Xin; Cen, Yurong; Wang, Qin

    2016-01-01

    Previous studies have demonstrated that mesenchymal stem cell (MSC) transplantation reduces the severity of collagen-induced arthritis (CIA) in mice, which is a model for rheumatoid arthritis (RA) in humans. However, the underlying molecular mechanisms remain ill-defined. Here, we showed that MSC transplantation reduced the activities of NF-κB signaling and decreased microRNA-548e (miR-548e) levels in the joint tissue in CIA-mice, seemingly through activation of transforming growth factor β receptor signaling. Bioinformatics analyses revealed that miR-548e inhibited protein translation of the NF-κB inhibitor, IκB, through binding to the 3′-UTR of the IκB mRNA. MSCs co-transplanted with adeno-associated virus (AAV) carrying miR-548e abolished the therapeutic effects of MSCs on CIA. On the other hand, transplantation of AAV carrying antisense of miR-548e (as-miR-548e) partially mimicked the effects of MSC transplantation on CIA. Together, these data suggest that MSC transplantation may alleviate experimental RA partially through suppressing miR-548e-mediated IκB inhibition. PMID:27354158

  17. Sustainable operation of submerged Anammox membrane bioreactor with recycling biogas sparging for alleviating membrane fouling.

    PubMed

    Li, Ziyin; Xu, Xindi; Xu, Xiaochen; Yang, FengLin; Zhang, ShuShen

    2015-12-01

    A submerged anaerobic ammonium oxidizing (Anammox) membrane bioreactor with recycling biogas sparging for alleviating membrane fouling has been successfully operated for 100d. Based on the batch tests, a recycling biogas sparging rate at 0.2m(3)h(-1) was fixed as an ultimate value for the sustainable operation. The mixed liquor volatile suspended solid (VSS) of the inoculum for the long operation was around 3000mgL(-1). With recycling biogas sparging rate increasing stepwise from 0 to 0.2m(3)h(-1), the reactor reached an influent total nitrogen (TN) up to 1.7gL(-1), a stable TN removal efficiency of 83% and a maximum specific Anammox activity (SAA) of 0.56kg TNkg(-1) VSSd(-1). With recycling biogas sparging rate at 0.2 m(3) h(-1) (corresponding to an aeration intensity of 118m(3)m(-2)h(-1)), the membrane operation circle could prolong by around 20 times compared to that without gas sparging. Furthermore, mechanism of membrane fouling was proposed. And with recycling biogas sparging, the VSS and EPS content increasing rate in cake layer were far less than the ones without biogas sparging. The TN removal performance and sustainable membrane operation of this system showed the appealing potential of the submerged Anammox MBR with recycling biogas sparging in treating high-strength nitrogen-containing wastewaters.

  18. Distinct physiological responses of tomato and cucumber plants in silicon-mediated alleviation of cadmium stress

    PubMed Central

    Wu, Jiawen; Guo, Jia; Hu, Yanhong; Gong, Haijun

    2015-01-01

    The alleviative effects of silicon (Si) on cadmium (Cd) toxicity were investigated in cucumber (Cucumis sativus L.) and tomato (Solanum lycopersicum L.) grown hydroponically. The growth of both plant species was inhibited by 100 μM Cd, but Si application counteracted the adverse effects on growth. Si application significantly decreased the Cd concentrations in shoots of both species and roots of cucumber. The root-to-shoot transport of Cd was depressed by added Si in tomato whereas it was increased by added Si in cucumber. The total content of organic acids was decreased in tomato leaves but increased in cucumber roots and leaves by Si application under Cd stress. Si application also increased the cell wall polysaccharide levels in the roots of both species under Cd toxicity. Si-mediated changes in levels of organic acids and cell wall polysaccharides might contribute to the differences in Cd transport in the two species. In addition, Si application also mitigated Cd-induced oxidative damage in both species. The results indicate that there were different mechanisms for Si-mediated decrease in shoot Cd accumulation: in tomato, Si supply decreased root-to-shoot Cd transport; whereas in cucumber, Si supply reduced the Cd uptake by roots. It is suggested that Si-mediated Cd tolerance is associated with different physiological responses in tomato and cucumber plants. PMID:26136764

  19. Polyhydroxyfullerene binds cadmium ions and alleviates metal-induced oxidative stress in Saccharomyces cerevisiae.

    PubMed

    Pradhan, Arunava; Pinheiro, José Paulo; Seena, Sahadevan; Pascoal, Cláudia; Cássio, Fernanda

    2014-09-01

    The water-soluble polyhydroxyfullerene (PHF) is a functionalized carbon nanomaterial with several industrial and commercial applications. There have been controversial reports on the toxicity and/or antioxidant properties of fullerenes and their derivatives. Conversely, metals have been recognized as toxic mainly due to their ability to induce oxidative stress in living organisms. We investigated the interactive effects of PHF and cadmium ions (Cd) on the model yeast Saccharomyces cerevisiae by exposing cells to Cd (≤5 mg liter(-1)) in the absence or presence of PHF (≤500 mg liter(-1)) at different pHs (5.8 to 6.8). In the absence of Cd, PHF stimulated yeast growth up to 10.4%. Cd inhibited growth up to 79.7%, induced intracellular accumulation of reactive oxygen species (ROS), and promoted plasma membrane disruption in a dose- and pH-dependent manner. The negative effects of Cd on growth were attenuated by the presence of PHF, and maximum growth recovery (53.8%) was obtained at the highest PHF concentration and pH. The coexposure to Cd and PHF decreased ROS accumulation up to 36.7% and membrane disruption up to 30.7% in a dose- and pH-dependent manner. Two mechanisms helped to explain the role of PHF in alleviating Cd toxicity to yeasts: PHF decreased Cd-induced oxidative stress and bound significant amounts of Cd in the extracellular medium, reducing its bioavailability to the cells.

  20. TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration.

    PubMed

    Ma, Li; Zhang, Hui; Liu, Na; Wang, Pei-qi; Guo, Wen-zhi; Fu, Qiang; Jiao, Lin-bo; Ma, Ya-qun; Mi, Wei-Dong

    2016-03-01

    Translocator protein 18 kDa (TSPO) is now an attractive drug target for controlling neuroinflammation. Studies applying TSPO ligands to neurodegenerative diseases, especially Alzheimer's disease (AD), were rare. Our study was aimed to evaluate the effect of PK11195, a specific TSPO ligand, in an animal model of neuroinflammation caused by systemic LPS administration. C57/BL6 mice were treated with lipopolysaccharide (LPS, 500 μg/kg, i.p.) three days after PK11195 administration (3mg/kg, i.p.). The drugs were not discontinued until the mice were sacrificed. Cognitive function was assessed by Morris water maze (MWM) seven days after LPS injection. Chronic LPS-injection in mice was characterized by cognitive dysfunction, increased expression of cyclooxygenase (COX)-2 and TSPO, elevated Aβ content with increased expression of β-site APP cleaving enzyme-1 (BACE-1) and insulin-degrading enzyme (IDE) as well as decreased brain progesterone and brain-derived neurophic factor (BDNF) level. PK11195 pretreatment protected cognitive function in LPS-injected animals and normalized the inflammatory proteins. Moreover, PK11195 pre-administration decreased elevated hippocampal Aβx-42 levels and increased brain levels of progesterone, allopregnanolone. However, LPS-induced BDNF decrease was not reversed by PK11195 administration. Our data demonstrated that PK11195 could protect cognitive deficits induced by chronic LPS administration. The underling mechanism may involve alleviated neuroinflammation, increased synthesis of neurosteroid and decreased Aβ accumulation accompanied by down-regulation of BACE-1.

  1. Essential structural elements in tRNAPro for EF-P-mediated alleviation of translation stalling

    PubMed Central

    Katoh, Takayuki; Wohlgemuth, Ingo; Nagano, Masanobu; Rodnina, Marina V.; Suga, Hiroaki

    2016-01-01

    The ribosome stalls on translation of polyproline sequences due to inefficient peptide bond formation between consecutive prolines. The translation factor EF-P is able to alleviate this stalling by accelerating Pro-Pro formation. However, the mechanism by which EF-P recognizes the stalled complexes and accelerates peptide bond formation is not known. Here, we use genetic code reprogramming through a flexible in-vitro translation (FIT) system to investigate how mutations in tRNAPro affect EF-P function. We show that the 9-nt D-loop closed by the stable D-stem sequence in tRNAPro is a crucial recognition determinant for EF-P. Such D-arm structures are shared only among the tRNAPro isoacceptors and tRNAfMet in Escherichia coli, and the D-arm of tRNAfMet is essential for EF-P-induced acceleration of fMet–puromycin formation. Thus, the activity of EF-P is controlled by recognition elements in the tRNA D-arm. PMID:27216360

  2. Polyhydroxyfullerene Binds Cadmium Ions and Alleviates Metal-Induced Oxidative Stress in Saccharomyces cerevisiae

    PubMed Central

    Pradhan, Arunava; Pinheiro, José Paulo; Seena, Sahadevan; Pascoal, Cláudia

    2014-01-01

    The water-soluble polyhydroxyfullerene (PHF) is a functionalized carbon nanomaterial with several industrial and commercial applications. There have been controversial reports on the toxicity and/or antioxidant properties of fullerenes and their derivatives. Conversely, metals have been recognized as toxic mainly due to their ability to induce oxidative stress in living organisms. We investigated the interactive effects of PHF and cadmium ions (Cd) on the model yeast Saccharomyces cerevisiae by exposing cells to Cd (≤5 mg liter−1) in the absence or presence of PHF (≤500 mg liter−1) at different pHs (5.8 to 6.8). In the absence of Cd, PHF stimulated yeast growth up to 10.4%. Cd inhibited growth up to 79.7%, induced intracellular accumulation of reactive oxygen species (ROS), and promoted plasma membrane disruption in a dose- and pH-dependent manner. The negative effects of Cd on growth were attenuated by the presence of PHF, and maximum growth recovery (53.8%) was obtained at the highest PHF concentration and pH. The coexposure to Cd and PHF decreased ROS accumulation up to 36.7% and membrane disruption up to 30.7% in a dose- and pH-dependent manner. Two mechanisms helped to explain the role of PHF in alleviating Cd toxicity to yeasts: PHF decreased Cd-induced oxidative stress and bound significant amounts of Cd in the extracellular medium, reducing its bioavailability to the cells. PMID:25038095

  3. Atg4b-Dependent Autophagic Flux Alleviates Huntington’s Disease Progression

    PubMed Central

    Proenca, Catia C.; Stoehr, Natacha; Bernhard, Mario; Seger, Shanon; Genoud, Christel; Roscic, Ana; Paganetti, Paolo; Liu, Shanming; Murphy, Leon O.; Kuhn, Rainer; Bouwmeester, Tewis; Galimberti, Ivan

    2013-01-01

    The accumulation of aggregated mutant huntingtin (mHtt) inclusion bodies is involved in Huntigton’s disease (HD) progression. Medium sized-spiny neurons (MSNs) in the corpus striatum are highly vulnerable to mHtt aggregate accumulation and degeneration, but the mechanisms and pathways involved remain elusive. Here we have developed a new model to study MSNs degeneration in the context of HD. We produced organotypic cortico-striatal slice cultures (CStS) from HD transgenic mice mimicking specific features of HD progression. We then show that induction of autophagy using catalytic inhibitors of mTOR prevents MSNs degeneration in HD CStS. Furthermore, disrupting autophagic flux by overexpressing Atg4b in neurons and slice cultures, accelerated mHtt aggregation and neuronal death, suggesting that Atg4b-dependent autophagic flux influences HD progression. Under these circumstances induction of autophagy using catalytic inhibitors of mTOR was inefficient and did not affect mHtt aggregate accumulation and toxicity, indicating that mTOR inhibition alleviates HD progression by inducing Atg4b-dependent autophagic flux. These results establish modulators of Atg4b-dependent autophagic flux as new potential targets in the treatment of HD. PMID:23861892

  4. Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF.

    PubMed

    Pun, San; Santos, Alexandre Ferrão; Saxena, Smita; Xu, Lan; Caroni, Pico

    2006-03-01

    Neurodegenerative diseases can have long preclinical phases and insidious progression patterns, but the mechanisms of disease progression are poorly understood. Because quantitative accounts of neuronal circuitry affected by disease have been lacking, it has remained unclear whether disease progression reflects processes of stochastic loss or temporally defined selective vulnerabilities of distinct synapses or axons. Here we derive a quantitative topographic map of muscle innervation in the hindlimb. We show that in two mouse models of motoneuron disease (G93A SOD1 and G85R SOD1), axons of fast-fatiguable motoneurons are affected synchronously, long before symptoms appear. Fast-fatigue-resistant motoneuron axons are affected at symptom-onset, whereas axons of slow motoneurons are resistant. Axonal vulnerability leads to synaptic vesicle stalling and accumulation of BC12a1-a, an anti-apoptotic protein. It is alleviated by ciliary neurotrophic factor and triggers proteasome-dependent pruning of peripheral axon branches. Thus, motoneuron disease involves predictable, selective vulnerability patterns by physiological subtypes of axons, episodes of abrupt pruning in the target region and compensation by resistant axons.

  5. Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid

    PubMed Central

    Zhu, He; Long, Min-Hui; Wu, Jie; Wang, Meng-Meng; Li, Xiu-Yang; Shen, Hong; Xu, Jin-Di; Zhou, Li; Fang, Zhi-Jun; Luo, Yi; Li, Song-Lin

    2015-01-01

    Cyclophosphamide (CP), a chemotherapeutic agent, is restricted due to its side effects, especially hepatotoxicity. Ginseng has often been clinically used with CP in China, but whether and how ginseng reduces the hepatotoxicity is unknown. In this study, the hepatoprotective effects and mechanisms under the combined usage were investigated. It was found that ginseng could ameliorate CP-induced elevations of ALP, ALT, ALS, MDA and hepatic deterioration, enhance antioxidant enzymes’ activities and GSH’s level. Metabolomics study revealed that 33 endogenous metabolites were changed by CP, 19 of which were reversed when ginseng was co-administrated via two main pathways, i.e., GSH metabolism and primary bile acids synthesis. Furthermore, ginseng could induce expression of GCLC, GCLM, GS and GST, which associate with the disposition of GSH, and expression of FXR, CYP7A1, NTCP and MRP 3, which play important roles in the synthesis and transport of bile acids. In addition, NRF 2, one of regulatory elements on the expression of GCLC, GCLM, GS, GST, NTCP and MRP3, was up-regulated when ginseng was co-administrated. In conclusion, ginseng could alleviate CP-induced hepatotoxicity via modulating the disordered homeostasis of GSH and bile acid, which might be mediated by inducing the expression of NRF 2 in liver. PMID:26625948

  6. Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

    PubMed

    Lee, Kyoo-A; Song, You Chan; Kim, Ga-Young; Choi, Gyeyoung; Lee, Yoon-Sook; Lee, Jung-Mi; Kang, Chang-Yuil

    2012-07-01

    Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

  7. Nitrogen availability regulates proline and ethylene production and alleviates salinity stress in mustard (Brassica juncea).

    PubMed

    Iqbal, Noushina; Umar, Shahid; Khan, Nafees A

    2015-04-15

    Proline content and ethylene production have been shown to be involved in salt tolerance mechanisms in plants. To assess the role of nitrogen (N) in the protection of photosynthesis under salt stress, the effect of N (0, 5, 10, 20 mM) on proline and ethylene was studied in mustard (Brassica juncea). Sufficient N (10 mM) optimized proline production under non-saline conditions through an increase in proline-metabolizing enzymes, leading to osmotic balance and protection of photosynthesis through optimal ethylene production. Excess N (20 mM), in the absence of salt stress, inhibited photosynthesis and caused higher ethylene evolution but lower proline production compared to sufficient N. In contrast, under salt stress with an increased demand for N, excess N optimized ethylene production, which regulates the proline content resulting in recovered photosynthesis. The effect of excess N on photosynthesis under salt stress was further substantiated by the application of the ethylene biosynthesis inhibitor, 1-aminoethoxy vinylglycine (AVG), which inhibited proline production and photosynthesis. Without salt stress, AVG promoted photosynthesis in plants receiving excess N by inhibiting stress ethylene production. The results suggest that a regulatory interaction exists between ethylene, proline and N for salt tolerance. Nitrogen differentially regulates proline production and ethylene formation to alleviate the adverse effect of salinity on photosynthesis in mustard.

  8. Model Predictive Wind Turbine Control with Move-Blocking Strategy for Load Alleviation and Power Leveling

    NASA Astrophysics Data System (ADS)

    Jassmann, U.; Dickler, S.; Zierath, J.; Hakenberg, M.; Abel, D.

    2016-09-01

    This contribution presents a Model Predictive Controller (MPC) with moveblocking strategy for combined power leveling and load alleviation in wind turbine operation with a focus on extreme loads. The controller is designed for a 3 MW wind turbine developed by W2E Wind to Energy GmbH and compared to a baseline controller, using a classic control scheme, which currently operates the wind turbine. All simulations are carried out with a detailed multibody simulation turbine model implemented in alaska/Wind. The performance of the two different controllers is compared using a 50-year Extreme Operation Gust event, since it is one of the main design drivers for the wind turbine considered in this work. The implemented MPC is able to level electrical output power and reduce mechanical loads at the same time. Without de-rating the achieved control results, a move-blocking strategy is utilized and allowed to reduce the computational burden of the MPC by more than 50% compared to a baseline MPC implementation. This even allows to run the MPC on a state of the art Programmable Logic Controller.

  9. Mesenchymal stem cells alleviate experimental rheumatoid arthritis through microRNA-regulated IκB expression.

    PubMed

    Yan, Xin; Cen, Yurong; Wang, Qin

    2016-01-01

    Previous studies have demonstrated that mesenchymal stem cell (MSC) transplantation reduces the severity of collagen-induced arthritis (CIA) in mice, which is a model for rheumatoid arthritis (RA) in humans. However, the underlying molecular mechanisms remain ill-defined. Here, we showed that MSC transplantation reduced the activities of NF-κB signaling and decreased microRNA-548e (miR-548e) levels in the joint tissue in CIA-mice, seemingly through activation of transforming growth factor β receptor signaling. Bioinformatics analyses revealed that miR-548e inhibited protein translation of the NF-κB inhibitor, IκB, through binding to the 3'-UTR of the IκB mRNA. MSCs co-transplanted with adeno-associated virus (AAV) carrying miR-548e abolished the therapeutic effects of MSCs on CIA. On the other hand, transplantation of AAV carrying antisense of miR-548e (as-miR-548e) partially mimicked the effects of MSC transplantation on CIA. Together, these data suggest that MSC transplantation may alleviate experimental RA partially through suppressing miR-548e-mediated IκB inhibition. PMID:27354158

  10. Does supplemental 18:0 alleviate fish oil-induced milk fat depression in dairy ewes?

    PubMed

    Toral, P G; Hervás, G; Carreño, D; Frutos, P

    2016-02-01

    Supplementation of dairy ewe diet with marine lipids may be an effective strategy for modulating milk fatty acid composition but induces milk fat depression (MFD). This syndrome has been associated with a shortage of 18:0 for uptake and Δ(9)-desaturation that may impair the capacity of the mammary gland to achieve an adequate fluidity for milk fat secretion. On this basis, it was suggested that supplemental 18:0 may contribute to alleviate marine lipid-induced MFD in sheep. To test this hypothesis, 12 lactating ewes were allocated to 1 of 3 lots and used in a 3×3 Latin square design with 3 periods of 28 d each and 3 experimental treatments: a total mixed ration without lipid supplementation (control) or supplemented with 20 g/kg of DM of fish oil alone (FO) or in combination with 20 g/kg of DM of 18:0 (FOSA). Diets were offered ad libitum, and animal performance and rumen and milk fatty acid composition were studied at the end of each period. After completing the Latin square trial and following a change-over design, the in vivo digestibility of supplemental 18:0 was estimated using 6 lactating sheep. As expected, diet supplementation with fish oil increased the milk content of some potentially health-promoting fatty acids (e.g., cis-9,trans-11 18:2, trans-11 18:1, 20:5n-3, 22:5n-3, and 22:6n-3), but reduced milk fat concentration and yield (-20% in both FO and FOSA treatments). Thus, although reductions in milk 18:0 and cis-9 18:1 output caused by FO (-81 and -51%, respectively) were partially reversed with FOSA diet (-49 and -27%, respectively), the addition of 18:0 to the diet did not prove useful to alleviate MFD. This response, which could not be fully accounted for by the low digestibility coefficient of supplemental 18:0, may challenge the theory of a shortage of this fatty acid as a mechanism to explain fish oil-induced MFD in sheep. Effects of FO and FOSA on rumen and milk fatty acid composition would support that increases in the concentration of some

  11. Does supplemental 18:0 alleviate fish oil-induced milk fat depression in dairy ewes?

    PubMed

    Toral, P G; Hervás, G; Carreño, D; Frutos, P

    2016-02-01

    Supplementation of dairy ewe diet with marine lipids may be an effective strategy for modulating milk fatty acid composition but induces milk fat depression (MFD). This syndrome has been associated with a shortage of 18:0 for uptake and Δ(9)-desaturation that may impair the capacity of the mammary gland to achieve an adequate fluidity for milk fat secretion. On this basis, it was suggested that supplemental 18:0 may contribute to alleviate marine lipid-induced MFD in sheep. To test this hypothesis, 12 lactating ewes were allocated to 1 of 3 lots and used in a 3×3 Latin square design with 3 periods of 28 d each and 3 experimental treatments: a total mixed ration without lipid supplementation (control) or supplemented with 20 g/kg of DM of fish oil alone (FO) or in combination with 20 g/kg of DM of 18:0 (FOSA). Diets were offered ad libitum, and animal performance and rumen and milk fatty acid composition were studied at the end of each period. After completing the Latin square trial and following a change-over design, the in vivo digestibility of supplemental 18:0 was estimated using 6 lactating sheep. As expected, diet supplementation with fish oil increased the milk content of some potentially health-promoting fatty acids (e.g., cis-9,trans-11 18:2, trans-11 18:1, 20:5n-3, 22:5n-3, and 22:6n-3), but reduced milk fat concentration and yield (-20% in both FO and FOSA treatments). Thus, although reductions in milk 18:0 and cis-9 18:1 output caused by FO (-81 and -51%, respectively) were partially reversed with FOSA diet (-49 and -27%, respectively), the addition of 18:0 to the diet did not prove useful to alleviate MFD. This response, which could not be fully accounted for by the low digestibility coefficient of supplemental 18:0, may challenge the theory of a shortage of this fatty acid as a mechanism to explain fish oil-induced MFD in sheep. Effects of FO and FOSA on rumen and milk fatty acid composition would support that increases in the concentration of some

  12. Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a Mouse Model of Incisional Pain

    PubMed Central

    Reddyjarugu, Balagangadharreddy; Pavek, Todd; Southard, Teresa; Barry, Jason; Singh, Bhupinder

    2015-01-01

    Pain management in laboratory animals is generally accomplished by using opioids and NSAIDs. However, opioid use is hindered by controlled substance requirements and a relatively short duration of action. In this study, we compared the analgesic efficacy of firocoxib (a cyclooxygenase-2-selective NSAID) with that of buprenorphine in the mouse model of plantar incisional pain by objective measurement of mechanical allodynia and thermal hyperalgesia using von Frey and Hargreaves equipment, respectively. Our experimental design included 5 treatment groups: firocoxib at 10 mg/kg IP every 24 h (F10 group); firocoxib at 20 mg/kg IP every 24 h (F20); buprenorphine at 0.2 mg/kg SC every 8 h; intraperitoneal normal saline every 24 h; and sham group (anesthesia, no incision) treated with firocoxib at 20 mg/kg IP every 24 h (sham+F20). All mice underwent nociceptive assays at 24 h before and 4, 24, 48, and 72 h after surgery. Buprenorphine alleviated allodynia at all time points after incision. The F10 treatment alleviated allodynia at 4, 24, and 48 h, whereas F20 alleviated allodynia at 24, 48, and 72 h. None of the treatments alleviated thermal hyperalgesia at 4h. Except for F10 and buprenorphine at 24 h, all treatments alleviated thermal hyperalgesia at 24, 48, and 72 h. No significant differences were noted between the 2 doses of firocoxib and buprenorphine regarding mechanical allodynia and thermal hyperalgesia at all time points. In conclusion, the analgesic efficacy of firocoxib is comparable to that of buprenorphine in this mouse pain model. PMID:26224441

  13. Alleviation of high light-induced photoinhibition in cyanobacteria by artificially conferred biosilica shells.

    PubMed

    Xiong, Wei; Yang, Zhou; Zhai, Hailei; Wang, Guangchuan; Xu, Xurong; Ma, Weimin; Tang, Ruikang

    2013-09-01

    Bioinspired by diatoms, biomimetic silicification confers an artificial shell on cyanobacteria to alleviate photoinhibition; thus, the photosynthesis of the resulting cyanobacteria@SiO2 becomes more efficient under high light conditions.

  14. Peripheral neurobiologic mechanisms of antiallodynic effect of warm water immersion therapy on persistent inflammatory pain.

    PubMed

    Martins, Daniel F; Brito, Rômulo N; Stramosk, Juliana; Batisti, Ana P; Madeira, Fernanda; Turnes, Bruna L; Mazzardo-Martins, Leidiane; Santos, Adair R S; Piovezan, Anna P

    2015-01-01

    Water immersion is widely used in physiotherapy and might relieve pain, probably by activating several distinct somatosensory modalities, including tactile, pressure, and thermal sensations. However, the endogenous mechanisms behind this effect remain poorly understood. This study examined whether warm water immersion therapy (WWIT) produces an antiallodynic effect in a model of localized inflammation and whether peripheral opioid, cannabinoid, and adenosine receptors are involved in this effect. Mice were injected with complete Freund's adjuvant (CFA; intraplantar; i.pl.). The withdrawal frequency to mechanical stimuli (von Frey test) was used to determine 1) the effect of WWIT against CFA-induced allodynia and 2) the effect of i.pl. preadministration of naloxone (a nonselective opioid receptor antagonist; 5 µg/paw), caffeine (a nonselective adenosine receptor antagonist; 150 nmol/paw), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A1 receptor antagonist; 10 nmol/paw), and AM630 (a selective cannabinoid receptor type 2 antagonist; 4 µg/paw) on the antiallodynic effect of WWIT against CFA-induced allodynia. Moreover, the influence of WWIT on paw inflammatory edema was measured with a digital micrometer. WWIT produced a significant time-dependent reduction of paw inflammatory allodynia but did not influence paw edema induced by CFA. Naloxone, caffeine, DPCPX, and AM630 injected in the right, but not in the left, hind paw significantly reversed the antiallodynic effect of WWIT. This is the first study to demonstrate the involvement of peripheral receptors in the antiallodynic effect of WWIT in a murine model of persistent inflammatory pain.

  15. Sulfur Mediated Alleviation of Mn Toxicity in Polish Wheat Relates to Regulating Mn Allocation and Improving Antioxidant System

    PubMed Central

    Sheng, Huajin; Zeng, Jian; Liu, Yang; Wang, Xiaolu; Wang, Yi; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong

    2016-01-01

    Sulfur (S) is an essential macronutrient that has been proved to play an important role in regulating plant responses to various biotic and abiotic stresses. The present study was designed to investigate the effect of S status on polish wheat plant response to Mn toxicity. Results showed that Mn stress inhibited plant growth, disturbed photosynthesis and induced oxidative stress. In response to Mn stress, polish wheat plant activated several detoxification mechanisms to counteract Mn toxicity, including enhanced antioxidant defense system, increased Mn distribution in the cell wall and up-regulated genes involved in S assimilation. Moderate S application was found to alleviate Mn toxicity mainly by sequestering excess Mn into vacuoles, inhibiting Mn translocation from roots to shoots, stimulating activities of antioxidant enzymes and enhancing GSH production via up-regulating genes involved in S metabolism. However, application of high level S to Mn-stressed plants did not significantly alleviated Mn toxicity likely due to osmotic stress. In conclusion, moderate S application is beneficial to polish wheat plant against Mn toxicity, S exerts its effects via stimulating the antioxidant defense system and regulating the translocation and subcellular distribution of Mn, in which processes GSH plays an indispensable role.

  16. Sulfur Mediated Alleviation of Mn Toxicity in Polish Wheat Relates to Regulating Mn Allocation and Improving Antioxidant System

    PubMed Central

    Sheng, Huajin; Zeng, Jian; Liu, Yang; Wang, Xiaolu; Wang, Yi; Kang, Houyang; Fan, Xing; Sha, Lina; Zhang, Haiqin; Zhou, Yonghong

    2016-01-01

    Sulfur (S) is an essential macronutrient that has been proved to play an important role in regulating plant responses to various biotic and abiotic stresses. The present study was designed to investigate the effect of S status on polish wheat plant response to Mn toxicity. Results showed that Mn stress inhibited plant growth, disturbed photosynthesis and induced oxidative stress. In response to Mn stress, polish wheat plant activated several detoxification mechanisms to counteract Mn toxicity, including enhanced antioxidant defense system, increased Mn distribution in the cell wall and up-regulated genes involved in S assimilation. Moderate S application was found to alleviate Mn toxicity mainly by sequestering excess Mn into vacuoles, inhibiting Mn translocation from roots to shoots, stimulating activities of antioxidant enzymes and enhancing GSH production via up-regulating genes involved in S metabolism. However, application of high level S to Mn-stressed plants did not significantly alleviated Mn toxicity likely due to osmotic stress. In conclusion, moderate S application is beneficial to polish wheat plant against Mn toxicity, S exerts its effects via stimulating the antioxidant defense system and regulating the translocation and subcellular distribution of Mn, in which processes GSH plays an indispensable role. PMID:27695467

  17. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

    PubMed

    Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

    2015-12-01

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets. PMID:26520392

  18. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

    PubMed

    Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

    2015-12-01

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets.

  19. A comparison of the results of dynamic wind-tunnel tests with theoretical predictions for an aeromechanical gust-alleviation system for light airplanes

    NASA Technical Reports Server (NTRS)

    Stewart, E. C.; Redd, L. T.

    1977-01-01

    Dynamic wind tunnel tests have been conducted on a 1/6-scale model of a general aviation airplane equipped with an all-mechanical gust alleviation system which uses auxiliary aerodynamic surfaces to drive the flaps. The longitudinal short period motions were studied under simulated gust conditions in order to verify the mathematical model used in a previous study to predict the performance of the full scale system and determine the amount of normal acceleration alleviation which could be attained. The model responses were measured for different configurations with the system active and without the system active for comparison. The tests confirmed the general relationships between the experimental variables and the model responses predicted by the mathematical model, but there were significant differences in the magnitudes of the responses. The experimental results for the model were used to estimate a reduction of 30 percent in the rms normal acceleration response of a similar full scale airplane in atmospheric turbulence.

  20. Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis in vivo and in vitro.

    PubMed

    Chen, Zhiguang; Xue, Jinqi; Shen, Tao; Ba, Gen; Yu, Dongdong; Fu, Qin

    2016-02-01

    Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti-inflammation and anti-cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid-induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)-induced osteoporosis in vivo and Dex-induced osteoblast apoptosis in vivo and in vitro. The GIO rat model was induced by subcutaneous injection of Dex for 60 days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X-ray absorptiometry. Subsequently, curcumin administration (100 mg/kg) for 60 days obviously increased BMD and bone-alkaline phosphatase, decreased carboxy-terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex-induced osteoporosis. Mechanically, curcumin remarkably reversed Dex-induced femoral osteoblast apoptosis in vivo. In cultured primary osteoblasts, pretreatment with curcumin concentration-dependently decreased the number of Dex-induced apoptotic osteoblasts by down-regulating the ratio of Bax/Bcl-2 as well as the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex-induced osteoblasts by up-regulating the expression level of p-ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.

  1. Seed treatment with Trichoderma harzianum alleviates biotic, abiotic, and physiological stresses in germinating seeds and seedlings.

    PubMed

    Mastouri, Fatemeh; Björkman, Thomas; Harman, Gary E

    2010-11-01

    Trichoderma spp. are endophytic plant symbionts that are widely used as seed treatments to control diseases and to enhance plant growth and yield. Although some recent work has been published on their abilities to alleviate abiotic stresses, specific knowledge of mechanisms, abilities to control multiple plant stress factors, their effects on seed and seedlings is lacking. We examined the effects of seed treatment with T. harzianum strain T22 on germination of seed exposed to biotic stress (seed and seedling disease caused by Pythium ultimum) and abiotic stresses (osmotic, salinity, chilling, or heat stress). We also evaluated the ability of the beneficial fungus to overcome physiological stress (poor seed quality induced by seed aging). If seed were not under any of the stresses noted above, T22 generally had little effect upon seedling performance. However, under stress, treated seed germinated consistently faster and more uniformly than untreated seeds whether the stress was osmotic, salt, or suboptimal temperatures. The consistent response to varying stresses suggests a common mechanism through which the plant-fungus association enhances tolerance to a wide range of abiotic stresses as well as biotic stress. A common factor that negatively affects plants under these stress conditions is accumulation of toxic reactive oxygen species (ROS), and we tested the hypothesis that T22 reduced damages resulting from accumulation of ROS in stressed plants. Treatment of seeds reduced accumulation of lipid peroxides in seedlings under osmotic stress or in aged seeds. In addition, we showed that the effect of exogenous application of an antioxidant, glutathione, or application of T22, resulted in a similar positive effect on seed germination under osmotic stress or in aged seed. This evidence supports the model that T. harzianum strain T22 increases seedling vigor and ameliorates stress by inducing physiological protection in plants against oxidative damage.

  2. Analgesic Effects of Bee Venom Derived Phospholipase A(2) in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain.

    PubMed

    Li, Dongxing; Lee, Younju; Kim, Woojin; Lee, Kyungjin; Bae, Hyunsu; Kim, Sun Kwang

    2015-06-29

    A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system.

  3. Analgesic Effects of Bee Venom Derived Phospholipase A2 in a Mouse Model of Oxaliplatin-Induced Neuropathic Pain

    PubMed Central

    Li, Dongxing; Lee, Younju; Kim, Woojin; Lee, Kyungjin; Bae, Hyunsu; Kim, Sun Kwang

    2015-01-01

    A single infusion of oxaliplatin, which is widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs that are triggered or aggravated when exposed to cold or mechanical stimuli. Bee Venom (BV) has been traditionally used in Korea to treat various pain symptoms. Our recent study demonstrated that BV alleviates oxaliplatin-induced cold allodynia in rats, via noradrenergic and serotonergic analgesic pathways. In this study, we have further investigated whether BV derived phospholipase A2 (bvPLA2) attenuates oxaliplatin-induced cold and mechanical allodynia in mice and its mechanism. The behavioral signs of cold and mechanical allodynia were evaluated by acetone and a von Frey hair test on the hind paw, respectively. The significant allodynia signs were observed from one day after an oxaliplatin injection (6 mg/kg, i.p.). Daily administration of bvPLA2 (0.2 mg/kg, i.p.) for five consecutive days markedly attenuated cold and mechanical allodynia, which was more potent than the effect of BV (1 mg/kg, i.p.). The depletion of noradrenaline by an injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 50 mg/kg, i.p.) blocked the analgesic effect of bvPLA2, whereas the depletion of serotonin by injecting DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for three successive days did not. Furthermore, idazoxan (α2-adrenegic receptor antagonist, 1 mg/kg, i.p.) completely blocked bvPLA2-induced anti-allodynic action, whereas prazosin (α1-adrenegic antagonist, 10 mg/kg, i.p.) did not. These results suggest that bvPLA2 treatment strongly alleviates oxaliplatin-induced acute cold and mechanical allodynia in mice through the activation of the noradrenergic system, via α2-adrenegic receptors, but not via the serotonergic system. PMID:26131771

  4. Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats.

    PubMed

    Ge, Chen-Xu; Yu, Rong; Xu, Min-Xuan; Li, Pei-Qin; Fan, Chen-Yu; Li, Jian-Mei; Kong, Ling-Dong

    2016-01-01

    Betaine has been proven effective in treating nonalcoholic fatty liver disease (NAFLD) in animal models, however, its molecular mechanisms remain elusive. The aims of this study were to explore the mechanisms mediating the anti-inflammatory and anti-lipogenic actions of betaine in fructose-fed rats. In this study, betaine improved insulin resistance, reduced body weight gain and serum lipid levels, and prevented hepatic lipid accumulation in fructose-fed rats. It up-regulated hepatic expression of liver X receptor-alpha (LXRα) and peroxisome proliferator-activated receptor-alpha (PPARα), with the attenuation of the changes of their target genes, including hepatic carnitine palmitoyl transferase (CPT) 1α, glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1, apolipoprotein B, sterol regulatory element-binding protein 1c and adipocyte differentiation-related protein, involved in fatty acid oxidation and lipid storage in these model rats. Furthermore, betaine alleviated ER stress and inhibited acetyl-CoA carboxylase α, CPT II, stearoyl-CoA desaturase 1 and fatty acid synthase expression involved in fatty acid synthesis in the liver of fructose-fed rats. Betaine suppressed hepatic gluconeogenesis in fructose-fed rats by moderating protein kinase B -forkhead box protein O1 pathway, as well as p38 mitogen-activated protein kinase and mammalian target of rapamycin activity. Moreover, betaine inhibited hepatic nuclear factor kappa B /nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome activation-mediated inflammation in this animal model. These results demonstrated that betaine ameliorated hepatic lipid accumulation, gluconeogenesis, and inflammation through restoring LXRα and PPARα expression and alleviating ER stress in fructose-fed rats. This study provides the potential mechanisms of betaine involved in the treatment of NAFLD.

  5. Pathological mechanism of musculoskeletal manifestations associated with CRPS type II: an animal study.

    PubMed

    Ota, Hideyuki; Arai, Tetsuya; Iwatsuki, Katsuyuki; Urano, Hideki; Kurahashi, Toshikazu; Kato, Shuichi; Yamamoto, Michiro; Hirata, Hitoshi

    2014-10-01

    Patients with complex regional pain syndrome (CRPS) often complain of abnormal sensations beyond the affected body part, but causes of this spread of musculoskeletal manifestations into contiguous areas remain unclear. In addition, immobilization can predispose to the development of CRPS. We examined functional, biochemical, and histological alterations in affected parts, including contiguous zones, using an animal model. Ten-week-old male Wistar rats were assigned to 5 groups: a normal group receiving no treatment, a sham operation group with surgical exploration, an immobilization group with surgical exploration plus internal knee joint immobilization, a surgical neuropathy group prepared by spinal nerve ligation (SNL) of the left L5 nerve root, and a surgical neuropathy+immobilization group with simultaneous SNL and knee joint immobilization. Mechanical allodynia and knee contracture were compared between groups, and tissues were harvested for histological assessments and gene and protein expression analyses. Neither surgical procedures nor immobilization induced detectable mechanical sensitivity. However, the addition of nerve injury resulted in detectable mechanical allodynia, and immobilization not only accelerated hyperalgesia, but also resulted in muscle fibrosis. Nerve growth factor (NGF) and other mediators of neurogenic inflammation were highly expressed not only in denervated muscles, but also in innervated muscles in contiguous areas, suggesting the spread of NGF production beyond the myotome of the injured nerve. Transforming growth factor β was involved in the development of contracture in CRPS. These findings imply that neuroinflammatory components play major roles in the progression and dispersion of both sensory pathologies and pathologies that are exacerbated by immobilization.

  6. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

    SciTech Connect

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2013-11-15

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

  7. Alleviating effects of exogenous NO on tomato seedlings under combined Cu and Cd stress.

    PubMed

    Wang, Yi-Jun; Dong, Yu-Xiu; Wang, Juan; Cui, Xiu-Min

    2016-03-01

    To investigate the effect of NO on the different origin and regulation of oxidative stress of Cu and/or Cd, tomato seedlings were treated with Cu, Cd, or Cu + Cd in a nutrient solution culture system. The main effect of Cu(2+) was a significant reduction in root activity and nitrate reductase (NR) activity, which was similar to that under 50 μM Cd treatment, but promoted Cu accumulation. The supply of Cu under Cd treatment decreased Cd concentration, while not altered Cu concentration by contrast with Cu treatment, which is suggestive of a replacement of Cu(2+) with Cd(2+) and effective decrease in the boiotoxicity of 50 μM Cd(2+) to tomato seedlings. However, NO alleviated the restriction to NR activity significantly and made the biomass of tomato seedlings recover under Cd treatment, and also increased root activity under Cu and Cu + Cd treatment. Exogenous NO markedly reduced the absorption and transportation of Cu but did not obviously change the translocation of Cd to the aboveground parts under Cu + Cd treatment. Both metals induced lipid peroxidation via the decreasing activation of antioxidant enzymes. The antioxidant enzyme system worked differently under Cu, Cd, or Cu + Cd stress. The activities of peroxidase (POD) and catalase (CAT) were higher under single Cd stress than under the control. Meanwhile, Cu + Cd treatment decreased the activities of POD, superoxide dismutase (SOD), and ascorbic acid peroxidase (APX). Exogenous NO increased POD and SOD activities in the leaves and roots, and CAT activity in the roots under combined Cu and Cd stress. These results suggest that a different response and regulation mechanism that involves exogenous NO is present in tomato seedlings under Cu and Cd stress.

  8. Alleviation of myocardial ischaemia after administration of the cardioselective beta adrenoceptor antagonist bevantolol.

    PubMed

    Hartog, J M; Verdouw, P D

    1986-04-01

    A 15 min reduction in blood flow in the left anterior descending coronary artery to 35% of baseline in open chest anaesthetised pigs produced a 25% decrease in cardiac output and a similar fall in maximum left ventricular dP/dt, whereas left ventricular filling pressure increased from 10(1) to 14(1) mmHg. The decrease in perfusion of the myocardial area nourished by the left anterior descending coronary artery was not evenly distributed since the endocardial to epicardial flow ratio decreased from 0.93(0.07) to 0.48(0.06). Regional myocardial wall thickening of the ischaemic segment decreased from 0.36(0.03) to 0.14(0.03), whereas the arterial-coronary venous differences in pH and PCO2 tripled. Subsequently, eight animals received 1.5 mg X kg-1 of the cardioselective beta adrenoceptor antagonist bevantolol, whereas seven other animals were treated with the solvent. In the following 15 min the cardiovascular performance of the solvent treated animals did not change appreciably, although there was a tendency to further deterioration. Bevantolol did not improve transmural myocardial blood flow to the ischaemic zone but caused a redistribution in favour of the endocardial layers since the endocardial to epicardial flow ratio almost returned to baseline. These changes in flow were accompanied by a narrowing of the arterial-coronary venous differences in pH and PCO2, but regional myocardial function did not improve. In another series of experiments, however, bevantolol (1.5 mg X kg-1) decreased the velocity of regional wall thickening of normal myocardium by 22(2)% as a result of its negative inotropic properties. Thus bevantolol appears to alleviate ischaemia, and the increase in diastolic perfusion time (17%) may be one of the major mechanisms.

  9. Poverty-alleviation program participation and salivary cortisol in very low-income children.

    PubMed

    Fernald, Lia C H; Gunnar, Megan R

    2009-06-01

    Correlational studies have shown associations between social class and salivary cortisol suggestive of a causal link between childhood poverty and activity of the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. Using a quasi-experimental design, we evaluated the associations between a family's participation in a large-scale, conditional cash transfer program in Mexico (Oportunidades, formerly Progresa) during the child's early years of life and children's salivary cortisol (baseline and responsivity). We also examined whether maternal depressive symptoms moderated the effect of program participation. Low-income households (income <20th percentile nationally) from rural Mexico were enrolled in a large-scale poverty-alleviation program between 1998 and 1999. A comparison group of households from demographically similar communities was recruited in 2003. Following 3.5 years of participation in the Oportunidades program, three saliva samples were obtained from children aged 2-6 years from intervention and comparison households (n=1197). Maternal depressive symptoms were obtained using the Center for Epidemiologic Studies-Depression Scale (CES-D). Results were that children who had been in the Oportunidades program had lower salivary cortisol levels when compared with those who had not participated in the program, while controlling for a wide range of individual-, household- and community-level variables. Reactivity patterns of salivary cortisol did not differ between intervention and comparison children. Maternal depression moderated the association between Oportunidades program participation and baseline salivary cortisol in children. Specifically, there was a large and significant Oportunidades program effect of lowering cortisol in children of mothers with high depressive symptoms but not in children of mothers with low depressive symptomatology. These findings provide the strongest evidence to date that the economic circumstances of a family

  10. Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

    PubMed

    Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

    2016-09-01

    Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5 In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity. PMID:27342873

  11. Thermal treatment and leaching of biochar alleviates plant growth inhibition from mobile organic compounds

    PubMed Central

    Sackett, Tara E.; Thomas, Sean C.

    2016-01-01

    Recent meta-analyses of plant responses to biochar boast positive average effects of between 10 and 40%. Plant responses, however, vary greatly across systems, and null or negative biochar effects are increasingly reported. The mechanisms responsible for such responses remain unclear. In a glasshouse experiment we tested the effects of three forestry residue wood biochars, applied at five dosages (0, 5, 10, 20, and 50 t/ha) to a temperate forest drystic cambisol as direct surface applications and as complete soil mixes on the herbaceous pioneers Lolium multiflorum and Trifolium repens. Null and negative effects of biochar on growth were found in most cases. One potential cause for null and negative plant responses to biochar is plant exposure to mobile compounds produced during pyrolysis that leach or evolve following additions of biochars to soil. In a second glasshouse experiment we examined the effects of simple leaching and heating techniques to ameliorate potentially phytotoxic effects of volatile and leachable compounds released from biochar. We used Solid Phase Microextraction (SPME)–gas chromatography–mass spectrometry (GC-MS) to qualitatively describe organic compounds in both biochar (through headspace extraction), and in the water leachates (through direct injection). Convection heating and water leaching of biochar prior to application alleviated growth inhibition. Additionally, growth was inhibited when filtrate from water-leached biochar was applied following germination. SPME-GC-MS detected primarily short-chained carboxylic acids and phenolics in both the leachates and solid chars, with relatively high concentrations of several known phytotoxic compounds including acetic acid, butyric acid, 2,4-di-tert-butylphenol and benzoic acid. We speculate that variable plant responses to phytotoxic organic compounds leached from biochars may largely explain negative plant growth responses and also account for strongly species-specific patterns of plant

  12. Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension.

    PubMed

    Bunbupha, Sarawoot; Prachaney, Parichat; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Welbat, Jariya Umka; Pakdeechote, Poungrat

    2015-11-01

    A previous study demonstrated the antihypertensive effect of asiatic acid. The current study investigates the effect of asiatic acid on cardiovascular remodelling and possible mechanisms involved in Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg per day) for 3 weeks in order to induce hypertension. Hypertensive rats were administered asiatic acid (20 mg/kg per day) or vehicle for a further 2 weeks. It was found that hypertensive rats showed high systolic blood pressure, left ventricular (LV) hypertrophy, increases in LV fibrosis, aortic wall thickness and aortic collagen deposition (P < 0.05). Moreover, decreased plasma nitrate and nitrite (NOx) and increased plasma tumor necrosis factor alpha (TNF-α) were observed in hypertensive rats (P < 0.05). This was consistent with downregulation of endothelial nitric oxide synthase (eNOS) expression and upregulation of inducible nitric oxide synthase (iNOS) expression in heart and aortic tissues (P < 0.05). Levels of malondialdehyde (MDA) in plasma, aortic and heart tissues were significantly increased in hypertensive rats (P < 0.05). Asiatic acid markedly reduced blood pressure, alleviated cardiovascular remodelling, and restored plasma NOx and TNF-α as well as eNOS/iNOS expression in heart and aortic tissues (P < 0.05). Additionally, there was a significant reduction of MDA levels in the tissues of treated hypertensive rats. In conclusion, this study demonstrates the therapeutic effects of asiatic acid on blood pressure and cardiovascular remodelling, which is possibly related to the restoration of eNOS/iNOS expression, and the resulting anti-inflammatory and antioxidant activities. PMID:26234646

  13. Interception of Vapor Flow near Soil Surface for Water Conservation and Drought Alleviation

    NASA Astrophysics Data System (ADS)

    Wang, Z.; Wang, Y.; Gao, Z.; Hishida, K.; Zhang, Y.

    2015-12-01

    Liquid and vapor flow of water in soil and the eventual vaporization of all waters near the soil surface are mechanisms controlling the near-surface evaporation. Interception and prevention of the vapor form of flow is critical for soil water conservation and drought alleviation in the arid and semiarid regions. Researches are conducted to quantify the amount of near-surface vapor flow in the semi-arid Loess Plateau of China and the central California of USA. Quantitative leaf water absorption and desorption functions were derived and tested based on laboratory experiments. Results show that plant leaves absorb and release water at different speeds depending on species and varieties. The "ideal" native plants in the dry climates can quickly absorb water and slowly release it. This water-holding capacity of a plant is characterized by the plant's water retention curves. Field studies are conducted to measure the dynamic water movements from the soil surface to ten meters below the surface in an attempt to quantify the maximum depths of water extraction due to different vegetation types and mulching measures at the surface. Results show that condensation is usually formed on soil surface membranes during the daily hours when the temperature gradients are inverted toward the soil surface. The soil temperature becomes stable at 13 Degree Celsius below the 4-meter depth in the Loess Plateau of China thus vapor flow is not likely deriving from deeper layers. However, the liquid flow may move in and out depending on water potential gradients and hydraulic conductivity of the layers. The near-surface vapor flow can be effectively intercepted by various mulching measures including gravel-and-sand cover, plant residue and plastic membranes. New studies are attempted to quantify the role of vapor flow for the survival of giant sequoias in the southern Sierra Nevada Mountains of California.

  14. Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy.

    PubMed

    Nelson, Michael D; Rosenberry, Ryan; Barresi, Rita; Tsimerinov, Evgeny I; Rader, Florian; Tang, Xiu; Mason, O'Neil; Schwartz, Avery; Stabler, Thomas; Shidban, Sarah; Mobaligh, Neigena; Hogan, Shomari; Elashoff, Robert; Allen, Jason D; Victor, Ronald G

    2015-12-01

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. BMD is caused by in-frame mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the sarcolemma. Among these is neuronal nitric oxide synthase mu (nNOSμ), which requires specific spectrin-like repeats (SR16/17) in dystrophin's rod domain and the adaptor protein α-syntrophin for sarcolemmal targeting. When healthy skeletal muscle is exercised, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates α-adrenergic vasoconstriction, thus optimizing perfusion. In the mdx mouse model of dystrophinopathy, this protective mechanism (functional sympatholysis) is defective, resulting in functional muscle ischaemia. Treatment with a NO-donating non-steroidal anti-inflammatory drug (NSAID) alleviates this ischaemia and improves the murine dystrophic phenotype. In the present study, we report that, in 13 men with BMD, sympatholysis is defective mainly in patients whose mutations disrupt sarcolemmal targeting of nNOSμ, with the vasoconstrictor response measured as a decrease in muscle oxygenation (near infrared spectroscopy) to reflex sympathetic activation. Then, in a single-arm, open-label trial in 11 BMD patients and a double-blind, placebo-controlled cross-over trial in six patients, we show that acute treatment with oral sodium nitrate, an inorganic NO donor without a NSIAD moiety, restores sympatholysis and improves post-exercise hyperaemia (Doppler ultrasound). By contrast, sodium nitrate improves neither sympatholysis, nor hyperaemia in healthy controls. Thus, a simple NO donor recapitulates the vasoregulatory actions of sarcolemmal nNOS in BMD patients, and constitutes a putative novel therapy for this disease.

  15. Intestinal parasitic infections amongst Orang Asli (indigenous) in Malaysia: has socioeconomic development alleviated the problem?

    PubMed

    Lim, Y A L; Romano, N; Colin, N; Chow, S C; Smith, H V

    2009-08-01

    ensure the whole mechanism of delivery and empowerment by the government agencies become more efficient and productive in alleviating intestinal parasitic infections in these communities.

  16. Sodium nitroprusside-mediated alleviation of iron deficiency and modulation of antioxidant responses in maize plants

    PubMed Central

    Kumar, Praveen; Tewari, Rajesh Kumar; Sharma, Parma Nand

    2010-01-01

    Background and aims Nitric oxide (NO) has been reported to alleviate Fe-deficiency effects, possibly by enhancing the functional Fe status of plants. This study examines changes in tissue Fe status and oxidative metabolism in Fe-deficient maize (Zea mays L.) plants enriched with NO using sodium nitroprusside (SNP) as a source. Methodology Measurements included changes in concentrations of H2O2, non-protein thiols, levels of lipid peroxidation and activities of superoxide dismutase (SOD) and of the Fe-requiring antioxidant haem enzymes catalase, peroxidase and ascorbate peroxidases. Internal NO in Fe-deficient maize plants was manipulated with SNP and the NO scavenger, methylene blue (MB). A key control was treatment with sodium ferrocyanide (SF), a non-NO-supplying analogue of SNP. Principal results SNP but not SF caused re-greening of leaves in Fe-deficient maize plants over 10–20 days, increased in vivo NO content, raised chlorophyll and carotenoid concentrations, promoted growth in dry weight, increased the activities of H2O2-scavenging haem enzymes and enhanced lipid peroxidation, while decreasing SOD activity and H2O2 concentrations. The NO scavenger, MB, blocked the effects of the SNP. Although SNP and SF each donated Fe and increased active Fe, only SNP increased leaf chlorophyll. Conclusions NO plays a role in Fe nutrition, independently of its effect on total or active Fe status. The most probable mechanism of NO involvement is to increase the intracellular availability of Fe by means of modulating redox. This is likely to be achieved by enhancing the chemical reduction of foliar Fe(III) to Fe(II). PMID:22476060

  17. Thermal treatment and leaching of biochar alleviates plant growth inhibition from mobile organic compounds.

    PubMed

    Gale, Nigel V; Sackett, Tara E; Thomas, Sean C

    2016-01-01

    Recent meta-analyses of plant responses to biochar boast positive average effects of between 10 and 40%. Plant responses, however, vary greatly across systems, and null or negative biochar effects are increasingly reported. The mechanisms responsible for such responses remain unclear. In a glasshouse experiment we tested the effects of three forestry residue wood biochars, applied at five dosages (0, 5, 10, 20, and 50 t/ha) to a temperate forest drystic cambisol as direct surface applications and as complete soil mixes on the herbaceous pioneers Lolium multiflorum and Trifolium repens. Null and negative effects of biochar on growth were found in most cases. One potential cause for null and negative plant responses to biochar is plant exposure to mobile compounds produced during pyrolysis that leach or evolve following additions of biochars to soil. In a second glasshouse experiment we examined the effects of simple leaching and heating techniques to ameliorate potentially phytotoxic effects of volatile and leachable compounds released from biochar. We used Solid Phase Microextraction (SPME)-gas chromatography-mass spectrometry (GC-MS) to qualitatively describe organic compounds in both biochar (through headspace extraction), and in the water leachates (through direct injection). Convection heating and water leaching of biochar prior to application alleviated growth inhibition. Additionally, growth was inhibited when filtrate from water-leached biochar was applied following germination. SPME-GC-MS detected primarily short-chained carboxylic acids and phenolics in both the leachates and solid chars, with relatively high concentrations of several known phytotoxic compounds including acetic acid, butyric acid, 2,4-di-tert-butylphenol and benzoic acid. We speculate that variable plant responses to phytotoxic organic compounds leached from biochars may largely explain negative plant growth responses and also account for strongly species-specific patterns of plant

  18. Intestinal parasitic infections amongst Orang Asli (indigenous) in Malaysia: has socioeconomic development alleviated the problem?

    PubMed

    Lim, Y A L; Romano, N; Colin, N; Chow, S C; Smith, H V

    2009-08-01

    ensure the whole mechanism of delivery and empowerment by the government agencies become more efficient and productive in alleviating intestinal parasitic infections in these communities. PMID:19901897

  19. Thermal treatment and leaching of biochar alleviates plant growth inhibition from mobile organic compounds

    PubMed Central

    Sackett, Tara E.; Thomas, Sean C.

    2016-01-01

    Recent meta-analyses of plant responses to biochar boast positive average effects of between 10 and 40%. Plant responses, however, vary greatly across systems, and null or negative biochar effects are increasingly reported. The mechanisms responsible for such responses remain unclear. In a glasshouse experiment we tested the effects of three forestry residue wood biochars, applied at five dosages (0, 5, 10, 20, and 50 t/ha) to a temperate forest drystic cambisol as direct surface applications and as complete soil mixes on the herbaceous pioneers Lolium multiflorum and Trifolium repens. Null and negative effects of biochar on growth were found in most cases. One potential cause for null and negative plant responses to biochar is plant exposure to mobile compounds produced during pyrolysis that leach or evolve following additions of biochars to soil. In a second glasshouse experiment we examined the effects of simple leaching and heating techniques to ameliorate potentially phytotoxic effects of volatile and leachable compounds released from biochar. We used Solid Phase Microextraction (SPME)–gas chromatography–mass spectrometry (GC-MS) to qualitatively describe organic compounds in both biochar (through headspace extraction), and in the water leachates (through direct injection). Convection heating and water leaching of biochar prior to application alleviated growth inhibition. Additionally, growth was inhibited when filtrate from water-leached biochar was applied following germination. SPME-GC-MS detected primarily short-chained carboxylic acids and phenolics in both the leachates and solid chars, with relatively high concentrations of several known phytotoxic compounds including acetic acid, butyric acid, 2,4-di-tert-butylphenol and benzoic acid. We speculate that variable plant responses to phytotoxic organic compounds leached from biochars may largely explain negative plant growth responses and also account for strongly species-specific patterns of plant

  20. Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits

    PubMed Central

    Zhang, Mao; Ma, Yue-feng; Gan, Jian-xin; Jiang, Guan-yu; Xu, Shan-xiang; Tao, Xiang-luo; Hong, An; Li, Jiao-kun

    2005-01-01

    The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 μg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 μg/(kg·h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-α was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-α and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities. PMID:15973765

  1. Effects of a poverty-alleviation intervention on salivary cortisol in very low-income children

    PubMed Central

    Fernald, Lia; Gunnar, Megan R

    2009-01-01

    Correlational studies have shown associations between social class and salivary cortisol suggestive of a causal link between childhood poverty and activity of the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. Using a quasi-experimental design, we evaluated the association between a family’s participation in a large-scale, conditional cash transfer program in Mexico (Oportunidades, formerly Progresa) during the child’s early years of life and children’s salivary cortisol (baseline and responsivity). We also examined whether maternal depressive symptoms moderated the impact of program participation. Low-income households (income <20th percentile nationally) from rural Mexico were enrolled in a large-scale poverty-alleviation program between 1998 and 1999. A comparison group of households from demographically similar communities was recruited in 2003. Following 3.5 years of the Oportunidades program, three saliva samples were obtained from children age 2-6 years old from intervention and comparison households (n=1197). Maternal depressive symptoms were obtained using the Center for Epidemiologic Studies-Depression Scale (CES-D). Children who had been in the Oportunidades program had lower salivary cortisol levels when compared with those who had not participated in the program, while controlling for a wide range of individual-, household- and community-level variables. Reactivity patterns did not differ between intervention and comparison children. Maternal depression moderated the association between Oportunidades program participation and baseline salivary cortisol in children. Specifically, there was a large and significant Oportunidades program effect of lowering cortisol in children of mothers with high depressive symptoms but not in children of mothers with low depressive symptomatology. These findings provide the strongest evidence to date that the economic circumstances of the family impact the child’s developing stress system

  2. Thermal treatment and leaching of biochar alleviates plant growth inhibition from mobile organic compounds.

    PubMed

    Gale, Nigel V; Sackett, Tara E; Thomas, Sean C

    2016-01-01

    Recent meta-analyses of plant responses to biochar boast positive average effects of between 10 and 40%. Plant responses, however, vary greatly across systems, and null or negative biochar effects are increasingly reported. The mechanisms responsible for such responses remain unclear. In a glasshouse experiment we tested the effects of three forestry residue wood biochars, applied at five dosages (0, 5, 10, 20, and 50 t/ha) to a temperate forest drystic cambisol as direct surface applications and as complete soil mixes on the herbaceous pioneers Lolium multiflorum and Trifolium repens. Null and negative effects of biochar on growth were found in most cases. One potential cause for null and negative plant responses to biochar is plant exposure to mobile compounds produced during pyrolysis that leach or evolve following additions of biochars to soil. In a second glasshouse experiment we examined the effects of simple leaching and heating techniques to ameliorate potentially phytotoxic effects of volatile and leachable compounds released from biochar. We used Solid Phase Microextraction (SPME)-gas chromatography-mass spectrometry (GC-MS) to qualitatively describe organic compounds in both biochar (through headspace extraction), and in the water leachates (through direct injection). Convection heating and water leaching of biochar prior to application alleviated growth inhibition. Additionally, growth was inhibited when filtrate from water-leached biochar was applied following germination. SPME-GC-MS detected primarily short-chained carboxylic acids and phenolics in both the leachates and solid chars, with relatively high concentrations of several known phytotoxic compounds including acetic acid, butyric acid, 2,4-di-tert-butylphenol and benzoic acid. We speculate that variable plant responses to phytotoxic organic compounds leached from biochars may largely explain negative plant growth responses and also account for strongly species-specific patterns of plant

  3. Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

    PubMed

    Li, Xiaolong; Zhang, Xianxiang; Yang, Enqin; Zhang, Nanyang; Cao, Shougen; Zhou, Yanbing

    2015-09-01

    The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

  4. Lactococcus lactis expressing food-grade β-galactosidase alleviates lactose intolerance symptoms in post-weaning Balb/c mice.

    PubMed

    Li, Jingjie; Zhang, Wen; Wang, Chuan; Yu, Qian; Dai, Ruirui; Pei, Xiaofang

    2012-12-01

    The endogenous β-galactosidase expressed in intestinal microbes is demonstrated to help humans in lactose usage, and treatment associated with the promotion of beneficial microorganism in the gut is correlated with lactose tolerance. From this point, a kind of recombinant live β-galactosidase delivery system using food-grade protein expression techniques and selected probiotics as vehicle was promoted by us for the purpose of application in lactose intolerance subjects. Previously, a recombinant Lactococcus lactis MG1363 strain expressing food-grade β-galactosidase, the L. lactis MG1363/FGZW, was successfully constructed and evaluated in vitro. This study was conducted to in vivo evaluate its efficacy on alleviating lactose intolerance symptoms in post-weaning Balb/c mice, which were orally administered with 1 × 10⁶ CFU or 1 × 10⁸ CFU of L. lactis MG1363/FGZW daily for 4 weeks before lactose challenge. In comparison with naïve mice, the mice administered with L. lactis MG1363/FGZW showed significant alleviation of diarrhea symptoms in less total feces weight within 6 h post-challenge and suppressed intestinal motility after lactose challenge, although there was no significant increase of β-galactosidase activity in small intestine. The alleviation also correlated with higher species abundance, more Bifidobacterium colonization, and stronger colonization resistance in mice intestinal microflora. Therefore, this recombinant L. lactis strain effectively alleviated diarrhea symptom induced by lactose uptake in lactose intolerance model mice with the probable mechanism of promotion of lactic acid bacteria to differentiate and predominantly colonize in gut microbial community, thus making it a promising probiotic for lactose intolerance subjects.

  5. Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism.

    PubMed

    Hu, Pei; Mei, Qi-Yong; Ma, Li; Cui, Wu-Geng; Zhou, Wen-Hua; Zhou, Dong-Sheng; Zhao, Qing; Xu, Dong-Ying; Zhao, Xin; Lu, Qin; Hu, Zhen-Yu

    2015-11-15

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30 mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity. PMID:26494631

  6. Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism.

    PubMed

    Hu, Pei; Mei, Qi-Yong; Ma, Li; Cui, Wu-Geng; Zhou, Wen-Hua; Zhou, Dong-Sheng; Zhao, Qing; Xu, Dong-Ying; Zhao, Xin; Lu, Qin; Hu, Zhen-Yu

    2015-11-15

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30 mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity.

  7. Transcutaneous electric acupoint stimulation alleviates remifentanil-induced hyperalgesia in patients undergoing thyroidectomy: a randomized controlled trial

    PubMed Central

    Chen, Yanqing; Yao, Yusheng; Wu, Yihuan; Dai, Dongsheng; Zhao, Qiuyan; Qiu, Liangcheng

    2015-01-01

    Background: In this prospective, randomized, double-blind study, we verified the hypothesis that TEAS can alleviate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy. Methods: 60 American Society of Anesthesiologists physical status (ASA) I-IIpatients, aged 18-60 year, scheduled for thyroidectomy were randomly allocated to TEAS or sham groups. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4) and Neiguan (PC6) before anesthesia. Anesthesia was maintained with sevoflurane adjusted to bispectral index (40-60) and target remifentanil 5.0 ng/ml. Mechanical pain thresholds were assessed using electronic von Frey. The primary outcome was mechanical pain thresholds. Secondary outcomes included postoperative pain scores, the time to first rescue analgesic, cumulative number of rescue analgesia, and side effects, including postoperative nausea and vomiting (PONV), dizziness and shivering in 24 h postoperatively. Results: Baseline mechanical pain thresholds were similar between the groups. The analysis revealed the decrease in mechanical threshold was greater in the sham group than the TEAS group (P < 0.001). Postoperative pain scores and cumulative number of rescue analgesia were lower in the TEAS group (P < 0.05). In addition, TEAS group patients reduced the incidence of PONV and shivering. Conclusion: Preoperative TEAS can attenuate remifentanil-induced hyperalgesia in patients undergoing thyroidectomy. PMID:26131165

  8. The role of forestry development in China in alleviating greenhouse effects

    SciTech Connect

    Liu Hong

    1996-12-31

    Forestry development in China has gained great achievements and made great progress in realizing sustainable forest management and alleviating global climate change. The main measures to mitigate greenhouse effects through the means of forestry development include afforestation to increase the forested area, fuel wood forest development, management improvement, wise utilization, international cooperation, investment increase, forest related scientific research, strengthening the forest law enforcement system. Climate change as well as how to alleviate the greenhouse effects is a hot topic at present. This paper describes the achievements of China`s forestry development and its role to alleviate the greenhouse effects, and puts forward the measures to mitigate greenhouse effects through the means of forestry development.

  9. Antidepressants suppress neuropathic pain by a peripheral β2-adrenoceptor mediated anti-TNFα mechanism.

    PubMed

    Bohren, Yohann; Tessier, Luc-Henri; Megat, Salim; Petitjean, Hugues; Hugel, Sylvain; Daniel, Dorothée; Kremer, Mélanie; Fournel, Sylvie; Hein, Lutz; Schlichter, Rémy; Freund-Mercier, Marie-José; Yalcin, Ipek; Barrot, Michel

    2013-12-01

    Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. It is usually chronic and challenging to treat. Some antidepressants are first-line pharmacological treatments for neuropathic pain. The noradrenaline that is recruited by the action of the antidepressants on reuptake transporters has been proposed to act through β2-adrenoceptors (β2-ARs) to lead to the observed therapeutic effect. However, the complex downstream mechanism mediating this action remained to be identified. In this study, we demonstrate in a mouse model of neuropathic pain that an antidepressant's effect on neuropathic allodynia involves the peripheral nervous system and the inhibition of cytokine tumor necrosis factor α (TNFα) production. The antiallodynic action of nortriptyline is indeed lost after peripheral sympathectomy, but not after lesion of central descending noradrenergic pathways. More particularly, we report that antidepressant-recruited noradrenaline acts, within dorsal root ganglia, on β2-ARs expressed by non-neuronal satellite cells. This stimulation of β2-ARs decreases the neuropathy-induced production of membrane-bound TNFα, resulting in relief of neuropathic allodynia. This indirect anti-TNFα action was observed with the tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline reuptake inhibitor venlafaxine and the β2-AR agonist terbutaline. Our data revealed an original therapeutic mechanism that may open novel research avenues for the management of painful peripheral neuropathies. PMID:23978467

  10. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

    PubMed Central

    Leweke, F M; Piomelli, D; Pahlisch, F; Muhl, D; Gerth, C W; Hoyer, C; Klosterkötter, J; Hellmich, M; Koethe, D

    2012-01-01

    Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia. PMID:22832859

  11. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.

    PubMed

    Leweke, F M; Piomelli, D; Pahlisch, F; Muhl, D; Gerth, C W; Hoyer, C; Klosterkötter, J; Hellmich, M; Koethe, D

    2012-03-20

    Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.

  12. Analysis of helicopter blade-vortex interaction noise with application to adaptive-passive and active alleviation methods

    NASA Astrophysics Data System (ADS)

    Tauszig, Lionel Christian

    ) has been studied as an active method for BVI noise alleviation. Good validation of a baseline case without Higher Harmonic Control (HHC) is obtained. However the present analysis is unable to capture all the features of two specific HHC pitch input schedules examined. Some partial insight on the mechanisms at work is provided.

  13. 6-Gingerol alleviates exaggerated vasoconstriction in diabetic rat aorta through direct vasodilation and nitric oxide generation

    PubMed Central

    Ghareib, Salah A; El-Bassossy, Hany M; Elberry, Ahmed A; Azhar, Ahmad; Watson, Malcolm L; Banjar, Zainy Mohammed

    2015-01-01

    The aim of the present study is to investigate the effect and potential mechanism of action of 6-gingerol on alterations of vascular reactivity in the isolated aorta from diabetic rats. Male Wistar rats were divided into two experimental groups, control and diabetics. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg kg−1), and the rats were left for 10 weeks to develop vascular complications. The effect of in vitro incubation with 6-gingerol (0.3–3 μM) on the vasoconstrictor response of the isolated diabetic aortae to phenylephrine and the vasodilator response to acetylcholine was examined. Effect of 6-gingerol was also examined on aortae incubated with methylglyoxal as an advanced glycation end product (AGE). To investigate the mechanism of action of 6-gingerol, the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride (100 μM), guanylate cyclase inhibitor methylene blue (5 μM), calcium-activated potassium channel blocker tetraethylammonium chloride (10 mM), and cyclooxygenase inhibitor indomethacin (5 μM) were added 30 minutes before assessing the direct vasorelaxant effect of 6-gingerol. Moreover, in vitro effects of 6-gingerol on NO release and the effect of 6-gingerol on AGE production were examined. Results showed that incubation of aortae with 6-gingerol (0.3–10 μM) alleviated the exaggerated vasoconstriction of diabetic aortae to phenylephrine in a concentration-dependent manner with no significant effect on the impaired relaxatory response to acetylcholine. Similar results were seen in the aortae exposed to methylglyoxal. In addition, 6-gingerol induced a direct vasodilation effect that was significantly inhibited by Nω-nitro-l-arginine methyl ester hydrochloride and methylene blue. Furthermore, 6-gingerol stimulated aortic NO generation but had no effect on AGE formation. In conclusion, 6-gingerol ameliorates enhanced vascular contraction in diabetic aortae, which may be partially

  14. [Study of effect of Humifuse Euphorbia Herb on alleviating insulin resistance in type 2 diabetic model KK-Ay mice].

    PubMed

    Wang, Lin-lin; Fu, Hong; Li, Wei-wei; Song, Fang-jiao; Song, Yi-xiang; Yu, Qian; Liu, Geng-xin; Wang, Xue-mei

    2015-05-01

    [To explore the effect of Humifuse Euphorbia Herb ( HEH) on alleviating insulin resistance in type 2 diabetic KK-Ay mice. Totally 40 KK-Ay mice fed with high-fat diet were divided into four groups: the metformin group, the model group, the HEH low-dose group and the HEH high-dose group, and orally administrated with metformin hydrochloride (250 mg x kg(-1)), distilled water, humifuse euphorbia herb 1 g x kg(-1) and 2 g x kg(-1). Besides, C57BL/6J mice with ordinary feed were taken as the normal control group and orally administrated with equal distilled water. The oral administration for the five groups lasted for eight weeks. Before and after the experiment, weight, fasting glucose and insulin tolerance were determined. The morphological changes in pancreas were observed through hematoxylin-eosin (HE) staining on pancreatic tissue sections. The serum insulin, TNF-α, IL-6, adiponectin (ADPN) and leptin (LEP) were detected by ELISA. The results showed that HEH could reduce weight and fasting glucose in KK-Ay mice, alleviate hyperinsulinemia, reduce blood glucose-time AUC, increase 30-min blood glucose decline rate, relieve insulin resistance, significantly ameliorate the pathomorphological changes in pancreas in each group, decrease serum TNF-α, IL-6 and leptin levels in KK-Ay mice and rise serum ADPN level. This study proved that humifuse euphorbia herb can ameliorate the insulin resistance in KK-Ay mice, and its mechanism may be related to the effect on inflammatory factors and adipocytokines. PMID:26390662

  15. Drug-mediated ototoxicity and tinnitus: alleviation with melatonin.

    PubMed

    Reiter, R J; Tan, D-X; Korkmaz, A; Fuentes-Broto, L

    2011-04-01

    This review evaluates the published basic science and clinical reports related to the role of melatonin in reducing the side effects of aminoglycosides and the cancer chemotherapeutic agent cisplatin, in the cochlea and vestibule of the inner ear. A thorough search of the literature was performed using available databases for the purpose of uncovering articles applicable to the current review. Cochlear function was most frequently evaluated by measuring otoacoustic emissions and their distortion products after animals were treated with cytotoxic drugs alone or in combination with melatonin. Vestibular damage due to aminoglycosides was evaluated by estimating hair cell loss in explanted utricles of newborn rats. Tinnitus was assessed in patients who received melatonin using a visual analogue scale or the Tinnitus Handicap Inventory. Compared to a mixture of antioxidants which included tocopherol, ascorbate, glutathione and N-acetyl-cysteine, melatonin, also a documented antioxidant, was estimated to be up to 150 times more effective in limiting the cochlear side effects, evaluated using otoacoustic emission distortion products, of gentamicin, tobramycin and cisplatin. In a dose-response manner, melatonin also reduced vestibular hair cell loss due to gentamicin treatment in explanted utricles of newborn rats. Finally, melatonin (3 mg daily) limited subjective tinnitus in patients. These findings suggest the potential use of melatonin to combat the ototoxicity of aminoglycosides and cancer chemotherapeutic agents. Additional studies at both the experimental and clinical levels should be performed to further document the actions of melatonin at the cochlear and vestibular levels to further clarify the protective mechanisms of action of this ubiquitously-acting molecule. Melatonin's low cost and minimal toxicity profile supports its use to protect the inner ear from drug-mediated damage. PMID:21673362

  16. Oleanolic acid alleviated pressure overload-induced cardiac remodeling.

    PubMed

    Liao, Hai-Han; Zhang, Nan; Feng, Hong; Zhang, Ning; Ma, Zhen-Guo; Yang, Zheng; Yuan, Yuan; Bian, Zhou-Yan; Tang, Qi-Zhu

    2015-11-01

    Previous study has demonstrated that oleanolic acid (OA) possessing the anti-inflammatory and anti-oxidant properties blunted high-glucose-induced diabetic cardiomyopathy and ameliorated experimental autoimmune myocarditis in mice. However, little is known about its effects on pressure overload-induced cardiac remodeling. Herein, we investigated the effect of OA on cardiac remodeling and underlying mechanism. Mice, subjected to aortic banding (AB), were randomly assigned into control group and experimental group. OA premixed in diets was administered to mice after 3 days of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed after 8 weeks' treatment of OA. Histologic examination and molecular analyses were used to assess cardiac hypertrophy and tissue fibrosis. In addition, the inhibitory effects of OA on H9c2 cardiomyocytes and cardiac primary fibroblast responded to the stimulation of AngII were also investigated. OA ameliorated the systolic and diastolic dysfunction induced by pressure overload evidenced by echocardiography and catheter-based measurements. OA also decreased the mRNA expression of cardiac hypertrophy and fibrosis markers evidenced by RT-PCR. It has been shown in our study that pressure overload activated the phosphorylations of Akt, mTOR, p70s6k, S6, GSK3β, and FoxO3a, and treatment of OA attenuated the phosphorylation of these proteins. In addition, hypertrophy of cardiomyocytes and fibrosis markers induced by AngII was inhibited by OA in vitro. Our findings uncover that OA suppressed AB-induced cardiac hypertrophy, partly by inhibiting the activity of Akt/mTOR pathway, and suggest that treatment of OA may have a benefit on retarding the progress of cardiac remodeling under long terms of pressure overload. PMID:26215454

  17. Hyperoside Induces Endogenous Antioxidant System to Alleviate Oxidative Stress

    PubMed Central

    Park, Ji Young; Han, Xia; Piao, Mei Jing; Oh, Min Chang; Fernando, Pattage Madushan Dilhara Jayatissa; Kang, Kyoung Ah; Ryu, Yea Seong; Jung, Uhee; Kim, In Gyu; Hyun, Jin Won

    2016-01-01

    Background: Hyperoside, a flavonoid which is mainly found in Hypericum perforatum L., has many biological effects. One of the most important effects is to prevent the oxidative stress induced by reactive oxygen species. However, the molecular mechanisms underlying its effect are not fully understood. Oxidative stress is implicated in the occurrence of various physical diseases. A wide array of enzymatic antioxidant defense systems include NADH: quinone oxidoreductase 1, superoxide dismutase, and heme oxygenase-1 (HO-1). In the present study, the protective effects of hyperoside against hydrogen peroxide-induced oxidative stress in human lens epithelial cells, HLE-B3, were investigated in terms of HO-1 induction. Methods: The protein and mRNA expressions of HO-1 were examined by Western blotting and reverse transcriptase-PCR assays, respectively. To evaluate the ability of hyperoside to activate nuclear factor erythroid 2-related factor 2 (Nrf2), Western blotting and electrophoretic mobility shift assay were performed with nuclear extracts prepared from HLE-B3 cells treated with hyperoside. The activation of extracellular signal-regulated kinase (ERK), the upstream kinase of Nrf2 signaling, was monitored by Western blot analysis. The protective effect of hyperoside in HLE-B3 cells against hydrogen peroxide was performed by MTT assay. Results: Hyperoside increased both the mRNA and protein expression of HO-1 in a time- and dose-dependent manner. In addition, hyperoside elevated the level of of Nrf2 and its antioxidant response element-binding activity, which was modulated by upstream of ERK. Moreover, it activated ERK and restored cell viability which was decreased by hydrogen peroxide. Conclusions: Hyperoside is an effective compound to protect cells against oxidative stress via HO-1 induction. PMID:27051648

  18. Seed priming to alleviate salinity stress in germinating seeds.

    PubMed

    Ibrahim, Ehab A

    2016-03-15

    Salinity is one of the major abiotic stresses that affect crop production in arid and semiarid areas. Seed germination and seedling growth are the stages most sensitive to salinity. Salt stress causes adverse physiological and biochemical changes in germinating seeds. It can affect the seed germination and stand establishment through osmotic stress, ion-specific effects and oxidative stress. The salinity delays or prevents the seed germination through various factors, such as a reduction in water availability, changes in the mobilization of stored reserves and affecting the structural organization of proteins. Various techniques can improve emergence and stand establishment under salt conditions. One of the most frequently utilized is seed priming. The process of seed priming involves prior exposure to an abiotic stress, making a seed more resistant to future exposure. Seed priming stimulates the pre-germination metabolic processes and makes the seed ready for radicle protrusion. It increases the antioxidant system activity and the repair of membranes. These changes promote seed vigor during germination and emergence under salinity stress. The aim of this paper is to review the recent literature on the response of plants to seed priming under salinity stress. The mechanism of the effect of salinity on seed germination is discussed and the seed priming process is summarized. Physiological, biochemical and molecular changes induced by priming that lead to seed enhancement are covered. Plants' responses to some priming agents under salinity stress are reported based on the best available data. For a great number of crops, little information exists and further research is needed. PMID:26812088

  19. Seed priming to alleviate salinity stress in germinating seeds.

    PubMed

    Ibrahim, Ehab A

    2016-03-15

    Salinity is one of the major abiotic stresses that affect crop production in arid and semiarid areas. Seed germination and seedling growth are the stages most sensitive to salinity. Salt stress causes adverse physiological and biochemical changes in germinating seeds. It can affect the seed germination and stand establishment through osmotic stress, ion-specific effects and oxidative stress. The salinity delays or prevents the seed germination through various factors, such as a reduction in water availability, changes in the mobilization of stored reserves and affecting the structural organization of proteins. Various techniques can improve emergence and stand establishment under salt conditions. One of the most frequently utilized is seed priming. The process of seed priming involves prior exposure to an abiotic stress, making a seed more resistant to future exposure. Seed priming stimulates the pre-germination metabolic processes and makes the seed ready for radicle protrusion. It increases the antioxidant system activity and the repair of membranes. These changes promote seed vigor during germination and emergence under salinity stress. The aim of this paper is to review the recent literature on the response of plants to seed priming under salinity stress. The mechanism of the effect of salinity on seed germination is discussed and the seed priming process is summarized. Physiological, biochemical and molecular changes induced by priming that lead to seed enhancement are covered. Plants' responses to some priming agents under salinity stress are reported based on the best available data. For a great number of crops, little information exists and further research is needed.

  20. Functional electrical therapy for hemiparesis alleviates disability and enhances neuroplasticity.

    PubMed

    Tarkka, Ina M; Pitkänen, Kauko; Popovic, Dejan B; Vanninen, Ritva; Könönen, Mervi

    2011-01-01

    Impaired motor and sensory function is common in the upper limb in humans after cerebrovascular stroke and it often remains as a permanent disability. Functional electrical stimulation therapy is known to enhance the motor function of the paretic hand; however, the mechanism of this enhancement is not known. We studied whether neural plasticity has a role in this therapy-induced enhancement of the hand motor function in 20 hemiparetic subjects with chronic stroke (age 53 ± 6 years; 7 females and 13 males; 10 with cerebral infarction and 10 with cerebral haemorrhage; and time since incident 2.4 ± 2.0 years). These subjects were randomized to functional electrical therapy or conventional physiotherapy group. Both groups received upper limb treatment (twice daily sessions) for two weeks. Behavioral hand motor function and neurophysiologic transcranial magnetic stimulation (TMS) tests were applied before and after the treatment and at 6-months follow-up. TMS is useful in assessing excitability changes in the primary motor cortex. Faster corticospinal conduction and newly found muscular responses were observed in the paretic upper limb in the functional electrical therapy group but not in the conventional therapy group after the intervention. Behaviourally, faster movement times were observed in the functional electrical therapy group but not in the conventionally treated group. Despite the small number of heterogeneous subjects, functional exercise augmented with individualized electrical therapy of the paretic upper limb may enhance neuroplasticity, observed as corticospinal facilitation, in chronic stroke subjects, along with moderate improvements in the voluntary motor control of the affected limb. PMID:21878747

  1. Transplant-mediated enhancement of spinal cord GABAergic inhibition reverses paclitaxel-induced mechanical and heat hypersensitivity.

    PubMed

    Bráz, João M; Wang, Xidao; Guan, Zhonghui; Rubenstein, John L; Basbaum, Allan I

    2015-06-01

    Decreased spinal cord GABAergic inhibition is a major contributor to the persistent neuropathic pain that can follow peripheral nerve injury. Recently, we reported that restoring spinal cord GABAergic signaling by intraspinal transplantation of cortical precursors of GABAergic interneurons from the embryonic medial ganglionic eminence (MGE) can reverse the mechanical hypersensitivity (allodynia) that characterizes a neuropathic pain model in the mouse. We show that MGE cell transplants are also effective against both the mechanical allodynia and the heat hyperalgesia produced in a paclitaxel-induced chemotherapy model of neuropathic pain. To test the necessity of GABA release by the transplants, we also studied the utility of transplanting MGE cells from mice with a deletion of VGAT, the vesicular GABA transporter. Transplants from these mice, in which GABA is synthesized but cannot be stored or released, had no effect on mechanical hypersensitivity or heat hyperalgesia in the paclitaxel model. Taken together, these results demonstrate the therapeutic potential of GABAergic precursor cell transplantation in diverse neuropathic pain models and support our contention that restoration of inhibitory controls through release of GABA from the transplants is their mode of action. PMID:25760475

  2. Symptom monitoring, alleviation, and self-care among Mexican Americans during cancer treatment.

    PubMed

    Williams, Phoebe D; Lantican, Leticia S; Bader, Julia O; Lerma, Daniela

    2014-10-01

    Monitoring the occurrence and severity of symptoms among Mexican American adults undergoing cancer treatments, along with their self-care to alleviate symptoms, are understudied; the current study aimed to fill this gap in the literature. A total of 67 Mexican Americans receiving outpatient oncology treatments in the southwestern United States participated. Instruments included a patient-report checklist, the Therapy-Related Symptom Checklist (TRSC), the Symptom Alleviation: Self-Care Methods tool, and a demographic and health information form. At least 40% of participants reported the occurrence of 12 symptoms: hair loss, feeling sluggish, nausea, taste change, loss of appetite, depression, difficulty sleeping, weight loss, difficulty concentrating, constipation, skin changes, and numb fingers and toes. More than a third also reported pain, vomiting, decreased interest in sexual activity, cough, and sore throat. The helpful self-care strategies reported included diet and nutrition changes; lifestyle changes; and mind, body control, and spiritual activities. Patient report of symptoms during cancer treatments was facilitated by the use of the TRSC. Patients use symptom alleviation strategies to help relieve symptoms during their cancer treatment. The ability to perform appropriate, effective self-care methods to alleviate the symptoms may influence adherence to the treatment regimen. PMID:25253108

  3. A Purposeful MOOC to Alleviate Insufficient CS Education in Finnish Schools

    ERIC Educational Resources Information Center

    Kurhila, Jaakko; Vihavainen, Arto

    2015-01-01

    The Finnish national school curriculum, effective from 2004, does not include any topics related to Computer Science (CS). To alleviate the problem that school students are not able to study CS-related topics, the Department of Computer Science at the University of Helsinki prepared a completely online course that is open to pupils and students in…

  4. Food Stamp and School Lunch Programs Alleviate Food Insecurity in Rural America. Fact Sheet

    ERIC Educational Resources Information Center

    Smith, Kristin; Savage, Sarah

    2007-01-01

    The Food Stamp and the National School Lunch Programs play a vital role in helping poor, rural Americans obtain a more nutritious diet and alleviate food insecurity and hunger. This fact sheet looks at the extent to which rural America depends on these programs and describes characteristics of beneficiaries of these federal nutrition assistance…

  5. The Use of the Ombudsman's Services for Alleviating International Students' Difficulties

    ERIC Educational Resources Information Center

    Katsara, Ourania

    2015-01-01

    This article offers some suggestions regarding the development of a support strategy by ombudsmen in order to alleviate international students' difficulties when studying in host universities. It is also shown how the Organisational Justice Theory can be used as a framework for understanding the role of ombudsman in higher education settings and…

  6. Substitutive Competition: Virtual Pets as Competitive Buffers to Alleviate Possible Negative Influence on Pupils

    ERIC Educational Resources Information Center

    Chen, Zhi-Hong; Chou, Chih-Yueh; Biswas, Gautam; Chan, Tak-Wai

    2012-01-01

    Although competition is regarded as a powerful motivator in game-based learning, it might have a negative influence, such as damage to confidence, on students who lose the competition. In this paper, we propose an indirect approach, substitutive competition, to alleviate such negative influences. The approach is used to develop a My-Pet v3 system,…

  7. 13 CFR 310.2 - Pressing need; alleviation of unemployment or underemployment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... unemployment or underemployment. 310.2 Section 310.2 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE SPECIAL IMPACT AREAS § 310.2 Pressing need; alleviation of unemployment or... Special Need. (b) For purposes of this part, excessive unemployment exists if the twenty-four (24)...

  8. 13 CFR 310.2 - Pressing need; alleviation of unemployment or underemployment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... unemployment or underemployment. 310.2 Section 310.2 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE SPECIAL IMPACT AREAS § 310.2 Pressing need; alleviation of unemployment or... Special Need. (b) For purposes of this part, excessive unemployment exists if the twenty-four (24)...

  9. 13 CFR 310.2 - Pressing need; alleviation of unemployment or underemployment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... unemployment or underemployment. 310.2 Section 310.2 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE SPECIAL IMPACT AREAS § 310.2 Pressing need; alleviation of unemployment or... Special Need. (b) For purposes of this part, excessive unemployment exists if the twenty-four (24)...

  10. 13 CFR 310.2 - Pressing need; alleviation of unemployment or underemployment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... unemployment or underemployment. 310.2 Section 310.2 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE SPECIAL IMPACT AREAS § 310.2 Pressing need; alleviation of unemployment or... Special Need. (b) For purposes of this part, excessive unemployment exists if the twenty-four (24)...

  11. 13 CFR 310.2 - Pressing need; alleviation of unemployment or underemployment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... unemployment or underemployment. 310.2 Section 310.2 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE SPECIAL IMPACT AREAS § 310.2 Pressing need; alleviation of unemployment or... Special Need. (b) For purposes of this part, excessive unemployment exists if the twenty-four (24)...

  12. Natural Products for the Prevention and Alleviation of Risk Factors for Diabetes: Chromium and Cinnamon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products are widespread for the alleviation and prevention of the risk factors of the metabolic syndrome and diabetes. We have shown that glucose, insulin, cholesterol, and hemoglobin A1c levels are all improved in people with type 2 diabetes following chromium supplementation in a double-b...

  13. Young Children's Ideas about the Nature, Causes, Justification, and Alleviation of Poverty

    ERIC Educational Resources Information Center

    Chafel, Judith A.; Neitzel, Carin

    2005-01-01

    Sixty-four 8-year-old boys and girls from urban and rural settings and representing different races and socioeconomic status backgrounds responded to questions about the nature, causes, justification, and alleviation of poverty. Much of what the children said indicated that they had not yet internalized prevailing adult norms and values about the…

  14. Symptom monitoring, alleviation, and self-care among Mexican Americans during cancer treatment.

    PubMed

    Williams, Phoebe D; Lantican, Leticia S; Bader, Julia O; Lerma, Daniela

    2014-10-01

    Monitoring the occurrence and severity of symptoms among Mexican American adults undergoing cancer treatments, along with their self-care to alleviate symptoms, are understudied; the current study aimed to fill this gap in the literature. A total of 67 Mexican Americans receiving outpatient oncology treatments in the southwestern United States participated. Instruments included a patient-report checklist, the Therapy-Related Symptom Checklist (TRSC), the Symptom Alleviation: Self-Care Methods tool, and a demographic and health information form. At least 40% of participants reported the occurrence of 12 symptoms: hair loss, feeling sluggish, nausea, taste change, loss of appetite, depression, difficulty sleeping, weight loss, difficulty concentrating, constipation, skin changes, and numb fingers and toes. More than a third also reported pain, vomiting, decreased interest in sexual activity, cough, and sore throat. The helpful self-care strategies reported included diet and nutrition changes; lifestyle changes; and mind, body control, and spiritual activities. Patient report of symptoms during cancer treatments was facilitated by the use of the TRSC. Patients use symptom alleviation strategies to help relieve symptoms during their cancer treatment. The ability to perform appropriate, effective self-care methods to alleviate the symptoms may influence adherence to the treatment regimen.

  15. Muscle activity pattern dependent pain development and alleviation.

    PubMed

    Sjøgaard, Gisela; Søgaard, Karen

    2014-12-01

    Muscle activity is for decades considered to provide health benefits irrespectively of the muscle activity pattern performed and whether it is during e.g. sports, transportation, or occupational work tasks. Accordingly, the international recommendations for public health-promoting physical activity do not distinguish between occupational and leisure time physical activity. However, in this body of literature, attention has not been paid to the extensive documentation on occupational physical activity imposing a risk of impairment of health - in particular musculoskeletal health in terms of muscle pain. Focusing on muscle activity patterns and musculoskeletal health it is pertinent to elucidate the more specific aspects regarding exposure profiles and body regional pain. Static sustained muscle contraction for prolonged periods often occurs in the neck/shoulder area during occupational tasks and may underlie muscle pain development in spite of rather low relative muscle load. Causal mechanisms include a stereotype recruitment of low threshold motor units (activating type 1 muscle fibers) characterized by a lack of temporal as well as spatial variation in recruitment. In contrast during physical activities at leisure and sport the motor recruitment patterns are more dynamic including regularly relatively high muscle forces - also activating type 2 muscles fibers - as well as periods of full relaxation even of the type 1 muscle fibers. Such activity is unrelated to muscle pain development if adequate recovery is granted. However, delayed muscle soreness may develop following intensive eccentric muscle activity (e.g. down-hill skiing) with peak pain levels in thigh muscles 1-2 days after the exercise bout and a total recovery within 1 week. This acute pain profile is in contrast to the chronic muscle pain profile related to repetitive monotonous work tasks. The painful muscles show adverse functional, morphological, hormonal, as well as metabolic characteristics. Of

  16. Chrysin and luteolin alleviate vascular complications associated with insulin resistance mainly through PPAR-γ activation.

    PubMed

    El-Bassossy, Hany M; Abo-Warda, Shaymaa M; Fahmy, Ahmed

    2014-01-01

    Chrysin and luteolin are two flavonoids with Peroxisome proliferators-activated receptor γ (PPAR-γ) stimulating activity. Here, we investigated the protective effect of chrysin and luteolin from vascular complications associated with insulin resistance (IR). IR was induced in rats by drinking fructose for 12 weeks while chrysin and luteolin were given for 6 weeks with or without PPAR-γ antagonist, bisphenol A diglycidyl ether (BADGE). Then, blood pressure (BP) was recorded and serum levels of glucose, insulin, advanced glycation end products (AGEs) and lipids were measured. Concentration response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in thoracic aorta rings. Aortic reactive oxygen species (ROS) and nitric oxide (NO) generation were also studied. Chrysin and luteolin significantly alleviated systolic BP elevations caused by IR, while the co-administration of BADGE prevented chrysin alleviation. Although, neither chrysin nor luteolin affected ACh impaired vasodilatation, they both alleviated exaggerated vasoconstrictions to PE and KCl in IR animals. In addition, incubation of the aorta from IR animals with chrysin or luteolin prevented exaggerated vasoconstrictions to PE and KCl. On the other hand, co-administration of BADGE or co-incubation with GW9662, the selective PPAR-γ antagonist, prevented chrysin alleviation. Both chrysin and luteolin inhibited the developed hyperinsulinemia and increases in serum AGEs, lipids while, BADGE reduced the effect of chrysin on hyperinsulinemia and dyslipidemia. Chrysin and luteolin markedly inhibited elevated NO and ROS in IR aortae while BADGE did not change their effect on NO and ROS. In conclusion, chrysin and luteolin alleviate vascular complications associated with IR mainly through PPAR-γ dependent pathways.

  17. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    PubMed

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. PMID:26454262

  18. Arbuscular mycorrhizal symbiosis elicits shoot proteome changes that are modified during cadmium stress alleviation in Medicago truncatula

    PubMed Central

    2011-01-01

    Background Arbuscular mycorrhizal (AM) fungi, which engage a mutualistic symbiosis with the roots of most plant species, have received much attention for their ability to alleviate heavy metal stress in plants, including cadmium (Cd). While the molecular bases of Cd tolerance displayed by mycorrhizal plants have been extensively analysed in roots, very little is known regarding the mechanisms by which legume aboveground organs can escape metal toxicity upon AM symbiosis. As a model system to address this question, we used Glomus irregulare-colonised Medicago truncatula plants, which were previously shown to accumulate and tolerate heavy metal in their shoots when grown in a substrate spiked with 2 mg Cd kg-1. Results The measurement of three indicators for metal phytoextraction showed that shoots of mycorrhizal M. truncatula plants have a capacity for extracting Cd that is not related to an increase in root-to-shoot translocation rate, but to a high level of allocation plasticity. When analysing the photosynthetic performance in metal-treated mycorrhizal plants relative to those only Cd-supplied, it turned out that the presence of G. irregulare partially alleviated the negative effects of Cd on photosynthesis. To test the mechanisms by which shoots of Cd-treated mycorrhizal plants avoid metal toxicity, we performed a 2-DE/MALDI/TOF-based comparative proteomic analysis of the M. truncatula shoot responses upon mycorrhization and Cd exposure. Whereas the metal-responsive shoot proteins currently identified in non-mycorrhizal M. truncatula indicated that Cd impaired CO2 assimilation, the mycorrhiza-responsive shoot proteome was characterised by an increase in photosynthesis-related proteins coupled to a reduction in glugoneogenesis/glycolysis and antioxidant processes. By contrast, Cd was found to trigger the opposite response coupled the up-accumulation of molecular chaperones in shoot of mycorrhizal plants relative to those metal-free. Conclusion Besides drawing a

  19. Rootstock alleviates PEG-induced water stress in grafted pepper seedlings: physiological responses.

    PubMed

    Penella, Consuelo; Nebauer, Sergio G; Bautista, Alberto San; López-Galarza, Salvador; Calatayud, Ángeles

    2014-06-15

    Recent studies have shown that tolerance to abiotic stress, including water stress, is improved by grafting. In a previous work, we took advantage of the natural variability of Capsicum spp. and selected accessions tolerant and sensitive to water stress as rootstocks. The behavior of commercial cultivar 'Verset' seedlings grafted onto the selected rootstocks at two levels of water stress provoked by adding 3.5 and 7% PEG (polyethylene glycol) was examined over 14 days. The objective was to identify the physiological traits responsible for the tolerance provided by the rootstock in order to determine if the tolerance is based on the maintenance of the water relations under water stress or through the activation of protective mechanisms. To achieve this goal, various physiological parameters were measured, including: water relations; proline accumulation; gas exchange; chlorophyll fluorescence; nitrate reductase activity; and antioxidant capacity. Our results indicate that the effect of water stress on the measured parameters depends on the duration and intensity of the stress level, as well as the rootstock used. Under control conditions (0% PEG) all plant combinations showed similar values for all measured parameters. In general terms, PEG provoked a strong decrease in the gas exchange parameters in the cultivar grafted onto the sensitive accessions, as also observed in the ungrafted plants. This effect was related to lower relative water content in the plants, provoked by an inefficient osmotic adjustment that was dependent on reduced proline accumulation. At the end of the experiment, chronic photoinhibition was observed in these plants. However, the plants grafted onto the tolerant rootstocks, despite the reduction in photosynthetic rate, maintained the protective capacity of the photosynthetic machinery mediated by osmotic adjustment (based on higher proline content). In addition, water stress limited uptake and further NO3(-) transfer to the leaves. Increased

  20. Prostaglandin E1 alleviates neuropathic pain and neural dysfunction from entrapment neuropathy associated with diabetes mellitus.

    PubMed

    Natsume, Tadahiro; Iwatsuki, Katsuyuki; Nishizuka, Takanobu; Arai, Tetsuya; Yamamoto, Michiro; Hirata, Hitoshi

    2014-10-01

    In this report, we present the results of investigation of the effects of prostaglandin E1 (PGE1) on entrapment neuropathy using a diabetic rat. A total of 60 male Sprague-Dawley rats were used in the study. The model of tibial nerve entrapment neuropathy associated with diabetes mellitus was created by streptozotocin-induced diabetic rats reared in cages with wire grid flooring. Rats were assigned to four groups: nondiabetic (n = 15), untreated diabetic (n = 15), diabetic treated with 30 μg/kg PGE1 (n = 15), and diabetic treated with 100 μg/kg PGE1 (n = 15). Pain tests and electrophysiological tests were performed at 0, 2, and 4 weeks, and assessments of gait, histology, and mRNA expression levels were performed at 4 weeks after initiating the PGE1 administration. In the 30 and 100 μg groups, the mechanical withdrawal thresholds measured by pain tests at 4 weeks (36.2 ± 16.4 g and 31.7 ± 15.3 g, respectively) and the motor conduction velocity (24.0 ± 0.2 m/s and 24.4 ± 0.3 m/s, respectively) were significantly higher than the untreated diabetic group (all P < 0.05) and lower than the nondiabetic group (all P < 0.001). In the gait analysis, the mean intensities in the 30 and 100 μg group (128.0 ± 20.1 a.u. and 109.0 ± 27.8 a.u., respectively) were significantly higher than the untreated diabetic (P < 0.01) and were not significantly different from the nondiabetic group (P = 0.81). Fiber density (P = 0.46) and fiber diameter (P = 0.15) did not show any significant differences. PGE1 significantly decreased nerve growth factor (NGF) mRNA and increased vascular endothelial growth factor (VEGF) mRNA in the tibial nerve (both P < 0.01). In conclusion, neurological deteriorations of diabetic rats were alleviated with PGE1, which is associated with inhibition of NGF and enhancement of VEGF at the entrapment site.

  1. The antiallodynic action of nortriptyline and terbutaline is mediated by β(2) adrenoceptors and δ opioid receptors in the ob/ob model of diabetic polyneuropathy.

    PubMed

    Choucair-Jaafar, Nada; Salvat, Eric; Freund-Mercier, Marie-José; Barrot, Michel

    2014-02-10

    Peripheral polyneuropathy is a frequent complication of diabetes. One of its consequences is neuropathic pain which is often chronic and difficult to treat. This pain management classically involves anticonvulsant drugs or tricyclic antidepressant drugs (TCA). We have previously shown that β2 adrenoceptors and δ opioid receptors are critical for TCA action in a traumatic model of neuropathic pain. In the present work, we used the obese leptin deficient mice (ob/ob) which are a genetic model of type 2 diabetes in order to study the treatment of diabetic polyneuropathy. ob/ob mice with hyperglycemia develop tactile bilateral allodynia. We investigated the action of the TCA nortriptyline and the β2 adrenoceptor agonist terbutaline on this neuropathic allodynia. The consequences of acute and chronic treatments were tested, and mechanical allodynia was assessed by using von Frey hairs. Chronic but not acute treatment with nortriptyline alleviates allodynia caused by the diabetic neuropathy. This effect depends on β2 adrenoceptors but not on α2 adrenoceptors, as shown by the blockade with repeated co-administration of the β2 adrenoceptor antagonist ICI118551 but not with repeated co-administration of the α2 adrenoceptor antagonist yohimbine. Direct stimulation of β2 adrenoceptors appears sufficient to relieve allodynia, as shown with chronic terbutaline treatment. δ but not mu opioid receptors seem important to these action since acute naltrindole, but not acute naloxonazine, reverses the effect of chronic nortriptyline or terbutaline treatment.

  2. Diets enriched in trans-11 vaccenic acid alleviate ectopic lipid accumulation in a rat model of NAFLD and metabolic syndrome.

    PubMed

    Jacome-Sosa, M Miriam; Borthwick, Faye; Mangat, Rabban; Uwiera, Richard; Reaney, Martin J; Shen, Jianheng; Quiroga, Ariel D; Jacobs, René L; Lehner, Richard; Proctor, Spencer D; Nelson, Randal C

    2014-07-01

    Trans11-18:1 (vaccenic acid, VA) is one of the most predominant naturally occurring trans fats in our food chain and has recently been shown to exert hypolipidemic effects in animal models. In this study, we reveal new mechanism(s) by which VA can alter body fat distribution, energy utilization and dysfunctional lipid metabolism in an animal model of obesity displaying features of the metabolic syndrome (MetS). Obese JCR:LA-cp rats were assigned to a control diet that included dairy-derived fat or the control diet supplemented with 1% VA. VA reduced total body fat (-6%), stimulated adipose tissue redistribution [reduced mesenteric fat (-17%) while increasing inguinal fat mass (29%)] and decreased adipocyte size (-44%) versus control rats. VA supplementation also increased metabolic rate (7%) concomitantly with an increased preference for whole-body glucose utilization for oxidation and increased insulin sensitivity [lower HOMA-IR (-59%)]. Further, VA decreased nonalcoholic fatty liver disease activity scores (-34%) and reduced hepatic (-27%) and intestinal (-39%) triglyceride secretion relative to control diet, while exerting differential transcriptional regulation of SREBP1 and FAS amongst other key genes in the liver and the intestine. Adding VA to dairy fat alleviates features of MetS potentially by remodeling adipose tissue and attenuating ectopic lipid accumulation in a rat model of obesity and MetS. Increasing VA content in the diet (naturally or by fortification) may be a useful approach to maximize the health value of dairy-derived fats. PMID:24775093

  3. Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways

    PubMed Central

    Zhang, Yang; Wang, Jing-Hao; Zhang, Yi-Yuan; Wang, Ying-Zhe; Wang, Jin; Zhao, Yue; Jin, Xue-Xin; Xue, Gen-Long; Li, Peng-Hui; Sun, Yi-Lin; Huang, Qi-He; Song, Xiao-Tong; Zhang, Zhi-Ren; Gao, Xu; Yang, Bao-Feng; Du, Zhi-Min; Pan, Zhen-Wei

    2016-01-01

    Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and interstitial fibrosis was apparently alleviated in comparison with wildtype (WT) diabetic mice induced by streptozotocin (STZ). Treatment with IL-6 significantly promoted the proliferation and collagen production of cultured cardiac fibroblasts (CFs). High glucose treatment increased collagen production, which were mitigated in CFs from IL-6 KO mice. Moreover, IL-6 knockout alleviated the up-regulation of TGFβ1 in diabetic hearts of mice and cultured CFs treated with high glucose or IL-6. Furthermore, the expression of miR-29 reduced upon IL-6 treatment, while increased in IL-6 KO hearts. Overexpression of miR-29 blocked the pro-fibrotic effects of IL-6 on cultured CFs. In summary, deletion of IL-6 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The mechanism involves the regulation of IL-6 on TGFβ1 and miR-29 pathway. This study indicates the therapeutic potential of IL-6 suppression on diabetic cardiomyopathy disease associated with fibrosis. PMID:26972749

  4. Herbaspirillum sp. strain GW103 alleviates salt stress in Brassica rapa L. ssp. pekinensis.

    PubMed

    Lee, Gun Woong; Lee, Kui-Jae; Chae, Jong-Chan

    2016-05-01

    Mutual interactions between plant and rhizosphere bacteria facilitate plant growth and reduce risks of biotic and abiotic stresses. The present study demonstrates alleviation of salt stress in Brassica rapa L. ssp. perkinensis (Chinese cabbage) by Herbaspirillum sp. strain GW103 isolated from rhizosphere soil of Phragmites australis. The strain was capable of producing plant beneficial factors, such as auxin, siderophore, and 1-aminocylopropane-1-carboxylic acid deaminase. Treatment of strain GW103 on Chinese cabbage under salt stress increased K(+)/Na(+) ratio in roots generating balance in the ratio of ion homeostasis and consequently contributed to the increase of biomass. In addition, root colonization potential of the strain was observed by green fluorescent protein (GFP)-tagging approach. These results strongly suggest the beneficial impact of strain GW103 by inducing the alleviation of salt stress and development of stress tolerance in Chinese cabbage via plant-microbe interaction.

  5. Metacognitive emotion regulation: children's awareness that changing thoughts and goals can alleviate negative emotions.

    PubMed

    Davis, Elizabeth L; Levine, Linda J; Lench, Heather C; Quas, Jodi A

    2010-08-01

    Metacognitive emotion regulation strategies involve deliberately changing thoughts or goals to alleviate negative emotions. Adults commonly engage in this type of emotion regulation, but little is known about the developmental roots of this ability. Two studies were designed to assess whether 5- and 6-year-old children can generate such strategies and, if so, the types of metacognitive strategies they use. In Study 1, children described how story protagonists could alleviate negative emotions. In Study 2, children recalled times that they personally had felt sad, angry, and scared and described how they had regulated their emotions. In contrast to research suggesting that young children cannot use metacognitive regulation strategies, the majority of children in both studies described such strategies. Children were surprisingly sophisticated in their suggestions for how to cope with negative emotions and tailored their regulatory responses to specific emotional situations.

  6. Decerebrate mammalian preparations: unalleviated or fully alleviated pain? A review and opinion.

    PubMed

    Silverman, Jerald; Garnett, Nelson L; Giszter, Simon F; Heckman, Charles J; Kulpa-Eddy, Jodie A; Lemay, Michel A; Perry, Constance K; Pinter, Martin

    2005-07-01

    In experimental decerebration of mammals, the cerebral cortex and thalamus are surgically or otherwise inactivated under traditional (pharmacologic) general anesthesia. Once the effects of the pharmacologic anesthesia have dissipated, the animal remains alive, but there is neither pain sensation nor consciousness. Because the Animal Welfare Act and its regulations recognize drugs as the only means to alleviate pain, it is unclear whether a decerebrate animal should be placed in U.S. Department of Agriculture (USDA) pain and distress category D (pain or distress alleviated by drugs) or E (unalleviated pain or distress). We present a rationale for including decerebrate animals in USDA category D. We also provide a general review of decerebration and suggestions for institutional animal care and use committees having to evaluate decerebration protocols.

  7. Herbaspirillum sp. strain GW103 alleviates salt stress in Brassica rapa L. ssp. pekinensis.

    PubMed

    Lee, Gun Woong; Lee, Kui-Jae; Chae, Jong-Chan

    2016-05-01

    Mutual interactions between plant and rhizosphere bacteria facilitate plant growth and reduce risks of biotic and abiotic stresses. The present study demonstrates alleviation of salt stress in Brassica rapa L. ssp. perkinensis (Chinese cabbage) by Herbaspirillum sp. strain GW103 isolated from rhizosphere soil of Phragmites australis. The strain was capable of producing plant beneficial factors, such as auxin, siderophore, and 1-aminocylopropane-1-carboxylic acid deaminase. Treatment of strain GW103 on Chinese cabbage under salt stress increased K(+)/Na(+) ratio in roots generating balance in the ratio of ion homeostasis and consequently contributed to the increase of biomass. In addition, root colonization potential of the strain was observed by green fluorescent protein (GFP)-tagging approach. These results strongly suggest the beneficial impact of strain GW103 by inducing the alleviation of salt stress and development of stress tolerance in Chinese cabbage via plant-microbe interaction. PMID:26358119

  8. An integration programme of poverty alleviation and development with family planning.

    PubMed

    1997-04-01

    The State Council (the central government) recently issued a Circular for Speeding Up the Integration of Poverty Alleviation and Development with the Family Planning Programme during the Ninth Five-year Plan (1996-2000). The Circular was jointly submitted by the State Family Planning Commission and the Leading Group for Poverty Alleviation and Development. The document sets the two major tasks as solving the basic needs for food and clothing of the rural destitute and the control of over-rapid growth of China's population. Practice indicates that a close Integration Programme is the best way for impoverished farmers to alleviate poverty and become better-off. Overpopulation and low educational attainments and poor health quality of population in backward areas are the major factors retarding socioeconomic development. Therefore, it is inevitable to integrate poverty alleviation with family planning. It is a path with Chinese characteristics for a balanced population and sustainable socioeconomic development. The targets of the Integration Programme are as follows: The first is that preferential policies should be worked out to guarantee family planning acceptors, especially households with an only daughter or two daughters, are the first to be helped to eradicate poverty and become well-off. They should become good examples for other rural poor in practicing fewer but healthier births, and generating family income. The second target is that the population plans for the poor counties identified by the central government and provincial governments must be fulfilled. This should contribute to breaking the vicious circle of poverty leading to more children, in turn generating more poverty. The circular demands that more efforts should focus on the training of cadres for the Integrated Programme and on services for poor family planning acceptors.

  9. Assessing poverty-alleviation outcomes of an enterprise-led approach to sanitation.

    PubMed

    London, Ted; Esper, Heather

    2014-12-01

    Inadequate sanitation negatively affects the lives of billions of people in the base of the pyramid (BoP) in the developing world, and has a particularly substantial impact on the well-being of millions of young children. Given the magnitude of the challenge and the limitations of existing approaches, enterprise-led approaches to providing public goods are generating growing interest. Emphasizing convergent innovation, enterprises targeting the BoP are presented as potentially sustainable and scalable interventions that generate positive poverty-alleviation effects. Yet our understanding of who is affected, and how, remains limited. To begin to address this gap, we apply a multidimensional framework to an urban-based, sanitation-oriented BoP enterprise, focusing on its poverty-alleviation effects on young children. Our analysis indicates that the enterprise's effects include changes in capability, economic, and relationship well-being and that these changes can be positive or negative. We also find that the impact varies depending on the role of the stakeholder in the business model and the age of the child. Our results contribute to a better understanding of how to assess the effectiveness of a sanitation intervention and how to evaluate the poverty-alleviation implications of an enterprise-led approach. PMID:24697785

  10. The efficacy of Iranian herbal medicines in alleviating hot flashes: A systematic review

    PubMed Central

    Ghazanfarpour, Masumeh; Sadeghi, Ramin; Abdolahian, Somayeh; Latifnejad Roudsari, Robab

    2016-01-01

    Background: Hot flashes are the most common symptoms experienced by women around the time of menopause. Many women are interested in herbal medicines because of fear of side effects of hormone therapy. Objective: The aim of this systematic review was to assess the effectiveness of Iranian herbal medicines in alleviating hot flashes. Materials and Methods: MEDLINE (1966 to January 2015), Scopus (1996 to January 2015), and Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 1, 2015) were searched along with, SID, Iran Medex, Magiran, Medlib and Irandoc. Nineteen randomized controlled trials met the inclusion criteria. Results: Overall, studies showed that Anise (Pimpinella anisum), licorice (Glycyrrhizaglabra), Soy, Black cohosh, Red clover, Evening primrose, Flaxseed, Salvia officinalis, Passiflora، itex Agnus Castus, Piascledine (Avacado plus soybean oil), St. John's wort (Hypericum perforatum), and valerian can alleviate the side effects of hot flashes. Conclusion: This research demonstrated the efficacy of herbal medicines in alleviating hot flashes, which are embraced both with people and health providers of Iran Therefore, herbal medicine can be seen as an alternative treatment for women experiencing hot flashes. PMID:27294213

  11. Cost-Effectiveness of Payments for Ecosystem Services with Dual Goals of Environment and Poverty Alleviation

    NASA Astrophysics Data System (ADS)

    Gauvin, Crystal; Uchida, Emi; Rozelle, Scott; Xu, Jintao; Zhan, Jinyan

    2010-03-01

    The goal of this article is to understand strategies by which both the environmental and poverty alleviation objectives of PES programs can be achieved cost effectively. To meet this goal, we first create a conceptual framework to understand the implications of alternative targeting when policy makers have both environmental and poverty alleviation goals. We then use the Grain for Green program in China, the largest PES program in the developing world, as a case study. We also use a data set from a survey that we designed and implemented to evaluate the program. Using the data set we first evaluate what factors determined selection of program areas for the Grain for Green program. We then demonstrate the heterogeneity of parcels and households and examine the correlations across households and their parcels in terms of their potential environmental benefits, opportunity costs of participating, and the asset levels of households as an indicator of poverty. Finally, we compare five alternative targeting criteria and simulate their performance in terms of cost effectiveness in meeting both the environmental and poverty alleviation goals when given a fixed budget. Based on our simulations, we find that there is a substantial gain in the cost effectiveness of the program by targeting parcels based on the “gold standard,” i.e., targeting parcels with low opportunity cost and high environmental benefit managed by poorer households.

  12. Assessing poverty-alleviation outcomes of an enterprise-led approach to sanitation.

    PubMed

    London, Ted; Esper, Heather

    2014-12-01

    Inadequate sanitation negatively affects the lives of billions of people in the base of the pyramid (BoP) in the developing world, and has a particularly substantial impact on the well-being of millions of young children. Given the magnitude of the challenge and the limitations of existing approaches, enterprise-led approaches to providing public goods are generating growing interest. Emphasizing convergent innovation, enterprises targeting the BoP are presented as potentially sustainable and scalable interventions that generate positive poverty-alleviation effects. Yet our understanding of who is affected, and how, remains limited. To begin to address this gap, we apply a multidimensional framework to an urban-based, sanitation-oriented BoP enterprise, focusing on its poverty-alleviation effects on young children. Our analysis indicates that the enterprise's effects include changes in capability, economic, and relationship well-being and that these changes can be positive or negative. We also find that the impact varies depending on the role of the stakeholder in the business model and the age of the child. Our results contribute to a better understanding of how to assess the effectiveness of a sanitation intervention and how to evaluate the poverty-alleviation implications of an enterprise-led approach.

  13. Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion.

    PubMed

    Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

    2015-01-01

    Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0-3), but not the late stage after rUCCAO (day 4-32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD.

  14. Akt2 Knockout Alleviates Prolonged Caloric Restriction-Induced Change in Cardiac Contractile Function through Regulation of Autophagy

    PubMed Central

    Zhang, Yingmei; Han, Xuefeng; Hu, Nan; Huff, Anna F.; Gao, Feng; Ren, Jun

    2014-01-01

    Caloric restriction leads to changes in heart geometry and function although the underlying mechanism remains elusive. Autophagy, a conserved pathway for degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of Akt2 in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved. Wild-type (WT) and Akt2 knockout mice were caloric restricted (by 40%) for 30 weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties, autophagy and its regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased left ventricular mass, left ventricular diameters and cardiac output), cardiomyocyte contractile and intracellular Ca2+ properties associated with dampened SERCA2a phosphorylation, upregulated phospholamban and autophagy (Beclin-1, Atg7, LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK, Akt2 and the Akt downstream signal molecule TSC2, the effects of which with the exception of autophagy protein markers (Beclin-1, Atg7, LC3B) and AMPK were mitigated or significantly alleviated by Akt2 knockout. Lysosomal inhibition using bafilomycin A1 negated Akt2 knockout-induced protective effect on p62. Evaluation of downstream signaling molecules of Akt and AMPK including mTOR and ULK1 revealed that caloric restriction suppressed and promoted phosphorylation of mTOR and ULK1, respectively, without affecting total mTOR and ULK1 expression. Akt2 knockout significantly augmented caloric restriction-induced responses on mTOR and ULK1. Taken together, these data suggest a beneficial role of Akt2 knockout in preservation of cardiac homeostasis against prolonged caloric restriction-induced pathological changes possibly through facilitating autophagy. PMID:24368095

  15. The experience of cash transfers in alleviating childhood poverty in South Africa: mothers' experiences of the Child Support Grant.

    PubMed

    Zembe-Mkabile, Wanga; Surender, Rebecca; Surrender, Rebecca; Sanders, David; Jackson, Debra; Doherty, Tanya

    2015-01-01

    Cash transfer (CT) programmes are increasingly being used as policy instruments to address child poverty and child health outcomes in developing countries. As the largest cash-transfer programme in Africa, the South African Child Support Grant (CSG) provides an important opportunity to further understand how a CT of its kind works in a developing country context. We explored the experiences and views of CSG recipients and non-recipients from four diverse settings in South Africa. Four major themes emerged from the data: barriers to accessing the CSG; how the CSG is utilised and the ways in which it makes a difference; the mechanisms for supplementing the CSG; and the impact of not receiving the grant. Findings show that administrative factors continue to be the greatest barrier to CSG receipt, pointing to the need for further improvements in managing queues, waiting times and coordination between departments for applicants trying to submit their applications. Many recipients, especially those where the grant was the only source of income, acknowledged the importance of the CSG, while also emphasising its inadequacy. To maximise their impact, CT programmes such as the CSG need to be fully funded and form part of a broader basket of poverty alleviation strategies.

  16. The experience of cash transfers in alleviating childhood poverty in South Africa: Mothers' experiences of the Child Support Grant

    PubMed Central

    Zembe-Mkabile, Wanga; Surrender, Rebecca; Sanders, David; Jackson, Debra; Doherty, Tanya

    2015-01-01

    Cash transfer (CT) programmes are increasingly being used as policy instruments to address child poverty and child health outcomes in developing countries. As the largest cash-transfer programme in Africa, the South African Child Support Grant (CSG) provides an important opportunity to further understand how a CT of its kind works in a developing country context. We explored the experiences and views of CSG recipients and non-recipients from four diverse settings in South Africa. Four major themes emerged from the data: barriers to accessing the CSG; how the CSG is utilised and the ways in which it makes a difference; the mechanisms for supplementing the CSG; and the impact of not receiving the grant. Findings show that administrative factors continue to be the greatest barrier to CSG receipt, pointing to the need for further improvements in managing queues, waiting times and coordination between departments for applicants trying to submit their applications. Many recipients, especially those where the grant was the only source of income, acknowledged the importance of the CSG, while also emphasising its inadequacy. To maximise their impact, CT programmes such as the CSG need to be fully funded and form part of a broader basket of poverty alleviation strategies. PMID:25685927

  17. Electroacupuncture alleviates cerebral ischemia and reperfusion injury via modulation of the ERK1/2 signaling pathway

    PubMed Central

    Jin, Xiao-lu; Li, Peng-fei; Zhang, Chun-bing; Wu, Jin-ping; Feng, Xi-lian; Zhang, Ying; Shen, Mei-hong

    2016-01-01

    Electroacupuncture (EA) has anti-oxidative and anti-inflammatory actions, but whether the neuroprotective effect of EA against cerebral ischemia-reperfusion (I/R) injury involves modulation of the extracellular regulated kinase 1/2 (ERK1/2) signaling pathway is unclear. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats for 2 hours followed by reperfusion for 24 hours. A 30-minute period of EA stimulation was applied to both Baihui (DU20) and Dazhui (DU14) acupoints in each rat (10 mm EA penetration depth, continuous wave with a frequency of 3 Hz, and a current intensity of 1–3 mA) when reperfusion was initiated. EA significantly reduced infarct volume, alleviated neuronal injury, and improved neurological function in rats with MCAO. Furthermore, high mRNA expression of Bax and low mRNA expression of Bcl-2 induced by MCAO was prevented by EA. EA substantially restored total glutathione reductase (GR), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels. Additionally, Nrf2 and glutamylcysteine synthetase (GCS) expression levels were markedly increased by EA. Interestingly, the neuroprotective effects of EA were attenuated when ERK1/2 activity was blocked by PD98059 (a specific MEK inhibitor). Collectively, our findings indicate that activation of the ERK1/2 signaling pathway contributes to the neuroprotective effects of EA. Our study provides a better understanding of the regulatory mechanisms underlying the therapeutic effectiveness of EA. PMID:27630691

  18. Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide

    PubMed Central

    Paul, Manoj; Hemshekhar, Mahadevappa; Thushara, Ram M.; Sundaram, Mahalingam S.; NaveenKumar, Somanathapura K.; Naveen, Shivanna; Devaraja, Sannaningaiah; Somyajit, Kumar; West, Robert; Basappa; Nayaka, Siddaiah C.; Zakai, Uzma I.; Nagaraju, Ganesh; Rangappa, Kanchugarakoppal S.; Kemparaju, Kempaiah; Girish, Kesturu S.

    2015-01-01

    Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions. PMID:26083398

  19. Electroacupuncture alleviates cerebral ischemia and reperfusion injury via modulation of the ERK1/2 signaling pathway.

    PubMed

    Jin, Xiao-Lu; Li, Peng-Fei; Zhang, Chun-Bing; Wu, Jin-Ping; Feng, Xi-Lian; Zhang, Ying; Shen, Mei-Hong

    2016-07-01

    Electroacupuncture (EA) has anti-oxidative and anti-inflammatory actions, but whether the neuroprotective effect of EA against cerebral ischemia-reperfusion (I/R) injury involves modulation of the extracellular regulated kinase 1/2 (ERK1/2) signaling pathway is unclear. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats for 2 hours followed by reperfusion for 24 hours. A 30-minute period of EA stimulation was applied to both Baihui (DU20) and Dazhui (DU14) acupoints in each rat (10 mm EA penetration depth, continuous wave with a frequency of 3 Hz, and a current intensity of 1-3 mA) when reperfusion was initiated. EA significantly reduced infarct volume, alleviated neuronal injury, and improved neurological function in rats with MCAO. Furthermore, high mRNA expression of Bax and low mRNA expression of Bcl-2 induced by MCAO was prevented by EA. EA substantially restored total glutathione reductase (GR), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels. Additionally, Nrf2 and glutamylcysteine synthetase (GCS) expression levels were markedly increased by EA. Interestingly, the neuroprotective effects of EA were attenuated when ERK1/2 activity was blocked by PD98059 (a specific MEK inhibitor). Collectively, our findings indicate that activation of the ERK1/2 signaling pathway contributes to the neuroprotective effects of EA. Our study provides a better understanding of the regulatory mechanisms underlying the therapeutic effectiveness of EA. PMID:27630691

  20. Danshensu alleviates cardiac ischaemia/reperfusion injury by inhibiting autophagy and apoptosis via activation of mTOR signalling.

    PubMed

    Fan, Guanwei; Yu, Jiahui; Asare, Patrick Fordjour; Wang, Lingyan; Zhang, Han; Zhang, Boli; Zhu, Yan; Gao, Xiumei

    2016-10-01

    The traditional Chinese medicine Danshensu (DSS) has a protective effect on cardiac ischaemia/reperfusion (I/R) injury. However, the molecular mechanisms underlying the DSS action remain undefined. We investigated the potential role of DSS in autophagy and apoptosis using cardiac I/R injury models of cardiomyocytes and isolated rat hearts. Cultured neonatal rat cardiomyocytes were subjected to 6 hrs of hypoxia followed by 18 hrs of reoxygenation to induce cell damage. The isolated rat hearts were used to perform global ischaemia for 30 min., followed by 60 min. reperfusion. Ischaemia/reperfusion injury decreased the haemodynamic parameters on cardiac function, damaged cardiomyocytes or even caused cell death. Pre-treatment of DSS significantly improved cell survival and protected against I/R-induced deterioration of cardiac function. The improved cell survival upon DSS treatment was associated with activation of mammalian target of rapamycin (mTOR) (as manifested by increased phosphorylation of S6K and S6), which was accompanied with attenuated autophagy flux and decreased expression of autophagy- and apoptosis-related proteins (including p62, LC3-II, Beclin-1, Bax, and Caspase-3) at both protein and mRNA levels. These results suggest that alleviation of cardiac I/R injury by pre-treatment with DSS may be attributable to inhibiting excessive autophagy and apoptosis through mTOR activation. PMID:27385290

  1. Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats.

    PubMed

    Zuo, Xialin; Hou, Qinghua; Jin, Jizi; Zhan, Lixuan; Li, Xinyu; Sun, Weiwen; Lin, Kunqin; Xu, En

    2016-09-01

    Secondary degeneration in areas beyond ischemic foci can inhibit poststroke recovery. The cysteine protease Cathepsin B (CathB) regulates cell death and intracellular protein catabolism. To investigate the roles of CathB in the development of secondary degeneration in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after focal cerebral infarction, infarct volumes, immunohistochemistry and immunofluorescence, and Western blotting analyses were conducted in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats. We observed marked neuron loss and gliosis in the ipsilateral thalamus after dMCAO, and the expression of CathB and cleaved caspase-3 in the VPN was significantly upregulated; glial cells were the major source of CathB. Although it had no effect on infarct volume, delayed intracerebroventricular treatment with the membrane-permeable CathB inhibitor CA-074Me suppressed the expression of CathB and cleaved caspase-3 in ipsilateral VPN and accordingly alleviated the secondary degeneration. These data indicate that CathB mediates a novel mechanism of secondary degeneration in the VPN of the ipsilateral thalamus after focal cortical infarction and suggest that CathB might be a therapeutic target for the prevention of secondary degeneration in patients after stroke.

  2. Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice

    PubMed Central

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-01-01

    Although recent studies have reported that Lactobacillus rhamnosus GG (LGG), the most extensively studied probiotic strain, exerts an anti-hyperglycemic effect on several rodent models, the underlying mechanism remains unclear. In this study, twenty male C57BL/KsJ-db/db (db/db) mice were divided into 2 groups, LGG-treated and control group, which received a daily dose of LGG (1 × 108 CFU per mouse) and PBS orally for 4 weeks, respectively. We observed that glucose tolerance was significantly improved in LGG-treated db/db mice. Insulin-stimulated Akt phosphorylation and GLUT4 translocation were higher in skeletal muscle of LGG-treated mice relative to their controls. It was also observed that LGG treatment caused significant reductions in endoplasmic reticulum (ER) stress in skeletal muscle and M1-like macrophage activation in white adipose tissues. Our results indicate that the anti-diabetic effect of LGG in db/db mice is associated with alleviated ER stress and suppressed macrophage activation, resulting in enhanced insulin sensitivity. These findings suggest a therapeutic potential of probiotics for prevention and treatment of type 2 diabetes. PMID:26060355

  3. Rhubarb Enema Attenuates Renal Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats by Alleviating Indoxyl Sulfate Overload

    PubMed Central

    Lu, Fuhua; Liu, Xusheng; Zou, Chuan

    2015-01-01

    Aim To investigate the effects of rhubarb enema treatment using a 5/6 nephrectomized rat model and study its mechanisms. Methods Twenty-eight Sprague Dawley rats were divided into three groups: sham operation group (n = 8), 5/6 nephrectomized (5/6Nx) (n = 10), and 5/6Nx with rhubarb enema treatment (n = 10). The rhubarb enema was continuous for 1.0 month. Serum creatinine, serum indoxyl sulfate (IS) level, renal pathology, tubulointerstitial fibrosis, and renal oxidative stress were assessed. Results 5/6Nx rats showed increasing levels of serum creatinine and severe pathological lesions. Their serum creatinine levels obviously decreased after rhubarb enema treatment (P < 0.05 vs 5/6Nx group). The administration of rhubarb enema attenuated the histopathological changes in 5/6Nx rats. In addition, 5/6Nx rats showed an enhanced extent of tubulointerstitial fibrosis compared with sham rats, and administration of rhubarb enema to 5/6Nx rats ameliorated tubulointerstitial fibrosis. 5/6Nx rats showed increased serum levels of IS, renal oxidative stress, and NF-κB compared with sham rats, whereas administration of rhubarb enema to 5/6Nx rats decreased serum levels of IS, renal oxidative stress, and NF-κB levels. Conclusion Rhubarb enema treatment ameliorates tubulointerstitial fibrosis in the kidneys of 5/6Nx rats, most likely by alleviating IS overload and reducing kidney oxidative stress and inflammatory injury. PMID:26671452

  4. Trichosanthes dioica fruit ameliorates experimentally induced arsenic toxicity in male albino rats through the alleviation of oxidative stress.

    PubMed

    Bhattacharya, Sanjib; Haldar, Pallab Kanti

    2012-08-01

    The present work was focused to evaluate the ameliorative property of aqueous extract of Trichosanthes dioica fruit (AQ T. dioica fruit) against arsenic-induced toxicity in male Wistar albino rats. AQ T. dioica fruit was administered orally to rats at 50 and 100 mg/kg body weight for 20 consecutive days prior to oral administration of sodium arsenite (10 mg/kg) for 10 days. Then the rats were sacrificed for the evaluation of body weights, organ weights, hematological profile, serum biochemical profile, and hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation. Pretreatment with AQ T. dioica fruit at both doses markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profile in arsenic-treated animals. Further, AQ T. dioica fruit pretreatment significantly modulated all the aforesaid hepatic and renal biochemical perturbations and reduced DNA fragmentation in arsenic-intoxicated rats. Therefore, from the present findings, it can be concluded that T. dioica fruit possessed remarkable value in amelioration of arsenic-induced hepatic and renal toxicity, mediated by alleviation of arsenic-induced oxidative stress by multiple mechanisms in male albino rats.

  5. Natural organic matter-induced alleviation of the phytotoxicity to rice (Oryza sativa L.) caused by copper oxide nanoparticles.

    PubMed

    Peng, Cheng; Zhang, Hai; Fang, Huaxiang; Xu, Chen; Huang, Haomin; Wang, Yi; Sun, Lijuan; Yuan, Xiaofeng; Chen, Yingxu; Shi, Jiyan

    2015-09-01

    Natural organic matter (NOM) can interact with engineered nanoparticles (NPs) in the environment and modify their behavior and toxicity to organisms. In the present study, the phytotoxicity of copper oxide (CuO) NPs to rice seedlings in the presence of humic acid as a model NOM was investigated. The results showed that CuO NPs induced the inhibition of root elongation, aberrations in root morphology and ultrastructure, and losses of cell viability and membrane integrity. The adverse effects partly resulted from the generation of reactive oxygen species caused by CuO NPs, which led to lipid peroxidation, mitochondrial dysfunction, and programmed cell death in rice seedlings. However, all the phytotoxicity was alleviated with the addition of humic acid because humic acid coatings on nanoparticle surfaces enhanced electrostatic and steric repulsion between the CuO NPs and the plant cell wall/membrane, reducing contact between NPs and plant and CuO NP-induced oxidative damage to plant cells. The present study's results shed light on the mechanism underlying NP phytotoxicity and highlight the influence of NOM on the bioavailability and toxicity of NPs.

  6. Current developments in arbuscular mycorrhizal fungi research and its role in salinity stress alleviation: a biotechnological perspective.

    PubMed

    Kumar, Ashwani; Dames, Joanna F; Gupta, Aditi; Sharma, Satyawati; Gilbert, Jack A; Ahmad, Parvaiz

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF) form widespread symbiotic associations with 80% of known land plants. They play a major role in plant nutrition, growth, water absorption, nutrient cycling and protection from pathogens, and as a result, contribute to ecosystem processes. Salinity stress conditions undoubtedly limit plant productivity and, therefore, the role of AMF as a biological tool for improving plant salt stress tolerance, is gaining economic importance worldwide. However, this approach requires a better understanding of how plants and AMF intimately interact with each other in saline environments and how this interaction leads to physiological changes in plants. This knowledge is important to develop sustainable strategies for successful utilization of AMF to improve plant health under a variety of stress conditions. Recent advances in the field of molecular biology, "omics" technology and advanced microscopy can provide new insight about these mechanisms of interaction between AMF and plants, as well as other microbes. This review mainly discusses the effect of salinity on AMF and plants, and role of AMF in alleviation of salinity stress including insight on methods for AMF identification. The focus remains on latest advancements in mycorrhizal research that can potentially offer an integrative understanding of the role of AMF in salinity tolerance and sustainable crop production. PMID:24708070

  7. Use of lanthanides to alleviate the effects of metal ion-deficiency in Desmodesmus quadricauda (Sphaeropleales, Chlorophyta)

    PubMed Central

    Goecke, Franz; Jerez, Celia G.; Zachleder, Vilém; Figueroa, Félix L.; Bišová, Kateřina; Řezanka, Tomáš; Vítová, Milada

    2015-01-01

    Lanthanides are biologically non-essential elements with wide applications in technology and industry. Their concentration as environmental contaminants is, therefore, increasing. Although non-essential, lanthanides have been proposed (and even used) to produce beneficial effects in plants, even though their mechanisms of action are unclear. Recently, it was suggested that they may replace essential elements. We tested the effect of low concentrations of lanthanides on the common freshwater microalga Desmodesmus quadricauda, grown under conditions of metal ion-deficiency (lower calcium or manganese concentrations). Our goal was to test if lanthanides can replace essential metals in their functions. Physiological stress was recorded by studying growth and photosynthetic activity using a pulse amplitude modulation (PAM) fluorimeter. We found that nutrient stress reduced parameters of growth and photosynthesis, such as maximal quantum yield, relative electron transport rate, photon capturing efficiency and light saturation irradiance. After adding low concentrations of five lanthanides, we confirmed that they can produce a stimulatory effect on microalgae, depending on the nutrient (metal) deprivation. In the case of a calcium deficit, the addition of lanthanides partly alleviated the adverse effects, probably by a partial substitution of the element. In contrast, with manganese deprivation (and at even lower concentrations), lanthanides enhanced the deleterious effect on cellular growth and photosynthetic competence. These results show that lanthanides can replace essential elements, but their effects on microalgae depend on stress and the nutritional state of the microalgae, raising the possibility of environmental impacts at even low concentrations. PMID:25674079

  8. Electroacupuncture alleviates cerebral ischemia and reperfusion injury via modulation of the ERK1/2 signaling pathway

    PubMed Central

    Jin, Xiao-lu; Li, Peng-fei; Zhang, Chun-bing; Wu, Jin-ping; Feng, Xi-lian; Zhang, Ying; Shen, Mei-hong

    2016-01-01

    Electroacupuncture (EA) has anti-oxidative and anti-inflammatory actions, but whether the neuroprotective effect of EA against cerebral ischemia-reperfusion (I/R) injury involves modulation of the extracellular regulated kinase 1/2 (ERK1/2) signaling pathway is unclear. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats for 2 hours followed by reperfusion for 24 hours. A 30-minute period of EA stimulation was applied to both Baihui (DU20) and Dazhui (DU14) acupoints in each rat (10 mm EA penetration depth, continuous wave with a frequency of 3 Hz, and a current intensity of 1–3 mA) when reperfusion was initiated. EA significantly reduced infarct volume, alleviated neuronal injury, and improved neurological function in rats with MCAO. Furthermore, high mRNA expression of Bax and low mRNA expression of Bcl-2 induced by MCAO was prevented by EA. EA substantially restored total glutathione reductase (GR), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels. Additionally, Nrf2 and glutamylcysteine synthetase (GCS) expression levels were markedly increased by EA. Interestingly, the neuroprotective effects of EA were attenuated when ERK1/2 activity was blocked by PD98059 (a specific MEK inhibitor). Collectively, our findings indicate that activation of the ERK1/2 signaling pathway contributes to the neuroprotective effects of EA. Our study provides a better understanding of the regulatory mechanisms underlying the therapeutic effectiveness of EA.

  9. Evaluation of arbuscular mycorrhizal fungi capacity to alleviate abiotic stress of olive (Olea europaea L.) plants at different transplant conditions.

    PubMed

    Bompadre, María Josefina; Pérgola, Mariana; Fernández Bidondo, Laura; Colombo, Roxana Paula; Silvani, Vanesa Analía; Pardo, Alejandro Guillermo; Ocampo, Juan Antonio; Godeas, Alicia Margarita

    2014-01-01

    The capacity of roots to sense soil physicochemical parameters plays an essential role in maintaining plant nutritional and developmental functions under abiotic stress. These conditions generate reactive oxygen species (ROS) in plant tissues causing oxidation of proteins and lipids among others. Some plants have developed adaptive mechanisms to counteract such adverse conditions such as symbiotic association with arbuscular mycorrhizal fungi (AMF). AMF enhance plant growth and improve transplant survival by protecting host plants against environmental stresses. The aim of this study was to evaluate the alleviation of transplanting stress by two strains of Rhizophagus irregularis (GC2 and GA5) in olive. Our results show that olive plants have an additional energetic expense in growth due to an adaptative response to the growing stage and to the mycorrhizal colonization at the first transplant. However, at the second transplant the coinoculation improves olive plant growth and protects against oxidative stress followed by the GA5-inoculation. In conclusion, a combination of two AMF strains at the beginning of olive propagation produces vigorous plants successfully protected in field cultivation even with an additional cost at the beginning of growth.

  10. Evaluation of Arbuscular Mycorrhizal Fungi Capacity to Alleviate Abiotic Stress of Olive (Olea europaea L.) Plants at Different Transplant Conditions

    PubMed Central

    Bompadre, María Josefina; Pérgola, Mariana; Fernández Bidondo, Laura; Colombo, Roxana Paula; Silvani, Vanesa Analía; Pardo, Alejandro Guillermo; Ocampo, Juan Antonio; Godeas, Alicia Margarita

    2014-01-01

    The capacity of roots to sense soil physicochemical parameters plays an essential role in maintaining plant nutritional and developmental functions under abiotic stress. These conditions generate reactive oxygen species (ROS) in plant tissues causing oxidation of proteins and lipids among others. Some plants have developed adaptive mechanisms to counteract such adverse conditions such as symbiotic association with arbuscular mycorrhizal fungi (AMF). AMF enhance plant growth and improve transplant survival by protecting host plants against environmental stresses. The aim of this study was to evaluate the alleviation of transplanting stress by two strains of Rhizophagus irregularis (GC2 and GA5) in olive. Our results show that olive plants have an additional energetic expense in growth due to an adaptative response to the growing stage and to the mycorrhizal colonization at the first transplant. However, at the second transplant the coinoculation improves olive plant growth and protects against oxidative stress followed by the GA5-inoculation. In conclusion, a combination of two AMF strains at the beginning of olive propagation produces vigorous plants successfully protected in field cultivation even with an additional cost at the beginning of growth. PMID:24688382

  11. Evaluation of arbuscular mycorrhizal fungi capacity to alleviate abiotic stress of olive (Olea europaea L.) plants at different transplant conditions.

    PubMed

    Bompadre, María Josefina; Pérgola, Mariana; Fernández Bidondo, Laura; Colombo, Roxana Paula; Silvani, Vanesa Analía; Pardo, Alejandro Guillermo; Ocampo, Juan Antonio; Godeas, Alicia Margarita

    2014-01-01

    The capacity of roots to sense soil physicochemical parameters plays an essential role in maintaining plant nutritional and developmental functions under abiotic stress. These conditions generate reactive oxygen species (ROS) in plant tissues causing oxidation of proteins and lipids among others. Some plants have developed adaptive mechanisms to counteract such adverse conditions such as symbiotic association with arbuscular mycorrhizal fungi (AMF). AMF enhance plant growth and improve transplant survival by protecting host plants against environmental stresses. The aim of this study was to evaluate the alleviation of transplanting stress by two strains of Rhizophagus irregularis (GC2 and GA5) in olive. Our results show that olive plants have an additional energetic expense in growth due to an adaptative response to the growing stage and to the mycorrhizal colonization at the first transplant. However, at the second transplant the coinoculation improves olive plant growth and protects against oxidative stress followed by the GA5-inoculation. In conclusion, a combination of two AMF strains at the beginning of olive propagation produces vigorous plants successfully protected in field cultivation even with an additional cost at the beginning of growth. PMID:24688382

  12. [Alleviative effects of nitric oxide on the biological damage of spirulina platensis induced by enhanced ultraviolet-B].

    PubMed

    Xue, Lin-gui; Li, Shi-weng; Xu, Shi-jian; An, Li-zhe; Wang, Xun-ling

    2006-08-01

    Continuing depletion of the stratospheric ozone layer by atmospheric pollutants, in particular chlorofluorocarbons (CFCs), has resulted in an increasing incidence of solar UV-B (280-320 nm) at the Earth's surface. Enhanced UV-B radiation has been considered as important global environmental problem and results in important effects to mankind and the entire global ecosystem. Nitric oxide (NO) is not only a toxic molecule, one of reactive nitrogen species (RNS), but also an important redox-active signaling molecule. NO is really a double-edged sword, it can be either beneficial and activate defense responses in plants and animals or toxic, together with ROS. Besides those, NO can also act as a signal molecule and play very important roles in life of organisms. To study the effects of NO on the biological specific property of enhanced UV-B stressed Spirulina platensis, the chlorophyll-a, protein contents and biomass were investigated under enhanced UV-B radiation and its combination with different chemical treatment. The changes of chlorophyll-a, protein contents and biomass confirmed that 0.5 mmol/L sodium nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the biological damage of cyanobacteria-Spirulina platensis 794 caused by enhanced ultraviolet-B. Further results proved that NO significantly increase the content of protein and proline. Meanwhile, the accumulation of reduced glutathione (GSH) in S. platensis cells were raised under normal growth condition. But exogenous NO could decrease the increasing of reduced glutathione (GSH) in enhanced UV-B stressed S. platensis cells. These results suggest that NO has protective effect and can strongly alleviate biological damage caused by UV-B stress in S. platensis 794 cells. For the first time, reported the effect of NO on the regulating ability of biological damage of S. platensis induced by enhanced UV-B. Therefore, further investigations will be necessary to inquire into the interaction and

  13. Acute Limonene Toxicity in Escherichia coli Is Caused by Limonene Hydroperoxide and Alleviated by a Point Mutation in Alkyl Hydroperoxidase AhpC.

    PubMed

    Chubukov, Victor; Mingardon, Florence; Schackwitz, Wendy; Baidoo, Edward E K; Alonso-Gutierrez, Jorge; Hu, Qijun; Lee, Taek Soon; Keasling, Jay D; Mukhopadhyay, Aindrila

    2015-07-01

    Limonene, a major component of citrus peel oil, has a number of applications related to microbiology. The antimicrobial properties of limonene make it a popular disinfectant and food preservative, while its potential as a biofuel component has made it the target of renewable production efforts through microbial metabolic engineering. For both applications, an understanding of microbial sensitivity or tolerance to limonene is crucial, but the mechanism of limonene toxicity remains enigmatic. In this study, we characterized a limonene-tolerant strain of Escherichia coli and found a mutation in ahpC, encoding alkyl hydroperoxidase, which alleviated limonene toxicity. We show that the acute toxicity previously attributed to limonene is largely due to the common oxidation product limonene hydroperoxide, which forms spontaneously in aerobic environments. The mutant AhpC protein with an L-to-Q change at position 177 (AhpC(L177Q)) was able to alleviate this toxicity by reducing the hydroperoxide to a more benign compound. We show that the degree of limonene toxicity is a function of its oxidation level and that nonoxidized limonene has relatively little toxicity to wild-type E. coli cells. Our results have implications for both the renewable production of limonene and the applications of limonene as an antimicrobial. PMID:25934627

  14. Acute Limonene Toxicity in Escherichia coli Is Caused by Limonene Hydroperoxide and Alleviated by a Point Mutation in Alkyl Hydroperoxidase AhpC

    PubMed Central

    Chubukov, Victor; Mingardon, Florence; Schackwitz, Wendy; Baidoo, Edward E. K.; Alonso-Gutierrez, Jorge; Hu, Qijun; Lee, Taek Soon; Keasling, Jay D.

    2015-01-01

    Limonene, a major component of citrus peel oil, has a number of applications related to microbiology. The antimicrobial properties of limonene make it a popular disinfectant and food preservative, while its potential as a biofuel component has made it the target of renewable production efforts through microbial metabolic engineering. For both applications, an understanding of microbial sensitivity or tolerance to limonene is crucial, but the mechanism of limonene toxicity remains enigmatic. In this study, we characterized a limonene-tolerant strain of Escherichia coli and found a mutation in ahpC, encoding alkyl hydroperoxidase, which alleviated limonene toxicity. We show that the acute toxicity previously attributed to limonene is largely due to the common oxidation product limonene hydroperoxide, which forms spontaneously in aerobic environments. The mutant AhpC protein with an L-to-Q change at position 177 (AhpCL177Q) was able to alleviate this toxicity by reducing the hydroperoxide to a more benign compound. We show that the degree of limonene toxicity is a function of its oxidation level and that nonoxidized limonene has relatively little toxicity to wild-type E. coli cells. Our results have implications for both the renewable production of limonene and the applications of limonene as an antimicrobial. PMID:25934627

  15. Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

    PubMed Central

    2014-01-01

    Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

  16. Bone marrow derived mesenchymal stem cells alleviated brain injury via down-regulation of interleukin-1β in focal cerebral ischemic rats

    PubMed Central

    Zhao, Yansong; Wang, Xiaoli; Dong, Peng; Xu, Qinyan; Ma, Ze; Mu, Qingjie; Sun, Xihe; Jiang, Zhengchen; Wang, Xin

    2016-01-01

    Interleukin-1β (IL-1β) plays an important role in brain injury after focal ischemia, and bone marrow-derived mesenchymal stem cells (BMSCs) are capable of reducing the expression of IL-1β, we investigated the effects of BMSCs transplantation on brain edema and cerebral infarction as well as the underlying mechanisms via IL-1β. Male Sprague-Dawley rats were randomly divided into five groups: Normal + phosphate-buffered saline (PBS), middle cerebral artery occlusion (MCAO) + PBS, Normal + BMSCs, MCAO + BMSCs and MCAO + IL-1ra (an antagonist of IL-1β). BMSCs were transplanted 24 hours after MCAO, and brain edema was evaluated by Magnetic Resonance Imaging (MRI) and brain water content method after BMSCs transplantation. The expression of NeuN and AQP4 was analyzed by immunofluorescence staining. Protein level of AQP4 and IL-1β was detected by western blot analysis 48 hours after transplantation. The results showed that BMSCs transplantation reduced brain edema by measurement of brain water content and ADC Value of MRI, as well as the expression of AQP4 and IL-1β. It was also found that BMSCs transplantation could alleviate the cerebral infarction volume and neuronal damage. Both the brain edema and the cerebral infarction were associated with IL-1β expression. In conclusion, BMSCs transplantation was capable of alleviating brain edema as well as reducing cerebral infarction via down-regulation of IL-1β expression, thus repair the injured brain in focal cerebral ischemic rats. PMID:27186280

  17. Pea lectin receptor-like kinase functions in salinity adaptation without yield penalty, by alleviating osmotic and ionic stresses and upregulating stress-responsive genes.

    PubMed

    Vaid, Neha; Pandey, Prashant; Srivastava, Vineet Kumar; Tuteja, Narendra

    2015-05-01

    Lectin receptor-like kinases (LecRLKs) are members of RLK family composed of lectin-like extracellular recognition domain, transmembrane domain and cytoplasmic kinase domain. LecRLKs are plasma membrane proteins believed to be involved in signal transduction. However, most of the members of the protein family even in plants have not been functionally well characterized. Herein, we show that Pisum sativum LecRLK (PsLecRLK) localized in plasma membrane systems and/or other regions of the cell and its transcript upregulated under salinity stress. Overexpression of PsLecRLK in transgenic tobacco plants confers salinity stress tolerance by alleviating both the ionic as well the osmotic component of salinity stress. The transgenic plants show better tissue compartmentalization of Na(+) and higher ROS scavenging activity which probably results in lower membrane damage, improved growth and yield maintenance even under salinity stress. Also, expression of several genes involved in cellular homeostasis is perturbed by PsLecRLK overexpression. Alleviation of osmotic and ionic components of salinity stress along with reduced oxidative damage and upregulation of stress-responsive genes in transgenic plants under salinity stress conditions could be possible mechanism facilitating enhanced stress tolerance. This study presents PsLecRLK as a promising candidate for crop improvement and also opens up new avenue to investigate its signalling pathway.

  18. Acute Limonene Toxicity in Escherichia coli Is Caused by Limonene Hydroperoxide and Alleviated by a Point Mutation in Alkyl Hydroperoxidase AhpC.

    PubMed

    Chubukov, Victor; Mingardon, Florence; Schackwitz, Wendy; Baidoo, Edward E K; Alonso-Gutierrez, Jorge; Hu, Qijun; Lee, Taek Soon; Keasling, Jay D; Mukhopadhyay, Aindrila

    2015-07-01

    Limonene, a major component of citrus peel oil, has a number of applications related to microbiology. The antimicrobial properties of limonene make it a popular disinfectant and food preservative, while its potential as a biofuel component has made it the target of renewable production efforts through microbial metabolic engineering. For both applications, an understanding of microbial sensitivity or tolerance to limonene is crucial, but the mechanism of limonene toxicity remains enigmatic. In this study, we characterized a limonene-tolerant strain of Escherichia coli and found a mutation in ahpC, encoding alkyl hydroperoxidase, which alleviated limonene toxicity. We show that the acute toxicity previously attributed to limonene is largely due to the common oxidation product limonene hydroperoxide, which forms spontaneously in aerobic environments. The mutant AhpC protein with an L-to-Q change at position 177 (AhpC(L177Q)) was able to alleviate this toxicity by reducing the hydroperoxide to a more benign compound. We show that the degree of limonene toxicity is a function of its oxidation level and that nonoxidized limonene has relatively little toxicity to wild-type E. coli cells. Our results have implications for both the renewable production of limonene and the applications of limonene as an antimicrobial.

  19. He-Ne laser influenced actin filaments alleviate the damage of UV-B in wheat

    NASA Astrophysics Data System (ADS)

    Chen, Huize; Han, Rong

    2015-01-01

    This work investigated the use of a He-Ne laser in alleviating the damaging effects of ultraviolet-B (UV-B) radiation on wheat seedlings by influenced actin filaments. Triticum aestivum seedlings were irradiated with either enhanced UV-B (10.08 KJ m-2 d-1) or a combination of UV-B light and the He-Ne laser. Plants were also exposed to the He-Ne laser alone. In order to compare the effect of the He-Ne laser, red light (same power and wavelength as the He-Ne laser) treatment and the combined UV-B and red light treatment were added. Moreover, wheat seedlings were treated with actin special drugs, including cytochalasin B (CB) and jasplakinolide (JAS). We analyzed the growth of the seedlings, the distribution of actin filaments (AFs), DNA laddering and ACTIN expression in the different groups. The results showed that enhanced UV-B produced negative effects on the growth of wheat seedlings while implementing the He-Ne laser partially alleviated the injury. With the red light treatment, there are no positive effects. The ACTIN expression stayed the same in the different treatments, while the distribution and the protein content are different. The Fourier transform infrared (FTIR) microspectroscopic results further established significant changes in the chemical composition of the wall material. These results suggested that the He-Ne laser alleviated the damaging effects of UV-B radiation in wheat seedlings by changing the characteristics of the AFs.

  20. Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period

    PubMed Central

    Zhang, Mao; Zhan, Xiao L; Ma, Zi Y; Chen, Xing S; Cai, Qi Y

    2015-01-01

    Multiple sclerosis (MS) is a disease induced by demyelination in the central nervous system, and the remission period of MS is crucial for remyelination. In addition, abnormal levels of thyroid hormone (TH) have been identified in MS. However, in the clinic, insufficient attention has been paid to the role of TH in the remission period. Indeed, TH not only functions in the development of the brain but also affects myelination. Therefore, it is necessary to observe the effect of TH on remyelination during this period. A model of demyelination induced by cuprizone (CPZ) was used to observe the function of TH in remyelination during the remission period of MS. Through weighing and behavioral tests, we found that TH improved the physical symptoms of mice impaired by CPZ. Supplementation of TH led to the repair of myelin as detected by immunohistochemistry and western blot. In addition, a sufficient TH supply resulted in an increase in myelinated axons without affecting myelin thickness and g ratio in the corpus callosum, as detected by electron microscopy. Double immunostaining with myelin basic protein and neurofilament 200 (NF200) showed that the CPZ-induced impairment of axons was alleviated by TH. Conversely, insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of mitochondria. Furthermore, we found that an adequate supply of TH promoted the proliferation and differentiation of oligodendrocyte lineage cells by immunofluorescence, which was beneficial to remyelination. Further, we found that TH reduced the number of astrocytes without affecting microglia. Conclusively, it was shown that TH alleviated demyelination induced by CPZ by promoting the development of oligodendrocyte lineage cells and remyelination. The critical time for remyelination is the remission period of MS. TH plays a significant role in alleviating demyelination during the remission period in the clinical treatment of MS. PMID:25577802

  1. Potassium nitrate application alleviates sodium chloride stress in winter wheat cultivars differing in salt tolerance.

    PubMed

    Zheng, Yanhai; Jia, Aijun; Ning, Tangyuan; Xu, Jialin; Li, Zengjia; Jiang, Gaoming

    2008-09-29

    A sand culture experiment was conducted to answer the question whether or not exogenous KNO(3) can alleviate adverse effects of salt stress in winter wheat by monitoring plant growth, K(+)/Na(+) accumulation and the activity of some antioxidant enzymes. Seeds of two wheat cultivars (CVs), DK961 (salt-tolerant) and JN17 (salt-sensitive), were planted in sandboxes and controls germinated and raised with Hoagland nutrient solution (6 mM KNO(3), no NaCl). Experimental seeds were exposed to seven modified Hoagland solutions containing increased levels of KNO(3) (11, 16, 21 mM) or 100 mM NaCl in combination with the four KNO(3) concentrations (6, 11, 16 and 21 mM). Plants were harvested 30 d after imbibition, with controls approximately 22 cm in height. Both CVs showed significant reduction in plant height, root length and dry weight of shoots and roots under KNO(3) or NaCl stress. However, the combination of increased KNO(3) and NaCl alleviated symptoms of the individual salt stresses by improving growth of shoots and roots, reducing electrolyte leakage, malondialdehyde and soluble sugar contents and enhancing the activities of antioxidant enzymes. The salt-tolerant cultivar accumulated more K(+) in both shoots and roots compared with the higher Na(+) accumulation typical for the salt-sensitive cultivar. Soluble sugar content and activities of antioxidant enzymes were found to be more stable in the salt-tolerant cultivar. Our findings suggest that the optimal K(+)/Na(+) ratio of the nutrient solution should be 16:100 for both the salt-tolerant and the salt-sensitive cultivar under the experimental conditions used, and that the alleviation of NaCl stress symptoms through simultaneously applied elevated KNO(3) was more effective in the salt-tolerant than in the salt-sensitive cultivar.

  2. β-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe−/− Mice

    PubMed Central

    Gopal, Kaliappan; Nagarajan, Perumal; Jedy, Jose; Raj, Avinash T.; Gnanaselvi, S. Kalai; Jahan, Parveen; Sharma, Yogendra; Shankar, Esaki M.; Kumar, Jerald M.

    2013-01-01

    Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and β-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and β-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe−/− mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with α-tocopherol and β-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002) increased (2.24±0.20 mm) in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm). Interestingly, β-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, β-carotene significantly decreased the aortic diameter (1.33±0.12 mm) in the aneurysm-induced mice (β-carotene, P = 0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of β-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe−/− mice. PMID:23826202

  3. Tannic acid alleviates bulk and nanoparticle Nd2O3 toxicity in pumpkin: a physiological and molecular response.

    PubMed

    Chen, Guangcai; Ma, Chuanxin; Mukherjee, Arnab; Musante, Craig; Zhang, Jianfeng; White, Jason C; Dhankher, Om Parkash; Xing, Baoshan

    2016-11-01

    The effect of dissolved organic matter (DOM) on nanoparticle toxicity to plants is poorly understood. In this study, tannic acid (TA) was selected as a DOM surrogate to explore the mechanisms of neodymium oxide NPs (Nd2O3 NPs) phytotoxicity to pumpkin (Cucurbita maxima). The results from the tested concentrations showed that 100 mg L(-1) Nd2O3 NPs were significantly toxic to pumpkin in term of fresh biomass, and the similar results from the bulk particles and the ionic treatments were also evident. Exposure to 100 mg L(-1) of Nd2O3 NPs and BPs in 1/5 strength Hoagland's solution not only significantly inhibited pumpkin growth, but also decreased the S, Ca, K and Mg levels in plant tissues. However, 60 mg L(-1) TA significantly moderated the observed phytotoxicity, decreased Nd accumulation in the roots, and notably restored S, Ca, K and Mg levels in NPs and BPs treated pumpkin. TA at 60 mg L(-1) increased superoxide dismutase (SOD) activity in both roots (17.5%) and leaves (42.9%), and catalase (CAT) activity (243.1%) in the roots exposed to Nd2O3 NPs. This finding was confirmed by the observed up-regulation of transcript levels of SOD and CAT in Nd2O3 NPs treated pumpkin analyzed by quantitative reverse transcription polymerase chain reaction. These results suggest that TA alleviates Nd2O3 BPs/NPs toxicity through alteration of the particle surface charge, thus reducing the contact and uptake of NPs by pumpkin. In addition, TA promotes antioxidant enzymatic activity by elevating the transcript levels of genes involved in ROS scavenging. Our results shed light on the mechanisms underlying the influence of DOM on the bioavailability and toxicity of NPs to terrestrial plants.

  4. Fat Grafting in Burn Scar Alleviates Neuropathic Pain via Anti-Inflammation Effect in Scar and Spinal Cord.

    PubMed

    Huang, Shu-Hung; Wu, Sheng-Hua; Lee, Su-Shin; Chang, Kao-Ping; Chai, Chee-Yin; Yeh, Jwu-Lai; Lin, Sin-Daw; Kwan, Aij-Lie; David Wang, Hui-Min; Lai, Chung-Sheng

    2015-01-01

    Burn-induced neuropathic pain is complex, and fat grafting has reportedly improved neuropathic pain. However, the mechanism of fat grafting in improving neuropathic pain is unclear. Previous investigations have found that neuroinflammation causes neuropathic pain, and anti-inflammatory targeting may provide potential therapeutic opportunities in neuropathic pain. We hypothesized that fat grafting in burn scars improves the neuropathic pain through anti-inflammation. Burn-induced scar pain was confirmed using a mechanical response test 4 weeks after burn injuries, and autologous fat grafting in the scar area was performed simultaneously. After 4 weeks, the animals were sacrificed, and specimens were collected for the inflammation test, including COX-2, iNOS, and nNOS in the injured skin and spinal cord dorsal horns through immunohistochemistry and Western assays. Furthermore, pro-inflammatory cytokines (IL-1 β and TNF-α) in the spinal cord were collected. Double immunofluorescent staining images for measuring p-IκB, p-NFκB, p-JNK, and TUNEL as well as Western blots of AKT, Bax/Bcl-2 for the inflammatory process, and apoptosis were analyzed. Fat grafting significantly reduced COX2, nNOS, and iNOS in the skin and spinal cord dorsal horns, as well as IL-1β and TNF-α, compared with the burn group. Moreover, regarding the anti-inflammatory effect, the apoptosis cells in the spinal cord significantly decreased after the fat grafting in the burn injury group. Fat grafting was effective in treating burn-induced neuropathic pain through the alleviation of neuroinflammation and ameliorated spinal neuronal apoptosis. PMID:26368011

  5. Tannic acid alleviates bulk and nanoparticle Nd2O3 toxicity in pumpkin: a physiological and molecular response.

    PubMed

    Chen, Guangcai; Ma, Chuanxin; Mukherjee, Arnab; Musante, Craig; Zhang, Jianfeng; White, Jason C; Dhankher, Om Parkash; Xing, Baoshan

    2016-11-01

    The effect of dissolved organic matter (DOM) on nanoparticle toxicity to plants is poorly understood. In this study, tannic acid (TA) was selected as a DOM surrogate to explore the mechanisms of neodymium oxide NPs (Nd2O3 NPs) phytotoxicity to pumpkin (Cucurbita maxima). The results from the tested concentrations showed that 100 mg L(-1) Nd2O3 NPs were significantly toxic to pumpkin in term of fresh biomass, and the similar results from the bulk particles and the ionic treatments were also evident. Exposure to 100 mg L(-1) of Nd2O3 NPs and BPs in 1/5 strength Hoagland's solution not only significantly inhibited pumpkin growth, but also decreased the S, Ca, K and Mg levels in plant tissues. However, 60 mg L(-1) TA significantly moderated the observed phytotoxicity, decreased Nd accumulation in the roots, and notably restored S, Ca, K and Mg levels in NPs and BPs treated pumpkin. TA at 60 mg L(-1) increased superoxide dismutase (SOD) activity in both roots (17.5%) and leaves (42.9%), and catalase (CAT) activity (243.1%) in the roots exposed to Nd2O3 NPs. This finding was confirmed by the observed up-regulation of transcript levels of SOD and CAT in Nd2O3 NPs treated pumpkin analyzed by quantitative reverse transcription polymerase chain reaction. These results suggest that TA alleviates Nd2O3 BPs/NPs toxicity through alteration of the particle surface charge, thus reducing the contact and uptake of NPs by pumpkin. In addition, TA promotes antioxidant enzymatic activity by elevating the transcript levels of genes involved in ROS scavenging. Our results shed light on the mechanisms underlying the influence of DOM on the bioavailability and toxicity of NPs to terrestrial plants. PMID:27308847

  6. Discussion of an aeromechanical gust alleviation system to improve the ride comfort of light airplanes

    NASA Technical Reports Server (NTRS)

    Stewart, E. C.

    1975-01-01

    A discussion of an on-going NASA research project of a gust alleviation system to improve the ride comfort of a light airplane is presented. The discussion includes a description of the proposed system which uses auxiliary aerodynamic surfaces to drive the trailing-edge flaps. The results of analytical work on the effects of the system on stability and effectiveness of the system are presented. Static wind-tunnel tests of the system installed in a 1/6-scale model of a popular light airplane are also described. Problem areas which may need future investigation are discussed.

  7. Method for alleviating thermal stress damage in laminates. [metal matrix composites

    NASA Technical Reports Server (NTRS)

    Hoffman, C. A.; Weeton, J. W.; Orth, N. W. (Inventor)

    1980-01-01

    A method is provided for alleviating the stress damage in metallic matrix composites, such as laminated sheet or foil composites. Discontinuities are positively introduced into the interface between the layers so as to reduce the thermal stress produced by unequal expansion of the materials making up the composite. Although a number of discrete elements could be used to form one of the layers and thus carry out this purpose, the discontinuities are preferably produced by simply drilling holes in the metallic matrix layer or by forming grooves in a grid pattern in this layer.

  8. Side-force alleviation on slender, pointed forebodies at high angles of attack

    NASA Technical Reports Server (NTRS)

    Rao, D. M.

    1978-01-01

    A new device was proposed for alleviating high angle-of-attack side force on slender, pointed forebodies. A symmetrical pair of separation strips in the form of helical ridges are applied to the forebody to disrupt the primary lee-side vortices and thereby avoid the instability that produces vortex asymmetry. Preliminary wind tunnel tests at Mach 0.3 and Reynolds no. 5,250,000 on a variety of forebody configurations and on a wing-body combination at angles of attack up to 56 degrees, demonstrated the effectiveness of the device.

  9. Inertial and aerodynamic tuning of passive devices for load alleviation on wind turbines

    NASA Astrophysics Data System (ADS)

    Croce, A.; Gualdoni, F.; Montinari, P.; Riboldi, C. E. D.; Bottasso, C. L.

    2016-09-01

    This paper describes tuning concepts for passive devices aimed at load alleviation in wind turbines. Two types of tuning are considered: inertial and aerodynamic. The first concept is illustrated with reference to a passive flap, while the second with reference to a passive tip. In both cases, the goal is to reduce loads with devices that are as simple as possible, and do not require sensors nor actuators. The main features and critical issues of each concept are highlighted and illustrated with reference to a large conceptual 10 MW wind turbine.

  10. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury

    PubMed Central

    Ko, Miau-Hwa; Yang, Ming-Ling; Youn, Su-Chung; Tseng, To-Jung

    2016-01-01

    Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCγ) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCγ activation and mTOR-dependent PKCγ synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCγ- and phospho-mTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCγ activation and mTOR-dependent PKCγ synthesis participate

  11. Poverty alleviation strategies in eastern China lead to critical ecological dynamics.

    PubMed

    Zhang, Ke; Dearing, John A; Dawson, Terence P; Dong, Xuhui; Yang, Xiangdong; Zhang, Weiguo

    2015-02-15

    Poverty alleviation linked to agricultural intensification has been achieved in many regions but there is often only limited understanding of the impacts on ecological dynamics. A central need is to observe long term changes in regulating and supporting services as the basis for assessing the likelihood of sustainable agriculture or ecological collapse. We show how the analyses of 55 time-series of social, economic and ecological conditions can provide an evolutionary perspective for the modern Lower Yangtze River Basin region since the 1950s with powerful insights about the sustainability of modern ecosystem services. Increasing trends in provisioning ecosystem services within the region over the past 60 years reflect economic growth and successful poverty alleviation but are paralleled by steep losses in a range of regulating ecosystem services mainly since the 1980s. Increasing connectedness across the social and ecological domains after 1985 points to a greater uniformity in the drivers of the rural economy. Regime shifts and heightened levels of variability since the 1970s in local ecosystem services indicate progressive loss of resilience across the region. Of special concern are water quality services that have already passed critical transitions in several areas. Viewed collectively, our results suggest that the regional social-ecological system passed a tipping point in the late 1970s and is now in a transient phase heading towards a new steady state. However, the long-term relationship between economic growth and ecological degradation shows no sign of decoupling as demanded by the need to reverse an unsustainable trajectory.

  12. Specific immunotherapy plus Clostridium butyricum alleviates ulcerative colitis in patients with food allergy

    PubMed Central

    Bin Lan, B; Yang, Fan; Lu, Dong; Lin, Zhenlv

    2016-01-01

    The aberrant T cell activation plays an important role in the pathogenesis of intestinal inflammation, such as ulcerative colitis (UC). C. butyricum (Cb) is a probiotic and has been employed in the treatment of immune diseases. This study tests a hypothesis that specific immunotherapy (SIT) plus oral Cb (an over-the-counter probiotic) alleviates the UC symptoms. In this study, we conducted a randomized, double-blind, clinical study at our hospital. A total of 80 patients with relapsing-remitting ulcerative colitis and high levels of specific IgE antibody was randomly divided into 4 groups, and were treated with SIT or/and Cb, or placebo, respectively for 1 year. The results showed that a food antigen-specific Th2 polarization immune response was observed in UC patients with food allergy (FA). The frequency of regulatory B cells was significantly less in UC patients with FA as compared with healthy subjects. The UC patients with FA were treated with SIT and Cb showed significant amelioration of UC clinical symptoms, reduction of using UC-control medicines, and suppression of the skewed Th2 polarization, which did not occur in those treated with either SIT alone, or Cb alone, or placebo. In conclusion, combination of SIT and Cb efficiently alleviates a fraction of UC patients. PMID:27167186

  13. Hydrogen sulfide alleviates hypoxia-induced root tip death in Pisum sativum.

    PubMed

    Cheng, Wei; Zhang, Liang; Jiao, Chengjin; Su, Miao; Yang, Tao; Zhou, Lina; Peng, Renyi; Wang, Ranran; Wang, Chongying

    2013-09-01

    Flooding of soils often results in hypoxic conditions surrounding plant roots, which is a harmful abiotic stress to crops. Hydrogen sulfide (H2S) is a highly diffusible, gaseous molecule that modulates cell signaling and is involved in hypoxia signaling in animal cells. However, there have been no previous studies of H2S in plant cells in response to hypoxia. The effects of H2S on hypoxia-induced root tip death were studied in pea (Pisum sativum) via analysis of endogenous H2S and reactive oxygen species (ROS) levels. The activities of key enzymes involved in antioxidative and H2S metabolic pathways were determined using spectrophotometric assays. Ethylene was measured by gas chromatography. We found that exogenous H2S pretreatment dramatically alleviated hypoxia-induced root tip death by protecting root tip cell membranes from ROS damage induced by hypoxia and by stimulating a quiescence strategy through inhibiting ethylene production. Conversely, root tip death induced by hypoxia was strongly enhanced by inhibition of the key enzymes responsible for endogenous H2S biosynthesis. Our results demonstrated that exogenous H2S pretreatment significantly alleviates hypoxia-induced root tip death in pea seedlings and, therefore, enhances the tolerance of the plant to hypoxic stress.

  14. A Probiotic Preparation Alleviates Atopic Dermatitis-Like Skin Lesions in Murine Models.

    PubMed

    Kim, Min-Soo; Kim, Jin-Eung; Yoon, Yeo-Sang; Seo, Jae-Gu; Chung, Myung-Jun; Yum, Do-Young

    2016-04-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that encompasses immunologic responses. AD is frequently associated with elevated immunoglobulin (Ig) E levels, and common environmental factors contribute to its pathogenesis. Several recent studies have documented the role of specific lactic acid bacteria in the treatment and prevention of AD in humans and mice. In this study, the efficacy of Duolac ATP, a probiotic preparation, was determined in a mouse model with AD-like skin lesions. Alterations in the cytokine levels and histological staining suggested the alleviation of AD. The in vivo test showed that T helper (Th)2 cytokines, IgE, interleukin (IL)-4, and IL-5, were significantly downregulated, whereas Th1 cytokines, IL-12p40 and interferon (IFN)-γ, were upregulated in all groups of mice treated with Duolac ATP compared to that observed in the group of mice treated with 1-chloro-2,4-dinitrobenzene (DNCB) alone. Moreover, the scratch score decreased in all mice treated with Duolac ATP. Staining of the dorsal area of the mice in each group with hematoxylin and eosin and toluidine blue further confirmed the alleviation of AD in mice orally treated with Duolac ATP. These results suggest that Duolac ATP inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Thus, Duolac ATP is beneficial and effective for the treatment of AD-like skin lesions. PMID:27123166

  15. Exogenous spermidine alleviates oxidative damage and reduce yield loss in rice submerged at tillering stage

    PubMed Central

    Liu, Ming; Chu, Meijie; Ding, Yanfeng; Wang, Shaohua; Liu, Zhenghui; Tang, She; Ding, Chengqiang; Li, Ganghua

    2015-01-01

    To figure out whether spermidine (Spd) can alleviate oxidative damage on rice (Oryza sativa L.) caused by submergence stress, Ningjing 3 was used in this study. The results showed that, spraying Spd on rice leaves at a concentration of 0.5 mM promoted the growth recovery of rice after drainage, such as green leaves, tillers, and aboveground dry mass. According to physiological analysis, Spd accelerate restored chlorophylls damage by submergence, and decreased the rate of O2·− generation and H2O2 content, inhibited submergence-induced lipid peroxidation. Spd also helped to maintain antioxidant enzyme activities after drainage, such as superoxide dismutase, peroxidase, and GR, which ultimately improved the recovery ability of submerged rice. With the effect of Spd, the rice yields increased by 12.1, 17.9, 13.5, and 18.0%, of which submerged for 1, 3, 5, 7 days, respectively. It is supposed that exogenous Spd really has an alleviate effect on submergence damage and reduce yield loss of rice. PMID:26583021

  16. Alleviating versus stimulating effects of bicarbonate on the growth of Vallisneria natans under ammonia stress.

    PubMed

    Dou, Yanyan; Wang, Baozhong; Chen, Liangyan; Yin, Daqiang

    2013-08-01

    Bicarbonate plays a crucial role in limiting the growth of submersed aquatic macrophytes in eutrophic lakes, and high ammonia is often toxic to macrophytes. In order to evaluate the combined effect of HCO3 (-) and total ammonia (i.e., the total of NH3 and NH4 (+)) on submersed macrophytes Vallisneria natans, the growth and physiological response of V. natans in the presence of HCO3 (-) and ammonia were studied. The results showed that with the increase of ammonia, morphological parameters of V. natans declined. In contrast, increased HCO3 (-) concentration stimulated the growth of V. natans, especially when the NH4 (+)-N/NO3 (-)-N ratio was 1:7. High ammonia concentration induced excess free amino acids (FAA) accumulation and soluble carbohydrates (SC) depletion in plant tissues. However, the elevated HCO3 (-) promoted the synthesis of SC and rendered the decrease of FAA/SC ratio. The results also suggested that HCO3 (-) could partially alleviate the stress of ammonia, as evidenced by the decrease of FAA/SC ratio and the growth enhancement of V. natans when the ammonia concentration was 0.58 mg L(-1). Given the fact that HCO3 (-) is probably the dominant available carbon source in most eutrophic lakes, the ability of V. natans to use HCO3 (-) for SC synthesis may explain the alleviating effect of HCO3 (-) on V. natans under ammonia stress. PMID:23381797

  17. Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats

    PubMed Central

    Chai, Ning-Li; Zhang, Xiao-Bin; Chen, Si-Wen; Fan, Ke-Xing; Linghu, En-Qiang

    2016-01-01

    AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis. METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs’ phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs. RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization. CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN. PMID:27468195

  18. Dietary Astragalus polysaccharide alleviated immunological stress in broilers exposed to lipopolysaccharide.

    PubMed

    Liu, Lei; Shen, Jing; Zhao, Chao; Wang, Xiaofei; Yao, Junhu; Gong, Yuesheng; Yang, Xiaojun

    2015-01-01

    This study was conducted to investigate whether dietary Astragalus polysaccharide (APS) could alleviate immunological stress response of chickens after challenge with lipopolysaccharide (LPS). A total of 360 one-day-old commercial Arbor Acres broilers were randomly assigned in a 2 × 2 factorial design. The main factors were immunological stress (LPS or saline) and dietary APS (0 or 3g APS/kg feed). At 12, 14, 33 and 35 days of age, chickens were injected intramuscularly with either 500 μg/kg body weight of LPS or sterile saline. The results showed that the decreased daily feed intake and daily weight gain caused by immunological stress were dramatically attenuated by APS supplementation. The LPS challenge led to an increased mRNA abundance of TLR4, NF-κB, IL-1β, IL-6, avian uncoupling protein, α1-acid glycoprotein, hemopexin and y(+)LAT2. However, these negative effects of the LPS administration were ameliorated by APS supplementation. Moreover, dietary APS inhibited the LPS-induced depression of amino acid digestibilities. In conclusion, APS is able to alleviate LPS-induced immunological stress response in chickens. The beneficial effect may be attributed to suppressing the expression of pro-inflammatory cytokines through reducing the TLR4 and NF-κB genes transcription, and therewith improving energy and protein metabolism. PMID:25239195

  19. Cloning and Characterization of a Human Genomic Sequence that Alleviates Repeat-Induced Gene Silencing

    PubMed Central

    Miura, Osamu; Ohyama, Takashi; Shimizu, Noriaki

    2016-01-01

    Plasmids bearing a mammalian replication initiation region (IR) and a nuclear matrix attachment region (MAR) are spontaneously amplified in transfected mammalian cells, and such amplification generates chromosomal homogeneously staining regions (HSRs) or extrachromosomal double minutes (DMs). This method provides a novel, efficient, and rapid way to establish cells that stably produce high levels of recombinant proteins. However, because IR/MAR plasmids are amplified as repeats, they are frequently targeted by repeat-induced gene silencing (RIGS), which silences a variety of repeated sequences in transgenes and the genome. To address this problem, we developed a novel screening system using the IR/MAR plasmid to isolate human genome sequences that alleviate RIGS. The screen identified a 3,271 bp sequence (B-3-31) that elevated transgene expression without affecting the amplification process. Neither non-B structure (i.e., the inverted repeats or bending) nor known epigenetic modifier elements such as MARs, insulators, UCOEs, or STARs could explain the anti-silencing activity of B-3-31. Instead, the activity was distributed throughout the entire B-3-31 sequence, which was extremely A/T-rich and CpG-poor. Because B-3-31 effectively and reproducibly alleviated RIGS of repeated genes, it could be used to increase recombinant protein production. PMID:27078685

  20. Contributions to Active Buffeting Alleviation Programs by the NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Moses, Robert W.

    1999-01-01

    Buffeting is an aeroelastic phenomenon which plagues high performance aircraft, especially those with twin vertical tails like the F/A-18, at high angles of attack. This buffeting is a concern from fatigue and inspection points of view. By means of wind-tunnel and flight tests, this phenomenon is well studied to the point that buffet loads can be estimated and fatigue life can be increased by structural enhancements to the airframe. In more recent years, buffeting alleviation through active control of smart materials has been highly researched in wind-tunnel proof-of-concept demonstrations and full-scale ground tests using the F/A-18 as a test bed. Because the F/A-18 resides in fleets outside as well as inside the United States, these tests have evolved into international collaborative research activities with Australia and Canada, coordinated by the Air Force Research Laboratory (AFRL) and conducted under the auspices of The Technical Cooperation Program (TTCP). With the recent successes and advances in smart materials, the main focus of these buffeting alleviation tests has also evolved to a new level: utilize the F/A-18 as a prototype to mature smart materials for suppressing vibrations of aerospace structures. The role of the NASA Langley Research Center (LaRC) in these programs is presented.

  1. New Intervention Model of Regional Transfer Network System to Alleviate Crowding of Regional Emergency Medical Center

    PubMed Central

    2016-01-01

    Emergency department (ED) crowding is a serious problem in most tertiary hospitals in Korea. Although several intervention models have been established to alleviate ED crowding, they are limited to a single hospital-based approach. This study was conducted to determine whether the new regional intervention model could alleviate ED crowding in a regional emergency medical center. This study was designed as a “before and after study” and included patients who visited the tertiary hospital ED from November 2011 to October 2013. One tertiary hospital and 32 secondary hospitals were included in the study. A transfer coordinator conducted inter-hospital transfers from a tertiary hospital to a secondary hospital for suitable patients. A total of 1,607 and 2,591 patients transferred from a tertiary hospital before and after the study, respectively (P < 0.001). We found that the median ED length of stay (LOS) decreased significantly from 3.68 hours (interquartile range [IQR], 1.85 to 9.73) to 3.20 hours (IQR, 1.62 to 8.33) in the patient group after implementation of the Regional Transfer Network System (RTNS) (P < 0.001). The results of multivariate analysis showed a negative association between implementation of the RTNS and ED LOS (beta coefficient -0.743; 95% confidence interval -0.914 to -0.572; P < 0.001). In conclusion, the ED LOS in the tertiary hospital decreased after implementation of the RTNS. PMID:27134506

  2. Trichoderma spp. alleviate phytotoxicity in lettuce plants (Lactuca sativa L.) irrigated with arsenic-contaminated water.

    PubMed

    Caporale, Antonio G; Sommella, Alessia; Lorito, Matteo; Lombardi, Nadia; Azam, Shah M G G; Pigna, Massimo; Ruocco, Michelina

    2014-09-15

    The influence of two strains of Trichoderma (T. harzianum strain T22 and T. atroviride strain P1) on the growth of lettuce plants (Lactuca sativa L.) irrigated with As-contaminated water, and their effect on the uptake and accumulation of the contaminant in the plant roots and leaves, were studied. Accumulation of this non-essential element occurred mainly into the root system and reduced both biomass development and net photosynthesis rate (while altering the plant P status). Plant growth-promoting fungi (PGPF) of both Trichoderma species alleviated, at least in part, the phytotoxicity of As, essentially by decreasing its accumulation in the tissues and enhancing plant growth, P status and net photosynthesis rate. Our results indicate that inoculation of lettuce with selected Trichoderma strains may be helpful, beside the classical biocontrol application, in alleviating abiotic stresses such as that caused by irrigation with As-contaminated water, and in reducing the concentration of this metalloid in the edible part of the plant.

  3. NASA Langley Research Center's Contributions to International Active Buffeting Alleviation Programs

    NASA Technical Reports Server (NTRS)

    Moses, Robert W.

    2000-01-01

    Buffeting is an aeroelastic phenomenon which plagues high performance aircraft, especially those with twin vertical tails like the F/A-18, at high angles of attack. This buffeting is a concern from fatigue and inspection points of view. By means of wind-tunnel and flight tests, this phenomenon is well studied to the point that buffet loads can be estimated and fatigue life can be increased by structural enhancements to the airframe. In more recent years, buffeting alleviation through active control of smart materials has been highly researched in wind-tunnel proof-of-concept demonstrations and full-scale ground tests using the F/A-18 as a test bed. Because the F/A-18 resides in fleets outside as well as inside the United States, these tests have evolved into international collaborative research activities with Australia and Canada, coordinated by the Air Force Research Laboratory (AFRL) and conducted under the auspices of The Technical Cooperation Program (TTCP). With the recent successes and advances in smart materials, the main focus of these buffeting alleviation tests has also evolved to a new level: utilize the F/A-18 as a prototype to mature smart materials for suppressing vibrations of aerospace structures. The role of the NASA Langley Research Center (LaRC) in these programs is presented.

  4. Alleviation of side force on tangent-ogive forebodies using passive porosity

    NASA Technical Reports Server (NTRS)

    Bauer, Steven X. S.; Hemsch, Michael J.

    1992-01-01

    An experimental investigation to determine the effectiveness of porosity for alleviating side forces on forebodies was conducted in the NASA Langley Research Center 7 x 10 ft High-Speed Wind Tunnel. The study consisted of a comparison of experimental force, moment, and surface pressure results obtained on a fineness ratio 5.0 tangent-ogive porous forebody with 0.020 in. hole diameter and 22 percent porosity with results obtained on a solid forebody. The forebodies were tested with cylindrical afterbodies. The solid forebody was tested with transition grit to simulate fully turbulent conditions and without transition grit to simulate free transition conditions. The extent of porosity on the forebody was varied to determine the extent of porosity needed to alleviate side forces. Static longitudinal and lateral-directional stability and surface pressure data were obtained at Mach numbers of 0.2, 0.5, and 0.8. The angle of attack range was from 5 to 45 deg and roll angles from -90 to 180 deg. The solid forebody exhibited large asymmetries at moderate to high angles of attack causing large side forces and yawing moments. The porous forebody exhibited no significant side forces or yawing moments at any angle of attack tested.

  5. Cloning and Characterization of a Human Genomic Sequence that Alleviates Repeat-Induced Gene Silencing.

    PubMed

    Fukuma, Miki; Ganmyo, Yuto; Miura, Osamu; Ohyama, Takashi; Shimizu, Noriaki

    2016-01-01

    Plasmids bearing a mammalian replication initiation region (IR) and a nuclear matrix attachment region (MAR) are spontaneously amplified in transfected mammalian cells, and such amplification generates chromosomal homogeneously staining regions (HSRs) or extrachromosomal double minutes (DMs). This method provides a novel, efficient, and rapid way to establish cells that stably produce high levels of recombinant proteins. However, because IR/MAR plasmids are amplified as repeats, they are frequently targeted by repeat-induced gene silencing (RIGS), which silences a variety of repeated sequences in transgenes and the genome. To address this problem, we developed a novel screening system using the IR/MAR plasmid to isolate human genome sequences that alleviate RIGS. The screen identified a 3,271 bp sequence (B-3-31) that elevated transgene expression without affecting the amplification process. Neither non-B structure (i.e., the inverted repeats or bending) nor known epigenetic modifier elements such as MARs, insulators, UCOEs, or STARs could explain the anti-silencing activity of B-3-31. Instead, the activity was distributed throughout the entire B-3-31 sequence, which was extremely A/T-rich and CpG-poor. Because B-3-31 effectively and reproducibly alleviated RIGS of repeated genes, it could be used to increase recombinant protein production.

  6. Telmisartan alleviates rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats.

    PubMed

    Ma, L; Ji, J L; Ji, H; Yu, X; Ding, L J; Liu, K; Li, Y Q

    2010-07-01

    In the present study, we systematically examined telmisartan, an angiotensin AT(1) receptor antagonist, on rosiglitazone-induced bone loss in ovariectomized spontaneously hypertensive rats. Telmisartan (5 mg/kg/d, 90 days) was found to be able to significantly alleviate rosiglitazone (10 mg/kg/d, 90 days)-induced decrease in BMD of femur and lumbar vertebrae. The BMD changes were associated with positive biomechanical changes of lumbar vertebrae, improvements in microarchitecture of tibial metaphysic and normalized serum osteocalcin (OC) levels and urinary deoxypyridinoline/creatinine (DPD/Cr) ratio. MicroCT analysis of the tibial metaphysis showed that telmisartan significantly prevented the decreases in bone volume/tissue volume (BV/TV), connect density (Conn. D.), trabecular number (Tb. N.) and trabecular thickness (Tb. Th.), and increase in trabecular separation (Tb. Sp.) induced by rosiglitazone. Histomorphometric analysis also showed that telmisartan had protective effects on rosiglitazone-reduced bone formation indices such as histomorphometric bone volume fraction (BV/TV-Histo), mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR/BS). Our study clearly showed that telmisartan alleviated rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats. The relief of bone loss provides a possible therapeutic application of telmisartan with rosiglitazone for the treatment of elderly women patients afflicted with metabolic syndrome.

  7. Cloning and Characterization of a Human Genomic Sequence that Alleviates Repeat-Induced Gene Silencing.

    PubMed

    Fukuma, Miki; Ganmyo, Yuto; Miura, Osamu; Ohyama, Takashi; Shimizu, Noriaki

    2016-01-01

    Plasmids bearing a mammalian replication initiation region (IR) and a nuclear matrix attachment region (MAR) are spontaneously amplified in transfected mammalian cells, and such amplification generates chromosomal homogeneously staining regions (HSRs) or extrachromosomal double minutes (DMs). This method provides a novel, efficient, and rapid way to establish cells that stably produce high levels of recombinant proteins. However, because IR/MAR plasmids are amplified as repeats, they are frequently targeted by repeat-induced gene silencing (RIGS), which silences a variety of repeated sequences in transgenes and the genome. To address this problem, we developed a novel screening system using the IR/MAR plasmid to isolate human genome sequences that alleviate RIGS. The screen identified a 3,271 bp sequence (B-3-31) that elevated transgene expression without affecting the amplification process. Neither non-B structure (i.e., the inverted repeats or bending) nor known epigenetic modifier elements such as MARs, insulators, UCOEs, or STARs could explain the anti-silencing activity of B-3-31. Instead, the activity was distributed throughout the entire B-3-31 sequence, which was extremely A/T-rich and CpG-poor. Because B-3-31 effectively and reproducibly alleviated RIGS of repeated genes, it could be used to increase recombinant protein production. PMID:27078685

  8. Application of an adaptive blade control algorithm to a gust alleviation system

    NASA Technical Reports Server (NTRS)

    Saito, S.

    1984-01-01

    The feasibility of an adaptive control system designed to alleviate helicopter gust induced vibration was analytically investigated for an articulated rotor system. This control system is based on discrete optimal control theory, and is composed of a set of measurements (oscillatory hub forces and moments), an identification system using a Kalman filter, a control system based on the minimization of the quadratic performance function, and a simulation system of the helicopter rotor. The gust models are step and sinusoidal vertical gusts. Control inputs are selected at the gust frequency, subharmonic frequency, and superharmonic frequency, and are superimposed on the basic collective and cyclic control inputs. The response to be reduced is selected to be that at the gust frequency because this is the dominant response compared with sub- and superharmonics. Numerical calculations show that the adaptive blade pitch control algorithm satisfactorily alleviates the hub gust response. Almost 100 percent reduction of the perturbation thrust response to a step gust and more than 50 percent reduction to a sinusoidal gust are achieved in the numerical simulations.

  9. Application of an adaptive blade control algorithm to a gust alleviation system

    NASA Technical Reports Server (NTRS)

    Saito, S.

    1983-01-01

    The feasibility of an adaptive control system designed to alleviate helicopter gust induced vibration was analytically investigated for an articulated rotor system. This control system is based on discrete optimal control theory, and is composed of a set of measurements (oscillatory hub forces and moments), an identification system using a Kalman filter, a control system based on the minimization of the quadratic performance function, and a simulation system of the helicopter rotor. The gust models are step and sinusoidal vertical gusts. Control inputs are selected at the gust frequency, subharmonic frequency, and superharmonic frequency, and are superimposed on the basic collective and cyclic control inputs. The response to be reduced is selected to be that at the gust frequency because this is the dominant response compared with sub- and superharmonics. Numerical calculations show that the adaptive blade pitch control algorithm satisfactorily alleviates the hub gust response. Almost 100% reduction of the perturbation thrust response to a step gust and more than 50% reduction to a sinusoidal gust are achieved in the numerical simulations.

  10. Dietary Astragalus polysaccharide alleviated immunological stress in broilers exposed to lipopolysaccharide.

    PubMed

    Liu, Lei; Shen, Jing; Zhao, Chao; Wang, Xiaofei; Yao, Junhu; Gong, Yuesheng; Yang, Xiaojun

    2015-01-01

    This study was conducted to investigate whether dietary Astragalus polysaccharide (APS) could alleviate immunological stress response of chickens after challenge with lipopolysaccharide (LPS). A total of 360 one-day-old commercial Arbor Acres broilers were randomly assigned in a 2 × 2 factorial design. The main factors were immunological stress (LPS or saline) and dietary APS (0 or 3g APS/kg feed). At 12, 14, 33 and 35 days of age, chickens were injected intramuscularly with either 500 μg/kg body weight of LPS or sterile saline. The results showed that the decreased daily feed intake and daily weight gain caused by immunological stress were dramatically attenuated by APS supplementation. The LPS challenge led to an increased mRNA abundance of TLR4, NF-κB, IL-1β, IL-6, avian uncoupling protein, α1-acid glycoprotein, hemopexin and y(+)LAT2. However, these negative effects of the LPS administration were ameliorated by APS supplementation. Moreover, dietary APS inhibited the LPS-induced depression of amino acid digestibilities. In conclusion, APS is able to alleviate LPS-induced immunological stress response in chickens. The beneficial effect may be attributed to suppressing the expression of pro-inflammatory cytokines through reducing the TLR4 and NF-κB genes transcription, and therewith improving energy and protein metabolism.

  11. Sodium chloride alleviates cadmium toxicity by reducing nitric oxide accumulation in tobacco.

    PubMed

    Zhang, Binglin; Shang, Shenghua; Jabben, Zahra; Zhang, Guoping

    2014-12-01

    Nitric oxide (NO) is involved in regulating the response of plants to Cd toxicity. In this study, we examined possible involvement of NO in the alleviation of Cd toxicity by NaCl in tobacco plants. Two independent experiments were conducted to investigate the changes of NO accumulation and Cd concentration in tobacco plants after the addition of a NO donor, sodium nitroprusside dehydrate (SNP), or a NO inhibitor, nitro-l-arginine methyl ester (l-NAME) in the solution containing NaCl and Cd. NO accumulation in tobacco roots was enhanced when plants were exposed to Cd, but reduced in the treatments of NaCl or l-NAME. NO production was not enhanced even when SNP (NO donor) was added to the solution containing Cd and NaCl. Root number was reduced in plants exposed to Cd, and increased by the addition of NaCl and reduced by the addition of SNP. Addition of NaCl or l-NAME to the Cd-containing solution reduced Cd concentration in plant tissues, with l-NAME having a more dramatic effect. It can be concluded that alleviation of Cd toxicity by NaCl contributed to reduction of NO accumulation in plants.

  12. A Probiotic Preparation Alleviates Atopic Dermatitis-Like Skin Lesions in Murine Models

    PubMed Central

    Kim, Min-Soo; Kim, Jin-Eung; Yoon, Yeo-Sang; Seo, Jae-Gu; Chung, Myung-Jun; Yum, Do-Young

    2016-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that encompasses immunologic responses. AD is frequently associated with elevated immunoglobulin (Ig) E levels, and common environmental factors contribute to its pathogenesis. Several recent studies have documented the role of specific lactic acid bacteria in the treatment and prevention of AD in humans and mice. In this study, the efficacy of Duolac ATP, a probiotic preparation, was determined in a mouse model with AD-like skin lesions. Alterations in the cytokine levels and histological staining suggested the alleviation of AD. The in vivo test showed that T helper (Th)2 cytokines, IgE, interleukin (IL)-4, and IL-5, were significantly downregulated, whereas Th1 cytokines, IL-12p40 and interferon (IFN)-γ, were upregulated in all groups of mice treated with Duolac ATP compared to that observed in the group of mice treated with 1-chloro-2,4-dinitrobenzene (DNCB) alone. Moreover, the scratch score decreased in all mice treated with Duolac ATP. Staining of the dorsal area of the mice in each group with hematoxylin and eosin and toluidine blue further confirmed the alleviation of AD in mice orally treated with Duolac ATP. These results suggest that Duolac ATP inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Thus, Duolac ATP is beneficial and effective for the treatment of AD-like skin lesions. PMID:27123166

  13. Role of Ulva lactuca Extract in Alleviation of Salinity Stress on Wheat Seedlings

    PubMed Central

    Ibrahim, Wael M.; Ali, Refaat M.; Hemida, Khaulood A.; Sayed, Makram A.

    2014-01-01

    Seaweeds are potentially excellent sources of highly bioactive materials that could represent useful leads in the alleviation of salinity stress. The effects of presoaking wheat grains in water extract of Ulva lactuca on growth, some enzymatic activities, and protein pattern of salinized plants were investigated in this study. Algal presoaking of grains demonstrated a highly significant enhancement in the percentage of seed germination and growth parameters. The activity of superoxide dismutase (SOD) and catalase (CAT) increased with increasing the algal extract concentration while activity of ascorbate peroxidase (APX) and glutathione reductase (GR) was decreased with increasing concentration of algal extract more than 1% (w/v). The protein pattern of wheat seedling showed 12 newly formed bands as result of algal extract treatments compared with control. The bioactive components in U. lactuca extract such as ascorbic acid, betaine, glutathione, and proline could potentially participate in the alleviation of salinity stress. Therefore, algal presoaking is proved to be an effective technique to improve the growth of wheat seedlings under salt stress conditions. PMID:25436231

  14. Trichoderma spp. alleviate phytotoxicity in lettuce plants (Lactuca sativa L.) irrigated with arsenic-contaminated water.

    PubMed

    Caporale, Antonio G; Sommella, Alessia; Lorito, Matteo; Lombardi, Nadia; Azam, Shah M G G; Pigna, Massimo; Ruocco, Michelina

    2014-09-15

    The influence of two strains of Trichoderma (T. harzianum strain T22 and T. atroviride strain P1) on the growth of lettuce plants (Lactuca sativa L.) irrigated with As-contaminated water, and their effect on the uptake and accumulation of the contaminant in the plant roots and leaves, were studied. Accumulation of this non-essential element occurred mainly into the root system and reduced both biomass development and net photosynthesis rate (while altering the plant P status). Plant growth-promoting fungi (PGPF) of both Trichoderma species alleviated, at least in part, the phytotoxicity of As, essentially by decreasing its accumulation in the tissues and enhancing plant growth, P status and net photosynthesis rate. Our results indicate that inoculation of lettuce with selected Trichoderma strains may be helpful, beside the classical biocontrol application, in alleviating abiotic stresses such as that caused by irrigation with As-contaminated water, and in reducing the concentration of this metalloid in the edible part of the plant. PMID:25046759

  15. An Approach to Alleviate the False Alarm in Building Change Detection from Urban Vhr Image

    NASA Astrophysics Data System (ADS)

    Chen, J.; Hou, J. L.; Deng, M.

    2016-06-01

    Building change detection from very-high-resolution (VHR) urban remote sensing image frequently encounter the challenge of serious false alarm caused by different illumination or viewing angles in bi-temporal images. An approach to alleviate the false alarm in urban building change detection is proposed in this paper. Firstly, as shadows casted by urban buildings are of distinct spectral and shape feature, it adopts a supervised object-based classification technique to extract them in this paper. Secondly, on the opposite direction of sunlight illumination, a straight line is drawn along the principal orientation of building in every extracted shadow region. Starting from the straight line and moving toward the sunlight direction, a rectangular area is constructed to cover partial shadow and rooftop of each building. Thirdly, an algebra and geometry invariant based method is used to abstract the spatial topological relationship of the potential unchanged buildings from all central points of the rectangular area. Finally, based on an oriented texture curvature descriptor, an index is established to determine the actual false alarm in building change detection result. The experiment results validate that the proposed method can be used as an effective framework to alleviate the false alarm in building change detection from urban VHR image.

  16. Brassinosteroid alleviates polychlorinated biphenyls-induced oxidative stress by enhancing antioxidant enzymes activity in tomato.

    PubMed

    Ahammed, Golam Jalal; Ruan, Yi-Ping; Zhou, Jie; Xia, Xiao-Jian; Shi, Kai; Zhou, Yan-Hong; Yu, Jing-Quan

    2013-03-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants often found in the atmosphere. Phytoremediation of airborne PCBs is an emerging new concept to minimize potential human exposure. However, effects of atmospheric PCBs on plant growth, photosynthesis and antioxidant defence system are poorly understood area. Brassinosteroids have been reported to alleviate different abiotic stresses including organic pollutants-induced stress. Hence, we studied the effects of PCBs and 24-epibrassinolide (EBR) on biomass accumulation, photosynthetic machinery and antioxidant system in tomato plants. PCBs (0.4, 2.0 and 10 μg/l) mist spray significantly decreased dry weight, photosynthesis, chlorophyll contents in a dose dependent manner. Both stomatal and non-stomatal factors were involved in PCBs-induced photosynthetic inhibition. Likewise, the maximal photochemical efficiency of PSII (Fv/Fm), the quantum efficiency of PSII photochemistry (Φ(PSII)) and photochemical quenching coefficient were increasingly decreased by various levels of PCBs, suggesting an induction of photoinhibition. Increased accumulation of H(2)O(2) and O(2)(-) accompanied with high lipid peroxidation confirmed occurrence of oxidative stress upon PCBs exposure. Meanwhile, antioxidant enzymes activity was decreased following exposure to PCBs. Foliar application of EBR (100 nM) increased biomass, photosynthetic capacity, chlorophyll contents and alleviated photoinhibition by enhancing Fv/Fm, Φ(PSII) and qP. EBR significantly decreased harmful ROS accumulation and lipid peroxidation through the induction of antioxidant enzymes activity. Our results suggest a protective role of EBR against PCBs stress which may strengthen phytoremediation approaches by enhancing plant tolerance.

  17. Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

    PubMed

    Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

    2015-04-01

    Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

  18. Selenium and spermine alleviate cadmium induced toxicity in the red seaweed Gracilaria dura by regulating antioxidants and DNA methylation.

    PubMed

    Kumar, Manoj; Bijo, A J; Baghel, Ravi S; Reddy, C R K; Jha, Bhavanath

    2012-02-01

    The protective role of exogenously supplied selenium (Se) and polyamines (PAs) such as putrescine (Put) and spermine (Spm) in detoxifying the cadmium (Cd) induced toxicity was studied in the marine red alga Gracilaria dura in laboratory conditions. The Cd exposure (0.4 mM) impede the growth of alga while triggering the reactive oxygen species (ROS viz. O(2)(•-) and H(2)O(2)) generation, inhibition of antioxidant system, and enhancing the lipoxygenase (LOX) activity, malondialdehyde (MDA) level and demethylation of DNA. Additions of Se (50 μM) and/or Spm (1 mM) to the culture medium in contrast to Put, efficiently ameliorated the Cd toxicity by decreasing the accumulation of ROS and MDA contents, while restoring or enhancing the level of enzymatic and nonenzymatic antioxidants and their redox ratio, phycobiliproteins and phytochelatins, over the controls. The isoforms of antioxidant enzymes namely superoxide dismutase (Mn-SOD, ~150 kDa; Fe-SOD ~120 kDa), glutathione peroxidase (GSH-Px, ~120 and 140 kDa), glutathione reductase (GR, ~110 kDa) regulated differentially to Se and/or Spm supplementation. Furthermore, it has also resulted in enhanced levels of endogenous PAs (specially free and bound insoluble Put and Spm) and n-6 PUFAs (C20-3, n-6 and C20-4, n-6). This is for the first time wherein Se and Spm were found to regulate the stabilization of DNA methylation by reducing the events of cytosine demethylation in a mechanism to alleviate the Cd stress in marine alga. The present findings reveal that both Se and Spm play a crucial role in controlling the Cd induced oxidative stress in G. dura.

  19. A recombinant slow-release PACAP-derived peptide alleviates diabetes by promoting both insulin secretion and actions.

    PubMed

    Ma, Yi; Fang, Shixiong; Zhao, Shaojun; Wang, Xiaoli; Wang, Dongbo; Ma, Min; Luo, Tianjie; Hong, An

    2015-05-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroendocrine factor that activates both the receptor VPAC1 and VPAC2. Although PACAP possesses insulinotropic activity, its therapeutic application is limited by the extremely short acting half-life and the stimulatory effects on glucagon production via a VPAC1-dependent mechanism. Here we have generated a recombinant PACAP-derived peptide (named as MHDBAY) comprising a 7-mer albumin-binding peptide identified by phage display screening (WQRPSSW), a cleavage peptide for Factor Xa (FXa) and dipeptidyl peptidase IV (DPP IV), and a 31-amino acid PACAP-derived peptide (DBAY) that can specifically bind to the VPAC2 receptor. MHDBAY binds to albumin both in vitro and in animals, thereby leading to an orderly slow release of the active peptide DBAY via the protease cleavage. In db/db mice and New Zealand rabbits, the circulating half-life of MHDBAY is approximately 12.2 h, which is 146-fold longer than DBAY (∼5 min). A single injection of MHDBAY into db/db diabetic mice markedly increases insulin secretion, thereby leading to sustained alleviation of hyperglycemia. The potency and duration of MHDBAY in increasing insulin secretion and decreasing blood glucose levels is much greater than Exendin-4, an anti-diabetic drug via its insulinotropic actions. Furthermore, chronic administration of MHDBAY by daily injection for 8 weeks significantly improves both glucose and lipid profiles and also greatly increases insulin sensitivity in db/db mice. These findings suggest that serum albumin may act as a reservoir for slow-release of small bioactive peptides, and MHDBAY may represent a promising therapeutic peptide for diabetes.

  20. Ocean acidification alleviates low-temperature effects on growth and photosynthesis of the red alga Neosiphonia harveyi (Rhodophyta).

    PubMed

    Olischläger, Mark; Wiencke, Christian

    2013-12-01

    This study aimed to examine interactive effects between ocean acidification and temperature on the photosynthetic and growth performance of Neosiphonia harveyi. N. harveyi was cultivated at 10 and 17.5 °C at present (~380 µatm), expected future (~800 µatm), and high (~1500 µatm) pCO2. Chlorophyll a fluorescence, net photosynthesis, and growth were measured. The state of the carbon-concentrating mechanism (CCM) was examined by pH-drift experiments (with algae cultivated at 10 °C only) using ethoxyzolamide, an inhibitor of external and internal carbonic anhydrases (exCA and intCA, respectively). Furthermore, the inhibitory effect of acetazolamide (an inhibitor of exCA) and Tris (an inhibitor of the acidification of the diffusive boundary layer) on net photosynthesis was measured at both temperatures. Temperature affected photosynthesis (in terms of photosynthetic efficiency, light saturation point, and net photosynthesis) and growth at present pCO2, but these effects decreased with increasing pCO2. The relevance of the CCM decreased at 10 °C. A pCO2 effect on the CCM could only be shown if intCA and exCA were inhibited. The experiments demonstrate for the first time interactions between ocean acidification and temperature on the performance of a non-calcifying macroalga and show that the effects of low temperature on photosynthesis can be alleviated by increasing pCO2. The findings indicate that the carbon acquisition mediated by exCA and acidification of the diffusive boundary layer decrease at low temperatures but are not affected by the cultivation level of pCO2, whereas the activity of intCA is affected by pCO2. Ecologically, the findings suggest that ocean acidification might affect the biogeographical distribution of N. harveyi.

  1. Clinical challenges in mechanical ventilation.

    PubMed

    Goligher, Ewan C; Ferguson, Niall D; Brochard, Laurent J

    2016-04-30

    Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non-invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator-induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. PMID:27203509

  2. Butyrate alleviates metabolic impairments and protects pancreatic β cell function in pregnant mice with obesity.

    PubMed

    Li, Hua-Ping; Chen, Xuan; Li, Ming-Qing

    2013-01-01

    The relative or absolute deficiency of pancreatic β-cell mass function underlies the pathogenesis of diabetes. It is necessary to alleviate the metabolic stress and reduce the demand for insulin to decrease the effects of mutations affecting β-cell expansion. Butyrate is a natural nutrient existed in food and can also be produced physiologically through the intestinal fermentation of fiber. Pregnancy and obesity model would be helpful for understanding how β-cell adapt to insulin resistance and how butyrate alleviate the metabolic impairment and protect pancreatic β cell function in pregnant mice with obesity. C57BL/6J female mice were divided into three groups and fed with high fat food (HF group, 40% energy from fat), high fat with sodium butyrate food (HSF group, 95% HF with 5% butyrate), or control food (CF group, 14% energy from fat), respectively. The feeding would last for 14 weeks before mating and throughout the gestation period. A subset of dams were sacrificed at gestational day (GD) 14.5 to evaluate the changes of metabolism and β-cell function, mass, proliferation and apoptosis, inflammatory reaction of islet from different diet. Pancreases were double immuno-labeled to assess the islet morphology, insulin expression, expression of proliferation gene PCNA and anti-apoptosis gene bcl-2. Moreover, we detected the expression of NF-κB, phosphorylated NF-κB (pNF-κB) to evaluate the islet inflammatory response with immunohistochemistry. Mice fed with HSF showed obviously changes including the decreased values of weight gain, glucose, insulin, triglyceride and total cholesterol level of blood compared with high fat diet group, and the reduced circulating maternal pro-inflammation factors at GD14.5. Mice fed with HF displayed β-cell hyperplasia with a greater β-cell size and β-cell area in pancreas. Furthermore, the higher ratio of apoptosis and inflammatory response were found in HF group compared with HSF and CF group, while the proliferation

  3. Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children☆

    PubMed Central

    Zhang, Chenhong; Yin, Aihua; Li, Hongde; Wang, Ruirui; Wu, Guojun; Shen, Jian; Zhang, Menghui; Wang, Linghua; Hou, Yaping; Ouyang, Haimei; Zhang, Yan; Zheng, Yinan; Wang, Jicheng; Lv, Xiaofei; Wang, Yulan; Zhang, Feng; Zeng, Benhua; Li, Wenxia; Yan, Feiyan; Zhao, Yufeng; Pang, Xiaoyan; Zhang, Xiaojun; Fu, Huaqing; Chen, Feng; Zhao, Naisi; Hamaker, Bruce R.; Bridgewater, Laura C.; Weinkove, David; Clement, Karine; Dore, Joel; Holmes, Elaine; Xiao, Huasheng; Zhao, Guoping; Yang, Shengli; Bork, Peer; Nicholson, Jeremy K.; Wei, Hong; Tang, Huiru; Zhang, Xiaozhuang; Zhao, Liping

    2015-01-01

    Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation. Research in context Poorly managed diet and genetic mutations are the two primary driving forces behind the devastating epidemic of obesity-related diseases. Lack of understanding of the molecular chain of causation between the driving forces and the disease endpoints retards progress in prevention and treatment of the diseases. We found

  4. Analytical design and evaluation of an active control system for helicopter vibration reduction and gust response alleviation

    NASA Technical Reports Server (NTRS)

    Taylor, R. B.; Zwicke, P. E.; Gold, P.; Miao, W.

    1980-01-01

    An analytical study was conducted to define the basic configuration of an active control system for helicopter vibration and gust response alleviation. The study culminated in a control system design which has two separate systems: narrow band loop for vibration reduction and wider band loop for gust response alleviation. The narrow band vibration loop utilizes the standard swashplate control configuration to input controller for the vibration loop is based on adaptive optimal control theory and is designed to adapt to any flight condition including maneuvers and transients. The prime characteristics of the vibration control system is its real time capability. The gust alleviation control system studied consists of optimal sampled data feedback gains together with an optimal one-step-ahead prediction. The prediction permits the estimation of the gust disturbance which can then be used to minimize the gust effects on the helicopter.

  5. A progress report on the Malaga Bend Experimental Salinity Alleviation Project, Eddy County, New Mexico

    USGS Publications Warehouse

    Cox, E.R.; Havens, J.S.

    1965-01-01

    At Malaga Bend on the Pecos River in Eddy County, New Mexico, a