Assessment of antinociceptive, antipyretic and antimicrobial activity of Piper cubeba L. essential oil in animal models.

PubMed

Mothana, Ramzi; Alsaid, Mansour; Khaled, Jamal M; Alharbi, Naiyf S; Alatar, Abdulrahman; Raish, Mohammad; Al-Yahya, Mohammed; Rafatullah, Syed; Parvez, Mohammad Khalid; Ahamad, Syed Rizwan

2016-03-01

This study was designed to investigate the possible antiniciceptive, antipyretic and antimicrobial activities of the essential oil obtained from the fruits of Piper Cubeba (L.). To assess the antinociceptive and antipyretic activities, three doses (150, 300 and 600 mg/kg, i.p.) were tested in acetic acid-induced abdominal writhing, tail flick reaction and hot-plate and Brewer's yeast-induced hyperpyrexia test models in animals. Moreover, the antimicrobial activity was examined using agar diffusion method and broth micro-dilution assay for minimum inhibitory concentrations (MIC). The Piper Cubeba essential oil (PCEO) showed a marked antinociception (17, 30 and 54%) and an increase in reaction time in mice in the flick tailed and hot-plate tests. The brewer's yeast induced hyperpyrexia was decreased in a dose dependent manner. PCEO also exhibited a strong antimicrobial potential. These findings confirm the traditional analgesic indications of P. cubeba oil and provide persuasive evidence and support its use in Arab traditional medicine.

Analgesic activity of Nelsonia canescens (Lam.) Spreng.root in albino rats

PubMed Central

Mohaddesi, Behzad; Dwivedi, Ravindra; Ashok, B. K.; Aghera, Hetal; Acharya, Rabinarayan; Shukla, V. J.

2013-01-01

Present study was undertaken to evaluate analgesic activity of root of Nelsonia canescens (Lam.) Spreng, a folklore medicinal plant used as the one of the source plant of Rasna. Study was carried out at two dose levels (270 mg/kg and 540 mg/kg) in albino rats. Analgesic activity was evaluated in formalin induced paw licking, and tail flick methods whereas indomethacin and pentazocine were used as standard analgesic drugs, respectively. At both the dose levels, test drug non-significantly decreased paw licking response at both time intervals. In tail flick model, the administration of the test drug increased pain threshold response in a dose dependent manner. In therapeutically equivalent dose level, analgesic activity was observed only after 180 min while in TED ×2 treated group analgesia was observed at 30 min and lasted even up to 240 min. The results suggested that N.canescens root possess moderate analgesic activity. PMID:24250136

Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

PubMed

Ikeda, H; Ikegami, M; Kai, M; Ohsawa, M; Kamei, J

2013-10-10

The role of spinal cannabinoid systems in neuropathic pain of streptozotocin (STZ)-induced diabetic mice was studied. In normal mice, injection of the cannabinoid receptor agonist WIN-55,212-2 (1 and 3μg, i.t.) dose-dependently prolonged the tail-flick latency, whereas there were no changes with the injection of either cannabinoid CB1 (AM 251, 1 μg, i.t.) or CB2 (AM 630, 4 μg, i.t.) receptor antagonists. AM 251 (1 μg, i.t.), but not AM 630 (4 μg, i.t.), significantly inhibited the prolongation of the tail-flick latency induced by WIN-55,212-2 (3 μg, i.t.). In STZ-induced diabetic mice, the tail-flick latency was significantly shorter than that in normal mice. A low dose of WIN-55,212-2 (1 μg, i.t.) significantly recovered the tail-flick latency in STZ-induced diabetic mice. The effect of WIN-55,212-2 (1 μg, i.t.) in STZ-induced diabetic mice was significantly inhibited by AM 630 (4 μg, i.t.), but not AM 251 (1 μg). The selective cannabinoid CB2 receptor agonist L-759,656 (19 and 38 μg, i.t.) also dose-dependently recovered the tail-flick latency in STZ-induced diabetic mice, and this recovery was inhibited by AM 630 (4 μg, i.t.). The protein levels of cannabinoid CB1 receptors, CB2 receptors and diacylglycerol lipase α (DGL-α), the enzyme that synthesizes endocannabinoid 2-arachidonoylglycerol, in the spinal cord were examined using Western blotting. The protein levels of both cannabinoid CB1 and CB2 receptors were increased in STZ-induced diabetic mice, whereas the protein level of DGL-α was significantly decreased. These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Phytohormone abscisic acid elicits antinociceptive effects in rats through the activation of opioid and peroxisome proliferator-activated receptors β/δ.

PubMed

Mollashahi, Mahtab; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed

2018-08-05

The phytohormone abscisic acid exists in animal tissues particularly in the brain. However, its neurophysiological effects have not yet been fully clarified. This study was designed to evaluate the possible antinociceptive effects of abscisic acid on animal models of pain and determine its possible signaling mechanism. Tail-flick, hot-plate and formalin tests were used to assess the nociceptive threshold. All experiments were carried out on male Wistar rats. To determine the role of Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and opioid receptors on the induction of abscisic acid antinociception, specific antagonists were injected 15 min before abscisic acid. The data showed that abscisic acid (5, 10 and 15 µg/rat, i.c.v.) significantly decreased pain responses in formalin test. In addition, it could also produce dose-dependent antinociceptive effect in tail-flick and hot-plate tests. Administration of PPARβ/δ antagonist (GSK0660, 80 nM, i.c.v.) significantly attenuated the antinociceptive effect of abscisic acid in all tests. The antinociceptive effects of abscisic acid were completely inhibited by naloxone (6 µg, i.c.v.) during the time course of tail-flick and hot-plate tests. The results indicated that the central injection of abscisic acid has potent pain-relieving property which is mediated partly via the PPAR β/δ and opioid signaling. Copyright © 2018 Elsevier B.V. All rights reserved.

Analgesic Effect of Xenon in Rat Model of Inflammatory Pain.

PubMed

Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V

2017-02-01

The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.

Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats.

PubMed

Esmaeili-Mahani, Saeed; Rezaeezadeh-Roukerd, Maryam; Esmaeilpour, Khadije; Abbasnejad, Mehdi; Rasoulian, Bahram; Sheibani, Vahid; Kaeidi, Ayat; Hajializadeh, Zahra

2010-10-28

Olive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified. All experiments were carried out on male Wistar rats. The tail-flick, hot-plate and formalin tests were used to assess the effect of OLE on nociceptive threshold. To determine the effect of OLE on analgesic and hyperalgesic effects of morphine, OLE (6, 12 and 25 mg/kg i.p.) that had no significant nociceptive effect, was injected concomitant with morphine (5 mg/kg and 1 μg/kg i.p., respectively). The tail-flick test was used to assess the effect of OLE on anti- and pro-nociceptive effects of morphine. The data showed that OLE (50-200 mg/kg i.p.) could produce dose-dependent analgesic effect on tail-flick and hot-plate tests. Administration of 200 mg/kg OLE (i.p.) caused significant decrease in pain responses in the first and the second phases of formalin test. In addition, OLE could potentiate the antinociceptive effect of 5 mg/kg morphine and block low-dose morphine-induced hyperalgesia. Our results indicate that olive leaf extract has analgesic property in several models of pain and useful influence on morphine analgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Differential analgesic effects of a mu-opioid peptide, [Dmt(1)]DALDA, and morphine.

PubMed

Shimoyama, Megumi; Szeto, Hazel H; Schiller, Peter W; Tagaito, Yugo; Tokairin, Hideyuki; Eun, Chong moon; Shimoyama, Naohito

2009-01-01

H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA. We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects. [Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone. Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.

Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis.

PubMed

Lian, Yu-Ling; Cheng, Ming-Jun; Zhang, Xian-Xia; Wang, Li

2017-08-01

Pain is the most pronounced complaint of women with endometriosis, however the underlying mechanism is still poorly understood. In the present study, the authors evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) of dorsal root ganglia (DRG) on endometriosis-associated pain. A total of 36 SD rats were randomly divided into a sham group (n=9) and a Model group (n=27), accepted auto‑transplanted pieces of fat or uterus to the pelvic cavity. At 4 weeks, the Model group was randomly subdivided into the following groups: ENDO group (no treatment, n=9), BCTC group (Model + BCTC, an antagonist of TRPV1, n=9), Vehicle group (Model + cyclodextrin, the vehicle of BCTC, n=9). Tail‑flick test was performed prior to surgery, 1 h prior to and following treatment of BCTC or cyclodextrin. The expression of TRPV1, substance P (SP), calcitonin gene‑related peptide (CGRP) in L1‑L6 DRG was measured via immunohistochemistry, western blotting and RT‑qPCR. The results indicated that the Model group exhibited a significant decrease in tail flick latency compared to pre‑surgical baseline, and the expression of TRPV1, SP, CGRP protein and mRNA in L1‑L6 DRG significantly increased compared to the sham group. BCTC significantly improved tail flick latency, and downregulated the expression of TRPV1, SP and CGRP protein and mRNA levels in L1‑L6 DRG compared to ENDO group. However, there were no significant differences of those in Vehicle group compared with the ENDO group. Taken together, the current study provides evidence that TRPV1 expressed in DRG may serve an important role in endometriosis-associated pain.

The antinociceptive effect and mechanisms of action of pregabalin in mice.

PubMed

Kaygisiz, Bilgin; Kilic, Fatma Sultan; Senguleroglu, Nuri; Baydemir, Canan; Erol, Kevser

2015-02-01

Pregabalin, a potent anticonvulsant agent, is used in treatment-resistant epileptic patients. It is reported that pregabalin also has analgesic effect in different pain syndromes. However, there is limited data on its antinociceptive mechanisms of action. We aimed to investigate the central and peripheral antinociceptive effects of pregabalin and the contribution of nitrergic, serotonergic, and opioidergic pathways in mice. We used tail flick, tail clip and hot plate tests to investigate the central antinociceptive effects and acetic acid-induced writhing test to assess peripheral antinociceptive effects of pregabalin (10, 30, 100mg/kg). We also combined pregabalin (100mg/kg) with, a nonspecific nitric oxide synthase inhibitor l-NAME (100mg/kg), a serotonin receptor antagonist cyproheptadine (50 μg/kg), and an opioid receptor antagonist naloxone (1mg/kg). Pregabalin 30 mg/kg enhanced the percentage of maximal possible effect (% MPE) in tail flick test. Pregabalin 100mg/kg significantly increased % MPE in tail clip and tail flick tests and decreased the number of writhings. Pregabalin made no significant alteration in hot plate test at all doses. The combined use of pregabalin 100mg/kg with l-NAME, cyproheptadine, and naloxone showed that % MPE was reduced only in the combination of pregabalin with naloxone and solely in tail clip test while no significant difference was observed in writhing test. We suggest that pregabalin (30 and 100mg/kg) presents central spinal but not central supraspinal antinociceptive effect and pregabalin 100mg/kg shows peripheral antinociceptive effect. The opioidergic pathway seems to mediate the central spinal antinociceptive effect of pregabalin while nitrergic and serotonergic pathways are not involved. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

PubMed

Mehta, Ashish K; Bhati, Yogendra; Tripathi, Chakra D; Sharma, Krishna K

2014-08-01

Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

Distinct effect of orphanin FQ in nucleus raphe magnus and nucleus reticularis gigantocellularis on the rat tail flick reflex.

PubMed

Yang, Z; Zhang, Y; Wu, G

2001-06-22

The aim of the present study is to investigate the effects of orphanin FQ (OFQ) microinjected into the nucleus raphe magnus (NRM) and the nucleus reticularis gigantocellularis (NGC) on pain modulation. The tail-flick latency (TFL) was used as a behavioral index of nociceptive responsiveness. The result showed microinjection of OFQ into the NRM significantly increased the TFL, whereas microinjection of OFQ into the NGC decreased the TFL, suggesting the analgesic effect of OFQ in the NRM and the hyperalgesic effect of OFQ in the NGC. As there are three classes of putative pain modulating neurons in the rostral ventromedial medulla (RVM), the hyperalgesic or analgesic effect of OFQ in the RVM might depend upon the different class of the neurons being acted.

Bioadhesive films containing benzocaine: correlation between in vitro permeation and in vivo local anesthetic effect.

PubMed

de Araujo, Daniele Ribeiro; Padula, Cristina; Cereda, Cíntia Maria Saia; Tófoli, Giovana Radomille; Brito, Rui Barbosa; de Paula, Eneida; Nicoli, Sara; Santi, Patrizia

2010-08-01

The aim of this work was to develop anesthetic bioadhesive films containing benzocaine and study their in vitro skin permeation and in vivo performance, in comparison with commercial formulations. Films containing 3% and 5% w/w of benzocaine were prepared and characterized by weight, drug content, thickness and morphology. In vitro permeation assays were performed in vertical diffusion cells using full-thickness pig ear skin as barrier. Intensity and duration of analgesia were evaluated in rats by tail-flick test, and skin histological analysis was carried out. Tail-flick test showed that the duration of benzocaine-induced analgesia was significantly prolonged with the films compared to commercial creams, in agreement with the higher in vitro permeation. Histological analysis of the rat tail skin did not reveal morphological tissue changes nor cell infiltration signs after application of the commercial creams or films. Results from our study indicate that the films developed in this work can be considered as innovative dermal/transdermal therapeutic systems for benzocaine local delivery.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening

PubMed Central

Dunder, Ricardo José; Luiz-Ferreira, Anderson; de Almeida, Ana Cristina Alves; de-Faria, Felipe Meira; Takayama, Christiane; Socca, Eduardo Augusto Rabelo; Salvador, Marcos José; Mello, Gláucia Coelho; dos Santos, Catarina; de Oliva-Neto, Pedro; Souza-Brito, Alba Regina Monteiro

2013-01-01

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties. PMID:23778651

Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats.

PubMed

Abelson, Klas S P; Höglund, A Urban

2002-04-01

Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10-300 microg/kg) and atropine (0.1, 10, 5000 microg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2-C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 microg/kg), or subcutaneously with oxotremorine (30, 100, 300 microg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 microg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 microg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

Vitamin A depletion alters sensitivity of motor behavior to MK-801 in C57BL/6J mice.

PubMed

Zhang, Ming; Ji, Baohu; Zou, Hong; Shi, Junwei; Zhang, Zhao; Li, Xingwang; Zhu, Hui; Feng, Guoyin; Jin, Meilei; Yu, Lei; He, Lin; Wan, Chunling

2010-01-22

Vitamin A and its derivatives (retinoids) are crucial for the development, maintenance and morphogenesis of the central nervous system (CNS). Although motor impairment has been reported in postnatal vitamin A depletion rodents, the effect of vitamin A depletion on homeostasis maintaining capability in response to external interference is not clear. In the current study, we measured the effect of vitamin A depletion on motor ability and pain sensitivity under two different conditions: 1. prior to any injection and 2. after the injection of an N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801). Vitamin A depletion mice showed decreased body weight, enhanced locomotor activity, increased rearing and less tail flick latency. Vitamin A depletion also induced hypersensitivity of stereotypy, ataxia, rearing, and tail flick latency to MK-801, but hyposensitivity of locomotion to MK-801. These findings suggest that vitamin A depletion affect broad basal behavior and disrupt homeostasis maintaining capability in response to glutamate perturbation. We provide a useful animal model for assessing the role of vitamin A depletion in regulating animal behavior, and for detecting how neurotransmitter pathways might be involved in vitamin A depletion related behavioral abnormalities.

Effect of subcutaneous Meloxicam on indicators of acute pain and distress after castration and branding in 2 mo old beef calves.

PubMed

Meléndez, D M; Marti, S; Pajor, E A; Moya, D; Gellatly, D; Janzen, E D; Schwartzkopf-Genswein, K S

2018-06-15

The aim of this study was to assess knife castration and knife castration + branding in 2-mo old calves, and the effect of a single dose of s.c. meloxicam at mitigating pain indicators. Seventy-one Angus crossbred bull calves (128 ± 18.5 kg of BW) were used in a 3 × 2 factorial design where main factors included procedure: sham (control calves, CT; n = 23), knife (KN; n = 24) or knife + branding (BK; n = 24) and medication: single s.c. administration of lactated ringer solution (NM; n = 35) or a single dose of 0.5 mg/kg of s.c. meloxicam (M; n = 36). Physiological samples were collected at T0, 60, 90, 120 and 180 min and on d 1, 2, 3 and 7 after procedure, while behavioral observations were evaluated at 2 to 4 h and 1, 2, 3 and 7 days after procedure. A procedure × time effect (P < 0.01) was observed for cortisol, where KN and BK calves had greater (P ≤ 0.01 ) cortisol concentrations than CT calves 60 min after the procedure, while BK calves had the greatest (P < 0.05) cortisol concentrations, followed by KN calves and by CT calves 90, 120 and 180 min after the procedure. A procedure × time effect (P = 0.01) was observed for tail flicks, where KN and BK calves had a greater (P < 0.05) number of tail flicks than CT calves on d 1 and 3, while BK calves had the greatest number of tail flicks, followed by KN calves, and then by CT calves on d 2. Haptoglobin had a procedure × medication × time interaction (P = 0.05), where BK-NM calves had greater haptoglobin concentrations than BK-M, KN-M and CT calves on d 1 and 3, while BK-NM and KN-NM calves had greater haptoglobin concentrations than BK-M, KN-M and CT calves on d 2 after the procedure. Lying duration and tail flicks had a medication effect (P = 0.04; P < 0.01) where M calves had greater (P < 0.05) lying duration and lower (P < 0.05) number of tail flicks than NM calves 2 to 4 h after procedure. No medication effects (P > 0.10) were observed for salivary cortisol, substance P and scrotal temperature min after the procedure or for cortisol, substance P, serum amyloid A, stride length or behavioral observations on d after the procedure. Overall, BK calves presented greater physiological and behavioral indicators of acute pain than KN calves, suggesting that the combination of knife castration + branding was more painful. Meloxicam administered s.c. was effective at reducing physiological and behavioral indicators of acute pain associated with knife castration and knife castration + branding.

The anti-nociceptive potential of tilmicosin against chemical-induced but not thermal-induced pain in mice

PubMed Central

El-Mahmoudy, A; Gheith, I

2015-01-01

The aim of the present study was to assess the analgesic activity of the macrolide antibiotic tilmicosin at dose levels of 20 and 40 mg/kg of body weight, subcutaneously, against chemical- and thermal-induced acute pains, using acetic acid-induced writhing, formalin-induced pain, hot-plate, and tail-flick models in mice. Tilmicosin showed a dose-dependent significant decrease in the number of writhes in the acetic acid-induced writhing test and significant decrease in hind paw-licking time in the late phase of the formalin test. However, it did not cause any significant changes in the reaction times to heat stimuli in the hot-plate and tail-flick models. In chemically-induced pains, both dose levels of tilmicosin showed significant effects compared to those of the corresponding standard peripheral analgesic, acetylsalicylic acid (200 mg/kg of body weight, subcutaneously) being 26.37 ± 2.88 and 43.64 ± 3.85% vs. 73.35 ± 1.44% in acetic acid test; and 19.23 ± 3.85 and 44.90 ± 1.80% vs. 73.63 ± 2.39% in the late phase of formalin test, respectively. These results may indicate that tilmicosin possesses a significant peripheral but not central analgesic potential that may be beneficial in symptomatic relief of pain when it is used in therapy, in addition to its well-established antibacterial effect. PMID:26519523

Intrathecal clonidine and bupivacaine have synergistic analgesia for acute thermally or inflammatory-induced pain in rats.

PubMed

Nishiyama, Tomoki; Hanaoka, Kazuo

2004-04-01

We investigated the interaction between spinally administered bupivacaine and clonidine using an animal model of acute and inflammatory pain. Rats implanted with lumbar intrathecal catheters were injected intrathecally with saline (control), bupivacaine (1 to 100 microg), or clonidine (0.1 to 3 microg) and tested for their responses to thermal stimulation to the tail (tail flick test) and subcutaneous formalin injection into the hindpaw (formalin test). The effects of the combination of bupivacaine and clonidine on both stimuli were tested by isobolographic analysis. General behavior and motor function were examined as side effects. The 50% effective doses of bupivacaine and clonidine were significantly smaller when combined compared with each single drug in both the tail flick test (2.82 and 0.11 microg versus 7.1 and 0.29 microg, respectively) and phase 1 (0.24 and 0.009 microg versus 5.7 and 0.15 microg) and phase 2 (0.31 and 0.012 microg versus 3.2 and 0.16 microg) of the formalin test. Side effects were decreased by the combination. These results suggest a favorable combination of intrathecal bupivacaine and clonidine in the management of acute and inflammatory pain. The analgesic interaction between intrathecally administered bupivacaine and clonidine was examined during acute thermal and inflammatory-induced pain in rats. The analgesia produced by the combination of these two drugs was synergistic in both acute thermal and inflammatory induced pain, with a decrease in behavioral side effects.

Antinociceptive activity of Sempervivum tectorum L. extract in rats.

PubMed

Kekesi, Gabriella; Dobos, Ildiko; Benedek, György; Horvath, Gyöngyi

2003-11-01

The extract of Sempervivum tectorum L. (Crassulaceae) containing several flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous studies have demonstrated that various flavonoids or flavonoid-containing plant extracts produce significant antinociception, but no data are available concerning their antinociceptive effect especially at the spinal level. The purpose of the present study was to investigate the antinociceptive activity of Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in awake rats. The pain sensitivity was assessed by the acute tail- flick test in intact rats and by the paw withdrawal test after carrageenan-induced inflammation using heat stimulus. The plant extract was administered intraperitoneally and intrathecally in rats. The intraperitoneal injection of a high dose of the extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal latency of the inflamed paw. The intrathecal administration (30-300 micro g) caused a small, but significant increase (10%-15%) in tail- flick latency. In the carrageenan-induced inflammatory model, the intrathecally applied extract (30-1000 micro g) significantly decreased, but did not relieve the thermal hyperalgesia. The results suggest that the spinal cord does not seem to play an important role in the antinociceptive effects of this plant extract. Copyright 2003 John Wiley & Sons, Ltd.

Anti-inflammatory, analgesic and anti-pyretic activities of standardized root extract of Jasminum sambac.

PubMed

Sengar, Nidhi; Joshi, Apurva; Prasad, Satyendra K; Hemalatha, S

2015-02-03

The plant Jasminum sambac L. (Oleaceae) is cultivated throughout India. The leaves and roots of the plant are used traditionally in the treatment of inflammation, fever and pain. The leaves of the plant have been reported to posses significant anti-inflammatory and analgesic activities. To scientifically validate anti-inflammatory, analgesic and anti-pyretic activities of roots from Jasminum sambac. Ethanol root extract of Jasminum sambac (EJS) was standardized using HPTLC and was subjected to acute oral toxicity study. Further, analgesic activity of EJS at 100, 200 and 400mg/kg, p.o. was evaluated using writhing test on Swiss albino mice and tail-flick test on Charles Foster albino rats. Anti-inflammatory activity of EJS was assessed by carrageenan-induced rat paw edema, cotton pellet-induced granuloma and Freund׳s adjuvant-induced arthritis models, while antipyretic activity was evaluated using Brewer׳s yeast induced pyrexia. In addition, biochemical parameters such as alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in blood serum and edematous tissue of rats exposed to acute (carrageenan) and granulomatous tissue in sub-chronic (cotton pellet granuloma) inflammation models were also evaluated. Phytochemical analysis of EJS revealed the presence of flavonoids, phenols, saponins, tannins and carbohydrates in major quantities, while the quantity of hesperidin in EJS (using HPTLC) was found to be 4.25%w/w. EJS at 400mg/kg, p.o. reduced writhing count up to 49.21%, whereas in tail-flick test, EJS in a dose dependent manner increased latency in flicking tail. EJS at 400mg/kg, p.o. showed significant anti-inflammatory activity after 2nd, 3rd, 4th and 6thh of treatment in carrageenan-induced edema, while a 33.58% inhibition in cotton pellet induced granuloma formation was observed at same dose level. EJS significantly (p<0.001) inhibited adjuvant-induced arthritis and also showed significant antipyretic activity. Further, a significant reversal in alterations of all the biochemical parameters (except ALP) in tissues was also observed. The study confirms the anti-inflammatory, analgesic and antipyretic activity of EJS which may be attributed to the presence of various phytoconstituents quantified especially hesperidin which have already been reported for its significant role in the treatment of inflammation and associated problems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat.

PubMed

Haghparast, Abbas; Soltani-Hekmat, Ava; Khani, Abbas; Komaki, Alireza

2007-10-29

Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia. Previous studies have shown that antinociceptive response of CnF-microinjected morphine can be modulated by the specific subtypes of glutamatergic receptors within the CnF. In this study, we evaluated the role of NMDA and kainate/AMPA receptors that are widely distributed within the NRM on morphine-induced antinociception elicited from the CnF. Hundred and five male Wistar rats weighing 250-300 g were used. Morphine (10, 20 and 40 microg) and NMDA receptor antagonist, MK-801 (10 microg) or kainate/AMPA receptor antagonist, DNQX (0.5 microg) in 0.5 microl saline were stereotaxically microinjected into the CnF and NRM, respectively. The latency of tail-flick response was measured at set intervals (2, 7, 12, 17, 22, 27 min after microinjection) by using an automated tail-flick analgesiometer. The results showed that morphine microinjection into the CnF dose-dependently causes increase in tail-flick latency (TFL). MK-801 microinjected into the NRM, just 1 min before morphine injection into the CnF, significantly attenuated antinociceptive effects of morphine. On the other hand, DNQX microinjected into the NRM, significantly increased TFL after local application of morphine into the CnF. We suggest that morphine related antinociceptive effect elicited from the CnF is mediated, in part, by NMDA receptor at the level of the NRM whereas kainite/AMPA receptor has a net inhibitory influence at the same pathway.

Comparative effects of Rauwolfia vomitoria and chlorpromazine on social behaviour and pain

PubMed Central

Bisong, Sunday; Brown, Richard; Osim, Eme

2011-01-01

Background: Rauwolfia vomitoria has been used in Nigeria to manage psychiatric disorders despite orthodox medicine. Aims: This research was therefore aimed at comparing the effects of R. vomitoria, chlorpromazine and reserpine on social behaviour and pain in mice. Materials and Methods: Ninety male CD-1 mice (32 – 38g body weight) were grouped into 3 with 5 subgroups (n=6) each. Mice were given chlorpromazine (0.0, 0.25, 1.0, 2.0, 4.0 mg/kg i.p.), 30 minutes before testing and R. vomitoria (0.0, 0.25, 1.0, 2.0, 4.0 mg/kg, i.p.) and reserpine (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p) 24 hours before testing. Nesting score assessed social behaviour while the tail flick and hot plate analgesiometers assessed pain. Results: Chlorpromazine dose-dependently decreased nesting score (F4,25 = 5.5660; p< 0.01), indicating decreased social behaviour (social loss) in the mice. Although R. vomitoria did not affect nesting score, reserpine decreased the nesting score (social loss). In the pain test, chlorpromazine did not alter tail flick latency but decreased hind paw lick latency in the hot plate at 2.0 and 4.0 mg/kg (p< 0.01), indicating increased pain sensitivity at these doses which may indirectly increase social withdrawal and thus aggravating depression. R. vomitoria however, increased tail flick and hind paw lick latencies in the hot plate test (p< 0.05) indicating decreased pain sensitivity. Reserpine, like R. vomitoria, increased latency of hind paw lick in the hot plate. Conclusion: R. vomitoria has a high potential as an antipsychotic and may have advantage over chlorpromazine; it is not necessary to isolate active components from this herb. PMID:22540065

Resveratrol-induced antinociception is involved in calcium channels and calcium/caffeine-sensitive pools.

PubMed

Pan, Xiaoyu; Chen, Jiechun; Wang, Weijie; Chen, Ling; Wang, Lin; Ma, Quan; Zhang, Jianbo; Chen, Lichao; Wang, Gang; Zhang, Meixi; Wu, Hao; Cheng, Ruochuan

2017-02-07

Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) levels in the spinal cord were also investigated when treated with the above drugs. The results showed that resveratrol increased the tail flick latency in the tail-flick test, in dose-dependent manner. N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK 801 potentiated the antinociceptive effects of sub-threshold dose of resveratrol at 10 mg/kg. Ca2+ channel blocker, however, abolished the antinociceptive effects of resveratrol. In contrast to these results, EGTA or ryanodine treatment (i.c.v.) potentiated resveratrol-induced antinociception. There was a significant decrease in p-CaMKII and an increase in BDNF expression in the spinal cord when combined with MK 801, nimodipine, ryanodine and EGTA. While an increase in p-CaMKII level and a decrease in BDNF expression were observed when high dose of resveratrol combined with CaCl2. These findings suggest that resveratrol exhibits the antinociceptive effects by inhibition of calcium channels and calcium/caffeine-sensitive pools.

Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.

PubMed

Baeta-Corral, Raquel; Defrin, Ruti; Pick, Chagi G; Giménez-Llort, Lydia

2015-07-23

Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Study the Antinociceptive Effect of Intracerebroventricular Injection of Aqueous Extract of Origanum Vulgare Leaves in Rat: Possible Involvement of Opioid System

PubMed Central

Pahlavan, Yasaman; Sepehri, Gholamreza; Sheibani, Vahid; Afarinesh khaki, Mohammadreza; Gojazadeh, Morteza; Pahlavan, Bahare; Pahlavan, Fereshteh

2013-01-01

Objective(s): The aim of study was to investigate the antinociceptive effect of intracerebroventricular (ICV) microinjection of Origanum vulgare (ORG) extract and possible involvement of opioid receptors. Materials and Methods: Cannula was inserted into left ventricle of male rats. Five days after surgery Tail Flick Latency (TFL) was measured after ICV microinjection of, ORG (1, 3 and 6 µg / rat). Effective dose of ORG was injected ICV in concomitant with morphine (2 mg/kg, IP), naloxone (2 mg / kg, IP) and saline (0.5 µl/rat) and TFL was recorded. Results: The co- administration of ORG extract with morphine showed a significant increase in TFL and naloxone, pretreatment significantly inhibited the antinociceptive activity of ORG and morphine. Conclusion: The aqueous extract of ORG possesses antinociceptive activities in the tail-flick test in a dose dependent manner. ORG - induced antinociception may have been mediated by opioid systems. PMID:24379969

Diazepam-stress interactions in the rat: effects on autoanalgesia and a plus-maze model of anxiety.

PubMed

Taukulis, H K; Goggin, C E

1990-03-01

On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property.

The anti-nociceptive potential of tilmicosin against chemical-induced but not thermal-induced pain in mice.

PubMed

El-Mahmoudy, A; Gheith, I

2016-03-01

The aim of the present study was to assess the analgesic activity of the macrolide antibiotic tilmicosin at dose levels of 20 and 40 mg/kg of body weight, subcutaneously, against chemical- and thermal-induced acute pains, using acetic acid-induced writhing, formalin-induced pain, hot-plate, and tail-flick models in mice. Tilmicosin showed a dose-dependent significant decrease in the number of writhes in the acetic acid-induced writhing test and significant decrease in hind paw-licking time in the late phase of the formalin test. However, it did not cause any significant changes in the reaction times to heat stimuli in the hot-plate and tail-flick models. In chemically-induced pains, both dose levels of tilmicosin showed significant effects compared to those of the corresponding standard peripheral analgesic, acetylsalicylic acid (200 mg/kg of body weight, subcutaneously) being 26.37±2.88 and 43.64±3.85% vs. 73.35±1.44% in acetic acid test; and 19.23±3.85 and 44.90±1.80% vs. 73.63±2.39% in the late phase of formalin test, respectively. These results may indicate that tilmicosin possesses a significant peripheral but not central analgesic potential that may be beneficial in symptomatic relief of pain when it is used in therapy, in addition to its well-established antibacterial effect. © The Author(s) 2015.

Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties

PubMed Central

Das, Narhari; Abdur Rahman, S. M.

2016-01-01

Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. PMID:27478435

Evaluation of analgesic activity of Terminalia arjuna (Roxb.) Wight and Arn bark: A tribal claim.

PubMed

Gupta, Anurag; Nishteswar, K; Shukla, Vinay J; Ashok, B K

2014-01-01

Plants occupy an important place in folk medicine all over the world for centuries and indigenous communities have developed their own specific knowledge on plant resources, uses, management, and conservation. Research interest and activities in the area of ethno medicine have increased tremendously in the last decade. Currently, scientists are evincing keen interest in the scientific evaluation of ethno medical claims. Bark powder of Arjuna (Terminalia arjuna [Roxb.] Wight and Arn) is used by tribals for the management of some painful conditions. To evaluate analgesic activity of T. arjuna bark in rodents. For evaluation of analgesic activity, different experimental models, that is, the acetic acid-induced writhing syndrome in mice, formaldehyde-induced paw licking response and tail flick test in rats were designed. Experiments were carried out at two-dose levels, that is, therapeutically equivalent dose (TED) and TED × 2. Animals were divided into three groups (six animals in each group), first group serving as a control group, second and third group labeled as test drug group. Test drug at both the doses significantly decreased the writhing syndrome in comparison to control the group. In comparison to control the group, incidences of formalin-induced paw licking were reduced in test drug groups in both early and late phases of pain. In tail flick response, threshold was significantly increased in both test drug groups at every time intervals. Study showed that stem bark of T. arjuna possesses analgesic activity in all experimental models.

Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain.

PubMed

Veneroni, O; Maj, R; Calabresi, M; Faravelli, L; Fariello, R G; Salvati, P

2003-03-01

NW-1029, a benzylamino propanamide derivative, was selected among several molecules of this chemical class on the basis of its affinity for the [(3)H]batracotoxin ligand displacement of the Na(+) channel complex and also on the basis of its voltage and use-dependent inhibitory action on the Na(+) currents of the rat DRG (dorsal root ganglia) sensory neuron. This study evaluated the analgesic activity of NW-1029 in animal models of inflammatory and neuropathic pain (formalin test in mice, complete Freund's adjuvant and chronic constriction injury in rats) as well as in acute pain test (hot-plate and tail-flick in rats). Orally administered NW-1029 dose-dependently reduced cumulative licking time in the early and late phase of the formalin test (ED(50)=10.1 mg/kg in the late phase). In the CFA model, NW-1029 reversed mechanical allodynia (von Frey test) after both i.p. and p.o. administration (ED(50)=0.57 and 0.53 mg/kg), respectively. Similarly, NW-1029 reversed mechanical allodynia in the CCI model after both i.p. and p.o. administration yielding an ED(50) of 0.89 and 0.67 mg/kg, respectively. No effects were observed in the hot-plate and tail-flick tests up to 30 mg/kg p.o. The compound orally administered (0.1-10 mg/kg) was well tolerated, without signs of neurological impairment up to high doses (ED(50)=470 and 245 mg/kg in rat and mice Rotarod test, respectively). These results indicate that NW-1029 has anti-nociceptive properties in models of inflammatory and neuropathic pain.

The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain

PubMed Central

Wilkerson, Jenny L; Kulkarni, Abhijit; Toma, Wisam; AlSharari, Shakir; Gul, Zulfiye; Lichtman, Aron H; Papke, Roger L; Damaj, M Imad

2016-01-01

Background and Purpose Orthosteric agonists and positive allosteric modulators (PAMs) of the α7 nicotinic ACh receptor (nAChR) represent novel therapeutic approaches for pain modulation. Moreover, compounds with dual function as allosteric agonists and PAMs, known as ago‐PAMs, add further regulation of receptor function. Experimental Approach Initial studies examined the α7 ago‐PAM, GAT107, in the formalin, complete Freund's adjuvant (CFA), LPS inflammatory pain models, the chronic constriction injury neuropathic pain model and the tail flick and hot plate acute thermal nociceptive assays. Additional studies examined the locus of action of GAT107 and immunohistochemical markers in the dorsal horn of the spinal cord in the CFA model. Key Results Complementary pharmacological and genetic approaches confirmed that the dose‐dependent antinociceptive effects of GAT107 were mediated through α7 nAChR. However, GAT107 was inactive in the tail flick and hot plate assays. In addition, GAT107 blocked conditioned place aversion elicited by acetic acid injection. Furthermore, intrathecal, but not intraplantar, injections of GAT107 reversed nociception in the CFA model, suggesting a spinal component of action. Immunohistochemical evaluation revealed an increase in the expression of astrocyte‐specific glial fibrillary acidic protein and phosphorylated p38MAPK within the spinal cords of mice treated with CFA, which was attenuated by intrathecal GAT107 treatment. Importantly, GAT107 did not elicit motor impairment and continued to produce antinociceptive effects after subchronic administration in both phases of the formalin test. Conclusions and Implications Collectively, these results provide the first proof of principle that α7 ago‐PAMs represent an effective pharmacological strategy for treating inflammatory and neuropathic pain. PMID:27243753

Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: role of endogenous opioids, K(ATP)-channels and adenosine.

PubMed

Lopes, Synara C; da Silva, Ana Virginia L; Arruda, Bruno Rodrigues; Morais, Talita C; Rios, Jeison Barros; Trevisan, Maria Teresa S; Rao, Vietla S; Santos, Flávia A

2013-09-01

This study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100 mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30 mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with L-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of K(ATP) channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10-100 mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, K(ATP)-channels and adenosine receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions.

PubMed

Altier, N; Stewart, J

1997-12-01

Experiments were designed to examine the analgesic effects induced by selective tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (NAS). Rats were tested in the formalin test for tonic pain following an injection of 0.05 ml of 2.5% formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist, GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist, senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic pain after infusions of the tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water at 10 min intervals for 1 h immediately after intra-VTA infusions of either GR-73632 (0.5 nmol/side), senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (NAS) of GR-73632 (0.005, 0.5 or 1.5 nmol/side), senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and NAS, the NK-1 and the NK-3 agonists caused significant analgesia in the formalin test, although the NK-1 agonist appeared to be more effective. Naltrexone (2.0 mg/kg) pretreatment failed to reverse the analgesic effects in the formalin test induced by intra-VTA infusions of the substance P (SP) analog, DiMe-C7 (3.0 microg/side), GR-73632 (0.5 nmol/side), or senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or pain-induced analgesia.

An alternative choice of lidocaine-loaded liposomes: lidocaine-loaded lipid-polymer hybrid nanoparticles for local anesthetic therapy.

PubMed

Wang, Jianguo; Zhang, Laizhu; Chi, Huimin; Wang, Shilei

2016-05-01

The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid-polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Their in vitro skin permeation was studied using a Franz diffusion cell mounted with depilated mouse skin in vitro. In vivo local anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. Compared with LA-LPs, LA-LPNs showed significantly better in vitro skin permeation ability and in vivo local anesthetic effects. The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy.

Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy.

PubMed

Micov, Ana; Tomić, Maja; Pecikoza, Uroš; Ugrešić, Nenad; Stepanović-Petrović, Radica

2015-07-01

Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antinociceptive activity and mechanism of action of hydroalcoholic extract and dichloromethane fraction of Amphilophium crucigerum seeds in mice.

PubMed

De Prá, Samira Dal Toé; Ferro, Paula Ronsani; Milioli, Alessandra Marcon; Rigo, Flávia Karine; Chipindo, Orlando Justo; Camponogara, Camila; Casoti, Rosana; Manfron, Melânia Palermo; de Oliveira, Sara Marchesan; Ferreira, Juliano; Trevisan, Gabriela

2017-01-04

The medicinal plant generally known as monkey's comb (Amphilophium crucigerum) has been popularly described for the treatment of neuropathic and inflammatory pain, specially seeds preparations. The goal of the present study was to evaluate the antinociceptive effect of the crude extract (Crd) and dichloromethane fraction (Dcm) of A. crucigerum seeds, and investigate the involvement of transient receptor potential vanilloid 1 (TRPV1) receptor in this effect. Male Swiss mice were used in this study. The effects of Crd and Dcm was tested on capsaicin-induced Ca 2+ influx or the specific binding of [ 3 H]-resiniferatoxin. Moreover, after treatment with Crd or Dcm, animals were exposed to acute pain (hot water tail-flick and capsaicin intraplantar test) or chronic pain models (injection of complete Freund's adjuvant or partial ligation of the sciatic nerve). Acute adverse effects were also noted: locomotor activity, corporal temperature, hepatic or renal damage, gastrointestinal transit alteration, and ulcerogenic activity. The oral administration of Crd or Dcm resulted in an antinociceptive effect in the hot water tail-flick (48°C) and capsaicin intraplantar tests. Furthermore, these preparations exhibited antinociceptive and anti-inflammatory effects in a chronic inflammatory pain model, and antinociceptive effects in a neuropathic pain model. Moreover, Crd and Dcm reduced capsaicin-induced Ca 2+ influx and diminished the [ 3 H]-resiniferatoxin specific binding to spinal cord membranes. Acute adverse events were not found with Crd or Dcm administration. In conclusion, our results support the analgesic effect of A. crucigerum and suggest the presence of compounds that may act as TRPV1 antagonists. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Antinociceptive Effects of Tualang Honey in Male Sprague-Dawley Rats: A Preliminary Study

PubMed Central

Aziz, Che Badariah Abd; Ismail, Che Aishah Nazariah; Hussin, Che Maraina Che; Mohamed, Mahaneem

2014-01-01

Tualang honey (蜂蜜 Fēng Mì) is known to have anti-inflammatory property, but its antinociceptive property has not been extensively investigated. In this study, we examined the preemptive effects on administering different doses of Tualang honey and prednisolone on the nociceptive response in male Sprague-Dawley rats. Thirty-five male Sprague-Dawley rats were randomized into five groups (n = 7) and each group received either distilled water, Tualang honey (0.2, 1.2 or 2.4 g/kg) or prednisolone (10 mg/kg) for 10 days. The response to noxious thermal stimulus was assessed using tail flick test on Day 10. The well-being of the rats was also assessed by monitoring their food intake and body weight. Data were analyzed using one-way Analysis of Variance (ANOVA) with post-hoc Scheffe's test and P value less than 0.05 was considered significant. In tail flick test, the tail flick latency time was significantly higher in the groups that received 1.2 g/kg and 2.4 g/kg of Tualang honey and 10 mg/kg of prednisolone, compared to the control group (P < 0.05). There was significant reduction in the total food pellet intake in the groups receiving prednisolone and Tualang honey (1.2 g/kg and 2.4 g/kg) compared to controls; however, the body weight gain was only significantly reduced in the prednisolone group. All the parameters were not significantly affected in the group receiving 0.2 g/kg of Tualang honey. In conclusion, preemptive administration of Tualang honey (1.2 g/kg and 2.4 g/kg) and prednisolone (10 mg/kg) had reduced the pain responses. The reduced weight gain in the prednisolone group is an unwanted effect due to its metabolic and central actions. Further studies are required to confirm the antinociceptive effects and elucidate the mechanism of antinociceptive action of Tualang honey in the rats. PMID:25379476

Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice.

PubMed

Kambur, Oleg; Männistö, Pekka T; Viljakka, Kaarin; Reenilä, Ilkka; Lemberg, Kim; Kontinen, Vesa K; Karayiorgou, Maria; Gogos, Joseph A; Kalso, Eija

2008-10-01

Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.

The dynamic instability in the hook/flagellum system that triggers bacterial flicks

NASA Astrophysics Data System (ADS)

Jabbarzadeh, Mehdi; Fu, Henry

2017-11-01

Dynamical bending, buckling, and polymorphic transformations of the flagellum are known to affect bacterial motility, but run-reverse-flick motility of monotrichous bacteria also involves the even more flexible hook, which connects the flagellum to the cell body. Here, we identify the dynamic buckling mechanism that produces flicks in Vibrio alginolyticus. Estimates of forces and torques on the hook from experimental observations suggest that flicks are triggered at stresses below the hook's static Euler buckling criterion. Using an accurate linearization of the Kirchoff rod model for the hook in a model of a swimming bacterium with rigid flagellum, we show that as hook stiffness decreases there is a transition from on-axis flagellar rotation with small hook deflections to flagellar precession with large deflections. When flagellum flexibility is incorporated, the precession is disrupted by significant flagellar bending - i.e., incipient flicks. The predicted onset of dynamic instabilities corresponds well with experimentally observed flick events.

The behavioural importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha.

PubMed

Azami, J; Green, D L; Roberts, M H; Monhemius, R

2001-05-01

We have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic activation of descending inhibition of the nociceptive response of spinal multireceptive cells occurs in the nucleus reticularis gigantocellularis pars alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are responsible for activating this inhibition via a pathway which runs in the contralateral dorsolateral funiculus. The effects of dynamically activating this system by noxious stimulation on behavioural responses to noxious stimuli have not been established. Here we demonstrate the effects of GiA on the behavioural response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is possible that chronic pain states may also activate GiA. We have therefore investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310 g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6 days. The responses of each animal during the formalin test (Pain 4 (1977) 161) and the tail flick test (Pain 12 (1982) 229) were recorded on different days. Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were performed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However microinjection of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4 +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection of GABA to GiA increased the behavioural response to formalin between 10 and 20 min post-injection, while microinjection of DLH reduced this response at all time points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioural response to contralaterally applied formalin from 15 min post-injection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA to GiA significantly increased the behavioural response to formalin from 20 to 50 min post-injection. The inactivation of GiA only causes behavioural effects in nociceptive tests of a long enough duration to activate the system (i.e. the formalin test but not the tail flick test). Chemical activation of the system affects both tests. These data strongly support the concept of an important analgesic system which is activated in response to noxious stimulation, and subsequently acts to reduce behavioural responses to noxious stimuli.

Analgesia induced by morphine microinjected into the nucleus raphe magnus: effects on tonic pain.

PubMed

Dualé, Christian; Sierralta, Fernando; Dallel, Radhouane

2007-07-01

One of the possible sites of action of the analgesic effect of morphine is the Nucleus Raphe Magnus, as morphine injected into this structure induces analgesia in transient pain models. In order to test if morphine in the Nucleus Raphe Magnus is also analgesic in a tonic pain model, 5 microg of morphine or saline (control) were microinjected into the Nucleus Raphe Magnus of the rat. Analgesic effects were assessed following nociceptive stimulation using transient heating of the tail (phasic pain) and subcutaneous orofacial injection of 1.5 % formalin (tonic pain). While morphine was strongly analgesic for the tail-flick response (p <0.0001 compared to control), analgesia on the response to formalin was also observed for both early (p = 0.007) and late responses (p = 0.02). However, the response to formalin was not completely blunted. These results suggest that the Nucleus Raphe Magnus is not the exclusive site of action of morphine-induced analgesia in clinical conditions.

1996 Toxic Hazards Research Annual Report.

DTIC Science & Technology

1998-01-01

gasoline , diesel fuel, and jet propulsion (JP) fuel (Staats, 1994). Millions of dollars are spent each year at petroleum contaminated sites for remediation...of locomotor activity and auditory startle reflex tests will be provided in the detailed technical report (in progress). Body Weights and Food...Olfactory Sensitization, Acoustic Startle, Prepulse Inhibition and Habituation, Total Locomotor Activity, Tail Flick Analgesia, and the Treadmill Test of

[Analgesic and anti-inflammatory effects of the flower of Althaea rosea (L.) Cav].

PubMed

Wang, D F; Shang, J Y; Yu, Q H

1989-01-01

The ethanolic extract of the flower of Althaea rosea inhibits significantly the acetic acid-induced twisting of mice and the heat induced (tail) flicking of rats, the acetic acid-induced increase in permeability of abdominal bloud capillaries, the edema of the rat paw induced by carrageenin or dextran, and the release of PGE from inflammatory tissue.

Central analgesic activity of the aqueous and ethanolic extracts of the leaves of Albizia lebbeck: role of the GABAergic and serotonergic pathways.

PubMed

Meshram, Girish G; Kumar, Anil; Rizvi, Waseem; Tripathi, C D; Khan, R A

2015-01-01

Albizia lebbeck Benth. is extensively used in Indian traditional medicine for treating several painful and inflammatory disorders. The possible central analgesic activity and the underlying mechanism of action of the aqueous (AE) and ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar rats using Eddy's hot plate and the tail flick tests. In order to investigate the underlying mechanism of action, rats were pretreated with naloxone, bicuculline or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE and EE caused a significant (p<0.05) elevation in the mean basal reaction time in the hot plate method and an increase in the latency time in the tail flick method. In rats pretreated with bicuculline and methysergide, a significant (p<0.05) reduction in the analgesic activity was observed in comparison to AE and EE. Thus, AE and EE exhibited significant central analgesic activity and act possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins found in the leaves could be responsible for the observed effect.

Acute increases in arterial blood pressure produced by occlusion of the abdominal aorta induces antinociception: peripheral and central substrates.

PubMed

Thurston, C L; Randich, A

1990-06-11

Occlusion of the abdominal aorta proximal to the renal arteries results in an increase in arterial blood pressure, inhibition of forepaw and hindpaw withdrawal to a noxious mechanical stimulus, and inhibition of the tail-flick reflex to noxious heat. Occlusion of the abdominal aorta distal to the renal arteries does not elevate arterial blood pressure and produces no antinociceptive effects. Occlusion of the vena cava lowers arterial blood pressure and produces no antinociception. The inhibitory effects of occlusion of the abdominal aorta depend upon activation of high pressure baroreceptors since bilateral sinoaortic denervation, but not bilateral vagotomy, eliminates the inhibition with respect to all behavioral measures. The inhibitory effects with respect to the tail-flick reflex also depend upon activation of a descending inhibitory system since reversible cold block of the spinal cord at the level of the second thoracic vertebra eliminates the antinociception. This antinociception is also eliminated following intrathecal administration of the noradrenergic receptor antagonist phentolamine, but not by intrathecal administration of either methysergide or naloxone. These data support the view that activation of high pressure baroreceptors by increases in arterial blood pressure produces antinociception via activation of a spinopetal noradrenergic system.

Antinociceptive activity of a polysaccharide from the roots of Sophora flavescens.

PubMed

Jia, Ruimei; Li, Quancheng; Shen, Weixi; Zhang, Jiuwei; Zheng, Lihong; Wang, Guonian

2016-12-01

A polysaccharide (SFWP), with a molecular weight of 51kDa, was successfully purified from the roots of Sophora flavescens and the antinociceptive actions of SFWP were evaluated using acetic acid induced writhing, tail flick, and formalin tests in mice. GC-MS results showed that SFWP had a backbone composed of (1→2)-linked Glc, (1→2,6)-inkedGal and (1→3,6)-inked Man residues, which were terminated with (1→)-inked Xyl and (1→)-inked Ara at O-6 of (1→2,6)-inkedGal and (1→3,6)-inked Man along the main chain, in the ratio of 2.0: 1.02: 1.09: 1.10: 0.98. Data showed that SFWP (100, 200 and 400mg/kg) significantly reduced the number of writhings induced by acetic acid in a dose-dependent manner. However, SFWP did not produce analgesia in tail-flick test. Moreover SFWP strongly attenuated the formalin-induced flinching behaviour in the second phases but not in the first phase in a dose-dependent manner. These results revealed that SFWP could be used safely to attenuate both inflammatory and peripheral neuropathic pain. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice.

PubMed

de Moura, Roberto Soares; Rios, Anna Amélia S; Santos, Edmar J A; Nascimento, Ana Beatriz Amorim; de Castro Resende, Angela; Neto, Miguel Lemos; de Oliveira, Luiz Fernando; Mendes Ribeiro, Antonio Cláudio; Tano, Tania

2004-06-01

The mechanism underlying the analgesic effect of clonidine, an alpha(2)-adrenoceptor agonist, remains uncertain. Activation of alpha(2)-adrenoceptor induces the release of nitric oxide (NO) from endothelial cells, which has led us to test the hypothesis that the observed antinociceptive effect induced by the systemic administration of clonidine depends on the NO-cGMP pathway. The possible involvement of an opioid link in the antinociceptive effect of clonidine was also evaluated. The antinociceptive effect induced by systemic administration (intravenous or intraperitoneal) of clonidine was evaluated using the rat paw formalin, mice tail-flick and writhing tests. Clonidine (3-120 microg/kg) induces a dose-dependent antinociceptive effect in the formalin, tail-flick and writhing tests. The antinociceptive effect of clonidine in a dose that had no sedative effect assessed by rota rod test, was significantly reduced by NO-synthase and guanylyl cyclase inhibition. The antinociceptive effect of morphine, but not clonidine, was inhibited by naloxone. Our current results suggest that the antinociceptive effect of systemic clonidine does not involve the opioid receptor and is modulated by the NO-cGMP pathway.

Analgesic and anti-inflammatory activities of fixed oil of Macrotyloma uniflorum (Lam.) Verdc. in mice and rats.

PubMed

Fatima, Syeda Anum; Baig, Sadia Ghousia; Hasan, Muhammad Mohtasheemul; Ahmed, Salman; Salma, -

2018-03-01

Macrotyloma uniflorum commonly known as horse gram or kulthi bean is grown as a pulse for livestock and human consumption. The beans contain about 1.3% fat, 18% protein, 15% carbohydrate along with vitamins and minerals. In traditional medicine it is used as antihyperglycemic, antioxidant, antihypertensive and diuretic. Other important medicinal uses include treatment of renal stones, obesity, piles, oedema and fever. The present study evaluated analgesic (by acetic acid induced writhing, hot plate and tail flick tests in mice) and anti-inflammatory (carrageenan induced paw edema in rats) activities of Macrotyloma uniflorum fixed oil (MUFO). Four groups were included in study: Group-I: Normal Saline Control (2ml/kg), Group-II: MUFO (2ml/kg), Group-III: MUFO (4ml/kg), and Group-IV: Standard Acetyl salicylic acid (ASA 300mg/kg). All results were significant however delayed onset of action was observed in tail flick and paw edema tests. Acute oral toxicity of the oil was also checked in mice and was found safe upto 4ml/kg dose, as no signs of toxicity and mortality were observed. It is concluded that Macrotyloma uniflorum fixed oil may possess analgesic and anti-inflammatory activity which can be related with a peripheral mechanism of action.

Spinal antinociceptive effects of [D-Ala2]deltorphin II, a novel and highly selective delta-opioid receptor agonist.

PubMed

Improta, G; Broccardo, M

1992-01-01

Pharmacological assays in isolated tissues and binding tests have recently shown that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2, isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin I and II, respectively, possess a higher affinity and selectivity for delta-opioid receptors than any other known natural compound. Since much evidence supports the role of spinal delta-opioid sites in producing antinociceptive effects, we investigated whether analgesia might be detected by direct spinal cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu-selective agonist, were compared at different postinjection times by means of the tail-flick test. The DADELT II produced a dose-related inhibition of the tail-flick response, which lasted 10-60 min depending on the dose and appeared to be of shorter duration than the analgesia produced in rats after intrathecal injection of dermorphin (20-120 min). The analgesic effect of infused or injected DADELT II was completely abolished by naltrindole, the highly selective delta antagonist. These results confirm the involvement of delta receptors in spinal analgesic activity in the rat.

Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy.

PubMed

Romero, M T; Cooper, M L; Komisaruk, B R; Bodnar, R J

1988-01-01

Both gender-specific and gonadectomy-specific effects have been observed for the analgesic responses following continuous and intermittent cold-water swims (CCWS and ICWS respectively): female rats display significantly less analgesia than males, and gonadectomized rats display significantly less analgesia than sham-operated controls. The present study evaluated the effects of steroid replacement therapy with testosterone propionate (TP: 2 mg/kg, SC) upon CCWS and ICWS analgesia on the tail-flick and jump tests and hypothermia in sham-operated or gonadectomized male and female rats. Thirty days following surgery, rats received either no treatment, a sesame oil vehicle or TP for 14 days prior to, and then during testing. Relative to the no treatment condition, repeated vehicle injections in sham-operated rats eliminated the gender-specific, but did not affect the gonadectomy-specific effects upon CCWS and ICWS analgesia. TP reversed the deficits in CCWS and ICWS analgesia observed in both castrated and ovariectomized rats on both pain tests. TP only potentiated CCWS analgesia in sham-operated males on the tail-flick test. TP potentiated CCWS and ICWS hypothermia in gonadectomized rats and in male sham-operated rats. These data indicate that gonadal steroids play a major modulatory role in the etiology of swim analgesia, and that the observed gender effects are sensitive to possible adaptational variables.

Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies.

PubMed

Kaeidi, Ayat; Esmaeili-Mahani, Saeed; Sheibani, Vahid; Abbasnejad, Mehdi; Rasoulian, Bahram; Hajializadeh, Zahra; Afrazi, Samira

2011-06-14

Since the leaves of olive have been recommended in the literature as a remedy for the treatment of diabetes and they also contain antioxidant agents, we decided to investigate the possible effects of olive leaf extract (OLE) on in vitro and in vivo models of diabetic pain neuropathy. The high glucose-induced cell damage in naive and NGF-treated Pheochromocytoma (PC12) cells and streptozotocin-induced diabetic rats were used. Tail-flick test was used to access nociceptive threshold. Cell viability was determined by MTT assay. Biochemical markers of neural apoptosis were evaluated using immunoblotting. We found that elevation of glucose (4 times of normal) sequentially increases functional cell damage and caspase-3 activation in NGF-treated PC12 cells. Incubation of cells with OLE (200, 400 and 600 μg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathic pain which was evident from decreased tail-flick latency (thermal hyperalgesia). Activated caspase 3 and Bax/Bcl2 ratio were significantly increased in spinal cord of diabetic animals. OLE treatment (300 and 500 mg/kg per day) ameliorated hyperalgesia, inhibited caspase 3 activation and decreased Bax/Bcl2 ratio. Furthermore, OLE exhibited potent DPPH free radical scavenging capacity. The results suggest that olive leaf extract inhibits high glucose-induced neural damage and suppresses diabetes-induced thermal hyperalgesia. The mechanisms of these effects may be due, at least in part, to reduce neuronal apoptosis and suggest therapeutic potential of olive leaf extract in attenuation of diabetic neuropathic pain. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Inhaled delivery of Δ(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

PubMed

Nguyen, Jacques D; Aarde, Shawn M; Vandewater, Sophia A; Grant, Yanabel; Stouffer, David G; Parsons, Loren H; Cole, Maury; Taffe, Michael A

2016-10-01

Most human Δ(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano(®), e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ∼40 min of exposure, was of comparable magnitude (∼3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Do terrestrial hermit crabs sniff? Air flow and odorant capture by flicking antennules

PubMed Central

Koehl, M. A. R.

2016-01-01

Capture of odorant molecules by olfactory organs from the surrounding fluid is the first step of smelling. Sniffing intermittently moves fluid across sensory surfaces, increasing delivery rates of molecules to chemosensory receptors and providing discrete odour samples. Aquatic malacostracan crustaceans sniff by flicking olfactory antennules bearing arrays of chemosensory hairs (aesthetascs), capturing water in the arrays during downstroke and holding the sample during return stroke. Terrestrial malacostracans also flick antennules, but how their flicking affects odour capture from air is not understood. The terrestrial hermit crab, Coenobita rugosus, uses antennules bearing shingle-shaped aesthetascs to capture odours. We used particle image velocimetry to measure fine-scale fluid flow relative to a dynamically scaled physical model of a flicking antennule, and computational simulations to calculate diffusion to aesthetascs by odorant molecules carried in that flow. Air does not flow into the aesthetasc array during flick downstrokes or recovery strokes. Odorants are captured from air flowing around the outside of the array during flick downstrokes, when aesthetascs face upstream and molecule capture rates are 21% higher than for stationary antennules. Bursts of flicking followed by pauses deliver discrete odour samples to olfactory sensors, causing intermittency in odour capture by a different mechanism than aquatic crustaceans use. PMID:26763332

Do terrestrial hermit crabs sniff? Air flow and odorant capture by flicking antennules.

PubMed

Waldrop, Lindsay D; Koehl, M A R

2016-01-01

Capture of odorant molecules by olfactory organs from the surrounding fluid is the first step of smelling. Sniffing intermittently moves fluid across sensory surfaces, increasing delivery rates of molecules to chemosensory receptors and providing discrete odour samples. Aquatic malacostracan crustaceans sniff by flicking olfactory antennules bearing arrays of chemosensory hairs (aesthetascs), capturing water in the arrays during downstroke and holding the sample during return stroke. Terrestrial malacostracans also flick antennules, but how their flicking affects odour capture from air is not understood. The terrestrial hermit crab, Coenobita rugosus, uses antennules bearing shingle-shaped aesthetascs to capture odours. We used particle image velocimetry to measure fine-scale fluid flow relative to a dynamically scaled physical model of a flicking antennule, and computational simulations to calculate diffusion to aesthetascs by odorant molecules carried in that flow. Air does not flow into the aesthetasc array during flick downstrokes or recovery strokes. Odorants are captured from air flowing around the outside of the array during flick downstrokes, when aesthetascs face upstream and molecule capture rates are 21% higher than for stationary antennules. Bursts of flicking followed by pauses deliver discrete odour samples to olfactory sensors, causing intermittency in odour capture by a different mechanism than aquatic crustaceans use. © 2016 The Author(s).

Pharmacological evaluation of Musa seminifera Lour. fruit.

PubMed

Saha, Sanjib; Hossain, Faroque; Anisuzzman, Md; Islam, Md Khirul

2013-07-01

To study potential antioxidant, analgesic, antidiarrheal, and antibacterial activities of the ethanol extract of Musa seminifera Lour. fruit in different established in vivo and in vitro experimental models. In vitro antioxidant activity was studied in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay. Phenolic content was determined using Folin-Ciocalteu's reagent. Reducing ability was evaluated by ferric reducing power assay. Peripherally and centrally acting analgesic activity was studied in three different in vivo models, namely, acetic acid-induced writhing, hot-plate test, and tail-flick test in Swiss albino mice. In vivo antidiarrheal activity was evaluated in castor oil- and magnesium sulfate-induced diarrhea in mice. Gastrointestinal motility test was also carried out in mice. All studies in mice were undertaken at the doses of 250 and 500 mg/kg body weight. Antibacterial activity was assessed by disk diffusion assay against some Gram-positive and Gram-negative bacterial strains. Acute toxicity test was conducted to assess the safe doses of the extract. The extract showed 50% inhibitory concentration value of 12.65 μg/mL in DPPH radical-scavenging assay. Phenolic content was found to be 589.83 mg gallic acid equivalent per 100 g of dried fruits extract. Reducing power was in a concentration-dependent manner, and strongly comparable with the standard ascorbic acid. The extract demonstrated significant inhibition of writhing in acetic acid-induced writhing test at both dose levels (P<0.01). The extract also raised pain threshold in both hot-plate and tail-flick test in a dose-dependent manner, and the results were statistically significant (P<0.01). The extract significantly (P<0.01) increased latent period, and decreased defecation in both castor oil- and magnesium sulfate-induced diarrhea. The extract also decreased gastrointestinal motility in mice. In disk diffusion assay, the extract showed potential antibacterial activity against all the tested bacterial strains. The results suggest that the ethanol extract of M. seminifera fruit has potential antioxidant, analgesic, antidiarrheal, and antibacterial activities.

Antinociception and anti-inflammation induced by simvastatin in algesiometric assays in mice.

PubMed

Miranda, Hugo F; Noriega, Viviana; Olavarria, Loreto; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2011-12-01

Statins, belonging to a well-known drug class used for lowering cholesterol through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also have other pleiotropic properties, such as anti-inflammatory action. The purpose of this study was to evaluate the antinociceptive and anti-inflammatory effects of simvastatin in five models of nociceptive behaviour. Oral gavage administration of simvastatin induced a dose-dependent inhibition of nociception for 1 day in the acetic acid writhing (ED(50) = 5.59 ± 0.07), tail-flick (ED(50) = 112.96 ± 8.00), hot-plate (ED(50) = 134.87 ± 2.20), formalin hind paw (ED(50) = 19.86 ± 1.12 in phase I and 23.30 ± 2.05 in phase II) and orofacial formalin (ED(50) = 5.54 ± 2.74 in phase I and 11.48 ± 1.88 in phase II) tests. However, after 3 days, the values were in the acetic acid writhing (ED(50) = 6.14 ± 0.51), tail-flick (ED(50) = 154 ± 8.88), hot-plate (ED(50) = 136.14 ± 2.94), formalin hind paw (ED(50) = 15.93 ± 0.42 in phase I and 17.10 ± 1.80 in phase II) and orofacial formalin (ED(50) = 6.79 ± 0.66 in phase I and 5.80 ± 1.49 in phase II) tests. This study demonstrated the antinociceptive and anti-inflammatory activities of simvastatin in five models of tonic or phasic pain. These actions seem to be related to the inhibition of cytokine and prostanoid release and stimulation of nitric oxide synthesis. A possible clinical role of simvastatin could be related to the potentially beneficial effects in the neuropathic pain, and by their pleiotropic properties, they could play a clinical role in anti-inflammatory disease. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Peripheral and central determinants of a nociceptive reaction: an approach to psychophysics in the rat.

PubMed

Benoist, Jean-Michel; Pincedé, Ivanne; Ballantyne, Kay; Plaghki, Léon; Le Bars, Daniel

2008-09-03

The quantitative end-point for many behavioral tests of nociception is the reaction time, i.e. the time lapse between the beginning of the application of a stimulus, e.g. heat, and the evoked response. Since it is technically impossible to heat the skin instantaneously by conventional means, the question of the significance of the reaction time to radiant heat remains open. We developed a theoretical framework, a related experimental paradigm and a model to analyze in psychophysical terms the "tail-flick" responses of rats to random variations of noxious radiant heat. A CO(2) laser was used to avoid the drawbacks associated with standard methods of thermal stimulation. Heating of the skin was recorded with an infrared camera and was stopped by the reaction of the animal. For the first time, we define and determine two key descriptors of the behavioral response, namely the behavioral threshold (Tbeta) and the behavioral latency (Lbeta). By employing more than one site of stimulation, the paradigm allows determination of the conduction velocity of the peripheral fibers that trigger the response (V) and an estimation of the latency (Ld) of the central decision-making process. Ld (approximately 130 ms) is unaffected by ambient or skin temperature changes that affect the behavioral threshold (approximately 42.2-44.9 degrees C in the 20-30 degrees C range), behavioral latency (<500 ms), and the conduction velocity of the peripheral fibers that trigger the response (approximately 0.35-0.76 m/s in the 20-30 degrees C range). We propose a simple model that is verified experimentally and that computes the variations in the so-called "tail-flick latency" (TFL) caused by changes in either the power of the radiant heat source, the initial temperature of the skin, or the site of stimulation along the tail. This approach enables the behavioral determinations of latent psychophysical (Tbeta, Lbeta, Ld) and neurophysiological (V) variables that have been previously inaccessible with conventional methods. Such an approach satisfies the repeated requests for improving nociceptive tests and offers a potentially heuristic progress for studying nociceptive behavior on more firm physiological and psychophysical grounds. The validity of using a reaction time of a behavioral response to an increasing heat stimulus as a "pain index" is challenged. This is illustrated by the predicted temperature-dependent variations of the behavioral TFL elicited by spontaneous variations of the temperature of the tail for thermoregulation.

Is 2-Hydroxypropyl-β-cyclodextrin a Suitable Carrier for Central Administration of Δ9 -Tetrahydrocannabinol? Preclinical Evidence.

PubMed

Agabio, R; Sanna, F; Lobina, C; Monduzzi, M; Nairi, V; Cugia, F; Mameli, S; Pisanu, G M; Gessa, G L; Melis, M R

2017-12-01

Preclinical Research Δ 9 -Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPβCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPβCD (30 and 135 μg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 μg of THC/HPβCD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 μg THC/HPβCD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HPβCD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411-419, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation.

PubMed

Sharma, Neelam; Arora, Sandeep; Madan, Jitender

2018-02-01

Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was <5% which signified haemocompatibility of formulation. ED50 in rat tail-flick anti-nociceptive test was found ∼18.12 mg/kg. In post-operative pain model, reversal of mechanical allodynia and thermal hyperalgesia by NPH-MS was statistically significant (p < .001) as compared with NPH till 24 h post-dose.

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity

PubMed Central

Madaan, Reecha; Kumar, S.

2012-01-01

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1st h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum. PMID:23716876

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity.

PubMed

Madaan, Reecha; Kumar, S

2012-09-01

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1(st) h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum.

Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products.

PubMed

Liou, Shorong-Shii; Liu, I-Min; Lai, Mei Chou; Cheng, Juei-Tang

2005-07-14

The antinociceptive effects of crude Fuzei, the root of Aconitum carmichaeli and of Fuzei processed by three different methods were determined in mice and rats using the light tail-flick assay. A dose-dependent and significant increase in pain threshold was found at 60 min post treatment, with doses of 20-60 mg/kg crude Fuzei. The analgesic effects of processed Fuzei (20-60 mg/kg) exhibited a dose-dependent inhibition of tail-flick, but the effects were lower than those produced by crude Fuzei in the same tests. The analgesic effect of Yan-Fuzei, the salt baking product, was the most potent of the processed products and was nearly that provided by crude Fuzei. Although the concentrations of aconitine were significantly lower in the processed Fuzei than in the crude Fuzei, a higher oral LD50 was found for all of the processed Fuzei formulations. Moreover, antinociception of crude Fuzei and its processed products was attenuated but not totally blocked by naloxone at doses sufficient to block opioid mu-receptors. Furthermore, the analgesic effect of crude Fuzei and its processed products was decreased in opioid mu-receptor knockout mice, but the effect remained unaltered in mice with opioid mu-receptors, indicating that the analgesic effect of Fuzei is centrally mediated. These results demonstrate that Fuzei processed by salt baking possesses analgesic effects within a large therapeutic range, probably via a mechanism involving central opioid receptors that mediate the antinociception.

Occurrence of substance P(1-7) in the metabolism of substance P and its antinociceptive activity at the mouse spinal cord level.

PubMed

Sakurada, C; Watanabe, C; Sakurada, T

2004-04-01

Substance P (SP), which is known as a pain transmitter or modulator in the spinal cord, was degraded by the synaptic membranes of the mouse spinal cord. The major metabolites of SP were phenylalanine, SP(1-6), SP(1-7), SP(1-9), SP(8-9) and SP(10-11). Degradation of SP was inhibited by a metal chelator, o-phenanthroline, and also by specific inhibitors of endopeptidase-24.11, thiorphan and phosphoramidon. In contrast, captopril (a specific inhibitor of angiotensin-converting enzyme), bestatin (a specific inhibitor of aminopeptidase) and Z-321 (a specific inhibitor of prolylendopeptidase) showed little effect on the degradation of SP. The accumulation of the major cleavage products was strongly inhibited by phosphoramidon and thirophan, as well as the initial cleavage of SP. Thus, endopeptidase-24.11 plays a major role in SP degradation in the mouse spinal cord. Additional in vivo experiments were performed to investigate the antinociceptive effect of SP(1-7), a major product of SP that was detected after incubation with spinal synaptic membranes. In the mouse tail-flick test, the intrathecal administration of SP(1-7) (1.0-4.0 pmol) increased tail-flick latency in a dose-dependent manner. These results suggest that degradation of SP by spinal endopeptidase-24.11 may lead to the formation of SP(1-7), which has an ability to produce antinociceptive effects at the mouse spinal cord level.

Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain.

PubMed

Salehi, Forouz; Hosseini-Zare, Mahshid S; Aghajani, Haleh; Seyedi, Seyedeh Yalda; Hosseini-Zare, Maryam S; Sharifzadeh, Mohammad

2017-08-01

The aim of this study was to determine the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal nociception in a mouse model of acute pain. Here, we studied the effect of H-89 (protein kinase A inhibitor), bucladesine (Db-cAMP) (membrane-permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H-89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db-cAMP (50, 100, and 300 nm/mouse) were administered intraperitoneally (I.p.) 15 min before a tail-flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail-flick test, respectively. I.p. administration of H-89 and PTX significantly decreased the thermal-induced pain sensation in their low applied doses. Db-cAMP, however, decreased the pain sensation in a dose-dependent manner. The highest applied dose of H-89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db-cAMP in doses of 50 and 100 nm/mouse. Surprisingly, Db-cAMP decreased the antinociceptive effect of the lowest dose of H-89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H-89 on pain sensation; however, the highest dose of H-89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co-administration of Db-cAMP and PTX increased the antinociceptive effect of each compound on thermal-induced pain. In conclusion, PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Antinociceptive effects of clebopride in the mouse.

PubMed

Bittencourt, S C; De Lima, T C; Morato, G S

1995-09-01

1. The effects of the substituted benzamide clebopride, an orthopramide, on nociception of chemical and thermal stimuli were investigated. 2. Clebopride (0.5, 1.0 and 2.0 mg/kg) promoted significant analgesia in the tail-flick and hot-plate tests and against abdominal constrictions produced by acetic acid or acetylcholine. 3. The analgesic effects of clebopride were not influenced by pretreatment with naltrexone (1-3 mg/kg). 4. The results suggest that clebopride induces analgesia against both thermal and chemical nociceptive stimuli, which is not mediated via opioid mechanisms.

Evaluation of antinociceptive activity of aqueous extract of bark of psidium guajava in albino rats and albino mice.

PubMed

Sekhar, N Chandra; Jayasree, T; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-09-01

Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. AEPG antinociceptive activity involves activation of the peripheral and central mechanisms.

Indomethacin uptake into poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane) network: In vitro and in vivo controlled release study.

PubMed

Nita, Loredana E; Chiriac, Aurica P; Nistor, Manuela T; Tartau, Liliana

2012-04-15

Networks based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane), synthesized through radical dispersion polymerization, were used as template for indomethacin (INN) as model drug. The copolymers were characterized by swelling studies at three pH values (2.4, 5.5 and 7.4) and two temperatures (room temperature 24 °C and physiological temperature 37 °C). Fourier transform infrared (FTIR) spectroscopic analysis was used to sustain the copolymer structures. Scanning electron microscopy (SEM) and thermogravimetric (TG) investigations were used to examine microstructure and appreciate the thermal stability of the polymer samples. The studies of the INN drug release from the copolymer networks were in vitro performed. The in vivo study results (biocompatibility tests, somatic nociceptive experimental model (tail flick test) and visceral nociceptive experimental model (writhing test)) are also reported in this paper. Copyright © 2012 Elsevier B.V. All rights reserved.

Antinociception induced by atorvastatin in different pain models.

PubMed

Garcia, G G; Miranda, H F; Noriega, V; Sierralta, F; Olavarría, L; Zepeda, R J; Prieto, J C

2011-11-01

Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. It is assumed that the beneficial effects of statin therapy are entirely due to cholesterol reduction. Statins have an additional activity (pleiotropic effect) that has been associated to their anti-inflammatory effects. The aim of the present study was to assess the antinociceptive activity of atorvastatin in five animal pain models. The daily administration of 3-100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent antinociception in the writhing, tail-flick, orofacial formalin and formalin hind paw tests. However, this antinociceptive activity of atorvastatin was detectable only at high concentrations in the hot plate assay. The data obtained in the present study demonstrates the effect of atorvastatin to reduce nociception and inflammation in different animal pain models. Copyright © 2011 Elsevier Inc. All rights reserved.

Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action

PubMed Central

Maione, Sabatino; Piscitelli, Fabiana; Gatta, Luisa; Vita, Daniela; De Petrocellis, Luciano; Palazzo, Enza; de Novellis, Vito; Di Marzo, Vincenzo

2011-01-01

BACKGROUND AND PURPOSE Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception. EXPERIMENTAL APPROACH Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey. KEY RESULTS Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB1 adenosine A1 and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD. CONCLUSIONS AND IMPLICATIONS CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action. PMID:20942863

Antagonists to TRPV1, ASICs and P2X have a potential role to prevent the triggering of regional bone metabolic disorder and pain-like behavior in tail-suspended mice.

PubMed

Hanaka, Megumi; Iba, Kousuke; Dohke, Takayuki; Kanaya, Kumiko; Okazaki, Shunichiro; Yamashita, Toshihiko

2018-05-01

Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice. The hind limb-unloaded mice were subjected to tail suspension with the hind limbs elevated for 14days. The effects of the TRPV1, ASIC3, P2X2/3 antagonists on pain-like behaviors as assessed by the von Frey test, paw flick test and spontaneous pain scale; the expressions of TRPV1, ASICs, and P2X2 in the bone; and the effects of those antagonists on osteoblast and osteoclast regulators were examined. In addition, we evaluated the preventive effect of continuous treatment with a TRPV1 antagonist on the trigger for pain-like behavior and bone loss in tail-suspended mice. Pain-like behaviors were significantly improved by the treatment with TRPV1, ASIC, P2X antagonists; TRPV1, ASICs and P2X were expressed in the bone tissues; and the antagonists to these receptors down-regulated the expression of osteoblast and osteoclast regulators in tail-suspended mice. In addition, continuous treatment with a TRPV1 antagonist during tail-suspension prevented the induction of pain-like behaviors and regional bone loss in the unloaded hind limbs. We, therefore, believe that those receptor antagonists have a potential role in preventing the triggering of skeletal pain with associated regional bone metabolic disorder. Copyright © 2018 Elsevier Inc. All rights reserved.

Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase.

PubMed

Marcus, David J; Zee, Michael; Hughes, Alex; Yuill, Matthew B; Hohmann, Andrea G; Mackie, Ken; Guindon, Josée; Morgan, Daniel J

2015-06-12

Morphine and fentanyl are opioid analgesics in wide clinical use that act through the μ-opioid receptor (MOR). However, one limitation of their long-term effectiveness is the development of tolerance. Receptor desensitization has been proposed as a putative mechanism driving tolerance to G protein-coupled receptor (GPCR) agonists. Recent studies have found that tolerance to morphine is mediated by the c-Jun N-terminal Kinase (JNK) signaling pathway. The goal of the present study was to test the hypotheses that: 1) JNK inhibition will be antinociceptive on its own; 2) JNK inhibition will augment morphine antinociception and; 3) JNK mediates chronic tolerance for the antinociceptive effects of morphine using acute (hotplate and tail-flick), inflammatory (10 μl of formalin 2.5%) and chemotherapy (cisplatin 5 mg/kg ip once weekly)-induced neuropathic pain assays. We found that JNK inhibition by SP600125 (3 mg/kg) produces a greater antinociceptive effect than morphine (6 mg/kg) alone in the formalin test. Moreover, co-administration of morphine (6 mg/kg) with SP600125 (3 mg/kg) produced a sub-additive antinociceptive effect in the formalin test. We also show that pre-treatment with SP600125 (3 or 10 mg/kg), attenuates tolerance to the antinociceptive effects of morphine (10 mg/kg), but not fentanyl (0.3 mg/kg), in the tail-flick and hotplate tests. Pre-treatment with SP600125 also attenuates tolerance to the hypothermic effects of both morphine and fentanyl. We also examined the role of JNK in morphine tolerance in a cisplatin-induced model of neuropathic pain. Interestingly, treatment with SP600125 (3 mg/kg) alone attenuated mechanical and cold allodynia in a chemotherapy-induced pain model using cisplatin. Strikingly, SP600125 (3 mg/kg) pre-treatment prolonged the anti-allodynic effect of morphine by several days (5 and 7 days for mechanical and cold, respectively). These results demonstrate that JNK signaling plays a crucial role in mediating antinociception as well as chronic tolerance to the antinociceptive effects of morphine in acute, inflammatory, and neuropathic pain states. Thus, inhibition of JNK signaling pathway, via SP600125, represents an efficacious pharmacological approach to delay tolerance to the antinociceptive effects of chronic morphine in diverse pain models.

Human beta-endorphin: synthesis and biological activity of analogs with substitutions in positions 2, 9, 18, 27 and 31.

PubMed

Yeung, H W; Yamashiro, D; Tseng, L F; Chang, W C; Li, C H

1981-02-01

Four analogs of the opioid peptide human beta-endorphin (Bh-EP) have been synthesized: [D-Lys9, Phe27, Gly31]-beta h-EP, [D-PHe18,Phe27,Gly31]-beta h-EP, [D-Thr2,D-Lys9,Phe27,Gly31]-beta h-EP, and [D-Thr2,D-Phe18,Phe27,Gly31]-beta h-EP. All are practically indistinguishable from beta h-EP in the guinea pig ileum assay. All show diminished analgesic potency in the mouse tail-flick assay.

Protective role of Delphinium denudatum (Jadwar) against morphine induced tolerance and dependence in mice.

PubMed

Zafar, S; Ahmad, M A; Siddiqui, T A

2001-11-01

Chronic treatment with Delphinium denudatum (Dd) (Jadwar) (family: Ranunculaceae, 200-1600 mg/kg) suppressed morphine withdrawal jumps in a dose-dependent manner, a sign of the development of dependence to opiate as assessed by naloxone (2 mg/kg) precipitation withdrawal on day 10 of testing in mice. Repeated administration of Dd (200-1600 mg/kg) for 9 days attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg), also produces significant change in tail-flick latency from the saline pretreated group in a dose-dependent manner.

Neuroprotective and antinociceptive effects of rosemary (Rosmarinus officinalis L.) extract in rats with painful diabetic neuropathy.

PubMed

Rasoulian, Bahram; Hajializadeh, Zahra; Esmaeili-Mahani, Saeed; Rashidipour, Marzieh; Fatemi, Iman; Kaeidi, Ayat

2018-05-12

Diabetes mellitus is associated with the development of neuronal tissue damage in different central and peripheral nervous system regions. A common complication of diabetes is painful diabetic peripheral neuropathy. We have explored the antihyperalgesic and neuroprotective properties of Rosmarinus officinalis L. extract (RE) in a rat model of streptozotocin (STZ)-induced diabetes. The nociceptive threshold and motor coordination of these diabetic rats was assessed using the tail-flick and rotarod treadmill tests, respectively. Activated caspase-3 and the Bax:Bcl-2 ratio, both biochemical indicators of apoptosis, were assessed in the dorsal half of the lumbar spinal cord tissue by western blotting. Treatment of the diabetic rats with RE improved hyperglycemia, hyperalgesia and motor deficit, suppressed caspase-3 activation and reduced the Bax:Bcl-2 ratio, suggesting that the RE has antihyperalgesic and neuroprotective effects in this rat model of STZ-induced diabetes. Cellular mechanisms underlying the observed effects may, at least partially, be related to the inhibition of neuronal apoptosis.

Antinociceptive and free radical scavenging activities of Cocos nucifera L. (Palmae) husk fiber aqueous extract.

PubMed

Alviano, Daniela S; Rodrigues, Karen F; Leitão, Suzana G; Rodrigues, Marcio L; Matheus, Maria Eline; Fernandes, Patrícia D; Antoniolli, Angelo R; Alviano, Celuta S

2004-06-01

In the current study, the analgesic and free radical scavenging properties of an aqueous extract from the husk fiber of Cocos nucifera L. (Palmae) were demonstrated by the use of in vivo and in vitro models. The orally administered Cocos nucifera aqueous extract (200 or 400 mg/kg) inhibited the acetic acid-induced writhing response in mice. Tail flick and hot plate assays demonstrated that treatment of animals with this plant extract at 200 mg/kg induced attenuation in the response to a heat stimulus. A LD(50) of 2.30 g/kg was obtained in acute toxicity tests. Topic treatment of rabbits with the Cocos nucifera extract indicated that it does not induce any significant dermic or ocular irritation. In vitro experiments using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) photometric assay demonstrated that this plant extract also possesses free radical scavenging properties.

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

PubMed

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats.

PubMed

Haghparast, Abbas; Ordikhani-Seyedlar, Mehdi; Ziaei, Maryam

2008-06-27

Several lines of investigation show that the rostral ventromedial medulla is a critical relay for midbrain regions, including the nucleus cuneiformis (CnF), which control nociception at the spinal cord. There is some evidence that local stimulation or morphine administration into the CnF produces the effective analgesia through the nucleus raphe magnus (NRM). The present study tries to determine the effect of morphine-induced analgesia following microinjection into the CnF in the absence of NRM. Seven days after the cannulae implantation, morphine was microinjected bilaterally into the CnF at the doses of 0.25, 1, 2.5, 5, 7.5 and 10 microg/0.3 microl saline per side. The morphine-induced antinociceptive effect measured by tail-flick test at 30, 60, 90 and 120 min after microinjection. The results showed that bilateral microinjection of morphine into the CnF dose-dependently causes increase in tail-flick latency (TFL). The 50% effective dose of morphine was determined and microinjected into the CnF (2.5 microg/0.3 microl saline per side) in rats after NRM electrolytic lesion (1 mA, 30 s). Lesion of the NRM significantly decreased TFLs, 30 (P<0.01) and 60 (P<0.05) but not 90-120 min after morphine microinjection into the CnF, compared with sham-lesion group. We concluded that morphine induces the analgesic effects through the opioid receptors in the CnF. It is also appeared that morphine-induced antinociception decreases following the NRM lesion but it seems that there are some other descending pain modulatory pathways that activate in the absence of NRM.

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

PubMed Central

Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

2015-01-01

Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

Effects of curcumin and captopril on the functions of kidney and nerve in streptozotocin-induced diabetic rats: role of angiotensin converting enzyme 1.

PubMed

Abd Allah, Eman S H; Gomaa, Asmaa M S

2015-10-01

Oxidative stress and inflammation are involved in the development and progression of diabetes and its complications. The renin-angiotensin system also plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that curcumin and captopril would restore the kidney and nerve functions of diabetic rats through their angiotensin converting enzyme 1 (ACE1) inhibiting activity as well as their antioxidant and anti-inflammatory effects. Diabetes was induced by a single intraperitoneal injection of streptozotocin (100 mg·kg(-1) body weight). One week after induction of diabetes, rats were treated with 100 mg·kg(-1)·day(-1) curcumin or 50 mg·kg(-1)·day(-1) captopril orally for 6 weeks. Compared with diabetic control rats, curcumin- or captopril-treated diabetic rats had significantly improved blood glucose, lipid profile, kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), and pain thresholds assessed by Von Frey filaments, hot plate test, and tail-flick test. Diabetic control rats showed increased levels of total peroxide, renal and neural tumor necrosis factor-α and interleukin-10, and renal ACE1 compared with nondiabetic rats. Although treatment with either curcumin or captopril restored the altered variables, captopril was more effective in reducing these variables. ACE1 was positively correlated with BUN and creatinine and negatively correlated with paw withdrawal threshold, hot plate reaction time, and tail-flick latency, suggesting a possible causal relationship. We conclude that curcumin and captopril protect against diabetic nephropathy and neuropathy by inhibiting ACE1 as well as oxidation and inflammation. These findings suggest that curcumin and captopril may have a role in the treatment of diabetic nephropathy and neuropathy.

Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain.

PubMed

Altier, N; Stewart, J

1993-11-19

Experiments were designed to examine the analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5% formalin into one hind paw. Formalin-induced pain responses were continuously recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min; the analgesia was more potent and longer-lasting when DiMe-C7 was infused after, rather than prior to, the early pain phase. In another set of experiments, rats were tested in the formalin test immediately following bilateral infusions of amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed to alter pain responses when infused into the mPFC, but both doses attenuated pain responses during 25 min when infused into the NAS. There was no evidence for pain inhibition in the tail-flick test for phasic pain following either intra-VTA DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra-NAS amphetamine produces analgesia in the formalin, but not the tail-flick test, suggests that activation of mesolimbic dopamine (DA) neurons contributes to suppression of tonic pain. Because stressors attenuate tonic pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of pain- or stress-induced pain inhibitory system.

Involvement of 5-HT(2) serotonergic receptors of the nucleus raphe magnus and nucleus reticularis gigantocellularis/paragigantocellularis complex neural networks in the antinociceptive phenomenon that follows the post-ictal immobility syndrome.

PubMed

de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Ferreira, Célio Marcos Dos Reis; Coimbra, Norberto Cysne

2006-09-01

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.

Antinociception after both peripheral and intrathecal injection of oxotremorine is modulated by spinal nitric oxide.

PubMed

Machelska, H; Pavone, F; Capone, F; Przewłocka, B

1999-03-01

The present study investigated the role of spinal nitric oxide (NO) in the antinociception induced by intraperitoneal (i.p.) and intrathecal (i.th.) injection of oxotremorine. The experiments were carried out on male Wistar rats, which had cannulas chronically implanted in the lumbar enlargement of the spinal cord. Antinociceptive effects were evaluated using a tail-flick and a paw pressure test. To raise the spinal NO level, the rats received the NO donor, 3-morpholino-sydnonimine (SIN-1, 10 and 100 microg/5 microl); to lower the NO level, the inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME, 50 and 400 microg/5 microl), was administered. Both those substances were injected i.th. Systemic injections of oxotremorine (0.02 and 0.1 mg/kg) produced a significant increase in the thermal nociceptive threshold, while the mechanical threshold was affected only by the higher dose (0.1 mg/kg) of the muscarinic agonist. I.th. injections of oxotremorine (0.1 ng, 1 ng, 1 microg/5 microl) produced significant antinociception in both those tests. I.th. administration of SIN-1 in doses which themselves did not affect the nociceptive threshold antagonized both the peripheral and central oxotremorine antinociception. I.th. administration of L-NAME (50 and 400 microg/5 microl) did not change the nociceptive threshold, but dose-dependently potentiated the effects of oxotremorine injected i.p. in both tests; however, the effect of i.th. administration of oxotremorine was potentiated only in the tail-flick test. Our results demonstrate that irrespective of the way of its injection, the antinociceptive effect of oxotremorine is modulated by activity of the spinal NO. Moreover, our results further support the hypothesis that NO present in the spinal cord exerts pronociceptive effects.

Evaluation of Antinociceptive Activity of Aqueous Extract of Bark of Psidium Guajava in Albino Rats and Albino Mice

PubMed Central

Jayasree, T.; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-01-01

Background: Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. Aim: To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Materials and Methods: Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. Results: The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. Conclusion: AEPG antinociceptive activity involves activation of the peripheral and central mechanisms. PMID:25386462

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

PubMed

Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

2017-12-05

Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

Entanglement between thermoregulation and nociception in the rat: the case of morphine

PubMed Central

El Bitar, Nabil; Pollin, Bernard; Karroum, Elias; Pincedé, Ivanne

2016-01-01

In thermoneutral conditions, rats display cyclic variations of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Systemic morphine elicits their vasoconstriction followed by hyperthermia in a naloxone-reversible and dose-dependent fashion. The dose-response curves were steep with ED50 in the 0.5–1 mg/kg range. Given the pivotal functional role of the rostral ventromedial medulla (RVM) in nociception and the rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, the RVM/rMR was blocked by muscimol: it suppressed the effects of morphine. “On-” and “off-” neurons recorded in the RVM/rMR are activated and inhibited by thermal nociceptive stimuli, respectively. They are also implicated in regulating the cyclic variations of the vasomotion of the tail and paws seen in thermoneutral conditions. Morphine elicited abrupt inhibition and activation of the firing of on- and off-cells recorded in the RVM/rMR. By using a model that takes into account the power of the radiant heat source, initial skin temperature, core body temperature, and peripheral nerve conduction distance, one can argue that the morphine-induced increase of reaction time is mainly related to the morphine-induced vasoconstriction. This statement was confirmed by analyzing in psychophysical terms the tail-flick response to random variations of noxious radiant heat. Although the increase of a reaction time to radiant heat is generally interpreted in terms of analgesia, the present data question the validity of using such an approach to build a pain index. PMID:27605533

Evaluation of analgesic activity of various extracts of Sida tiagii Bhandari.

PubMed

Kumawat, Ram Kumar; Kumar, Suresh; Sharma, Sunil

2012-01-01

Sida tiagii Bhandari mostly found in India and Pakistan which belongs to family Malvaceae, is traditionally used as analgesic, anti-inflammatory, sedative, anxiolytic, anti-seizure and anti-platelet. The present study was done to explore the analgesic activity of various extracts of fruits of the plant Sida tiagii Bhandari. The grinded fruits were extracted with 90% ethanol and partitioned with n-hexane (n-hexane extract; HS) and ethyl acetate (ethyl acetate extract; EAS), successively. The residual ethanol fraction (residual ethanol extract; RES) was also prepared by drying on water bath separately. All three extracts were administered orally at a dose of 200 mg/kg and 500 mg/kg of body weight. The analgesic activity of above extracts was evaluated by using acetic acid induced writhing, tail immersion and tail flick tests in Swiss albino mice. The EAS extract was found to reduce pain and RES extract of Sida tiagii B. was found to have good analgesic activity in comparison to other extracts.

A three-dimensional kinematic analysis of tongue flicking in Python molurus.

PubMed

de Groot, Jurriaan H; van der Sluijs, Inke; Snelderwaard, Peter Ch; van Leeuwen, Johan L

2004-02-01

The forked snake tongue is a muscular organ without hard skeletal support. A functional interpretation of the variable arrangement of the intrinsic muscles along the tongue requires a quantitative analysis of the motion performance during tongue protrusion and flicking. Therefore, high-speed fluoroscopy and high-speed stereo photogrammetry were used to analyse the three-dimensional shape changes of the tongue in Python molurus bivittatus (Boidae). The posterior protruding part of the tongue elongated up to 130% while the flicking anterior portion elongated maximally 60%. The differences in tongue strains relate to the absence or presence, respectively, of longitudinal muscle fibres in the peripheral tongue. Maximum overall protrusion velocity (4.3 m s(-1)) occurred initially when the tongue tip left the mouth. Maximum tongue length of approximately 0.01 body length (20 mm) was reached during the first tongue flick. These observations are discussed within the scope of the biomechanical constraints of hydrostatic tongue protrusion: a negative forward pressure gradient, longitudinal tongue compliance and axial tongue stiffness. The three-dimensional deformation varied along the tongue with a mean curvature of 0.06 mm(-1) and a maximum value of 0.5 mm(-1). At the basis of the anterior forked portion of the tongue tips, extreme curvatures up to 2.0 mm(-1) were observed. These quantitative results support previously proposed inferences about a hydrostatic elongation mechanism and may serve to evaluate future dynamic models of tongue flicking.

Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – neurokinin-1 antagonist peptidomimetics

PubMed Central

Guillemyn, Karel; Kleczkowska, Patrycia; Lesniak, Anna; Dyniewicz, Jolanta; Van der Poorten, Olivier; Van den Eynde, Isabelle; Keresztes, Attila; Varga, Eva; Lai, Josephine; Porreca, Frank; Chung, Nga N.; Lemieux, Carole; Mika, Joanna; Rojewska, Ewelina; Makuch, Wioletta; Van Duppen, Joost; Przewlocka, Barbara; Broeck, Jozef Vanden; Lipkowski, Andrzej W.; Schiller, Peter W.; Tourwé, Dirk; Ballet, Steven

2014-01-01

A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3’,5’-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-β-Ala-NMe-Bn) were selected for in vivo behavioral assays, which were conducted in acute (tail-flick) and neuropathic pain models (cold plate and von Frey) in rats. Compared to the parent opioid compound 33 (without NK1R pharmacophore), hybrid 22 was more active in the neuropathic pain models. Attenuation of neuropathic pain emerged from NK1R antagonism as demonstrated by the pure NK1R antagonist 6. Surprisingly, despite a lower in vitro activity at NK1R in comparison with 4, compound 22 was more active in the neuropathic pain models. Although potent analgesic effects were observed for 4 and 22, upon chronic administration, both manifested a tolerance profile similar to that of morphine and cross tolerance with morphine in a neuropathic pain model in rat. PMID:25544687

Scouting new sigma receptor ligands: Synthesis, pharmacological evaluation and molecular modeling of 1,3-dioxolane-based structures and derivatives.

PubMed

Franchini, Silvia; Battisti, Umberto Maria; Prandi, Adolfo; Tait, Annalisa; Borsari, Chiara; Cichero, Elena; Fossa, Paola; Cilia, Antonio; Prezzavento, Orazio; Ronsisvalle, Simone; Aricò, Giuseppina; Parenti, Carmela; Brasili, Livio

2016-04-13

Herein we report the synthesis and biological activity of new sigma receptor (σR) ligands obtained by combining different substituted five-membered heterocyclic rings with appropriate σR pharmacophoric amines. Radioligand binding assay, performed on guinea pig brain membranes, identified 25b (1-(1,4-dioxaspiro[4.5]decan-2-ylmethyl)-4-benzylpiperazine) as the most interesting compound of the series, displaying high affinity and selectivity for σ1R (pKiσ1 = 9.13; σ1/σ2 = 47). The ability of 25b to modulate the analgesic effect of the κ agonist (-)-U-50,488H and μ agonist morphine was evaluated in vivo by radiant heat tail-flick test. It exhibited anti-opioid effects on both κ and μ receptor-mediated analgesia, suggesting an agonistic behavior at σ1R. Docking studies were performed on the theoretical σ1R homology model. The present work represents a new starting point for the design of more potent and selective σ1R ligands. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

PubMed

Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

1980-04-01

Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency.

Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.

PubMed Central

Li, C H; Tseng, L F; Ferrara, P; Yamashiro, D

1980-01-01

Biological activities of synthetic camel beta-endorphin and human beta-endorphin (beta h-EP) have been measured by the radioreceptor binding assay, using [Tyr27-3H]-beta h-EP as the primary ligand and by the tail-flick test for analgesic potency. Four synthetic analogs of beta h-EP, namely [Gly31]-beta h-EP-Gly-NH2, [Gly31]-beta h-EP-Gly-Gly-NH2, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, and [CH3(CH2)4NH231]-beta h-EP, have also been assayed by the same procedures. Results indicate a clear dissociation of radioreceptor binding activity from analgesic potency. PMID:6246537

Response to Arend Flick

ERIC Educational Resources Information Center

RiCharde, R. Stephen

2009-01-01

This article presents the author's response to Arend Flick. The author states that Flick is correct that the issue of rubrics is broader than interrater reliability, though it is the assessment practitioner's primary armament against what the author has heard dubbed "refried bean counting" (insinuating that assessment statistics are not just bean…

A biomechanical comparison in the lower limb and lumbar spine between a hit and drag flick in field hockey.

PubMed

Ng, Leo; Rosalie, Simon M; Sherry, Dorianne; Loh, Wei Bing; Sjurseth, Andreas M; Iyengar, Shrikant; Wild, Catherine Y

2018-03-01

Research has revealed that field hockey drag flickers have greater odds of hip and lumbar injuries compared to non-drag flickers (DF). This study aimed to compare the biomechanics of a field hockey hit and a specialised field hockey drag flick. Eighteen male and seven female specialised hockey DF performed a hit and a drag flick in a motion analysis laboratory with an 18-camera three-dimensional motion analysis system and a calibrated multichannel force platform to examine differences in lower limb and lumbar kinematics and kinetics. Results revealed that drag flicks were performed with more of a forward lunge on the left lower limb resulting in significantly greater left ankle dorsiflexion, knee, hip and lumbar flexion (Ps<0.001) compared to a hit. Drag flicks were also performed with significantly greater lateral flexion (P < 0.002) and rotation of the lumbar spine (P < 0.006) compared to a hit. Differences in kinematics lead to greater shear, compression and tensile forces in multiple left lower limb and lumbar joints in the drag flick compared to the hit (P < 0.05). The biomechanical differences in drag flicks compared to a hit may have ramifications with respect to injury in field hockey drag flickers.

Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion.

PubMed

Ogata, M; Noda, K; Akita, H; Ishibashi, H

2015-03-19

Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment during adulthood and the neonatal period exhibit akinetic motor activity and spontaneous motor hyperactivity during adolescence, respectively, indicating that the behavioral effects of dopamine depletion depend on the period of lesion development. Dopamine depletion during adulthood induces hyperalgesic response to mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal dopamine depletion on nociceptive response in adolescent rats are yet to be examined. The latter aspect was addressed in this study, and behavioral responses were examined using von-Frey, tail flick, and formalin tests. The formalin test revealed that rats with neonatal dopamine depletion exhibited a significant increase in nociceptive response during interphase (6-15min post formalin injection) and phase 2 (16-75min post formalin injection). This increase in nociceptive response to the formalin injection was not reversed by pretreatment with methamphetamine, which ameliorates motor hyperactivity observed in adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail flick tests failed to reveal significant differences in withdrawal thresholds between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal response to the formalin injection into the rat hind paw was also examined through immunohistochemical analysis of c-Fos protein. Significantly increased numbers of c-Fos-immunoreactive cells were observed in laminae I-II and V-VI of the ipsilateral spinal cord to the site of the formalin injection in rats with neonatal dopamine depletion compared with vehicle-treated rats. These results suggest that the dopaminergic neural system plays a crucial role in the development of a neural network for tonic pain, including the spinal neural circuit for nociceptive transmission, and that the mechanism underlying hyperalgesia to tonic pain is not always consistent with that of spontaneous motor hyperactivity induced by neonatal dopamine depletion. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice.

PubMed

Fitting, Sylvia; Stevens, David L; Khan, Fayez A; Scoggins, Krista L; Enga, Rachel M; Beardsley, Patrick M; Knapp, Pamela E; Dewey, William L; Hauser, Kurt F

2016-01-01

Despite considerable evidence that chronic opiate use selectively affects the pathophysiologic consequences of human immunodeficiency virus type 1 (HIV-1) infection in the nervous system, few studies have examined whether neuro-acquired immune deficiency syndrome (neuroAIDS) might intrinsically alter the pharmacologic responses to chronic opiate exposure. This is an important matter because HIV-1 and opiate abuse are interrelated epidemics, and HIV-1 patients are often prescribed opiates as a treatment of HIV-1-related neuropathic pain. Tolerance and physical dependence are inevitable consequences of frequent and repeated administration of morphine. In the present study, mice expressing HIV-1 Tat in a doxycycline (DOX)-inducible manner [Tat(+)], their Tat(-) controls, and control C57BL/6 mice were chronically exposed to placebo or 75-mg morphine pellets to explore the effects of Tat induction on morphine tolerance and dependence. Antinociceptive tolerance and locomotor activity tolerance were assessed using tail-flick and locomotor activity assays, respectively, and physical dependence was measured with the platform-jumping assay and recording of other withdrawal signs. We found that Tat(+) mice treated with DOX [Tat(+)/DOX] developed an increased tolerance in the tail-flick assay compared with control Tat(-)/DOX and/or C57/DOX mice. Equivalent tolerance was developed in all mice when assessed by locomotor activity. Further, Tat(+)/DOX mice expressed reduced levels of physical dependence to chronic morphine exposure after a 1-mg/kg naloxone challenge compared with control Tat(-)/DOX and/or C57/DOX mice. Assuming the results seen in Tat transgenic mice can be generalized to neuroAIDS, our findings suggest that HIV-1-infected individuals may display heightened analgesic tolerance to similar doses of opiates compared with uninfected individuals and show fewer symptoms of physical dependence. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity.

PubMed

Zádor, Ferenc; Balogh, Mihály; Váradi, András; Zádori, Zoltán S; Király, Kornél; Szűcs, Edina; Varga, Bence; Lázár, Bernadette; Hosztafi, Sándor; Riba, Pál; Benyhe, Sándor; Fürst, Susanna; Al-Khrasani, Mahmoud

2017-11-05

14-O-methyl (14-O-Me) group in morphine-6-O-sulfate (M6SU) or oxymorphone has been reported to be essential for enhanced affinity, potency and antinociceptive effect of these opioids. Herein we report on the pharmacological properties (potency, affinity and efficacy) of the new compound, 14-O-methylmorphine (14-O-MeM) in in vitro. Additionally, we also investigated the antinociceptive effect of the novel compound, as well as its inhibitory action on gastrointestinal transit in in vivo. The potency and efficacy of test compound were measured by [ 35 S]GTPγS binding, isolated mouse vas deferens (MVD) and rat vas deferens (RVD) assays. The affinity of 14-O-MeM for opioid receptors was assessed by radioligand binding and MVD assays. The antinociceptive and gastrointestinal effects of the novel compound were evaluated in the rat tail-flick test and charcoal meal test, respectively. Morphine, DAMGO, Ile 5,6 deltorphin II, deltorphin II and U-69593 were used as reference compounds. 14-O-MeM showed higher efficacy (E max ) and potency (EC 50 ) than morphine in MVD, RVD or [ 35 S]GTPγS binding. In addition, 14-O-MeM compared to morphine showed higher affinity for μ-opioid receptor (MOR). In vivo, in rat tail-flick test 14-O-MeM proved to be stronger antinociceptive agent than morphine after peripheral or central administration. Additionally, both compounds inhibited the gastrointestinal peristalsis. However, when the antinociceptive and antitransit doses for each test compound are compared, 14-O-MeM proved to have slightly more favorable pharmacological profile. Our results affirm that 14-O-MeM, an opioid of high efficacy and affinity for MOR can be considered as a novel analgesic agent of potential clinical value. Copyright © 2017 Elsevier B.V. All rights reserved.

Antinociceptive and Anti-inflammatory Effects of Triterpenes from Pluchea quitoc DC. Aerial Parts

PubMed Central

Nobre da Silva, Francisco Alcione; de Farias Freire, Sônia Maria; da Rocha Borges, Marilene Oliveira; Vidal Barros, Francisco Erivaldo; da de Sousa, Maria; de Sousa Ribeiro, Maria Nilce; Pinheiro Guilhon, Giselle Maria Skelding; Müller, Adolfo Henrique; Romão Borges, Antonio Carlos

2017-01-01

Background: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as “quitoco,” “caculucage,” “tabacarana” and “madre-cravo,” is indicated for inflammatory conditions such as bronchitis, arthritis, and inflammation in the uterus and digestive system. Objective: This study evaluated the analgesic and anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc aerial parts. Materials and Methods: The triterpenes compounds β-amyrin, taraxasterol and pseudo-taraxasterol in a mixture (T); β-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture (Ta); β-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with β-amyrin, taraxasterol and pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception and inflammation. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing and tail-flick tests while leukocyte migration to the peritoneal cavity was used for anti-inflammatory profile. Results: The oral administration of T or Tafe (40 mg/kg and 70 mg/kg) and Ta (70 mg/kg) to mice reduced acetic acid-induced writhing. The tail-flick response of mice was not affected by T or Tafe (40 mg/kg). T or Tafe (40 mg/kg) and Ta (70 mg/kg) also inhibited peritoneal leukocyte infiltration following the injection of carrageenan. Conclusion: The results demonstrate the anti-inflammatory and peripheral antinociceptive activity of the triterpenes β-amyrin, taraxasterol, and pseudo-taraxasterol that were decreased when these were acetylated; while the acetylated triterpenes in mixture with myristyloxy triterpenes improved this activity. These compounds seem, at least in part, to be related to the plant’s reported activity. SUMMARY The mixtures of hydroxylated, acetylated, and myristate triterpenes isolated from hexanic extracts of Pluchea quitoc DC. were analyzed in the models of nociception and inflammation in mice. The results demonstrate the anti-inflammatory and peripheral antinociceptive activity of the triterpenes β-amyrin, taraxasterol, and pseudo-taraxasterol. This study showed too that the activity of triterpenes may be decreased by their being acetylated, while the acetylated triterpenes in mixture with myristate triterpenes improved this activity. Abbreviations Used: T: Triterpenes compounds β-amyrin, taraxasterol, and pseudo-taraxasterol in a mixture, Ta: Triterpenes compounds β-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture, Tafe: Triterpenes compounds β-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with β-amyrin, taraxasterol and pseudo-taraxasterol myristates, Ctrl: Control, Indo: Indomethacin, Dexa: Dexamethasone, EtOAc: Ethyl acetate, MeOH: Methanol. PMID:29333034

Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.

PubMed

Moustafa, Passant E; Abdelkader, Noha F; El Awdan, Sally A; El-Shabrawy, Osama A; Zaki, Hala F

2018-04-27

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored animals' body weight, reduced blood glucose, glycated hemoglobin and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents.

The interaction of tetrahydroisoquinoline derivatives with antinociceptive action of morphine and oxotremorine in mice.

PubMed

Vetulani, J; Pavone, F; Przewłocka, B; Borghi, V; Nalepa, I

2003-11-01

To extend our earlier data on synergistic action of tetrahydroisoquinolines and morphine, we have investigated the analgesic effects of 1,2,3,4-tetrahydroisoquinoline (TIQ) and its 1-methyl-(1-MeTIQ) and N-methyl (N-MeTIQ) analogs on analgesia induced by morphine and oxotremorine. 1-MeTIQ and N-MeTIQ induced a moderate, delayed and prolonged analgesic action measured in the tail-flick test in CD-1 mice; 1-MeTIQ and TIQ prolonged the opiate (morphine, 2.5 mg/kg i.p.) analgesia while TIQ and N-TIQ potentiated cholinergic (oxotremorine, 0.02 mg/kg i.p.) analgesia. The involvement of the opioid and noradrenergic systems in this effect is discussed.

NMDA or non-NMDA receptor antagonism within the amygdaloid central nucleus suppresses the affective dimension of pain in rats: evidence for hemispheric synergy.

PubMed

Spuz, Catherine A; Borszcz, George S

2012-04-01

The amygdala contributes to generation of affective behaviors to threats. The prototypical threat to an individual is exposure to a noxious stimulus and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study evaluated the contribution of glutamate receptors in CeA to generation of the affective response to acute pain in rats. Vocalizations that occur following a brief noxious tail shock (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by bilateral injection into CeA of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (AP5, 1 μg, 2 μg, or 4 μg) or the non-NMDA receptor antagonist 6-Cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, .25 μg, .5 μg, 1 μg, or 2 μg). Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of AP5 or CNQX into CeA. Unilateral administration of AP5 or CNQX into CeA of either hemisphere also selectively elevated vocalization thresholds. Bilateral administration of AP5 or CNQX produced greater increases in vocalization thresholds than the same doses of antagonists administered unilaterality into either hemisphere indicating synergistic hemispheric interactions. The amygdala contributes to production of emotional responses to environmental threats. Blocking glutamate neurotransmission within the central nucleus of the amygdala suppressed rats' emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

A novel dual-wavelength laser stimulator to elicit transient and tonic nociceptive stimulation.

PubMed

Dong, Xiaoxi; Liu, Tianjun; Wang, Han; Yang, Jichun; Chen, Zhuying; Hu, Yong; Li, Yingxin

2017-07-01

This study aimed to develop a new laser stimulator to elicit both transient and sustained heat stimulation with a dual-wavelength laser system as a tool for the investigation of both transient and tonic experimental models of pain. The laser stimulator used a 980-nm pulsed laser to generate transient heat stimulation and a 1940-nm continuous-wave (CW) laser to provide sustained heat stimulation. The laser with 980-nm wavelength can elicit transient pain with less thermal injury, while the 1940-nm CW laser can effectively stimulate both superficial and deep nociceptors to elicit tonic pain. A proportional integral-derivative (PID) temperature feedback control system was implemented to ensure constancy of temperature during heat stimulation. The performance of this stimulator was evaluated by in vitro and in vivo animal experiments. In vitro experiments on totally 120 specimens fresh pig skin included transient heat stimulation by 980-nm laser (1.5 J, 10 ms), sustained heat stimulation by 1940-nm laser (50-55 °C temperature control mode or 1.5 W, 5 min continuous power supply), and the combination of transient/sustained heat stimulation by dual lasers (1.5 J, 10 ms, 980-nm pulse laser, and 1940-nm laser with 50-55 °C temperature control mode). Hemoglobin brushing and wind-cooling methods were tested to find better stimulation model. A classic tail-flick latency (TFL) experiment with 20 Wistar rats was used to evaluate the in vivo efficacy of transient and tonic pain stimulation with 15 J, 100 ms 980-nm single laser pulse, and 1.5 W constant 1940-nm laser power. Ideal stimulation parameters to generate transient pain were found to be a 26.6 °C peak temperature rise and 0.67 s pain duration. In our model of tonic pain, 5 min of tonic stimulation produced a temperature change of 53.7 ± 1.3 °C with 1.6 ± 0.2% variation. When the transient and tonic stimulation protocols were combined, no significant difference was observed depending on the order of stimuli. Obvious tail-flick movements were observed. The TFL value of transient pain was 3.0 ± 0.8 s, and it was 4.4 ± 1.8 s for tonic pain stimulation. This study shows that our novel design can provide effective stimulation of transient pain and stable tonic pain. Furthermore, it can also provide a reliable combination of transient and consistent stimulations for basic studies of pain perception.

Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

PubMed

Rehni, Ashish K; Singh, Nirmal; Jindal, Seema

2007-12-01

The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.

Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

PubMed

Kögel, Babette; Terlinden, Rolf; Schneider, Johannes

2014-05-01

To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs. Prospective part-randomized pre-clinical research trial. Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months. On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1). Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs. Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Contribution of amygdala CRF neurons to chronic pain.

PubMed

Andreoli, Matthew; Marketkar, Tanvi; Dimitrov, Eugene

2017-12-01

We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over-activation of amygdala CRF neurons is very likely an important contributing factor for pain chronification. Copyright © 2017 Elsevier Inc. All rights reserved.

Intrinsic connections within the pedunculopontine tegmental nucleus are critical to the elaboration of post-ictal antinociception.

PubMed

Mazzei-Silva, Elaine Cristina; de Oliveira, Rithiele Cristina; dos Anjos Garcia, Tayllon; Falconi-Sobrinho, Luiz Luciano; Almada, Rafael Carvalho; Coimbra, Norberto Cysne

2014-08-01

This study investigated the intrinsic connections of a key-structure of the endogenous pain inhibitory system, the pedunculopontine tegmental nucleus (PPTN), in post-ictal antinociceptive process through synaptic inactivation of the PPTN with cobalt chloride. Male Wistar rats (n = 6 or 7 per group), weighing 250-280 g, had the tail-flick baseline recorded and were submitted to a stereotaxic surgery for the introduction of a guide-cannula aiming at the PPTN. After 5 days of postoperative recovery, cobalt chloride (1 mM/0.2 µL) or physiological saline (0.2 µL) were microinjected into the PPTN and after 5 min, the tail-withdrawal latency was measured again at 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 min after seizures evoked by intraperitoneal injection of pentylenetetrazole (64 mg/kg). The synaptic inactivation of PPTN decreased the post-ictal antinociceptive phenomenon, suggesting the involvement of PPTN intrinsic connections in the modulation of pain, during tonic-clonic seizures. These results showed that the PPTN may be crucially involved in the neural network that organizes the post-ictal analgesia. © 2014 Wiley Periodicals, Inc.

Ontogenetic scaling of the olfactory antennae and flicking behavior of the shore crab, Hemigrapsus oregonensis.

PubMed

Waldrop, Lindsay D

2013-07-01

Malacostracan crustaceans such as crabs flick antennae with arrays of olfactory sensilla called aesthetascs through the water to sense odors. Flicking by crabs consists of a quick downstroke, in which aesthetascs are deflected laterally (splayed), and a slower, reversed return stroke, in which aesthetascs clump together. This motion causes water to be flushed within and then held in between aesthetascs to deliver odor molecules to olfactory receptors. Although this odor sampling method relies on a narrow range of speeds, sizes, and specific arrangements of aesthetascs, most crabs dramatically change these during ontogeny. In this study, the morphometrics of the aesthetascs, array, and antennae and the flicking kinematics of the Oregon shore crab, Hemigrapsus oregonensis (Decapoda: Brachyura), are examined to determine their scaling relationships during ontogeny. The morphometrics of the array and antennae increase more slowly than would be predicted by isometry. Juvenile crabs' aesthetascs splay relatively further apart than adults, likely due to changing material properties of aesthetasc cuticle during growth. These results suggest that disproportionate growth and altered aesthetasc splay during flicking will mediate the size changes due to growth that would otherwise lead to a loss of function.

Evaluation of antinociceptive effect of Petiveria alliacea (Guiné) in animals.

PubMed

de Lima, T C; Morato, G S; Takahashi, R N

1991-01-01

Petiveria alliacea (Phytolaccaceae) is a bush widely distributed in South America including Brazil, where it is popularly known as "guiné", "pipi", "tipi" or "erva-de-tipi". Brazilian folk medicine attributes to the hot water infusion of its roots or leaves the following pharmacological properties: antipyretic, antispasmodic, abortifacient, antirrheumatic, diuretic, analgesic and sedative. The present study has evaluated the alleged effects of P. alliacea on central nervous system (CNS), particularly, the sedative and analgesic properties of root crude aqueous extract of this plant in mice and rats. This extract showed an antinociceptive effect in acetic acid--acetylcholine--and hypertonic saline--induced abdominal constrictions, but not in hot-plate and tail flick tests. P. alliacea did not produce any CNS depressor effect. Thus its antinociceptive action in animals can be responsible by its popular use as an analgesic.

Antinociceptive and anticonvulsant activities of hydroalcoholic extract of Jasminum grandiflorum (jasmine) leaves in experimental animals.

PubMed

Gupta, Rajesh K; Reddy, Pooja S

2013-10-01

Jasminum grandiflorum belongs to the family Oleaceae and is known to have anti-inflammatory, antimicrobial, antioxidant, and antiulcer activities. The present study was undertaken to study its analgesic and anticonvulsant effects in rats and mice. The antinociceptive activity of the hydroalcoholic extract of J. grandiflorum leaves (HEJGL) was studied using tail flick and acetic acid - induced writhing method. Similarly, its anticonvulsant activity was observed by maximal electroshock (MES) method and pentylenetetrazol (PTZ) method. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Dunnett's test. At doses of 50, 100, and 200 mg/kg, HEJGL showed significant analgesic and anticonvulsant effects in experimental animals. In view of its analgesic and anticonvulsant activity, the JGL extract can be used in painful conditions as well as in seizure disorders.

Antinociceptive and anticonvulsant activities of hydroalcoholic extract of Jasminum grandiflorum (jasmine) leaves in experimental animals

PubMed Central

Gupta, Rajesh K.; Reddy, Pooja S.

2013-01-01

Jasminum grandiflorum belongs to the family Oleaceae and is known to have anti-inflammatory, antimicrobial, antioxidant, and antiulcer activities. The present study was undertaken to study its analgesic and anticonvulsant effects in rats and mice. The antinociceptive activity of the hydroalcoholic extract of J. grandiflorum leaves (HEJGL) was studied using tail flick and acetic acid – induced writhing method. Similarly, its anticonvulsant activity was observed by maximal electroshock (MES) method and pentylenetetrazol (PTZ) method. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Dunnett's test. At doses of 50, 100, and 200 mg/kg, HEJGL showed significant analgesic and anticonvulsant effects in experimental animals. In view of its analgesic and anticonvulsant activity, the JGL extract can be used in painful conditions as well as in seizure disorders. PMID:24174823

Antipyretic and analgesic activities of Caesalpinia bonducella seed kernel extract.

PubMed

Archana, P; Tandan, S K; Chandra, S; Lal, J

2005-05-01

Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected for its antipyretic and antinociceptive activities in adult albino rats or mice of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract had significant central analgesic activity in hot plate and tail flick methods. It also exhibited marked peripheral analgesic effect in both acetic acid-induced writhing test in mice and Randall-Selitto assay in rats. It also significantly inhibited the formalin-induced hind paw licking in mice. In conclusion, the present study suggests that the ethanolic extract of Caesalpinia bonducella seed kernel possesses potent antipyretic and antinociceptive activities and thus, validates its use in the treatment of pain and pyretic disorders. Copyright (c) 2005 John Wiley & Sons, Ltd.

The spatial and temporal patterns of odors sampled by lobsters and crabs in a turbulent plume.

PubMed

Reidenbach, Matthew A; Koehl, M A R

2011-09-15

Odors are dispersed across aquatic habitats by turbulent water flow as filamentous, intermittent plumes. Many crustaceans sniff (take discrete samples of ambient water and the odors it carries) by flicking their olfactory antennules. We used planar laser-induced fluorescence to investigate how flicking antennules of different morphologies (long antennules of spiny lobsters, Panulirus argus; short antennules of blue crabs, Callinectes sapidus) sample fluctuating odor signals at different positions in a turbulent odor plume in a flume to determine whether the patterns of concentrations captured can provide information about an animal's position relative to the odor source. Lobster antennules intercept odors during a greater percentage of flicks and encounter higher peak concentrations than do crab antennules, but because crabs flick at higher frequency, the duration of odor-free gaps between encountered odor pulses is similar. For flicking antennules there were longer time gaps between odor encounters as the downstream distance to the odor source decreases, but shorter gaps along the plume centerline than near the edge. In contrast to the case for antennule flicking, almost all odor-free gaps were <500 ms at all positions in the plume if concentration was measured continuously at the same height as the antennules. Variance in concentration is lower and mean concentration is greater near the substratum, where leg chemosensors continuously sample the plume, than in the water where antennules sniff. Concentrations sampled by legs increase as an animal nears an odor source, but decrease for antennules. Both legs and antennules encounter higher concentrations near the centerline than at the edge of the plume.

Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom in experimental animal models.

PubMed

Ghosh, Susmita; Saha, Partha Pratim; Dasgupta, Subir C; Gomes, Antony

2016-09-01

Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund’s complete adjuvant (FCA) in male Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic activity showed that BFV significantly reduced the paw and ankle diameters; urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-α/IL-1β/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly increased in FCA induced arthritic animals. Joint histopathology study indicated the partial restoration of joint structure. Treatment with BFV significantly reduced the mean latency time of tail flick response, acetic acid induced writhing response and formalin induced licking response in male albino mice. BFV treatment also significantly reduced carrageenan induced paw edema and xylene induced ear edema in male albino mice. The results indicated that BFV possess antinociceptive, anti-inflammatory and antiarthritic properties and further studies are warranted to find the active constituents present in BFV.

Antinociceptive Activity of an Ethanol Extract of Justicia spicigera.

PubMed

Zapata-Morales, Juan Ramón; Alonso-Castro, Angel Josabad; Domínguez, Fabiola; Carranza-Álvarez, Candy; Castellanos, Luis Manuel Orozco; Martínez-Medina, Rosa María; Pérez-Urizar, José

2016-06-01

Preclinical Research The aim of the present study was to evaluate the antinociceptive and sedative activity of an ethanol extract of Justicia spicigera an evergreen used in Mexican traditional medicine for the relief of pain, wounds, fever and inflammation. At 200 mg/kg po, the maximum dose examined, the ethanol extract of J. spicigera (JSE) had analgesic activity in mice in the acetic acid writhing test, the second phase of the formalin test and the tail flick test that was similar in efficacy to the NSAID, naproxen (150 mg/kg po). JSE was inactive in the hot plate test and and the ketamine-induced sleeping time test; it had no sedative effects. These results show that the ethanol extract from the leaves of J. spicigera has antinociceptive effects in mice without inducing sedation. Drug Dev Res 77 : 180-186, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Chemical discrimination by tongue-flicking in lizards: A review with hypotheses on its origin and its ecological and phylogenetic relationships.

PubMed

Cooper, W E

1994-02-01

Tongue-flicking is a synapomorphy of squamate reptiles functioning to sample chemicals for vomerolfactory analysis, which became possible in primitive squamates when ducts opened from the vomeronasal organs to the roof of the mouth. Extant iguanian lizards in families that do not use the tongue to sample chemical prey cues prior to attack partially protrude it in two feeding contexts: during capture by lingual prehension and after oral contact with prey. These lizards do not exhibit strike-induced chemosensory searching. Lingual prey prehension is present in iguanian lizards and inSphenodon, the sister taxon of Squamata. During attempts to capture prey, the tongues of primitive squamates inevitably made incidental contact with environmental substrates bearing chemicals deposited by prey, conspecifics, and predators. Such contact presumably induced selection for tongue-flicking and ability to identify biologically important chemicals. Most iguanian lizards are ambush foragers that use immobility as a major antipredatory defense. Because tongue-flicking at an ambush post would not allow chemical search beyond the vicinity of the head and would render them easier for predators and prey to detect, typical iguanians tongue-flick neither while foraging nor to identify predators. They do detect pheromones by tongue-flicking. Scleroglossan lizards are typically active foragers that rely on speed to escape. Being freer to move the tongue, they have evolved lingual sampling allowing detection of chemical cues of conspecifics, predators, and prey, as well as strike-induced chemosensory searching, some can follow pheromone trails by tongue-flicking. Some families have lingual morphology and behavior specialized for chemosensory sampling. In varanids and snakes, the taxa showing the greatest lingual specialization, additional prey-related chemosensory behaviors have evolved. In iguanian and scleroglossan families that have secondarily adopted the foraging mode typical of the other taxon, prey chemical discrimination involving tongue-flicking and strike-induced chemosensory searching are typical for the foraging mode rather than the taxon. Because foraging mode and state of prey chemical discrimination are stable within squamate families and to a large extent in higher taxa, both features have been retained from the ancestral condition in most families. However, in three cases in which foraging mode has changed from its ancestral state, the state of prey chemical discrimination has also changed, indicating that prey chemical discrimination is adaptively adjusted to foraging mode. Indeed, acquisition of lingually mediated prey chemical discrimination may have made feasible the evolution of active foraging, which in turn appears to have profoundly influenced the further evolution of squamate chemosensory structures and behavior, placing a selective premium on features enhancing the tongue's efficiency as a chemical sampling device. The advent of tongue-flicking to sample prey chemicals and thus detect hidden prey may have allowed generalist (cruise) or ambush foragers, if early squamates were such, to become specialists in active foraging. Alternatively, if the common ancestors of squamates were active foragers, the adoption of ambush foraging would have selected against participation of the tongue in locating prey. Acting jointly, tongue-flicking and active foraging have had momentous consequences for squamate diversification. Specialization for active foraging would appear to have had ramifying effects on antipredatory defenses, body form, territoriality, mating systems, and reproductive physiology.

Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception.

PubMed

de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Falconi-Sobrinho, Luiz Luciano; Biagioni, Audrey Franceschi; Almada, Rafael Carvalho; Dos Anjos-Garcia, Tayllon; Bazaglia-de-Sousa, Guilherme; Khan, Asmat Ullah; Coimbra, Norberto Cysne

2018-05-12

Generalised tonic-clonic seizures, generated by abnormal neuronal hyper-activity, cause a significant and long-lasting increase in the nociceptive threshold. The pedunculopontine tegmental nucleus (PPTN) plays a crucial role in the regulation of seizures as well as the modulation of pain, but its role in postictal antinociceptive processes remains unclear. In the present study, we aimed to investigate the involvement of PPTN neurons in the postictal antinociception. Wistar rats had their tail-flick baseline recorded and were injected with ibotenic acid (1.0 μg/0.2 μL) into the PPTN, aiming to promote a local neurotoxic lesion. Five days after the neuronal damage, pentylenetetrazole (PTZ; 64 mg/kg) was intraperitoneally administered to induce tonic-clonic seizures. The tail-withdrawal latency was measured immediately after the seizures (0 min) and subsequently at 10-min intervals until 130 min after the seizures were induced pharmacologically. Ibotenic acid microinjected into the PPTN did not reduce the PTZ-induced seizure duration and severity, but it diminished the postictal antinociception from 0 to 130 min after the end of the PTZ-induced tonic-clonic seizures. These results suggest that the postictal antinociception depends on the PPTN neuronal cells integrity. Copyright © 2018 Elsevier Inc. All rights reserved.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models.

PubMed

Woode, Eric; Ameyaw, Elvis O; Boakye-Gyasi, Eric; Abotsi, Wonder K M

2012-10-01

Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg(-1), p.o.) and XA (10-100 mg kg(-1), p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg(-1), i.p.) and diclofenac (1-10 mg kg(-1), i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: I. Acute pain.

PubMed

Meléndez, D M; Marti, S; Pajor, E A; Moya, D; Heuston, C E M; Gellatly, D; Janzen, E D; Schwartzkopf-Genswein, K S

2017-10-01

Three experiments evaluated the effect of band and knife castration on acute pain for the first 7 d after the procedure on 1-wk-, 2-mo-, and 4-mo-old calves. All calves were blocked by age and weight and randomly assigned to 1 of 3 treatments: sham castration (control, CT), band castration (BA), and knife castration (KN). Experiment 1 evaluated 1-wk-old Angus bull calves ( = 34; 43.0 ± 6.61 kg BW), Exp. 2 evaluated 2-mo-old Angus bull calves ( = 34; 91.5 ± 11.93 kg BW), and Exp. 3 evaluated 4-mo-old Angus bull calves ( = 35; 157.6 ± 22.52 kg BW). For all experiments, physiological and behavioral parameters were collected before (d -1 and immediately before castration [T0]) and after (60 and 120 min and on d 7) castration to assess acute pain. Physiological measures included complete blood cell count, cortisol, substance P, and scrotal temperature. Behavioral measures consisted of a visual analog scale, stride length, and time and frequency budgets for walking, standing, lying, tail flicking, foot stamping, and head turning. Performance parameters included initial and final BW and ADG. In Exp. 1, tail flicking was greater ( = 0.02) in KN calves compared to BA calves 2 to 4 h after castration, although no differences were seen between BA and KN compared to CT calves. In Exp. 2, a treatment × time interaction ( = 0.02) was observed for cortisol, where KN calves had greater cortisol concentrations 120 min after castration compared to BA and CT calves; KN calves also lay down and ate less ( < 0.01; = 0.02) and stood and walked more ( < 0.01; = 0.05) compared to BA and CT calves 2 to 4 h after castration. In Exp. 3, a treatment × time interaction ( < 0.01) was observed for cortisol concentrations in which all treatments were different from one another at 60 and 120 min, with BA calves having the greatest concentrations, KN calves being intermediate, and CT having the lowest concentrations. Overall, KN and BA castrated calves presented physiological and behavioral changes associated with acute pain; however, 2-mo-old BA calves presented the fewest behavioral changes and no physiological changes associated with acute pain compared to CT calves.

Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation.

PubMed

Iwamoto, Tatsushige; Takasugi, Yoshihiro; Higashino, Hideaki; Ito, Hiroyuki; Koga, Yoshihisa; Nakao, Shinichi

2011-02-01

Systemic carbamazepine, a voltage-gated sodium channel blocker, has been reported to dose-dependently reduce inflammatory hyperalgesia. However, the antinociceptive effects of carbamazepine on the spinal cord in inflammatory conditions are unclear. The aim of the present study was to evaluate the antinociceptive effects of carbamazepine on the spinal cord in a chronic inflammatory condition. In Sprague-Dawley rats, a chronic inflammatory condition was induced by complete Freund's adjuvant (CFA) inoculation into the tail. Tail flick (TF) latencies were measured following intraperitoneal carbamazepine, or intrathecal carbamazepine or tetrodotoxin injection in intact rats and in the chronic inflammatory rats. From the values of TF latency at 60 min after drug injection, the effective dose required to produce 50% response (ED(50)) of each drug was derived. Carbamazepine attenuated thermal responses with both systemic and intrathecal administration. The effect was more evident in rats with chronic inflammation than in intact rats; the ED(50s) of intraperitoneal carbamazepine in intact and inflamed rats were 12.39 and 1.54 mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048 nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED(50s) of 1.006 pmol in intact rats and 0.310 pmol in inflamed rats. The relative potencies of intrathecal carbamazepine versus tetrodotoxin for inhibition were approximately 1:150-1:300 in intact and inflamed rats. These results indicate that the inhibition of voltage-gated sodium channels, at least tetrodotoxin-sensitive channels, may contribute to the antinociceptive effect of carbamazepine on CFA-induced inflammatory pain, since lower doses of intrathecal carbamazepine and tetrodotoxin attenuated thermal responses to a greater extent in inflamed rats than in intact rats.

Peripheral and Central Determinants of a Nociceptive Reaction: An Approach to Psychophysics in the Rat

PubMed Central

Ballantyne, Kay; Plaghki, Léon; Le Bars, Daniel

2008-01-01

Background The quantitative end-point for many behavioral tests of nociception is the reaction time, i.e. the time lapse between the beginning of the application of a stimulus, e.g. heat, and the evoked response. Since it is technically impossible to heat the skin instantaneously by conventional means, the question of the significance of the reaction time to radiant heat remains open. We developed a theoretical framework, a related experimental paradigm and a model to analyze in psychophysical terms the “tail-flick” responses of rats to random variations of noxious radiant heat. Methodology/Principal Findings A CO2 laser was used to avoid the drawbacks associated with standard methods of thermal stimulation. Heating of the skin was recorded with an infrared camera and was stopped by the reaction of the animal. For the first time, we define and determine two key descriptors of the behavioral response, namely the behavioral threshold (Tβ) and the behavioral latency (Lβ). By employing more than one site of stimulation, the paradigm allows determination of the conduction velocity of the peripheral fibers that trigger the response (V) and an estimation of the latency (Ld) of the central decision-making process. Ld (∼130 ms) is unaffected by ambient or skin temperature changes that affect the behavioral threshold (∼42.2–44.9°C in the 20–30°C range), behavioral latency (<500 ms), and the conduction velocity of the peripheral fibers that trigger the response (∼0.35–0.76 m/s in the 20–30°C range). We propose a simple model that is verified experimentally and that computes the variations in the so-called “tail-flick latency” (TFL) caused by changes in either the power of the radiant heat source, the initial temperature of the skin, or the site of stimulation along the tail. Conclusions/Significance This approach enables the behavioral determinations of latent psychophysical (Tβ, Lβ, Ld) and neurophysiological (V) variables that have been previously inaccessible with conventional methods. Such an approach satisfies the repeated requests for improving nociceptive tests and offers a potentially heuristic progress for studying nociceptive behavior on more firm physiological and psychophysical grounds. The validity of using a reaction time of a behavioral response to an increasing heat stimulus as a “pain index” is challenged. This is illustrated by the predicted temperature-dependent variations of the behavioral TFL elicited by spontaneous variations of the temperature of the tail for thermoregulation. PMID:18769624

Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

PubMed

Oyama, Tatsuya; Homan, Takashi; Kyotani, Junko; Oka, Michiko

2012-02-15

Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that μ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity. Copyright © 2011 Elsevier B.V. All rights reserved.

Antinociceptive effects of MSVIII-19, a functional antagonist of the GluK1 kainate receptor

PubMed Central

Qiu, Chang-Shen; Wyhe, Leanne Lash-Van; Sasaki, Makoto; Sakai, Ryuichi; Swanson, Geoffrey T.; Gereau, Robert W.

2011-01-01

The ionotropic glutamate receptor subunit, GluK1 (GluR5), is expressed in many regions of nervous system related to sensory transmission. Recently, a selective ligand for the GluK1 receptor, MSVIII-19 (8,9-dideoxy-neodysiherbaine), was synthesized as a derivative of dysiherbaine, a toxin isolated from the marine sponge Lendenfeldia chodrodes. MSVIII-19 potently desensitizes GluK1 receptors without channel activation, rendering it useful as a functional antagonist. Given the high selectivity for GluK1 and the proposed role for this glutamate receptor in nociception, we sought to test the analgesic potential of MSVIII-19 in a series of models of inflammatory, neuropathic, and visceral pain in mice. MSVIII-19 delivered intrathecally (i.t.) dose-dependently reduced formalin-induced spontaneous behaviors and reduced thermal hypersensitivity 3 hours after formalin injection and 24 hours after complete freund’s adjuvant-induced inflammation, but had no effect on mechanical sensitivity in the same models. I.T. MSVIII-19 significantly reduced both thermal hyperalgesia and mechanical hypersensitivity in the chronic constriction injury model of neuropathic pain, but had no effect in the acetic acid model of visceral pain. Peripheral administration of MSVIII-19 had no analgesic efficacy in any of these models. Finally, i.t. MSVIII-19 did not alter responses in tail flick tests or performance on the accelerating RotaRod. These data suggest that spinal administration of MSVIII-19 reverses hypersensitivity in several models of pain in mice, supporting the clinical potential of GluK1 antagonists for the management of pain. PMID:21324591

Evaluation of the antiulcerogenic and analgesic activities of Cordia verbenacea DC. (Boraginaceae).

PubMed

Roldão, Erika de Freitas; Witaicenis, Aline; Seito, Leonardo Noboru; Hiruma-Lima, Clélia Akiko; Di Stasi, Luiz Claudio

2008-09-02

Cordia verbenacea is a medicinal plant popularly used in Brazil as anti-inflammatory, antiulcer and anti-rheumatic agent without detailed pharmacological and toxicological studies. The study was aimed to investigate the effects of Cordia verbenacea in antiulcer, analgesic and antioxidant assays, as well as to evaluate its toxic effects and phytochemical profile. Antiulcer activity of plant extract was evaluated using ethanol/HCl, ethanol and piroxican-induced gastric lesions methods. The pH, volume and total acid of gastric juice were determined by pylorus-ligated assay. Analgesic activity was evaluated by writhing, tail-flick and hot-plate tests. Antioxidant activity was determined by in vitro lipoperoxidation assay. Acute toxicity and number of deaths were evaluated by Hippocratic screening. The ethanol leaf extract shows a potent antiulcer activity in the ethanol/HCl and absolute ethanol-induced gastric lesions. The IC(50) value of plant extract on the lipid peroxidation was 76.11mug/ml. Preliminary phytochemical tests were positive for flavonoids, steroids, saponins, fixed acids, alkaloids and phenols. In the analgesic models the extract did not present any activity. Cordial verbenaceae showed a potent antiulcer activity at the dose of 125mg/kg and this effect may be associated with an improvement in stomach antioxidant mechanisms.

Application of the Strategic Alignment Model and Information Technology Governance Concepts to Support Network Centric Warfare

DTIC Science & Technology

2006-03-01

Defense, Editor. 2001. 12. Defense, D.o., Department of Defense Architecture Framework Deskbook. 2004, Department of Defense. 13. Denzin , N. and...Y. Lincoln , Handbook of Qualitative Research. 2000, California: Sage. 14. Flick, U., An Introduction to Qualitative research: Theory, method and

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models

PubMed Central

Woode, Eric; Ameyaw, Elvis O.; Boakye-Gyasi, Eric; Abotsi, Wonder K. M.

2012-01-01

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg-1, p.o.) and XA (10-100 mg kg-1, p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg-1, i.p.) and diclofenac (1-10 mg kg-1, i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid. PMID:23248562

The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors.

PubMed

Tomić, Maja A; Pecikoza, Uroš B; Micov, Ana M; Stepanović-Petrović, Radica M

2015-12-01

Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.

Phorbol ester suppression of opioid analgesia in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, L.J.; Wang, X.J.; Han, J.S.

1990-01-01

Protein kinase C (PKC) has been shown to be an important substrate in intracellular signal transduction. Very little is known concerning its possible role in mediating opiate-induced analgesia. In the present study, 12-O-tetradecanoylphorbol 13-acetate (TPA), a selective activator of PKC, was injected intrathecally (ith) to assess its influence on the analgesia induced by intrathecal injection of the mu opioid agonist PL017, the delta agonist DPDPE and the kappa agonist 66A-078. Radiant heat-induced tail flick latency (TFL) was taken as an index of nociception. TPA in the dose of 25-50 ng, which did not affect the baseline TFL, produced a markedmore » suppression of opioid antinociception, with a higher potency in blocking mu and delta than the kappa effect. In addition, mu and delta agonists induced remarkable decreases in spinal cyclic AMP (cAMP) content whereas the kappa effect was weak. The results suggest a cross-talk between the PKC system and the signal transduction pathway subserving opioid analgesia.« less

Synthesis, spectroscopic characterization and biological activities of N4O2 Schiff base ligand and its metal complexes of Co(II), Ni(II), Cu(II) and Zn(II)

NASA Astrophysics Data System (ADS)

Al-Resayes, Saud I.; Shakir, Mohammad; Abbasi, Ambreen; Amin, Kr. Mohammad Yusuf; Lateef, Abdul

The Schiff base ligand, bis(indoline-2-one)triethylenetetramine (L) obtained from condensation of triethylenetetramine and isatin was used to synthesize the complexes of type, [ML]Cl2 [M = Co(II), Ni(II), Cu(II) and Zn(II)]. L was characterized on the basis of the results of elemental analysis, FT-IR, 1H and 13C NMR, mass spectroscopic studies. The stoichiometry, bonding and stereochemistries of complexes were ascertained on the basis of results of elemental analysis, magnetic susceptibility values, molar conductance and various spectroscopic studies. EPR, UV-vis and magnetic moments revealed an octahedral geometry for complexes. L and its Cu(II) and Zn(II) complexes were screened for their antibacterial activity. Analgesic activity of Cu(II) and Zn(II) complexes was also tested in rats by tail flick method. Both complexes were found to possess good antibacterial and moderate analgesic activity.

Analgesic and anti-inflammatory activities of 80% methanol root extract of Jasminum abyssinicum Hochst. ex. Dc. (Oleaceae) in mice.

PubMed

Tadiwos, Yohannes; Nedi, Teshome; Engidawork, Ephrem

2017-04-18

Pain and inflammation are associated with the pathophysiology of various clinical conditions. Most analgesic and anti-inflammatory drugs available in the market present a wide range of problems. The current study was aimed at investigating the analgesic and anti-inflammatory activity of 80% methanol extract of J. abyssinicum root. The analgesic activity was determined using tail-flick test and acetic acid induced writhing, whereas anti-inflammatory activity was determined by carrageenan induced paw edema and formalin induced pedal edema, carried out in vivo. The test group received three different doses of the extract (50mg/kg, 100mg/kg and 200mg/kg) orally. The positive control group received diclofenac (10mg/kg), aspirin (100mg/kg or 150mg/kg) or morphine (20mg/kg) orally. The negative control group received vehicle (2% Tween 80, 10ml/kg) orally. Furthermore, preliminary phytochemical screening was carried out. Oral administration of J. abbysinicum 80% methanol extract (at all doses) significantly (p<0.001) inhibit pain sensation in the pain models. Similarly, the extract demonstrated anti-inflammatory effect in the inflammation models in mice. Preliminary phytochemical screening showed the presence of saponins, flavonoids, terpenoids, triterpenens and glycosides. The data obtained from the present study indicates that the extract possessed a significant analgesic and anti-inflammatory activity, upholding the folkloric use of the plant. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance.

PubMed

Fairbanks, C A; Wilcox, G L

1997-09-01

The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 degrees C) tail flick test in mice. Intrathecal pretreatment with morphine (40 nmol) produced a 9.6-fold rightward shift in the morphine dose-response curve. This shift confirmed the induction of acute spinal morphine tolerance. Intrathecal copretreatment with the receptor antagonists (competitive and noncompetitive, respectively) dizolcipine (MK801, 3 nmol) or LY235959 (4 pmol) and morphine [40 nmol, intrathecally (i.t.)] attenuated acute tolerance to morphine measured 8 hr later. A 60-min pretreatment of 7-nitroindazole (6 nmol, i.t.), a selective neuronal NOS inhibitor, followed by administration of morphine (40 nmol, i.t.) blocked the induction of morphine tolerance. Intrathecal copretreatment with morphine (40 nmol, i.t.) and agmatine (4 nmol, i.t.), an imidazoline, receptor agonist and putative nitric oxide synthase inhibitor, almost completely abolished acute spinal morphine tolerance. The results of these experiments agree with previous reports using models of chronically induced morphine tolerance. This evidence supports the proposal that the mechanisms responsible for acute morphine tolerance parallel those underlying chronic morphine tolerance. This study attests to the powerful predictive value of acute induction as a model for morphine tolerance.

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models.

PubMed

Tamrat, Yohannes; Nedi, Teshome; Assefa, Solomon; Teklehaymanot, Tilahun; Shibeshi, Workineh

2017-09-29

Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation. Successive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80). In all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg. This study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs.

Berberine Ameliorates Diabetic Neuropathy: TRPV1 Modulation by PKC Pathway.

PubMed

Zan, Yan; Kuai, Cui-Xing; Qiu, Zhi-Xia; Huang, Fang

2017-01-01

In recent years, berberine has increasingly become a topic of research as a treatment for diabetes due to its repair function, which recovers damaged pancreatic β cells. However, it is the complications of diabetes that seriously affect patients' life quality and longevity, among which diabetic neuropathy and the consequent acute pain are the most common. In this study, we established STZ-induced diabetic models to observe whether berberine, a main constitute of Coptis chinensis Franch which has shown good hypoglycemic effects, could relieve diabetes-induced pain and explored its possible mechanism in rats and mice. Behavior assays showed increasing mechanical allodynia and thermal hyperalgesia thresholds by the Von Frey test and tail flick test during the treatment of berberine. It was found that the administration of berberine (20, 60 mg/kg; 30, 90 mg/kg) suppressed the expression of PKCε and TRPV1 which could be activated by hyperglycemia-induced inflammatory reaction. Our results also presented its capability to reduce the over expression of TNF-[Formula: see text] in diabetic rats and mice. TNF-[Formula: see text] is an inflammatory cytokine, which is closely related to diabetic peripheral neuropathy (DPN). Consequently, we supposed that berberine exerts its therapeutic effects in part by suppressing the inflammatory process and blocking the PKC pathway to inhibit TRPV1 activation, which damages neurons and causes diabetic pain.

Evaluation and comparison of antinociceptive activity of aspartame with sucrose.

PubMed

Rani, Seema; Gupta, Mahesh C

2012-01-01

Artificial sweeteners are low-calorie substances used to sweeten a wide variety of foods. At present they are used increasingly not only by diabetics, but also by the general public as a mean of controlling the weight. This study was carried out to evaluate and compare antinociceptive activity of the artificial sweeteners, aspartame and sucrose and to study the mechanisms involved in this analgesic activity. Forty eight white albino Wistar rats were divided into two groups of 24 rats each. Group 1 received sucrose and group 2 received aspartame solution ad libitum for 14 days as their only source of liquid. On 14(th) day, both groups of rats were divided into 3 subgroups having 8 rats each. Group Ia and IIa served as control. Group Ib and IIb were given naloxone and Ic and IIc received ketanserin, the opioid and serotonergic receptor antagonists, respectively. Tail withdrawal latencies (tail flick analgesiometer) and paw licking/jumping latencies (Eddy's hot plate method) were increased significantly in both aspartame and sucrose group. The analgesia produced by aspartame was comparable with sucrose. The opioid receptor antagonist naloxone and the 5-HT(2A/2C) serotonergic receptor antagonist ketanserin partly reversed the antinociceptive effect of these sweeteners. Thus, the artificial sweetening agent aspartame showed antinociceptive activity like sucrose in rats. Reduction in antinociceptive activity of aspartame and sucrose by opioid and serotoninergic antagonists demonstrate the involvement of both opioid and serotonergic system.

Instability of hooks during bacterial flagellar swimming

NASA Astrophysics Data System (ADS)

Jabbarzadeh, Mehdi; Fu, Henry C.; Henry Fu Team

2016-11-01

In bacteria, a flexible hook transmits torque from the rotary motor at the cell body to the flagellum. Previously, the hook has been modeled as a Kirchhoff rod between the cell body and rotating flagellum. To study effects of the hook's flexibility on the bacteria's swimming speed and trajectory for wide range hook stiffnesses and flagellum configurations, we develop an efficient simplified spring model for the hook by linearizing the Kirchhoff rod. We treat the hydrodynamics of the cell body and helical flagellum using resistance matrices calculated by the method of regularized Stokeslets. We investigate flagellar and swimming dynamics for a range of hook flexibilities and flagellar orientations relative to the cell body and compare the results to models without hook flexibility. We investigate in detail parameters corresponding to E. coli and Vibrio alginolyticus. Generally, the flagellum changes orientation relative to the cell body, undergoing an orbit with the period of the motor rotation. We find that as the hook stiffness decreases, steady-state orbits of the flagellum first become unstable before the hook buckles, which may suggest a new mechanism of flick initiation in run-reverse-flick motility. We also find that for some parameter ranges, there are multiple stable steady state orbits, which may have implications for the tumbling and turning of bacteria.

Chemosensory responses to sugar and fat by the omnivorous lizard Gallotia caesaris: with behavioral evidence suggesting a role for gustation.

PubMed

Cooper, W E; Pérez-Mellado, V

2001-07-01

Many lizards can identify food using only chemical cues, as indicated by tongue-flicking for chemical sampling and biting, but the effectiveness of the chemical components of food are unknown, as is the relationship between response strength and concentration. We investigated responses by the omnivorous lizard Gallotia caesaris to representatives of two major categories of organic food chemicals, lipids and carbohydrates. The stimuli, pork fat and sucrose solutions of varying concentration, were presented to lizards on cotton swabs and their lingual and biting behaviors were observed during 60-s tests. In the first experiment, fat elicited more tongue-flicks and bites than saturated sucrose or water (odorless control), biting being limited to the fat condition. Lizards licked at high rates, but exclusively in response to sucrose. A lick was a lingual protrusion in which the dorsal surface of the tongue contacted the swab, in contrast to the anteroventral contact made during tongue-flicks. In a second experiment, the number of licks, but not the number of tongue-flicks, increased with the concentration of sucrose. The results indicate that lipids contribute to prey chemical discrimination and are adequate to release some attacks, but are not as effective as releasers of attack as mixtures of prey chemicals obtained from prey surfaces. The findings with respect to licking are novel, and suggest that licking may be a response to gustatory stimulation by sugar, in contrast to previously observed prey chemical discriminations shown to require vomerolfaction.

Interaction between visual and chemical cues in a Liolaemus lizard: a multimodal approach.

PubMed

Vicente, Natalin S; Halloy, Monique

2017-12-01

Multimodal communication involves the use of signals and cues across two or more sensory modalities. The genus Liolaemus (Iguania: Liolaemidae) offers a great potential for studies on the ecology and evolution of multimodal communication, including visual and chemical signals. In this study, we analyzed the response of male and female Liolaemus pacha to chemical, visual and combined (multimodal) stimuli. Using cue-isolation tests, we registered the number of tongue flicks and headbob displays from exposure to signals in each modality. Number of tongue flicks was greater when a chemical stimulus was presented alone than in the presence of visual or multimodal stimuli. In contrast, headbob displays were fewer in number with visual and chemical stimuli alone, but significantly higher in number when combined. Female signallers triggered significantly more tongue flicks than male signallers, suggesting that chemical cues are involved in sexual recognition. We did not find an inhibition between chemical and visual cues. On the contrary, we observed a dominance of the chemical modality, because when presented with visual stimuli, lizards also responded with more tongue flicks than headbob displays. The total response produced by multimodal stimuli was similar to that of the chemical stimuli alone, possibly suggesting non-redundancy. We discuss whether the visual component of a multimodal signal could attract attention at a distance, increasing the effectiveness of transmission and reception of the information in chemical cues. Copyright © 2017 Elsevier GmbH. All rights reserved.

S-adenosyl methionine (SAM) attenuates the development of tolerance to analgesic activity of morphine in rats.

PubMed

Katyal, Jatinder; Kumar, Hemant; Joshi, Dinesh; Gupta, Yogendra Kumar

2017-04-03

Development of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance. Male 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7mg/kg), intraperitoneally (i.p.), once daily for 5days developed tolerance to analgesic effect. To evaluate the effect of SAM on morphine tolerance, SAM 800mg/kg was administered orally (p.o.), 45min prior to each dose of morphine. The analgesic activity of SAM and opioidergic component in its activity was also evaluated. Co-administration of morphine and SAM reversed morphine tolerance. SAM exhibited analgesic effect after repeated administration which was reversed by naloxone administration. Since safety of SAM on chronic use is documented it can be a good option in morphine tolerance. Role in drug addiction and withdrawal should also be evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

A bioactive sesquiterpene from Bixa orellana.

PubMed

Raga, Dennis D; Espiritu, Rafael A; Shen, Chien-Chang; Ragasa, Consolacion Y

2011-01-01

A dichloromethane extract of the air-dried leaves of Bixa orellana afforded ishwarane 1, phytol 2, polyprenol 3, and a mixture of stigmasterol 4a and sitosterol 4b by silica gel chromatography. The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy. Compound 1 at three doses (25, 50, and 100 mg/kg BW) was tested for prophylactic, gastrointestinal motility, analgesic, hypoglycemic, and antimicrobial potentials. Results of the prophylactic assay demonstrated the anti-toxic property of 1 at 100 mg/kg BW. A 50 mg/kg BW dose of 1 resulted in a more propulsive movement of the gastrointestinal tract (88.38 ± 13.59%) compared to the negative control (78.47 ± 10.61%). Tail flick and acetic acid writhing tests indicated that 100 mg/kg BW 1 had minimal analgesic activity. Compound 1 demonstrated no hypoglycemic potential on the animals tested. Compound 1 exhibited moderate antifungal activity against C. albicans, low activity against T. mentagrophytes, and low antibacterial activity against E. coli, S. aureus, and P. aeruginosa. It was inactive against B. subtilis and A. niger.

Tolerance of snakes to hypergravity

NASA Technical Reports Server (NTRS)

Lillywhite, H. B.; Ballard, R. E.; Hargens, A. R.

1996-01-01

Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.

Antinociceptive properties of physalins from Physalis angulata.

PubMed

Lima, Milena da Silva; Evangelista, Afrânio Ferreira; Santos, Gisele Graça Leite Dos; Ribeiro, Ivone Maria; Tomassini, Therezinha Coelho Barbosa; Pereira Soares, Milena Botelho; Villarreal, Cristiane Flora

2014-11-26

Pain is the most common reason a patient sees a physician. Nevertheless, the use of typical painkillers is not completely effective in controlling all pain syndromes; therefore further attempts have been made to develop improved analgesic drugs. The present study was undertaken to evaluate the antinociceptive properties of physalins B (1), D (2), F (3), and G (4) isolated from Physalis angulata in inflammatory and centrally mediated pain tests in mice. Systemic pretreatment with 1-4 produced dose-related antinociceptive effects on the writhing and formalin tests, traditional screening tools for the assessment of analgesic drugs. On the other hand, only 3 inhibited inflammatory parameters such as hyperalgesia, edema, and local production of TNF-α following induction with complete Freund's adjuvant. Treatment with 1, 3, and 4 produced an antinociceptive effect on the tail flick test, suggesting a centrally mediated antinociception. Reinforcing this idea, 2-4 enhanced the mice latency reaction time during the hot plate test. Mice treated with physalins did not demonstrate motor performance alterations. These results suggest that 1-4 present antinociceptive properties associated with central, but not anti-inflammatory, events and indicate a new pharmacological property of physalins.

Fabrication of topical metered dose film forming sprays for pain management.

PubMed

Ranade, Sneha; Bajaj, Amrita; Londhe, Vaishali; Babul, Najib; Kao, Danny

2017-03-30

Topical film-forming metered dose spray formulations were designed for management of pain. Ropivacaine, a local anesthetic is explored for its topical efficacy in alleviating pain. Metered dose spray containers, organic solvents, film forming polymers and permeation enhancers were utilized to fabricate the Metered Dose topical spray. Factors like viscosity, spray pattern, spray angle, volume of actuation, droplet size distribution of the metered dose spray formulation and drying time, flexibility and wash-ability of the film formed after spraying were assessed. Permeation of the drug into the porcine skin was observed based on ex-vivo diffusion studies and confocal microscopy. The results indicated a high level of drug concentration in the skin layers. Anti-nociceptive efficacy of the formulations was assessed on Wistar rats by hot plate and tail flick tests, based on the response to pain perception. The results were comparable to the conventional lidocaine gel. Topical film forming sprays have the ability to provide an accurate, long lasting and patient compliant delivery of drugs on the skin as compared to conventional gels. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.

PubMed

Abe, Kenji; Ishida, Kota; Kato, Masatoshi; Shigenaga, Toshiro; Taguchi, Kyoji; Miyatake, Tadashi

2002-11-01

To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats. After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold and effects of morphine (5 mg/kg, ip) using the hot-plate (HP) and tail-flick (TF) tests. Systemic administration of morphine inhibited HP and TF responses in control rats. Microinjection of AF64A (2 nmol/site) into the NRM significantly decreased the threshold of HP response after 14 d, whereas the TF response was not affected. Morphine-induced antinociception was significantly attenuated in rats administered AF64A. Extracellular acetylcholine was attenuated after 14 d to below detectable levels in rats given AF64A. Naloxone (1 microg/site) microinjected into control rat NRM also antagonized the antinociceptive effect of systemic morphine. These findings suggest that cholinergic neuron activation in the NRM modulates the antinociceptive effect of morphine simultaneously with the opiate system.

Behavioural sensitivity of a key Southern Ocean species (Antarctic krill, Euphausia superba) to p,p'-DDE exposure.

PubMed

Poulsen, Anita H; Kawaguchi, So; King, Catherine K; King, Robert A; Bengtson Nash, Susan M

2012-01-01

Persistent organic pollutants (POPs) have been frequently measured throughout the Southern Ocean food web for which little information is available to assess the potential risks of POP exposure. The current study evaluated the toxicological sensitivity of a key Southern Ocean species, Antarctic krill, to aqueous exposure of p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE). Behavioural endpoints were used as indicators of sublethal toxicity. Immediate behavioural responses (partial immobility and tail flicking) most likely reflect neurotoxicity, while the p,p'-DDE body residue causing a median level of sublethal toxicity in Antarctic krill following 96h exposure (IEC50(sublethal toxicity)=3.9±0.21mmol/kg lipid weight) is comparable to those known to cause sublethal narcosis in temperate aquatic species. Critical body residues (CBRs) were more reproducible across tests than effective seawater concentrations. These findings support the concept of the CBR approach, that effective tissue residues are comparable across species and geographical ranges despite differences in environmental factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of tizanidine and morphine with regard to tolerance-developing ability to antinociceptive action.

PubMed

Nabeshima, T; Yamada, S; Sugimoto, A; Matsuno, K; Kameyama, T

1986-10-01

The antinociceptive, tolerance-developing and anti-withdrawal activities of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzo-thiadiazole] were investigated by comparing its effects with those of morphine and clonidine in tail-flick-, hot plate-, acetic acid-induced writhing-, and naloxone-precipitated withdrawal jumping-tests. The antinociceptive action of tizanidine was not altered by naloxone, while that of morphine was antagonized. Tolerance to the tizanidine-induced antinociceptive action and to motor incoordination was developed by successive administration of tizanidine. In the tizanidine-tolerant mice, the antinociceptive action of morphine was significantly decreased, but not sleeping time induced by pentobarbital. The action of tizanidine was not modified in the morphine-tolerant mice. Tizanidine failed to induce morphine-withdrawal jumping and to inhibit naloxone-precipitated withdrawal jumping in the morphine-dependent mice. Cross tolerance to the antinociceptive action induced by tizanidine and clonidine was developed. These results suggest that alpha 2-adrenoreceptors may be involved in the action mechanism of tizanidine, but not opioid receptors. Functional tolerance to tizanidine action may be developed by successive administration of tizanidine.

COX-2 expression and function in the hyperalgesic response to paw inflammation in mice

PubMed Central

Jain, Naveen K.; Ishikawa, Tomo-o; Spigelman, Igor; Herschman, Harvey R.

2009-01-01

Peripheral inflammation and edema are often accompanied by primary and secondary hyperalgesia which are mediated by both peripheral and central mechanisms. The role of cyclooxygenase-2 (COX-2)-mediated prostanoid production in hyperalgesia is a topic of substantial current interest. We have established a murine foot-pad inflammation model in which both pharmacologic and genetic tools can be used to characterize the role of COX-2 in hyperalgesia. Zymosan, an extract from yeast, injected into the plantar surface of the hind paw induces an edema response and an increase in COX-2 expression in the hindpaw, spinal cord and brain. Zymosan-induced primary hyperalgesia, measured as a decrease in hindpaw withdrawal latency in response to a thermal stimulus, is long-lasting and is not inhibited by pre-treatment with the systemic COX-2 selective inhibitor, parecoxib (20 mg/kg). In contrast, the central component of hyperalgesia, measured as a reduction in tail flick latency in response to heat, is reduced by parecoxib. Zymosan-induced primary hyperalgesia in Cox-2−/− mice is similar to that of their Cox-2+/+ littermate controls. However, the central component of hyperalgesia is substantially reduced in Cox-2−/− versus Cox-2+/+ mice, and returns to baseline values much more rapidly. Thus pharmacological data suggest, and genetic experiments confirm, (i) that primary hyperalgesia in response to zymosan inflammation in the mouse paw is not mediated by COX-2 function and (ii) that COX-2 function plays a major role in the central component of hyperalgesia in this model of inflammation. PMID:18829279

Synthesis, Modeling, and Pharmacological Evaluation of UMB 425, a Mixed μ Agonist/δ Antagonist Opioid Analgesic with Reduced Tolerance Liabilities

PubMed Central

2013-01-01

Opioid narcotics are used for the treatment of moderate-to-severe pain and primarily exert their analgesic effects through μ receptors. Although traditional μ agonists can cause undesired side effects, including tolerance, addition of δ antagonists can attenuate said side effects. Herein, we report 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor synthesized from thebaine. Although UMB 425 lacks δ-specific motifs, conformationally sampled pharmacophore models for μ and δ receptors predict it to have efficacy similar to morphine at μ receptors and similar to naltrexone at δ receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. As predicted, UMB 425 exhibits a mixed μ agonist/δ antagonist profile as determined in receptor binding and [35S]GTPγS functional assays in CHO cells. In vivo studies in mice show that UMB 425 displays potent antinociception in the hot plate and tail-flick assays. The antinociceptive effects of UMB 425 are blocked by naloxone, but not by the κ-selective antagonist norbinaltorphimine. During a 6-day tolerance paradigm, UMB 425 maintains significantly greater antinociception compared to morphine. These studies thus indicate that, even in the absence of δ-specific motifs fused to the C-ring, UMB 425 has mixed μ agonist/δ antagonist properties in vitro that translate to reduced tolerance liabilities in vivo. PMID:23713721

Opiate System Mediate the Antinociceptive Effects of Coriandrum sativum in Mice

PubMed Central

Taherian, Abbas Ali; Vafaei, Abbas Ali; Ameri, Javad

2012-01-01

Our previous study showed that Coriandrum sativum (CS) has antinociceptive effects, but the mechanisms that mediate this effect are not clear. The present study was designed to test the role of opiate system in the antinociceptive effects of CS on acute and chronic pain in mice using Hot Plate (HP), Tail Flick (TF) and Formalin (FT) tests and also to compare its effect with dexamethasone (DEX) and stress (ST). Young adult male albino mice (25-30 g) in 33 groups (n = 8 in each group) were used in this study. CS (125 250, 500 and 1000 mg/Kg IP), DEX (0.5, 1 and 2 mg/Kg IP), vehicle (VEH) or swim stress were used 30 min before the pain evaluation tests. Acute and chronic pain was assessed by HP, TF and FT models. In addition, Naloxone (NAL, 2 mg/Kg, IP) was injected 15 min before the CS extract administration in order to assess the role of opiate system in the antinociception of CS. Results indicated that CS, DEX and ST have analgesic effects (p < 0.01) in comparison with the control group and higher dose of CS was more effective (p < 0.001). Besides, pretreatment of NAL modulates the antinociceptive effects of CS in all models (p < 0.001). The above findings showed that CS, DEX and ST have modulator effects on pain. These findings further indicate that the CS extract has more analgesic effects than DEX and ST and also provides the evidence for the existence of an interaction between antinociceptive effects of CS and opiate system. PMID:24250493

Phytochemical composition and antinociceptive activity of Bauhinia glauca subsp. hupehana in rats.

PubMed

Xu, Jinlong; Zhao, Qizhi; Wei, Lei; Yang, Yu; Xu, Rui; Yu, Nengjiang; Zhao, Yimin

2015-01-01

In traditional medicine, Bauhinia glauca subsp. hupehana has long been used as an analgesic agent in China. The aim of this study was to evaluate the antinociceptive activity of the ethanol extract of the aerial parts of B. glauca subsp. hupehana (BHE) in rats and its chemical fingerprint. The antinociceptive activity of BHE was assessed in mice using chemically and heat-induced pain models, such as the acetic acid-induced writhing, hot plate, tail-flick and glutamate tests. Naltrexone hydrochloride, a non-selective opioid receptor antagonist, was utilized to determine the involvement of the opioid system. In addition to this, the involvements of the cGMP and ATP-sensitive K+ channel pathways were also detected using methylene blue and glibenclamide. The oral administration of BHE (at doses of 50, 100 and 200 mg/kg) produced significant and dose-related inhibitions in both the chemically and heat-induced pain models. Interestingly, in the abdominal constriction test, when the dose of BHE was increased to 800 mg/kg (p.o., n = 10), the inhibition rate was 100%. The antinociceptive mechanism may involve the cGMP pathway and ATP sensitive K+ channel pathway. The central antinociceptive effect was not antagonized by naltrexone. One phenolic acid, one lignin and five flavonoids were isolated from BHE. The antinociceptive activity of BHE was most likely due to the presence of the flavonoids. The acute toxicity results showed that BHE was safe at a high dose (2 g/kg, p.o.). The current investigation demonstrates that B. glauca subsp. hupehana is a potential candidate for the development of novel, non-opioid, analgesic phytomedicines.

Interaction between the mu-agonist dermorphin and the delta-agonist [D-Ala2, Glu4]deltorphin in supraspinal antinociception and delta-opioid receptor binding.

PubMed Central

Negri, L.; Improta, G.; Lattanzi, R.; Potenza, R. L.; Luchetti, F.; Melchiorri, P.

1995-01-01

1. In rats, the interaction between the mu-opioid agonist dermorphin and the delta-opioid agonist [D-Ala2, Glu4]deltorphin was studied in binding experiments to delta-opioid receptors and in the antinociceptive test to radiant heat. 2. When injected i.c.v., doses of [D-Ala2, Glu4]deltorphin higher than 20 nmol produced antinociception in the rat tail-flick test to radiant heat. Lower doses were inactive. None of the doses tested elicited the maximum achievable response. This partial antinociception was accomplished with an in vivo occupancy of more than 97% of brain delta-opioid receptors and of 17% of mu-opioid receptors. Naloxone (0.1 mg kg-1, s.c.), and naloxonazine (10 mg kg-1, i.v., 24 h before), but not the selective delta-opioid antagonist naltrindole, antagonized the antinociception. 3. In vitro competitive inhibition studies in rat brain membranes showed that [D-Ala2, Glu4]deltorphin displaced [3H]-naltrindole from two delta-binding sites of high and low affinity. The addition of 100 microM Gpp[NH]p produced a three fold increase in the [D-Ala2, Glu4]deltorphin Ki value for both binding sites. The addition of 10 nM dermorphin increased the Ki value of the delta-agonist for the high affinity site five times. When Gpp[NH]p was added to the incubation medium together with 10 nM dermorphin, the high affinity Ki of the delta-agonist increased 15 times. 4. Co-administration into the rat brain ventricles of subanalgesic doses of dermorphin and [D-Ala2, Glu4]deltorphin resulted in synergistic antinociceptive responses. 5. Pretreatment with naloxone or with the non-equilibrium mu-antagonists naloxonazine and beta-funaltrexamine completely abolished the antinociceptive response of the mu-delta agonist combinations. 6. Pretreatment with the delta-opioid antagonists naltrindole and DALCE reduced the antinociceptive response of the dermorphin-[D-Ala2, Glu4]deltorphin combinations to a value near that observed after the mu-agonist alone. At the dosage used, naltrindole occupied more than 98% of brain delta-opioid receptors without affecting mu-opioid-receptors. 7. These data suggest that in the rat tail-flick test to radiant heat, mu- and delta-opioid agonists co-operate positively in evoking an antinociceptive response. Although interactions between different opioid pathways cannot be excluded, in vitro binding results indicate that this co-operative antinociception is probably mediated by co-activation of the delta-opioid receptors at the cellular level by the mu- and delta-agonist. PMID:8680727

Effects of inferior olive lesion on fear-conditioned bradycardia

PubMed Central

Kotajima, Hiroko; Sakai, Kazuhisa; Hashikawa, Tsutomu

2014-01-01

The inferior olive (IO) sends excitatory inputs to the cerebellar cortex and cerebellar nuclei through the climbing fibers. In eyeblink conditioning, a model of motor learning, the inactivation of or a lesion in the IO impairs the acquisition or expression of conditioned eyeblink responses. Additionally, climbing fibers originating from the IO are believed to transmit the unconditioned stimulus to the cerebellum in eyeblink conditioning. Studies using fear-conditioned bradycardia showed that the cerebellum is associated with adaptive control of heart rate. However, the role of inputs from the IO to the cerebellum in fear-conditioned bradycardia has not yet been investigated. To examine this possible role, we tested fear-conditioned bradycardia in mice by selective disruption of the IO using 3-acetylpyridine. In a rotarod test, mice with an IO lesion were unable to remain on the rod. The number of neurons of IO nuclei in these mice was decreased to ∼40% compared with control mice. Mice with an IO lesion did not show changes in the mean heart rate or in heart rate responses to a conditioned stimulus, or in their responses to a painful stimulus in a tail-flick test. However, they did show impairment of the acquisition/expression of conditioned bradycardia and attenuation of heart rate responses to a pain stimulus used as an unconditioned stimulus. These results indicate that the IO inputs to the cerebellum play a key role in the acquisition/expression of conditioned bradycardia. PMID:24784584

In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats.

PubMed

Mahdi, Harith Jameel; Khan, Nurzalina Abdul Karim; Asmawi, Mohd Zaini Bin; Mahmud, Roziahanim; A/L Murugaiyah, Vikneswaran

2018-03-01

The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

PubMed Central

Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

2013-01-01

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

Pharmacokinetics and effect of intravenous nalbuphine in weaned Holstein calves after surgical castration.

PubMed

Coetzee, J F; Lechtenberg, K F; Stock, M L; Kukanich, B

2014-04-01

The objective of this study was to investigate the pharmacokinetics and effect of nalbuphine administered intravenously to calves immediately prior to surgical castration. Ten healthy calves were randomly assigned to two treatments (n = 5): (i) 0.9% sodium chloride (CONT) placebo, (ii) nalbuphine hydrochloride (NAL) (0.4 mg/kg). Blood samples collected over 10 h postcastration were analyzed for nalbuphine and cortisol concentrations. Additionally, heart rate, respiratory rate, rectal temperature, and step count was compared between groups using a random-effects mixed model. Changes in behavior and attitude were assessed using a six-point ordinal scoring system and compared using chi-square analysis. Plasma NAL concentrations were only detectable for 3 h postadministration (T½ = 0.68 h; Range: 0.53-0.79 h). There was no effect of NAL treatment prior to castration on cortisol concentrations (P = 0.99), heart rate (P = 0.73), respiratory rate (P = 0.59), rectal temperature (P = 0.22), and step count (P = 0.08) but fewer calves showed signs of head shaking, kicking, and tail flicking in the NAL group compared with the CONT group (P = 0.036). Therefore, we conclude that a single intravenous injection of nalbuphine at 0.4 mg/kg reduced some pain-related behaviors but did not significantly eliminate the physiological signs of distress in calves after surgical castration. © 2013 John Wiley & Sons Ltd.

Finite element method simulating temperature distribution in skin induced by 980-nm pulsed laser based on pain stimulation.

PubMed

Wang, Han; Dong, Xiao-Xi; Yang, Ji-Chun; Huang, He; Li, Ying-Xin; Zhang, Hai-Xia

2017-07-01

For predicting the temperature distribution within skin tissue in 980-nm laser-evoked potentials (LEPs) experiments, a five-layer finite element model (FEM-5) was constructed based on Pennes bio-heat conduction equation and the Lambert-Beer law. The prediction results of the FEM-5 model were verified by ex vivo pig skin and in vivo rat experiments. Thirty ex vivo pig skin samples were used to verify the temperature distribution predicted by the model. The output energy of the laser was 1.8, 3, and 4.4 J. The laser spot radius was 1 mm. The experiment time was 30 s. The laser stimulated the surface of the ex vivo pig skin beginning at 10 s and lasted for 40 ms. A thermocouple thermometer was used to measure the temperature of the surface and internal layers of the ex vivo pig skin, and the sampling frequency was set to 60 Hz. For the in vivo experiments, nine adult male Wistar rats weighing 180 ± 10 g were used to verify the prediction results of the model by tail-flick latency. The output energy of the laser was 1.4 and 2.08 J. The pulsed width was 40 ms. The laser spot radius was 1 mm. The Pearson product-moment correlation and Kruskal-Wallis test were used to analyze the correlation and the difference of data. The results of all experiments showed that the measured and predicted data had no significant difference (P > 0.05) and good correlation (r > 0.9). The safe laser output energy range (1.8-3 J) was also predicted. Using the FEM-5 model prediction, the effective pain depth could be accurately controlled, and the nociceptors could be selectively activated. The FEM-5 model can be extended to guide experimental research and clinical applications for humans.

Solar transformation: Sun on the reservation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Epstein, R.T.

1994-01-01

To most Americans, the simple act of flicking on the light is as taken for granted as breathing air-without so much as a thought about its possible environmental consequences. But to Sylvia Brownskill and hundreds on the New Mexico Navajo Indian reservation, accessing electricity without harming the environment is of the utmost importance-and until recently, virtually impossible. Four years ago, however, practical technology for producing {open_quotes}clean{close_quotes} energy became available, and now even in the most remote locations of the reservation can flick on a light switch, knowing that the electricity generated is produced in its entirety by the power ofmore » the sun.« less

Development, characterization, and in vitro and in vivo evaluation of benzocaine- and lidocaine-loaded nanostructrured lipid carriers.

PubMed

Puglia, Carmelo; Sarpietro, Maria Grazia; Bonina, Francesco; Castelli, Francesco; Zammataro, Magda; Chiechio, Santina

2011-05-01

The present study concerns the in vitro and in vivo evaluation of benzocaine (BENZO) and lidocaine (LIDO) topical delivery from nanostructured lipid carriers (NLCs). Morphology and dimensional distribution of NLCs have been, respectively, characterized by differential scanning calorimetry (DSC) and photon correlation spectroscopy. The release pattern of BENZO and LIDO from NLCs was evaluated in vitro determining drug percutaneous absorption through excised human skin. Radiant heat tail-flick test was carried out in mice to determine the antinociceptive effect of BENZO and LIDO from NLC. DSC studies revealed that the inner oil phase of NLC plays a significant role in stabilizing the particle architecture and increasing the drug solubility. In vitro evidences show that BENZO and LIDO, when incorporated in viscosized NLC dispersions, exhibited a lower flux with respect to formulations containing the free drugs in the aqueous phase. In vivo study enabled to demonstrate that BENZO and LIDO can be released in a prolonged fashion when incorporated into lipid carriers. The results obtained pointed out NLC capability to act as an effective drug reservoir, thus prolonging the anesthetic effect of BENZO and LIDO. Copyright © 2010 Wiley-Liss, Inc.

Water/oil type microemulsion systems containing lidocaine hydrochloride: in vitro and in vivo evaluation.

PubMed

Dogrul, Ahmet; Arslan, Seyda Akkus; Tirnaksiz, Figen

2014-01-01

The purpose of this study was to develop a water/oil microemulsion containing lidocaine hydrochloride (4%) and to compare its local anaesthetic efficacy with commercial products. A pseudoternary diagram (Km:1/1 or 1/2) was constructed using lecithin/ethanol/oil/water. The droplet size, viscosity and release of the microemulsions were evaluated. Tail flick tests were conducted for in vivo effectiveness; the initiation time of effect, maximum effect, time to reach maximum effect, and relative efficacy were evaluated. The drug caused a significant increase in droplet size. The use of olive oil resulted in a decrease in the solubilisation parameter, as well as a reduction in the release. The droplet size and viscosity of the microemulsion composed of Miglyol/lecithin/ethanol/water/drug (Km:1/2) was lower than other microemulsions (8.38 nm, 6.9 mPa), and its release rate (1.61 mg/h) was higher. This system had a faster and more efficient anaesthetic effect than the other microemulsions and commercial products. Results indicate that a water/oil type microemulsion (Miglyol/lecithin/ethanol/water) has promising potential to increase the local anaesthetic effect.

Antinociception induced by chronic exposure of rats to cigarette smoke.

PubMed

Anderson, Kenton L; Pinkerton, Kent E; Uyeminami, Dale; Simons, Christopher T; Carstens, Mirela Iodi; Carstens, E

2004-08-05

To investigate if chronic exposure to cigarette smoke induces analgesia, rats were exposed to concentrated cigarette smoke in an environmental chamber over four successive 5-day blocks (6 h/day), with 2 smoke-free days between blocks. A control group was exposed to room air. Tail flick latencies increased significantly (analgesia) during each smoke exposure block, with a relative decline in analgesia across blocks (tolerance) and a return to control levels during the first three smoke-free interludes while remaining higher after the conclusion of the 4-week exposure period. Mechanical (von Frey) withdrawal thresholds declined over time in smoke-exposed and control groups, with the smoke-exposed group showing significantly lower thresholds. Plasma nicotine reached 95.4 +/- 32 (S.D.) ng/ml at the end of weekly smoke exposure and declined to 44.9 +/- 10.6 ng/ml 24 h after withdrawal. Rats lost weight during smoke exposure and quickly regained weight during smoke-free interludes and at the cessation of smoke exposure. Analgesia may contribute to the initiation of smoking, and rapid reversal of the analgesic effect following acute exposure may contribute to the difficulty in quitting smoking.

Spinal cord distribution of sup 3 H-morphine after intrathecal administration: Relationship to analgesia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishio, Y.; Sinatra, R.S.; Kitahata, L.M.

1989-09-01

The distribution of intrathecally administered {sup 3}H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In ratsmore » tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.« less

Melatonin reverses morphine tolerance by inhibiting microglia activation and HSP27 expression.

PubMed

Lin, Sheng-Hsiung; Huang, Ya-Ni; Kao, Jen-Hsin; Tien, Lu-Tai; Tsai, Ru-Yin; Wong, Chih-Shung

2016-05-01

Melatonin has been reported to attenuate opioid tolerance. In this study, we explored the possible mechanism of melatonin in diminishing morphine tolerance. Two intrathecal (i.t.) catheters were implanted in male Wistar rats for drug delivery. One was linked to a mini-osmotic pump for morphine or saline infusion. On the seventh day, 50μg of melatonin or vehicle was injected through the other catheter instantly after discontinuation of morphine or saline infusion; 3h later, 15μg of morphine or saline was injected. The antinociceptive response was then measured using the tail-flick test every 30min for 120min. The results showed that chronic morphine infusion elicited antinociceptive tolerance and upregulated heat shock protein 27 (HSP27) expression in the dorsal horn of the rat spinal cord. Melatonin pretreatment partially restored morphine's antinociceptive effect in morphine-tolerant rats and reversed morphine-induced HSP27 upregulation. In addition, chronic morphine infusion induced microglial cell activation and was reversed by melatonin treatment. The present study provides evidence that melatonin, acting via inhibiting morphine-induced neuroinflammation, can be useful as a therapeutic adjuvant for patients under long-term opioid treatment for pain relief. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioral Assessment of NIH Swiss Mice Acutely Intoxicated with Tetramethylenedisulfotetramine

PubMed Central

Flannery, Brenna M.; Silverman, Jill L.; Bruun, Donald A.; Puhger, Kyle R.; McCoy, Mark R.; Hammock, Bruce D.; Crawley, Jacqueline N.; Lein, Pamela J.

2014-01-01

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison that is thought to trigger seizures by inhibiting the function of the type A gamma-aminobutyric acid receptor (GABAAR). Acute intoxication with TETS can cause vomiting, convulsions, status epilepticus (SE) and even death. Clinical case reports indicate that individuals who survive poisoning may exhibit long-term neuropsychological issues and cognitive deficits. Therefore, the objective of this research was to determine whether a recently described mouse model of acute TETS intoxication exhibits persistent behavioral deficits. Young adult male NIH Swiss mice received a seizure-inducing dose of TETS (0.15 mg/kg, ip) and then were rescued from lethality by administration of diazepam (5 mg/kg, ip) approximately 20 min post-TETS-exposure. TETS-intoxicated mice typically exhibited 2 clonic seizures prior to administration of diazepam with no subsequent seizures post-diazepam injection as assessed using behavioral criteria. Seizures lasted an average of 72 seconds. Locomotor activity, anxiety-like and depression-relevant behaviors and cognition were assessed at 1 week, 1 month and 2 months post-TETS exposure using open field, elevated-plus maze, light↔dark transitions, tail suspension, forced swim and novel object recognition tasks. Interestingly, preliminary validation tests indicated that NIH Swiss mice do not respond to the shock in fear conditioning tasks. Subsequent evaluation of hot plate and tail flick nociception tasks revealed that this strain exhibits significantly decreased pain sensitivity relative to age- and sex-matched C57BL/6J mice, which displayed normal contextual fear conditioning. NIH Swiss mice acutely intoxicated with TETS exhibited no significant anxiety-related, depression-relevant, learning or memory deficits relative to vehicle controls at any of the time points assessed with the exception of significantly increased locomotor activity at 2 months post-TETS intoxication. The general absence of long-term behavioral deficits in TETS-intoxicated mice on these six assays suggests that the neurobehavioral consequences of TETS exposure described in human survivors of acute TETS intoxication are likely due to sustained seizure activity, rather than a direct effect of the chemical itself. Future research efforts are directed towards developing an animal model that better recapitulates the SE and seizure duration reported in humans acutely intoxicated with TETS. PMID:25446016

Hermit Thrush (Catharus guttatus)

USGS Publications Warehouse

Wood, Petra; Donovan, Therese M.

2012-01-01

With spotted breast and reddish tail, the Hermit Thrush lives up to its name. Although celebrated for its ethereal song, it is mostly a quiet and unobtrusive bird that spends much of its time in the lower branches of the undergrowth or on the forest floor, often seen flicking its wings while perched and quickly raising and slowly lowering its tail. A highly variable species in color and size, the Hermit Thrush's morphological characteristics and plumage have been well studied, with 12-13 subspecies now recognized (see Systematics).This thrush is one of the most widely distributed forest-nesting migratory birds in North America and the only forest thrush whose population has increased or remained stable over the past 20 years. Its extensive breeding range includes the northern hardwood forest, as well as most of the boreal and mountainous coniferous forest areas north of Mexico, with relatively recent expansions into New England and the southern Appalachians. In migration, the species moves to lower elevations and southward, spreading out to winter over much of the southern United States, through Mexico to Guatemala and east to Bermuda. It is the only species of Catharus that winters in North America, switching from a breeding diet of mainly arthropods to a wintering diet heavily supplemented with fruits.Much has been learned about this widely distributed species since the original Birds of North America account of 1996. New information pertaining to its song, migratory behavior, winter territoriality, survival, and diet has been added, as well as many new insights into the potential effects of forest management and other human disturbances. Still lacking are detailed nesting studies, studies of juvenile dispersal, of daily activities and time budgets, and of migratory routes.

The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches

PubMed Central

Espírito-Santo, Renan Fernandes; Meira, Cassio Santana; Costa, Rafael dos Santos; Souza Filho, Otávio Passos; Evangelista, Afranio Ferreira; Trossini, Gustavo Henrique Goulart; Ferreira, Glaucio Monteiro; Velozo, Eudes da Silva; Pereira Soares, Milena Botelho

2017-01-01

Braylin belongs to the group of natural coumarins, a group of compounds with a wide range of pharmacological properties. Here we characterized the pharmacological properties of braylin in vitro, in silico and in vivo in models of inflammatory/immune responses. In in vitro assays, braylin exhibited concentration-dependent suppressive activity on activated macrophages. Braylin (10–40 μM) reduced the production of nitrite, IL-1β, TNF-α and IL-6 by J774 cells or peritoneal exudate macrophages stimulated with LPS and IFN-γ. Molecular docking calculations suggested that braylin present an interaction pose to act as a glucocorticoid receptor ligand. Corroborating this idea, the inhibitory effect of braylin on macrophages was prevented by RU486, a glucocorticoid receptor antagonist. Furthermore, treatment with braylin strongly reduced the NF-κB-dependent transcriptional activity on RAW 264.7 cells. Using the complete Freund’s adjuvant (CFA)-induced paw inflammation model in mice, the pharmacological properties of braylin were demonstrated in vivo. Braylin (12.5–100 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on CFA model. Braylin did not produce antinociception on the tail flick and hot plate tests in mice, suggesting that braylin-induced antinociception is not a centrally-mediated action. Braylin exhibited immunomodulatory properties on the CFA model, inhibiting the production of pro-inflammatory cytokines IL-1β, TNF-α and IL-6, while increased the anti-inflammatory cytokine TGF-β. Our results show, for the first time, anti-inflammatory, antinociceptive and immunomodulatory effects of braylin, which possibly act through the glucocorticoid receptor activation and by inhibition of the transcriptional activity of NF-κB. Because braylin is a phosphodiesterase-4 inhibitor, this coumarin could represent an ideal prototype of glucocorticoid receptor ligand, able to induce synergic immunomodulatory effects. PMID:28594906

Synthesis and Nicotinic Acetylcholine Receptor In Vitro and In Vivo Pharmacological Properties of 2'-Fluoro-3'-(substituted phenyl)deschloroepibatidine Analogues of 2'-Fluoro-3'-(4-nitrophenyl)deschloroepibatidine (4-Nitro-PFEB or RTI-7527-102)

PubMed Central

Ondachi, Pauline; Castro, Ana; Luetje, Charles W.; Damaj, M. Imad; Mascarella, S. Wayne; Navarro, Hernán A.; Carroll, F. Ivy

2012-01-01

Herein, we report the synthesis and nicotinic acetylcholine receptor (nAChR) in vitro and in vivo pharmacological properties of 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines 5b–g, analogues of 3'-(4-nitrophenyl) compound 5a. All compounds had high affinity for the α4β2-nAChR and low affinity for α7-nAChR. Initial electrophysiological studies showed that all analogues were antagonists at α4β2-, α3β4-, and α7-nAChRs. The 4-carbamoylphenyl analogue 5g was highly selective for α4β2-nAChR over α3β4- and α7-nAChRs. All the analogues were antagonists of nicotine-induced antinociception in the tail-flick test. Molecular modeling docking studies using agonist-bound form of the X-ray crystal structure of the acetylcholine binding protein suggested several different binding modes for epibatidine, varenicline, and 5a–5g. In particular, a unique binding mode for 5g was suggested by these docking simulations. The high binding affinity, in vitro efficacy, and selectivity of 5g for α4β2-nAChR combined with its nAChR functional antagonist properties suggest that 5g will be a valuable pharmacological tool for studying the nAChR and may have potential as a pharmacotherapy for addiction and other CNS disorders. PMID:22742586

A specialized fungal parasite (Massospora cicadina) hijacks the sexual signals of periodical cicadas (Hemiptera: Cicadidae: Magicicada).

PubMed

Cooley, John R; Marshall, David C; Hill, Kathy B R

2018-01-23

Male periodical cicadas (Magicicada spp.) infected with conidiospore-producing ("Stage I") infections of the entomopathogenic fungus Massospora cicadina exhibit precisely timed wing-flick signaling behavior normally seen only in sexually receptive female cicadas. Male wing-flicks attract copulation attempts from conspecific males in the chorus; close contact apparently spreads the infective conidiospores. In contrast, males with "Stage II" infections that produce resting spores that wait for the next cicada generation do not produce female-specific signals. We propose that these complex fungus-induced behavioral changes, which resemble apparently independently derived changes in other cicada-Massospora systems, represent a fungus "extended phenotype" that hijacks cicadas, turning them into vehicles for fungus transmission at the expense of the cicadas' own interests.

CB1 receptor mediated analgesia from the Nucleus Reticularis Gigantocellularis pars alpha is activated in an animal model of neuropathic pain.

PubMed

Monhemius, R; Azami, J; Green, D L; Roberts, M H

2001-07-20

Cannabinoids are known to suppress responses to noxious stimulation in animals and man. Recent research has suggested a role for endogenous cannabinoids in the descending inhibition of dorsal horn cells via a supraspinal site of action. We have recently demonstrated [J. Physiol. 506(2) (1998) 459] that the nucleus reticularis gigantocellularis pars alpha (GiA) is a major source of such descending modulation, and importantly, that this system is activated in response to noxious stimulation. We have therefore investigated the role of CB1 receptor activation in mediating the antinociceptive effects of activation of GiA in models of acute and chronic pain. Microinjections (0.5 microl 60% DMSO) of either WIN 55,212-2 (5 microg, selective CB1 agonist), SR141716A (50 microg, competitive CB1 antagonist), both compounds together, or vehicle alone into GiA were performed prior to these tests in a randomised, blind manner. In control animals, WIN 55,212-2 markedly increased withdrawal latencies in the tail flick test and reduced responses to subcutaneous formalin. These effects were blocked by co-administration of SR141716A. These data suggest that activation of cannabinoid CB1 receptor subtypes in GiA leads to behavioural analgesia. In animals with partial sciatic nerve ligation, microinjection of drugs and injection of formalin were performed contralaterally to the site of ligation. Partial sciatic nerve ligation significantly reduced behavioural responses to contralaterally applied formalin. Microinjection of SR141716A to GiA reversed this inhibition of responses to formalin in animals with partial sciatic nerve ligation. These data provide evidence that endogenous CB1 receptor ligands are involved in GiA mediated antinociception, and that this system is important for the modulation of nociceptive transmission in an animal model of chronic neuropathic pain.

Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin.

PubMed

Raza, Kaisar; Singh, Bhupinder; Mahajan, Anadi; Negi, Poonam; Bhatia, Amit; Katare, O P

2011-05-01

Capsaicin, extracted from the fruits of Capsicum, is a powerful local stimulant with strong rubifacient action, devoid of vesication. Topical use of capsaicin is quite common in the treatment of various pain-associated musculo-skeletal disorders, itching and neuropathy. Despite its high pharmacodynamic potential, the patient compliance to the drug is reported to be poor owing to multiple skin problems like irritation, burning sensation, and erythma. The present study targets the encasement of drug in the interiors of flexible membrane vesicles (FMVs), as these are reported to have better penetration in the deeper layers of skin, thus leading to enhanced localization of drug and consequently, decreased skin irritation. Multilamellar drug-loaded FMVs, prepared by thin-film hydration were evaluated for their efficacy in vitro and in vivo. When compared with conventional liposomes, the formulated FMVs showed higher skin retention during ex vivo permeation studies employing LACA mice skin, higher analgesic potential using radiant tail-flick method in mice, and better flexibility in regaining their size. Being less of an irritant, these vesicular carriers were also found to be more comfortable on human skin. Thus, the capsaicin-loaded FMVs offer high potential as topical drug delivery technologies with improved patient acceptance and effectiveness.

A comparative profile of methanol extracts of Allium cepa and Allium sativum in diabetic neuropathy in mice

PubMed Central

Bhanot, Abhishek; Shri, Richa

2010-01-01

Introduction: Diabetic Neuropathy (DN) is a major microvascular complication of uncontrolled diabetes. This may result from increased oxidative stress that accompanies diabetes. Hence plants with antioxidant action play an important role in management of diabetes and its complications. Materials and Methods: This study was designed to evaluate preventive as well as curative effect of methanol extracts of outer scales and edible portions of two plants with established antioxidant action - Allium cepa and Allium sativum, in induced DN in albino mice. Mice were divided into control, diabetic and test extracts treated groups. Test extracts were administered daily at a dose of 200 mg/kg p.o. for 21 days, in the preventive group prior to onset of DN, and in the curative group after the onset of DN. Hyperalgesia and oxidative stress markers were assessed. STZ-diabetic mice showed a significant thermal hyperalgesia (as assessed by the tail-flick test), indicating development of DN. Results: Treatment with test extracts prevented loss in body weight, decreased plasma glucose level, and significantly ameliorated the hyperalgesia, TBARS, serum nitrite and GSH levels in diabetic mice. Conclusion: Methanol extract of outer scales of onion has shown most significant improvement; may be due to higher content of phenolic compounds in outer scales of A. cepa. PMID:21713142

The noradrenaline precursor L-threo-3,4-dihydroxyphenylserine exhibits antinociceptive activity via central alpha-adrenoceptors in the mouse.

PubMed Central

Kawabata, A.; Kasamatsu, K.; Umeda, N.; Takagi, H.

1994-01-01

1. Systemic (s.c. or p.o.) administration of L-threo-3,4-dihydroxyphenylserine (droxidopa, L-threo-DOPS; L-DOPS), a noradrenaline precursor, at a dose-range of 100-800 mg kg-1, produced naloxone-resistant antinociception in a dose-dependent manner in the mouse, as assessed by the tail flick test, kaolin-induced writhing test and formalin-induced nociception test. 2. Antinociception elicited by L-DOPS (400 mg kg-1, s.c.) was not affected by s.c. injection of benserazide, a peripherally preferential L-aromatic amino acid decarboxylase inhibitor, but was suppressed by its intracerebroventricular (i.c.v.) injection. 3. I.c.v. or intrathecal (i.t.) administration of the non-selective alpha-blocker, phentolamine, significantly reduced L-DOPS-induced antinociception. 4. I.c.v. administration of the alpha 1-blocker, prazosin, but not the alpha 2-blocker, yohimbine, abolished the antinociceptive effects of L-DOPS. In contrast, both blockers, when administered i.t., exhibited significant inhibitory effects. 5. These results suggest that systemic L-DOPS produces opioid-independent antinociception, mediated by supraspinal alpha 1-adrenoceptors and by spinal alpha 1- and alpha 2-adrenoceptors and may predict additional therapeutic applications of L-DOPS as an analgesic. PMID:7911717

Assessment of the analgesic, anti-inflammatory and sedative effects of the dichloromethanol extract of Schinus molle.

PubMed

Taylor, A; Oyedeji, O O; Aremu, O; Oyemitan, I; Gwebu, E T; Oyedeji, A O; Nkeh-Chungag, B N

2016-01-01

Determination of the active fraction and compounds of the dichloromethanol extract of Schinus molle seeds and evaluation of their biological effects. Dried seeds of Schinus molle were sequentially extracted in hexane, acetyl acetate and dichloromethane. The dichloromethane extract was separated into two fractions (1 and 2) by column chromatography. Fraction 2 was further separated into its two constituent compounds which were characterized as belonging to the lanosteroid group of compounds. Both factions were tested for their analgesic, anti-inflammatory and sedative effects. The two fractions significantly increased (p<0.05) the tail flick latency though fraction 2 provided better and more long lasting protection against thermal pain. On the other hand, the anti-inflammatory effect of ibuprofen, though inferior to the anti-inflammatory effect of fraction 2 was better than the effects of fraction 1. Fraction 2 significantly (p<0.01) reduced rat paw oedema compared to the saline treatment group throughout the experiments while fraction 2 compared to fraction 1 showed significantly (p<0.01) greater inflammatory effects. On the other hand both fractions lacked significant sedative effects. Given that fraction 2 had only two constituent compounds (isomasticadienonic and Masticatrienonate), one or both of these compounds should be contributing to the observed analgesic and anti-inflammatory effects.

Effect of Bacopa monniera extract on methylmercury-induced behavioral and histopathological changes in rats.

PubMed

Christinal, Johnson; Sumathi, Thangarajan

2013-10-01

Methylmercury (MeHg) is a well-recognized environmental contaminant with established health risk to human beings by fish and marine mammal consumption. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. This study was aimed to evaluate the effect of B. monniera extract (BME) on MeHg-induced toxicity in rat cerebellum. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with BME (40 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After treatment period, MeHg exposure significantly decreases the body weight and also caused the following behavioral changes. Decrease tail flick response, longer immobility time, significant decrease in motor activity, and spatial short-term memory. BME pretreatment reverted the behavioral changes to normal. MeHg exposure decreases the DNA and RNA content in cerebellum and also caused some pathological changes in cerebellum. Pretreatment with BME restored all the changes to near normal. These findings suggest that BME has a potent efficacy to alleviate MeHg-induced toxicity in rat cerebellum.

Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in μ-opioid receptor knockout mice

PubMed Central

Ide, Soichiro; Minami, Masabumi; Ishihara, Kumatoshi; Uhl, George R.; Satoh, Masamichi; Sora, Ichiro; Ikeda, Kazutaka

2012-01-01

Butorphanol is hypothesized to induce analgesia via opioid pathways, although the precise mechanisms for its effects remain unknown. In this study, we investigated the role of the μ-opioid receptor (MOP) in thermal, mechanical, and visceral chemical antinociception induced by butorphanol using MOP knockout (KO) mice. Butorphanol-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice compared with wildtype mice. The results obtained from our butorphanol-induced mechanical antinociception experiments, assessed by the Randall-Selitto test, were similar to the results obtained from the thermal antinociception experiments in these mice. Interestingly, however, butorphanol retained its ability to induce significant visceral chemical antinociception, assessed by the writhing test, in homozygous MOP-KO mice. The butorphanol-induced visceral chemical antinociception that was retained in homozygous MOP-KO mice was completely blocked by pretreatment with nor-binaltorphimine, a κ-opioid receptor (KOP) antagonist. In vitro binding and cyclic adenosine monophosphate assays also showed that butorphanol possessed higher affinity for KOPs and MOPs than for δ-opioid receptors. These results molecular pharmacologically confirmed previous studies implicating MOPs, and partially KOPs, in mediating butorphanol-induced analgesia. PMID:18417173

Considerations in video playback design: using optic flow analysis to examine motion characteristics of live and computer-generated animation sequences.

PubMed

Woo, Kevin L; Rieucau, Guillaume

2008-07-01

The increasing use of the video playback technique in behavioural ecology reveals a growing need to ensure better control of the visual stimuli that focal animals experience. Technological advances now allow researchers to develop computer-generated animations instead of using video sequences of live-acting demonstrators. However, care must be taken to match the motion characteristics (speed and velocity) of the animation to the original video source. Here, we presented a tool based on the use of an optic flow analysis program to measure the resemblance of motion characteristics of computer-generated animations compared to videos of live-acting animals. We examined three distinct displays (tail-flick (TF), push-up body rock (PUBR), and slow arm wave (SAW)) exhibited by animations of Jacky dragons (Amphibolurus muricatus) that were compared to the original video sequences of live lizards. We found no significant differences between the motion characteristics of videos and animations across all three displays. Our results showed that our animations are similar the speed and velocity features of each display. Researchers need to ensure that similar motion characteristics in animation and video stimuli are represented, and this feature is a critical component in the future success of the video playback technique.

The Anti-Inflammatory Activity of Boron Derivatives in Rodents

PubMed Central

Hall, Iris H.; Burnham, Bruce S.; Chen, Shang Y.; Sood, Anup; Spielvogel, Bernard F.; Morse, Karen W.

1995-01-01

Acyclic amine-carboxyboranes were effective anti-inflammatory agents in mice at 8 mg/kg x 2. These amine-carboxyboranes were more effective than the standard indomethacin at 8 mg/kg x 2, pentoxifylline at 50 mg/kg x 2, and phenylbutazone at 50 mg/kg x 2. The heterocyclic amine derivatives as well as amine-carbamoylboranes, carboalkoxyboranes, and cyanoboranes were generally less active. However, selected aminomethyl-phosphonate-N-cyanoboranes demonstrated greater than 60% reduction of induced inflammation. The boron compounds were also active in the rat induced edema, chronic arthritis, and pleurisy screens, demonstrating activity similar to the standard indomethacin. The compounds were effecive in reducing local pain and decreased the tail flick reflex to pain. The derivatives which demonstrated good anti-inflammatory activity were effective inhibitors of hydrolytic lysosomal, and proteolytic enzyme activities with IC50 50 values equal to -6M in mouse macrophages, human leukocytes, and Be Sal osteofibrolytic cells. In these same cell lines, the agents blocked prostaglandin cyclooxygenase activity with IC50 values of -6M. In mouse macrophage and human leukocytes, 5′ lipoxygenase activity was also inhibited by the boron derivatives with IC50 values of 10-6M. These IC50 values for inhibition of these enzyme activities are consistent with published values of known anti-inflammatory agents which target these enzymes. PMID:18472741

Screening of analgesic activity of Tunisian Urtica dioica and analysis of its major bioactive compounds by GCMS.

PubMed

Dhouibi, Raouia; Moalla, Dorsaf; Ksouda, Kamilia; Ben Salem, Maryem; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Affes, Hanen

2017-11-20

The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p < .001) at a dose of 400 mg/kg. Even with a low dose, we noticed an analgesic activity with many tests. The GC-MS analysis of the ethanol extract of leaf revealed many compounds; 2-methyltetradecane dodecane, 2,6,11-trimethyl-; 2,6,11-trimethyldodecane, and trimethylhexane which are pharmaceutically the most important. These findings justify that UD can be a valuable natural analgesic source which seemed to provide potential phototherapeutics against various ailments. The analysis of ethanolic extract of UD by GCMS revealed the presence of several compounds including polyphenols, flavonoids, triterpenes which can explain the analgesic effect of UD and its mechanism of action. Hence, UD could be another therapeutic alternative for relieving pain and for minimising the use of drugs that have long-term secondary effects.

Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

PubMed

Verginadis, Ioannis I; Simos, Yannis V; Velalopoulou, Anastasia P; Vadalouca, Athina N; Kalfakakou, Vicky P; Karkabounas, Spyridon Ch; Evangelou, Angelos M

2012-12-01

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

Antinociceptive activity of Inula britannica L. and patuletin: In vivo and possible mechanisms studies.

PubMed

Zarei, Mohammad; Mohammadi, Saeed; Komaki, Alireza

2018-06-12

Inula britannica L. is a predominant medicinal plant traditionally utilized in the treatments of arthritis and back pain in Iranian folk medicine. The purpose of this research was to evaluate the antinociceptive effects of Inula britannica L. flower essential oil (IBLEO) and one of its major constituents, Patuletin (Pn), in male mice. In this study, we used pain assessment tests including acetic acid-induced writhing, tail-flick (TF), formalin induced paw licking (FIPL) model, and glutamate-induced paw licking (GPL). For understanding the supposed antinociceptive mechanisms of IBLEO, opioid and L-arginine/NO/cGMP/ KATP pathways were examined. In the TF, writhing, GPL, and FIPL tests, a dosage of 100 mg/kg of IBLEO showed noteworthy antinociceptive effects in comparison with control (p < 0.05). In writhing test, administration of selective opioid antagonists (naltrindole, nor-binaltorphimine, and naloxonazine) attenuated the antinociceptive effect of IBLEO in comparison with control (p < 0.001). Both methylene blue and glibenclamide blocked the antinociceptive effect of IBLEO (p < 0.05), but the administration of L-arginine or sodium nitroprusside fundamentally potentiated the antinociception induced by IBLEO in phase II of the FIPL (p < 0.05). Additionally, patuletin showed significant antinociceptive effects in writhing, FIPL, and GPL tests (p < 0.01). The results of this examination showed that IBLEO and Pn have antinociceptive effects. The modulation of glutamatergic systems by opioid receptors could be involved, at least in part, in these effects. Our data also suggest the activation of the L-arginine/NO/cGMP/KATP pathway in IBLEO antinociceptive effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

PubMed

Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

2018-04-02

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

Lack of synergistic interaction between the two mechanisms of action of tapentadol in gastrointestinal transit.

PubMed

Cowan, A; Raffa, R B; Tallarida, C S; Tallarida, R J; Christoph, T; Schröder, W; Tzschentke, T M

2014-09-01

A multi-mechanistic approach offers potential enhancement of analgesic efficacy, but therapeutic gain could be offset by an increase in adverse events. The centrally acting analgesic tapentadol [(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride] combines μ-opioid receptor (MOR) agonism and neuronal noradrenaline reuptake inhibition (NRI), both of which contribute to its analgesic effects. Previously, isobolographic analysis of occupation-effect data and a theoretically equivalent methodology determining interactions from the effect scale demonstrated pronounced synergistic interaction between the two mechanisms of action of tapentadol in two models of antinociception (low-intensity tail-flick and spinal nerve ligation). The present study investigated the nature of interaction of the two mechanisms on a surrogate measure for gastrointestinal adverse effect (inhibition of gastrointestinal transit). Dose-response curves were generated in rats for tapentadol alone or in combination with the opioid receptor antagonist, naloxone, or the α2 -adrenoceptor antagonist, yohimbine, to reveal the effect of tapentadol based upon MOR agonism, NRI, and combined mechanisms. The dose-effect curve of tapentadol was shifted to the right by both antagonists, thereby providing data to distinguish between MOR agonism and NRI. Analysis revealed a simple additive interaction between the two mechanisms on this endpoint, in contrast to the synergistic interaction previously demonstrated for antinociception. We believe this is the first published evaluation of mechanistic interaction for a surrogate measure of adverse effect of a single compound with two mechanisms of action, and the results suggest that there is a greater separation between the analgesic and gastrointestinal effects of tapentadol than expected based upon its analgesic efficacy. © 2014 European Pain Federation - EFIC®

Pain management by a new series of dual inhibitors of enkephalin degrading enzymes: long lasting antinociceptive properties and potentiation by CCK2 antagonist or methadone.

PubMed

Le Guen, Stéphanie; Mas Nieto, Magdalena; Canestrelli, Corinne; Chen, Huixiong; Fournié-Zaluski, Marie-Claude; Cupo, Annie; Maldonado, Rafaël; Roques, Bernard P; Noble, Florence

2003-07-01

The discovery that the endogenous morphine-like peptides named enkephalins are inactivated by two metallopeptidases, neutral endopeptidase and aminopeptidase N, which can be blocked by dual inhibitors, represents a promising way to develop 'physiological' analgesics devoid of the side effects of morphine. A new series of dual aminophosphinic inhibitors of the two enkephalin-catabolizing enzymes has been recently designed. In this study, one of these inhibitors, RB3007, was tested in various assays commonly used to select analgesics (mouse hot-plate test, rat tail-flick test, writhing and formalin tests in mice, and paw pressure test in rats), and the extracellular levels of the endogenous enkephalins in the ventrolateral periaqueductal grey have been measured by microdialysis after systemic administration of RB3007. In the mouse hot-plate test, the dual inhibitor induced long-lasting (2 h) antinociceptive effects with a maximum of 35% analgesia 60 min after i.v. or i.p. administration. These antinociceptive responses were antagonized by prior injection of naloxone (0.1 mg/kg, s.c.). Similar long lasting effects were observed in the other animal models used. Very interestingly, injection of RB3007 (50 mg/kg, i.p.) significantly increased (82%) the extracellular levels of Met-enkephalin with a peak 60 min after i.p. injection. This increase parallels the antinociceptive responses observed. In addition, strong facilitatory effects of subanalgesic doses of the CCK(2) receptor antagonist, PD-134,308 or the synthetic opioid agonist, methadone on RB3007-induced antinociceptive responses were observed. These findings may constitute promising data for future development of a new class of analgesics that could be of major interest in a number of severe and persistent pain syndromes.

Association of down-regulation of calcitonin gene-related peptide and substance P with increase of myocardial vulnerability in diabetic neuropathic rats.

PubMed

Li, Tu-Ping; Guo, Zheng; Liu, Chao-Jie; Sun, Tao; Chen, Lu; Zhao, Xin

2017-10-01

Diabetic patients present high co-morbidities of neuropathy and severer consequences of coronary heart disease. But the pathological mechanism is still unclear. Here we investigated a potential association of diabetic impairment of sensory nerves with increase of vulnerability of myocardium in acute myocardial ischemia/reperfusion. A rat model of diabetes mellitus was induced by high fat and sugar diet plus a small dose of streptozotocin. Impairment of sensory nerves was evaluated by measurement of changes in tail flick latency to noxious thermal stimulation and calcitonin gene-related peptide (CGRP) and substance P (SP) in the dorsal root ganglia (DRG) and the myocardium of the heart were examined. The myocardial injury was examined by infarct size, apoptosis ratio of cardiomyocytes and cardiac troponin I in the animals underwent acute myocardial ischemia (for 30min) and reperfusion (for 120min). The effects of CGRP and SP on cardiomyocyte injury induced by high glucose and hypoxia/reoxygenation were tested in cultured myocytes. The diabetic animals presented significant elevation of noxious thermal threshold with obvious reduction of the contents of CGRP and SP in the DRG and the myocardium. Importantly, the diabetic animals showed significant increases of infarct size, myocyte apoptosis and serum cardiac troponin I after acute myocardial ischemia/reperfusion, compared to the non-diabetic control. Furthermore, exogenously administered CGRP and SP attenuated the myocyte injury induced by the high concentration of glucose and hypoxia/reoxygenation. These findings suggested that impairment of sensory nerves with significant reduction of CGRP and SP in DRG, ventricular myocardium and serum may be associated with increase of myocardial vulnerability in acute myocardial ischemia/reperfusion in streptozotocin-induced diabetic rats. Copyright © 2017 Elsevier Inc. All rights reserved.

(-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

PubMed

Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

2014-02-01

Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h. Copyright © 2013 Elsevier Ltd. All rights reserved.

Flexible histone tails in a new mesoscopic oligonucleosome model.

PubMed

Arya, Gaurav; Zhang, Qing; Schlick, Tamar

2006-07-01

We describe a new mesoscopic model of oligonucleosomes that incorporates flexible histone tails. The nucleosome cores are modeled using the discrete surface-charge optimization model, which treats the nucleosome as an electrostatic surface represented by hundreds of point charges; the linker DNAs are treated using a discrete elastic chain model; and the histone tails are modeled using a bead/chain hydrodynamic approach as chains of connected beads where each bead represents five protein residues. Appropriate charges and force fields are assigned to each histone chain so as to reproduce the electrostatic potential, structure, and dynamics of the corresponding atomistic histone tails at different salt conditions. The dynamics of resulting oligonucleosomes at different sizes and varying salt concentrations are simulated by Brownian dynamics with complete hydrodynamic interactions. The analyses demonstrate that the new mesoscopic model reproduces experimental results better than its predecessors, which modeled histone tails as rigid entities. In particular, our model with flexible histone tails: correctly accounts for salt-dependent conformational changes in the histone tails; yields the experimentally obtained values of histone-tail mediated core/core attraction energies; and considers the partial shielding of electrostatic repulsion between DNA linkers as a result of the spatial distribution of histone tails. These effects are crucial for regulating chromatin structure but are absent or improperly treated in models with rigid histone tails. The development of this model of oligonucleosomes thus opens new avenues for studying the role of histone tails and their variants in mediating gene expression through modulation of chromatin structure.

Responses by king snakes (Lampropeltis getulus) to chemicals from colubrid and crotaline snakes.

PubMed

Weldon, P J; Schell, F M

1984-10-01

Four litters of king snakes (Lampropeltis getulus), a snake-eating species, were tested for responses to chemicals from colubrid and crotaline snakes. King snakes presented with swabs rubbed against the dorsal skin of living snakes and with swabs treated with methylene chloride extracts of shed snake skins tongue-flicked more to swabs from a northern copperhead (Agkistrodon contortrix), a crotaline, than to swabs from some colubrid snakes or to blank swabs. Six out of 10 king snakes in one litter attacked and attempted to ingest swabs treated with snake skin chemicals, implicating these chemicals as feeding stimuli for these ophiophagous snakes. Ingestively naive king snakes presented with plain air and snake odors in an olfactometer tongue-flicked more to snake odors. This study and others suggest that crotaline and colubrid snakes can be distinguished by chemical cues.

The effects of early experience on subsequent feeding responses in the Tegu, Tupinambis teguixin (Squamata : Teiidae).

PubMed

Punzo, F

2003-01-01

The purpose of this study was to assess the effects of early feeding experiences on subsequent responses to prey in the tegu, Tupinambis teguixin. Five-day old lizards were exposed to the odors of various prey and control substances on cotton-tipped applicators with the tongue-flick attack score (TFAS) chosen as the dependent variable. Each lizard was exposed to four stimuli: two controls (deionised water and cologne), and extracts from a mouse Mus musculus, and a lizard Ameiva ameiva, in a repeated measures, randomized block design, receiving one stimulus training session / day over a 40-day period. Tongue-flicks directed toward the applicator were counted over a 1 min period as well as the amount of time that elapsed from the first tongue flick to any bite that may have occurred. Live neonatal mice (but not A. ameiva), offered on a weekly basis, were used as a food source for tegus over a 10-month period. After 10 months, tegus were exposed to applicators containing control odors as well as those containing extracts from mice and lizards (A. ameiva). Mouse extracts elicited significantly higher TFAS as compared to those elicited by A. ameiva or control odors, suggesting that prey odors encountered in the environment shortly after hatching can influence prey preferences by these lizards later in life. These results also indicate that tegu lizards can learn to use specific odor cues associated with naturally occurring prey as releasers for subsequent hunting behaviors.

Antennular Morphology and Contribution of Aesthetascs in the Detection of Food-related Compounds in the Shrimp Palaemon adspersus Rathke, 1837 (Decapoda: Palaemonidae).

PubMed

Solari, Paolo; Sollai, Giorgia; Masala, Carla; Loy, Francesco; Palmas, Francesco; Sabatini, Andrea; Crnjar, Roberto

2017-04-01

Shrimp are an essential ecological component of marine ecosystems, and have commercial importance for human consumption and aquaculture. Like other decapod crustaceans, shrimp rely on chemical senses to detect and localize food resources by means of chemosensilla that are located mainly on the cephalothoracic appendages. Using the shrimp Palaemon adspersus, a model organism with omnivorous feeding behavior, we aimed to provide comparative information on the role of aesthetascs, antennular sensilla, and flicking behavior in food detection. To this end, we examined i) the morphology of antennular sensilla by field emission scanning electron microscopy, ii) the shrimp's sensitivity to a number of food-related compounds (amino acids and sugars) by means of whole-animal bioassays, and iii) the contribution of the aesthetasc sensilla to food detection. Our results showed that, aside from the aesthetascs, only three other main morphotypes of setae with chemoreceptive features were present in the antennules, thus accounting for relatively simple sensillar equipment. Nevertheless, we found broad-spectrum sensitivity of the shrimp to a number of amino acids (i.e., isoleucine, leucine, methionine, phenylalanine, glycine, tryptophan, cysteine, and tyrosine) and carbohydrates (trehalose, maltose, cellobiose, and fructose) that was consistent with the omnivorous or scavenging habits of the animal. Although aesthetasc ablation attenuated flicking behavior in a chemical stimulus-independent manner, success in detection and short-range localization of food did not rely on the presence of aesthetasc sensilla. This finding confirms the existence of a non-aesthetasc alternative pathway for feeding, with functional redundancy in simple generalist feeder models such as shrimp.

Numerical modeling of cracking pattern's influence on the dynamic response of thickened tailings disposals: a periodic approach

NASA Astrophysics Data System (ADS)

Ferrer, Gabriel; Sáez, Esteban; Ledezma, Christian

2018-01-01

Copper production is an essential component of the Chilean economy. During the extraction process of copper, large quantities of waste materials (tailings) are produced, which are typically stored in large tailing ponds. Thickened Tailings Disposal (TTD) is an alternative to conventional tailings ponds. In TTD, a considerable amount of water is extracted from the tailings before their deposition. Once a thickened tailings layer is deposited, it loses water and it shrinks, forming a relatively regular structure of tailings blocks with vertical cracks in between, which are then filled up with "fresh" tailings once the new upper layer is deposited. The dynamic response of a representative column of this complex structure made out of tailings blocks with softer material in between was analyzed using a periodic half-space finite element model. The tailings' behavior was modeled using an elasto-plastic multi-yielding constitutive model, and Chilean earthquake records were used for the seismic analyses. Special attention was given to the liquefaction potential evaluation of TTD.

Hydrodynamic Characteristics of a Low-drag, Planing-tail Flying-boat Hull

NASA Technical Reports Server (NTRS)

Suydam, Henry B

1948-01-01

The hydrodynamic characteristics of a flying-boat incorporating a low-drag, planing-tail hull were determined from model tests made in Langley tank number 2 and compared with tests of the same flying boat incorporating a conventional-type hull. The planing-tail model, with which stable take-offs were possible for a large range of elevator positions at all center-of-gravity locations tested, had more take-off stability than the conventional model. No upper-limit porpoising was encountered by the planing-tail model. The maximum changes in rise during landings were lower for the planing-tail model than for the conventional model at most contact trims, an indication of improved landing stability for the planing-tail model. The hydrodynamic resistance of the planing-tail hull was lower than the conventional hull at all speeds, and the load-resistance ratio was higher for the planing-tail hull, being especially high at the hump. The static trim of the planing-tail hull was much higher than the conventional hull, but the variation of trim with speed during take-off was smaller.

New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ⁶,1-Benzothiazine-3-Carboxylates.

PubMed

Azotla-Cruz, Liliana; Lijanova, Irina V; Ukrainets, Igor V; Likhanova, Natalya V; Olivares-Xometl, Octavio; Bereznyakova, Natalya L

2017-01-12

According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N -alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K₂CO₃ system the reaction of methyl 4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N -substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (¹Н and 13 С) spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N -benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1 H -2λ⁶,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N- methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

Peripheral antinociceptive effects of the cyclic endomorphin-1 analog c[YpwFG] in a mouse visceral pain model.

PubMed

Bedini, Andrea; Baiula, Monica; Gentilucci, Luca; Tolomelli, Alessandra; De Marco, Rossella; Spampinato, Santi

2010-11-01

We previously described a novel cyclic endomorphin-1 analog c[Tyr-D-Pro-D-Trp-Phe-Gly] (c[YpwFG]), acting as a mu-opioid receptor (MOR) agonist. This study reports that c[YpwFG] is more lipophilic and resistant to enzymatic hydrolysis than endomorphin-1 and produces preemptive antinociception in a mouse visceral pain model when injected intraperitoneally (i.p.) or subcutaneously (s.c.) before 0.6% acetic acid, employed to evoke abdominal writhing (i.p. ED(50)=1.24 mg/kg; s.c. ED(50)=2.13 mg/kg). This effect is reversed by the selective MOR antagonist β-funaltrexamine and by a high dose of the mu(1)-opioid receptor-selective antagonist naloxonazine. Conversely, the kappa-opioid receptor antagonist nor-binaltorphimine and the delta-opioid receptor antagonist naltrindole are ineffective. c[YpwFG] produces antinociception when injected i.p. after acetic acid (ED(50)=4.80 mg/kg), and only at a dose of 20mg/kg did it elicit a moderate antinociceptive response in the mouse, evaluated by the tail flick assay. Administration of a lower dose of c[YpwFG] (10mg/kg i.p.) apparently produces a considerable part of antinociception on acetic acid-induced writhes through peripheral opioid receptors as this action is fully prevented by i.p. naloxone methiodide, which does not readily cross the blood-brain barrier; whereas this opioid antagonist injected intracerebroventricularly (i.c.v.) is not effective. Antinociception produced by a higher dose of c[YpwFG] (20mg/kg i.p.) is partially reversed by naloxone methiodide i.c.v. administered. Thus, only at the dose of 20mg/kg c[YpwFG] can produce antinociception through both peripheral and central opioid receptors. In conclusion, c[YpwFG] displays sufficient metabolic stability to be effective after peripheral administration and demonstrates the therapeutic potential of endomorphin derivatives as novel analgesic agents to control visceral pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Predatory behavior inTupinambis teguixin (Sauria: Teiidae). I. Tongue-flicking responses to chemical food stimuli.

PubMed

Yanosky, A A; Iriart, D E; Mercolli, C

1993-02-01

Black tegu lizards (Tupinambis teguixin) have the ability to detect food odors and discriminate between them and nonfood odors. This was tested by offering chemical stimuli on cotton-tipped applicators to the animals. Stimuli were from two plant and two animal species known to be principal items in these lizards' diets, demineralized water as an odorless control, and eaude-cologne as an odorous control lacking feeding or social importance. Tongueflick attack score, latency to attack, preattack tongue-flicks, and number of attacks were analyzed. The results clearly demonstrated that this species responds to chemical food stimuli, but does not respond to odorless nonfood stimuli. Responses differed among food types. There were no sex differences. These results are in agreement with the prediction that lizards having forked tongues and an active foraging mode rely on chemical cues for feeding.

77 FR 2241 - Radio Broadcasting Services; Ehrenberg, First Mesa, Kachina Village, Wickenburg, and Williams, AZ...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... terminated without considering these proposals. The first proposal, RM-11517, filed by Rocket Radio, Inc..., Washington, DC 20007-3501 (Counsel to Rocket Radio, Inc.); and Scott R. Flick, Esq., Pillsbury Winthrop Shaw...

Evaluation of the safety and usability of touch gestures in operating in-vehicle information systems with visual occlusion.

PubMed

Kim, Huhn; Song, Haewon

2014-05-01

Nowadays, many automobile manufacturers are interested in applying the touch gestures that are used in smart phones to operate their in-vehicle information systems (IVISs). In this study, an experiment was performed to verify the applicability of touch gestures in the operation of IVISs from the viewpoints of both driving safety and usability. In the experiment, two devices were used: one was the Apple iPad, with which various touch gestures such as flicking, panning, and pinching were enabled; the other was the SK EnNavi, which only allowed tapping touch gestures. The participants performed the touch operations using the two devices under visually occluded situations, which is a well-known technique for estimating load of visual attention while driving. In scrolling through a list, the flicking gestures required more time than the tapping gestures. Interestingly, both the flicking and simple tapping gestures required slightly higher visual attention. In moving a map, the average time taken per operation and the visual attention load required for the panning gestures did not differ from those of the simple tapping gestures that are used in existing car navigation systems. In zooming in/out of a map, the average time taken per pinching gesture was similar to that of the tapping gesture but required higher visual attention. Moreover, pinching gestures at a display angle of 75° required that the participants severely bend their wrists. Because the display angles of many car navigation systems tends to be more than 75°, pinching gestures can cause severe fatigue on users' wrists. Furthermore, contrary to participants' evaluation of other gestures, several participants answered that the pinching gesture was not necessary when operating IVISs. It was found that the panning gesture is the only touch gesture that can be used without negative consequences when operating IVISs while driving. The flicking gesture is likely to be used if the screen moving speed is slower or if the car is in heavy traffic. However, the pinching gesture is not an appropriate method of operating IVISs while driving in the various scenarios examined in this study. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study

PubMed Central

Mandillo, Silvia; Tucci, Valter; Hölter, Sabine M.; Meziane, Hamid; Banchaabouchi, Mumna Al; Kallnik, Magdalena; Lad, Heena V.; Nolan, Patrick M.; Ouagazzal, Abdel-Mouttalib; Coghill, Emma L.; Gale, Karin; Golini, Elisabetta; Jacquot, Sylvie; Krezel, Wojtek; Parker, Andy; Riet, Fabrice; Schneider, Ilka; Marazziti, Daniela; Auwerx, Johan; Brown, Steve D. M.; Chambon, Pierre; Rosenthal, Nadia; Tocchini-Valentini, Glauco; Wurst, Wolfgang

2008-01-01

Establishing standard operating procedures (SOPs) as tools for the analysis of behavioral phenotypes is fundamental to mouse functional genomics. It is essential that the tests designed provide reliable measures of the process under investigation but most importantly that these are reproducible across both time and laboratories. For this reason, we devised and tested a set of SOPs to investigate mouse behavior. Five research centers were involved across France, Germany, Italy, and the UK in this study, as part of the EUMORPHIA program. All the procedures underwent a cross-validation experimental study to investigate the robustness of the designed protocols. Four inbred reference strains (C57BL/6J, C3HeB/FeJ, BALB/cByJ, 129S2/SvPas), reflecting their use as common background strains in mutagenesis programs, were analyzed to validate these tests. We demonstrate that the operating procedures employed, which includes open field, SHIRPA, grip-strength, rotarod, Y-maze, prepulse inhibition of acoustic startle response, and tail flick tests, generated reproducible results between laboratories for a number of the test output parameters. However, we also identified several uncontrolled variables that constitute confounding factors in behavioral phenotyping. The EUMORPHIA SOPs described here are an important start-point for the ongoing development of increasingly robust phenotyping platforms and their application in large-scale, multicentre mouse phenotyping programs. PMID:18505770

Development and Evaluation of a Novel Mucoadhesive Film Containing Acmella oleracea Extract for Oral Mucosa Topical Anesthesia

PubMed Central

Santana de Freitas-Blanco, Verônica; Franz-Montan, Michelle; Groppo, Francisco Carlos; de Carvalho, João Ernesto; Figueira, Glyn Mara; Serpe, Luciano; Oliveira Sousa, Ilza Maria; Guilherme Damasio, Viviane Aparecida; Yamane, Lais Thiemi; de Paula, Eneida; Ferreira Rodrigues, Rodney Alexandre

2016-01-01

Purpose To develop an anesthetic mucoadhesive film containing Acmella oleracea (jambu) extract for topical use on oral mucosa. Methods Ethanolic extracts from aerial parts of jambu were prepared by maceration. Pigment removal was obtained by adsorption with activated carbon. Three mucoadhesive films were developed using a film casting method: 10 or 20% of crude jambu extract (10% JB and 20% JB), and 10% of crude jambu extract treated with activated carbon (10% JBC). The mucoadhesive films were characterized regarding their uniformity, thickness, pH, and spilanthol content, and their stability was evaluated during 120 days. Gas chromatography was used to quantify the amount of spilanthol. In vitro tests determined the permeation of spilanthol across pig esophageal epithelium mucosa in Franz diffusion cells. Topical anesthetic efficacy was assessed in vivo using a tail flick test in mice. Results The three mucoadhesive films showed physical stability and visual appearances suitable for use on oral mucosa. The permeation study revealed that the spilanthol from 10% JBC presented higher flux and permeability coefficient values, compared to 10% or 20% JB (p < 0.001). Moreover, 10% JBC showed better topical anesthetic efficacy than the other films (p < 0.01). Conclusion Mucoadhesive film containing crude extract of jambu treated with activated carbon is a potential alternative for oral, topical use, encouraging future clinical studies. PMID:27626796

Anti-rheumatoid Arthritis Effect of Kaejadan via Analgesic and Antiinflammatory Activity in vivo and in vitro.

PubMed

Yoon, Jung Jae; Sohn, Eun Jung; Kim, Jung Hyo; Seo, Jai Wha; Kim, Sung-Hoon

2017-03-01

Although Kaejadan (KJD), an herbal cocktail of three medicinal plants (Lithospermum erythrorhizon, Cinnamomum loureirii, and Salvia miltiorrhiza), has been traditionally used for the treatment of rheumatoid arthritis, its scientific evidence is not fully understood. Hence, we investigated antiinflammatory and analgesic mechanism of KJD in vivo and in vitro. Kaejadan suppressed the number of writhing responses in mice treated by acetic acid and showed antinociceptive effect by tail-flick test. Kaejadan abrogated serotonin or carrageenan or Freund's complete adjuvant (FCA)-induced paw edema and also reduced the level of Evans Blue for vascular permeability. Furthermore, KJD effectively reduced the positive responses for C-reactive protein and rheumatoid arthritis test in FCA-treated rats. Of note, KJD inhibited the level of lipid peroxide malondialdehyde and enhanced the level of superoxide dismutase in the hepatic tissues of FCA-treated rats. Additionally, KJD abrogated the levels of IL-1β and IL-6 in lipopolysaccharide and IFN-γ-exposed RAW 264.7 cells. Also, KJD reduced the expression of cyclooxygenase 2 or inducible nitric oxide synthase at protein and mRNA levels in IFN-γ and lipopolysaccharide-exposed RAW 264.7 cells. Overall, our findings demonstrate that KJD exerts antiinflammatory and analgesic effects via enhancement of antioxidant activity and inhibition of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Identification of spinal 5-HT sub 3 receptors and their role in the modulation of nociceptive responses in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glaum, S.R.

1988-01-01

The project consisted of two related studies: (1) the characterization of serotonin binding sites in crude and purified synaptic membranes prepared from the rat spinal cord, and (2) the association of serotonin binding sites with functional 5-HT receptor responses in the modulation of nociceptive information at the level of the spinal cord. The first series of experiments involved the preparation of membranes from the dorsal and ventral halves of the rat spinal cord and the demonstration of specific ({sup 3}H)serotonin binding to these membranes. High affinity binding sites which conformed to the 5-HT{sub 3} subtype were identified in dorsal, butmore » not ventral spinal cord synaptic membranes. These experiments also confirmed the presence of high affinity ({sup 3}H)5-HT binding sites in dorsal spinal cord synaptic membranes of the 5-HT{sub 1} subtype. The second group of studies demonstrated the ability of selective 5-HT{sub 3} antagonists to inhibit the antinociceptive response to intrathecally administered 5-HT, as measured by a change in tail flick and hot plate latencies. Intrathecal pretreatment with the selective 5-HT{sub 3} antagonists ICS 205-930 or MDL 72222 abolished the antinociceptive effects of 5-HT. Furthermore, the selective 5-HT{sub 3} agonist 2-methyl-5-HT mimicked the antinociceptive effects of 5-HT.« less

Nicotinic receptor involvement in antinociception induced by exposure to cigarette smoke.

PubMed

Simons, Christopher T; Cuellar, Jason M; Moore, Justin A; Pinkerton, Kent E; Uyeminami, Dale; Carstens, Mirela Iodi; Carstens, E

2005-12-02

Direct exposure of rats to tobacco smoke induces antinociception. We presently investigated if this antinociception is mediated via nicotinic and/or mu-opioid receptors. Adult male rats were surgically implanted with Alzet osmotic minipumps that delivered either saline (control), the nicotinic antagonist mecamylamine, or the opiate antagonist naltrexone (3 mg/kg/day i.v. for 21 days). Nocifensive responses were assessed on alternate days using tail-flick reflex latency (TFL) over a 3-week period. During the second week, the rats were exposed to concentrated cigarette smoke in an environmental chamber for 6 h/day for 5 consecutive days; a control group was similarly exposed to filtered cigarette smoke. Rats receiving mecamylamine and naltrexone exhibited a significant weight loss after the first day of infusion. All treatment groups additionally exhibited significant weight loss during exposure to unfiltered or filtered smoke. The saline group exhibited significant antinociception on the first day of smoke exposure with rapid development of tolerance. The mecamylamine and naltrexone groups did not exhibit significant antinociception. Controls exposed to filtered smoke (with approximately 50% lower nicotine concentration) also exhibited significant analgesia on the first exposure day with rapid development of tolerance. Exposure to high levels of cigarette smoke, or to filtered smoke with a lower nicotine concentration in the vapor phase, induces antinociception with rapid development of tolerance. The antinociceptive effect appears to be mediated via nicotinic and mu-opioid receptors.

Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

PubMed

Zhang, L X; Li, X L; Wang, L; Han, J S

1997-01-16

Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

Endogenous opioid peptide-mediated neurotransmission in central and pericentral nuclei of the inferior colliculus recruits μ1-opioid receptor to modulate post-ictal antinociception.

PubMed

Felippotti, Tatiana Tocchini; de Freitas, Renato Leonardo; Coimbra, Norberto Cysne

2012-02-01

The aim of the present work was to investigate the involvement of the μ1-endogenous opioid peptide receptor-mediated system in post-ictal antinociception. Antinociceptive responses were determined by the tail-flick test after pre-treatment with the selective μ1-opioid receptor antagonist naloxonazine, peripherally or centrally administered at different doses. Peripheral subchronic (24 h) pre-treatment with naloxonazine antagonised the antinociception elicited by tonic-clonic seizures. Acute (10 min) pre-treatment, however, did not have the same effect. In addition, microinjections of naloxonazine into the central, dorsal cortical and external cortical nuclei of the inferior colliculus antagonised tonic-clonic seizure-induced antinociception. Neither acute (10-min) peripheral pre-treatment with naloxonazine nor subchronic intramesencephalic blockade of μ1-opioid receptors resulted in consistent statistically significant differences in the severity of tonic-clonic seizures shown by Racine's index (1972), although the intracollicular specific antagonism of μ1-opioid receptor decreased the duration of seizures. μ1-Opioid receptors and the inferior colliculus have been implicated in several endogenous opioid peptide-mediated responses such as antinociception and convulsion. The present findings suggest the involvement of μ1-opiate receptors of central and pericentral nuclei of the inferior colliculus in the modulation of tonic-clonic seizures and in the organisation of post-ictal antinociception. Copyright © 2011 Elsevier Ltd. All rights reserved.

Influence of oxcarbazepine on the antinociceptive action of morphine and metamizole in mice.

PubMed

Pakulska, Wanda; Czarnecka, Elzbieta

2009-01-01

Numerous methods of management applied in order to obtain higher therapeutic efficacy of drugs with minimum adverse effects include taking advantage of interactions taking place between individual agents. Analgesics are combined with drugs belonging to other therapeutic groups, including, more and more frequently, antiepileptic agents. The influence of oxcarbazepine (10 mg/kg) on the antinociceptive effect of morphine (10 mg/kg) and metamizole (500 mg/kg) was investigated in mice using the hot-plate and tail-flick tests. All drugs were injected intraperitoneally (i.p.). Oxcarbazepine was administered 30 min prior to the injection of analgesic drugs. The reactions to noxious stimuli were measured 30, 60 and 90 min after the administration of an analgesic. The study was further conducted for 10 days with repeated drug doses. Single administration of oxcarbazepine enhanced the antinociceptive effect of a single dose of morphine, and 10-day administration led to a decrease of morphine tolerance in the hot-plate test. Oxcarbazepine administered in a single dose did not affect significantly the antinociceptive effect of metamizole in either of the tests. Multiple administration of oxcarbazepine enhanced the antinociceptive effect of metamizole in the hot-plate test. Oxcarbazepine alone, administered in a single and repeated doses, demonstrated an antinociceptive effect, but only for the hot-plate test, which indicates involvement of supraspinal structures in antinociception.

Sound production and mechanism in Heniochus chrysostomus (Chaetodontidae).

PubMed

Parmentier, Eric; Boyle, Kelly S; Berten, Laetitia; Brié, Christophe; Lecchini, David

2011-08-15

The diversity in calls and sonic mechanisms appears to be important in Chaetodontidae. Calls in Chaetodon multicinctus seem to include tail slap, jump, pelvic fin flick and dorsal-anal fin erection behaviors. Pulsatile sounds are associated with dorsal elevation of the head, anterior extension of the ventral pectoral girdle and dorsal elevation of the caudal skeleton in Forcipiger flavissiumus. In Hemitaurichthys polylepis, extrinsic swimbladder muscles could be involved in sounds originating from the swimbladder and correspond to the inward buckling of tissues situated dorsally in front of the swimbladder. These examples suggest that this mode of communication could be present in other members of the family. Sounds made by the pennant bannerfish (Heniochus chrysostomus) were recorded for the first time on coral reefs and when fish were hand held. In hand-held fishes, three types of calls were recorded: isolated pulses (51%), trains of four to 11 pulses (19%) and trains preceded by an isolated pulse (29%). Call frequencies were harmonic and had a fundamental frequency between 130 and 180 Hz. The fundamental frequency, sound amplitude and sound duration were not related to fish size. Data from morphology, sound analysis and electromyography recordings highlight that the calls are made by extrinsic sonic drumming muscles in association with the articulated bones of the ribcage. The pennant bannerfish system differs from other Chaetodontidae in terms of sound characteristics, associated body movements and, consequently, mechanism.

Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine-mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception.

PubMed

de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Biagioni, Audrey Franceschi; Falconi-Sobrinho, Luiz Luciano; Dos Anjos-Garcia, Tayllon; Coimbra, Norberto Cysne

2016-10-01

Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1μg, 3μg and 5μg/0.2μL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail-flick test. Pre-treatment of the LC with 1μg, 3μg and 5μg/0.2μL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception. Copyright © 2016 Elsevier Inc. All rights reserved.

Further studies on lead compounds containing the opioid pharmacophore Dmt-Tic.

PubMed

Balboni, Gianfranco; Fiorini, Stella; Baldisserotto, Anna; Trapella, Claudio; Sasaki, Yusuke; Ambo, Akihiro; Marczak, Ewa D; Lazarus, Lawrence H; Salvadori, Severo

2008-08-28

Some reference opioids containing the Dmt-Tic pharmacophore, especially the delta agonists H-Dmt-Tic-Gly-NH-Ph (1) and H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid (4) (UFP-512) were evaluated for the influence of the substitution of Gly with aspartic acid, its chirality, and the importance of the -NH-Ph and N(1)H-Bid hydrogens in the inductions of delta agonism. The results provide the following conclusions: (i) Asp increases delta selectivity by lowering the mu affinity; (ii) -NH-Ph and N(1)H-Bid nitrogens methylation transforms the delta agonists into delta antagonists; (iii) the substitution of Gly with L-Asp/D-Asp in the delta agonist H-Dmt-Tic-Gly-NH-Ph gave delta antagonists; the same substitution in the delta agonist H-Dmt-Tic-NH-CH2-Bid yielded more selective agonists, H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid and H-Dmt-Tic-NH-(R)CH(CH2-COOH)-Bid; (iv) L-Asp seems important only in functional bioactivity, not in receptor affinity; (v) H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid(N(1)-Me) (10) evidenced analgesia similar to 4, which was reversed by naltrindole only in the tail flick. 4 and 10 had opposite behaviours in mice; 4 caused agitation, 10 gave sedation and convulsions.

Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle.

PubMed

Paulino, Niraldo; Dantas, Andreia Pires; Bankova, Vassya; Longhi, Daniela Taggliari; Scremin, Amarilis; de Castro, Solange Lisboa; Calixto, João Batista

2003-11-01

Propolis is a bee product, which has long been used in folk medicine for the management of different diseases. In this study we evaluated the analgesic and anti-inflammatory effects of a standard ethanolic extract of Bulgarian propolis (Et-Blg) in mice and its in vitro effect on airway smooth muscle. Et-Blg inhibited acetic acid-induced abdominal contortions with an ID(50) = 7.4 +/- 0.7 mg. kg(-1). In the formalin test, the extract caused a significant reduction in pain in mice treated with 100 mg. kg(-1) Et-Blg during the neurogenic phase and for the inflammatory phase with all doses of the extract, with an ID(50) = 2.5 +/- 0.4 mg. kg(-1). Et-Blg inhibited also the capsaicin-induced ear edema in mice; however, this extract was ineffective when assessed in the tail-flick and hot-plate thermal assays. The analgesic effect of Et-Blg was associated with the inhibition of inflammatory responses and not to a simple irritation of nervous terminals. In vitro, this extract inhibited the contraction of trachea smooth muscle induced by histamine (IC(50) = 50 +/- 5 microg. mL(-1)), capsaicin (IC(50) = 26.8 +/- 3 microg. mL(-1)), 80 mM KCl (IC(50) = 27.8 +/- 3 microg. mL(-1)), and carbachol (IC(50) = 54 +/- 2 microg. mL(-1)).

A nonsingular model of the open magnetosphere

NASA Technical Reports Server (NTRS)

Toffoletto, F. R.; Hill, T. W.

1993-01-01

We present a modified version of the Toffoletto and Hill (1989) open magnetosphere model that incorporates a tail-like interconection field with a discontinuity 10 represent the slow-mode expansion fan that defines the high-latitude tail magnetopause. (The interconnection field is defined as the perturbation on an initially closed magnetosphere model to make it open.) The expansion fan controls the open field line region in the tail, and the intersection of the fan with the tail current sheet is, by design, the x line. The new interconnection field allows greater control of the tail field structure; in particular, it enables us to eliminate the nightside mapping singularity that occurs in previous models when the interplanetary magnetic field is nonsouthward. Also, in contrast to earlier models, the far tail x line extends farther downstream on the flanks than in the center of the tail, consistent with observations.

Fingerstroke time estimates for touchscreen-based mobile gaming interaction.

PubMed

Lee, Ahreum; Song, Kiburm; Ryu, Hokyoung Blake; Kim, Jieun; Kwon, Gyuhyun

2015-12-01

The growing popularity of gaming applications and ever-faster mobile carrier networks have called attention to an intriguing issue that is closely related to command input performance. A challenging mirroring game service, which simultaneously provides game service to both PC and mobile phone users, allows them to play games against each other with very different control interfaces. Thus, for efficient mobile game design, it is essential to apply a new predictive model for measuring how potential touch input compares to the PC interfaces. The present study empirically tests the keystroke-level model (KLM) for predicting the time performance of basic interaction controls on the touch-sensitive smartphone interface (i.e., tapping, pointing, dragging, and flicking). A modified KLM, tentatively called the fingerstroke-level model (FLM), is proposed using time estimates on regression models. Copyright © 2015 Elsevier B.V. All rights reserved.

[N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats].

PubMed

Yu, Ling; Xue, Fu-Shan; Li, Cheng-Wen; Xu, Ya-Chao; Zhang, Guo-Hua; Liu, Kun-Peng; Liu, Yi; Sun, Hai-Tao

2006-12-25

The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in group 3, but the expressions of the NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4. As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A) mRNA were significantly inhibited in group 6. These results suggest that the expressions of nNOS and NMDA receptors in spinal cord and midbrain were significantly up-regulated in the rats with morphine analgesia tolerance. Chronic co-administration of L-NAME could effectively inhibit the morphine-induced overexpressions of nNOS and NMDA receptors, and postpone the development of morphine analgesia tolerance. Based on the results of this study, it is concluded that NO/NMDA receptor in spinal cord and midbrain is closely related to the development of morphine analgesia tolerance.

Sprinklers and shade cool cows and reduce insect-avoidance behavior in pasture-based dairy systems.

PubMed

Kendall, P E; Verkerk, G A; Webster, J R; Tucker, C B

2007-08-01

The body temperature of dairy cows in pastoral systems during summer reaches a peak during and following the p.m. milking. Shade and sprinklers can be used separately or in combination at the milking parlor to reduce heat load. Farmers anecdotally report that the use of sprinklers reduces irritation from insects that occurs while cows are waiting for milking. Once daily, we assessed the effectiveness of short-term exposure to shade and sprinklers for cooling cows [via respiration rate and body (vaginal) temperature] and reducing insect-avoidance behaviors before the p.m. milking in a pasture-based dairy system. Head position was measured as an indicator of whether cattle were avoiding water from the sprinklers. Forty-eight Holstein-Friesian dairy cows were divided into 12 groups (4 cows per group, n = 3 groups/treatment) and were exposed to 1 of 4 treatments for 90 min before the p.m. milking: 1) shade, 2) sprinklers, 3) shade and sprinklers, or 4) uncooled control. Respiration rate was reduced by 30% with shade alone compared with controls [54 vs. 78 +/- 2.3 ( +/- SED) breaths/min, respectively]. Sprinklers alone (30 +/- 2.3 breaths/min) and the combined effects of shade and sprinklers (24 +/- 2.3 breaths/min) reduced the respiration rate by 60 and 67%, respectively, compared with controls. Shaded cows had lower body temperatures during the 90-min treatment period compared with controls (shade: 38.6 degrees C; shade and sprinklers: 38.6 degrees C; control: 38.9 +/- 0.09 degrees C). The decrease in body temperature of cows under sprinklers was more marked than for shade alone and remained lower for at least 4 h after milking (sprinklers: 38.7 degrees C; shade and sprinklers: 38.6 degrees C; shade: 38.9 degrees C; control: 39.2 +/- 0.10 degrees C). The sprinkler treatment reduced the number of tail flicks (control: 12.6 vs. sprinklers: 6.6 +/- 2.4 flicks/min) and hoof stamps (control: 4.4 vs. sprinkler: 2.2 +/- 0.5 stamps/min). Cows exposed to sprinklers spent more time with their heads lowered compared with cows in the shaded and control treatments. The reductions in body temperature and respiration rate attributable to shade and sprinklers were greatest when the temperature-humidity index and heat-load index were > or = 69 and 77, respectively, and cows benefited from cooling when these levels were exceeded.

14 CFR 23.347 - Unsymmetrical flight conditions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Unsymmetrical flight conditions. 23.347 Section 23.347 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... the reacting inertia forces. (b) Acrobatic category airplanes certified for flick maneuvers (snap roll...

14 CFR 23.347 - Unsymmetrical flight conditions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Unsymmetrical flight conditions. 23.347 Section 23.347 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... the reacting inertia forces. (b) Acrobatic category airplanes certified for flick maneuvers (snap roll...

14 CFR 23.347 - Unsymmetrical flight conditions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Unsymmetrical flight conditions. 23.347 Section 23.347 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... the reacting inertia forces. (b) Acrobatic category airplanes certified for flick maneuvers (snap roll...

14 CFR 23.347 - Unsymmetrical flight conditions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Unsymmetrical flight conditions. 23.347 Section 23.347 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... the reacting inertia forces. (b) Acrobatic category airplanes certified for flick maneuvers (snap roll...

14 CFR 23.347 - Unsymmetrical flight conditions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Unsymmetrical flight conditions. 23.347 Section 23.347 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... the reacting inertia forces. (b) Acrobatic category airplanes certified for flick maneuvers (snap roll...

THE PHYSIOLOGICAL AND MORPHOLOGICAL BASIS FOR OLFACTORY PERCEPTION OF STEROIDS DURING AGONISITC BEHAVIOR IN LOBSTER

EPA Science Inventory

During fighting, American lobsters urinate on each other with antennule flicking highest during this period. Blocking excretion of urine obliterates previously established dominance relationships, suggesting that individual recognition requires a urine signal (Breithaupt et al.,...

With a flick of the lid: a novel trapping mechanism in Nepenthes gracilis pitcher plants.

PubMed

Bauer, Ulrike; Di Giusto, Bruno; Skepper, Jeremy; Grafe, T Ulmar; Federle, Walter

2012-01-01

Carnivorous pitcher plants capture prey with modified leaves (pitchers), using diverse mechanisms such as 'insect aquaplaning' on the wet pitcher rim, slippery wax crystals on the inner pitcher wall, and viscoelastic retentive fluids. Here we describe a new trapping mechanism for Nepenthes gracilis which has evolved a unique, semi-slippery wax crystal surface on the underside of the pitcher lid and utilises the impact of rain drops to 'flick' insects into the trap. Depending on the experimental conditions (simulated 'rain', wet after 'rain', or dry), insects were captured mainly by the lid, the peristome, or the inner pitcher wall, respectively. The application of an anti-slip coating to the lower lid surface reduced prey capture in the field. Compared to sympatric N. rafflesiana, N. gracilis pitchers secreted more nectar under the lid and less on the peristome, thereby directing prey mainly towards the lid. The direct contribution to prey capture represents a novel function of the pitcher lid.

Understanding the effects of electromagnetic field emissions from Marine Renewable Energy Devices (MREDs) on the commercially important edible crab, Cancer pagurus (L.).

PubMed

Scott, Kevin; Harsanyi, Petra; Lyndon, Alastair R

2018-06-01

The effects of simulated electromagnetic fields (EMF), emitted from sub-sea power cables, on the commercially important decapod, edible crab (Cancer pagurus), were assessed. Stress related parameters were measured (l-Lactate, d-Glucose, Haemocyanin and respiration rate) along with behavioural and response parameters (antennular flicking, activity level, attraction/avoidance, shelter preference and time spent resting/roaming) during 24-h periods. Exposure to EMF had no effect on Haemocyanin concentrations, respiration rate, activity level or antennular flicking rate. EMF exposure significantly disrupted haemolymph l-Lactate and d-Glucose natural circadian rhythms. Crabs showed a clear attraction to EMF exposed shelter (69%) compared to control shelter (9%) and significantly reduced their time spent roaming by 21%. Consequently, EMF emitted from Marine Renewable Energy Devices (MREDs) will likely affect edible crabs both behaviourally and physiologically, suggesting that the impact of EMF on crustaceans must be considered when planning MREDs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolved to fail: Bacteria induce flagellar buckling to reorient

NASA Astrophysics Data System (ADS)

Son, Kwangmin; Guasto, Jeffrey S.; Stocker, Roman

2012-11-01

Many marine bacteria swim with a single helical flagellum connected to a rotary motor via a 100 nm long universal joint called the ``hook.'' While these bacteria have seemingly just one degree of freedom, allowing them to swim only back and forth, they in fact exhibit large angular reorientations mediated by off-axis ``flicks'' of their flagellum. High-speed video microscopy revealed the mechanism underpinning this turning behavior: the buckling of the hook during the exceedingly brief (10 ms) forward run that follows a reversal. Direct measurements of the hook's mechanical properties corroborated this result, as the hook's structural stability is governed by the Sperm number, which compares the compressive load from propulsion to the elastic restoring force of the hook. Upon decreasing the Sperm number below a critical value by reducing the swimming speed, the frequency of flicks diminishes sharply, consistent with the criticality of buckling. This elegant, under-actuated turning mechanism appears widespread among marine bacteria and may provide a novel design concept in micro-robotics.

Responses by corn snakes (Elaphe guttata) to chemicals from heterospecific snakes.

PubMed

Weldon, P J; Ford, N B; Perry-Richardson, J J

1990-01-01

Young corn snakes,Elaphe guttata, were tested for responses to chemicals from heterospecific snakes. Corn snakes exhibited more tongue-flicks to swabs freshly rubbed against the skin of an ophiophagous kingsnake,Lampropeltis getulus, than to blank swabs. Responses toL. getulus and a nonophiophagous western plains garter snake,Thamnophis radix haydeni, did not differ significantly. Corn snakes exhibited more tongue-flicks to swabs treated with chloroform extracts of the shed skins ofL. getulus; an ophiophagous eastern coachwhip,Masticophis flagellum; and a nonophiophagous gray ratsnake,Elaphe obsoleta, than to blank swabs, but they did not discriminate between ophiophagous and nonophiophagous species in every case. Corn snakes, when offered shelters containing bedding from the home cages of a nonophiophagous water snake,Nerodia erythrogaster, an occasionally ophiophagous water moccasin,Agkistrodon pisdvorus; orL. getulus and untreated bedding, failed to reside under snake-scented shelters at a rate significantly different from that expected by chance. The responses of corn snakes are compared with those reported for other snakes presented with heterospecific snake chemicals.

Modeling of Longitudinal Unsteady Aerodynamics of a Wing-Tail Combination

NASA Technical Reports Server (NTRS)

Klein, Vladislav

1999-01-01

Aerodynamic equations for the longitudinal motion of an aircraft with a horizontal tail were developed. In this development emphasis was given on obtaining model structure suitable for model identification from experimental data. The resulting aerodynamic models included unsteady effects in the form of linear indicial functions. These functions represented responses in the lift on the wing and tail alone, and interference between those two lifting surfaces. The effect of the wing on the tail was formulated for two different expressions concerning the downwash angle at the tail. The first expression used the Cowley-Glauert approximation known-as "lag-in-downwash," the second took into account growth of the wing circulation and delay in the development of the lift on the tail. Both approaches were demonstrated in two examples using the geometry of a fighter aircraft and a large transport. It was shown that the differences in the two downwash formulations would increase for an aircraft with long tail arm performing low-speed, rapid maneuvers.

Effects of aerodynamic interaction between main and tail rotors on helicopter hover performance and noise

NASA Technical Reports Server (NTRS)

Menger, R. P.; Wood, T. L.; Brieger, J. T.

1983-01-01

A model test was conducted to determine the effects of aerodynamic interaction between main rotor, tail rotor, and vertical fin on helicopter performance and noise in hover out of ground effect. The experimental data were obtained from hover tests performed with a .151 scale Model 222 main rotor, tail rotor and vertical fin. Of primary interest was the effect of location of the tail rotor with respect to the main rotor. Penalties on main rotor power due to interaction with the tail rotor ranged up to 3% depending upon tail rotor location and orientation. Penalties on tail rotor power due to fin blockage alone ranged up to 10% for pusher tail rotors and up to 50% for tractor tail rotors. The main rotor wake had only a second order effect on these tail rotor/fin interactions. Design charts are presented showing the penalties on main rotor power as a function of the relative location of the tail rotor.

A potential role for bat tail membranes in flight control.

PubMed

Gardiner, James D; Dimitriadis, Grigorios; Codd, Jonathan R; Nudds, Robert L

2011-03-30

Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus indicated that the positioning of the tail membrane (uropatagium) can significantly influence flight control. Adjusting tail position by increasing the angle of the legs ventrally relative to the body has a two-fold effect; increasing leg-induced wing camber (i.e., locally increased camber of the inner wing surface) and increasing the angle of attack of the tail membrane. We also used our model to examine the effects of flying with and without a tail membrane. For the bat model with a tail membrane increasing leg angle increased the lift, drag and pitching moment (nose-down) produced. However, removing the tail membrane significantly reduced the change in pitching moment with increasing leg angle, but it had no significant effect on the level of lift produced. The drag on the model also significantly increased with the removal of the tail membrane. The tail membrane, therefore, is potentially important for controlling the level of pitching moment produced by bats and an aid to flight control, specifically improving agility and manoeuvrability. Although the tail of bats is different from that of birds, in that it is only divided from the wings by the legs, it nonetheless, may, in addition to its prey capturing function, fulfil a similar role in aiding flight control.

A Potential Role for Bat Tail Membranes in Flight Control

PubMed Central

Gardiner, James D.; Dimitriadis, Grigorios; Codd, Jonathan R.; Nudds, Robert L.

2011-01-01

Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus indicated that the positioning of the tail membrane (uropatagium) can significantly influence flight control. Adjusting tail position by increasing the angle of the legs ventrally relative to the body has a two-fold effect; increasing leg-induced wing camber (i.e., locally increased camber of the inner wing surface) and increasing the angle of attack of the tail membrane. We also used our model to examine the effects of flying with and without a tail membrane. For the bat model with a tail membrane increasing leg angle increased the lift, drag and pitching moment (nose-down) produced. However, removing the tail membrane significantly reduced the change in pitching moment with increasing leg angle, but it had no significant effect on the level of lift produced. The drag on the model also significantly increased with the removal of the tail membrane. The tail membrane, therefore, is potentially important for controlling the level of pitching moment produced by bats and an aid to flight control, specifically improving agility and manoeuvrability. Although the tail of bats is different from that of birds, in that it is only divided from the wings by the legs, it nonetheless, may, in addition to its prey capturing function, fulfil a similar role in aiding flight control. PMID:21479137

Some Effects of Horizontal-Tail Position on the Vertical-Tail Pressure Distributions of a Complete Model in Sideslip at High Subsonic Speeds

NASA Technical Reports Server (NTRS)

Alford, William J., Jr.

1958-01-01

An investigation has been made in the Langley high-speed 7- by 10-foot tunnel of some effects of horizontal-tail position on the vertical-tail pressure distributions of a complete model in sideslip at high subsonic speeds. The wing of the model was swept back 28.82 deg at the quarter-chord line and had an aspect ratio of 3.50, a taper ratio of 0.067, and NACA 65A004 airfoil sections parallel to the model plane of symmetry. Tests were made with the horizontal tail off, on the wing-chord plane extended, and in T-tail arrangements in forward and rearward locations. The test Mach numbers ranged from 0.60 to 0.92, which corresponds to a Reynolds number range from approximately 2.93 x 10(exp 6) to 3.69 x 10(exp 6), based on the wing mean aerodynamic chord. The sideslip angles varied from -3.9 deg to 12.7 deg at several selected angles of attack. The results indicated that, for a given angle of sideslip, increases in angle of attack caused reductions in the vertical-tail loads in the vicinity of the root chord and increases at the midspan and tip locations, with rearward movements in the local chordwise centers of pressure for the midspan locations and forward movements near the tip of the vertical tail. At the higher angles of attack all configurations investigated experienced outboard and rearward shifts in the center of pressure of the total vertical-tail load. Location of the horizontal tail on the wing- chord plane extended produced only small effects on the vertical-tail loads and centers of pressure. Locating the horizontal tail at the tip of the vertical tail in the forward position caused increases in the vertical-tail loads; this configuration, however, experienced considerable reduction in loads with increasing Mach number. Location of the horizontal tail at the tip of the vertical tail in the rearward position produced the largest increases in vertical-tail loads per degree sideslip angle; this configuration experienced the smallest variations of loads with Mach number of any of the configurations investigated.

A Simple Engineering Analysis of Solar Particle Event High Energy Tails and Their Impact on Vehicle Design

NASA Technical Reports Server (NTRS)

Singleterry, Robert C., Jr.; Walker, Steven A.; Clowdsley, Martha S.

2016-01-01

The mathematical models for Solar Particle Event (SPE) high energy tails are constructed with several di erent algorithms. Since limited measured data exist above energies around 400 MeV, this paper arbitrarily de nes the high energy tail as any proton with an energy above 400 MeV. In order to better understand the importance of accurately modeling the high energy tail for SPE spectra, the contribution to astronaut whole body e ective dose equivalent of the high energy portions of three di erent SPE models has been evaluated. To ensure completeness of this analysis, simple and complex geometries were used. This analysis showed that the high energy tail of certain SPEs can be relevant to astronaut exposure and hence safety. Therefore, models of high energy tails for SPEs should be well analyzed and based on data if possible.

Modeling the emission, transport and deposition of contaminated dust from a mine tailing site.

PubMed

Stovern, Michael; Betterton, Eric A; Sáez, A Eduardo; Villar, Omar Ignacio Felix; Rine, Kyle P; Russell, Mackenzie R; King, Matt

2014-01-01

Mining operations are potential sources of airborne particulate metal and metalloid contaminants through both direct smelter emissions and wind erosion of mine tailings. The warmer, drier conditions predicted for the Southwestern US by climate models may make contaminated atmospheric dust and aerosols increasingly important, due to potential deleterious effects on human health and ecology. Dust emissions and dispersion of contaminants from the Iron King Mine tailings in Dewey-Humboldt, Arizona, a Superfund site, are currently being investigated through in situ field measurements and computational fluid dynamics modeling. These tailings are significantly contaminated with lead and arsenic with an average soil concentration of 1616 and 1420 ppm, respectively. Similar levels of these contaminants have also been measured in soil samples taken from the area surrounding the mine tailings. Using a computational fluid dynamics model, we have been able to model dust transport from the mine tailings to the surrounding region. The model includes a distributed Eulerian model to simulate fine aerosol transport and a Lagrangian approach to model fate and transport of larger particles. In order to improve the accuracy of the dust transport simulations both regional topographical features and local weather patterns have been incorporated into the model simulations.

A Noninvasive Technique for Blocking Vomeronasal Chemoreception in Rattlesnakes

ERIC Educational Resources Information Center

Stark, C. Patrick; Chiszar, David; Smith, Hobart M.

2006-01-01

To examine the effects of vomeronasal deprivation on strike-induced chemosensory searching (SICS) in rattlesnakes we used a newly developed technique to anesthetize the vomeronasal organs. We compared rate of tongue flicking after striking prey in avomic rattlesnakes to vomic controls. Avomic rattlesnakes exhibited significantly fewer tongue…

Muscarinic Antagonists Free of Hallucinogenic Properties.

DTIC Science & Technology

1984-12-01

catatonic response again decreased to control levels. QNB, QNX and QNA were all potent stimulators of the limb flick response in rats. All three compounds...tested, 5.0 mg/Kg. QNA QNA interferes with the catatonic response in a manner quite similar to QNXFig. 1). The dose-response curve for QNA overlays that

Grasp Preparation Improves Change Detection for Congruent Objects

ERIC Educational Resources Information Center

Symes, Ed; Tucker, Mike; Ellis, Rob; Vainio, Lari; Ottoboni, Giovanni

2008-01-01

A series of experiments provided converging support for the hypothesis that action preparation biases selective attention to action-congruent object features. When visual transients are masked in so-called "change-blindness scenes," viewers are blind to substantial changes between 2 otherwise identical pictures that flick back and forth. The…

Analgesic activity of a triterpene isolated from Scoparia dulcis L. (Vassourinha).

PubMed

Freire, S M; Torres, L M; Roque, N F; Souccar, C; Lapa, A J

1991-01-01

Analgesic and anti-inflammatory activities of water (WE) and ethanolic (EE) extracts of Scoparia dulcis L. were investigated in rats and mice, and compared to the effects induced by Glutinol, a triterpene isolated by purification of EE. Oral administration (p.o.) of either WE or EE (up to 2 g/kg) did not alter the normal spontaneous activity of mice and rats. The sleeping time induced by sodium pentobarbital (50 mg/kg, i.p.) was prolonged by 2 fold in mice pretreated with 0.5 g/kg EE, p.o. Neither extract altered the tail flick response of mice in immersion test, but previous administration of EE (0.5 g/kg, p.o.) reduced writhings induced by 0.8% acetic acid (0.1 ml/10 g, i.p.) in mice by 47%. EE (0.5 and 1 g/kg, p.o.) inhibited the paw edema induced by carrageenan in rats by respectively 46% and 58% after 2 h, being ineffective on the paw edema induced by dextran. No significant analgesic or anti-edema effects were detected in animals pretreated with WE (1 g/kg, p.o.). Administration of Glutinol (30 mg/kg, p.o.) reduced writhing induced by acetic acid in mice by 40% and the carrageenan induced paw edema in rats by 73%. The results indicate that the analgesic activity of S. dulcis L. may be explained by an anti-inflammatory activity probably related to the triterpene Glutinol.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

PubMed

Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

2009-01-03

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

Fentanyl-related designer drugs W-18 and W-15 lack appreciable opioid activity in vitro and in vivo.

PubMed

Huang, Xi-Ping; Che, Tao; Mangano, Thomas J; Le Rouzic, Valerie; Pan, Ying-Xian; Majumdar, Susruta; Cameron, Michael D; Baumann, Michael H; Pasternak, Gavril W; Roth, Bryan L

2017-11-16

W-18 (4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide) represent two emerging drugs of abuse chemically related to the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide). Here, we describe the comprehensive pharmacological profiles of W-18 and W-15, as examination of their structural features predicted that they might lack opioid activity. We found W-18 and W-15 to be without detectible activity at μ, δ, κ, and nociception opioid receptors in a variety of assays. We also tested W-18 and W-15 for activity as allosteric modulators at opioid receptors and found them devoid of significant positive or negative allosteric modulatory activity. Comprehensive profiling at essentially all the druggable GPCRs in the human genome using the PRESTO-Tango platform revealed no significant activity. Weak activity at the sigma receptors and the peripheral benzodiazepine receptor was found for W-18 (Ki = 271 nM). W-18 showed no activity in either the radiant heat tail-flick or the writhing assays and also did not induce classical opioid behaviors. W-18 is extensively metabolized, but its metabolites also lack opioid activity. Thus, although W-18 and W-15 have been suggested to be potent opioid agonists, our results reveal no significant activity at these or other known targets for psychoactive drugs.

Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus.

PubMed

Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz

2011-01-01

Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

Nerve growth factor pretreatment inhibits lidocaine-induced myelin damage via increasing BDNF expression and inhibiting p38 mitogen activation in the rat spinal cord

PubMed Central

Zhao, Guangyi; Li, Dan; Ding, Xudong; Li, Lu

2017-01-01

The present study aimed to investigate the effect of exogenous nerve growth factor (NGF) pretreatment on demyelination in the spinal cord of lidocaine-treated rats, and explored the potential neuroprotective mechanisms of NGF. A total of 36 rats were randomly assigned to three groups (n=12 per group): Sham group; Lido group, received intrathecal injection of lidocaine; NGF group, received intrathecal injection of NGF followed by intrathecal injection of lidocaine. Tail-flick tests were used to evaluate neurobehavioral function. Ultrastructural alternations were analyzed by transmission electron microscopy. Immunofluorescence was used to examine the expression of myelin basic protein (MBP) and brain-derived neurotrophic factor (BDNF). ELISA was used to determine serum levels of MBP and proteolipid protein (PLP). Western blotting was used to detect the expression of phosphorylated mitogen activated protein kinase (MAPK). NGF pretreatment reduced lidocaine-induced neurobehavioral damage, nerve fiber demyelination, accompanied by a decrease in MBP expression in the spinal cord and an increase in MBP and PLP in serum. In addition, NGF pretreatment increased BDNF expression in the spinal cord of lidocaine-treated rats. Furthermore, NGF pretreatment reduced p38 MAPK phosphorylation in the spinal cord of lidocaine-treated rats. NGF treatment reduces lidocaine-induced neurotoxicity via the upregulation of BDNF and inhibition of p38 MAPK. NGF therapy may improve the clinical use of lidocaine in intravertebral anesthesia. PMID:28849178

Behavioral phenotyping of mice in pharmacological and toxicological research.

PubMed

Karl, Tim; Pabst, Reinhard; von Hörsten, Stephan

2003-07-01

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.

Magnesium and other bivalent cations influence upon sodium montelukast effect in experimental-induced thermoalgesia.

PubMed

Nechifor, Mihai; Cuciureanu, Magda; Chelarescu, Dan; Ciubotariu, Diana; Pascu, Mihaela

2008-03-01

We tested the influence of magnesium, zinc and copper upon the montelukast (MK, antagonist of cysteinyl leukotriene receptor type 1) effect in experimentally-induced thermoalgesia. We worked on 5 groups of 10 adults, each Wistar rats, that received: group I-control; group II: MK (10 mg/kg) unique administration; group III: MgCl2 (1 mM/kg/day) i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day; group IV: ZnCl2, (0.1 mM/kg/day), i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day; group V: copper acetate (0.05 mM/kg/day), i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day. We determined the thermoalgesic sensitivity (TS) using a tail flick analgesia meter, initially, 3 days after daily cation administration and 3 hours after MK administration. Our data show that MK has a statistically significant reduction of TS vs control group (3.76 +/- 1.04 s vs 1.81 +/- 0.98 s, p < 0.05). Copper and magnesium administration do not significantly change the MK effect to decrease TS. The co-administration of zinc and MK statistically significantly increased the TS of the group that received only MK (2.51 +/- 0.21 s vs 3.76 +/- 1.04 s, p < 0.05). Animals that received only cations (in the above mentioned doses) did not significantly change TS.

Behavioral and endocrine changes following antisense oligonucleotide-induced reduction in the rat NOP receptor.

PubMed

Blakley, Gregory G; Pohorecky, Larissa A; Benjamin, Daniel

2004-02-01

Compared with the use of classic receptor ligands, antisense oligonucleotides (ASO) targeted at specific central nervous system receptors are an effective alternative in experiments designed to examine the behavioral role of such systems. The nociception/orphaninFQ (N/OFQ) system has been implicated in mediating endocrine function, feeding, stress, pain, anxiety, and the rewarding effects of drugs of abuse. The objective of the current study was to examine whether long-term ASO-induced downregulation of N/OFQ's receptor (NOP) produced changes in endocrine, anxiety, nociception and ethanol's (EtOH's) locomotor activating properties. Male Long Evans rats were implanted with osmotic mini-pumps containing ASO for the NOP receptor. ASO was chronically infused for 26 days and, during this time, multiple behavioral and physiological measurements were conducted. ASO infusion significantly reduced expression of the NOP receptor in brain, confirmed by significant reductions of OFQ-stimulated [(35)S]-GTPgammaS binding in the paraventricular nucleus, prefrontal cortex, and septum. Behavioral changes were observed in ASO-treated animals including higher body temperature, increased water intake, decreased corticosterone (CORT) levels, decreased grooming in the open field, increased tail-flick latency, shorter durations on the open arms of the elevated plus maze, and heightened locomotor activity following EtOH. These behavioral, physiological and endocrine changes are relatively consistent with previous findings with agonists and antagonists for the NOP receptor and, taken together, suggest that ASO-induced downregulation of the NOP receptor is an effective method for studying the N/OFQ system.

Characterization and Modeling of Dust Emissions from an Instrumented Mine Tailings Site

NASA Astrophysics Data System (ADS)

Betterton, E. A.; Stovern, M.; Saez, A.; Csavina, J. L.; Felix Villar, O. I.; Field, J. P.; Rine, K. P.; Russell, M. R.; Saliba, P.

2012-12-01

Mining operations are potential sources of airborne particulate metal and metalloid contaminants through both direct smelter emissions and wind erosion of mine tailings. The warmer, drier conditions predicted for the Southwestern US by climate models may make contaminated atmospheric dust and aerosols increasingly important, due to potential deleterious effects on human health and ecology. Dust emissions and dispersion of contaminants from the Iron King Mine tailings in Dewey-Humboldt, Arizona, a Superfund site, are currently being investigated through in situ field measurements and computational fluid dynamics modeling. These tailings are heavily contaminated with lead and arsenic. We report on the chemical characterization of atmospheric dust and aerosol sampled near the mine tailings. Instrumented eddy flux towers were also setup on the mine tailings to give both spatial and temporal dust observations. The eddy flux towers have multiple DUSTTRAK monitors as well as weather stations. These in situ observations allow us to assess spatial distribution of suspended particulate. Using the DUSTTRAK flux tower observations at 10-second resolution in conjunction with a computational fluid dynamics model, we have been able to model dust transport from the mine tailings to downwind areas. In order to improve the accuracy of the dust transport simulations both regional topographical features and local weather patterns have been incorporated into the model simulations.

Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation.

PubMed

Kumar, Priyank; Sunkaraneni, Soujanya; Sirohi, Sunil; Dighe, Shveta V; Walker, Ellen A; Yoburn, Byron C

2008-11-12

This study examined the antinociceptive (analgesic) efficacy of hydromorphone and hydromorphone-induced tolerance and regulation of mu-opioid receptor density. Initially s.c. hydromorphone's time of peak analgesic (tail-flick) effect (45 min) and ED50 using standard and cumulative dosing protocols (0.22 mg/kg, 0.37 mg/kg, respectively) were determined. The apparent analgesic efficacy (tau) of hydromorphone was then estimated using the operational model of agonism and the irreversible mu-opioid receptor antagonist clocinnamox. Mice were injected with clocinnamox (0.32-25.6 mg/kg, i.p.) and 24 h later, the analgesic potency of hydromorphone was determined. The tau value for hydromorphone was 35, which suggested that hydromorphone is a lower analgesic efficacy opioid agonist. To examine hydromorphone-induced tolerance, mice were continuously infused s.c. with hydromorphone (2.1-31.5 mg/kg/day) for 7 days and then morphine cumulative dose response studies were performed. Other groups of mice were injected with hydromorphone (2.2-22 mg/kg/day) once, or intermittently every 24 h for 7 days. Twenty-four hours after the last injection, mice were tested using morphine cumulative dosing studies. There was more tolerance with infusion treatments compared to intermittent treatment. When compared to higher analgesic efficacy opioids, hydromorphone infusions induced substantially more tolerance. Finally, the effect of chronic infusion (31.5 mg/kg/day) and 7 day intermittent (22 mg/kg/day) hydromorphone treatment on spinal cord mu-opioid receptor density was determined. Hydromorphone did not produce any change in mu-opioid receptor density following either treatment. These results support suggestions that analgesic efficacy is correlated with tolerance magnitude and regulation of mu-opioid receptors when opioid agonists are continuously administered. Taken together, these studies indicate that analgesic efficacy and treatment protocol are important in determining tolerance and regulation of mu-opioid receptors.

Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels.

PubMed

Marics, Irène; Malapert, Pascale; Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz

2014-01-01

The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation.

Possible mechanism of protective effect of thalidomide in STZ-induced-neuropathic pain behavior in rats.

PubMed

Taliyan, Rajeev; Sharma, Pyare Lal

2012-04-01

Diabetes-induced neuropathic pain is recognized as one of the most difficult type of pain to treat and conventional analgesics are well known to be partially effective or associated with potential toxicity. Recently, it has been demonstrated that thalidomide, besides its teratogenic potential, reduced chronic pain in an SNL experimental pain model. The present study was designed to investigate the effect of thalidomide on streptozotocin (STZ)-induced neuropathic pain in rats. Streptozotocin (20 mg/kg, i.p, daily × 4 days) was administered to induce diabetes in the rats. Nociceptive latency was measured using tail-flick and paw-withdrawal test. Thermal hyperalgesia and mechanical allodynia were measured using planter test and dynamic aesthesiometer (Ugo-Basile, Italy), respectively. Urinary and serum nitrite concentration was estimated using Greiss reagent method. Spleen homogenate supernatant was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 ul, i.v) daily for 28 days. Pain threshold progressively decreased in STZ-treated rats, as compared with control rats. 3 weeks after induction of diabetes, the rat exhibited thermal hyperalgesia and mechanical allodynia. The analgesic effect of morphine (8 mg/kg, s.c.) was significantly decreased in both diabetic and in SHS-treated non-diabetic rats. Administration of thalidomide (25 and 50 mg/kg, i.p), a TNF-α inhibitor, significantly prevented hyperglycemia-induced thermal hyperalgesia and mechanical allodynia and also attenuated the increase in serum and urinary nitrite concentration, as compared with untreated diabetic rats. Also, thalidomide (25 and 50 mg/kg, i.p) 1 h before or concurrently with morphine significantly restored the analgesic effect of morphine in diabetic rats. It may be concluded that thalidomide has a beneficial effect in neuropathic pain by decreasing cytokines (TNF-α) and nitric oxide level and may provide a novel promising therapeutic approach for managing painful diabetic neuropathy.

Anti-inflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis.

PubMed

Kodithuwakku, Nandani Darshika; Pan, Min; Zhu, Yi-lin; Zhang, Yan-yan; Feng, Yi-dong; Fang, Wei-rong; Li, Yun-man

2013-12-12

Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis. Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations. To investigate the effects on gout arthritis, ankle joint of rats induced by MSU crystals and assessed for edema and histopathological changes. In vitro, prepared serum was incubated with urate crystal induced HUVE cells and the release of TNF-α and IL-1β determined by ELISA. Shuang-Qi gout capsule showed significant and dose dependent anti-inflammatory effect via reducing edema and pain, throughout all the models. The high dose of Shuang-Qi gout capsule and Indomethacin significantly attenuated the edema. Histopathological results showed that high and medium dose of Shuang-Qi gout capsule and Indomethacin reduced gouty joint inflammatory features, while the high dose of Shuang-Qi gout capsule showed a better therapeutic effect. High and medium dose of Shuang-Qi gout capsule significantly reduced the release of TNF-α and IL-1β (p<0.05). Shuang-Qi gout capsule can effectively inhibit the inflammation, analgesia, through the modulation of emission of pro-inflammatory cytokines and the curative effect is dose dependent. Conversely, these MSU induced in vivo and in vitro studies of Shuang-Qi gout capsule suggest that, Shuang-Qi gout capsule may be a potential agent for treatment in gouty arthritis. © 2013 Published by Elsevier Ireland Ltd.

In vivo anti-inflammatory and anti-nociceptive activities of Cheilanthes farinosa.

PubMed

Yonathan, Mariamawit; Asres, Kaleab; Assefa, Ashenafi; Bucar, Franz

2006-12-06

In Ethiopia inflammatory skin diseases are among the most common health problems treated with traditional remedies which mainly comprise medicinal plants. In the present work, the anti-inflammatory and anti-nociceptive activities of Cheilanthes farinosa (Forsk.) Kaulf (Adianthaceae), a fern used in many parts of Ethiopia to treat inflammatory skin disorders, were studied using in vivo models of inflammation and pain. The results of the study showed that the fronds Cheilanthes farinosa possess strong anti-inflammatory and anti-nociceptive properties. It was further demonstrated that the active ingredients of the fern reside mainly in the methanol fraction from which three compounds viz. the flavonol glycoside rutin, and the natural cinnamic acids, caffeic acid and its quinic acid derivative chlorogenic acid have been isolated. The methanol extract was also shown to potentiate the anti-inflammatory activity of acetyl salicylic acid. At the tested concentrations, the methanol extract displayed a better anti-nociceptive activity than that of ASA in both the early and late phases of formalin induced nociception in mice. However, the activity of the extract was more pronounced in the late phase, which is commonly associated with inflammatory pain. Evaluation of the pharmacological properties of the compounds isolated from the active fractions pointed out that chlorogenic acid possesses strong anti-inflammatory and anti-nociceptive activities while caffeic acid and rutin were inactive. Moreover, on molar basis chlorogenic acid was proved to be superior in its anti-inflammatory action to acetyl salicylic acid. It was therefore concluded that chlorogenic acid contributes, in full or in part, to the anti-inflammatory and anti-nociceptive activities of Cheilanthes farinosa. Both the methanolic extract and pure chlorogenic acid failed to display anti-nociceptive activity when tested by the tail-flick test indicating that the plant is not a centrally acting analgesic but instead exerts its analgesic activity by way of its antinflammtory action.

Acute Heat-Evoked Temperature Sensation Is Impaired but Not Abolished in Mice Lacking TRPV1 and TRPV3 Channels

PubMed Central

Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz

2014-01-01

The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation. PMID:24925072

[Behavioural studies during the gestational-lactation period in morphine treated rats].

PubMed

Sobor, Melinda; Timár, Júlia; Riba, Pál; Király, Kornél P; Al-Khrasani, Mahmoud; Gyarmati, Zsuzsanna; Fürst, Zsuzsanna

2013-12-01

Opioids impair the maternal behaviour of experimental animals. The effect of morphine on maternal behaviour in rat dams treated chronically with morphine during the whole pregnancy and lactation has not been yet analysed systematically. The aim of our work was to investigate the behavioural effects of moderate dose morphine administered constantly in the whole perinatal period in rats. Nulliparous female rats were treated with 10 mg/kg morphine s.c. once daily, from the day of mating. Maternal behaviour was observed, the effects of acute morphine treatment on the maternal behaviour and whether this effect could be antagonised by naloxone were also investigated. Physical and other behavioural (anxiety-like signals in elevated plus maze, changes in locomotor activity) withdrawal signs precipitated by naloxone were registered. After weaning sensitivity to the rewarding effect of morphine was measured by conditioned place preference and to the aversive effect of naloxone by conditioned place aversion tests. Antinociceptive test on tail-flick apparatus was performed to investigate the changes in morphine antinociceptive effects due to chronic morphine treatment. Maternal behaviour was significantly impaired in morphine-treated dams. This effect of morphine lasted c.a. 2-3 hours a day, it showed dose-dependency and was enhanced in MO-treated group (sensitisation). Only weak physical and no other behavioural (anxiety-like behaviour or hypolocomotion) withdrawal signs were precipitated by naloxone. The positive reinforcing effect of morphine and aversive effect of naloxone were markedly increased on conditioned place paradigm. Significant antinociceptive tolerance was not seen. Although human drug abuse can be hardly modelling under experimental circumstances, our constant, relatively moderate dose morphine treatment administered once daily during the whole pregnancy and lactation resulted in several subtle behavioural changes in dams. In perinatally opioid-exposed offspring short- and long-term behavioural disturbances can be detected which is well-known from literature. Besides direct pharmacological effects of morphine impaired maternal responsiveness and pup care could play a role in these disturbances.

Microscopic understanding of heavy-tailed return distributions in an agent-based model

NASA Astrophysics Data System (ADS)

Schmitt, Thilo A.; Schäfer, Rudi; Münnix, Michael C.; Guhr, Thomas

2012-11-01

The distribution of returns in financial time series exhibits heavy tails. It has been found that gaps between the orders in the order book lead to large price shifts and thereby to these heavy tails. We set up an agent-based model to study this issue and, in particular, how the gaps in the order book emerge. The trading mechanism in our model is based on a double-auction order book. In situations where the order book is densely occupied with limit orders we do not observe fat-tailed distributions. As soon as less liquidity is available, a gap structure forms which leads to return distributions with heavy tails. We show that return distributions with heavy tails are an order-book effect if the available liquidity is constrained. This is largely independent of specific trading strategies.

The roles of NMDA receptor activation and nucleus reticularis gigantocellularis in the time-dependent changes in descending inhibition after inflammation.

PubMed

Terayama, R; Dubner, R; Ren, K

2002-05-01

Previous studies indicate that descending modulation of nociception is progressively increased following persistent inflammation. The present study was designed to further examine the role of supraspinal neurons in descending modulation following persistent inflammation. Constant levels of paw withdrawal (PW) and tail flick (TF) latencies to noxious heat stimuli were achieved in lightly anesthetized rats (pentobarbital sodium 3-10 mg/kg/h, i.v.). Electrical stimulation (ES, 0.1 ms, 100 Hz, 20-200 A) was delivered to the rostral ventromedial medulla (RVM), mainly the nucleus raphe magnus (NRM). ES produced intensity-dependent inhibition of PW and TF. Following a unilateral hindpaw inflammation produced by injection of complete Freund's adjuvant (CFA), ES-produced inhibition underwent time-dependent changes. There was an initial decrease at 3 h after inflammation and a subsequent increase after inflammation in the excitability of RVM neurons and the inhibition of nocifensive responses. These changes were most robust after stimulation of the inflamed paw although similar findings were seen on the non-inflamed paw and tail. The inflammation-induced dynamic changes in descending modulation appeared to be correlated with changes in the activation of the N-methyl--aspartate (NMDA) excitatory amino acid receptor. Microinjection of an NMDA receptor antagonist, AP5 (1 pmol), resulted in an increase in the current intensity required for inhibition of the PW and TF. The effect of AP5 was less at 3 h after inflammation and significantly greater at 11-24 h after inflammation. In a subsequent experiment, ES-produced inhibition of nocifensive responses after inflammation was examined following selective chemical lesions of the nuclei reticularis gigantocellularis (NGC). Compared to vehicle-injected animals, microinjection of a soma-selective excitotoxin, ibotenic acid, enhanced ES-produced inhibition at 3 h but not at 24 h after inflammation. We propose that these time course changes reflect dynamic alterations in concomitant descending facilitation and inhibition. At early time points, NMDA receptor and NGC activation enhance descending facilitation; as time progresses, the dose-response curve of NMDA shifts to the left and descending inhibition dominates and masks any descending facilitation.

[Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].

PubMed

Suemaru, K; Kawasaki, H; Gomita, Y

1997-06-01

The repeated administration of nicotine at small doses, which do not produce whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of rats. The tremor is accompanied by locomotor hyperactivity without rigidity and immobility of the whole body, suggesting that the nicotine-induced tail-tremor model is useful for studying the mechanism underlying tremor associated with movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists. Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest is observed only in Parkinson's disease, which is improved with anti-muscalinic drugs. Essential tremor is one of the typical tremors connected with movement (postural and kinetic tremor) and is improved with beta-blocker. These findings and results suggest that nicotine-induced tail-tremor is useful for the study of essential tremor in animal models.

Adaptive Suction and Blowing for Twin-Tail Buffet Control

NASA Technical Reports Server (NTRS)

Kandil, Osama A.; Yang, Zhi

1999-01-01

Adaptive active flow control for twin-tail buffet alleviation is investigated. The concept behind this technique is to place control ports on the tail outer and inner surfaces with flow suction or blowing applied through these ports in order to minimize the pressure difference across the tail. The suction or blowing volume flow rate from each port is proportional to the pressure difference across the tail at this location. A parametric study of the effects of the number and location of these ports on the buffet response is carried out. The computational model consists of a sharp-edged delta wing of aspect ratio one and swept-back flexible twin tail with taper ratio of 0.23. This complex multidisciplinary problem is solved sequentially using three sets of equations for the fluid flow, aeroelastic response and grid deformation, using a dynamic multi-block grid structure. The computational model is pitched at 30 deg angle of attack. The freestream Mach number and Reynolds number are 0.3 and 1.25 million, respectively. The model is investigated for the inboard position of the twin tails, which corresponds to a separation distance between the twin tails of 33% of the wing span. Comparison of the time history and power spectral density responses of the tails for various distributions of the control ports are presented and discussed.

Supplementary Free-Spinning-Tunnel Tests of a 1/16-Scale Model of the McDonnell XB-85 Airplane Equipped with a Conventional-Tail Arrangement

NASA Technical Reports Server (NTRS)

Klinar, Walter J.

1947-01-01

Spin tests have been conducted in the Langley free-spinning tunnel on a 1/16-scale model of the McDonnell XP-85 airplane with the normal X-tail replaced with a short-coupled conventional tail arrangement. The effect of the conventional tail arrangement and the effects of various modifications upon the spin and recovery characteristics of the model were determined. The results of the tests indicated that installation of the conventional tail arrangement wil not provide satisfactory recoveries from spins of the airplane. Satisfactory recoveries will be obtainable, however, either by installing in addition a very large ventral fin (17.94 sq ft, full-scale) below the tail or by decreasing the width of the fuselage and making it flat sided rearward of the wing trailing edge.

Acoustic test of a model rotor and tail rotor: Results for the isolated rotors and combined configuration

NASA Technical Reports Server (NTRS)

Martin, R. M.; Burley, C. L.; Elliott, J. W.

1989-01-01

Acoustic data from a model scale main rotor and tail rotor experiment in the NASA Langley 14 by 22 Foot Subsonic Tunnel are presented for the main rotor and trail rotor in isolation and for the two rotors operating together. Results for the isolated main rotor show the importance of the rotor flapping conditions on mid-frequency noise content. High levels of main rotor retreating side blade-vortex interaction noise are shown to radiate downstream of the model. The isolated tail rotor noise results show the dominance of harmonic noise in the thrusting direction. The occurrence of tail rotor broadband noise is seen by the broadening of the tail rotor harmonics and is attributed to fuselage wake turbulence. The combined main and tail rotor data are presented to show the dominance of each rotor's different noise sources at different directivity locations.

Windblown Dust Deposition Forecasting and Spread of Contamination around Mine Tailings.

PubMed

Stovern, Michael; Guzmán, Héctor; Rine, Kyle P; Felix, Omar; King, Matthew; Ela, Wendell P; Betterton, Eric A; Sáez, Avelino Eduardo

2016-02-01

Wind erosion, transport and deposition of windblown dust from anthropogenic sources, such as mine tailings impoundments, can have significant effects on the surrounding environment. The lack of vegetation and the vertical protrusion of the mine tailings above the neighboring terrain make the tailings susceptible to wind erosion. Modeling the erosion, transport and deposition of particulate matter from mine tailings is a challenge for many reasons, including heterogeneity of the soil surface, vegetative canopy coverage, dynamic meteorological conditions and topographic influences. In this work, a previously developed Deposition Forecasting Model (DFM) that is specifically designed to model the transport of particulate matter from mine tailings impoundments is verified using dust collection and topsoil measurements. The DFM is initialized using data from an operational Weather Research and Forecasting (WRF) model. The forecast deposition patterns are compared to dust collected by inverted-disc samplers and determined through gravimetric, chemical composition and lead isotopic analysis. The DFM is capable of predicting dust deposition patterns from the tailings impoundment to the surrounding area. The methodology and approach employed in this work can be generalized to other contaminated sites from which dust transport to the local environment can be assessed as a potential route for human exposure.

Windblown Dust Deposition Forecasting and Spread of Contamination around Mine Tailings

PubMed Central

Stovern, Michael; Guzmán, Héctor; Rine, Kyle P.; Felix, Omar; King, Matthew; Ela, Wendell P.; Betterton, Eric A.; Sáez, Avelino Eduardo

2017-01-01

Wind erosion, transport and deposition of windblown dust from anthropogenic sources, such as mine tailings impoundments, can have significant effects on the surrounding environment. The lack of vegetation and the vertical protrusion of the mine tailings above the neighboring terrain make the tailings susceptible to wind erosion. Modeling the erosion, transport and deposition of particulate matter from mine tailings is a challenge for many reasons, including heterogeneity of the soil surface, vegetative canopy coverage, dynamic meteorological conditions and topographic influences. In this work, a previously developed Deposition Forecasting Model (DFM) that is specifically designed to model the transport of particulate matter from mine tailings impoundments is verified using dust collection and topsoil measurements. The DFM is initialized using data from an operational Weather Research and Forecasting (WRF) model. The forecast deposition patterns are compared to dust collected by inverted-disc samplers and determined through gravimetric, chemical composition and lead isotopic analysis. The DFM is capable of predicting dust deposition patterns from the tailings impoundment to the surrounding area. The methodology and approach employed in this work can be generalized to other contaminated sites from which dust transport to the local environment can be assessed as a potential route for human exposure. PMID:29082035

Gene expression results

EPA Pesticide Factsheets

qPCR results for VitellogeninThis dataset is associated with the following publication:Armstrong, B., J. Lazorchak , K. Jensen , H. Haring , M.E. Smith, R. Flick , D. Bencic , and A. Biales. Reproductive effects in fathead minnows (Pimphales promelas) following a 21 d exposure to 17α-ethinylestradiol. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, USA, 144(1): 366-373, (2015).

Limits of Precision for Human Eye Motor Control

DTIC Science & Technology

1989-11-01

APE (Watt & Andrews, 1981) or a staircase method similar to PEST (Taylor & Creelman , 1967) were used. The results from these different methods of...Freeman StCyr, G.J. & Fender, D.H. (1969) The interplay of drifts and flicks in binocular fixation. Vision Res. 9, 245-265 Taylor, M.M. & Creelman , C.D

Effects of hot-iron disbudding, using regional anaesthesia with and without carprofen, on cortisol and behaviour of calves.

PubMed

Stilwell, G; Lima, M S; Carvalho, R C; Broom, D M

2012-04-01

The objective of this study was to assess cortisol and behaviour changes in calves hot-iron disbudded after different analgesic protocols. We assessed the response of 27 calves at 1, 3, 6 and 24 h after disbudding with regional anaesthesia (DA), regional anaesthesia plus carprofen (DAC), disbudded only (D) or sham-disbudded (ND). At 1h cortisol was higher in D compared with all other groups. At 3h DA showed higher cortisol than ND but did not differ from baseline. At 15 min and 1h pain-related behaviours were more frequent in the D group than in all other groups. Group D (3 h) and DA (3 and 6 h) showed more ear flicks and head rubs compared with DAC and ND. We concluded that head rubbing, head shaking and ear flicking are useful behaviours for evaluating pain after hot-iron disbudding. Disbudding causes severe pain in calves and only the association of regional anaesthesia with carprofen assures good welfare for 24 h. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of a dust deposition forecast model for a mine tailings impoundment

NASA Astrophysics Data System (ADS)

Stovern, Michael

Wind erosion, transport and deposition of particulate matter can have significant impacts on the environment. It is observed that about 40% of the global land area and 30% of the earth's population lives in semiarid environments which are especially susceptible to wind erosion and airborne transport of contaminants. With the increased desertification caused by land use changes, anthropogenic activities and projected climate change impacts windblown dust will likely become more significant. An important anthropogenic source of windblown dust in this region is associated with mining operations including tailings impoundments. Tailings are especially susceptible to erosion due to their fine grain composition, lack of vegetative coverage and high height compared to the surrounding topography. This study is focused on emissions, dispersion and deposition of windblown dust from the Iron King mine tailings in Dewey-Humboldt, Arizona, a Superfund site. The tailings impoundment is heavily contaminated with lead and arsenic and is located directly adjacent to the town of Dewey-Humboldt. The study includes in situ field measurements, computational fluid dynamic modeling and the development of a windblown dust deposition forecasting model that predicts deposition patterns of dust originating from the tailings impoundment. Two instrumented eddy flux towers were setup on the tailings impoundment to monitor the aeolian and meteorological conditions. The in situ observations were used in conjunction with a computational fluid dynamic (CFD) model to simulate the transport of windblown dust from the mine tailings to the surrounding region. The CFD model simulations include gaseous plume dispersion to simulate the transport of the fine aerosols, while individual particle transport was used to track the trajectories of larger particles and to monitor their deposition locations. The CFD simulations were used to estimate deposition of tailings dust and identify topographic mechanisms that influence deposition. Simulation results indicated that particles preferentially deposit in regions of topographic upslope. In addition, turbulent wind fields enhanced deposition in the wake region downwind of the tailings. This study also describes a deposition forecasting model (DFM) that can be used to forecast the transport and deposition of windblown dust originating from a mine tailings impoundment. The DFM uses in situ observations from the tailings and theoretical simulations of aerosol transport to parameterize the model. The model was verified through the use of inverted-disc deposition samplers. The deposition forecasting model was initialized using data from an operational Weather Research and Forecasting (WRF) model and the forecast deposition patterns were compared to the inverted-disc samples through gravimetric, chemical composition and lead isotopic analysis. The DFM was verified over several month-long observing periods by comparing transects of arsenic and lead tracers measured by the samplers to the DFM PM27 forecast. Results from the sampling periods indicated that the DFM was able to accurately capture the regional deposition patterns of the tailings dust up to 1 km. Lead isotopes were used for source apportionment and showed spatial patterns consistent with the DFM and the observed weather conditions. By providing reasonably accurate estimates of contaminant deposition rates, the DFM can improve the assessment of human health impacts caused by windblown dust from the Iron King tailings impoundment.

Supersonic aerodynamic characteristics of a low-aspect-ratio missile model with wing and tail controls and with tails in line and interdigitated

NASA Technical Reports Server (NTRS)

Graves, E. B.

1972-01-01

A study has been made to determine the aerodynamic characteristics of a low-aspect ratio cruciform missile model with all-movable wings and tails. The configuration was tested at Mach numbers from 1.50 to 4.63 with the wings in the vertical and horizontal planes and with the wings in a 45 deg roll plane with tails in line and interdigitated.

Wind-tunnel Investigation of End-plate Effects of Horizontal Tails on a Vertical Tail Compared with Available Theory

NASA Technical Reports Server (NTRS)

Murray, Harry E

1946-01-01

A vertical-tail model with stub fuselage was tested in combination with various simulated horizontal tails to determine the effect of horizontal-tail span and location on the aerodynamic characteristics of the vertical tail. Available theoretical data on end-plate effects were collected and presented in the form most suitable for design purposes. Reasonable agreement was obtained between the measured and theoretical end-plate effects of horizontal tails on vertical tails, and the data indicated that the end-plate effect was determined more by the location of the horizontal tail than by the span of the horizontal tail. The horizontal tail gave most end-plate effect when located near either tip of the vertical tail and, when located near the base of the vertical tail, the end-plate effect was increased by moving the horizontal tail rearward.

Light-curve analysis of KOI 2700b: the second extrasolar planet with a comet-like tail

NASA Astrophysics Data System (ADS)

Garai, Z.

2018-03-01

Context. The Kepler object KOI 2700b (KIC 8639908b) was discovered recently as the second exoplanet with a comet-like tail. It exhibits a distinctly asymmetric transit profile, likely indicative of the emission of dusty effluents and reminiscent of KIC 12557548b, the first exoplanet with a comet-like tail. Aim. The scientific goal of this work is to verify the disintegrating-planet scenario of KOI 2700b by modeling its light curve and to put constraints on various tail and planet properties, as was done in the case of KIC 12557548b. Methods: We obtained the phase-folded and binned transit light curve of KOI 2700b, which we subsequently iteratively modeled using the radiative-transfer code SHELLSPEC. We modeled the comet-like tail as part of a ring around the parent star and we also included the solid body of the planet in the model. During the modeling we applied selected species and dust particle sizes. Results: We confirmed the disintegrating-planet scenario of KOI 2700b. Furthermore, via modeling, we derived some interesting features of KOI 2700b and its comet-like tail. It turns out that the orbital plane of the planet and its tail are not edge-on, but the orbital inclination angle is from the interval [85.1, 88.6] deg. In comparison with KIC 12557548b, KOI 2700b exhibits a relatively low dust density decreasing in its tail. We also derived the dust density at the beginning of the ring and the highest optical depth through the tail in front of the star, based on a tail-model with a cross-section of 0.05 × 0.05 R⊙ at the beginning and 0.09 × 0.09 R⊙ at its end. Our results show that the dimension of the planet is Rp/Rs ≤ 0.014 (Rp ≤ 0.871 R⊕, or ≤5551 km). We also estimated the mass-loss rate from KOI 2700b, and we obtained Ṁ values from the interval [5.05 × 107, 4.41 × 1015] g s-1. On the other hand, we could not draw any satisfactory conclusions about the typical grain size in the dust tail.

Random-Walk Type Model with Fat Tails for Financial Markets

NASA Astrophysics Data System (ADS)

Matuttis, Hans-Geors

Starting from the random-walk model, practices of financial markets are included into the random-walk so that fat tail distributions like those in the high frequency data of the SP500 index are reproduced, though the individual mechanisms are modeled by normally distributed data. The incorporation of local correlation narrows the distribution for "frequent" events, whereas global correlations due to technical analysis leads to fat tails. Delay of market transactions in the trading process shifts the fat tail probabilities downwards. Such an inclusion of reactions to market fluctuations leads to mini-trends which are distributed with unit variance.

The effect of density-of-state tails on band-to-band tunneling: Theory and application to tunnel field effect transistors

NASA Astrophysics Data System (ADS)

Sant, S.; Schenk, A.

2017-10-01

It is demonstrated how band tail states in the semiconductor influence the performance of a Tunnel Field Effect Transistor (TFET). As a consequence of the smoothened density of states (DOS) around the band edges, the energetic overlap of conduction and valence band states occurs gradually at the onset of band-to-band tunneling (BTBT), thus degrading the sub-threshold swing (SS) of the TFET. The effect of the band tail states on the current-voltage characteristics is modelled quantum-mechanically based on the idea of zero-phonon trap-assisted tunneling between band and tail states. The latter are assumed to arise from a 3-dimensional pseudo-delta potential proposed by Vinogradov [1]. This model potential allows the derivation of analytical expressions for the generation rate covering the whole range from very strong to very weak localization of the tail states. Comparison with direct BTBT in the one-band effective mass approximation reveals the essential features of tail-to-band tunneling. Furthermore, an analytical solution for the problem of tunneling from continuum states of the disturbed DOS to states in the opposite band is found, and the differences to direct BTBT are worked out. Based on the analytical expressions, a semi-classical model is implemented in a commercial device simulator which involves numerical integration along the tunnel paths. The impact of the tail states on the device performance is analyzed for a nanowire Gate-All-Around TFET. The simulations show that tail states notably impact the transfer characteristics of a TFET. It is found that exponentially decaying band tails result in a stronger degradation of the SS than tail states with a Gaussian decay of their density. The developed model allows more realistic simulations of TFETs including their non-idealities.

Research on Long Tail Recommendation Algorithm

NASA Astrophysics Data System (ADS)

Hu, Xuezhi; Zhang, Chuang; Wu, Ming; Zeng, Yang

2017-10-01

Most recommendation systems in the major electronic commerce platforms are influenced by the long tail effect more or less. There are sufficient researches of how to assess recommendation effect while no criteria to evaluate long tail recommendation rate. In this study, we first discussed the existing problems of recommending long tail products through specific experiments. Then we proposed a long tail evaluation criteria and compared the performance in long tail recommendation between different models.

The Effects of Horizontal-Tail Location and Wing Modifications on the High-Speed Stability and Control Characteristics of a 01.17-Scale Model of the McDonnell XF2H-1 Airplane (TED No, NACA DE336)

NASA Technical Reports Server (NTRS)

Emerson, Horace F.; Axelson, John A.

1949-01-01

An additional series of high-speed wind-tunnel tests of a modified 0.17-scale model of the McDonnell XF2H-1 airplane was conducted to evaluate the effects of a reduction in the thickness-to-chord ratios of the tail planes, the displacement of the horizontal tail relative to the vertical tail, and the extension of the trailing edge of the wing. Two tail-intersection fairings designed to improve the flow at the tail were also tested. The pitching-moment characteristics of the model were improved slightly by the use of the thinner tail sections. Rearward or rearward and downward displacements of the horizontal tail increased the critical Mach number at the tail intersection from 0.725 to a maximum of 0.80, but caused an excessive change in pitching-moment coefficient at the higher Mach numbers. Extending the trailing edge of the wing did not improve the static longitudinal-stability characteristics, but increased the pitching-down tendency between 0.725 and 0.825 Mach numbers prior to the pitching-up tendency. The extended wing did, however, increase the Mach numbers at which these tendencies occurred. The increase in the Mach numbers of divergence and the tuft studies indicate a probable increase in the buffet limit of the prototype airplane. No perceptible improvement of flow at the tail intersection was observed with the two fairings tested on the forward tail configuration.

Research investigation of helicopter main rotor/tail rotor interaction noise

NASA Technical Reports Server (NTRS)

Fitzgerald, J.; Kohlhepp, F.

1988-01-01

Acoustic measurements were obtained in a Langley 14 x 22 foot Subsonic Wind Tunnel to study the aeroacoustic interaction of 1/5th scale main rotor, tail rotor, and fuselage models. An extensive aeroacoustic data base was acquired for main rotor, tail rotor, fuselage aerodynamic interaction for moderate forward speed flight conditions. The details of the rotor models, experimental design and procedure, aerodynamic and acoustic data acquisition and reduction are presented. The model was initially operated in trim for selected fuselage angle of attack, main rotor tip-path-plane angle, and main rotor thrust combinations. The effects of repositioning the tail rotor in the main rotor wake and the corresponding tail rotor countertorque requirements were determined. Each rotor was subsequently tested in isolation at the thrust and angle of attack combinations for trim. The acoustic data indicated that the noise was primarily dominated by the main rotor, especially for moderate speed main rotor blade-vortex interaction conditions. The tail rotor noise increased when the main rotor was removed indicating that tail rotor inflow was improved with the main rotor present.

The tails of the satellite auroral footprints at Jupiter

NASA Astrophysics Data System (ADS)

Bonfond, B.; Saur, J.; Grodent, D.; Badman, S. V.; Bisikalo, D.; Shematovich, V.; Gérard, J.-C.; Radioti, A.

2017-08-01

The electromagnetic interaction between Io, Europa, and Ganymede and the rotating plasma that surrounds Jupiter has a signature in the aurora of the planet. This signature, called the satellite footprint, takes the form of a series of spots located slightly downstream of the feet of the field lines passing through the moon under consideration. In the case of Io, these spots are also followed by an extended tail in the downstream direction relative to the plasma flow encountering the moon. A few examples of a tail for the Europa footprint have also been reported in the northern hemisphere. Here we present a simplified Alfvénic model for footprint tails and simulations of vertical brightness profiles for various electron distributions, which favor such a model over quasi-static models. We also report here additional cases of Europa footprint tails, in both hemispheres, even though such detections are rare and difficult. Furthermore, we show that the Ganymede footprint can also be followed by a similar tail. Finally, we present a case of a 320° long Io footprint tail, while other cases in similar configurations do not display such a length.

Diagnostic Simulations of the Lunar Exosphere using Coma and Tail

NASA Astrophysics Data System (ADS)

Lee, Dong Wook; Kim, Sang J.

2017-10-01

The characteristics of the lunar exosphere can be constrained by comparing simulated models with observational data of the coma and tail (Lee et al., JGR, 2011); and thus far a few independent approaches on this issue have been performed and presented in the literature. Since there are two-different observational constraints for the lunar exosphere, it is interesting to find the best exospheric model that can account for the observed characteristics of the coma and tail. Considering various initial conditions of different sources and space weather, we present preliminary time-dependent simulations between the initial and final stages of the development of the lunar tail. Based on an updated 3-D model, we are planning to conduct numerous simulations to constrain the best model parameters from the coma images obtained from coronagraph observations supported by a NASA monitoring program (Morgan, Killen, and Potter, AGU, 2015) and future tail data.

Chromaticity effects on head-tail instabilities for broadband impedance using two particle model, Vlasov analysis, and simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chin, Yong Ho; Chao, Alexander Wu; Blaskiewicz, Michael M.

Effects of the chromaticity on head-tail instabilities for broadband impedances are comprehensively studied, using the two particle model, the Vlasov analysis and computer simulations. We show both in the two particle model and the Vlasov analysis with the trapezoidal (semiconstant) wake model that we can derive universal contour plots for the growth factor as a function of the two dimensionless parameters: the wakefield strength, Υ, and the difference of the betatron phase advances between the head and the tail, χ. They reveal how the chromaticity affects strong head-tail instabilities and excites head-tail instabilities. We also apply the LEP (Large Electron-Positronmore » Collider) broadband resonator model to the Vlasov approach and find that the results are in very good agreement with those of the trapezoidal wake model. The theoretical findings are also reinforced by the simulation results. In conclusion, the trapezoidal wake model turns out to be a very useful tool since it significantly simplifies the time domain analysis and provides well-behaved impedance at the same time.« less

Chromaticity effects on head-tail instabilities for broadband impedance using two particle model, Vlasov analysis, and simulations

DOE PAGES

Chin, Yong Ho; Chao, Alexander Wu; Blaskiewicz, Michael M.; ...

2017-07-28

Effects of the chromaticity on head-tail instabilities for broadband impedances are comprehensively studied, using the two particle model, the Vlasov analysis and computer simulations. We show both in the two particle model and the Vlasov analysis with the trapezoidal (semiconstant) wake model that we can derive universal contour plots for the growth factor as a function of the two dimensionless parameters: the wakefield strength, Υ, and the difference of the betatron phase advances between the head and the tail, χ. They reveal how the chromaticity affects strong head-tail instabilities and excites head-tail instabilities. We also apply the LEP (Large Electron-Positronmore » Collider) broadband resonator model to the Vlasov approach and find that the results are in very good agreement with those of the trapezoidal wake model. The theoretical findings are also reinforced by the simulation results. In conclusion, the trapezoidal wake model turns out to be a very useful tool since it significantly simplifies the time domain analysis and provides well-behaved impedance at the same time.« less

On the probability distribution of stock returns in the Mike-Farmer model

NASA Astrophysics Data System (ADS)

Gu, G.-F.; Zhou, W.-X.

2009-02-01

Recently, Mike and Farmer have constructed a very powerful and realistic behavioral model to mimick the dynamic process of stock price formation based on the empirical regularities of order placement and cancelation in a purely order-driven market, which can successfully reproduce the whole distribution of returns, not only the well-known power-law tails, together with several other important stylized facts. There are three key ingredients in the Mike-Farmer (MF) model: the long memory of order signs characterized by the Hurst index Hs, the distribution of relative order prices x in reference to the same best price described by a Student distribution (or Tsallis’ q-Gaussian), and the dynamics of order cancelation. They showed that different values of the Hurst index Hs and the freedom degree αx of the Student distribution can always produce power-law tails in the return distribution fr(r) with different tail exponent αr. In this paper, we study the origin of the power-law tails of the return distribution fr(r) in the MF model, based on extensive simulations with different combinations of the left part L(x) for x < 0 and the right part R(x) for x > 0 of fx(x). We find that power-law tails appear only when L(x) has a power-law tail, no matter R(x) has a power-law tail or not. In addition, we find that the distributions of returns in the MF model at different timescales can be well modeled by the Student distributions, whose tail exponents are close to the well-known cubic law and increase with the timescale.

Effectiveness of Flow Control for Alleviation of Twin-Tail Buffet

NASA Technical Reports Server (NTRS)

Sheta, Essam F.; Kandil, Osama A.; Yang, Zhi

1998-01-01

Effectiveness of active flow control for twin- tail buffet alleviation is investigated. Tangen- tial leading-edge blowing (TLEB) and flow suction along the vortex cores (FSVC) of the lead- ing edges of the delta wing are used to delay the vortex breakdown flow upstream of the twin tail. The combined effect of the TLEB and FSVC is also investigated. A parametric study of the effects of the spanwise position of the suction tubes and volumetric suction flow rate on the twin-tail buffet response are also investigated. The TLEB moves the path of leading-edge vortices laterally towards the twin tail, which increases the aero- dynamic damping on the tails. The FSVC effectively delays the breakdown location at high angles of attack. The computational model consists of a sharp-edged delta wing of aspect ratio one and swept-back flexible twin tail with taper ratio of 0.23. This complex multidisciplinary problem is solved sequentially using three sets of equations for the fluid flow, aeroelastic response and grid deformation, on a dynamic multi-block grid structure. The computational model is pitched at 30 deg. angle of attack. The freestream Mach number and Reynolds number are 0.3 and 1.25 million, respectively. The model is investigated for the inboard position of the twin tails, which corresponds to a separation distance between the twin tails of 33% of the wing span.

Lateral Stability Characteristics of a 1/8.33-Scale Powered Model of the Republic XF-12 Airplane

NASA Technical Reports Server (NTRS)

Pepper, Edward; Foster, Gerald V.

1947-01-01

The XF-12 airplane is a high-performance photo-reconnaissance aircraft designed for the Army Air Forces by the Republic Aviation Corporation. An investigation of a 1/8.33 - scale powered model was made in the Langley l9-foot pressure tunnel to obtain information relative to the aerodynamic design of the airplane. The model was tested with and without the original vertical tail. and with two revised tails. For the revised tail no. 1, the span of the original vertical .tail was increased about 15 percent and the portion of the vertical tail between the stabilizer and fuselage behind the rudder hinge line was allowed to deflect simultaneously with the main rudder. Revision no. 2 incorporated the increased span, but the lower rudder was locked in the neutral position. For all the tail arrangements investigated it was indicated that the airplane will possess positive effective dihedral and will be directionally stable regardless of flap or power condition. The rudder effectiveness is greater for the revised tails than for the original tail, but this is offset by the increase in directional stability caused by the revised tail. All the rudder arrangements appear inadequate in trimming out the resultant yawing moments at zero yaw in a take - off condition with the left-hand outboard propeller windmilling and the remaining engines developing take-off power.

Extreme Temperature Exceedances Change more Rapidly Under Future Warming in Regions of non-Gaussian Short Temperature Distribution Tails

NASA Astrophysics Data System (ADS)

Loikith, P. C.; Neelin, J. D.; Meyerson, J.

2017-12-01

Regions of shorter-than-Gaussian warm and cold side temperature distribution tails are shown to occur in spatially coherent patterns in the current climate. Under such conditions, warming may be manifested in more complex ways than if the underlying distribution were close to Gaussian. For example, under a uniform warm shift, the simplest prototype for future warming, a location with a short warm side tail would experience a greater increase in extreme warm exceedances compared to if the distribution were Gaussian. Similarly, for a location with a short cold side tail, a uniform warm shift would result in a rapid decrease in extreme cold exceedances. Both scenarios carry major societal and environmental implications including but not limited to negative impacts on human and ecosystem health, agriculture, and the economy. It is therefore important for climate models to be able to realistically reproduce short tails in simulations of historical climate in order to boost confidence in projections of future temperature extremes. Overall, climate models contributing to the fifth phase of the Coupled Model Intercomparison Project capture many of the principal observed regions of short tails. This suggests the underlying dynamics and physics occur on scales resolved by the models, and helps build confidence in model projections of extremes. Furthermore, most GCMs show more rapid changes in exceedances of extreme temperature thresholds in regions of short tails. Results therefore suggest that the shape of the tails of the underlying temperature distribution is an indicator of how rapidly a location will experience changes to extreme temperature occurrence under future warming.

Aerodynamic Loads at Mach Numbers from 0.70 to 2.22 on an Airplane Model Having a Wing and Canard of Triangular Plan Form and Either Single or Twin Vertical Tails Supplement I-Tabulated Data for the Model with Single Vertical Tails. Supplement 1; Tabulated Data for the Model with Single Vertical Tail

NASA Technical Reports Server (NTRS)

Peterson, Victor L.; Menees, Gene P.

1961-01-01

Tabulated results of a wind-tunnel investigation of the aerodynamic loads on a canard airplane model with a single vertical tail are presented for Mach numbers from 0.70 to 2.22. The Reynolds number for the measurements was 2.9 x 10(exp 6) based on the wing mean aerodynamic chord. The results include local static pressure coefficients measured on the wing, body, and vertical tail for angles of attack from -4 deg to + 16 deg, angles of sideslip of 0 deg and 5.3 deg, vertical-tail settings of 0 deg and 5 deg, and nominal canard deflections of 0 deg and 10 deg. Also included are section force and moment coefficients obtained from integrations of the local pressures and model-component force and moment coefficients obtained from integrations of the section coefficients. Geometric details of the model and the locations of the pressure orifices are shown. An index to the data contained herein is presented and definitions of nomenclature are given.

Tail dependence and information flow: Evidence from international equity markets

NASA Astrophysics Data System (ADS)

Al Rahahleh, Naseem; Bhatti, M. Ishaq; Adeinat, Iman

2017-05-01

Bhatti and Nguyen (2012) used the copula approach to measure the tail dependence between a number of international markets. They observed that some country pairs exhibit only left-tail dependence whereas others show only right-tail. However, the flow of information from uni-dimensional (one-tail) to bi-dimensional (two-tails) between various markets was not accounted for. In this study, we address the flow of information of this nature by using the dynamic conditional correlation (DCC-GARCH) model. More specifically, we use various versions of the DCC models to explain the nexus between the information flow of international equity and to explain the stochastic forward vs. backward dynamics of financial markets based on data for a 15-year period comprising 3,782 observations. We observed that the information flow between the US and Hong Kong markets and between the US and Australian markets are bi-directional. We also observed that the DCC model captures a wider co-movement structure and inter-connectedness compared to the symmetric Joe-Clayton copula.

Engaging Organic Chemistry Students Using ChemDraw for iPad

ERIC Educational Resources Information Center

Morsch, Layne A.; Lewis, Michael

2015-01-01

Drawing structures, mechanisms, and syntheses is a vital part of success in organic chemistry courses. ChemDraw for iPad has been used to increase classroom experiences in the preparation of high quality chemical drawings. The embedded Flick-to-Share allows for simple, real-time exchange of ChemDraw documents. ChemDraw for iPad also allows…

The Effect of Repetitive Saccade Execution on the Attention Network Test: Enhancing Executive Function with a Flick of the Eyes

ERIC Educational Resources Information Center

Edlin, James M.; Lyle, Keith B.

2013-01-01

The simple act of repeatedly looking left and right can enhance subsequent cognition, including divergent thinking, detection of matching letters from visual arrays, and memory retrieval. One hypothesis is that saccade execution enhances subsequent cognition by altering attentional control. To test this hypothesis, we compared performance…

Films and the English Class.

ERIC Educational Resources Information Center

Donelson, Kenneth, Ed.

1971-01-01

The importance of film in the English classroom and its vitality in the English curriculum are discussed. Articles that comprise this issue of the bulletin are: The Trouble with Film Teaching by James E. Cutts; "You Ain't Heard Nothin' Yet" or Send Your Students to the Flicks Tonight by Bob Haskett; It's the Reel Thing: The Verite of Cinema Is…

Aerodynamic Loads at Mach Numbers from 0.70 to 2.22 on an Airplane Model Having a Wing and Canard of Triangular Plan Form and Either Single or Twin Vertical Tails. Supplement 2; Tabulated Data for the Model with Twin Vertical Tails

NASA Technical Reports Server (NTRS)

Peterson, Victor L.; Menees, Gene P.

1961-01-01

Tabulated results of a wind-tunnel investigation of the aerodynamic loads on a canard airplane model with twin vertical tails are presented for Mach numbers from 0.70 to 2.22. The Reynolds number for the measurements was 2.9 x 10(exp 6) based on the wing mean aerodynamic chord. The results include local static-pressure coefficients measured on the wing, body, and one of the vertical tails for angles of attack from -4 degrees to 16 degree angles of sideslip of 0 degrees and 5.3 degrees, and nominal canard deflections of O degrees and 10 degrees. Also included are section force and moment coefficients obtained from integrations of the local pressures and model-component force and moment coefficients obtained from integrations of the section coefficients. Geometric details of the model are shown and the locations of the pressure orifices are shown. An index to the data contained herein is presented and definitions of nomenclature are given. Detailed descriptions of the model and experiments and a brief discussion of some of the results are given. Tabulated results of measurements of the aerodynamic loads on the same canard model but having a single vertical tail instead of twin vertical tails are presented.

Energy harvesting from the tail beating of a carangiform swimmer using ionic polymer-metal composites.

PubMed

Cha, Youngsu; Verotti, Matteo; Walcott, Horace; Peterson, Sean D; Porfiri, Maurizio

2013-09-01

In this paper, we study energy harvesting from the beating of a biomimetic fish tail using ionic polymer-metal composites. The design of the biomimetic tail is based on carangiform swimmers and is specifically inspired by the morphology of the heterocercal tail of thresher sharks. The tail is constituted of a soft silicone matrix molded in the form of the heterocercal tail and reinforced by a steel beam of rectangular cross section. We propose a modeling framework for the underwater vibration of the biomimetic tail, wherein the tail is assimilated to a cantilever beam with rectangular cross section and heterogeneous physical properties. We focus on base excitation in the form of a superimposed rotation about a fixed axis and we consider the regime of moderately large-amplitude vibrations. In this context, the effect of the encompassing fluid is described through a hydrodynamic function, which accounts for inertial, viscous and convective phenomena. The model is validated through experiments in which the base excitation is systematically varied and the motion of selected points on the biomimetic tail tracked in time. The feasibility of harvesting energy from an ionic polymer-metal composite attached to the vibrating structure is experimentally and theoretically assessed. The response of the transducer is described using a black-box model, where the voltage output is controlled by the rate of change of the mean curvature. Experiments are performed to elucidate the impact of the shunting resistance, the frequency of the base excitation and the placement of the ionic polymer-metal composite on energy harvesting from the considered biomimetic tail.

Feasibility Studies on Pipeline Disposal of Concentrated Copper Tailings Slurry for Waste Minimization

NASA Astrophysics Data System (ADS)

Senapati, Pradipta Kumar; Mishra, Barada Kanta

2017-06-01

The conventional lean phase copper tailings slurry disposal systems create pollution all around the disposal area through seepage and flooding of waste slurry water. In order to reduce water consumption and minimize pollution, the pipeline disposal of these waste slurries at high solids concentrations may be considered as a viable option. The paper presents the rheological and pipeline flow characteristics of copper tailings samples in the solids concentration range of 65-72 % by weight. The tailings slurry indicated non-Newtonian behaviour at these solids concentrations and the rheological data were best fitted by Bingham plastic model. The influence of solids concentration on yield stress and plastic viscosity for the copper tailings samples were discussed. Using a high concentration test loop, pipeline experiments were conducted in a 50 mm nominal bore (NB) pipe by varying the pipe flow velocity from 1.5 to 3.5 m/s. A non-Newtonian Bingham plastic pressure drop model predicted the experimental data reasonably well for the concentrated tailings slurry. The pressure drop model was used for higher size pipes and the operating conditions for pipeline disposal of concentrated copper tailings slurry in a 200 mm NB pipe with respect to specific power consumption were discussed.

Crucial advantages of tail use in the evolution of vertebrate terrestrial locomotion

NASA Astrophysics Data System (ADS)

Astley, Henry; McInroe, Benjamin; Kawano, Sandy; Blob, Rick; Goldman, Daniel

In the invasion of terrestrial environment, the first tetrapods faced the challenge of locomotion on flowable substrates (e.g. sand and mud), sometimes oriented at inclines. Although the morphology of many early tetrapods is known, robotic studies have revealed that effective locomotion on these substrates also depends strongly upon kinematics; slight differences in movements of the same appendage can lead to success or failure. Using a model organism (the mudskipper) and a robotic physical model, we demonstrate how muscular tails provided critical locomotor advantages on granular substrates that the first invaders of land likely encountered. Mudskippers use their tails for additional propulsion with increasing frequency as the slope of the granular material increases, and the decline in locomotor performance with slope is shallower when the tail is used. Experiments with a robotic model of the mudskipper showed that, while the tail did not always provide a benefit to locomotion, use of the tail made the robot's performance more robust, achieving effective locomotion on a wider range of slopes, limb postures and foot placements. These results suggest that, rather than simply being an inert appendage, the tails of early tetrapods were vital to their first forays into terrestrial habitats.

Reduced Fokker-Planck models for fast particle distribution across a transition layer of disparate plasma temperatures

NASA Astrophysics Data System (ADS)

Tang, Xian-Zhu; Berk, H. L.; Guo, Zehua; McDevitt, C. J.

2014-03-01

Across a transition layer of disparate plasma temperatures, the high energy tail of the plasma distribution can have appreciable deviations from the local Maxwellian distribution due to the Knudson layer effect. The Fokker-Planck equation for the tail particle population can be simplified in a series of practically useful limiting cases. The first is the approximation of background Maxwellian distribution for linearizing the collision operator. The second is the supra-thermal particle speed ordering of vTi ≪ v ≪ vTe for the tail ions and vTi ≪ vTe ≪ v for the tail electrons. Keeping both the collisional drag and energy scattering is essential for the collision operator to produce a Maxwellian tail distribution. The Fokker-Planck model for following the tail ion distribution for a given background plasma profile is explicitly worked out for systems of one spatial dimension, in both slab and spherical geometry. A third simplification is an expansion of the tail particle distribution using the spherical harmonics, which are eigenfunctions of the pitch angle scattering operator. This produces a set of coupled Fokker-Planck equations that contain energy-dependent spatial diffusion terms in two coordinates (position and energy), which originate from pitch angle scattering in the original Fokker-Planck equation. It is shown that the well-known diffusive Fokker-Planck model is a poor approximation of the two-mode truncation model, which itself has fundamental deficiency compared with the three-mode truncation model. The cause is the lack of even-symmetry representation in pitch dependence in the two-mode truncation model.

A first approximation kinetic model to predict methane generation from an oil sands tailings settling basin.

PubMed

Siddique, Tariq; Gupta, Rajender; Fedorak, Phillip M; MacKinnon, Michael D; Foght, Julia M

2008-08-01

A small fraction of the naphtha diluent used for oil sands processing escapes with tailings and supports methane (CH(4)) biogenesis in large anaerobic settling basins such as Mildred Lake Settling Basin (MLSB) in northern Alberta, Canada. Based on the rate of naphtha metabolism in tailings incubated in laboratory microcosms, a kinetic model comprising lag phase, rate of hydrocarbon metabolism and conversion to CH(4) was developed to predict CH(4) biogenesis and flux from MLSB. Zero- and first-order kinetic models, respectively predicted generation of 5.4 and 5.1 mmol CH(4) in naphtha-amended microcosms compared to 5.3 (+/-0.2) mmol CH(4) measured in microcosms during 46 weeks of incubation. These kinetic models also predicted well the CH(4) produced by tailings amended with either naphtha-range n-alkanes or BTEX compounds at concentrations similar to those expected in MLSB. Considering 25% of MLSB's 200 million m(3) tailings volume to be methanogenic, the zero- and first-order kinetic models applied over a wide range of naphtha concentrations (0.01-1.0 wt%) predicted production of 8.9-400 million l CH(4) day(-1) from MLSB, which exceeds the estimated production of 3-43 million l CH(4) day(-1). This discrepancy may result from heterogeneity and density of the tailings, presence of nutrients in the microcosms, and/or overestimation of the readily biodegradable fraction of the naphtha in MLSB tailings.

Experimental Investigation of the Effect of Vertical-tail Size and Length and of Fuselage Shape and Length on the Static Lateral Stability Characteristics of a Model with 45 Degree Sweptback Wing and Tail Surfaces

NASA Technical Reports Server (NTRS)

Queijo, M J; Wolhart, Walter D

1951-01-01

An investigation was made to determine the effects of vertical-tail size and length and of fuselage shape and length on the static lateral stability characteristics of a model with wing and vertical tails having the quarter-chord lines swept back 45 degrees. The results indicate that the directional instability of the various isolated fuselages was about two-thirds as large as that predicted by classical theory.

Simulation of windblown dust transport from a mine tailings impoundment using a computational fluid dynamics model

NASA Astrophysics Data System (ADS)

Stovern, Michael; Felix, Omar; Csavina, Janae; Rine, Kyle P.; Russell, MacKenzie R.; Jones, Robert M.; King, Matt; Betterton, Eric A.; Sáez, A. Eduardo

2014-09-01

Mining operations are potential sources of airborne particulate metal and metalloid contaminants through both direct smelter emissions and wind erosion of mine tailings. The warmer, drier conditions predicted for the Southwestern US by climate models may make contaminated atmospheric dust and aerosols increasingly important, due to potential deleterious effects on human health and ecology. Dust emissions and dispersion of dust and aerosol from the Iron King Mine tailings in Dewey-Humboldt, Arizona, a Superfund site, are currently being investigated through in situ field measurements and computational fluid dynamics modeling. These tailings are heavily contaminated with lead and arsenic. Using a computational fluid dynamics model, we model dust transport from the mine tailings to the surrounding region. The model includes gaseous plume dispersion to simulate the transport of the fine aerosols, while individual particle transport is used to track the trajectories of larger particles and to monitor their deposition locations. In order to improve the accuracy of the dust transport simulations, both regional topographical features and local weather patterns have been incorporated into the model simulations. Results show that local topography and wind velocity profiles are the major factors that control deposition.

Simulation of windblown dust transport from a mine tailings impoundment using a computational fluid dynamics model.

PubMed

Stovern, Michael; Felix, Omar; Csavina, Janae; Rine, Kyle P; Russell, MacKenzie R; Jones, Robert M; King, Matt; Betterton, Eric A; Sáez, A Eduardo

2014-09-01

Mining operations are potential sources of airborne particulate metal and metalloid contaminants through both direct smelter emissions and wind erosion of mine tailings. The warmer, drier conditions predicted for the Southwestern US by climate models may make contaminated atmospheric dust and aerosols increasingly important, due to potential deleterious effects on human health and ecology. Dust emissions and dispersion of dust and aerosol from the Iron King Mine tailings in Dewey-Humboldt, Arizona, a Superfund site, are currently being investigated through in situ field measurements and computational fluid dynamics modeling. These tailings are heavily contaminated with lead and arsenic. Using a computational fluid dynamics model, we model dust transport from the mine tailings to the surrounding region. The model includes gaseous plume dispersion to simulate the transport of the fine aerosols, while individual particle transport is used to track the trajectories of larger particles and to monitor their deposition locations. In order to improve the accuracy of the dust transport simulations, both regional topographical features and local weather patterns have been incorporated into the model simulations. Results show that local topography and wind velocity profiles are the major factors that control deposition.

Simulation of windblown dust transport from a mine tailings impoundment using a computational fluid dynamics model

PubMed Central

Stovern, Michael; Felix, Omar; Csavina, Janae; Rine, Kyle P.; Russell, MacKenzie R.; Jones, Robert M.; King, Matt; Betterton, Eric A.; Sáez, A. Eduardo

2014-01-01

Mining operations are potential sources of airborne particulate metal and metalloid contaminants through both direct smelter emissions and wind erosion of mine tailings. The warmer, drier conditions predicted for the Southwestern US by climate models may make contaminated atmospheric dust and aerosols increasingly important, due to potential deleterious effects on human health and ecology. Dust emissions and dispersion of dust and aerosol from the Iron King Mine tailings in Dewey-Humboldt, Arizona, a Superfund site, are currently being investigated through in situ field measurements and computational fluid dynamics modeling. These tailings are heavily contaminated with lead and arsenic. Using a computational fluid dynamics model, we model dust transport from the mine tailings to the surrounding region. The model includes gaseous plume dispersion to simulate the transport of the fine aerosols, while individual particle transport is used to track the trajectories of larger particles and to monitor their deposition locations. In order to improve the accuracy of the dust transport simulations, both regional topographical features and local weather patterns have been incorporated into the model simulations. Results show that local topography and wind velocity profiles are the major factors that control deposition. PMID:25621085

A proactive approach to sustainable management of mine tailings

NASA Astrophysics Data System (ADS)

Edraki, Mansour; Baumgartl, Thomas

2015-04-01

The reactive strategies to manage mine tailings i.e. containment of slurries of tailings in tailings storage facilities (TSF's) and remediation of tailings solids or tailings seepage water after the decommissioning of those facilities, can be technically inefficient to eliminate environmental risks (e.g. prevent dispersion of contaminants and catastrophic dam wall failures), pose a long term economic burden for companies, governments and society after mine closure, and often fail to meet community expectations. Most preventive environmental management practices promote proactive integrated approaches to waste management whereby the source of environmental issues are identified to help make a more informed decisions. They often use life cycle assessment to find the "hot spots" of environmental burdens. This kind of approach is often based on generic data and has rarely been used for tailings. Besides, life cycle assessments are less useful for designing operations or simulating changes in the process and consequent environmental outcomes. It is evident that an integrated approach for tailings research linked to better processing options is needed. A literature review revealed that there are only few examples of integrated approaches. The aim of this project is to develop new tailings management models by streamlining orebody characterization, process optimization and rehabilitation. The approach is based on continuous fingerprinting of geochemical processes from orebody to tailings storage facility, and benchmark the success of such proactive initiatives by evidence of no impacts and no future projected impacts on receiving environments. We present an approach for developing such a framework and preliminary results from a case study where combined grinding and flotation models developed using geometallurgical data from the orebody were constructed to predict the properties of tailings produced under various processing scenarios. The modelling scenarios based on the case study data provide the capacity to predict the composition of tailings and the resulting environmental management implications. For example, the type and content of clay minerals in tailings will affect the geotechnical stability and water recovery. Clay content will also influence decisions made for paste or thickened tailings and underground backfilling. It is possible by using an integrated assessment framework to evaluate more alternatives, including the production of additional saleable and benign streams, alternative tailings treatment and disposal, as well as options for reuse, recycling and pre-processing of existing tailings.

Comparing analgesia and μ-opioid receptor internalization produced by intrathecal enkephalin

PubMed Central

Chen, Wenling; Song, Bingbing; Lao, Lijun; Pérez, Orlando A.; Kim, Woojae; Marvizón, Juan Carlos G.

2007-01-01

Summary Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude μ-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or δ-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was ten times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia. PMID:17845806

Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine.

PubMed

Jokinen, Viljami; Lilius, Tuomas; Laitila, Jouko; Niemi, Mikko; Kambur, Oleg; Kalso, Eija; Rauhala, Pekka

2017-01-01

Spironolactone, eplerenone, chlorothiazide and furosemide are diuretics that have been suggested to have antinociceptive properties, for example via mineralocorticoid receptor antagonism. In co-administration, diuretics might enhance the antinociceptive effect of opioids via pharmacodynamic and pharmacokinetic mechanisms. Effects of spironolactone (100 mg/kg, i.p.), eplerenone (100 mg/kg, i.p.), chlorothiazide (50 mg/kg, i.p.) and furosemide (100 mg/kg, i.p.) were studied on acute oxycodone (0.75 mg/kg, s.c.)- and morphine (3 mg/kg, s.c.)-induced antinociception using tail-flick and hot plate tests in male Sprague Dawley rats. The diuretics were administered 30 min. before the opioids, and behavioural tests were performed 30 and 90 min. after the opioids. Concentrations of oxycodone, morphine and their major metabolites in plasma and brain were quantified by mass spectrometry. In the hot plate test at 30 and 90 min., spironolactone significantly enhanced the antinociceptive effect (% of maximum possible effect) of oxycodone from 10% to 78% and from 0% to 50%, respectively, and that of morphine from 12% to 73% and from 4% to 83%, respectively. The brain oxycodone and morphine concentrations were significantly increased at 30 min. (oxycodone, 46%) and at 90 min. (morphine, 190%). We did not detect any independent antinociceptive effects with the diuretics. Eplerenone and chlorothiazide did not enhance the antinociceptive effect of either opioid. The results suggest that spironolactone enhances the antinociceptive effect of both oxycodone and morphine by increasing their concentrations in the central nervous system. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect.

PubMed

Basha, Mona; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; El Awdan, Sally; Awad, Gamal

2015-01-01

The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.

Lidocaine alleviates morphine tolerance via AMPK-SOCS3-dependent neuroinflammation suppression in the spinal cord.

PubMed

Zhang, Yan; Tao, Gao-Jian; Hu, Liang; Qu, Jie; Han, Yuan; Zhang, Guangqin; Qian, Yanning; Jiang, Chun-Yi; Liu, Wen-Tao

2017-11-02

Morphine tolerance is a clinical challenge, and its pathogenesis is closely related to the neuroinflammation mediated by Toll-like receptor 4 (TLR4). In Chinese pain clinic, lidocaine is combined with morphine to treat chronic pain. We found that lidocaine sufficiently inhibited neuroinflammation induced by morphine and improved analgesic tolerance on the basis of non-affecting pain threshold. CD-1 mice were utilized for tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 was utilized to investigate the mechanism of lidocaine. Neuroinflammation-related cytokines were measured by western blotting and real-time PCR. The level of suppressor of cytokine signaling 3 (SOCS3) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-related signaling pathway was evaluated by western blotting, real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. Lidocaine potentiated an anti-nociceptive effect of morphine and attenuated the chronic analgesic tolerance. Lidocaine suppressed morphine-induced activation of microglia and downregulated inflammatory cytokines, interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) via upregulating SOCS3 by activating AMPK. Lidocaine enhanced AMPK phosphorylation in a calcium-dependent protein kinase kinase β (CaMKKβ)-dependent manner. Furthermore, lidocaine decreased the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear factor-κB (NF-κB) in accordance with the inhibitory effects to TLR4. Lidocaine as a prevalent local anesthetic suppresses morphine tolerance efficiently. AMPK-dependent upregulation of SOCS3 by lidocaine plays a crucial role in the improvement of analgesic tolerance.

Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice.

PubMed

Homayouni Moghadam, Farshad; Dehghan, Maryam; Zarepur, Ehsan; Dehlavi, Reyhaneh; Ghaseminia, Fatemeh; Ehsani, Shima; Mohammadzadeh, Golnaz; Barzegar, Kazem

2014-05-28

According to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy. in vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock׳s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10 days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies. in vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves. in vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Rats.

PubMed

Aghdam, Amir Mahmoudi; Shahabi, Parviz; Karimi-Sales, Elham; Ghiasi, Rafigheh; Sadigh-Eteghad, Saeed; Mahmoudi, Javad; Alipour, Mohammad Reza

2018-04-30

Diabetes is a common metabolic disease which leads to diabetic peripheral neuropathy. Recently, the role of microRNA-96 (miR-96) in alleviating neuropathic pain by inhibiting the expression of NaV1.3, an isoform of voltage-gated sodium channels, has been shown. Peripheral nerve injuries result in NaV1.3 elevation. Exercise has beneficial role in diabetes management and peripheral neuropathy. However, the effects of exercise on miR-96 and its target gene NaV1.3 in diabetic rats are unknown. Therefore, the present study investigated the effects of exercise training on the expression of miR-96 and NaV1.3 in diabetic rats. For this purpose, rats were randomly divided into four groups: control, exercise, diabetic and diabetic-exercise groups. Type 2 diabetes was induced by a high-fat diet and the administration of streptozotocin (STZ) (35 mg/kg, i.p.). The exercise groups were subjected to swimming exercise 5 days/week for 10 weeks. At the end of the treatment period, thermal pain threshold, determined through the tail-flick test, and the expression levels of miR-96 and its target gene NaV1.3 were determined by reverse transcription (RT)-PCR in the sciatic nerve tissues of the rats. Data of the present study indicated that diabetes diminished miR-96 expression levels, but significantly upregulated NaV1.3 expression in the sciatic nerve. On exercise training, miR-96 expression was reversed with concurrent down-regulation of the NaV1.3 expression. This study introduced a new and potential miRNA-dependent mechanism for exerciseinduced protective effects against diabetic thermal hyperalgesia.

Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

PubMed

Schunck, Rebeca Vargas Antunes; Macedo, Isabel Cristina; Laste, Gabriela; de Souza, Andressa; Valle, Marina Tuerlinckx Costa; Salomón, Janaína L O; Nunes, Ellen Almeida; Campos, Andreia Cristina Wildner; Gnoatto, Simone Cristina Baggio; Bergold, Ana Maria; Konrath, Eduardo L; Dallegrave, Eliane; Arbo, Marcelo Dutra; Torres, Iraci L S; Leal, Mirna Bainy

2017-08-01

Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Neural Correlates of the Antinociceptive Effects of Stimulating the Anterior Pretectal Nucleus in Rats.

PubMed

Genaro, Karina; Prado, Wiliam A

2016-11-01

Stimulation-evoked antinociception (SEA) from the anterior pretectal nucleus (APtN) activates mechanisms that descend to the spinal cord through the dorsolateral funiculus, but the encephalic route followed by the descending pathways from the APtN is not completely known. This study evaluated the changes in the SEA from the APtN in the Wistar rat tail-flick test after lidocaine-induced neural block or N-methyl-d-aspartate-induced neurotoxic lesion of the deep mesencephalic nucleus (DpMe), tegmental pedunculopontine nucleus (PPTg), or lateral paragigantocellular nucleus (LPGi). The SEA from the APtN was less intense after neural block of the contralateral DpMe or PPTg or the ipsilateral LPGi, but was not changed by the neural block of the ipsilateral DpMe or PPTg or the contralateral LPGi. Antinociception did not occur when APtN stimulation was carried out 5 minutes after lidocaine or 6 days after N-methyl-d-aspartate injections into the contralateral DpMe and the ipsilateral LPGi, or into the contralateral PPTg and the ipsilateral LPGi. We conclude that the SEA from the APtN activates 2 descending pain inhibitory pathways, one relaying in the ipsilateral LPGi and another relaying sequentially in the contralateral DpMe and PPTg. The antinociceptive effect of the APtN stimulation involves 2 descending pathways: one relaying in the ipsilateral LPGi and another descending contralaterally via relays in the DpMe and PPTg. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.

PubMed

Bruno, Alessandra Nejar; Fontella, Fernanda Urruth; Bonan, Carla Denise; Barreto-Chaves, Maria Luiza M; Dalmaz, Carla; Sarkis, João José Freitas

2006-02-28

Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.

Possible GABAergic modulation in the protective effect of zolpidem in acute hypoxic stress-induced behavior alterations and oxidative damage.

PubMed

Kumar, Anil; Goyal, Richa

2008-03-01

Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine functions. The free radical or oxidative stress theory holds that oxidative reactions are mainly underlying neurodegenerative disorders. In fact among complex metabolic reactions occurring during hypoxia, many could be related to the formation of oxygen derived free radicals, causing a wide spectrum of cell damage. In present study, we investigated possible involvement of GABAergic mechanism in the protective effect of zolpidem against acute hypoxia-induced behavioral modification and biochemical alterations in mice. Mice were subjected to acute hypoxic stress for a period of 2 h. Acute hypoxic stress for 2 h caused significant impairment in locomotor activity, anxiety-like behavior, and antinocioceptive effect in mice. Biochemical analysis revealed a significant increased malondialdehyde, nitrite concentrations and depleted reduced glutathione and catalase levels. Pretreatment with zolpidem (5 and 10 mg/kg, i.p.) significantly improved locomotor activity, anti-anxiety effect, reduced tail flick latency and attenuated oxidative damage (reduced malondialdehyde, nitrite concentration, and restoration of reduced glutathione and catalase levels) as compared to stressed control (hypoxia) (P < 0.05). Besides, protective effect of zolpidem (5 mg/kg) was blocked significantly by picrotoxin (1.0 mg/kg) or flumazenil (2 mg/kg) and potentiated by muscimol (0.05 mg/kg) in hypoxic animals (P < 0.05). These effects were significant as compared to zolpidem (5 mg/kg) per se (P < 0.05). Present study suggest that the possible involvement of GABAergic modulation in the protective effect of zolpidem against hypoxic stress.

Enhanced analgesic effects of tramadol and common trace element coadministration in mice.

PubMed

Alexa, Teodora; Marza, Aurelia; Voloseniuc, Tudor; Tamba, Bogdan

2015-10-01

Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadol's analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail-flick (TF) and hot-plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadol's analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol-alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drug's analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia. © 2015 Wiley Periodicals, Inc.

Behavioral evidence for the interaction of oleamide with multiple neurotransmitter systems.

PubMed

Fedorova, I; Hashimoto, A; Fecik, R A; Hedrick, M P; Hanus, L O; Boger, D L; Rice, K C; Basile, A S

2001-10-01

While the endogenous fatty acid amide oleamide has hypnotic properties, neither the breadth of its behavioral actions nor the mechanism(s) by which these behaviors may be mediated has been elucidated. Therefore, the effects of oleamide on the performance of rats in tests of motor function, analgesia, and anxiety were investigated. Oleamide reduced the distance traveled in the open field (ED50 = 14, 10-19 mg/kg, mean, 95% confidence interval), induced analgesia and hypothermia, but did not cause catalepsy. Moreover, a dose of oleamide without effect on motor function was anxiolytic in the social interaction test and elevated plus-maze. These actions of a single dose of oleamide lasted for 30 to 60 min. While rats became tolerant to oleamide following 8 days of repeated administration, oleamide is a poor inducer of physical dependence. Pretreatment with antagonists of the serotonin (5HT)1A, 5HT2C, and vanilloid receptors did not modify oleamide's effects. However, the cannabinoid receptor antagonist SR 141716A inhibited oleamide-induced analgesia in the tail-flick assay, the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline reversed the analgesia and hypothermia, and the dopamine D2 receptor antagonist L 741626 blocked oleamide's locomotor and analgesic actions. Interestingly, oleamide analogs resistant to hydrolysis by fatty acid amide hydrolase (FAAH) maintained but did not show increased behavioral potency or duration of action, whereas two FAAH inhibitors produced analogous behavioral effects. Thus, oleamide induces behaviors reminiscent of the actions of endogenous cannabinoids, but the involvement of GABAergic and dopaminergic systems, either directly or indirectly, in the actions of oleamide cannot be ruled out.

Structures far from the head of comet Kohoutek. II - A discussion of the Swan Cloud of January 11 and of the general morphology of cometary plasma tails

NASA Technical Reports Server (NTRS)

Niedner, M. B., Jr.; Brandt, J. C.

1980-01-01

Photographs show that the 'Swan Cloud' observed in comet Kohoutek on January 11, 1974 was an advanced stage of a plasma tail disconnection event, of which the rejected tail appeared to decelerate as it receded from the head. The event commenced with the development of strong tail ray activity followed by the actual tail disconnection, the merging of the disconnected tail with the new tail to form the Swan and the formation of arcade loops in the space between closing tail rays. The observed morphological sequence is easily understood in the sector boundary model (Niedner et al., 1978), and the arcade loops are proposed to be reconnected flux tubes between oppositely polarized tail rays in the incipient new tail which followed the disconnection

Aerodynamic characteristics of a canard-controlled missile at Mach numbers of 0.8, 1.3, and 1.75. [in the Ames 6 by 6 foot wind tunnel

NASA Technical Reports Server (NTRS)

Kassner, D. L.; Wettlaufer, B.

1977-01-01

A typical missile model with nose-mounted canards and cruciform tail surfaces was tested in the Ames 6- by 6-Foot Wind Tunnel to determine the contributions of the component aerodynamic surfaces to the static aerodynamic characteristics at Mach numbers of 0.8, 1.3, and 1.75 and Reynolds number of 625,000 based on body diameter. Data were obtained at angles of attack ranging from 0 deg to 24 deg for various stages of model build-up (i.e., with and without canard and/or tail surfaces). In addition, two different sets of canards and tail surfaces were investigated. For the canard and tail arrangements investigated, the model was trimmable at angles of attack up to about 7 deg with canard deflections of about 10 deg. Also, the tail arrangements studied provided ample pitch stability.

Stability and control characteristics of an airplane model having a 45.1 degree swept-back wing with aspect ratio 2.50 and taper ratio 0.42 and a 42.8 degree swept-back horizontal tail with aspect ratio 3.87 and taper ratio 0.49

NASA Technical Reports Server (NTRS)

Schuldenfrei, Marvin; Comisarow, Paul; Goodson, Kenneth W

1947-01-01

Tests were made of an airplane model having a 45.1 degree swept-back wing with aspect ratio 2.50 and taper ratio 0.42 and a 42.8 degree swept-back horizontal tail with aspect ratio 3.87 and taper ratio 0.49 to determine its low-speed stability and control characteristics. The test Reynolds number was 2.87 x 10(6) based on a mean aerodynamic chord of 2.47 feet except for some of the aileron tests which were made at a Reynolds number of 2.05 x 10(6). With the horizontal tail located near the fuselage juncture on the vertical tail, model results indicated static longitudinal instability above a lift coefficient that was 0.15 below the lift coefficient at which stall occurred. Static longitudinal stability, however, was manifested throughout the life range with the horizontal tail located near the top of the vertical tail. The use of 10 degrees negative dihedral on the wing had little effect on the static longitudinal stability characteristics. Preliminary tests of the complete model revealed an undesirable flat spot in the yawing-moment curves at low angles of attack, the directional stability being neutral for yaw angles of plus-or-minus 2 degrees. This undesirable characteristic was improved by replacing the thick original vertical tail with a thin vertical tail and by flattening the top of the dorsal fairing.

Stimulus Control: The Sought or Unsought Influence of the Objects We Tend to

ERIC Educational Resources Information Center

Morsella, Ezequiel; Larson, Lindsay R. L.; Zarolia, Pareezad; Bargh, John A.

2011-01-01

Does the mere presence of the things we have tended to influence our actions systematically, in ways that escape our awareness? For example, while entering a tool shed, does perceiving objects that we once tended to (e.g., tools, musical instruments) influence how we then execute a simple action (e.g., flicking the shed's light switch)? Ancient…

Development of a Math Input Interface with Flick Operation for Mobile Devices

ERIC Educational Resources Information Center

Nakamura, Yasuyuki; Nakahara, Takahiro

2016-01-01

Developing online test environments for e-learning for mobile devices will be useful to increase drill practice opportunities. In order to provide a drill practice environment for calculus using an online math test system, such as STACK, we develop a flickable math input interface that can be easily used on mobile devices. The number of taps…

"Giving Guilt the Flick"?: An Investigation of Mothers' Talk about Guilt in Relation to Infant Feeding

ERIC Educational Resources Information Center

Williams, Kate; Donaghue, Ngaire; Kurz, Tim

2013-01-01

Manuals offering advice to new parents on the topic of infant feeding have recently begun to attend to the possible implications of pro-breast-feeding discourses for mothers' subjective experiences, particularly with respect to guilt. In this article, we present a discursive analysis of focus groups with 35 Australian mothers in which we examine…

Geo-Semantic Framework for Integrating Long-Tail Data and Model Resources for Advancing Earth System Science

NASA Astrophysics Data System (ADS)

Elag, M.; Kumar, P.

2014-12-01

Often, scientists and small research groups collect data, which target to address issues and have limited geographic or temporal range. A large number of such collections together constitute a large database that is of immense value to Earth Science studies. Complexity of integrating these data include heterogeneity in dimensions, coordinate systems, scales, variables, providers, users and contexts. They have been defined as long-tail data. Similarly, we use "long-tail models" to characterize a heterogeneous collection of models and/or modules developed for targeted problems by individuals and small groups, which together provide a large valuable collection. Complexity of integrating across these models include differing variable names and units for the same concept, model runs at different time steps and spatial resolution, use of differing naming and reference conventions, etc. Ability to "integrate long-tail models and data" will provide an opportunity for the interoperability and reusability of communities' resources, where not only models can be combined in a workflow, but each model will be able to discover and (re)use data in application specific context of space, time and questions. This capability is essential to represent, understand, predict, and manage heterogeneous and interconnected processes and activities by harnessing the complex, heterogeneous, and extensive set of distributed resources. Because of the staggering production rate of long-tail models and data resulting from the advances in computational, sensing, and information technologies, an important challenge arises: how can geoinformatics bring together these resources seamlessly, given the inherent complexity among model and data resources that span across various domains. We will present a semantic-based framework to support integration of "long-tail" models and data. This builds on existing technologies including: (i) SEAD (Sustainable Environmental Actionable Data) which supports curation and preservation of long-tail data during its life-cycle; (ii) BrownDog, which enhances the machine interpretability of large unstructured and uncurated data; and (iii) CSDMS (Community Surface Dynamics Modeling System), which "componentizes" models by providing plug-and-play environment for models integration.

Velocity autocorrelation function in supercooled liquids: Long-time tails and anomalous shear-wave propagation.

PubMed

Peng, H L; Schober, H R; Voigtmann, Th

2016-12-01

Molecular dynamic simulations are performed to reveal the long-time behavior of the velocity autocorrelation function (VAF) by utilizing the finite-size effect in a Lennard-Jones binary mixture. Whereas in normal liquids the classical positive t^{-3/2} long-time tail is observed, we find in supercooled liquids a negative tail. It is strongly influenced by the transfer of the transverse current wave across the period boundary. The t^{-5/2} decay of the negative long-time tail is confirmed in the spectrum of VAF. Modeling the long-time transverse current within a generalized Maxwell model, we reproduce the negative long-time tail of the VAF, but with a slower algebraic t^{-2} decay.

A hybrid pareto mixture for conditional asymmetric fat-tailed distributions.

PubMed

Carreau, Julie; Bengio, Yoshua

2009-07-01

In many cases, we observe some variables X that contain predictive information over a scalar variable of interest Y , with (X,Y) pairs observed in a training set. We can take advantage of this information to estimate the conditional density p(Y|X = x). In this paper, we propose a conditional mixture model with hybrid Pareto components to estimate p(Y|X = x). The hybrid Pareto is a Gaussian whose upper tail has been replaced by a generalized Pareto tail. A third parameter, in addition to the location and spread parameters of the Gaussian, controls the heaviness of the upper tail. Using the hybrid Pareto in a mixture model results in a nonparametric estimator that can adapt to multimodality, asymmetry, and heavy tails. A conditional density estimator is built by modeling the parameters of the mixture estimator as functions of X. We use a neural network to implement these functions. Such conditional density estimators have important applications in many domains such as finance and insurance. We show experimentally that this novel approach better models the conditional density in terms of likelihood, compared to competing algorithms: conditional mixture models with other types of components and a classical kernel-based nonparametric model.

AGES OF STAR CLUSTERS IN THE TIDAL TAILS OF MERGING GALAXIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulia, A. J.; Chandar, R.; Whitmore, B. C.

We study the stellar content in the tidal tails of three nearby merging galaxies, NGC 520, NGC 2623, and NGC 3256, using BVI imaging taken with the Advanced Camera for Surveys on board the Hubble Space Telescope. The tidal tails in all three systems contain compact and fairly massive young star clusters, embedded in a sea of diffuse, unresolved stellar light. We compare the measured colors and luminosities with predictions from population synthesis models to estimate cluster ages and find that clusters began forming in tidal tails during or shortly after the formation of the tails themselves. We find amore » lack of very young clusters (≤10 Myr old), implying that eventually star formation shuts off in the tails as the gas is used up or dispersed. There are a few clusters in each tail with estimated ages that are older than the modeled tails themselves, suggesting that these may have been stripped out from the original galaxy disks. The luminosity function of the tail clusters can be described by a single power-law, dN/dL ∝ L{sup α}, with −2.6 < α < −2.0. We find a stellar age gradient across some of the tidal tails, which we interpret as a superposition of (1) newly formed stars and clusters along the dense center of the tail and (2) a sea of broadly distributed, older stellar material ejected from the progenitor galaxies.« less

Aerodynamic characteristics of a canard-controlled missile at Mach numbers of 1.5 and 2.0.

NASA Technical Reports Server (NTRS)

Kassner, D. L.; Wettlaufer, B.

1977-01-01

A typical missile model with nose mounted canards and cruciform tail surfaces was tested in the Ames 6- by 6-Foot Wind Tunnel to determine the contributions of the component aerodynamic surfaces to the static aerodynamic characteristics at Mach numbers of 1.5 and 2.0 and Reynolds number of 1 million based on body diameter. Data were obtained at angles of attack ranging from -3 deg to 12 deg for various stages of model build-up (i.e., with and without canard and/or tail surfaces). Results were obtained both with the model unrolled and rolled 45 deg. For the canard and tail arrangements investigated, the model was trimmable at angles of attack up to about 10 deg with canard deflections of 9 deg. Also, the tail arrangements studied provided ample pitch stability. there were no appreciable effects of model roll orientation.

Attenuation of tolerance to opioid-induced antinociception and protection against morphine-induced decrease of neurofilament proteins by idazoxan and other I2-imidazoline ligands.

PubMed

Boronat, M A; Olmos, G; García-Sevilla, J A

1998-09-01

1. Agmatine, the proposed endogenous ligand for imidazoline receptors, has been shown to attenuate tolerance to morphine-induced antinociception (Kolesnikov el al., 1996). The main aim of this study was to assess if idazoxan, an alpha2-adrenoceptor antagonist that also interacts with imidazoline receptors, could also modulate opioid tolerance in rats and to establish which type of imidazoline receptors (or other receptors) are involved. 2. Antinociceptive responses to opioid drugs were determined by the tail-flick test. The acute administration of morphine (10 mg kg(-1), i.p., 30 min) or pentazocine (10 mg kg(-1), i.p., 30 min) resulted in marked increases in tail-flick latencies (TFLs). As expected, the initial antinociceptive response to the opiates was lost after chronic (13 days) treatment (tolerance). When idazoxan (10 mg kg(-1), i.p.) was given chronically 30 min before the opiates it completely prevented morphine tolerance and markedly attenuated tolerance to pentazocine (TFLs increased by 71-143% at day 13). Idazoxan alone did not modify TFLs. 3. The concurrent chronic administration (10 mg kg(-1), i.p., 13 days) of 2-BFI, LSL 60101, and LSL 61122 (valldemossine), selective and potent I2-imidazoline receptor ligands, and morphine (10 mg kg(-1), i.p.), also prevented or attenuated morphine tolerance (TFLs increased by 64 172% at day 13). This attenuation of morphine tolerance was still apparent six days after discontinuation of the chronic treatment with LSL 60101-morphine. The acute treatment with these drugs did not potentiate morphine-induced antinociception. These drugs alone did not modify TFLs. Together, these results indicated the specific involvement of I2-imidazoline receptors in the modulation of opioid tolerance. 4. The concurrent chronic (13 days) administration of RX821002 (10 mg kg(-1), i.p.) and RS-15385-197 (1 mg kg(-1), i.p.), selective alpha2-adrenoceptor antagonists, and morphine (10 mg kg(-1), i.p.), did not attenuate morphine tolerance. Similarly, the concurrent chronic treatment of moxonidine (1 mg kg(-1), i.p.), a mixed I(1)-imidazoline receptor and alpha2-adrenoceptor agonist, and morphine (10 mg kg(-1), i.p.), did not alter the development of tolerance to the opiate. These results discounted the involvement of alpha2-adrenoceptors and I(1)-imidazoline receptors in the modulatory effect of idazoxan on opioid tolerance. 5. Idazoxan and other imidazol(ine) drugs fully inhibited [3H]-(+)-MK-801 binding to N-methyl-D-aspartate (NMDA) receptors in the rat cerebral cortex with low potencies (Ki: 37-190 microM). The potencies of the imidazolines idazoxan, RX821002 and moxonidine were similar, indicating a lack of relationship between potency on NMDA receptors and ability to attenuate opioid tolerance. These results suggested that modulation of opioid tolerance by idazoxan is not related to NMDA receptors blockade. 6. Chronic treatment (13 days) with morphine (10 mg kg(-1), i.p.) was associated with a marked decrease (49%) in immunolabelled neurofilament proteins (NF-L) in the frontal cortex of morphine-tolerant rats, suggesting the induction of neuronal damage. Chronic treatment (13 days) with idazoxan (10 mg kg(-1)) and LSL 60101 (10 mg kg(-1)) did not modify the levels of NF-L proteins in brain. Interestingly, the concurrent chronic treatment (13 days) of idazoxan or LSL 60101 and morphine, completely reversed the morphine-induced decrease in NF-L immunoreactivity, suggesting a neuroprotective role for these drugs. 7. Together, the results indicate that chronic treatment with I2-imidazoline ligands attenuates the development of tolerance to opiate drugs and may induce neuroprotective effects on chronic opiate treatment. Moreover, these findings offer the I2-imidazoline ligands as promising therapeutic coadjuvants in the management of chronic pain with opiate drugs.

A feasibility study regarding the addition of a fifth control to a rotorcraft in-flight simulator

NASA Technical Reports Server (NTRS)

Turner, Simon; Andrisani, Dominick, II

1992-01-01

The addition of a large movable horizontal tail surface to the control system of a rotorcraft in-flight simulator being developed from a Sikorsky UH-60A Black Hawk Helicopter is evaluated. The capabilities of the control surface as a trim control and as an active control are explored. The helicopter dynamics are modeled using the Generic Helicopter simulation program developed by Sikorsky Aircraft. The effect of the horizontal tail on the helicopter trim envelope is examined by plotting trim maps of the aircraft attitude and controls as a function of the flight speed and horizontal tail incidence. The control power of the tail surface relative to that of the other controls is examined by comparing control derivatives extracted from the simulation program over the flight speed envelope. The horizontal tail's contribution as an active control is evaluated using an explicit model following control synthesis involving a linear model of the helicopter in steady, level flight at a flight speed of eighty knots. The horizontal tail is found to provide additional control flexibility in the longitudinal axis. As a trim control, it provides effective control of the trim pitch attitude at mid to high forward speeds. As an active control, the horizontal tail provides useful pitching moment generating capabilities at mid to high forward speeds.

Anomalous transport in fracture networks: field scale experiments and modelling

NASA Astrophysics Data System (ADS)

Kang, P. K.; Le Borgne, T.; Bour, O.; Dentz, M.; Juanes, R.

2012-12-01

Anomalous transport is widely observed in different settings and scales of transport through porous and fractured geologic media. A common signature of anomalous transport is the late-time power law tailing in breakthrough curves (BTCs) during tracer tests. Various conceptual models of anomalous transport have been proposed, including multirate mass transfer, continuous time random walk, and stream tube models. Since different conceptual models can produce equally good fits to a single BTC, tracer test interpretation has been plagued with ambiguity. Here, we propose to resolve such ambiguity by analyzing BTCs obtained from both convergent and push-pull flow configurations at two different fracture planes. We conducted field tracer tests in a fractured granite formation close to Ploemeur, France. We observe that BTC tailing depends on the flow configuration and the injection fracture. Specifically the tailing disappears under push-pull geometry, and when we injected at a fracture with high flux (Figure 1). This indicates that for this fractured granite, BTC tailing is controlled by heterogeneous advection and not by matrix diffusion. To explain the change in tailing behavior for different flow configurations, we employ a simple lattice network model with heterogeneous conductivity distribution. The model assigns random conductivities to the fractures and solves the Darcy equation for an incompressible fluid, enforcing mass conservation at fracture intersections. The mass conservation constraint yields a correlated random flow through the fracture system. We investigate whether BTC tailing can be explained by the spatial distribution of preferential flow paths and stagnation zones, which is controlled by the conductivity variance and correlation length. By combining the results from the field tests and numerical modeling, we show that the reversibility of spreading is a key mechanism that needs to be captured. We also demonstrate the dominant role of the injection fracture on the tailing behavior: where we inject makes the difference in the tailing. Blue line is a BTC with injection into a slow velocity zone under convergent flow configuration. The late-time tailing observed for the convergent test diminished for push-pull experiment performed in the same zone(red line). Black line is a BTC with injection into a high velocity zone under convergent flow configuration. Insets: illustration of convergent and push-pull tracer tests using a double packer system.

Time interval between successive trading in foreign currency market: from microscopic to macroscopic

NASA Astrophysics Data System (ADS)

Sato, Aki-Hiro

2004-12-01

Recently, it has been shown that inter-transaction interval (ITI) distribution of foreign currency rates has a fat tail. In order to understand the statistical property of the ITI dealer model with N interactive agents is proposed. From numerical simulations it is confirmed that the ITI distribution of the dealer model has a power law tail. The random multiplicative process (RMP) can be approximately derived from the ITI of the dealer model. Consequently, we conclude that the power law tail of the ITI distribution of the dealer model is a result of the RMP.

Experiments on a Tail-wheel Shimmy

NASA Technical Reports Server (NTRS)

Harling, R; Dietz, O

1954-01-01

Model tests on the "running belt" and tests with a full-scale tail wheel were made on a rotating drum as well as on a runway in order to investigate the causes of the undesirable shimmy phenomena frequently occurring on airplane tail wheels, and the means of avoiding them. The small model (scale 1:10) permitted simulation of the mass, moments of inertia, and fuselage stiffness of the airplane and determination of their influence on the shimmy, whereas by means of the larger model with pneumatic tires (scale 1:2) more accurate investigations were made on the tail wheel itself. The results of drum and road tests show good agreement with one another and with model values. Detailed investigations were made regarding the dependence of the shimmy tendency on trail, rolling speed, load, size of tires, ground friction,and inclination of the swivel axis; furthermore, regarding the influence of devices with restoring effect on the tail wheel, and the friction damping required for prevention of shimmy. Finally observations from slow-motion pictures are reported and conclusions drawn concerning the influence of tire deformation.

Wind-Tunnel Investigation of Effects of Unsymmetrical Horizontal-Tail Arrangements on Power-on Static Longitudinal Stability of a Single-Engine Airplane Model

NASA Technical Reports Server (NTRS)

Purser, Paul E.; Spear, Margaret F.

1947-01-01

A wind-tunnel investigation has been made to determine the effects of unsymmetrical horizontal-tail arrangements on the power-on static longitudinal stability of a single-engine single-rotation airplane model. Although the tests and analyses showed that extreme asymmetry in the horizontal tail indicated a reduction in power effects on longitudinal stability for single-engine single-rotation airplanes, the particular "practical" arrangement tested did not show marked improvement. Differences in average downwash between the normal tail arrangement and various other tail arrangements estimated from computed values of propeller-slipstream rotation agreed with values estimated from pitching-moment test data for the flaps-up condition (low thrust and torque) and disagreed for the flaps-down condition (high thrust and torque). This disagreement indicated the necessity for continued research to determine the characteristics of the slip-stream behind various propeller-fuselage-wing combinations. Out-of-trim lateral forces and moments of the unsymmetrical tail arrangements that were best from consideration of longitudinal stability were no greater than those of the normal tail arrangement.

A coupled modelling effort to study the fate of contaminated sediments downstream of the Coles Hill deposit, Virginia, USA

NASA Astrophysics Data System (ADS)

Castro-Bolinaga, C. F.; Zavaleta, E. R.; Diplas, P.

2015-03-01

This paper presents the preliminary results of a coupled modelling effort to study the fate of tailings (radioactive waste-by product) downstream of the Coles Hill uranium deposit located in Virginia, USA. The implementation of the overall modelling process includes a one-dimensional hydraulic model to qualitatively characterize the sediment transport process under severe flooding conditions downstream of the potential mining site, a two-dimensional ANSYS Fluent model to simulate the release of tailings from a containment cell located partially above the local ground surface into the nearby streams, and a one-dimensional finite-volume sediment transport model to examine the propagation of a tailings sediment pulse in the river network located downstream. The findings of this investigation aim to assist in estimating the potential impacts that tailings would have if they were transported into rivers and reservoirs located downstream of the Coles Hill deposit that serve as municipal drinking water supplies.

Good Teachers (the Movie You Will Never See)

ERIC Educational Resources Information Center

Gillard, Colleen

2012-01-01

It began with a trip to the cinema to see Cameron Diaz in her new comedy, "Bad Teacher." It was a bad choice. Not a great flick, but as a parody of bad employees, in terms of things that can get one fired--drugs, alcohol , cheating, foul language, inappropriate sexual behavior--Diaz slams pedal to the metal. She nips out of airline booze bottles…

Actin-based propulsion of a microswimmer.

PubMed

Leshansky, A M

2006-07-01

A simple hydrodynamic model of actin-based propulsion of microparticles in dilute cell-free cytoplasmic extracts is presented. Under the basic assumption that actin polymerization at the particle surface acts as a force dipole, pushing apart the load and the free (nonanchored) actin tail, the propulsive velocity of the microparticle is determined as a function of the tail length, porosity, and particle shape. The anticipated velocities of the cargo displacement and the rearward motion of the tail are in good agreement with recently reported results of biomimetic experiments. A more detailed analysis of the particle-tail hydrodynamic interaction is presented and compared to the prediction of the simplified model.

Parametric Study of Synthetic-Jet-Based Flow Control on a Vertical Tail Model

NASA Astrophysics Data System (ADS)

Monastero, Marianne; Lindstrom, Annika; Beyar, Michael; Amitay, Michael

2015-11-01

Separation control over the rudder of the vertical tail of a commercial airplane using synthetic-jet-based flow control can lead to a reduction in tail size, with an associated decrease in drag and increase in fuel savings. A parametric, experimental study was undertaken using an array of finite span synthetic jets to investigate the sensitivity of the enhanced vertical tail side force to jet parameters, such as jet spanwise spacing and jet momentum coefficient. A generic wind tunnel model was designed and fabricated to fundamentally study the effects of the jet parameters at varying rudder deflection and model sideslip angles. Wind tunnel results obtained from pressure measurements and tuft flow visualization in the Rensselaer Polytechnic Subsonic Wind Tunnel show a decrease in separation severity and increase in model performance in comparison to the baseline, non-actuated case. The sensitivity to various parameters will be presented.

A study of static stability of airships

NASA Technical Reports Server (NTRS)

Rizzo, Frank

1924-01-01

The first section deals with the theoretical side of statical stability of airships in general. The second section deals with preliminary tests of the model and experiments for the determination of effects due to change of tail area, aspect ratio, tail form, and tail thickness.

Mapping eastern equine encephalitis virus risk for white-tailed deer in Michigan

PubMed Central

Downs, Joni A.; Hyzer, Garrett; Marion, Eric; Smith, Zachary J.; Kelen, Patrick Vander; Unnasch, Thomas R.

2015-01-01

Eastern equine encephalitis (EEE) is a mosquito-borne viral disease that is often fatal to humans and horses. Some species including white-tailed deer and passerine birds can survive infection with the EEE virus (EEEV) and develop antibodies that can be detected using laboratory techniques. In this way, collected serum samples from free ranging white-tailed deer can be used to monitor the presence of the virus in ecosystems. This study developed and tested a risk index model designed to predict EEEV activity in white-tailed deer in a three-county area of Michigan. The model evaluates EEEV risk on a continuous scale from 0.0 (no measurable risk) to 1.0 (highest possible risk). High risk habitats are identified as those preferred by white-tailed deer that are also located in close proximity to an abundance of wetlands and lowland forests, which support disease vectors and hosts. The model was developed based on relevant literature and was tested with known locations of infected deer that showed neurological symptoms. The risk index model accurately predicted the known locations, with the mean value for those sites equal to the 94th percentile of values in the study area. The risk map produced by the model could be used refine future EEEV monitoring efforts that use serum samples from free-ranging white-tailed deer to monitor viral activity. Alternatively, it could be used focus educational efforts targeted toward deer hunters that may have elevated risks of infection. PMID:26494931

Wind-Tunnel Investigation at Subsonic and Supersonic Speeds of a Fighter Model Employing a Low-Aspect-Ratio Unswept Wing and a Horizontal Tail Mounted Well Above the Wing Plane - Longitudinal Stability and Control

NASA Technical Reports Server (NTRS)

Smith, Williard G.

1954-01-01

Experimental results showing the static longitudinal-stability and control characteristics of a model of a fighter airplane employing a low-aspect-ratio unswept wing and an all-movable horizontal tail are presented. The investigation was made over a Mach number range from 0.60 to 0.90 and from 1.35 to 1.90 at a constant Reynolds number of 2.40 million, based on the wing mean aerodynamic chord. Because of the location of the horizontal tail at the tip of the vertical tail, interference was noted between the vertical tail and the horizontal tail and between the wing and the horizontal tail. This interference produced a positive pitching-moment coefficient at zero lift throughout the Mach number range of the tests, reduced the change in stability with increasing lift coefficient of the wing at moderate lift coefficients in the subsonic speed range, and reduced the stability at low lift coefficients at high supersonic speeds. The lift and pitching-moment effectiveness of the all movable tail was unaffected by the interference effects and was constant throughout the lift-coefficient range of the tests at each Mach number except 1.90.

Inspiration from nature: dynamic modelling of the musculoskeletal structure of the seahorse tail.

PubMed

Praet, Tomas; Adriaens, Dominique; Van Cauter, Sofie; Masschaele, Bert; De Beule, Matthieu; Verhegghe, Benedict

2012-10-01

Technological advances are often inspired by nature, considering that engineering is frequently faced by the same challenges as organisms in nature. One such interesting challenge is creating a structure that is at the same time stiff in a certain direction, yet flexible in another. The seahorse tail combines both radial stiffness and bending flexibility in a particularly elegant way: even though the tail is covered in a protective armour, it still shows sufficient flexibility to fully function as a prehensile organ. We therefore study the complex mechanics and dynamics of the musculoskeletal system of the seahorse tail from an engineering point of view. The seahorse tail derives its combination of flexibility and resilience from a chain of articulating skeletal segments. A versatile dynamic model of those segments was constructed, on the basis of automatic recognition of joint positions and muscle attachments. Both muscle structures that are thought to be responsible for ventral and ventral-lateral tail bending, namely the median ventral muscles and the hypaxial myomere muscles, were included in the model. Simulations on the model consist mainly of dynamic multi-body simulations. The results show that the sequential structure of uniformly shaped bony segments can remain flexible because of gliding joints that connect the corners of the segments. Radial stiffness on the other hand is obtained through the support that the central vertebra provides to the tail plating. Such insights could help in designing biomedical instruments that specifically require both high bending flexibility and radial stiffness (e.g. flexible stents and steerable catheters). Copyright © 2012 John Wiley & Sons, Ltd.

Modeling of behavioral responses for successful selection of easy-to-train rams for semen collection with an artificial vagina.

PubMed

Ambrosi, Claudia Pamela; Rubio, Natalia; Giménez, Gustavo; Venturino, Andrés; Aisen, Eduardo Gabriel; López Armengol, María Fernanda

2018-06-01

The aim of this study was to analyze the reproductive behavioral responses in Australian Merino rams, to identify those related to a faster training for semen collection with an artificial vagina. Eight Australian Merino rams, aged 1.5 years and with no prior sexual experience, were randomly selected from an extensively grazed flock. One immobilized ewe with no hormone stimulation was used for rams to sexually interact and mount. The frequencies of approaching, sniffing, flehmen, pushing, pawing with chin resting, and tongue flicking were recorded during eight training and three post-training assessments periods. In addition, the duration of sniffing and flehmen responses, as well as the time from when the ram started to approach the ewe until the mount with ejaculation (completed mount) were recorded. Descriptive, correlation, and modeling analyses were performed. Amongst the rams, four mounted the ewe and ejaculated for the first time during the training phase, and three mounted and ejaculated for the first time after the training phase. The remaining ram mounted the ewe and ejaculated for the first time during the post-training evaluation in the following year. A great variability in the behavior repertoire was observed among rams. The correlation analysis indicated that the completed mount was associated with the behaviors during the approaching response. The expression of the sniffing response decreased between the training phase and post-training evaluation, while the responses of pushing the ewe and tongue flicking ceased to occur. Pawing the side of the ewe with the chin resting on the back of the ewe and flehmen responses, however, continued between the training and post-training phases. This led to a decrease in the time from when the ram started to approach the ewe until the completed mount. It is concluded that the responses of approaching the ewe, pawing the side of the ewe with chin resting on the ewe, and sniffing of the ewe (the latter occurring only during the training phase) are behavioral indicators that could be used for selection of easy-to-train rams for purposes of semen collection with an artificial vagina. Copyright © 2018 Elsevier B.V. All rights reserved.

High Frequency Tail Characteristics in the Coastal Waters off Gopalpur, Northwest Bay of Bengal: A Nearshore Modelling Study

NASA Astrophysics Data System (ADS)

Umesh, P. A.; Bhaskaran, Prasad K.; Sandhya, K. G.; Nair, T. M. Balakrishnan

2017-12-01

Over the years, continued uncertainty amid - 4 and - 5 frequency exponent representation observed in the slope of the high-frequency tail of a wind-wave frequency spectrum is a major concern. To comprehend the nature of the high-frequency tail an effort has been made to assess the slope of the high-frequency tail with measured data recorded for 3 years off Gopalpur. The study demonstrates that the high-frequency slope of the spectra varied seasonally in the range of n = - 2.13 to - 3.48. The swell and wind sea parameters calculated by separation frequency method, shows that 64.6% of waves were dominant by swell and the rest 34.9% by sea annually. Single, double and multi-peaked spectra occur 12.23, 71.80 and 15.37% annually. To simulate wave spectra, the nested WAM-SWAN model is forced with ERA-Interim winds and 1D wave spectra comparisons, when performed, proved to be encouraging. From the comparisons of measured and theoretical spectra it is concluded that JONSWAP model could not describe the high-frequency tail of measured spectrum, as indicated by the very high Scatter Index ranging from 0.24 to 1.44. Whether there exists a correct slope for the high-frequency tail is still a question. Moreover, the philosophy of a unique slope at any coastal location remains uncertain for the wave modelling community.

Computational Investigation and Validation of Twin-Tail Buffet Response Including Dynamics and Control

NASA Technical Reports Server (NTRS)

Kandil, Osama A.

1998-01-01

Multidisciplinary tools for prediction of single rectangular-tail buffet are extended to single swept-back-tail buffet in transonic-speed flow, and multidisciplinary tools for prediction and control of twin-tail buffet are developed and presented. The configuration model consists of a sharp-edged delta wing with single or twin tails that are oriented normal to the wing surface. The tails are treated as cantilevered beams fixed at the root and allowed to oscillate in both bending and torsion. This complex multidisciplinary problem is solved sequentially using three sets of equations on a dynamic single or multi-block grid structure. The first set is the unsteady, compressible, Reynolds-averaged Navier-Stokes equations which are used for obtaining the flow field vector and the aerodynamic loads on the tails. The Navier-Stokes equations are solved accurately in time using the implicit, upwind, flux-difference splitting, finite volume scheme. The second set is the coupled bending and torsion aeroelastic equations of cantilevered beams which are used for obtaining the bending and torsion deflections of the tails. The aeroelastic equations'are solved accurately in time using, a fifth-order-accurate Runge-Kutta scheme. The third set is the grid-displacement equations and the rigid-body dynamics equations, which are used for updating the grid coordinates due to the tail deflections and rigid-body motions. The tail-buffet phenomenon is predicted for highly-swept, single vertical tail placed at the plane of geometric symmetry, and for highly-swept, vertical twin tails placed at three different spanwise separation distances. The investigation demonstrates the effects of structural inertial coupling and uncoupling of the bending and torsion modes of vibration, spanwise positions of the twin-tail, angle of attack, and pitching and rolling dynamic motions of the configuration model on the tail buffet loading and response. The fundamental issue of twin-tail buffet alleviation is addressed using two active flow-control methods. These methods are the tangential leading-edge blowing and the flow suction from the leading-edge vortex cores along their paths. Qualitative and quantitative comparisons with the available experimental data are presented. The comparisons indicate that the present multidisciplinary aeroelastic analysis tools are robust, accurate and efficient.

Flow Environment Study Near the Empennage of a 15-Percent Scale Helicopter Model

NASA Technical Reports Server (NTRS)

Gorton, Susan Althoff; Berry, John D.; Hodges, W. Todd; Reis, Deane G.

2000-01-01

Development of advanced rotorcraft configurations has highlighted a need for high-quality experimental data to support the development of flexible and accurate analytical design tools. To provide this type of data, a test program was conducted in the Langley 14- by 22-Foot Subsonic Tunnel to measure the flow near the empennage of a 15-percent scale powered helicopter model with an operating tail fan. Three-component velocity profiles were measured with laser velocimetry (LV) one chord forward of the horizontal tail for four advance ratios to evaluate the effect of the rotor wake impingement on the horizontal tail angle of attack. These velocity data indicate the horizontal tail can experience unsteady angle of attack variations of over 30 degrees due to the rotor wake influence. The horizontal tail is most affected by the rotor wake above advance ratios of 0.10. Velocity measurements of the flow on the inlet side of the tail fan were made for a low-speed flight condition using conventional LV techniques. The velocity data show an accelerated flow near the tail fan duct, and vorticity calculations track the passage of main rotor wake vortices through the measurement plane.

Diabetes-causing gene, kruppel-like factor 11, modulates the antinociceptive response of chronic ethanol intake.

PubMed

Ou, Xiao-Ming; Udemgba, Chinelo; Wang, Niping; Dai, Xiaoli; Lomberk, Gwen; Seo, Seungmae; Urrutia, Raul; Wang, Junming; Duncan, Jeremy; Harris, Sharonda; Fairbanks, Carolyn A; Zhang, Xiao

2014-02-01

Alcohol (EtOH [ethanol]) is an antinociceptive agent, working in part, by reducing sensitivity to painful stimuli. The transcription factor Kruppel-like factor 11 (KLF11), a human diabetes-causing gene that also regulates the neurotransmitter metabolic enzymes monoamine oxidase (MAO), has recently been identified as an EtOH-inducible gene. However, its role in antinociception remains unknown. Consequently, we investigated the function of KLF11 in chronic EtOH-induced antinociception using a genetically engineered knockout mouse model. Wild-type (Klf11(+/+) ) and KLF11 knockout (Klf11(-/-) ) mice were fed a liquid diet containing EtOH for 28 days with increasing amounts of EtOH from 0% up to a final concentration of 6.4%, representing a final diet containing 36% of calories primarily from EtOH. Control mice from both genotypes were fed liquid diet without EtOH for 28 days. The EtOH-induced antinociceptive effect was determined using the tail-flick test before and after EtOH exposure (on day 29). In addition, the enzyme activity and mRNA levels of MAO A and MAO B were measured by real-time RT-PCR and enzyme assays, respectively. EtOH produced an antinociceptive response to thermal pain in Klf11(+/+) mice, as expected. In contrast, deletion of KLF11 in the Klf11(-/-) mice abolished the EtOH-induced antinociceptive effect. The mRNA and protein levels of KLF11 were significantly increased in the brain prefrontal cortex of Klf11(+/+) mice exposed to EtOH compared with control Klf11(+/+) mice. Furthermore, MAO enzyme activities were affected differently in Klf11 wild-type versus Klf11 knockout mice exposed to chronic EtOH. Chronic EtOH intake significantly increased MAO B activity in Klf11(+/+) mice. The data show KLF11 modulation of EtOH-induced antinociception. The KLF11-targeted MAO B enzyme may contribute more significantly to EtOH-induced antinociception. Thus, this study revealed a new role for the KLF11 gene in the mechanisms underlying the antinociceptive effects of chronic EtOH exposure. Copyright © 2013 by the Research Society on Alcoholism.

Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats.

PubMed

Fatani, Amal Jamil; Al-Rejaie, Salim Salih; Abuohashish, Hatem Mustafa; Al-Assaf, Abdullah; Parmar, Mihir Yogeshkumar; Ola, Mohammad Shamsul; Ahmed, Mohammed Mahboobuddin

2015-05-01

The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators.

Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

PubMed Central

FATANI, AMAL JAMIL; AL-REJAIE, SALIM SALIH; ABUOHASHISH, HATEM MUSTAFA; AL-ASSAF, ABDULLAH; PARMAR, MIHIR YOGESHKUMAR; OLA, MOHAMMAD SHAMSUL; AHMED, MOHAMMED MAHBOOBUDDIN

2015-01-01

The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators. PMID:26136876

Diabetes Causing Gene, Kruppel-Like Factor 11, Modulates the Antinociceptive Response of Chronic Ethanol Intake

PubMed Central

Ou, Xiao-Ming; Udemgba, Chinelo; Wang, Niping; Dai, Xiaoli; Lomberk, Gwen; Seo, Seungmae; Urrutia, Raul; Wang, Junming; Duncan, Jeremy; Harris, Sharonda; Fairbanks, Carolyn A.; Zhang, Xiao

2017-01-01

Background Alcohol (ethanol) is an antinociceptive agent, working in part, by reducing sensitivity to painful stimuli. The transcription factor, Kruppel-like factor 11 (KLF11), a human diabetes-causing gene that also regulates the neurotransmitter-metabolic enzymes monoamine oxidase (MAOs), has recently been identified as an ethanol-inducible gene. However, its role in antinociception remains unknown. Consequently, we investigated the function of KLF11 in chronic ethanol-induced antinociception using a genetically engineered knockout mouse model. Methods Wild-type (Klf11+/+) and KLF11 knockout (Klf11−/−) mice were fed a liquid diet containing ethanol for 28 days with increasing amounts of ethanol from 0% up to a final concentration of 6.4%, representing a final diet containing 36% of calories primarily from ethanol. Control mice from both genotypes were fed liquid diet without ethanol for 28 days. The ethanol-induced antinociceptive effect was determined using the tail-flick test before and after ethanol exposure (on day 29). In addition, the enzyme activity and mRNA levels of MAO A and MAO B were measured by Real-time RT-PCR and enzyme assays, respectively. Results Ethanol produced an antinociceptive response to thermal pain in Klf11+/+ mice, as expected. In contrast, deletion of KLF11 in the Klf11−/− mice abolished the ethanol-induced antinociceptive effect. The mRNA and protein levels of KLF11were significantly increased in the brain prefrontal cortex of Klf11+/+ mice exposed to ethanol compared to control Klf11+/+ mice. Furthermore, MAO enzyme activities were affected differently in Klf11 wild-type versus Klf11 knockout mice exposed to chronic ethanol. Chronic ethanol intake significantly increased MAO-B activity in Klf1+/+ mice. Conclusions The data show KLF11 modulation of ethanol-induced antinociception. The KLF11-targeted MAO B enzyme, may contribute more significantly to ethanol-induced antinociception. Thus, this study revealed a new role for the KLF11 gene in the mechanisms underlying the antinociceptive effects of chronic ethanol exposure. PMID:24428663

Spectral properties of the Preisach hysteresis model with random input. II. Universality classes for symmetric elementary loops

NASA Astrophysics Data System (ADS)

Radons, Günter

2008-06-01

The Preisach model with symmetric elementary hysteresis loops and uncorrelated input is treated analytically in detail. It is shown that the appearance of long-time tails in the output correlations is a quite general feature of this model. The exponent η of the algebraic decay t-η , which may take any positive value, is determined by the tails of the input and the Preisach density. We identify the system classes leading to identical algebraic tails. These results imply the occurrence of 1/f noise for a large class of hysteretic systems.

A comparative study of the tail ion distribution with reduced Fokker-Planck models

NASA Astrophysics Data System (ADS)

McDevitt, C. J.; Tang, Xian-Zhu; Guo, Zehua; Berk, H. L.

2014-03-01

A series of reduced models are used to study the fast ion tail in the vicinity of a transition layer between plasmas at disparate temperatures and densities, which is typical of the gas and pusher interface in inertial confinement fusion targets. Emphasis is placed on utilizing progressively more comprehensive models in order to identify the essential physics for computing the fast ion tail at energies comparable to the Gamow peak. The resulting fast ion tail distribution is subsequently used to compute the fusion reactivity as a function of collisionality and temperature. While a significant reduction of the fusion reactivity in the hot spot compared to the nominal Maxwellian case is present, this reduction is found to be partially recovered by an increase of the fusion reactivity in the neighboring cold region.

Wind-Tunnel Tests of the 1/9-Scale Model of the Curtiss XP-62 Airplane with Various Vertical Tail Arrangements

NASA Technical Reports Server (NTRS)

Wallace, Arthur R.; Recant, I.G.

1943-01-01

The effect of various vertical tail arrangements upon the stability and control characteristics of an XP-62 fighter model was investigated. Rudder-free yaw characteristics with take-off power and flaps deflected were satisfactory after dorsal fin modifications. Directional stability was obtained with all modified vertical tails. Satisfactory rudder effectiveness resulted partly because the dual-rotation propellers produced no asymmetric yawing moments. Pedal forces in sideslips were undesirably large but may be easily reduced.

Trends in Human-Computer Interaction to Support Future Intelligence Analysis Capabilities

DTIC Science & Technology

2011-06-01

that allows data to be moved between different computing systems and displays. Figure 4- G-Speak gesture interaction (Oblong, 2011) 5.2 Multitouch ... Multitouch refers to a touchscreen interaction technique in which multiple simultaneous touchpoints and movements can be detected and used to...much of the style of interaction (such as rotate, pinch, zoom and flick movements) found in multitouch devices but can typically recognize more than

Chemosensory age discrimination in the snake Boa constrictor (Serpentes: Boidae).

PubMed

Gabirot, Marianne; Picerno, Pablo; Valencia, Jorge; Lopez, Pilar; Martin, José

2012-12-01

Many snakes are able to use their chemosensory system to detect scent of conspecifics, which is important in many social contexts. Age discrimination based on chemical cues may be especially important to ensure access to sexually mature potential partners. In this study, we used 24 individual Boa constrictor snakes (12 adults mature and 12 non-mature individuals) that had been captured in different areas of Ecuador, and were maintained in captivity at the Vivarium of Quito. We used tongue-flick experiments to examine whether these snakes were able to discriminate between scents from mature and non-mature individuals. Results showed that B. constrictor snakes used chemical cues to recognize conspecifics and that the scent of individuals of different ages elicited chemosensory responses of different magnitudes. The scents from adult conspecifics elicited the quickest and highest chemosensory responses (i.e., short latency times and high tongue-flick rates), although we did not find differential responses to scent of males and females. The magnitude of the responses was lower to scent of sub adult individuals, and then even lower to scent of juvenile snakes, but in all cases the scent of snakes was discriminated from a blank control. We discuss the potential chemical mechanisms that may allow age recognition and its implications for social and sexual behavior of this snake species.

The magnetosphere of Neptune - Its response to daily rotation

NASA Technical Reports Server (NTRS)

Voigt, Gerd-Hannes; Ness, Norman F.

1990-01-01

The Neptunian magnetosphere periodically changes every eight hours between a pole-on magnetosphere with only one polar cusp and an earth-type magnetosphere with two polar cusps. In the pole-on configuration, the tail current sheet has an almost circular shape with plasma currents closing entirely within the magnetosphere. Eight hours later the tail current sheet assumes an almost flat shape with plasma currents touching the magnetotail boundary and closing over the tail magnetopause. Magnetic field and tail current sheet configurations have been calculated in a three-dimensional model, but the plasma- and thermodynamic conditions were investigated in a simplified two-dimensional MHD equilibrium magnetosphere. It was found that the free energy in the tail region of the two-dimensional model becomes independent of the dipole tilt angle. It is conjectured that the Neptunian magnetotail might assume quasi-static equilibrium states that make the free energy of the system independent of its daily rotation.

Activation of Brainstem Pro-opiomelanocortin Neurons Produces Opioidergic Analgesia, Bradycardia and Bradypnoea

PubMed Central

Hirschberg, Stefan; Hill, Rob; Balthasar, Nina; Pickering, Anthony E.

2016-01-01

Opioids are widely used medicinally as analgesics and abused for hedonic effects, actions that are each complicated by substantial risks such as cardiorespiratory depression. These drugs mimic peptides such as β-endorphin, which has a key role in endogenous analgesia. The β-endorphin in the central nervous system originates from pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and nucleus of the solitary tract (NTS). Relatively little is known about the NTSPOMC neurons but their position within the sensory nucleus of the vagus led us to test the hypothesis that they play a role in modulation of cardiorespiratory and nociceptive control. The NTSPOMC neurons were targeted using viral vectors in a POMC-Cre mouse line to express either opto-genetic (channelrhodopsin-2) or chemo-genetic (Pharmacologically Selective Actuator Modules). Opto-genetic activation of the NTSPOMC neurons in the working heart brainstem preparation (n = 21) evoked a reliable, titratable and time-locked respiratory inhibition (120% increase in inter-breath interval) with a bradycardia (125±26 beats per minute) and augmented respiratory sinus arrhythmia (58% increase). Chemo-genetic activation of NTSPOMC neurons in vivo was anti-nociceptive in the tail flick assay (latency increased by 126±65%, p<0.001; n = 8). All effects of NTSPOMC activation were blocked by systemic naloxone (opioid antagonist) but not by SHU9119 (melanocortin receptor antagonist). The NTSPOMC neurons were found to project to key brainstem structures involved in cardiorespiratory control (nucleus ambiguus and ventral respiratory group) and endogenous analgesia (periaqueductal gray and midline raphe). Thus the NTSPOMC neurons may be capable of tuning behaviour by an opioidergic modulation of nociceptive, respiratory and cardiac control. PMID:27077912

Attenuation of Morphine-Induced Tolerance and Dependence by Pretreatment with Cerebrolysin in Male rats.

PubMed

Ghavimi, Hamed; Darvishi, Sara; Ghanbarzadeh, Saeed

2018-01-01

Dependence and tolerance to morphine are major problems which limit its chronic clinical application. This study was aimed to investigate the attenuation effect of Cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,), on the development of Morphine-induced dependence and tolerance. Male Wistar rats were selected randomly and divided into different groups (n=8) including: a control group, groups received additive doses of morphine (5-25 mg/kg, ip, at an interval of 12 h until tolerance completion), and groups pretreated with Cerebrolysin (40, 80 and 160 mg/kg, ip, before morphine administration). Development of tolerance was assessed by tail-flick test and the attenuation effect of Cerebrolysin on morphine-induced dependence was evaluated after injection of naloxone (4 mg/kg, ip, 12 h after the morning dose of morphine). Seven distinct withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, wet dog shake and teeth grinding were recorded for 45 min and total withdrawal score (TWS) was calculated. Results showed that administration of Cerebrolysin could prolonged development (10 and 14 days in administration of 80 mg/kg and 160 mg/kg Cerebrolysin) and completion (4, 10 and 14 days in administration of 40, 80 and 160 mg/kg Cerebrolysin, respectively) of tolerance. Results also indicated that administration of Cerebrolysin (40, 80 and 160 mg/kg) could significantly decreased the TWS value (62±2, 77±4 and 85±6%, respectively). In conclusion, it was found that pretreatment with Cerebrolysin could attenuated morphine-induced tolerance and dependence. © Georg Thieme Verlag KG Stuttgart · New York.

Dextromethorphan differentially affects opioid antinociception in rats

PubMed Central

Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh

2005-01-01

Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510

Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.

PubMed

Allen, Kyle D; Griffin, Timothy M; Rodriguiz, Ramona M; Wetsel, William C; Kraus, Virginia B; Huebner, Janet L; Boyd, Lawrence M; Setton, Lori A

2009-09-01

In mice with Col9a1 gene inactivation (Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1(-/-) mice for functional and symptomatic changes that may be associated with these pathologies. Col9a1(-/-) and wild-type mice were investigated for reflexes, functional impairment (beam walking, pole climbing, wire hang, grip strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair), and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance time, stride length, and step width. Postmortem, sera obtained from the mice were analyzed for hyaluronan, and their knees and spines were graded histologically for degeneration. Col9a1(-/-) mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1(-/-) mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire hang, rotarod, and pole climbing tasks. Male Col9a1(-/-) mice had the highest mean serum hyaluronan levels and strong histologic evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1(-/-) mice having an increased incidence of disc tears. These data describe a Col9a1(-/-) behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest that Col9a1(-/-) mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in male mice, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1(-/-) mice present behavioral changes consistent with anatomic signs of OA and intervertebral disc degeneration.

Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active

PubMed Central

Brown, Sarah M.; Holtzman, Michael; Kim, Thomas; Kharasch, Evan D.

2012-01-01

Background The long-lasting high affinity opioid buprenorphine has complex pharmacology including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacological activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine. Methods Competitive inhibition of radioligand binding to human mu, kappa, delta opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in Swiss Webster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing. Results Buprenorphine-3-glucuronide had high affinity for human mu (Ki = 4.9±2.7 pM), delta (Ki = 270±0.4 nM), and nociceptin (Ki = 36±0.3 μM) but not kappa receptors. Norbuprenorphine-3-glucuronide had affinity for human kappa (Ki = 300±0.5 nM) and nociceptin (Ki= 18±0.2 μM) but not mu or delta receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation. Conclusions Both glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine. PMID:22037640

Pregabalin role in inhibition of morphine analgesic tolerance and physical dependency in rats.

PubMed

Hasanein, Parisa; Shakeri, Saeed

2014-11-05

Pregabalin is recently proposed as analgesic or adjuvant in pain management. While previous preclinical investigations have evaluated pregabalin-opioid interactions, the effect of pregabalin on opioid tolerance and dependency has not yet been studied. Here we evaluated the effects of different doses of pregabalin (50, 100 and 200mg/kg, s.c.) on morphine-induced tolerance and dependency in rats. Adult male Wistar rats were rendered tolerant to analgesic effect of morphine by injection of morphine (10mg/kg, s.c.) twice daily for 7 days. To develop morphine dependence, rats were given escalating doses of morphine. To determine the effect of pregabalin on the development of morphine tolerance and dependence, different doses of pregabalin were administrated before morphine. The tail-flick and naloxone precipitation withdrawal tests were used to evaluate the degree of tolerance and dependence, respectively. Chronic morphine-injected rats showed significant decrements in the percentage maximum possible effect (%MPE) of morphine on the days 5 and 7 (32.5%±3.5, 21.5%±4, respectively) compared to the first day (100%) which showed morphine tolerance. Pregabalin 200mg/kg completely prevented the development of morphine tolerance. In addition, concomitant treatment of morphine with pregabalin attenuated almost all of the naloxone-induced withdrawal signs which include weight loss, jumping, penis licking, teeth chattering, wet dog shakes, rearing, standing, sniffing, face grooming and paw tremor. These data show that pregabaline has a potential anti-tolerant/anti-dependence property against chronic usage of morphine. Therefore, pregabalin appears to be a promising candidate for the treatment of opioid addiction after confirming by future clinical studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice.

PubMed

Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Micov, Ana M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-02-25

Antiepileptic and antidepressant drugs are the primary treatments for pain relief in diabetic neuropathy. Combination therapy is a valid approach in pain treatment, where a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. The nociceptive responses in normal and diabetic mice were assessed by the tail-flick test. The testing was performed before and three weeks after the diabetes induction with streptozotocin (150mg/kg; i.p.), when the antinociceptive effects of gabapentin, oxcarbazepine, amitriptyline and their two-drug combinations were examined. Gabapentin (10-40mg/kg; p.o.) and oxcarbazepine (20-80mg/kg; p.o.) produced a significant, dose-dependent antinociception in diabetic mice while amitriptyline (5-60mg/kg; p.o.) produced weak antinociceptive effect. In normal mice, neither of the drugs produced antinociception. Gabapentin and oxcarbazepine, co-administered in fixed-dose fractions of the ED(50) to diabetic mice, induced significant, dose-dependent antinociception. Isobolographic analysis revealed synergistic interaction. Oxcarbazepine (10-60mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) and gabapentin (10-30mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) combinations significantly and dose-dependently reduced nociception in diabetic mice. Analysis of the log dose-response curves for oxcarbazepine or gabapentin in a presence of amitriptyline and oxcarbazepine or gabapentin applied alone, revealed a synergism in oxcarbazepine-amitriptyline and additivity in gabapentin-amitriptyline combination. These findings provide new information about the combination therapy of painful diabetic neuropathy and should be explored further in patients with diabetic neuropathy.

In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection.

PubMed

Marshell, R; Kearney-Ramos, T; Brents, L K; Hyatt, W S; Tai, S; Prather, P L; Fantegrossi, W E

2014-09-01

Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke these drugs, but preclinical studies usually rely on injection for drug delivery. We used the cannabinoid tetrad and drug discrimination to compare in vivo effects of inhaled drugs with injected doses of these two SCBs, as well as with the phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Mice inhaled various doses of Δ(9)-THC, JWH-018 or JWH-073, or were injected intraperitoneally (IP) with these same compounds. Rectal temperature, tail flick latency in response to radiant heat, horizontal bar catalepsy, and suppression of locomotor activity were assessed in each animal. In separate studies, mice were trained to discriminate Δ(9)-THC (IP) from saline, and tests were performed with inhaled or injected doses of the SCBs. Both SCBs elicited Δ(9)-THC-like effects across both routes of administration, and effects following inhalation were attenuated by pretreatment with the CB1 antagonist/inverse agonist rimonabant. No cataleptic effects were observed following inhalation, but all compounds induced catalepsy following injection. Injected JWH-018 and JWH-073 fully substituted for Δ(9)-THC, but substitution was partial (JWH-073) or required relatively higher doses (JWH-018) when drugs were inhaled. These studies demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor-mediated Δ(9)-THC-like effects in mice when delivered via inhalation or via injection. Across these routes of administration, differences in cataleptic effects and, perhaps, discriminative stimulus effects, may implicate the involvement of active metabolites of these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Potentiation of oxycodone antinociception in mice by agmatine and BMS182874 via an imidazoline I2 receptor-mediated mechanism.

PubMed

Bhalla, Shaifali; Ali, Izna; Lee, Hyaera; Andurkar, Shridhar V; Gulati, Anil

2013-01-01

The potentiation of oxycodone antinociception by BMS182874 (endothelin-A (ET(A)) receptor antagonist) and agmatine (imidazoline receptor/α(2)-adrenoceptor agonist) is well-documented. It is also known that imidazoline receptors but not α(2)-adrenoceptors are involved in potentiation of oxycodone antinociception by agmatine and BMS182874 in mice. However, the involvement of specific imidazoline receptor subtypes (I(1), I(2), or both) in this interaction is not clearly understood. The present study was conducted to determine the involvement of imidazoline I(1) and I(2) receptors in agmatine- and BMS182874-induced potentiation of oxycodone antinociception in mice. Antinociceptive (tail flick and hot-plate) latencies were determined in male Swiss Webster mice treated with oxycodone, agmatine, BMS182874, and combined administration of oxycodone with agmatine or BMS182874. Efaroxan (imidazoline I(1) receptor antagonist) and BU224 (imidazoline I(2) receptor antagonist) were used to determine the involvement of I(1) and I(2) imidazoline receptors, respectively. Oxycodone produced significant antinociceptive response in mice which was not affected by efaroxan but was blocked by BU224. Agmatine-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. Similarly, BMS182874-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. This is the first report demonstrating that BMS182874- or agmatine-induced enhancement of oxycodone antinociception is blocked by BU224 but not by efaroxan. We conclude that imidazoline I(2) receptors but not imidazoline I(1) receptors are involved in BMS182874- and agmatine-induced potentiation of oxycodone antinociception in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

CC12, A High Affinity Ligand for 3H-Cimetidine Binding, is an Improgan Antagonist

PubMed Central

Hough, Lindsay B.; Nalwalk, Julia W.; Phillips, James G.; Kern, Brian; Shan, Zhixing; Wentland, Mark P.; de Esch, Iwan J.P.; Janssen, Elwin; Barr, Travis; Stadel, Rebecca

2007-01-01

Summary Improgan, a chemical congener of cimetidine, is a highly effective non-opioid analgesic when injected into the CNS. Despite extensive characterization, neither the improgan receptor, nor a pharmacological antagonist of improgan has been previously described. Presently, the specific binding of 3H-cimetidine (3HCIM) in brain fractions was used to discover 4(5)-((4-iodobenzyl)thiomethyl)-1H-imidazole, which behaved in vivo as the first improgan antagonist. The synthesis and pharmacological properties of this drug (named CC12) are described herein. In rats, CC12 (50 – 500 nmol, icv) produced dose-dependent inhibition of improgan (200 – 400 nmol) antinociception on the tail flick and hot plate tests. When given alone to rats, CC12 had no effects on nociceptive latencies, or on other observable behavioral or motor functions. Maximal inhibitory effects of CC12 (500 nmol) were fully surmounted with a large icv dose of improgan (800 nmol), demonstrating competitive antagonism. In mice, CC12 (200-400 nmol, icv) behaved as a partial agonist, producing incomplete improgan antagonism, but also limited antinociception when given alone. Radioligand binding, receptor autoradiography, and electrophysiology experiments showed that CC12's antagonist properties are not explained by activity at 25 sites relevant to analgesia, including known receptors for cannabinoids, opioids or histamine. The use of CC12 as an improgan antagonist will facilitate the characterization of improgan analgesia. Furthermore, because CC12 was also found presently to inhibit opioid and cannabinoid antinociception, it is suggested that this drug modifies a biochemical mechanism shared by several classes of analgesics. Elucidation of this mechanism will enhance understanding of the biochemistry of pain relief. PMID:17336343

Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

PubMed

Sumathi, Thangarajan; Christinal, Johnson

2016-07-01

Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity.

Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

PubMed Central

Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

2009-01-01

Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

The effect of forced swim stress on morphine sensitization: Involvement of D1/D2-like dopamine receptors within the nucleus accumbens.

PubMed

Charmchi, Elham; Zendehdel, Morteza; Haghparast, Abbas

2016-10-03

Nucleus accumbens (NAc) plays an essential role in morphine sensitization and suppression of pain. Repeated exposure to stress and morphine increases dopamine release in the NAc and may lead to morphine sensitization. This study was carried out in order to investigate the effect of forced swim stress (FSS), as a predominantly physical stressor and morphine on the development of morphine sensitization; focusing on the function of D1/D2-like dopamine receptors in the NAc in morphine sensitization. Eighty-five adult male Wistar rats were bilaterally implanted with cannulae in the NAc and various doses of SCH-23390 (0.125, 0.25, 1 and 4μg/0.5μl/NAc) as a D1 receptor antagonist and sulpiride (0.25, 1 and 4μg/0.5μl/NAc) as a D2 receptor antagonist were microinjected into the NAc, during a sensitization period of 3days, 5min before the induction of FSS. After 10min, animals received subcutaneous morphine injection (1mg/kg). The procedure was followed by 5days free of antagonist, morphine and stress; thereafter on the 9th day, the nociceptive response was evaluated by tail-flick test. The results revealed that the microinjection of sulpiride (at 1 and 4μg/0.5μl/NAc) or SCH-23390 (at 0.25, 1 and 4μg/0.5μl/NAc) prior to FSS and morphine disrupts the antinociceptive effects of morphine and morphine sensitization. Our findings suggest that FSS can potentiate the effect of morphine and causes morphine sensitization which induces antinociception. Copyright © 2016 Elsevier Inc. All rights reserved.

Spinal Endomorphin 2 Antinociception and the Mechanisms That Produce It Are Both Sex- and Stage of Estrus Cycle–Dependent in Rats

PubMed Central

Liu, Nai-Jiang; Gintzler, Alan R.

2014-01-01

Endomorphin 2 (EM2) is the predominant endogenous mu-opioid receptor (MOR) ligand in the spinal cord. Given its endogenous presence, antinociceptive responsiveness to the intrathecal application of EM2 most likely reflects its ability to modulate nociception when released in situ. In order to explore the physiological pliability of sex-dependent differences in spinal MOR-mediated antinociception, we investigated the antinociception produced by intrathecal EM2 in male, proestrus female, and diestrus female rats. Antinociception was reflected by changes in tail flick latency to radiant heat. In females, the spinal EM2 antinociceptive system oscillated between analgesically active and inactive states. During diestrus, when circulating estrogens are low, spinal EM2 antinociceptive responsiveness was minimal. In contrast, during proestrus, when circulating estrogens are high, spinal EM2 antinociception was robust and comparable in magnitude to that manifest by males. Furthermore, in proestrus females, spinal EM2 antinociception required spinal dynorphin and kappaopioid receptor activation, concomitant with MOR activation. This is required for neither spinal EM2 antinociception in males nor the antinociception elicited in proestrus females by spinal sufentanil or [d-Ala2,N-methyl-Phe4,Gly-ol5]-enkephalin, which are prototypic MOR-selective nonpeptide and peptide agonists, respectively. These results reveal that spinal EM2 antinociception and the signaling mechanisms used to produce it fundamentally differ in males and females. Perspective The inability to mount spinal EM2 antinociception during defined stages of the estrus (and presumably menstrual) cycle and impaired transition from spinal EM2 analgesically nonresponsive to responsive physiological states could be causally associated with the well-documented greater severity and frequency of chronic intractable pain syndromes in women vs men. PMID:24084000

Acetaminophen Modulates P-Glycoprotein Functional Expression at the Blood-Brain Barrier by a Constitutive Androstane Receptor–Dependent Mechanism

PubMed Central

Thompson, Brandon J.; Sanchez-Covarrubias, Lucy; Zhang, Yifeng; Laracuente, Mei-Li; Vanderah, Todd W.; Ronaldson, Patrick T.; Davis, Thomas P.

2013-01-01

Effective pharmacologic treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor constitutive androstane receptor (CAR) has been identified as a regulator of P-gp functional expression at the BBB. This is critical to pharmacotherapy of pain/inflammation, as patients are often administered acetaminophen (APAP), a CAR-activating ligand, in conjunction with an opioid. Our objective was to investigate, in vivo, the role of CAR in regulation of P-gp at the BBB. Following APAP treatment, P-gp protein expression was increased up to 1.4–1.6-fold in a concentration-dependent manner. Additionally, APAP increased P-gp transport of BODIPY-verapamil in freshly isolated rat brain capillaries. This APAP-induced increase in P-gp expression and activity was attenuated in the presence of CAR pathway inhibitor okadaic acid or transcriptional inhibitor actinomycin D, suggesting P-gp regulation is CAR-dependent. Furthermore, morphine brain accumulation was enhanced by P-gp inhibitors in APAP-treated animals, suggesting P-gp–mediated transport. A warm-water (50°C) tail-flick assay revealed a significant decrease in morphine analgesia in animals treated with morphine 3 or 6 hours after APAP treatment, as compared with animals treated concurrently. Taken together, our data imply that inclusion of APAP in a pain treatment regimen activates CAR at the BBB and increases P-gp functional expression, a clinically significant drug-drug interaction that modulates opioid analgesic efficacy. PMID:24019224

Transcranial direct current stimulation (tDCS) neuromodulatory effects on mechanical hyperalgesia and cortical BDNF levels in ovariectomized rats.

PubMed

da Silva Moreira, Sônia Fátima; Medeiros, Liciane Fernandes; de Souza, Andressa; de Oliveira, Carla; Scarabelot, Vanessa Leal; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-15

Epidemiological studies show that painful disorders are more prevalent in women than in men, and the transcranial direct current stimulation (tDCS) technique has been tested in chronic pain states. We explored the effect of tDCS on pain behavior and brain-derived neurotrophic factor (BDNF) levels in ovariectomized rats. Forty-five female Wistar adult rats were distributed into five groups: control (CT), ovariectomy + tDCS (OT), ovariectomy + sham tDCS (OS), sham ovariectomy + tDCS (ST), and sham ovariectomy+shamtDCS (SS). The rats were subjected to cathodal tDCS. The vaginal cytology and the estradiol levels confirmed the hormonal status. In addition, nociceptive behavior was evaluated using the tail-flick, von Frey, and hot-plate tests, as well as the BDNF levels in the serum, hypothalamus, hippocampus, spinal cord, and cerebral cortex. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical analysis, followed by the Bonferroni, and P-value b 0.05 was considered significant. The ovariectomized animals presented a hypersensitivity response in the hot-plate (P b 0.01) and von Frey (P b 0.05) tests, as well as increased serum BDNF (P b 0.05) and decreased hypothalamic BDNF (P b 0.01) levels. The OT, OS, ST, and SS groups showed decreased hippocampal BDNF levels as compared with the control group (P b 0.001). The interaction between tDCS and ovariectomy on the cortical BDNF levels (P b 0.01) was observed. The ovariectomy induced nociceptive hypersensitivity and altered serum and hypothalamic BDNF levels. The cathodal tDCS partially reversed nociceptive hypersensitivity.

New opioid receptor antagonist: Naltrexone-14-O-sulfate synthesis and pharmacology.

PubMed

Zádor, Ferenc; Király, Kornél; Váradi, András; Balogh, Mihály; Fehér, Ágnes; Kocsis, Dóra; Erdei, Anna I; Lackó, Erzsébet; Zádori, Zoltán S; Hosztafi, Sándor; Noszál, Béla; Riba, Pál; Benyhe, Sándor; Fürst, Susanna; Al-Khrasani, Mahmoud

2017-08-15

Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zwitterionic compounds have been reported to have limited CNS access. The current study, for the first time gives report on the synthesis and the in vitro [competition binding, G-protein activation, isolated mouse vas deferens (MVD) and mouse colon assay] pharmacology of the zwitterionic compound, naltrexone-14-O-sulfate. Naltrexone, naloxone, and its 14-O-sulfate analogue were used as reference compounds. In competition binding assays, naltrexone-14-O-sulfate showed lower affinity for µ, δ or κ opioid receptor than the parent molecule, naltrexone. However, the μ/κ opioid receptor selectivity ratio significantly improved, indicating better selectivity. Similar tendency was observed for naloxone-14-O-sulfate when compared to naloxone. Naltrexone-14-O-sulfate failed to activate [ 35 S]GTPγS-binding but inhibit the activation evoked by opioid agonists (DAMGO, Ile 5,6 deltorphin II and U69593), similarly to the reference compounds. Schild plot constructed in MVD revealed that naltrexone-14-O-sulfate acts as a competitive antagonist. In mouse colon, naltrexone-14-O-sulfate antagonized the inhibitory effect of morphine with lower affinity compared to naltrexone and higher affinity when compared to naloxone or naloxone-14-O-sulfate. In vivo (mouse tail-flick test), subcutaneously injected naltrexone-14-O-sulfate antagonized morphine's antinociception in a dose-dependent manner, indicating it's CNS penetration, which was unexpected from such zwitter ionic structure. Future studies are needed to evaluate it's pharmacokinetic profile. Copyright © 2017 Elsevier B.V. All rights reserved.

Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin

PubMed Central

Hogan, Dale; Baker, Alyssa L.; Morón, Jose A.; Carlton, Susan M.

2013-01-01

Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity – either hyperalgesia and/or allodynia. We hypothesize that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and test this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected i.p. with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 h for 48 h and sacrificed ~12 h following the last injection. Receptive fields of nociceptors were tested for mechanical, heat, and cold sensitivity. Activity was also measured during an initial 2 min period and during 5 min periods between stimuli. Aberrant activity was common in fibers from morphine-treated mice but rare in salinetreated mice. Resting background activity was elevated in C-fibers from morphinetreated mice. Both C- and Aδ -fibers had afterdischarge in response to mechanical, heat and/or cold stimulation of the skin as well as spontaneous, unevoked activity. Compared to saline, morphine treatment increased the proportion of fibers displaying polymodal rather than mechanical-only responses. A significant increase in Aδ-mechanoreceptive fibers responding to cold accounted for most of this change. In agreement with this, morphine-treated mice showed increased sensitivity in the cold tail flick test. In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity. Importantly, this activity is likely driving central sensitization, a phenomenon contributing to abnormal sensory processing and chronic pain. If similar changes occur in human patients, aberrant nociceptor activity is likely to be interpreted as pain, and could contribute to opioid-induced hyperalgesia. PMID:23711478

Antinociceptive synergism of MD-354 and clonidine. Part II. The alpha-adrenoceptor component.

PubMed

Young, Shawquia; Vainio, Minna; Scheinin, Mika; Dukat, Małgorzata

2010-08-01

Previously, we reported that antinociceptive synergism of a 5-HT(3)/alpha(2)-adrenoceptor ligand MD-354 (m-chlorophenylguanidine) and clonidine combination occurs, in part, through a 5-HT(3) receptor antagonist mechanism. In the present investigation, a possible role for alpha(2)-adrenoceptors was examined. Mechanistic studies using yohimbine (a subtype non-selective alpha(2)-adrenoceptor antagonist), BRL 44408 (a preferential alpha(2A)-adrenoceptor antagonist) and imiloxan (a preferential alpha(2B/C)-adrenoceptor antagonist) on the antinociceptive actions of a MD-354/clonidine combination were conducted. Subcutaneous pre-treatment with all three antagonists inhibited the antinociceptive synergism of MD-354 and clonidine in the mouse tail-flick assay in a dose-dependent manner (AD(50) = 0.33, 2.1, and 0.17 mg/kg, respectively). Enhancement of clonidine antinociception by MD-354 did not potentiate clonidine's locomotor suppressant activity in a mouse locomotor assay. When [ethyl-3H]RS-79948-197 was used as radioligand, MD-354 displayed almost equal affinity to alpha(2A)- and alpha(2B)-adrenoceptors (K(i) = 110 and 220 nM) and showed lower affinity at alpha(2C)-adrenoceptors (K(i) = 4,700 nM). MD-354 had no subtype-selectivity for the alpha(2)-adrenoceptor subtypes as an antagonist in functional [35S]GTPgammaS binding assays. MD-354 was a weak partial agonist at alpha(2A)-adrenoceptors. Overall, in addition to the 5-HT(3) receptor component, the present investigation found MD-354 to be a weak partial alpha(2A)-adrenoceptor agonist that enhances clonidine's thermal antinociceptive actions through an alpha(2)-adrenoceptor-mediated mechanism without augmenting sedation.

Effects of Topical Anaesthetic and Buccal Meloxicam Treatments on Concurrent Castration and Dehorning of Beef Calves.

PubMed

Van der Saag, Dominique; White, Peter; Ingram, Lachlan; Manning, Jaime; Windsor, Peter; Thomson, Peter; Lomax, Sabrina

2018-02-28

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied separately or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning/positive control (CONP); (2) castration and dehorning/negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and individual behaviours following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves ( p < 0.001). CONN calves spent less time lying compared to BMTA calves on all days ( p < 0.001). All dehorned and castrated calves spent more time walking ( p = 0.024) and less time eating ( p < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing ( p = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves ( p = 0.098) and tail flicks to be highest in CONN and BM calves ( p = 0.061). The findings of this study suggest that TA and MEL can potentially improve welfare and production of calves following surgical castration and amputation dehorning.

Ligand requirements for involvement of PKCε in synergistic analgesic interactions between spinal μ and δ opioid receptors.

PubMed

Schuster, D J; Metcalf, M D; Kitto, K F; Messing, R O; Fairbanks, C A; Wilcox, G L

2015-01-01

We recently found that PKCε was required for spinal analgesic synergy between two GPCRs, δ opioid receptors and α2 A adrenoceptors, co-located in the same cellular subpopulation. We sought to determine if co-delivery of μ and δ opioid receptor agonists would similarly result in synergy requiring PKCε. Combinations of μ and δ opioid receptor agonists were co-administered intrathecally by direct lumbar puncture to PKCε-wild-type (PKCε-WT) and -knockout (PKCε-KO) mice. Antinociception was assessed using the hot-water tail-flick assay. Drug interactions were evaluated by isobolographic analysis. All agonists produced comparable antinociception in both PKCε-WT and PKCε-KO mice. Of 19 agonist combinations that produced analgesic synergy, only 3 required PKCε for a synergistic interaction. In these three combinations, one of the agonists was morphine, although not all combinations involving morphine required PKCε. Morphine + deltorphin II and morphine + deltorphin I required PKCε for synergy, whereas a similar combination, morphine + deltorphin, did not. Additionally, morphine + oxymorphindole required PKCε for synergy, whereas a similar combination, morphine + oxycodindole, did not. We discovered biased agonism for a specific signalling pathway at the level of spinally co-delivered opioid agonists. As the bias is only revealed by an appropriate ligand combination and cannot be accounted for by a single drug, it is likely that the receptors these agonists act on are interacting with each other. Our results support the existence of μ and δ opioid receptor heteromers at the spinal level in vivo. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

Endothelin-converting enzyme 2 differentially regulates opioid receptor activity

PubMed Central

Gupta, A; Fujita, W; Gomes, I; Bobeck, E; Devi, L A

2015-01-01

BACKGROUND AND PURPOSE Opioid receptor function is modulated by post-activation events such as receptor endocytosis, recycling and/or degradation. While it is generally understood that the peptide ligand gets co-endocytosed with the receptor, relatively few studies have investigated the role of the endocytosed peptide and peptide processing enzymes in regulating receptor function. In this study, we focused on endothelin-converting enzyme 2 (ECE2), a member of the neprilysin family of metallopeptidases that exhibits an acidic pH optimum, localizes to an intracellular compartment and selectively processes neuropeptides including opioid peptides in vitro, and examined its role in modulating μ receptor recycling and resensitization. EXPERIMENTAL APPROACH The effect of ECE2 inhibition on hydrolysis of the endocytosed peptide was examined using thin-layer chromatography and on μ opioid receptor trafficking using either elisa or microscopy. The effect of ECE2 inhibition on receptor signalling was measured using a cAMP assay and, in vivo, on antinociception induced by intrathecally administered opioids by the tail-flick assay. KEY RESULTS The highly selective ECE2 inhibitor, S136492, significantly impaired μ receptor recycling and signalling by only those ligands that are ECE2 substrates and this was seen both in heterologous cells and in cells endogenously co-expressing μ receptors with ECE2. We also found that ECE2 inhibition attenuated antinociception mediated only by opioid peptides that are ECE2 substrates. CONCLUSIONS AND IMPLICATIONS These results suggest that ECE2, by selectively processing endogenous opioid peptides in the endocytic compartment, plays a role in modulating opioid receptor activity. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24990314

The benzomorphan-based LP1 ligand is a suitable MOR/DOR agonist for chronic pain treatment.

PubMed

Pasquinucci, Lorella; Parenti, Carmela; Turnaturi, Rita; Aricò, Giuseppina; Marrazzo, Agostino; Prezzavento, Orazio; Ronsisvalle, Simone; Georgoussi, Zafiroula; Fourla, Danai-Dionysia; Scoto, Giovanna M; Ronsisvalle, Giuseppe

2012-01-02

Powerful analgesics relieve pain primarily through activating mu opioid receptor (MOR), but the long-term use of MOR agonists, such as morphine, is limited by the rapid development of tolerance. Recently, it has been observed that simultaneous stimulation of the delta opioid receptor (DOR) and MOR limits the incidence of tolerance induced by MOR agonists. 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide (LP1) is a centrally acting agent with antinociceptive activity comparable to morphine and is able to bind and activate MOR and DOR. The aim of this work was to evaluate and compare the induction of tolerance to antinociceptive effects from treatment with LP1 and morphine. Here, we evaluated the pharmacological effects of LP1 administered at a dose of 4 mg/kg subcutaneously (s.c.) twice per day for 9 days to male Sprague-Dawley rats. In addition, the LP1 mechanism of action was assessed by measurement of LP1-induced [(35)S]GTPγS binding to the MOR and DOR. Data obtained from the radiant heat tail flick test showed that LP1 maintained its antinociceptive profile until the ninth day, while tolerance to morphine (10mg/kg s.c. twice per day) was observed on day 3. Moreover, LP1 significantly enhanced [(35)S]GTPγS binding in the membranes of HEK293 cells expressing either the MOR or the DOR. LP1 is a novel analgesic agent for chronic pain treatment, and its low tolerance-inducing capability may be correlated with its ability to bind both the MOR and DOR. Copyright © 2011 Elsevier Inc. All rights reserved.

Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies

PubMed Central

Silva, Rosa H. M.; Lima, Nathália de Fátima M.; Lopes, Alberto J. O.; Vasconcelos, Cleydlenne C.; de Mesquita, José W. C.; de Mesquita, Ludmilla S. S.; Lima, Fernando C. V. M.; Ribeiro, Maria N. de S.; Ramos, Ricardo M.; Cartágenes, Maria do Socorro de S.; Garcia, João B. S.

2017-01-01

Borreria verticillata (L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of B. verticillata hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by in vivo and in silico studies. In vivo assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0.9% NaCl control group (CTRL), 10 mg/kg memantine (MEM), 10 mg/kg indomethacin (INDO), 500 mg/kg EHBv (EHBv 500), 25 mg/kg FAc (FAc 25) and 50 mg/kg FAc (FAc 50). EHBv, FAc 25 and 50 treatments exhibited anti-edematous and peripheral antinociceptive effects. For in silico assessment, compounds identified in FAc were subjected to molecular docking with COX-2, GluN1a and GluN2B. Ursolic acid (UA) was the compound with best affinity parameters (binding energy and inhibition constant) for COX-2, GluN1a, GluN2B, and was selected for further analysis with molecular dynamics (MD) simulations. In MD simulations, UA exhibited highly frequent interactions with residues Arg120 and Glu524 in the COX-2 active site and NMDA, whereby it might prevent COX-2 and NMDA receptor activation. Treatment with UA 10 mg/Kg showed peripheral and central antinociceptive effect. The antinociceptive effect of B. verticillata might be predominantly attributed to peripheral actions, including the participation of anti-inflammatory components. Ursolic acid is the main active component and seems to be a promising source of COX-2 inhibitors and NMDA receptor antagonists. PMID:28588488

Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant rats.

PubMed

Chou, Kuang-Yi; Tsai, Ru-Yin; Tsai, Wei-Yuan; Wu, Ching-Tang; Yeh, Chun-Chang; Cherng, Chen-Hwan; Wong, Chih-Shung

2013-12-01

As known, long-term morphine infusion leads to tolerance. We previously demonstrated that both co-infusion and post-administration of ultra-low dose (±)-naloxone restores the antinociceptive effect of morphine in morphine-tolerant rats. However, whether the mechanism of the action of ultra-low dose (±)-naloxone is through opioid receptors or not. Therefore, in the present study, we further investigated the effect of ultra-low dose (+)-naloxone, it does not bind to opioid receptors, on the antinociceptive effect of morphine. Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one catheter was connected to a mini-osmotic pump, used for morphine (15 μg/h), ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone (15 pg/h) or saline (1 μl/h) infusion for 5 days. On day 5, either ultra-low dose (+)-naloxone (15 pg) or saline (5 μl) was injected via the other catheter immediately after discontinued morphine or saline infusion. Three hours later, morphine (15 μg in 5 μl saline) or saline were given intrathecally. All rats received nociceptive tail-flick test every 30 minutes for 120 minutes after morphine challenge at different temperature (45-52°C, respective). Our results showed that, both co-infusion and post-treatment of ultra-low dose (+)-naloxone with morphine preserves the antinociceptive effect of morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone further enhances the antinociceptive effect of morphine. This study provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant for patients who need long-term opioid administration for pain management. Copyright © 2013. Published by Elsevier B.V.

Rationally designed chimeric peptide of met-enkephalin and FMRFa-[D-Ala2,p-Cl-Phe4]YFa induce multiple opioid receptors mediated antinociception and up-regulate their expression.

PubMed

Vats, Ishwar Dutt; Chaudhary, Snehlata; Sharma, Ahuti; Nath, Mahendra; Pasha, Santosh

2010-07-25

The physiological role of NPFF/FMRFa family of peptides appears to be complex and exact mechanism of action of these peptides is not yet completely understood. In same line of scrutiny, another analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of met-enkephalin and FMRFamide, was rationally designed and synthesized which contain D-alanine and p-Cl-phenylalanine residues at 2nd and 4th positions, respectively i.e., Y-(D-Ala)-G-(p-Cl-Phe)-MKKKFMRFamide ([D-Ala(2), p-Cl-Phe(4)]YFa) in order to achieve improved bioavailability and blood brain barrier penetration. Therefore, present study investigates the possible antinociceptive effect of [D-Ala(2), p-Cl-Phe(4)]YFa on intra-peritoneal (i.p.) administration using tail-flick test in rats followed by its opioid receptor(s) specificity using mu, delta and kappa receptor antagonists. Further, its antinociceptive effect was examined during 6 days of chronic i.p. treatment and assessed effect of this treatment on differential expression of opioid receptors. [D-Ala(2), p-Cl-Phe(4)]YFa in comparison to parent peptide YFa, induce significantly higher dose dependent antinociception in rats which was mediated by all three opioid receptors (mu, delta and kappa). Importantly, it induced comparable antinociception in rats throughout the chronic i.p. treatment and significantly up-regulated the overall expression (mRNA and protein) of mu, delta and kappa opioid receptors. Therefore, pharmacological and molecular behavior of [D-Ala(2), p-Cl-Phe(4)]YFa demonstrate that incorporation of D-alanine and p-Cl-phenylalanine residues at appropriate positions in chimeric peptide leads to altered opioid receptor selectivity and enhanced antinociceptive potency, relative to parent peptide. (c) 2010 Elsevier B.V. All rights reserved.

Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

PubMed

Kawano, Susumu; Ito, Risa; Nishiyama, Miharu; Kubo, Mai; Matsushima, Tomoko; Minamisawa, Motoko; Ambo, Akihiro; Sasaki, Yusuke

2007-07-01

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100< pmol/mouse) than when administered i.t. (ED(50): 1.34-4.51 pmol/mouse). These results suggest the involvement of nociceptin-like agonistic effects of the Ac-RYYRIK pharmacophore in the peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.

Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Modulates Purinoceptor-Coupled Calcium Signaling and Murine Nociceptive Behavior.

PubMed

Liu, Pei-Shan; Chueh, Sheau-Huei; Chen, Chin-Chu; Lee, Li-Ya; Shiu, Li-Yen

2017-01-01

Hericium erinaceus is well known for the neurotrophic effect it confers by promoting nerve growth factor biosynthesis. We discovered a novel bioactivity of H. erinaceus in its ability to suppress adenosine triphosphate (ATP)-induced calcium signaling in neuronal PC12 cells. ATP, known primarily as a neurotransmitter, also acts on purinoceptors (P2 purinergic receptor [P2R]) to generate the cellular calcium signaling and secretion that mediate P2R physiological manifestations, including pain. Chronic pain reduces quality of life. However, constant analgesic administration can cause liver and kidney injury, as well as loss of the analgesic effect because of desensitization. In this study we investigated the analgesic potential of H. erinaceus through measurements of ATP-induced Ca2+ signaling in cell lines and observation of pain behaviors in mice. In P2R-coupled Ca2+ signaling measurements, extracts of H. erinaceus mycelia (HEEs) blocked ATP-induced Ca2+ signaling in both rat PC12 cells and human HOS cells. HEEs completely blocked ATP-induced Ca2+ signaling in human HOS cells, suggesting that this effect of HEEs is exerted through the P2R subtypes present in HOS cells, which include the P2X4, P2X7, P2Y2, and P2Y4 subtypes. In observations of animal behavior during pain, HEEs significantly reduced heat-induced pain, including postponing both the tail-flick response to heat stimulation and the paw-lifting response to a hot plate. This study demonstrates novel characteristics of H. erinaceus in reducing nociceptive behavior and blocking the functional activity of P2R. Further studies are required to verify this linkage and its molecular mechanisms.

Experimental study of main rotor tip geometry and tail rotor interactions in hover. Volume 1. Text and figures

NASA Technical Reports Server (NTRS)

Balch, D. T.; Lombardi, J.

1985-01-01

A model scale hover test was conducted in the Sikorsky Aircraft Model rotor hover Facility to identify and quantify the impact of the tail rotor on the demonstrated advantages of advanced geometry tip configurations. The test was conducted using the Basic Model Test Rig and two scaled main rotor systems, one representing a 1/5.727 scale UH-60A BLACK HAWK and the others a 1/4.71 scale S-76. Eight alternate rotor tip configurations were tested, 3 on the BLACK HAWK rotor and 6 on the S-76 rotor. Four of these tips were then selected for testing in close proximity to an operating tail rotor (operating in both tractor and pusher modes) to determine if the performance advantages that could be obtained from the use of advanced geometry tips in a main rotor only environment would still exist in the more complex flow field involving a tail rotor. The test showed that overall the tail rotor effects on the advanced tip configurations tested are not substantially different from the effects on conventional tips.

Average configuration of the distant (less than 220-earth-radii) magnetotail - Initial ISEE-3 magnetic field results

NASA Technical Reports Server (NTRS)

Slavin, J. A.; Tsurutani, B. T.; Smith, E. J.; Jones, D. E.; Sibeck, D. G.

1983-01-01

Magnetic field measurements from the first two passes of the ISEE-3 GEOTAIL Mission have been used to study the structure of the trans-lunar tail. Good agreement was found between the ISEE-3 magnetopause crossings and the Explorer 33, 35 model of Howe and Binsack (1972). Neutral sheet location was well ordered by the hinged current sheet models based upon near earth measurements. Between X = -20 and -120 earth radii the radius of the tail increases by about 30 percent while the lobe field strength decreases by approximately 60 percent. Beyond X = -100 to -1200 earth radii the tail diameter and lobe field magnitude become nearly constant at terminal values of approximately 60 earth radii and 9 nT, respectively. The distance at which the tail was observed to cease flaring, 100-120 earth radii, is in close agreement with the predictions of the analytic tail model of Coroniti and Kennel (1972). Overall, the findings of this study suggest that the magnetotail retains much of its near earth structure out to X = -220 earth radii.

Reproducing tailing in breakthrough curves: Are statistical models equally representative and predictive?

NASA Astrophysics Data System (ADS)

Pedretti, Daniele; Bianchi, Marco

2018-03-01

Breakthrough curves (BTCs) observed during tracer tests in highly heterogeneous aquifers display strong tailing. Power laws are popular models for both the empirical fitting of these curves, and the prediction of transport using upscaling models based on best-fitted estimated parameters (e.g. the power law slope or exponent). The predictive capacity of power law based upscaling models can be however questioned due to the difficulties to link model parameters with the aquifers' physical properties. This work analyzes two aspects that can limit the use of power laws as effective predictive tools: (a) the implication of statistical subsampling, which often renders power laws undistinguishable from other heavily tailed distributions, such as the logarithmic (LOG); (b) the difficulties to reconcile fitting parameters obtained from models with different formulations, such as the presence of a late-time cutoff in the power law model. Two rigorous and systematic stochastic analyses, one based on benchmark distributions and the other on BTCs obtained from transport simulations, are considered. It is found that a power law model without cutoff (PL) results in best-fitted exponents (αPL) falling in the range of typical experimental values reported in the literature (1.5 < αPL < 4). The PL exponent tends to lower values as the tailing becomes heavier. Strong fluctuations occur when the number of samples is limited, due to the effects of subsampling. On the other hand, when the power law model embeds a cutoff (PLCO), the best-fitted exponent (αCO) is insensitive to the degree of tailing and to the effects of subsampling and tends to a constant αCO ≈ 1. In the PLCO model, the cutoff rate (λ) is the parameter that fully reproduces the persistence of the tailing and is shown to be inversely correlated to the LOG scale parameter (i.e. with the skewness of the distribution). The theoretical results are consistent with the fitting analysis of a tracer test performed during the MADE-5 experiment. It is shown that a simple mechanistic upscaling model based on the PLCO formulation is able to predict the ensemble of BTCs from the stochastic transport simulations without the need of any fitted parameters. The model embeds the constant αCO = 1 and relies on a stratified description of the transport mechanisms to estimate λ. The PL fails to reproduce the ensemble of BTCs at late time, while the LOG model provides consistent results as the PLCO model, however without a clear mechanistic link between physical properties and model parameters. It is concluded that, while all parametric models may work equally well (or equally wrong) for the empirical fitting of the experimental BTCs tails due to the effects of subsampling, for predictive purposes this is not true. A careful selection of the proper heavily tailed models and corresponding parameters is required to ensure physically-based transport predictions.

Development of a Model for the Night Side Magnetopause using Global Simulations

NASA Technical Reports Server (NTRS)

Raeder, Joachim

1998-01-01

During the final year of this investigation we have finished several event studies that we considered necessary for the development of a tail magnetopause model and for the calibration of our simulation code. We have not reached the ultimate goal of the project, i.e., the development of an analytical tail magnetopause model. In the course of the investigation we have learned that such a model would be much more complex than we had anticipated. However, the investigations that we conducted towards this goal have led to significant results and discoveries that are of considerable value for understanding the tail magnetopause. These are summarized in the following sections.

Young calcareous soil chronosequences as a model for ecological restoration on alkaline mine tailings.

PubMed

Cross, Adam T; Lambers, Hans

2017-12-31

Tailings are artificial soil-forming substrates that have not been created by the natural processes of soil formation and weathering. The extreme pH environment and corresponding low availability of some macro- and micronutrients in alkaline tailings, coupled with hostile physical and geochemical conditions, present a challenging environment to native biota. Some significant nutritional constraints to ecosystem reconstruction on alkaline tailings include i) predominant or complete absence of combined nitrogen (N) and poor soil N retention; ii) the limited bioavailability of some micronutrients at high soil pH (e.g., Mn, Fe, Zn and Cu); and iii) potentially toxic levels of biologically available soil phosphorus (P) for P-sensitive plants. The short regulatory time frames (years) for mine closure on tailings landforms are at odds with the long time required for natural pedogenic processes to ameliorate these factors (thousands of years). However, there are similarities between the chemical composition and nutrient status of alkaline tailings and the poorly-developed, very young calcareous soils of biodiverse regions such as south-western Australia. We propose that basic knowledge of chronosequences that start with calcareous soils may provide an informative model for understanding the pedogenic processes required to accelerate soil formation on tailings. Development of a functional, stable root zone is crucial to successful ecological restoration on tailings, and three major processes should be facilitated as early as possible during processing or in the early stages of restoration to accelerate soil development on alkaline tailings: i) acidification of the upper tailings profile; ii) establishment of appropriate and resilient microbial communities; and iii) the early development of appropriate pioneer vegetation. Achieving successful ecological restoration outcomes on tailings landforms is likely one of the greatest challenges faced by restoration ecologists and the mining industry, and successful restoration on alkaline tailings likely depends upon careful management of substrate chemical conditions by targeted amendments. Copyright © 2017 Elsevier B.V. All rights reserved.

THE NARROW X-RAY TAIL AND DOUBLE Hα TAILS OF ESO 137-002 IN A3627

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, B.; Lin, X. B.; Kong, X.

2013-11-10

We present the analysis of a deep Chandra observation of a ∼2 L{sub *} late-type galaxy, ESO 137-002, in the closest rich cluster A3627. The Chandra data reveal a long (∼>40 kpc) and narrow tail with a nearly constant width (∼3 kpc) to the southeast of the galaxy, and a leading edge ∼1.5 kpc from the galaxy center on the upstream side of the tail. The tail is most likely caused by the nearly edge-on stripping of ESO 137-002's interstellar medium (ISM) by ram pressure, compared to the nearly face-on stripping of ESO 137-001 discussed in our previous work. Spectralmore » analysis of individual regions along the tail shows that the gas throughout it has a rather constant temperature, ∼1 keV, very close to the temperature of the tails of ESO 137-001, if the same atomic database is used. The derived gas abundance is low (∼0.2 solar with the single-kT model), an indication of the multiphase nature of the gas in the tail. The mass of the X-ray tail is only a small fraction (<5%) of the initial ISM mass of the galaxy, suggesting that the stripping is most likely at an early stage. However, with any of the single-kT, double-kT, and multi-kT models we tried, the tail is always 'over-pressured' relative to the surrounding intracluster medium (ICM), which could be due to the uncertainties in the abundance, thermal versus non-thermal X-ray emission, or magnetic support in the ICM. The Hα data from the Southern Observatory for Astrophysical Research show a ∼21 kpc tail spatially coincident with the X-ray tail, as well as a secondary tail (∼12 kpc long) to the east of the main tail diverging at an angle of ∼23° and starting at a distance of ∼7.5 kpc from the nucleus. At the position of the secondary Hα tail, the X-ray emission is also enhanced at the ∼2σ level. We compare the tails of ESO 137-001 and ESO 137-002, and also compare the tails to simulations. Both the similarities and differences of the tails pose challenges to the simulations. Several implications are briefly discussed.« less

Accidental Water Pollution Risk Analysis of Mine Tailings Ponds in Guanting Reservoir Watershed, Zhangjiakou City, China.

PubMed

Liu, Renzhi; Liu, Jing; Zhang, Zhijiao; Borthwick, Alistair; Zhang, Ke

2015-12-02

Over the past half century, a surprising number of major pollution incidents occurred due to tailings dam failures. Most previous studies of such incidents comprised forensic analyses of environmental impacts after a tailings dam failure, with few considering the combined pollution risk before incidents occur at a watershed-scale. We therefore propose Watershed-scale Tailings-pond Pollution Risk Analysis (WTPRA), designed for multiple mine tailings ponds, stemming from previous watershed-scale accidental pollution risk assessments. Transferred and combined risk is embedded using risk rankings of multiple routes of the "source-pathway-target" in the WTPRA. The previous approach is modified using multi-criteria analysis, dam failure models, and instantaneous water quality models, which are modified for application to multiple tailings ponds. The study area covers the basin of Gutanting Reservoir (the largest backup drinking water source for Beijing) in Zhangjiakou City, where many mine tailings ponds are located. The resultant map shows that risk is higher downstream of Gutanting Reservoir and in its two tributary basins (i.e., Qingshui River and Longyang River). Conversely, risk is lower in the midstream and upstream reaches. The analysis also indicates that the most hazardous mine tailings ponds are located in Chongli and Xuanhua, and that Guanting Reservoir is the most vulnerable receptor. Sensitivity and uncertainty analyses are performed to validate the robustness of the WTPRA method.

Accidental Water Pollution Risk Analysis of Mine Tailings Ponds in Guanting Reservoir Watershed, Zhangjiakou City, China

PubMed Central

Liu, Renzhi; Liu, Jing; Zhang, Zhijiao; Borthwick, Alistair; Zhang, Ke

2015-01-01

Over the past half century, a surprising number of major pollution incidents occurred due to tailings dam failures. Most previous studies of such incidents comprised forensic analyses of environmental impacts after a tailings dam failure, with few considering the combined pollution risk before incidents occur at a watershed-scale. We therefore propose Watershed-scale Tailings-pond Pollution Risk Analysis (WTPRA), designed for multiple mine tailings ponds, stemming from previous watershed-scale accidental pollution risk assessments. Transferred and combined risk is embedded using risk rankings of multiple routes of the “source-pathway-target” in the WTPRA. The previous approach is modified using multi-criteria analysis, dam failure models, and instantaneous water quality models, which are modified for application to multiple tailings ponds. The study area covers the basin of Gutanting Reservoir (the largest backup drinking water source for Beijing) in Zhangjiakou City, where many mine tailings ponds are located. The resultant map shows that risk is higher downstream of Gutanting Reservoir and in its two tributary basins (i.e., Qingshui River and Longyang River). Conversely, risk is lower in the midstream and upstream reaches. The analysis also indicates that the most hazardous mine tailings ponds are located in Chongli and Xuanhua, and that Guanting Reservoir is the most vulnerable receptor. Sensitivity and uncertainty analyses are performed to validate the robustness of the WTPRA method. PMID:26633450

A semi-automated vascular access system for preclinical models

NASA Astrophysics Data System (ADS)

Berry-Pusey, B. N.; Chang, Y. C.; Prince, S. W.; Chu, K.; David, J.; Taschereau, R.; Silverman, R. W.; Williams, D.; Ladno, W.; Stout, D.; Tsao, T. C.; Chatziioannou, A.

2013-08-01

Murine models are used extensively in biological and translational research. For many of these studies it is necessary to access the vasculature for the injection of biologically active agents. Among the possible methods for accessing the mouse vasculature, tail vein injections are a routine but critical step for many experimental protocols. To perform successful tail vein injections, a high skill set and experience is required, leaving most scientists ill-suited to perform this task. This can lead to a high variability between injections, which can impact experimental results. To allow more scientists to perform tail vein injections and to decrease the variability between injections, a vascular access system (VAS) that semi-automatically inserts a needle into the tail vein of a mouse was developed. The VAS uses near infrared light, image processing techniques, computer controlled motors, and a pressure feedback system to insert the needle and to validate its proper placement within the vein. The VAS was tested by injecting a commonly used radiolabeled probe (FDG) into the tail veins of five mice. These mice were then imaged using micro-positron emission tomography to measure the percentage of the injected probe remaining in the tail. These studies showed that, on average, the VAS leaves 3.4% of the injected probe in the tail. With these preliminary results, the VAS system demonstrates the potential for improving the accuracy of tail vein injections in mice.

Application of a life cycle assessment to compare environmental performance in coal mine tailings management.

PubMed

Adiansyah, Joni Safaat; Haque, Nawshad; Rosano, Michele; Biswas, Wahidul

2017-09-01

This study compares coal mine tailings management strategies using life cycle assessment (LCA) and land-use area metrics methods. Hybrid methods (the Australian indicator set and the ReCiPe method) were used to assess the environmental impacts of tailings management strategies. Several strategies were considered: belt filter press (OPT 1), tailings paste (OPT 2), thickened tailings (OPT 3), and variations of OPT 1 using combinations of technology improvement and renewable energy sources (OPT 1A-D). Electrical energy was found to contribute more than 90% of the environmental impacts. The magnitude of land-use impacts associated with OPT 3 (thickened tailings) were 2.3 and 1.55 times higher than OPT 1 (tailings cake) and OPT 2 (tailings paste) respectively, while OPT 1B (tailings belt filter press with technology improvement and solar energy) and 1D (tailings belt press filter with technology improvement and wind energy) had the lowest ratio of environmental impact to land-use. Further analysis of an economic cost model and reuse opportunities is required to aid decision making on sustainable tailings management and industrial symbiosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Active Vertical Tail Buffeting Alleviation on an F/A-18 Model in a Wind Tunnel

NASA Technical Reports Server (NTRS)

Moses, Robert W.

1999-01-01

A 1/6-scale F-18 wind-tunnel model was tested in the Transonic Dynamics Tunnel at the NASA Langley Research Center as part of the Actively Controlled Response Of Buffet-Affected Tails (ACROBAT) program to assess the use of active controls in reducing vertical tail buffeting. The starboard vertical tail was equipped with an active rudder and other aerodynamic devices, and the port vertical tail was equipped with piezoelectric actuators. The tunnel conditions were atmospheric air at a dynamic pressure of 14 psf. By using single-input-single-output control laws at gains well below the physical limits of the control effectors, the power spectral density of the root strains at the frequency of the first bending mode of the vertical tail was reduced by as much as 60 percent up to angles of attack of 37 degrees. Root mean square (RMS) values of root strain were reduced by as much as 19 percent. Stability margins indicate that a constant gain setting in the control law may be used throughout the range of angle of attack tested.

How extreme is extreme hourly precipitation?

NASA Astrophysics Data System (ADS)

Papalexiou, Simon Michael; Dialynas, Yannis G.; Pappas, Christoforos

2016-04-01

The importance of accurate representation of precipitation at fine time scales (e.g., hourly), directly associated with flash flood events, is crucial in hydrological design and prediction. The upper part of a probability distribution, known as the distribution tail, determines the behavior of extreme events. In general, and loosely speaking, tails can be categorized in two families: the subexponential and the hyperexponential family, with the first generating more intense and more frequent extremes compared to the latter. In past studies, the focus has been mainly on daily precipitation, with the Gamma distribution being the most popular model. Here, we investigate the behaviour of tails of hourly precipitation by comparing the upper part of empirical distributions of thousands of records with three general types of tails corresponding to the Pareto, Lognormal, and Weibull distributions. Specifically, we use thousands of hourly rainfall records from all over the USA. The analysis indicates that heavier-tailed distributions describe better the observed hourly rainfall extremes in comparison to lighter tails. Traditional representations of the marginal distribution of hourly rainfall may significantly deviate from observed behaviours of extremes, with direct implications on hydroclimatic variables modelling and engineering design.

Biomimetic model systems of rigid hair beds: Part I - Theory

NASA Astrophysics Data System (ADS)

Hood, Kaitlyn; Jammalamadaka, Mani S. S.; Hosoi, Anette

2017-11-01

Crustaceans - such as lobsters, crabs, and stomapods - have hairy appendages that they use to recognize and track odorants in the surrounding fluid. An array of rigid hairs impedes flow at different rates depending on the spacing between hairs and the Reynolds number, Re. At larger Reynolds numbers (Re >1), fluid travels through the hairs rather than around them, a phenomenon called leakiness. Crustaceans flick their appendages at different speeds in order to manipulate the leakiness between the hairs, allowing the hairs to either detect odors in a sample of fluid or collect a new sample. A single hair can be represented as a slender body attached at one end to a wall. Using both slender body theory and numerical methods, we observe that there is a region of flow around the hair that speeds up relative to the unobstructed flow. As the Reynolds number increases, this fast flow region moves closer to the hair. Using this model, we predict that an array of hairs can be engineered to have a desired leakiness profile.

Performance Enhancement of a Full-Scale Vertical Tail Model Equipped with Active Flow Control

NASA Technical Reports Server (NTRS)

Whalen, Edward A.; Lacy, Douglas; Lin, John C.; Andino, Marlyn Y.; Washburn, Anthony E.; Graff, Emilio; Wygnanski, Israel J.

2015-01-01

This paper describes wind tunnel test results from a joint NASA/Boeing research effort to advance active flow control (AFC) technology to enhance aerodynamic efficiency. A full-scale Boeing 757 vertical tail model equipped with sweeping jet actuators was tested at the National Full-Scale Aerodynamics Complex (NFAC) 40- by 80-Foot Wind Tunnel (40x80) at NASA Ames Research Center. The model was tested at a nominal airspeed of 100 knots and across rudder deflections and sideslip angles that covered the vertical tail flight envelope. A successful demonstration of AFC-enhanced vertical tail technology was achieved. A 31- actuator configuration significantly increased side force (by greater than 20%) at a maximum rudder deflection of 30deg. The successful demonstration of this application has cleared the way for a flight demonstration on the Boeing 757 ecoDemonstrator in 2015.

LDV Surveys Over a Fighter Model at Moderate to High Angles of Attack

NASA Technical Reports Server (NTRS)

Sellers, William L., III; Meyers, James F.; Hepner, Timothy E.

2004-01-01

The vortex flowfield over an advanced twin-tailed fighter configuration was measured in a low-speed wind tunnel at two angles of attack. The primary test data consisted of 3-component velocity surveys obtained using a Laser Doppler Velocimeter. Laser light sheet and surface flow visualization were also obtained to provide insight into the flowfield structure. Time-averaged velocities and the root mean square of the velocity fluctuations were obtained at two cross-sections above the model. At 15 degrees angle of attack, the vortices generated by the wing leading edge extension (LEX) were unburst over the model and passed outboard of the vertical tail. At 25 degrees angle of attack, the vortices burst in the vicinity of the wing-LEX intersection and impact directly on the vertical tails. The RMS levels of the velocity fluctuations reach values of approximately 30% in the region of the vertical tails.

Intermonolayer Friction and Surface Shear Viscosity of Lipid Bilayer Membranes

PubMed Central

den Otter, W. K.; Shkulipa, S. A.

2007-01-01

The flow behavior of lipid bilayer membranes is characterized by a surface viscosity for in-plane shear deformations, and an intermonolayer friction coefficient for slip between the two leaflets of the bilayer. Both properties have been studied for a variety of coarse-grained double-tailed model lipids, using equilibrium and nonequilibrium molecular dynamics simulations. For lipids with two identical tails, the surface shear viscosity rises rapidly with tail length, while the intermonolayer friction coefficient is less sensitive to the tail length. Interdigitation of lipid tails across the bilayer midsurface, as observed for lipids with two distinct tails, strongly enhances the intermonolayer friction coefficient, but hardly affects the surface shear viscosity. The simulation results are compared against the available experimental data. PMID:17468168

Poly A tail length analysis of in vitro transcribed mRNA by LC-MS.

PubMed

Beverly, Michael; Hagen, Caitlin; Slack, Olga

2018-02-01

The 3'-polyadenosine (poly A) tail of in vitro transcribed (IVT) mRNA was studied using liquid chromatography coupled to mass spectrometry (LC-MS). Poly A tails were cleaved from the mRNA using ribonuclease T1 followed by isolation with dT magnetic beads. Extracted tails were then analyzed by LC-MS which provided tail length information at single-nucleotide resolution. A 2100-nt mRNA with plasmid-encoded poly A tail lengths of either 27, 64, 100, or 117 nucleotides was used for these studies as enzymatically added poly A tails showed significant length heterogeneity. The number of As observed in the tails closely matched Sanger sequencing results of the DNA template, and even minor plasmid populations with sequence variations were detected. When the plasmid sequence contained a discreet number of poly As in the tail, analysis revealed a distribution that included tails longer than the encoded tail lengths. These observations were consistent with transcriptional slippage of T7 RNAP taking place within a poly A sequence. The type of RNAP did not alter the observed tail distribution, and comparison of T3, T7, and SP6 showed all three RNAPs produced equivalent tail length distributions. The addition of a sequence at the 3' end of the poly A tail did, however, produce narrower tail length distributions which supports a previously described model of slippage where the 3' end can be locked in place by having a G or C after the poly nucleotide region. Graphical abstract Determination of mRNA poly A tail length using magnetic beads and LC-MS.

Rotary balance data for a typical single-engine general aviation design for an angle-of-attack range of 8 deg to 90 deg. 2: Influence of horizontal tail location for Model D

NASA Technical Reports Server (NTRS)

Barnhart, B.

1982-01-01

The influence of horizontal tail location on the rotational flow aerodynamics is discussed for a 1/6-scale general aviation airplane model. The model was tested using various horizontal tail positions, with both a high and a low-wing location and for each of two body lengths. Data were measured, using a rotary balance, over an angle-of-attack range of 8 to 90 deg, and for clockwise and counter-clockwise rotations covering an Omega b/2V range of 0 to 0.9.

Predicting arsenic concentrations in porewaters of buried uranium mill tailings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langmuir, D.; Mahoney, J.; MacDonald, A.

The proposed JEB Tailings Management Facility (TMF) to be emplaced below the groundwater table in northern Saskatchewan, Canada, will contain uranium mill tailings from McClean Lake, Midwest and Cigar Lake ore bodies, which are high in arsenic (up to 10%) and nickel (up to 5%). A serious concern is the possibility that high arsenic and nickel concentrations may be released from the buried tailings, contaminating adjacent groundwaters and a nearby lake. Laboratory tests and geochemical modeling were performed to examine ways to reduce the arsenic and nickel concentrations in TMF porewaters so as to minimize such contamination from tailings buriedmore » for 50 years and longer. The tests were designed to mimic conditions in the mill neutralization circuit (3 hr tests at 25 C), and in the TMF after burial (5--49 day aging tests). The aging tests were run at 50, 25 and 4 C (the temperature in the TMF). In order to optimize the removal of arsenic by adsorption and precipitation, ferric sulfate was added to tailings raffinates having Fe/As ratios of less than 3--5. The acid raffinates were then neutralized by addition of slaked lime to nominal pH values of 7, 8, or 9. Analysis and modeling of the test results showed that with slaked lime addition to acid tailings raffinates, relatively amorphous scorodite (ferric arsenate) precipitates near pH 1, and is the dominant form of arsenate in slake limed tailings solids except those high in Ni and As and low in Fe, in which cabrerite-annabergite (Ni, Mg, Fe(II) arsenate) may also precipitate near pH 5--6. In addition to the arsenate precipitates, smaller amounts of arsenate are also adsorbed onto tailings solids. The aging tests showed that after burial of the tailings, arsenic concentrations may increase with time from the breakdown of the arsenate phases (chiefly scorodite). However, the tests indicate that the rate of change decreases and approaches zero after 72 hrs at 25 C, and may equal zero at all times in the TMF at 4 C. Consistent with a kinetic model that describes the rate of breakdown of scorodite to form hydrous ferric oxide, the rate of release of dissolved arsenate to tailings porewaters from slake limed tailings: (1) is proportional to pH above pH 6--7; (2) decreases exponentially as the total molar Fe/As ratio of tailings raffinates is increased from 1/1 to greater than 5/1; and (3) is proportional to temperature with an average Arrhenius activation energy of 13.4 {+-} 4.2 kcal/mol. Study results suggest that if ferric sulfate and slaked lime are added in the tailings neutralization circuit to give a raffinate Fe/As molar ratio of at least 3--5 and a nominal (initial) pH of 8 (final pH of 7--8), arsenic and nickel concentrations of 2 mg/L or less, are probable in porewaters of individual tailings in the TMF for 50 to 10,000 yrs after tailings disposal. However, the tailings will be mixed in the TMF, which will contain about 35% tailings with Fe/As = 3.0, and 65% tailings with Fe/As = 5.0--7.7. Thus, it seems likely that average arsenic pore water concentrations in the TMF may not exceed 1 mg/L.« less

Geochemical characterisation of seepage and drainage water quality from two sulphide mine tailings impoundments: Acid mine drainage versus neutral mine drainage

USGS Publications Warehouse

Heikkinen, P.M.; Raisanen, M.L.; Johnson, R.H.

2009-01-01

Seepage water and drainage water geochemistry (pH, EC, O2, redox, alkalinity, dissolved cations and trace metals, major anions, total element concentrations) were studied at two active sulphide mine tailings impoundments in Finland (the Hitura Ni mine and Luikonlahti Cu mine/talc processing plant). The data were used to assess the factors influencing tailings seepage quality and to identify constraints for water treatment. Changes in seepage water quality after equilibration with atmospheric conditions were evaluated based on geochemical modelling. At Luikonlahti, annual and seasonal changes were also studied. Seepage quality was largely influenced by the tailings mineralogy, and the serpentine-rich, low sulphide Hitura tailings produced neutral mine drainage with high Ni. In contrast, drainage from the high sulphide, multi-metal tailings of Luikonlahti represented typical acid mine drainage with elevated contents of Zn, Ni, Cu, and Co. Other factors affecting the seepage quality included weathering of the tailings along the seepage flow path, process water input, local hydrological settings, and structural changes in the tailings impoundment. Geochemical modelling showed that pH increased and some heavy metals were adsorbed to Fe precipitates after net alkaline waters equilibrated with the atmosphere. In the net acidic waters, pH decreased and no adsorption occurred. A combination of aerobic and anaerobic treatments is proposed for Hitura seepages to decrease the sulphate and metal loading. For Luikonlahti, prolonged monitoring of the seepage quality is suggested instead of treatment, since the water quality is still adjusting to recent modifications to the tailings impoundment.

Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

NASA Astrophysics Data System (ADS)

Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

Gravity alterations are widely recognized to influence living systems. They may cause temporary or permanent effects on physiology and development at different levels, from gene expression to morphogenesis. However, the molecular mechanisms underlying these effects are often unclear, and adequate model systems to study them are required. To address this problem we developed a new experimental model of how gravity affects morphogenesis during tail regeneration in the newt Pleurodeles waltl. The effects of increased gravity on newt tail morphogenesis were first documented in two joint Russian-US NASA spaceflight experiments in the Russian Foton-M2 (2005) and Foton-M3 (2007) missions. In these experiments the shape of newt tail regenerate was found to depend on the gravity level, being dorso-ventrally symmetrical in microgravity and in neutrally-buoyant aquarium controls, versus hook-like and bent downward in 1g controls. These 1g controls were conducted in spaceflight habitats using a water-saturated PVA sponge mat. These results were reproducible in multiple spaceflight, and ground laboratory studies, both in the US at NASA ARC and in Russia at IDB RAS, and were characterized in detail using morphometry and histology approaches. The role of hypergravity in shaping morphogenesis was confirmed at NASA ARC with an experiment in the ISS Testbed 8-foot diameter centrifuge operating at 2g. Animals that experienced two-week centrifugation (the period of time used in the Foton flights) developed the same hook-like regenerates as 1g controls, and morphometric analysis revealed no significant difference between 1g and 2g groups, however both were significantly different from aquarium controls. We hypothesize that exposure to 1g or 2g during tail morphogenesis constitutes excessive loading for newts that are adapted to microgravity-like conditions in their aquatic habitat. Because Heat Shock Proteins (HSPs) are stress-induced molecules that respond to a broad variety of factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

75 FR 55453 - Airworthiness Directives; Sikorsky Aircraft Corporation Model S-76A, S-76B, and S-76C Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-13

... track-and-balance of the tail rotor. Finally, this AD requires installing a vertical stabilizer..., track- and-balance of the tail rotor. Accomplishing the tail rotor track-and- balance would involve both...'' state-- almost to the point of takeoff, and the mechanic would accomplish the vibration measurements...

Reversing Breast Cancer-Induced Immune Suppression

DTIC Science & Technology

2014-09-01

Species MDSC: Myeloid-Derived Suppressor Cells PI: Propidium iodide xC-: System xC- xCT: Cystine/Glutamate Antiporter Project Summary Aim 1- In...animals may live longer due to enhanced resistance to metastasis. Resistance to metastasis requires a competent immune system [27]. Since Nrf2...Smith C, Chang MY, Parker KH, Beury DW, DuHadaway JB, Flick HE, Boulden J, Sutanto-Ward E, Soler AP, Laury-Kleintop LD, Mandik-Nayak L, Metz R, Ostrand

Quasi-steady state aerodynamics of the cheetah tail.

PubMed

Patel, Amir; Boje, Edward; Fisher, Callen; Louis, Leeann; Lane, Emily

2016-08-15

During high-speed pursuit of prey, the cheetah (Acinonyx jubatus) has been observed to swing its tail while manoeuvring (e.g. turning or braking) but the effect of these complex motions is not well understood. This study demonstrates the potential of the cheetah's long, furry tail to impart torques and forces on the body as a result of aerodynamic effects, in addition to the well-known inertial effects. The first-order aerodynamic forces on the tail are quantified through wind tunnel testing and it is observed that the fur nearly doubles the effective frontal area of the tail without much mass penalty. Simple dynamic models provide insight into manoeuvrability via simulation of pitch, roll and yaw tail motion primitives. The inertial and quasi-steady state aerodynamic effects of tail actuation are quantified and compared by calculating the angular impulse imparted onto the cheetah's body and its shown aerodynamic effects contribute to the tail's angular impulse, especially at the highest forward velocities. © 2016. Published by The Company of Biologists Ltd.

Quasi-steady state aerodynamics of the cheetah tail

PubMed Central

Boje, Edward; Fisher, Callen; Louis, Leeann; Lane, Emily

2016-01-01

ABSTRACT During high-speed pursuit of prey, the cheetah (Acinonyx jubatus) has been observed to swing its tail while manoeuvring (e.g. turning or braking) but the effect of these complex motions is not well understood. This study demonstrates the potential of the cheetah's long, furry tail to impart torques and forces on the body as a result of aerodynamic effects, in addition to the well-known inertial effects. The first-order aerodynamic forces on the tail are quantified through wind tunnel testing and it is observed that the fur nearly doubles the effective frontal area of the tail without much mass penalty. Simple dynamic models provide insight into manoeuvrability via simulation of pitch, roll and yaw tail motion primitives. The inertial and quasi-steady state aerodynamic effects of tail actuation are quantified and compared by calculating the angular impulse imparted onto the cheetah's body and its shown aerodynamic effects contribute to the tail's angular impulse, especially at the highest forward velocities. PMID:27412267

Laboratory investigation and simulation of breakthrough curves in karst conduits with pools

NASA Astrophysics Data System (ADS)

Zhao, Xiaoer; Chang, Yong; Wu, Jichun; Peng, Fu

2017-12-01

A series of laboratory experiments are performed under various hydrological conditions to analyze the effect of pools in pipes on breakthrough curves (BTCs). The BTCs are generated after instantaneous injections of NaCl tracer solution. In order to test the feasibility of reproducing the BTCs and obtain transport parameters, three modeling approaches have been applied: the equilibrium model, the linear graphical method and the two-region nonequilibrium model. The investigation results show that pools induce tailing of the BTCs, and the shapes of BTCs depend on pool geometries and hydrological conditions. The simulations reveal that the two-region nonequilibrium model yields the best fits to experimental BTCs because the model can describe the transient storage in pools by the partition coefficient and the mass transfer coefficient. The model parameters indicate that pools produce high dispersion. The increased tailing occurs mainly because the partition coefficient decreases, as the number of pools increases. When comparing the tracer BTCs obtained using the two types of pools with the same size, the more appreciable BTC tails that occur for symmetrical pools likely result mainly from the less intense exchange between the water in the pools and the water in the pipe, because the partition coefficients for the two types of pools are virtually identical. Dispersivity values decrease as flow rates increase; however, the trend in dispersion is not clear. The reduced tailing is attributed to a decrease in immobile water with increasing flow rate. It provides evidence for hydrodynamically controlled tailing effects.

Low-speed wind tunnel test results of the Canard Rotor/Wing concept

NASA Technical Reports Server (NTRS)

Bass, Steven M.; Thompson, Thomas L.; Rutherford, John W.; Swanson, Stephen

1993-01-01

The Canard Rotor/Wing (CRW), a high-speed rotorcraft concept, was tested at the National Aeronautics and Space Administration (NASA) Ames Research Center's 40- by 80-Foot Wind Tunnel in Mountain View, California. The 1/5-scale model was tested to identify certain low-speed, fixed-wing, aerodynamic characteristics of the configuration and investigate the effectiveness of two empennages, an H-Tail and a T-Tail. The paper addresses the principal test objectives and the results achieved in the wind tunnel test. These are summarized as: i) drag build-up and differences between the H-Tail and T-Tail configuration, ii) longitudinal stability of the H-Tail and T-Tail configurations in the conversion and cruise modes, iii) control derivatives for the canard and elevator in the conversion and cruise modes, iv) aerodynamic characteristics of varying the rotor/wing azimuth position, and v) canard and tail lift/trim capability for conversion conditions.

Heavy-Tailed Fluctuations in the Spiking Output Intensity of Semiconductor Lasers with Optical Feedback

PubMed Central

2016-01-01

Although heavy-tailed fluctuations are ubiquitous in complex systems, a good understanding of the mechanisms that generate them is still lacking. Optical complex systems are ideal candidates for investigating heavy-tailed fluctuations, as they allow recording large datasets under controllable experimental conditions. A dynamical regime that has attracted a lot of attention over the years is the so-called low-frequency fluctuations (LFFs) of semiconductor lasers with optical feedback. In this regime, the laser output intensity is characterized by abrupt and apparently random dropouts. The statistical analysis of the inter-dropout-intervals (IDIs) has provided many useful insights into the underlying dynamics. However, the presence of large temporal fluctuations in the IDI sequence has not yet been investigated. Here, by applying fluctuation analysis we show that the experimental distribution of IDI fluctuations is heavy-tailed, and specifically, is well-modeled by a non-Gaussian stable distribution. We find a good qualitative agreement with simulations of the Lang-Kobayashi model. Moreover, we uncover a transition from a less-heavy-tailed state at low pump current to a more-heavy-tailed state at higher pump current. Our results indicate that fluctuation analysis can be a useful tool for investigating the output signals of complex optical systems; it can be used for detecting underlying regime shifts, for model validation and parameter estimation. PMID:26901346

Postsacral vertebral morphology in relation to tail length among primates and other mammals.

PubMed

Russo, Gabrielle A

2015-02-01

Tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. One prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. However, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. This study quantifies postsacral vertebral morphology among living primates and other mammals known to differ in relative tail length (RTL). Linear and angular measurements with known biomechanical significance were collected on the first, mid-, and transition proximal postsacral vertebrae, and their relationship with RTL was assessed using phylogenetic generalized least-squares regression methods. Compared to shorter-tailed primates, longer-tailed primates possess a greater number of postsacral vertebral features associated with increased proximal tail flexibility (e.g., craniocaudally longer vertebral bodies), increased intervertebral body joint range of motion (e.g., more circularly shaped cranial articular surfaces), and increased leverage of tail musculature (e.g., longer spinous processes). These observations are corroborated by the comparative mammalian sample, which shows that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed (e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis) primates, respectively. Multivariate models demonstrate that the variables examined account for 70% (all mammals) to 94% (only primates) of the variance in RTL. Results of this study may be used to infer the tail lengths of extinct primates and other mammals, thereby improving our understanding about the evolution of tail reduction/loss. © 2014 Wiley Periodicals, Inc.

Benoit Mandelbrot in finance

NASA Astrophysics Data System (ADS)

Walter, Christian

2015-03-01

The following sections are included: * Introduction * The Noah and Joseph effects and the non-Gaussian and non-Brownian issues of the financial theory * The first model of Mandelbrot (1962): α-stable motion with paretian tails * The second model of Mandelbrot (1965): fractional brownian motion with aperiodic cycles * The third model of Mandelbrot (1967): time changed Brownian motion with stochastic clock * Appendix: a tale of fat tails * Bibliography

Ultrastructural Morphology of Sperm from Human Globozoospermia

PubMed Central

Ricci, Giuseppe; Andolfi, Laura; Luppi, Stefania; Boscolo, Rita; Zweyer, Marina; Trevisan, Elisa

2015-01-01

Globozoospermia is a rare disorder characterized by the presence of sperm with round head, lacking acrosome. Coiling tail around the nucleus has been reported since early human studies, but no specific significance has conferred it. By contrast, studies on animal models suggest that coiling tail around the nucleus could represent a crucial step of defective spermatogenesis, resulting in round-headed sperm. No observations, so far, support the transfer of this hypothesis to human globozoospermia. The purpose of this work was to compare ultrastructural morphology of human and mouse model globozoospermic sperm. Sperm have been investigated by using scanning and transmission electron microscopy. The images that we obtained show significant similarities to those described in GOPC knockout mice, an animal model of globozoospermia. By using this model as reference, we were able to identify the probable steps of the tail coiling process in human globozoospermia. Although we have no evidence that there is the same pathophysiology in man and knocked-out mouse, the similarities between these ultrastructural observations in human and those in the experimental model are very suggestive. This is the first demonstration of the existence of relevant morphological homologies between the tail coiling in animal model and human globozoospermia. PMID:26436098

New scaling model for variables and increments with heavy-tailed distributions

NASA Astrophysics Data System (ADS)

Riva, Monica; Neuman, Shlomo P.; Guadagnini, Alberto

2015-06-01

Many hydrological (as well as diverse earth, environmental, ecological, biological, physical, social, financial and other) variables, Y, exhibit frequency distributions that are difficult to reconcile with those of their spatial or temporal increments, ΔY. Whereas distributions of Y (or its logarithm) are at times slightly asymmetric with relatively mild peaks and tails, those of ΔY tend to be symmetric with peaks that grow sharper, and tails that become heavier, as the separation distance (lag) between pairs of Y values decreases. No statistical model known to us captures these behaviors of Y and ΔY in a unified and consistent manner. We propose a new, generalized sub-Gaussian model that does so. We derive analytical expressions for probability distribution functions (pdfs) of Y and ΔY as well as corresponding lead statistical moments. In our model the peak and tails of the ΔY pdf scale with lag in line with observed behavior. The model allows one to estimate, accurately and efficiently, all relevant parameters by analyzing jointly sample moments of Y and ΔY. We illustrate key features of our new model and method of inference on synthetically generated samples and neutron porosity data from a deep borehole.

Alleviation of environmental risks associated with severely contaminated mine tailings using amendments: Modeling of trace element speciation, solubility, and plant accumulation.

PubMed

Pardo, Tania; Bes, Cleménce; Bernal, Maria Pilar; Clemente, Rafael

2016-11-01

Tailings are considered one of the most relevant sources of contamination associated with mining activities. Phytostabilization of mine spoils may need the application of the adequate combination of amendments to facilitate plant establishment and reduce their environmental impact. Two pot experiments were set up to assess the capability of 2 inorganic materials (calcium carbonate and a red mud derivate, ViroBind TM ), alone or in combination with organic amendments, for the stabilization of highly acidic trace element-contaminated mine tailings using Atriplex halimus. The effects of the treatments on tailings and porewater physico-chemical properties and trace-element accumulation by the plants, as well as the processes governing trace elements speciation and solubility in soil solution and their bioavailability were modeled. The application of the amendments increased tailings pH and decreased (>99%) trace elements solubility in porewater, but also changed the speciation of soluble Cd, Cu, and Pb. All the treatments made A. halimus growth in the tailings possible; organic amendments increased plant biomass and nutritional status, and reduced trace-element accumulation in the plants. Tailings amendments modified trace-element speciation in porewater (favoring the formation of chlorides and/or organo-metallic forms) and their solubility and plant uptake, which were found to be mainly governed by tailing/porewater pH, electrical conductivity, and organic carbon content, as well as soluble/available trace-element concentrations. Environ Toxicol Chem 2016;35:2874-2884. © 2016 SETAC. © 2016 SETAC.

Does climate have heavy tails?

NASA Astrophysics Data System (ADS)

Bermejo, Miguel; Mudelsee, Manfred

2013-04-01

When we speak about a distribution with heavy tails, we are referring to the probability of the existence of extreme values will be relatively large. Several heavy-tail models are constructed from Poisson processes, which are the most tractable models. Among such processes, one of the most important are the Lévy processes, which are those process with independent, stationary increments and stochastic continuity. If the random component of a climate process that generates the data exhibits a heavy-tail distribution, and if that fact is ignored by assuming a finite-variance distribution, then there would be serious consequences (in the form, e.g., of bias) for the analysis of extreme values. Yet, it appears that it is an open question to what extent and degree climate data exhibit heavy-tail phenomena. We present a study about the statistical inference in the presence of heavy-tail distribution. In particular, we explore (1) the estimation of tail index of the marginal distribution using several estimation techniques (e.g., Hill estimator, Pickands estimator) and (2) the power of hypothesis tests. The performance of the different methods are compared using artificial time-series by means of Monte Carlo experiments. We systematically apply the heavy tail inference to observed climate data, in particular we focus on time series data. We study several proxy and directly observed climate variables from the instrumental period, the Holocene and the Pleistocene. This work receives financial support from the European Commission (Marie Curie Initial Training Network LINC, No. 289447, within the 7th Framework Programme).

A NASTRAN investigation of simulated projectile damage effects on a UH-1B tail boom model

NASA Technical Reports Server (NTRS)

Futterer, A. T.

1980-01-01

A NASTRAN model of a UH-1B tail boom that had been designed for another project was used to investigate the effect on structural integrity of simulated projectile damage. Elements representing skin, and sections of stringers, longerons and bulkheads were systematically deleted to represent projectile damage. The structure was loaded in a manner to represent the flight loads that would be imposed on the tail boom at a 130 knot cruise. The deflection of four points on the rear of the tail boom relative to the position of these points for the unloaded, undamaged condition of the tail boom was used as a measure of the loss of structural rigidity. The same procedure was then used with the material properties of the aluminum alloys replaced with the material properties of T300/5208 high strength graphite/epoxy fibrous composite material, (0, + or - 45, 90)s for the skin and (0, + or - 45)s for the longerons, stringers, and bulk heads.

Experimental study of main rotor tip geometry and tail rotor interactions in hover. Volume 2: Run log and tabulated data

NASA Technical Reports Server (NTRS)

Balch, D. T.; Lombardi, J.

1985-01-01

A model scale hover test was conducted in the Sikorsky Aircraft Model Rotor hover Facility to identify and quantify the impact of the tail rotor on the demonstrated advantages of advanced geometry tip configurations. The existence of mutual interference between hovering main rotor and a tail rotor was acknowledged in the test. The test was conducted using the Basic Model Test Rig and two scaled main rotor systems, one representing a 1/5.727 scale UH-60A BLACK HAWK and the others a 1/4.71 scale S-76. Eight alternate rotor tip configurations were tested, 3 on the BLACK HAWK rotor and 6 on the S-76 rotor. Four of these tips were then selected for testing in close proximity to an operating tail rotor (operating in both tractor and pusher modes) to determine if the performance advantages that could be obtained from the use of advanced geometry tips in a main rotor only environment would still exist in the more complex flow field involving a tail rotor. This volume contains the test run log and tabulated data.

Effect of nozzle and vertical-tail variables on the performance of a 3-surface F-15 model at transonic Mach numbers. [Langley 16 foot transonic tunnel

NASA Technical Reports Server (NTRS)

Pendergraft, O. C., Jr.; Bare, E. A.

1982-01-01

An investigation was conducted in the Langley 16 foot transonic tunnel to determine the longitudinal aerodynamic characteristics of twin two dimensional nozzles and twin baseline axisymmetric nozzles installed on a fully metric 0.047 scale model of the F-15 three surface configuration (canards, wing, horizontal tails). The effects on performance of two dimensional nozzle in flight thrust reversing, locations and orientation of the vertical tails, and deflections of the horizontal tails were also determined. Test data were obtained at static conditions and at Mach numbers from 0.60 to 1.20 over an angle of attack range from -2 deg to 15 deg. Nozzle pressure ratio was varied from jet off to about 6.5.

Atrophy and growth failure of rat hindlimb muscles in tail-cast suspension

NASA Technical Reports Server (NTRS)

Jaspers, S. R.; Tischler, M. E.

1984-01-01

The primary objective of the present study is related to an evaluation of a modified tail-cast suspension model as a means of identifying metabolic factors which control or are associated with muscle atrophy and growth failure. Two different control conditions (normal and tail-casted weight bearing) were studied to determine the appropriate control for tail-cast suspension. A description is presented of a model which is most useful for studying atrophy of hindlimb muscles under certain conditions. Female Sprague-Dawley rats were employed in the experiments. Attention is given to growth rate and urinary excretion of urea and ammonia in different types of rats, the relationship between body weight and skeletal muscle weight, and the relationship between animal body weight and rates of protein synthesis and protein degradation.

Experimental parametric studies of transonic T-tail flutter. [wind tunnel tests

NASA Technical Reports Server (NTRS)

Ruhlin, C. L.; Sandford, M. C.

1975-01-01

Wind-tunnel tests of the T-tail of a wide-body jet airplane were made at Mach numbers up to 1.02. The model consisted of a 1/13-size scaled version of the T-tail, fuselage, and inboard wing of the airplane. Two interchangeable T-tails were tested, one with design stiffness for flutter-clearance studies and one with reduced stiffness for flutter-trend studies. Transonic antisymmetric-flutter boundaries were determined for the models with variations in: (1) fin-spar stiffness, (2) stabilizer dihedral angle (-5 deg and 0 deg), (3) wing and forward-fuselage shape, and (4) nose shape of the fin-stabilizer juncture. A transonic symmetric-flutter boundary and flutter trends were established for variations in stabilizer pitch stiffness. Photographs of the test configurations are shown.

75 FR 47182 - Airworthiness Directives; GROB-WERKE GMBH & CO KG Models G102 ASTIR CS and G102 STANDARD ASTIR...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-05

... fuselage tail which could cause a displacement of the sailplane centre of gravity and consequently may lead... tanks could run down into the fuselage and fuselage tail which could cause a displacement of the... tanks could run down into the fuselage and fuselage tail which could cause a displacement of the...

Kinetic Study on the Removal of Iron from Gold Mine Tailings by Citric Acid

NASA Astrophysics Data System (ADS)

Mashifana, T.; Mavimbela, N.; Sithole, N.

2018-03-01

The Gold mining generates large volumes of tailings, with consequent disposal and environmental problems. Iron tends to react with sulphur to form pyrite and pyrrhotite which then react with rain water forming acid rain. The study focuses on the removal of iron (Fe) from Gold Mine tailings; Fe was leached using citric acid as a leaching reagent. Three parameters which have an effect on the removal of Fe from the gold mine tailings, namely; temperature (25 °C and 50 °C), reagent concentration (0.25 M, 0.5 M, 0.75 M and 1 M) and solid loading ratio (20 %, 30 % and 40 %) were investigated. It was found that the recovery of Fe from gold mine tailings increased with increasing temperature and reagent concentration, but decreased with increasing solid loading ratio. The optimum conditions for the recovery of Fe from gold mine tailings was found to be at a temperature of 50 ºC, reagent concentration of 1 M and solid loading of 20 %. Three linear kinetic models were investigated and Prout-Tompkins kinetic model was the best fit yielding linear graphs with the highest R2 values.

Effect of Tail Dihedral on Lateral Control Effectiveness at High Subsonic Speeds of Differentially Deflected Horizontal-Tail Surfaces on a Configuration having a Thin Highly Tapered Wing

NASA Technical Reports Server (NTRS)

Fournier, Paul G.

1959-01-01

Tests have been conducted in the Langley high-speed 7- by 10-foot tunnel to determine the effect of tail dihedral on lateral control effectiveness of a complete-model configuration having differentially deflected horizontal-tail surfaces. Limited tests were made to determine the lateral characteristics as well as the longitudinal characteristics in sideslip. The wing had an aspect ratio of 3, a taper ratio of 0.14, 28.80 deg sweep of the quarter-chord line with zero sweep at the 80-percent-chord line, and NACA 65A004 airfoil sections. The test Mach number range extended from 0.60 to 0.92. There are only small variations in the roll effectiveness parameter C(sub iota delta) with negative tail dihedral angle. The tail size used on the test model, however, is perhaps inadequate for providing the roll rates specified by current military requirements at subsonic speeds. The lateral aerodynamic characteristics were essentially constant throughout the range of sideslip angle from 12 deg to -12 deg. A general increase in yawing moment was noted with increased negative dihedral throughout the Mach number range.

Tabulated Pressure Coefficient Data from a Tail Loads Investigation on a 1/15-Scale Model of the Goodyear XZP5K Airship

NASA Technical Reports Server (NTRS)

Cannon, Michael D.

1956-01-01

This paper contains tail and hull loads data obtained in an investigation of a l/15-scale model of the Goodyear XZP5K airship. Data are presented in the form of tabulated pressure coefficients over a pitch and yaw range of +/-20 deg and 0 deg to 30 deg respectively, with various rudder and elevator deflections. Two tail configurations of different plan forms were tested on the model. The investigation was conducted in the Langley full-scale tunnel at a Reynolds number of approximately 16.5 x 10(exp 6) based on hull length, which corresponds to a Mach number of about 0.12.

[Effect of topical application of a recombinant adenovirus carrying promyelocytic leukemia gene in a psoriasis-like mouse model].

PubMed

Wang, Qiongyu; Zhang, Aijun; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

2013-03-01

To investigate the effects of topical treatment with adenovirus-mediated promyelocytic leukemia gene (PML) gene in a psoriasis-like mouse model. The effect of adenovirus-mediated PML gene on the granular layer of mouse tail scale epidermis and epithelial mitosis were observed on longitudinal histological sections prepared from the tail skin and vaginal epithelium of the mice. Adenovirus-mediated PML gene significantly inhibited mitosis of mouse vaginal epithelial cells and promoted the formation of granular layer in mouse tail scale epidermis. The therapeutic effect of PML gene in the psoriasis-like mouse model may be associated with increased granular cells and suppressed epidemic cell proliferation.

A Tale of Two Tails: Exploring Stellar Populations in the Tidal Tails of NGC 3256

NASA Astrophysics Data System (ADS)

Rodruck, Michael; Charlton, Jane C.; Konstantopoulos, Iraklis

2016-01-01

Galaxy interactions can inject material into the intergalactic medium via violent gravitational dynamics, often visualized in tidal tails. The composition of these tails has remained a mystery, as previous studies have focused on detecting tidal features, rather than the composite material itself. We have developed an observing program using deep, multiband imaging to probe the chaotic regions of tidal tails in search for an underlying stellar population. NGC 3256's twin tidal tails serve as a case study for this new technique. Our results show color values of u - g = 1.15 and r - i = 0.08 for the Western tail, and u - g = 1.33 and r - i = 0.22 for the Eastern tail, corresponding to discrepant ages between the tails of approximately 320 Myr and 785 Myr, respectively. With the interaction age of the system measured at 400 Myr, we find the stellar light in Western tail to be dominated by disrupted star clusters formed during and after the interaction, whereas the light from the Eastern tail is dominated by a 10 Gyr population originating from the host galaxies. We fit the Eastern tail color to a Mixed Stellar Population (MSP) model comprised 94% by mass of a 10 Gyr stellar population, and 6% of a 309 Myr population. We find 52% of the bolometric flux originating from this 10 Gyr population. We also detect a blue to red color gradient in each tail, running from galactic center to tail tip. In addition to tidal tail light, we detect 29 star cluster candidates (SCCs) in the Western tail and 19 in the Eastern, with mean ages of 282 Myr and 98 Myr respectively. Interestingly, we find an excess of very blue SCCs in the Eastern tail as compared to the Western tail, marking a recent, small episode of star formation.

The Role of Histone Tails in the Nucleosome: A Computational Study

PubMed Central

Erler, Jochen; Zhang, Ruihan; Petridis, Loukas; Cheng, Xiaolin; Smith, Jeremy C.; Langowski, Jörg

2014-01-01

Histone tails play an important role in gene transcription and expression. We present here a systematic computational study of the role of histone tails in the nucleosome, using replica exchange molecular dynamics simulations with an implicit solvent model and different well-established force fields. We performed simulations for all four histone tails, H4, H3, H2A, and H2B, isolated and with inclusion of the nucleosome. The results confirm predictions of previous theoretical studies for the secondary structure of the isolated tails but show a strong dependence on the force field used. In the presence of the entire nucleosome for all force fields, the secondary structure of the histone tails is destabilized. Specific contacts are found between charged lysine and arginine residues and DNA phosphate groups and other binding sites in the minor and major DNA grooves. Using cluster analysis, we found a single dominant configuration of binding to DNA for the H4 and H2A histone tails, whereas H3 and H2B show multiple binding configurations with an equal probability. The leading stabilizing contribution for those binding configurations is the attractive interaction between the positively charged lysine and arginine residues and the negatively charged phosphate groups, and thus the resulting charge neutralization. Finally, we present results of molecular dynamics simulations in explicit solvent to confirm our conclusions. Results from both implicit and explicit solvent models show that large portions of the histone tails are not bound to DNA, supporting the complex role of these tails in gene transcription and expression and making them possible candidates for binding sites of transcription factors, enzymes, and other proteins. PMID:25517156

The Energetic Neutral Atoms of the "Croissant" Heliosphere with Jets

NASA Astrophysics Data System (ADS)

Kornbleuth, M. Z.; Opher, M.; Michael, A.

2017-12-01

Opher et al. (2015) suggests the heliosphere may have two jets in the tail-ward direction driven to the north and south. This new model, the "Croissant Heliosphere", is in contrast to the classically accepted view of a comet-like tail. We investigate the effect of the heliosphere with jets model on energetic neutral atom (ENA) maps. Regardless of the existence of a split tail, other models show heliosheath plasma confined by the toroidal magnetic field in a "slinky" structure, similar to astrophysical jets bent by the interstellar medium. Therefore, the confinement of the plasma should appear in the ENA maps. ENA maps from the Interstellar Boundary Explorer (IBEX) have recently shown two high latitude lobes with excess ENA flux at higher energies in the tail of the heliosphere. These lobes could be a signature of the two jet structure of the heliosphere, while some have argued they are cause by the fast/slow solar wind profile. Here we present the ENA maps of the "Croissant Heliosphere" using initially a uniform solar wind. We incorporate pick-up ions (PUIs) into our model based on the kinetic modeling of Malama et al. (2006). We include the extinction of PUIs in the heliosheath and describe a locally created PUI population resulting from this extinction process. Additionally, we include the angular dependence of the PUIs based on the work of Vasyliunas & Siscoe (1976). With our model, we find that, in the presence of a uniform solar wind, the "heliosphere with jets" model is able to qualitatively reproduce the lobe structure of the tail seen in IBEX measurements. Turbulence also manifests itself within the lobes of the simulated ENA maps on the order of years. Finally we will present ENA maps using a time-dependent model of the heliosphere with the inclusion of solar cycle.

Effects of canard location on the aerodynamic characteristics of a blunt-nosed missile at Mach numbers of 1.5 and 2.0. [in the Ames 6x6 wind tunnel

NASA Technical Reports Server (NTRS)

Kassner, D. L.; Wettlaufer, B.

1977-01-01

A blunt-nosed missile model with nose-mounted canards and cruciform tail surfaces was tested in the Ames 6 by 6-Foot Wind Tunnel to determine the contributions of the component aerodynamic surfaces to the static aerodynamic characteristics at Mach numbers of 1.5 and 2.0 and Reynolds number of 1 million based on body diameter. Data were obtained at angles of attack ranging from -3 deg to 12 deg and canard-deflection angles from -3 deg to 15 deg for various stages of model build-up (i.e., with and without canard and/or tail surfaces). Results were obtained with the canards at two different nose locations. For the canard and tail arrangements investigated, the model was trimmable at angles of attack up to about 4 deg or 5 deg with canard deflections of 9 deg. For this blunt-nosed model, there was little effect of canard location on trim angle of attack. The tail arrangements studied provided ample pitch stability.

Experimental study of main rotor/tail rotor/airframe interactions in hover. Volume 1: Text and figures

NASA Technical Reports Server (NTRS)

Balch, D. T.; Saccullo, A.; Sheehy, T. W.

1983-01-01

To assist in identifying and quantifying the relevant parameters associated with the complex topic of main rotor/fuselage/tail rotor interference, a model scale hover test was conducted in the Model Rotor Hover Facility. The test was conducted using the basic model test rig, fuselage skins to represent a UH-60A BLACK HAWK helicopter, 4 sets of rotor blades of varying geometry (i.e., twist, airfoils and solidity) and a model tail rotor that could be relocated to give changes in rotor clearance (axially, laterally, and vertically), can't angle and operating model (pusher or tractor). The description of the models and the tests, data analysis and summary (including plots) are included. The customary system of units gas used for principal measurements and calculations. Expressions in both SI units and customary units are used with the SI units stated first and the customary units afterwords, in parenthesis.

Buckling Instabilities and Complex Dynamics in a Model of Uniflagellar Bacterial Locomotion

NASA Astrophysics Data System (ADS)

Nguyen, Frank; Graham, Michael

2015-11-01

Locomotion of microorganisms at low Reynolds number is a long studied problem. Of particular interest are organisms using a single flagellum to undergo a wide range of motions: pushing, pulling, and tumbling or flicking. Recent experiments have connected the stability of the hook protein, connecting cell motor and flagellum, to deviations from typical straight swimming trajectories. We seek physical explanations to these phenomena by developing a computationally inexpensive, rigid-body dynamic model of a uniflagellated organism with a flexible hook connection that captures the fundamental dynamics, kinematics, and configurations. Furthermore, the model addresses the effects of hook loading and geometry on the stability of the system. Simulations with low hook flexibility produce the classic straight trajectory, but a large flexibility produces helical trajectories, leading to directional changes when coupled with transient hook stiffening. Minima for critical flexibilities are found in certain subsets of parameter space, implying preferred geometries for certain swimming dynamics. The model verifies proposed mechanisms for swimming in various modes and highlights the role of flexibility in the biology of real organisms and the engineering of artificial microswimmers. This work was supported by NSF grant PHY-1304942.

Foraging mode and evolution of strike-induced chemosensory searching in lizards.

PubMed

Cooper, William E

2003-04-01

Strike-induced chemosensory searching (SICS) in lizards and snakes is a means of relocating prey by scent-trailing. The two main components of SICS are an elevated tongue-flick rate for vomerolfactory sampling after biting prey (PETF) and searching movements. In combination, these behaviors permit scent-trailing. Prey chemical discrimination, which is a prerequisite for SICS, is present in active foragers, but not in ambush foragers. Using comparative data. I show that searching movements and SICS have undergone correlated evolution with foraging mode and with prey chemical discrimination in lizards. This suggests that active foraging selects for prey chemical discrimination, which is then employed to search for escaped prey using the typical movements and tongue-flicking behaviors of active foragers. SICS in lizards is simply heightened active foraging after biting prey. In nonvenomous snakes, SICS is similar to that in lizards but is not restricted to active foragers. Only highly venomous snakes voluntarily release dangerous prey upon envenomation, pause to let the venom incapacitate the prey, and then relocate the prey by scent-trailing. PETF was observed in two ambush foragers and is not evolutionarily correlated with foraging mode or searching movements. Because it occurs in species lacking prey chemical discrimination, such PETF may be a response to gustatory cues or to internal chemicals not encountered on surfaces or trails of uninjured prey.

Laboratory Study on Disconnection Events in Comets

NASA Astrophysics Data System (ADS)

Li, Yan-Fei; Li, Yu-Tong; Wang, Wei-Min; Yuan, Da-Wei; et al.

2018-01-01

When comets interacting with solar wind, straight and narrow plasma tails will be often formed. The most remarkable phenomenon of the plasma tails is the disconnection event, in which a plasma tail is uprooted from the comet's head and moves away from the comet. In this paper, the interaction process between a comet and solar wind is simulated by using a laser-driven plasma cloud to hit a cylinder obstacle. A disconnected plasma tail is observed behind the obstacle by optical shadowgraphy and interferometry. Our particle-in-cell simulations show that the diference in thermal velocity between ions and electrons induces an electrostatic field behind the obstacle. This field can lead to the convergence of ions to the central region, resulting in a disconnected plasma tail. This electrostatic field-induced model may be a possible explanation for the disconnection events of cometary tails.

Biological intervertebral disc replacement: an in vivo model and comparison of two surgical techniques to approach the rat caudal disc

PubMed Central

Gebhard, Harry; James, Andrew R.; Bowles, Robby D.; Dyke, Jonathan P.; Saleh, Tatianna; Doty, Stephen P.; Bonassar, Lawrence J.; Härtl, Roger

2011-01-01

Study design: Prospective randomized animal study. Objective: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. Methods: The caudal 3/4 intervertebral disc (IVD) of the rat tail was approached by two surgical techniques: blunt dissection, stripping and retracting (Technique 1) or incising and repairing (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was dissected and removed, and then either discarded or reinserted. Outcome measures were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2-sequences for measurement of disc space height (DSH) and disc hydration). Microcomputed tomographic imaging (micro CT) was additionally performed postmortem. Results: No vascular injuries occurred and no systemic or local infections were observed over the course of 1 month. Tail movements were maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH with IVD reinsertion but not without. The DSH was demonstrated on MRI measurement. A new scoring system to assess IVD appearances was described. Conclusions: The rat tail model, with a tendon dividing surgical technique, can function as an orthotopic animal model for IVD research. Mechanical stimulation is maintained by preserved tail movements. 7T MRI is a feasible modality for longitudinal monitoring for the rat caudal disc. PMID:22956934

Global simulation of formation and evolution of plasmoid and flux-rope in the Earth's Magnetotail

NASA Astrophysics Data System (ADS)

Ge, Y.; Raeder, J.; Du, A.

2014-12-01

The observation of plasmoids and flux-ropes in the Earth's magnetotail was crucial to establish the simultaneous presence of multiple x-lines in the tail, and has become the basis for the Near Earth Neutral Line (NENL) model of substorms. While the "classical" NENL model envisions x-lines that extend across the entire tail, recent observations have shown that neither do the x-lines and resulting plasmoids encompass the entire tail, nor do the x-lines have to lie along the y-axis. The fragmentation of the tail by spatially and temporally limited x-lines has important consequences for the mass and energy budget of the tail. Recent ARTEMIS observations have shown that the plasmoids in the distant tail are limited in the Y direction and some flux ropes are tilted during their tailward propagation. Understanding their formation and evolution during their propagation through the magnetotail shall shred more light on the general energy and flux transport of the Earth's magnetosphere. In this study we simulate plasmoids and flux-ropes in the Earth's magnetotail using the Open Global Geospace Circulation Model (OpenGGCM). We investigate the generation mechanisms for tail plasmoids and flux-ropes and their evolution as they propagate in the magnetotail. The simulation results show that the limited extend of NENL controls the length or the Y scale of tail plasmoid and flux rope. In addition, by studying their 3D magnetic topology we find that the tilted flux rope forms due to a progressive spreading of reconnection line along the east-west direction, which produces and releases two ends of the flux rope at different times and in different speeds. By constructing a catalogue of observational signatures of plasmoid and flux rope we compare the differences of their signatures and find that large-scale plasmoids have much weaker core fields than that inside the small-scale flux ropes.

75 FR 70101 - Airworthiness Directives; Sikorsky Aircraft Corporation (Sikorsky) Model S-70A and S-70C Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... test (UT) inspection of the tail gearbox output bevel gear (gear) for a crack. If you find a crack... gear cracking incidents, one of which resulted in the tail rotor separating from the helicopter. The actions specified by this AD are intended to detect a crack in the gear to prevent a tail rotor separating...

Initial speed of knots in the plasma tail of C/2013 R1(Lovejoy)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yagi, Masafumi; Furusho, Reiko; Terai, Tsuyoshi

We report short-time variations in the plasma tail of C/2013 R1(Lovejoy). A series of short (2–3 minutes) exposure images with the 8.2 m Subaru telescope shows faint details of filaments and their motions over a 24 minute observing duration. We identified rapid movements of two knots in the plasma tail near the nucleus (∼3×10{sup 5} km). Their speeds are 20 and 25 km s{sup −1} along the tail and 3.8 and 2.2 km s{sup −1} across it, respectively. These measurements set a constraint on an acceleration model of plasma tail and knots as they set the initial speed just aftermore » their formation. We also found a rapid narrowing of the tail. After correcting the motion along the tail, the narrowing speed is estimated to be ∼8 km s{sup −1}. These rapid motions suggest the need for high time-resolution studies of comet plasma tails with a large telescope.« less

Implications of long tails in the distribution of mutant effects

NASA Astrophysics Data System (ADS)

Waxman, D.; Feng, J.

2005-07-01

Long-tailed distributions possess an infinite variance, yet a finite sample that is drawn from such a distribution has a finite variance. In this work we consider a model of a population subject to mutation, selection and drift. We investigate the implications of a long-tailed distribution of mutant allelic effects on the distribution of genotypic effects in a model with a continuum of allelic effects. While the analysis is confined to asexual populations, it does also have implications for sexual populations. We obtain analytical results for a selectively neutral population as well as one subject to selection. We supplement these analytical results with numerical simulations, to take into account genetic drift. We find that a long-tailed distribution of mutant effects may affect both the equilibrium and the evolutionary adaptive behaviour of a population.

Review: Biological and Molecular Differences between Tail Regeneration and Limb Scarring in Lizard: An Inspiring Model Addressing Limb Regeneration in Amniotes.

PubMed

Alibardi, Lorenzo

2017-09-01

Tissue regeneration in lizards represents a unique model of regeneration and scarring in amniotes. The tail and limb contain putative stem cells but also dedifferentiating cells contribute to regeneration. Following tail amputation, inflammation is low and cell proliferation high, leading to regeneration while the intense inflammation in the limb leads to low proliferation and scarring. FGFs stimulate tail and limb regeneration and are present in the wound epidermis and blastema while they disappear in the limb wound epidermis 2-3 weeks postamputation in the scarring outgrowth. FGFs localize in the tail blastema and the apical epidermal peg (AEP), an epidermal microregion that allows tail growth but is absent in the limb. Inflammatory cells invade the limb blastema and wound epidermis, impeding the formation of an AEP. An embryonic program of growth is activated in the tail, dominated by Wnt-positive and -negative regulators of cell proliferation and noncoding RNAs, that represent the key regenerative genes. The balanced actions of these regulators likely impede the formation of a tumor in the tail tip. Genes for FACIT and fibrillar collagens, protease inhibitors, and embryonic keratins are upregulated in the regenerating tail blastema. A strong downregulation of genes for both B and T-lymphocyte activation suggests the regenerating tail blastema is a temporal immune-tolerated organ, whereas a scarring program is activated in the limb. Wnt inhibitors, pro-inflammatory genes, negative regulators of cell proliferation, downregulation of myogenic genes, proteases, and oxidases favoring scarring are upregulated. The evolution of an efficient immune system may be the main limiting barrier for organ regeneration in amniotes, and the poor regeneration of mammals and birds is associated with the efficiency of their mature immune system. This does not tolerate embryonic antigens formed in reprogrammed embryonic cells (as for neoplastic cells) that are consequently eliminated impeding the regeneration of lost organs. © 2017 Wiley Periodicals, Inc.

Single molecule FRET observation of kinesin-1’s head-tail interaction on microtubule

PubMed Central

Aoki, Takahiro; Tomishige, Michio; Ariga, Takayuki

2013-01-01

Kinesin-1 (conventional kinesin) is a molecular motor that transports various cargo such as endoplasmic reticulum and mitochondria in cells. Its two head domains walk along microtubule by hydrolyzing ATP, while the tail domains at the end of the long stalk bind to the cargo. When a kinesin is not carrying cargo, its motility and ATPase activity is inhibited by direct interactions between the tail and head. However, the mechanism of this tail regulation is not well understood. Here, we apply single molecule fluorescence resonance energy transfer (smFRET) to observe this interaction in stalk-truncated kinesin. We found that kinesin with two tails forms a folding conformation and dissociates from microtubules, whereas kinesin with one tail remains bound to the micro-tubule and is immobile even in the presence of ATP. We further investigated the head-tail interaction as well as head-head coordination on the microtubule at various nucleotide conditions. From these results, we propose a two-step inhibition model for kinesin motility. PMID:27493553

On the validity of the dispersion model of hepatic drug elimination when intravascular transit time densities are long-tailed.

PubMed

Weiss, M; Stedtler, C; Roberts, M S

1997-09-01

The dispersion model with mixed boundary conditions uses a single parameter, the dispersion number, to describe the hepatic elimination of xenobiotics and endogenous substances. An implicit a priori assumption of the model is that the transit time density of intravascular indicators is approximately by an inverse Gaussian distribution. This approximation is limited in that the model poorly describes the tail part of the hepatic outflow curves of vascular indicators. A sum of two inverse Gaussian functions is proposed as an alternative, more flexible empirical model for transit time densities of vascular references. This model suggests that a more accurate description of the tail portion of vascular reference curves yields an elimination rate constant (or intrinsic clearance) which is 40% less than predicted by the dispersion model with mixed boundary conditions. The results emphasize the need to accurately describe outflow curves in using them as a basis for determining pharmacokinetic parameters using hepatic elimination models.

Atmospheric dispersion of radon around uranium mill tailings of the former Pridneprovsky Chemical Plant in Ukraine.

PubMed

Kovalets, Ivan V; Asker, Christian; Khalchenkov, Alexander V; Persson, Christer; Lavrova, Tatyana V

2017-06-01

Simulations of atmospheric dispersion of radon around the uranium mill tailings of the former Pridneprovsky Chemical Plant (PChP) in Ukraine were carried out with the aid of two atmospheric dispersion models: the Airviro Grid Model and the CALMET/CALPUFF model chain. The available measurement data of radon emission rates taken in the territories and the close vicinity of tailings were used in simulations. The results of simulations were compared to the yearly averaged measurements of concentration data. Both models were able to reasonably reproduce average radon concentration at the Sukhachivske site using averaged measured emission rates as input together with the measured meteorological data. At the same time, both models significantly underestimated concentrations as compared to measurements collected at the PChP industrial site. According to the results of both dispersion models, it was shown that only addition of significant radon emission rate from the whole territory of PChP in addition to emission rates from the tailings could explain the observed concentration measurements. With the aid of the uncertainty analysis, the radon emission rate from the whole territory of PChP was estimated to be between 1.5 and 3.5 Bq·m -2 s -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-dimensional Magnetohydrodynamical Simulations of the Morphology of Head-Tail Radio Galaxies Based on the Magnetic Tower Jet Model

NASA Astrophysics Data System (ADS)

Gan, Zhaoming; Li, Hui; Li, Shengtai; Yuan, Feng

2017-04-01

The distinctive morphology of head-tail radio galaxies reveals strong interactions between the radio jets and their intra-cluster environment, the general consensus on the morphology origin of head-tail sources is that radio jets are bent by violent intra-cluster weather. We demonstrate in this paper that such strong interactions provide a great opportunity to study the jet properties and also the dynamics of the intra-cluster medium (ICM). By three-dimensional magnetohydrodynamical simulations, we analyze the detailed bending process of a magnetically dominated jet, based on the magnetic tower jet model. We use stratified atmospheres modulated by wind/shock to mimic the violent intra-cluster weather. Core sloshing is found to be inevitable during the wind-cluster core interaction, which induces significant shear motion and could finally drive ICM turbulence around the jet, making it difficult for the jet to survive. We perform a detailed comparison between the behavior of pure hydrodynamical jets and the magnetic tower jet and find that the jet-lobe morphology could not survive against the violent disruption in all of our pure hydrodynamical jet models. On the other hand, the head-tail morphology is well reproduced by using a magnetic tower jet model bent by wind, in which hydrodynamical instabilities are naturally suppressed and the jet could always keep its integrity under the protection of its internal magnetic fields. Finally, we also check the possibility for jet bending by shock only. We find that shock could not bend the jet significantly, and thus could not be expected to explain the observed long tails in head-tail radio galaxies.

Three-dimensional Magnetohydrodynamical Simulations of the Morphology of Head–Tail Radio Galaxies Based on the Magnetic Tower Jet Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, Zhaoming; Yuan, Feng; Li, Hui

The distinctive morphology of head–tail radio galaxies reveals strong interactions between the radio jets and their intra-cluster environment, the general consensus on the morphology origin of head–tail sources is that radio jets are bent by violent intra-cluster weather. We demonstrate in this paper that such strong interactions provide a great opportunity to study the jet properties and also the dynamics of the intra-cluster medium (ICM). By three-dimensional magnetohydrodynamical simulations, we analyze the detailed bending process of a magnetically dominated jet, based on the magnetic tower jet model. We use stratified atmospheres modulated by wind/shock to mimic the violent intra-cluster weather.more » Core sloshing is found to be inevitable during the wind-cluster core interaction, which induces significant shear motion and could finally drive ICM turbulence around the jet, making it difficult for the jet to survive. We perform a detailed comparison between the behavior of pure hydrodynamical jets and the magnetic tower jet and find that the jet-lobe morphology could not survive against the violent disruption in all of our pure hydrodynamical jet models. On the other hand, the head–tail morphology is well reproduced by using a magnetic tower jet model bent by wind, in which hydrodynamical instabilities are naturally suppressed and the jet could always keep its integrity under the protection of its internal magnetic fields. Finally, we also check the possibility for jet bending by shock only. We find that shock could not bend the jet significantly, and thus could not be expected to explain the observed long tails in head–tail radio galaxies.« less

77 FR 16135 - Airworthiness Directives; Mooney Aviation Company, Inc. (Mooney) Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... certain Model M20R and M20TN airplanes. The existing AD currently requires inspecting the tail pitch trim... report of an incident on a Mooney Model M20TN airplane regarding failure of the tail pitch trim assembly... trim assembly for correct positioning and proper attachment and inspecting the Huck Bolt fasteners for...

The Distant Sodium Tail of Mercury

NASA Technical Reports Server (NTRS)

Potter, A. E.; Killen, R. M.; Morgan, T. H.

2001-01-01

Models of the sodium atmosphere of Mercury predict the possible existence of a cornet-like sodium tail. Detection and mapping of the predicted sodium tail would provide quantitative data on the energy of the process that produces sodium atoms from the planetary surface. Previous efforts to detect the sodium tail by means of observations done during daylight hours have been only partially successful because scattered sunlight obscured the weak sodium emissions in the tail. However, at greatest eastern elongation around the March equinox in the northern hemisphere, Mercury can be seen as an evening star in astronomical twilight. At this time, the intensity of scattered sunlight is low enough that sodium emissions as low as 500 Rayleighs can be detected. Additional information is contained in the original extended abstract.

Tail regeneration in Urodela: old model and new perspectives in studies

NASA Astrophysics Data System (ADS)

Grigoryan, E.; Anton, H.; Mitashov, V.

For better understanding of micro-"g" effect on nervous tissue regeneration we have chosen the regeneration of the Urodele tail, because it utilizes many developmental processes and represents the most convenient model for experiments in Space. The special interesting aspect lies in the ability of regenerates to differentiate the spinal cord (SC) and this, in turn, has a potential of practical application. Meanwhile there are conclusive evidences suggesting the production by SC cells the neurotrophic factors promoting cell proliferation and differentiation in growing tail regenerate. Previously our studies on tail regeneration in the adult newt showed that the force of gravity clearly inf luences the events underlying the regeneration. We reported the significant increase of tail regeneration rate and tissue volume of tail regenerates in the newts exposed to real and simulated low "g". In Bion 11 mission animals that were exposed 14 days in microgravity and whose tails were operated two and four weeks before launch demonstrated the regenerates achieved 1.5 - 2 times the volume of those in 1"g" control. Results of this experiment indicated also that the regeneration of central and peripheral neurons and nerve fibers was carrying out faster under low "g" conditions than in 1 "g" control. Similar data were obtained in several experiments remodeling physiological weightlessness by mean of the clinostat. It led us to the hypothesis that the stimulation of tail regeneration is linked with an over activation of neurotrophic factors produced by quickly growing SC neurons. Now we've completed the experiment on tail regeneration in the newts Tr. alpestris subjected to 5 day long clinorotation after 6 days post tail amputation. The rate of primary- and secondary regeneration was evaluated at different time points after treatment. Cell proliferation, differentiation and expression of neurotrophic proteins in SC and other major tissue-type of regenerate were investigated by immunohistochemistry. Results we've just obtained previously support our proposition on the accelerating effect of micro-"g" upon SC regeneration and then of other tail tissue in the newt. The effect, in turn, could be mediated by increased expression of neurotrophins.

Comprehensive Evaluation of Soil Near Uranium Tailings, Beishan City, China.

PubMed

Xun, Yan; Zhang, Xinjia; Chaoliang, Chen; Luo, Xuegang; Zhang, Yu

2018-06-01

To evaluate the impact of uranium tailings on soil composition and soil microbial, six soil samples at different distance from the uranium tailings (Beishan City, China) were collected for further analysis. Concentrations of radionuclides ( 238 U and 232 Th), heavy metals (Mn, Cd, Cr, Ni, Zn, and Pb) and organochlorine pesticide were determined by ICP-MS and GC, they were significantly higher than those of the control. And the Average Well Color Development as well as the Shannon, the Evenness, and the Simpson index were calculated to evaluate the soil microbial diversity. The carbon utilization model of soil microbial community was also analyzed by Biolog-eco. All results indicated that uranium tailings leaded to excessive radionuclides and heavy metals, and decreased the diversity of the soil microbial community. Our study will provide a valuable basis for soil quality evaluation around uranium tailing repositories and lay a foundation for the management and recovery of uranium tailings.

Effect of vertical-tail location on the aerodynamic characteristics at subsonic speeds of a close-coupled canard configuration

NASA Technical Reports Server (NTRS)

Huffman, J. K.

1975-01-01

The effects were studied of various vertical-tail configurations on the longitudinal and lateral directional-stability characteristics of a general research fighter model utilizing wing-body-canard. The study indicates that the addition of the high canard resulted in an increase in total lift at angles of attack above 4 deg with a maximum lift coefficient about twice as large as that for the wing-body configuration. For the wing-body (canard off) configuration, the center-line vertical tail indicates positive vertical-tail effectiveness throughout the test angle-of-attack range; however, for this configuration none of the wing-mounted vertical-tail locations tested resulted in a positive directional-stability increment at the higher angles of attack. For the wing-body-canard configuration several outboard locations of the wing-mounted vertical tails were found.

Conformational analysis of the partially disordered measles virus N(TAIL)-XD complex by SDSL EPR spectroscopy.

PubMed

Kavalenka, Aleh; Urbancic, Iztok; Belle, Valérie; Rouger, Sabrina; Costanzo, Stéphanie; Kure, Sandra; Fournel, André; Longhi, Sonia; Guigliarelli, Bruno; Strancar, Janez

2010-03-17

To characterize the structure of dynamic protein systems, such as partly disordered protein complexes, we propose a novel approach that relies on a combination of site-directed spin-labeled electron paramagnetic resonance spectroscopy and modeling of local rotation conformational spaces. We applied this approach to the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) both free and in complex with the X domain (XD, aa 459-507) of the viral phosphoprotein. By comparing measured and modeled temperature-dependent restrictions of the side-chain conformational spaces of 12 SL cysteine-substituted N(TAIL) variants, we showed that the 490-500 region of N(TAIL) is prestructured in the absence of the partner, and were able to quantitatively estimate, for the first time to our knowledge, the extent of the alpha-helical sampling of the free form. In addition, we showed that the 505-525 region of N(TAIL) conserves a significant degree of freedom even in the bound form. The latter two findings provide a mechanistic explanation for the reported rather high affinity of the N(TAIL)-XD binding reaction. Due to the nanosecond timescale of X-band EPR spectroscopy, we were also able to monitor the disordering in the 488-525 region of N(TAIL), in particular the unfolding of the alpha-helical region when the temperature was increased from 281 K to 310 K. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Effect of Dynamic Rolling Oscillations on Twin Tail Buffet Response

NASA Technical Reports Server (NTRS)

Sheta, Essam F.; Kandil, Osama A.

1999-01-01

The effect of dynamic rolling oscillations of delta-wing/twin-tail configuration on twin-tail buffet response is investigated. The computational model consists of a sharp-edged delta wing of aspect ratio one and swept-back flexible twin tail with taper ratio of 0.23. The configuration model is statically pitched at 30 deg. angle of attack and then forced to oscillate in roll around the symmetry axis at a constant amplitude of 4 deg. and reduced frequency of pi and 2(pi). The freestream Mach number and Reynolds number are 0.3 and 1.25 million, respectively. This multidisciplinary problem is solved using three sets of equations on a dynamic multi-block grid structure. The first set is the unsteady, full Navier-Stokes equations, the second set is the aeroelastic equations for coupled bending and torsion vibrations of the tails, and the third set is the grid-displacement equations. The configuration is investigated for inboard position of the twin tails which corresponds to a separation distance between the twin tails of 33% wing span. The computed results are compared with the results of stationary configuration, which previously have been validated using experimental data. The results conclusively showed that the rolling oscillations of the configuration have led to higher loads, higher deflections, and higher excitation peaks than those of the stationary configuration. Moreover, increasing the reduced frequency has led to higher loads and excitation peaks and lower bending and torsion deflections and acceleration.

Simulation of financial market via nonlinear Ising model

NASA Astrophysics Data System (ADS)

Ko, Bonggyun; Song, Jae Wook; Chang, Woojin

2016-09-01

In this research, we propose a practical method for simulating the financial return series whose distribution has a specific heaviness. We employ the Ising model for generating financial return series to be analogous to those of the real series. The similarity between real financial return series and simulated one is statistically verified based on their stylized facts including the power law behavior of tail distribution. We also suggest the scheme for setting the parameters in order to simulate the financial return series with specific tail behavior. The simulation method introduced in this paper is expected to be applied to the other financial products whose price return distribution is fat-tailed.

The role of ensemble post-processing for modeling the ensemble tail

NASA Astrophysics Data System (ADS)

Van De Vyver, Hans; Van Schaeybroeck, Bert; Vannitsem, Stéphane

2016-04-01

The past decades the numerical weather prediction community has witnessed a paradigm shift from deterministic to probabilistic forecast and state estimation (Buizza and Leutbecher, 2015; Buizza et al., 2008), in an attempt to quantify the uncertainties associated with initial-condition and model errors. An important benefit of a probabilistic framework is the improved prediction of extreme events. However, one may ask to what extent such model estimates contain information on the occurrence probability of extreme events and how this information can be optimally extracted. Different approaches have been proposed and applied on real-world systems which, based on extreme value theory, allow the estimation of extreme-event probabilities conditional on forecasts and state estimates (Ferro, 2007; Friederichs, 2010). Using ensemble predictions generated with a model of low dimensionality, a thorough investigation is presented quantifying the change of predictability of extreme events associated with ensemble post-processing and other influencing factors including the finite ensemble size, lead time and model assumption and the use of different covariates (ensemble mean, maximum, spread...) for modeling the tail distribution. Tail modeling is performed by deriving extreme-quantile estimates using peak-over-threshold representation (generalized Pareto distribution) or quantile regression. Common ensemble post-processing methods aim to improve mostly the ensemble mean and spread of a raw forecast (Van Schaeybroeck and Vannitsem, 2015). Conditional tail modeling, on the other hand, is a post-processing in itself, focusing on the tails only. Therefore, it is unclear how applying ensemble post-processing prior to conditional tail modeling impacts the skill of extreme-event predictions. This work is investigating this question in details. Buizza, Leutbecher, and Isaksen, 2008: Potential use of an ensemble of analyses in the ECMWF Ensemble Prediction System, Q. J. R. Meteorol. Soc. 134: 2051-2066.Buizza and Leutbecher, 2015: The forecast skill horizon, Q. J. R. Meteorol. Soc. 141: 3366-3382.Ferro, 2007: A probability model for verifying deterministic forecasts of extreme events. Weather and Forecasting 22 (5), 1089-1100.Friederichs, 2010: Statistical downscaling of extreme precipitation events using extreme value theory. Extremes 13, 109-132.Van Schaeybroeck and Vannitsem, 2015: Ensemble post-processing using member-by-member approaches: theoretical aspects. Q.J.R. Meteorol. Soc., 141: 807-818.

Three Dimensional Explicit Model for Cometary Tail Ions Interactions with Solar Wind

NASA Astrophysics Data System (ADS)

Al Bermani, M. J. F.; Alhamed, S. A.; Khalaf, S. Z.; Ali, H. Sh.; Selman, A. A.

2009-06-01

The different interactions between cometary tail and solar wind ions are studied in the present paper based on three-dimensional Lax explicit method. The model used in this research is based on the continuity equations describing the cometary tail-solar wind interactions. Three dimensional system was considered in this paper. Simulation of the physical system was achieved using computer code written using Matlab 7.0. The parameters studied here assumed Halley comet type and include the particle density rho, the particles velocity v, the magnetic field strength B, dynamic pressure p and internal energy E. The results of the present research showed that the interaction near the cometary nucleus is mainly affected by the new ions added to the plasma of the solar wind, which increases the average molecular weight and result in many unique characteristics of the cometary tail. These characteristics were explained in the presence of the IMF.

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.

Hydrology, water quality, and simulation of ground-water flow at a taconite-tailings basin near Keewatin, Minnesota

USGS Publications Warehouse

Myette, C.F.

1991-01-01

Numerical-model simulations of ground-water flow near the vicinity of the tailings basin indicate that, if areal recharge were doubled during spring and fall, water levels in wells could average about 4 feet above 1983 levels during these periods. Model results indicate that water levels in the tailings could possibly remain about 5 feet above 1983 levels at the end of the year. Water levels in the tailings at the outlet of the basin could be about 1 foot above 1983 levels during the spring stress period and could be nearly 1.5 feet above 1983 levels during the fall stress period. Under these hypothetical climatic conditions, ground-water contribution to discharge at the outlet could be about 50 cubic feet per second during spring and about 80 cubic feet per second during fall.

Tests of a Full-Scale Model of the Republic XF-91 Airplane in the Ames 40- by 80-Foot Wind Tunnel. Force and Moment Data

NASA Technical Reports Server (NTRS)

Hunten, Lynn W.; Dew, Joseph K.

1949-01-01

Wind-tunnel tests of a full-scale model of the Republic XF-91 airplane having swept-back wings and a vee tail were conducted to determine both the stability and control characteristics of the model longitudinally, laterally, and directionally. Configurations of the model were investigated involving such variables as external fuel tanks, a landing gear, trailing-edge flaps, leading-edge slats, and a range of wing incidences and tail incidences.

Space Shuttle Orbiter SILTS Pod Flow Angularity and Aerodynamic Heating Tests (OH-102A and OH-400).

DTIC Science & Technology

1979-11-01

fabricated from 17 - 4PH stainless steel and instrumented with tnermocouples. A photograph or the 9L-p model with the U.UJZJ scale vertical tail installed is...DISTRIBUTION STATE=MENT (of this ’Report) Approved for public release; distribution unlimited. 17 . DISTRIBUTION STATEMENT (of the abstract entered In...Model Installation ....... .................. . 17 3. Vertical Tail for Flow Angularity ..... .............. ... 18 4. Photograph of 56-) Model

Experimental trim drag values and flow-field measurements for a wide-body transport model with conventional and supercritical wings

NASA Technical Reports Server (NTRS)

Jacobs, P. F.

1982-01-01

The purpose of this study was to determine if advanced supercritical wings incur higher trim drag values at cruise conditions than current wide body technology wings. Relative trim drag increments were measured in an experimental wind tunnel investigation conducted in the Langley 8 Foot Transonic Pressure Tunnel. The tests utilized a high aspect ratio supercritical wing and a wide body aircraft wing, in conjunction with five different horizontal tail configurations, mounted on a representative wide body fuselage. The three low tail and two T-tail configurations were designed to measure the effects of horizontal tail size, location, and camber on the trim drag increments for the two wings. Longitudinal force and moment data were taken at a Mach number of 0.82 and design cruise lift coefficients for the wide body and supercritical wings of 0.45 and 0.55, respectively. The data indicate that the supercritical wing does not have significantly higher trim drag than the wide body wing. A reduction in tail size, combined with relaxed static stability, produced trim drag reductions for both wings. The cambered tails had higher trim drag increments than the symmetrical tails for both wings, and the T-tail configurations had lower trim drag increments than the low tail configurations.

Effect of Configuration Pitching Motion on Twin Tail Buffet Response

NASA Technical Reports Server (NTRS)

Sheta, Essam F.; Kandil, Osama A.

1998-01-01

The effect of dynamic pitch-up motion of delta wing on twin-tail buffet response is investigated. The computational model consists of a delta wing-twin tail configuration. The computations are carried out on a dynamic multi-block grid structure. This multidisciplinary problem is solved using three sets of equations which consists of the unsteady Navier-Stokes equations, the aeroelastic equations, and the grid displacement equations. The configuration is pitched-up from zero up to 60 deg. angle of attack, and the freestream Mach number and Reynolds number are 0.3 and 1.25 million, respectively. With the twin tail fixed as rigid surfaces and with no-forced pitch-up motion, the problem is solved for the initial flow conditions. Next, the problem is solved for the twin-tail response for uncoupled bending and torsional vibrations due to the unsteady loads on the twin tail and due to the forced pitch-up motion. The dynamic pitch-up problem is also solved for the flow response with the twin tail kept rigid. The configuration is investigated for inboard position of the twin tail which corresponds to a separation distance between the twin tail of 33% wing chord. The computed results are compared with the available experimental data.

A new model for the surface arrangement of myosin molecules in tarantula thick filaments.

PubMed

Offer, G; Knight, P J; Burgess, S A; Alamo, L; Padrón, R

2000-04-28

Three-dimensional reconstructions of the negatively stained thick filaments of tarantula muscle with a resolution of 50 A have previously suggested that the helical tracks of myosin heads are zigzagged, short diagonal ridges being connected by nearly axial links. However, surface views of lower contour levels reveal an additional J-shaped feature approximately the size and shape of a myosin head. We have modelled the surface array of myosin heads on the filaments using as a building block a model of a two-headed regulated myosin molecule in which the regulatory light chains of the two heads together form a compact head-tail junction. Four parameters defining the radius, orientation and rotation of each myosin molecule were varied. In addition, the heads were allowed independently to bend in a plane perpendicular to the coiled-coil tail at three sites, and to tilt with respect to the tail and to twist at one of these sites. After low-pass filtering, models were aligned with the reconstruction, scored by cross-correlation and refined by simulated annealing. Comparison of the geometry of the reconstruction and the distance between domains in the myosin molecule narrowed the choice of models to two main classes. A good match to the reconstruction was obtained with a model in which each ridge is formed from the motor domain of a head pointing to the bare zone together with the head-tail junction of a neighbouring molecule. The heads pointing to the Z-disc intermittently occupy the J-position. Each motor domain interacts with the essential and regulatory light chains of the neighbouring heads. A near-radial spoke in the reconstruction connecting the backbone to one end of the ridge can be identified as the start of the coiled-coil tail. Copyright 2000 Academic Press.

Maximum Likelihood Methods in Treating Outliers and Symmetrically Heavy-Tailed Distributions for Nonlinear Structural Equation Models with Missing Data

ERIC Educational Resources Information Center

Lee, Sik-Yum; Xia, Ye-Mao

2006-01-01

By means of more than a dozen user friendly packages, structural equation models (SEMs) are widely used in behavioral, education, social, and psychological research. As the underlying theory and methods in these packages are vulnerable to outliers and distributions with longer-than-normal tails, a fundamental problem in the field is the…

Transonic Free-Flight Investigation of the Longitudinal Aerodynamic Characteristics of a 1/10-Scale Steel-Wing Model of the Northrop MX-775A Missile with Leading-Edge Extensions, Inboard Trailing-Edge Flaps, and a Speed Brake on the Vertical Tail

NASA Technical Reports Server (NTRS)

Arbic, R. G.

1955-01-01

Results are presented of a free-flight investigation between Mach numbers of 0.7 to 1.3 and Reynolds numbers of 3.1 x 10(exp 6) to 7.0 x 10(exp 6) to determine the longitudinal aerodynamic characteristics of the Northrop MX-775A missile. This missile has a weng, body, and vertical tail, but has no horizontal tail. The basic wing plan form has an aspect ratio of 5.5, 45 deg of sweepback of the 0.406 streamwise chord line, and a taper ratio of 0.4. A 1/10-scale steel-wing model of the missile was flown with modifications to the basic wing plan form consisting of leading-edge chord-extensions deflected 7 deg downward together with the forward 15 percent of the wing chord, and inboard trailing-edge flaps deflected 5 deg downward. In addition, the model had a static-pressure tube mounted at the tip of the vertical tail for position-error measurements and had a speed brake also mounted on the vertical tail to trim the model to positive lift coefficients and to permit determination of the trim and drag effectiveness of the brake. The data are uncorrected for the effects of wing elasticity, but experimental wing influence coefficients are presented.

On the Hydrodynamics of Anomalocaris Tail Fins.

PubMed

Sheppard, K A; Rival, D E; Caron, J-B

2018-04-25

Anomalocaris canadensis, a soft-bodied stem-group arthropod from the Burgess Shale, is considered the largest predator of the Cambrian period. Thanks to a series of lateral flexible lobes along its dorso-ventrally compressed body, it is generally regarded as an efficient swimmer, well-adapted to its predatory lifestyle. Previous theoretical hydrodynamic simulations have suggested a possible optimum in swimming performance when the lateral lobes performed as a single undulatory lateral fin, comparable to the pectoral fins in skates and rays. However, the role of the unusual fan-like tail of Anomalocaris has not been previously explored. Swimming efficiency and maneuverability deduced from direct hydrodynamic analysis are here studied in a towing tank facility using a three-vane physical model designed as an abstraction of the tail fin. Through direct force measurements, it was found that the model exhibited a region of steady-state lift and drag enhancement at angles of attack greater than 25° when compared to a triangular-shaped reference model. This would suggest that the resultant normal force on the tail fin of Anomalocaris made it well-suited for turning maneuvers, giving it the ability to turn quickly and through small radii of curvature. These results are consistent with an active predatory lifestyle, although detailed kinematic studies integrating the full organism, including the lateral lobes, would be required to test the effect of the tail fin on overall swimming performance. This study also highlights a possible example of evolutionary convergence between the tails of Anomalocaris and birds, which, in both cases, are well-adapted to efficient turning maneuvers.

Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited.

PubMed

Khoshnood, Atefeh; Lukanov, Boris; Firoozabadi, Abbas

2016-03-08

Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces.

Ionosphere and atmosphere of the moon in the geomagnetic tail

NASA Technical Reports Server (NTRS)

Daily, W. D.; Barker, W. A.; Parkin, C. W.; Clark, M.; Dyal, P.

1977-01-01

The paper presents calculations of the densities and energies of the various constituents of the lunar ionosphere during the time that the moon is in the geomagnetic tail; the surface concentrations of neon and argon are calculated from a theoretical model to be 3,900 and 1,700, respectively. It is found that a hydrostatic model of the ionospheric plasma is inadequate because the gravitational potential energy of the plasma is considerably smaller than its thermal energy. A hydrodynamic model, comparable to that used to describe the solar wind, is developed to obtain plasma densities and flow velocities as functions of altitude. The electromagnetic properties of the quiescent ionosphere are then investigated, and it is concluded that plasma effects on lunar induction can be neglected for quiescent conditions in the geomagnetic tail lobes.

BIOMECHANICS. Why the seahorse tail is square.

PubMed

Porter, Michael M; Adriaens, Dominique; Hatton, Ross L; Meyers, Marc A; McKittrick, Joanna

2015-07-03

Whereas the predominant shapes of most animal tails are cylindrical, seahorse tails are square prisms. Seahorses use their tails as flexible grasping appendages, in spite of a rigid bony armor that fully encases their bodies. We explore the mechanics of two three-dimensional-printed models that mimic either the natural (square prism) or hypothetical (cylindrical) architecture of a seahorse tail to uncover whether or not the square geometry provides any functional advantages. Our results show that the square prism is more resilient when crushed and provides a mechanism for preserving articulatory organization upon extensive bending and twisting, as compared with its cylindrical counterpart. Thus, the square architecture is better than the circular one in the context of two integrated functions: grasping ability and crushing resistance. Copyright © 2015, American Association for the Advancement of Science.

Analytic model of aurorally coupled magnetospheric and ionospheric electrostatic potentials

NASA Technical Reports Server (NTRS)

Cornwall, J. M.

1994-01-01

This paper describes modest but significant improvements on earlier studies of electrostatic potential structure in the auroral region using the adiabatic auroral arc model. This model has crucial nonlinearities (connected, for example. with aurorally produced ionization) which have hampered analysis; earlier work has either been linear, which I will show is a poor approximation or, if nonlinear, either numerical or too specialized to study parametric dependencies. With certain simplifying assumptions I find new analytic nonlinear solutions fully exhibiting the parametric dependence of potentials on magnetospheric (e.g.. cross-tail potential) and ionospheric (e.g., recombination rate) parameters. No purely phenomenological parameters are introduced. The results are in reasonable agreement with observed average auroral potential drops, inverted-V scale sizes, and dissipation rates. The dissipation rate is quite comparable to tail energization and transport rates and should have a major effect on tail and magnetospheric dynamics. This paper gives various relations between the cross-tail potential and auroral parameters (e.g., total parallel currents and potential drops) which can be studied with existing data sets.

Microbial alignment in flow changes ocean light climate.

PubMed

Marcos; Seymour, Justin R; Luhar, Mitul; Durham, William M; Mitchell, James G; Macke, Andreas; Stocker, Roman

2011-03-08

The growth of microbial cultures in the laboratory often is assessed informally with a quick flick of the wrist: dense suspensions of microorganisms produce translucent "swirls" when agitated. Here, we rationalize the mechanism behind this phenomenon and show that the same process may affect the propagation of light through the upper ocean. Analogous to the shaken test tubes, the ocean can be characterized by intense fluid motion and abundant microorganisms. We demonstrate that the swirl patterns arise when elongated microorganisms align preferentially in the direction of fluid flow and alter light scattering. Using a combination of experiments and mathematical modeling, we find that this phenomenon can be recurrent under typical marine conditions. Moderate shear rates (0.1 s(-1)) can increase optical backscattering of natural microbial assemblages by more than 20%, and even small shear rates (0.001 s(-1)) can increase backscattering from blooms of large phytoplankton by more than 30%. These results imply that fluid flow, currently neglected in models of marine optics, may exert an important control on light propagation, influencing rates of global carbon fixation and how we estimate these rates via remote sensing.

Biomimetic model systems of rigid hair beds: Part II - Experiment

NASA Astrophysics Data System (ADS)

Jammalamadaka, Mani S. S.; Hood, Kaitlyn; Hosoi, Anette

2017-11-01

Crustaceans - such as lobsters, crabs and stomapods - have hairy appendages that they use to recognize and track odorants in the surrounding fluid. An array of rigid hairs impedes flow at different rates depending on the spacing between hairs and the Reynolds number, Re. At larger Reynolds number (Re>1), fluid travels through the hairs rather than around them, a phenomenon called leakiness. Crustaceans flick their appendages at different speeds in order to manipulate the leakiness between the hairs, allowing the hairs to either detect the odors in a sample of fluid or collect a new sample. Theoretical and numerical studies predict that there is a fast flow region near the hairs that moves closer to the hairs as Re increases. Here, we test this theory experimentally. We 3D printed rigid hairs with an aspect ratio of 30:1 in rectangular arrays with different hair packing fractions. We custom built an experimental setup which establishes poiseuille flow at intermediate Re, Re <=200. We track the flow dynamics through the hair beds using tracer particles and Particle Imaging Velocimetry. We will then compare the modelling predictions with the experimental outcomes.

Generalized run-and-turn motions: From bacteria to Lévy walks

NASA Astrophysics Data System (ADS)

Detcheverry, François

2017-07-01

Swimming bacteria exhibit a repertoire of motility patterns, in which persistent motion is interrupted by turning events. What are the statistical properties of such random walks? If some particular instances have long been studied, the general case where turning times do not follow a Poisson process has remained unsolved. We present a generic extension of the continuous time random walks formalism relying on operators and noncommutative calculus. The approach is first applied to a unimodal model of bacterial motion. We examine the existence of a minimum in velocity correlation function and discuss the maximum of diffusivity at an optimal value of rotational diffusion. The model is then extended to bimodal patterns and includes as particular cases all swimming strategies: run-and-tumble, run-stop, run-reverse and run-reverse-flick. We characterize their velocity correlation functions and investigate how bimodality affects diffusivity. Finally, the wider applicability of the method is illustrated by considering curved trajectories and Lévy walks. Our results are relevant for intermittent motion of living beings, be they swimming micro-organisms or crawling cells.

Environmental hazard assessment of a marine mine tailings deposit site and potential implications for deep-sea mining.

PubMed

Mestre, Nélia C; Rocha, Thiago L; Canals, Miquel; Cardoso, Cátia; Danovaro, Roberto; Dell'Anno, Antonio; Gambi, Cristina; Regoli, Francesco; Sanchez-Vidal, Anna; Bebianno, Maria João

2017-09-01

Portmán Bay is a heavily contaminated area resulting from decades of metal mine tailings disposal, and is considered a suitable shallow-water analogue to investigate the potential ecotoxicological impact of deep-sea mining. Resuspension plumes were artificially created by removing the top layer of the mine tailings deposit by bottom trawling. Mussels were deployed at three sites: i) off the mine tailings deposit area; ii) on the mine tailings deposit beyond the influence from the resuspension plumes; iii) under the influence of the artificially generated resuspension plumes. Surface sediment samples were collected at the same sites for metal analysis and ecotoxicity assessment. Metal concentrations and a battery of biomarkers (oxidative stress, metal exposure, biotransformation and oxidative damage) were measured in different mussel tissues. The environmental hazard posed by the resuspension plumes was investigated by a quantitative weight of evidence (WOE) model that integrated all the data. The resuspension of sediments loaded with metal mine tails demonstrated that chemical contaminants were released by trawling subsequently inducing ecotoxicological impact in mussels' health. Considering as sediment quality guidelines (SQGs) those indicated in Spanish action level B for the disposal of dredged material at sea, the WOE model indicates that the hazard is slight off the mine tailings deposit, moderate on the mine tailings deposit without the influence from the resuspension plumes, and major under the influence of the resuspension plumes. Portmán Bay mine tailings deposit is a by-product of sulphide mining, and despite differences in environmental setting, it can reflect the potential ecotoxic effects to marine fauna from the impact of resuspension of plumes created by deep-sea mining of polymetallic sulphides. A similar approach as in this study could be applied in other areas affected by sediment resuspension and for testing future deep-sea mining sites in order to assess the associated environmental hazards. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Langevin approach to multi-scale modeling

DOE PAGES

Hirvijoki, Eero

2018-04-13

In plasmas, distribution functions often demonstrate long anisotropic tails or otherwise significant deviations from local Maxwellians. The tails, especially if they are pulled out from the bulk, pose a serious challenge for numerical simulations as resolving both the bulk and the tail on the same mesh is often challenging. A multi-scale approach, providing evolution equations for the bulk and the tail individually, could offer a resolution in the sense that both populations could be treated on separate meshes or different reduction techniques applied to the bulk and the tail population. In this paper, we propose a multi-scale method which allowsmore » us to split a distribution function into a bulk and a tail so that both populations remain genuine, non-negative distribution functions and may carry density, momentum, and energy. The proposed method is based on the observation that the motion of an individual test particle in a plasma obeys a stochastic differential equation, also referred to as a Langevin equation. Finally, this allows us to define transition probabilities between the bulk and the tail and to provide evolution equations for both populations separately.« less

A Langevin approach to multi-scale modeling

NASA Astrophysics Data System (ADS)

Hirvijoki, Eero

2018-04-01

In plasmas, distribution functions often demonstrate long anisotropic tails or otherwise significant deviations from local Maxwellians. The tails, especially if they are pulled out from the bulk, pose a serious challenge for numerical simulations as resolving both the bulk and the tail on the same mesh is often challenging. A multi-scale approach, providing evolution equations for the bulk and the tail individually, could offer a resolution in the sense that both populations could be treated on separate meshes or different reduction techniques applied to the bulk and the tail population. In this letter, we propose a multi-scale method which allows us to split a distribution function into a bulk and a tail so that both populations remain genuine, non-negative distribution functions and may carry density, momentum, and energy. The proposed method is based on the observation that the motion of an individual test particle in a plasma obeys a stochastic differential equation, also referred to as a Langevin equation. This allows us to define transition probabilities between the bulk and the tail and to provide evolution equations for both populations separately.

A Langevin approach to multi-scale modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirvijoki, Eero

In plasmas, distribution functions often demonstrate long anisotropic tails or otherwise significant deviations from local Maxwellians. The tails, especially if they are pulled out from the bulk, pose a serious challenge for numerical simulations as resolving both the bulk and the tail on the same mesh is often challenging. A multi-scale approach, providing evolution equations for the bulk and the tail individually, could offer a resolution in the sense that both populations could be treated on separate meshes or different reduction techniques applied to the bulk and the tail population. In this paper, we propose a multi-scale method which allowsmore » us to split a distribution function into a bulk and a tail so that both populations remain genuine, non-negative distribution functions and may carry density, momentum, and energy. The proposed method is based on the observation that the motion of an individual test particle in a plasma obeys a stochastic differential equation, also referred to as a Langevin equation. Finally, this allows us to define transition probabilities between the bulk and the tail and to provide evolution equations for both populations separately.« less

Effectiveness of various cover scenarios on the rate of sulfide oxidation of mine tailings

NASA Astrophysics Data System (ADS)

Romano, Connie G.; Ulrich Mayer, K.; Jones, David R.; Ellerbroek, David A.; Blowes, David W.

2003-02-01

Long term environmentally sound disposal of the millions of tons of mining residue is a serious challenge to the international mining industry. This paper evaluates, through a numerical investigation, the potential performance of desulfurized tailings as a cover material for the reduction of acidic drainage from sulfidic tailings. This evaluation is facilitated through a comparison of various cover types as decommissioning options. The cover types considered consist of a desulfurized tailings material cover exposed to ambient climate conditions, a water cover (flooded tailings), and a combination cover type. As part of the evaluation of cover performances, the effect of climatic variability on the potential rate of sulfide oxidation in tailings with an open ground surface, was also assessed. The numerical analysis was conducted using the model PYROX, which was modified to allow for variably-saturated conditions, time varying moisture contents, and to account for the temperature dependence of Henry's law and gas diffusion. In the case study presented here, the benign cover material consists of a low sulfide waste stream (cassiterite float tails, CFT), a by-product of the production of tin concentrate (cassiterite, SnO 2). Modelling results after a simulation period of 100 years indicate that a water cover alone or an exposed CFT cover alone are both less effective options than the combined cover type. A water cover alone leads to a reduction of approximately 99.1%, in the oxidation rate relative to uncovered tailings while the combined cover type results in the lowest potential extent of sulfide oxidation after mine closure-an approximately 99.8% reduction. Importantly, a CFT cover exposed to ambient environmental conditions can still substantially reduce the sulfide oxidation rate, by approximately 75-82% over a 100-year time period, relative to uncovered tailings. Variability in precipitation (and hence percent saturation of the surface layer) had less of an effect on the potential sulfide oxidation rate than did the cover type. The performance of the exposed CFT cover varied by less than 10%, within the range of climatic conditions expected at the Renison Bell mine site in southwest Tasmania, Australia. Although the modelling results indicate that the combined water and CFT cover is the best option, this approach achieves only a minor improvement over the water cover alone.

Aerodynamic Loads at Mach Numbers from 0.70 to 2.22 on a Airplane Model Having a Wing and Canard of Triangular Plan Form and Either Single or Twin Vertical Tails

NASA Technical Reports Server (NTRS)

Peterson, Victor L.; Menees, Gene P.

1961-01-01

Results of an investigation of the aerodynamic loads on a canard airplane model are presented without detailed analysis for the Mach number range of 0.70 t o 2.22. The model consisted of a triangular wing and canard of aspect ratio 2 mounted on a Sears-Haack body of fineness ratio 12.5 and either a single body-mounted vertical tail or twin wing mounted vertical tails of low aspect ratio and sweptback plan form. The body, right wing panel, single vertical tail, and left twin vertical tail were instrumented for measuring pressures. Data were obtained for angles of attack ranging from -4 degrees to +16 degrees, nominal canard deflection angles of 0 degrees and 10 degrees, and angles of sideslip of 0 degrees and 5.3 degrees. The Reynolds number was 2.9 x 10(exp 6) based on the wing mean aerodynamic chord. Selected portions of the data are presented in graphical form and attention is directed to some of the results of the investigation. All of the experimental results have been tabulated in the form of pressure coefficients and integrations of the pressure coefficients and are available as supplements to this paper. A brief summary of the contents of the tabular material is given.

Subsonic Aerodynamic Characteristics of an Airplane Configuration with a 63 deg Sweptback Wing and Twin-Boom Tails

NASA Technical Reports Server (NTRS)

Savage, Howard F.; Edwards, George G.

1959-01-01

A wind-tunnel investigation has been conducted to determine the effects of an unconventional tail arrangement on the subsonic static longitudinal and lateral stability characteristics of a model having a 63 deg sweptback wing of aspect ratio 3.5 and a fuselage. Tail booms, extending rearward from approximately the midsemispan of each wing panel, supported independent tail assemblies well outboard of the usual position at the rear of the fuselage. The horizontal-tail surfaces had the leading edge swept back 45 deg and an aspect ratio of 2.4. The vertical tail surfaces were geometrically similar to one panel of the horizontal tail. For comparative purposes, the wing-body combination was also tested with conventional fuselage-mounted tail surfaces. The wind-tunnel tests were conducted at Mach numbers from 0.25 to 0.95 with a Reynolds number of 2,000,000, at a Mach number of 0.46 with a Reynolds number of 3,500,000, and at a Mach number of 0.20 with a Reynolds number of 7,000,000. The results of the investigation indicate that longitudinal stability existed to considerably higher lift coefficients for the outboard tail configuration than for the configuration with conventional tail. Wing fences were necessary with both configurations for the elimination of sudden changes in longitudinal stability at lift coefficients between 0.3 and 0.5. Sideslip angles up to 15 deg had only small effects upon the pitching-moment characteristics of the outboard tail configuration. There was an increase in the directional stability for the outboard tail configuration at the higher angles of attack as opposed to a decrease for the conventional tail configuration at most of the Mach numbers and Reynolds numbers of this investigation. The dihedral effect increased rapidly with increasing angle of attack for both the outboard and the conventional tail configurations but the increase was greater for the outboard tail configuration. The data indicate that the outboard tail is an effective roll control.

An analysis on 45° sweep tail angle for blended wing body aircraft to the aerodynamics coefficients by wind tunnel experiment

NASA Astrophysics Data System (ADS)

Latif, M. Z. A. Abd; Ahmad, M. A.; Nasir, R. E. Mohd; Wisnoe, W.; Saad, M. R.

2017-12-01

This paper presents the analysis of a model from UiTM Blended Wing Body (BWB) UAV, Baseline V that has been tested at UPNM high speed wind tunnel. Baseline V has a unique design due to different NACA sections used for its fuselage, body, wing root, midwing, wingtip, tail root, tail tip and the tail is swept 45° backward. The purpose of this experiment is to study the aerodynamic characteristics when the tail sweeps 45° backward. The experiments are conducted several times using 71.5% scaled down model at about 49.58 m/s airspeed or 25 Hz. The tail angle deflection is fixed and set at zero angle. All the data obtained is analyzed and presented in terms of coefficient of lift, coefficient of drag and also lift-to-drag ratio, and is plotted against various angles of attack. The angles of attack used for this experiments are between -10° to +30°. The blockage correction such as solid blockage, wake blockage and streamline curvature blockage are calculated in order to obtain true performance of the aircraft. From the observation, Baseline V shows that the aircraft tends to stall at around +15°. The maximum L/D ratio achieved for Baseline V is 20.8, however it decreases slightly to 20.7 after blockage corrections.

Mycobacterium ulcerans low infectious dose and mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer.

PubMed

Wallace, John R; Mangas, Kirstie M; Porter, Jessica L; Marcsisin, Renee; Pidot, Sacha J; Howden, Brian; Omansen, Till F; Zeng, Weiguang; Axford, Jason K; Johnson, Paul D R; Stinear, Timothy P

2017-04-01

Addressing the transmission enigma of the neglected disease Buruli ulcer (BU) is a World Health Organization priority. In Australia, we have observed an association between mosquitoes harboring the causative agent, Mycobacterium ulcerans, and BU. Here we tested a contaminated skin model of BU transmission by dipping the tails from healthy mice in cultures of the causative agent, Mycobacterium ulcerans. Tails were exposed to mosquito (Aedes notoscriptus and Aedes aegypti) blood feeding or punctured with sterile needles. Two of 12 of mice with M. ulcerans contaminated tails exposed to feeding A. notoscriptus mosquitoes developed BU. There were no mice exposed to A. aegypti that developed BU. Eighty-eight percent of mice (21/24) subjected to contaminated tail needle puncture developed BU. Mouse tails coated only in bacteria did not develop disease. A median incubation time of 12 weeks, consistent with data from human infections, was noted. We then specifically tested the M. ulcerans infectious dose-50 (ID50) in this contaminated skin surface infection model with needle puncture and observed an ID50 of 2.6 colony-forming units. We have uncovered a biologically plausible mechanical transmission mode of BU via natural or anthropogenic skin punctures.

Effects of afterbody boattail design and empennage arrangement on aeropropulsive characteristics of a twin-engine fighter model at transonic speeds

NASA Technical Reports Server (NTRS)

Bangert, Linda S.; Leavitt, Laurence D.; Reubush, David E.

1987-01-01

The effects of empennage arrangement and afterbody boattail design of nonaxisymmetric nozzles on the aeropropulsive characteristics of a twin-engine fighter-type model have been determined in an investigation conducted in the Langley 16-Foot Transonic Tunnel. Three nonaxisymmetric and one twin axisymmetric convergent-divergent nozzle configurations were tested with three different tail arrangements: a two-tail V-shaped arrangement; a staggered, conventional three-tail arrangement; and a four-tail arrangement similar to that on the F-18. Two of the nonaxisymmetric nozzles were also vectorable. Tests were conducted at Mach numbers from 0.60 to 1.20 over an angle-of-attack range from -3 deg to 9 deg. Nozzle pressure ratio was varied from 1 (jet off) to approximately 12, depending on Mach number. Results indicate that at design nozzle pressure ratio, the medium aspect ratio nozzle (with equal boattail angles on the nozzle sidewalls and upper and lower flaps) had the lowest zero angle of attack drag of the nonaxisymmetric nozzles for all tail configurations at subsonic Mach numbers. The drag levels of the twin axisymmetric nozzles were competitive with those of the medium-aspect-ratio nozzle at subsonic Mach number.

Modeling and statistical analysis of non-Gaussian random fields with heavy-tailed distributions.

PubMed

Nezhadhaghighi, Mohsen Ghasemi; Nakhlband, Abbas

2017-04-01

In this paper, we investigate and develop an alternative approach to the numerical analysis and characterization of random fluctuations with the heavy-tailed probability distribution function (PDF), such as turbulent heat flow and solar flare fluctuations. We identify the heavy-tailed random fluctuations based on the scaling properties of the tail exponent of the PDF, power-law growth of qth order correlation function, and the self-similar properties of the contour lines in two-dimensional random fields. Moreover, this work leads to a substitution for the fractional Edwards-Wilkinson (EW) equation that works in the presence of μ-stable Lévy noise. Our proposed model explains the configuration dynamics of the systems with heavy-tailed correlated random fluctuations. We also present an alternative solution to the fractional EW equation in the presence of μ-stable Lévy noise in the steady state, which is implemented numerically, using the μ-stable fractional Lévy motion. Based on the analysis of the self-similar properties of contour loops, we numerically show that the scaling properties of contour loop ensembles can qualitatively and quantitatively distinguish non-Gaussian random fields from Gaussian random fluctuations.

The Anna's hummingbird chirps with its tail: a new mechanism of sonation in birds

PubMed Central

Clark, Christopher James; Feo, Teresa J

2008-01-01

A diverse array of birds apparently make mechanical sounds (called sonations) with their feathers. Few studies have established that these sounds are non-vocal, and the mechanics of how these sounds are produced remains poorly studied. The loud, high-frequency chirp emitted by a male Anna's hummingbird (Calypte anna) during his display dive is a debated example. Production of the sound was originally attributed to the tail, but a more recent study argued that the sound is vocal. Here, we use high-speed video of diving birds, experimental manipulations on wild birds and laboratory experiments on individual feathers to show that the dive sound is made by tail feathers. High-speed video shows that fluttering of the trailing vane of the outermost tail feathers produces the sound. The mechanism is not a whistle, and we propose a flag model to explain the feather's fluttering and accompanying sound. The flag hypothesis predicts that subtle changes in feather shape will tune the frequency of sound produced by feathers. Many kinds of birds are reported to create aerodynamic sounds with their wings or tail, and this model may explain a wide diversity of non-vocal sounds produced by birds. PMID:18230592

High resolution flow field prediction for tail rotor aeroacoustics

NASA Technical Reports Server (NTRS)

Quackenbush, Todd R.; Bliss, Donald B.

1989-01-01

The prediction of tail rotor noise due to the impingement of the main rotor wake poses a significant challenge to current analysis methods in rotorcraft aeroacoustics. This paper describes the development of a new treatment of the tail rotor aerodynamic environment that permits highly accurate resolution of the incident flow field with modest computational effort relative to alternative models. The new approach incorporates an advanced full-span free wake model of the main rotor in a scheme which reconstructs high-resolution flow solutions from preliminary, computationally inexpensive simulations with coarse resolution. The heart of the approach is a novel method for using local velocity correction terms to capture the steep velocity gradients characteristic of the vortex-dominated incident flow. Sample calculations have been undertaken to examine the principal types of interactions between the tail rotor and the main rotor wake and to examine the performance of the new method. The results of these sample problems confirm the success of this approach in capturing the high-resolution flows necessary for analysis of rotor-wake/rotor interactions with dramatically reduced computational cost. Computations of radiated sound are also carried out that explore the role of various portions of the main rotor wake in generating tail rotor noise.

The tail of two models: Impact of circularity and biomass non-homogeneity on UV disinfection of wastewater flocs.

PubMed

Azimi, Y; Liu, Y; Tan, T C; Allen, D G; Farnood, R R

2017-12-01

The effects of floc structural characteristics, i.e. shape and dense biomass distribution, were evaluated on ultraviolet (UV) disinfection resistance, represented by the tailing level of the UV dose response curve (DRC). Ellipsoid-shaped flocs of similar volume and different projected circularities were constructed in-silico and a mathematical model was developed to compare their UV DRC tailing levels (indicative of UV-resistance). It was found that floc shape can significantly influence tailing level, and rounder flocs (i.e. flocs with higher circularity) were more UV-resistant. This result was confirmed experimentally by obtaining UV DRCs of two 75-90 μm floc populations with different percentages (20% vs. 30%) of flocs with circularities higher than 0.5. The population enriched in less circular flocs (i.e. 20% flocs with circularities >0.5) had a lower tailing level (at least by 1-log) compared to the other population. The second model was developed to describe variations in UV disinfection kinetics observed in flocs with transverse vs. radial biomass non-homogeneity, indicative of biofilm-originated vs. suspended flocs. The varied-density hemispheres model and shell-core model were developed to simulate transverse and radial non-homogeneity, respectively. The UV DRCs were mathematically constructed and biofilm-originated flocs showed higher UV resistance compared to suspended flocs. The calculated UV DRCs agreed well with the experimental data collected from activated sludge and trickling filter flocs (no fitting parameters were used). These findings provide useful information in terms of designing/modifying upstream processes for reducing UV disinfection energy demand. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-dimensional hydrogeological modeling to assess the elevated-water-table technique for controlling acid generation from an abandoned tailings site in Quebec, Canada

NASA Astrophysics Data System (ADS)

Ethier, Marie-Pier; Bussière, Bruno; Broda, Stefan; Aubertin, Michel

2018-01-01

The Manitou Mine sulphidic-tailings storage facility No. 2, near Val D'Or, Canada, was reclaimed in 2009 by elevating the water table and applying a monolayer cover made of tailings from nearby Goldex Mine. Previous studies showed that production of acid mine drainage can be controlled by lowering the oxygen flux through Manitou tailings with a water table maintained at the interface between the cover and reactive tailings. Simulations of different scenarios were performed using numerical hydrogeological modeling to evaluate the capacity of the reclamation works to maintain the phreatic surface at this interface. A large-scale numerical model was constructed and calibrated using 3 years of field measurements. This model reproduced the field measurements, including the existence of a western zone on the site where the phreatic level targeted is not always met during the summer. A sensitivity analysis was performed to assess the response of the model to varying saturated hydraulic conductivities, porosities, and grain-size distributions. Higher variations of the hydraulic heads, with respect to the calibrated scenario results, were observed when simulating a looser or coarser cover material. Long-term responses were simulated using: the normal climatic data, data for a normal climate with a 2-month dry spell, and a simplified climate-change case. Environmental quality targets were reached less frequently during summer for the dry spell simulation as well as for the simplified climate-change scenario. This study illustrates how numerical simulations can be used as a key tool to assess the eventual performance of various mine-site reclamation scenarios.

Three-dimensional hydrogeological modeling to assess the elevated-water-table technique for controlling acid generation from an abandoned tailings site in Quebec, Canada

NASA Astrophysics Data System (ADS)

Ethier, Marie-Pier; Bussière, Bruno; Broda, Stefan; Aubertin, Michel

2018-06-01

The Manitou Mine sulphidic-tailings storage facility No. 2, near Val D'Or, Canada, was reclaimed in 2009 by elevating the water table and applying a monolayer cover made of tailings from nearby Goldex Mine. Previous studies showed that production of acid mine drainage can be controlled by lowering the oxygen flux through Manitou tailings with a water table maintained at the interface between the cover and reactive tailings. Simulations of different scenarios were performed using numerical hydrogeological modeling to evaluate the capacity of the reclamation works to maintain the phreatic surface at this interface. A large-scale numerical model was constructed and calibrated using 3 years of field measurements. This model reproduced the field measurements, including the existence of a western zone on the site where the phreatic level targeted is not always met during the summer. A sensitivity analysis was performed to assess the response of the model to varying saturated hydraulic conductivities, porosities, and grain-size distributions. Higher variations of the hydraulic heads, with respect to the calibrated scenario results, were observed when simulating a looser or coarser cover material. Long-term responses were simulated using: the normal climatic data, data for a normal climate with a 2-month dry spell, and a simplified climate-change case. Environmental quality targets were reached less frequently during summer for the dry spell simulation as well as for the simplified climate-change scenario. This study illustrates how numerical simulations can be used as a key tool to assess the eventual performance of various mine-site reclamation scenarios.

Whole Genome Sequencing Identifies a Missense Mutation in HES7 Associated with Short Tails in Asian Domestic Cats.

PubMed

Xu, Xiao; Sun, Xin; Hu, Xue-Song; Zhuang, Yan; Liu, Yue-Chen; Meng, Hao; Miao, Lin; Yu, He; Luo, Shu-Jin

2016-08-25

Domestic cats exhibit abundant variations in tail morphology and serve as an excellent model to study the development and evolution of vertebrate tails. Cats with shortened and kinked tails were first recorded in the Malayan archipelago by Charles Darwin in 1868 and remain quite common today in Southeast and East Asia. To elucidate the genetic basis of short tails in Asian cats, we built a pedigree of 13 cats segregating at the trait with a founder from southern China and performed linkage mapping based on whole genome sequencing data from the pedigree. The short-tailed trait was mapped to a 5.6 Mb region of Chr E1, within which the substitution c. 5T > C in the somite segmentation-related gene HES7 was identified as the causal mutation resulting in a missense change (p.V2A). Validation in 245 unrelated cats confirmed the correlation between HES7-c. 5T > C and Chinese short-tailed feral cats as well as the Japanese Bobtail breed, indicating a common genetic basis of the two. In addition, some of our sampled kinked-tailed cats could not be explained by either HES7 or the Manx-related T-box, suggesting at least three independent events in the evolution of domestic cats giving rise to short-tailed traits.

Behavioural responses of dogs to asymmetrical tail wagging of a robotic dog replica.

PubMed

Artelle, K A; Dumoulin, L K; Reimchen, T E

2011-03-01

Recent evidence suggests that bilateral asymmetry in the amplitude of tail wagging of domestic dogs (Canis familiaris) is associated with approach (right wag) versus withdrawal (left wag) motivation and may be the by-product of hemispheric dominance. We consider whether such asymmetry in motion of the tail, a crucial appendage in intra-specific communication in all canids, provides visual information to a conspecific leading to differential behaviour. To evaluate this, we experimentally investigated the approach behaviour of free-ranging dogs to the asymmetric tail wagging of a life-size robotic dog replica. Our data, involving 452 separate interactions, showed a significantly greater proportion of dogs approaching the model continuously without stopping when the tail wagged to the left, compared with a right wag, which was more likely to yield stops. While the results indicate that laterality of a wagging tail provides behavioural information to conspecifics, the responses are not readily integrated into the predicted behaviour based on hemispheric dominance.

HARP model rotor test at the DNW. [Hughes Advanced Rotor Program

NASA Technical Reports Server (NTRS)

Dawson, Seth; Jordan, David; Smith, Charles; Ekins, James; Silverthorn, Lou

1989-01-01

Data from a test of a dynamically scaled model of the Hughes Advanced Rotor Program (HARP) bearingless model main rotor and 369K tail rotor are reported. The history of the HARP program and its goals are reviewed, and the main and tail rotor models are described. The test facilities and instrumentation are described, and wind tunnel test data are presented on hover, forward flight performance, and blade-vortex interaction. Performance data, acoustic data, and dynamic data from near field/far field and shear layer studies are presented.

Tail mean and related robust solution concepts

NASA Astrophysics Data System (ADS)

Ogryczak, Włodzimierz

2014-01-01

Robust optimisation might be viewed as a multicriteria optimisation problem where objectives correspond to the scenarios although their probabilities are unknown or imprecise. The simplest robust solution concept represents a conservative approach focused on the worst-case scenario results optimisation. A softer concept allows one to optimise the tail mean thus combining performances under multiple worst scenarios. We show that while considering robust models allowing the probabilities to vary only within given intervals, the tail mean represents the robust solution for only upper bounded probabilities. For any arbitrary intervals of probabilities the corresponding robust solution may be expressed by the optimisation of appropriately combined mean and tail mean criteria thus remaining easily implementable with auxiliary linear inequalities. Moreover, we use the tail mean concept to develope linear programming implementable robust solution concepts related to risk averse optimisation criteria.

Competition-Induced Criticality in a Model of Meme Popularity

NASA Astrophysics Data System (ADS)

Gleeson, James P.; Ward, Jonathan A.; O'Sullivan, Kevin P.; Lee, William T.

2014-01-01

Heavy-tailed distributions of meme popularity occur naturally in a model of meme diffusion on social networks. Competition between multiple memes for the limited resource of user attention is identified as the mechanism that poises the system at criticality. The popularity growth of each meme is described by a critical branching process, and asymptotic analysis predicts power-law distributions of popularity with very heavy tails (exponent α <2, unlike preferential-attachment models), similar to those seen in empirical data.

Competition-induced criticality in a model of meme popularity.

PubMed

Gleeson, James P; Ward, Jonathan A; O'Sullivan, Kevin P; Lee, William T

2014-01-31

Heavy-tailed distributions of meme popularity occur naturally in a model of meme diffusion on social networks. Competition between multiple memes for the limited resource of user attention is identified as the mechanism that poises the system at criticality. The popularity growth of each meme is described by a critical branching process, and asymptotic analysis predicts power-law distributions of popularity with very heavy tails (exponent α<2, unlike preferential-attachment models), similar to those seen in empirical data.

Fishnet model for failure probability tail of nacre-like imbricated lamellar materials

NASA Astrophysics Data System (ADS)

Luo, Wen; Bažant, Zdeněk P.

2017-12-01

Nacre, the iridescent material of the shells of pearl oysters and abalone, consists mostly of aragonite (a form of CaCO3), a brittle constituent of relatively low strength (≈10 MPa). Yet it has astonishing mean tensile strength (≈150 MPa) and fracture energy (≈350 to 1,240 J/m2). The reasons have recently become well understood: (i) the nanoscale thickness (≈300 nm) of nacre's building blocks, the aragonite lamellae (or platelets), and (ii) the imbricated, or staggered, arrangement of these lamellea, bound by biopolymer layers only ≈25 nm thick, occupying <5% of volume. These properties inspire manmade biomimetic materials. For engineering applications, however, the failure probability of ≤10-6 is generally required. To guarantee it, the type of probability density function (pdf) of strength, including its tail, must be determined. This objective, not pursued previously, is hardly achievable by experiments alone, since >10^8 tests of specimens would be needed. Here we outline a statistical model of strength that resembles a fishnet pulled diagonally, captures the tail of pdf of strength and, importantly, allows analytical safety assessments of nacreous materials. The analysis shows that, in terms of safety, the imbricated lamellar structure provides a major additional advantage—˜10% strength increase at tail failure probability 10^-6 and a 1 to 2 orders of magnitude tail probability decrease at fixed stress. Another advantage is that a high scatter of microstructure properties diminishes the strength difference between the mean and the probability tail, compared with the weakest link model. These advantages of nacre-like materials are here justified analytically and supported by millions of Monte Carlo simulations.