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.

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

Antihyperalgesic effects of ProTx-II, a Nav1.7 antagonist, and A803467, a Nav1.8 antagonist, in diabetic mice.

PubMed

Tanaka, Ken-Ichiro; Sekino, Shota; Ikegami, Megumi; Ikeda, Hiroko; Kamei, Junzo

2015-01-01

The present study investigated the effects of intrathecal administration of ProTx-II (tarantula venom peptide) and A803467 (5-[4-chloro-phenyl]-furan-2-carboxylic acid [3,5-dimethoxy-phenyl]-amide), selective Nav1.7 and Nav1.8 antagonists, respectively, on thermal hyperalgesia in a painful diabetic neuropathy model of mice. Intrathecal administration of ProTx-II at doses from 0.04 to 4 ng to diabetic mice dose-dependently and significantly increased the tail-flick latency. Intrathecal administration of A803467 at doses from 10 to 100 ng to diabetic mice also dose-dependently and significantly increased the tail-flick latency. However, intrathecal administration of either ProTx-II (4 ng) or A803467 (100 ng) had no effect on the tail-flick latency in nondiabetic mice. The expression of either the Nav1.7 or Nav1.8 sodium channel protein in the dorsal root ganglion in diabetic mice was not different from that in nondiabetic mice. The present results suggest that ProTx-II and A803467, highly selective blockers of Nav1.7 and Nav1.8 sodium channels, respectively, in the spinal cord, can have antihyperalgesic effects in diabetic mice.

The analgesic effect of orexin-A in a murine model of chemotherapy-induced neuropathic pain.

PubMed

Toyama, Satoshi; Shimoyama, Naohito; Shimoyama, Megumi

2017-02-01

Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN). Several chemotherapeutic agents used for the treatment of malignant diseases induce dose-limiting neuropathic pain that compromises patients' quality of life. Here, we examined the analgesic effect of orexin-A in a murine model of CIPN, and compared it with the effect of duloxetine, the only drug recommended for the treatment of CIPN pain in patients. CIPN was induced in male BALB/c mice by repeated intraperitoneal injection of oxaliplatin, a platinum chemotherapeutic agent used for the treatment of advanced colorectal cancer. Neuropathic mechanical allodynia was assessed by the von Frey test, and the effect on acute thermal pain was assessed by the tail flick test. Intracerebroventricularly administered orexin-A dose-dependently attenuated oxaliplatin-induced mechanical allodynia and increased tail flick latencies. Oxaliplatin-induced mechanical allodynia was completely reversed by orexin-A at a low dose that did not increase tail flick latency. Duloxetine only partially reversed mechanical allodynia and had no effect on tail flick latency. The analgesic effect of orexin-A on oxaliplatin-induced mechanical allodynia was completely antagonized by prior intraperitoneal injection of SB-408124 (orexin type-1 receptor antagonist), but not by prior intraperitoneal injection of TCS-OX2-29 (orexin type-2 receptor antagonist). Our findings suggest that orexin-A is more potent than duloxetine in relieving pain CIPN pain and its analgesic effect is mediated by orexin type-1 receptors. Orexin type-1 receptor agonists may have potential therapeutic roles in the treatment of CIPN pain in patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Systemic synergism between codeine and morphine in three pain models in mice.

PubMed

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

2013-01-01

The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes. This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models. Intrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip). This synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.

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.

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.

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.

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.

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.

The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber).

PubMed

Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K; Maloiy, Geoffrey M; Abelson, Klas S P

2014-01-01

The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in antinociception by investigating the involvement of muscarinic, nicotinic and opioid receptors in nociceptive tests in this species. The effects of systemic administration of the muscarinic receptor agonist oxotremorine and the nicotinic receptor agonist epibatidine were investigated in the tail-flick, the hot-plate, and the formalin tests. The effects of co-administration of the muscarinic receptor antagonist atropine, the nicotinic receptor antagonist mecamylamine, and the opioid receptor antagonist naloxone were also investigated. Oxotremorine and epibatidine induced a significant, dose-dependent antinociceptive effect in the tail-flick, hot-plate, and formalin tests, respectively. The effects of oxotremorine and epibatidine were blocked by atropine and mecamylamine, respectively. In all three nociceptive tests, naloxone in combination with oxotremorine or epibatidine enhanced the antinociceptive effects of the drugs. The present study demonstrated that stimulation of muscarinic and nicotinic receptors produces antinociceptive effects in the naked-mole rat. The reversal effect of atropine and mecamylamine suggests that this effect is mediated by cholinergic receptors. As naloxone increases the antinociceptive effects of cholinergic agonists, it is suggested that the cholinergic antinociception acts via a gateway facilitated by opioid receptor blockage; however, the precise interaction between these receptor systems needs further investigation.

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

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.

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

PubMed Central

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

2017-01-01

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. PMID:28627595

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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

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

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

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

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.

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.

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

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.

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.

[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.

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.

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.

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.

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

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.

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.

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

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.

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.

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

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.

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.

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

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.

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

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.

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

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.

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

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.

Experimental Study on Comprehensive Performance of Full Tailings Paste Filling in Jiaojia Gold Mine.

NASA Astrophysics Data System (ADS)

Zhang, Z. H.; Zou, Q. B.; Wang, P. Z.

2017-11-01

Filling mining method is the main method of modern underground mining. High concentration cementation is carried out using coarse tailing of +37 μm, and the mine has maturely used classified tailings paste filling technology. The gold mine studied on the performance of full tailings paste filling in order to maximize the use of tailings, reduce -37 μm fine tailings discharged into the tailing pond, reduce mining cost and eliminate security risks. The results show that: comprehensive index of full tailings paste filling is higher than that of classified tailings high concentration cementation filling, and the full tailings paste filling of 76% mass concentration has the best comprehensive index of slump, expansibility, yield stress and viscosity to meet the mining method requirements, which can effectively reduce the mining loss rate and dilution rate.

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.

Tail-scope: Using friends to estimate heavy tails of degree distributions in large-scale complex networks

NASA Astrophysics Data System (ADS)

Eom, Young-Ho; Jo, Hang-Hyun

2015-05-01

Many complex networks in natural and social phenomena have often been characterized by heavy-tailed degree distributions. However, due to rapidly growing size of network data and concerns on privacy issues about using these data, it becomes more difficult to analyze complete data sets. Thus, it is crucial to devise effective and efficient estimation methods for heavy tails of degree distributions in large-scale networks only using local information of a small fraction of sampled nodes. Here we propose a tail-scope method based on local observational bias of the friendship paradox. We show that the tail-scope method outperforms the uniform node sampling for estimating heavy tails of degree distributions, while the opposite tendency is observed in the range of small degrees. In order to take advantages of both sampling methods, we devise the hybrid method that successfully recovers the whole range of degree distributions. Our tail-scope method shows how structural heterogeneities of large-scale complex networks can be used to effectively reveal the network structure only with limited local information.

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...

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

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

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.

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.

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.

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.

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)).

The new idea of transporting tailings-logs in tailings slurry pipeline and the innovation of technology of mining waste-fill method

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

Lin Yu; Wang Fuji; Tao Yan

2000-07-01

This paper introduced a new idea of transporting mine tailings-logs in mine tailings-slurry pipeline and a new technology of mine cemented filing of tailings-logs with tailings-slurry. The hydraulic principles, the compaction of tailings-logs and the mechanic function of fillbody of tailings-logs cemented by tailings-slurry have been discussed.

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.

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.

Methods of natural gas liquefaction and natural gas liquefaction plants utilizing multiple and varying gas streams

DOEpatents

Wilding, Bruce M; Turner, Terry D

2014-12-02

A method of natural gas liquefaction may include cooling a gaseous NG process stream to form a liquid NG process stream. The method may further include directing the first tail gas stream out of a plant at a first pressure and directing a second tail gas stream out of the plant at a second pressure. An additional method of natural gas liquefaction may include separating CO.sub.2 from a liquid NG process stream and processing the CO.sub.2 to provide a CO.sub.2 product stream. Another method of natural gas liquefaction may include combining a marginal gaseous NG process stream with a secondary substantially pure NG stream to provide an improved gaseous NG process stream. Additionally, a NG liquefaction plant may include a first tail gas outlet, and at least a second tail gas outlet, the at least a second tail gas outlet separate from the first tail gas outlet.

Study on the Influence of Elevation of Tailing Dam on Stability

NASA Astrophysics Data System (ADS)

Wan, Shuai; Wang, Kun; Kong, Songtao; Zhao, Runan; Lan, Ying; Zhang, Run

2017-12-01

This paper takes Yunnan as the object of a tailing, by theoretical analysis and numerical calculation method of the effect of seismic load effect of elevation on the stability of the tailing, to analyse the stability of two point driven safety factor and liquefaction area. The Bishop method is adopted to simplify the calculation of dynamic safety factor and liquefaction area analysis using comparison method of shear stress to analyse liquefaction, so we obtained the influence of elevation on the stability of the tailing. Under the earthquake, with the elevation increased, the safety coefficient of dam body decreases, shallow tailing are susceptible to liquefy. Liquefaction area mainly concentrated in the bank below the water surface, to improve the scientific basis for the design and safety management of the tailing.

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.

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.

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…

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

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

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.

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.

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.

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.

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.

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.

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.

Mean Excess Function as a method of identifying sub-exponential tails: Application to extreme daily rainfall

NASA Astrophysics Data System (ADS)

Nerantzaki, Sofia; Papalexiou, Simon Michael

2017-04-01

Identifying precisely the distribution tail of a geophysical variable is tough, or, even impossible. First, the tail is the part of the distribution for which we have the less empirical information available; second, a universally accepted definition of tail does not and cannot exist; and third, a tail may change over time due to long-term changes. Unfortunately, the tail is the most important part of the distribution as it dictates the estimates of exceedance probabilities or return periods. Fortunately, based on their tail behavior, probability distributions can be generally categorized into two major families, i.e., sub-exponentials (heavy-tailed) and hyper-exponentials (light-tailed). This study aims to update the Mean Excess Function (MEF), providing a useful tool in order to asses which type of tail better describes empirical data. The MEF is based on the mean value of a variable over a threshold and results in a zero slope regression line when applied for the Exponential distribution. Here, we construct slope confidence intervals for the Exponential distribution as functions of sample size. The validation of the method using Monte Carlo techniques on four theoretical distributions covering major tail cases (Pareto type II, Log-normal, Weibull and Gamma) revealed that it performs well especially for large samples. Finally, the method is used to investigate the behavior of daily rainfall extremes; thousands of rainfall records were examined, from all over the world and with sample size over 100 years, revealing that heavy-tailed distributions can describe more accurately rainfall extremes.

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.

Unconventional tail configurations for transport aircraft

NASA Astrophysics Data System (ADS)

Sánchez-Carmona, A.; Cuerno-Rejado, C.; García-Hernández, L.

2017-06-01

This article presents the bases of a methodology in order to size unconventional tail configurations for transport aircraft. The case study of this paper is a V-tail con¦guration. Firstly, an aerodynamic study is developed for determining stability derivatives and aerodynamic forces. The objective is to size a tail such as it develops at least the same static stability derivatives than a conventional reference aircraft. The optimum is obtained minimizing its weight. The weight is estimated through two methods: adapted Farrar£s method and a statistical method. The solution reached is heavier than the reference, but it reduces the wetted area.

Polyadenylation state microarray (PASTA) analysis.

PubMed

Beilharz, Traude H; Preiss, Thomas

2011-01-01

Nearly all eukaryotic mRNAs terminate in a poly(A) tail that serves important roles in mRNA utilization. In the cytoplasm, the poly(A) tail promotes both mRNA stability and translation, and these functions are frequently regulated through changes in tail length. To identify the scope of poly(A) tail length control in a transcriptome, we developed the polyadenylation state microarray (PASTA) method. It involves the purification of mRNA based on poly(A) tail length using thermal elution from poly(U) sepharose, followed by microarray analysis of the resulting fractions. In this chapter we detail our PASTA approach and describe some methods for bulk and mRNA-specific poly(A) tail length measurements of use to monitor the procedure and independently verify the microarray data.

The Effects of Tail Docking Method on Piglets' Behavioral Responses to a Formalin Pain Test

USDA-ARS?s Scientific Manuscript database

Routine piglet production procedures, for example teeth clipping, tail docking and castration, most likely cause pain and are under increasing scrutiny from the animal rights lobby. The objectives of this study were to assess the impact of 2 alternative methods of tail-docking on subsequent response...

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).

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.

Radial-based tail methods for Monte Carlo simulations of cylindrical interfaces

NASA Astrophysics Data System (ADS)

Goujon, Florent; Bêche, Bruno; Malfreyt, Patrice; Ghoufi, Aziz

2018-03-01

In this work, we implement for the first time the radial-based tail methods for Monte Carlo simulations of cylindrical interfaces. The efficiency of this method is then evaluated through the calculation of surface tension and coexisting properties. We show that the inclusion of tail corrections during the course of the Monte Carlo simulation impacts the coexisting and the interfacial properties. We establish that the long range corrections to the surface tension are the same order of magnitude as those obtained from planar interface. We show that the slab-based tail method does not amend the localization of the Gibbs equimolar dividing surface. Additionally, a non-monotonic behavior of surface tension is exhibited as a function of the radius of the equimolar dividing surface.

Comparing Phlebotomy by Tail Tip Amputation, Facial Vein Puncture, and Tail Vein Incision in C57BL/6 Mice by Using Physiologic and Behavioral Metrics of Pain and Distress

PubMed Central

Moore, Elizabeth S; Cleland, Thomas A; Williams, Wendy O; Peterson, Christine M; Singh, Bhupinder; Southard, Teresa L; Pasch, Bret; Labitt, Rachael N; Daugherity, Erin K

2017-01-01

Tail tip amputation with minimal restraint is not widely used for mouse phlebotomy. In part, this infrequency may reflect policies influenced by tail tip amputation procedures for genotyping, which involve greater handling and tissue removal. To assess tail tip amputation with minimal restraint as a phlebotomy technique, we compared it with 2 more common methods: scruffing with facial vein puncture and lateral tail vein incision with minimal restraint. Blood glucose levels, audible and ultrasonic vocalizations, postphlebotomy activity and grooming behavior, open field and elevated plus maze behaviors, nest-building scores, and histologic changes at the phlebotomy site were evaluated. Mice in the facial vein phlebotomy group produced more audible vocalizations, exhibited lower postphlebotomy activity in the open field, and had more severe histologic changes than did mice in the tail incision and tail tip amputation groups. Facial vein phlebotomy did not affect grooming behavior relative to sham groups, whereas tail vein incision—but not tail tip amputation—increased tail grooming compared with that in control mice. Blood glucose levels, nest-building scores, and elevated plus maze behavior did not differ between groups, and no mice in any group produced ultrasonic vocalizations. Tail tip amputation mice did not perform differently than sham mice in any metric analyzed, indicating that this technique is a potentially superior method of blood collection in mice in terms of animal wellbeing. PMID:28535866

Comparing Phlebotomy by Tail Tip Amputation, Facial Vein Puncture, and Tail Vein Incision in C57BL/6 Mice by Using Physiologic and Behavioral Metrics of Pain and Distress.

PubMed

Moore, Elizabeth S; Cleland, Thomas A; Williams, Wendy O; Peterson, Christine M; Singh, Bhupinder; Southard, Teresa L; Pasch, Bret; Labitt, Rachael N; Daugherity, Erin K

2017-05-01

Tail tip amputation with minimal restraint is not widely used for mouse phlebotomy. In part, this infrequency may reflect policies influenced by tail tip amputation procedures for genotyping, which involve greater handling and tissue removal. To assess tail tip amputation with minimal restraint as a phlebotomy technique, we compared it with 2 more common methods: scruffing with facial vein puncture and lateral tail vein incision with minimal restraint. Blood glucose levels, audible and ultrasonic vocalizations, postphlebotomy activity and grooming behavior, open field and elevated plus maze behaviors, nest-building scores, and histologic changes at the phlebotomy site were evaluated. Mice in the facial vein phlebotomy group produced more audible vocalizations, exhibited lower postphlebotomy activity in the open field, and had more severe histologic changes than did mice in the tail incision and tail tip amputation groups. Facial vein phlebotomy did not affect grooming behavior relative to sham groups, whereas tail vein incision-but not tail tip amputation-increased tail grooming compared with that in control mice. Blood glucose levels, nest-building scores, and elevated plus maze behavior did not differ between groups, and no mice in any group produced ultrasonic vocalizations. Tail tip amputation mice did not perform differently than sham mice in any metric analyzed, indicating that this technique is a potentially superior method of blood collection in mice in terms of animal wellbeing.

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…

A tailing genome walking method suitable for genomes with high local GC content.

PubMed

Liu, Taian; Fang, Yongxiang; Yao, Wenjuan; Guan, Qisai; Bai, Gang; Jing, Zhizhong

2013-10-15

The tailing genome walking strategies are simple and efficient. However, they sometimes can be restricted due to the low stringency of homo-oligomeric primers. Here we modified their conventional tailing step by adding polythymidine and polyguanine to the target single-stranded DNA (ssDNA). The tailed ssDNA was then amplified exponentially with a specific primer in the known region and a primer comprising 5' polycytosine and 3' polyadenosine. The successful application of this novel method for identifying integration sites mediated by φC31 integrase in goat genome indicates that the method is more suitable for genomes with high complexity and local GC content. Copyright © 2013 Elsevier Inc. All rights reserved.

Reconciling PM10 analyses by different sampling methods for Iron King Mine tailings dust.

PubMed

Li, Xu; Félix, Omar I; Gonzales, Patricia; Sáez, Avelino Eduardo; Ela, Wendell P

2016-03-01

The overall project objective at the Iron King Mine Superfund site is to determine the level and potential risk associated with heavy metal exposure of the proximate population emanating from the site's tailings pile. To provide sufficient size-fractioned dust for multi-discipline research studies, a dust generator was built and is now being used to generate size-fractioned dust samples for toxicity investigations using in vitro cell culture and animal exposure experiments as well as studies on geochemical characterization and bioassay solubilization with simulated lung and gastric fluid extractants. The objective of this study is to provide a robust method for source identification by comparing the tailing sample produced by dust generator and that collected by MOUDI sampler. As and Pb concentrations of the PM10 fraction in the MOUDI sample were much lower than in tailing samples produced by the dust generator, indicating a dilution of Iron King tailing dust by dust from other sources. For source apportionment purposes, single element concentration method was used based on the assumption that the PM10 fraction comes from a background source plus the Iron King tailing source. The method's conclusion that nearly all arsenic and lead in the PM10 dust fraction originated from the tailings substantiates our previous Pb and Sr isotope study conclusion. As and Pb showed a similar mass fraction from Iron King for all sites suggesting that As and Pb have the same major emission source. Further validation of this simple source apportionment method is needed based on other elements and sites.

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

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.

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

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

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.

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

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.

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.

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.

Comparison of neural histomorphology in tail tips from pigs docked using clippers or cautery iron.

PubMed

Kells, N J; Beausoleil, N J; Johnson, C B; Sutherland, M A; Morrison, R S; Roe, W

2017-07-01

Tail docking of pigs is commonly performed to reduce the incidence of unwanted tail-biting behaviour. Two docking methods are commonly used: blunt trauma cutting (i.e. using side clippers), or cutting and concurrent cauterisation using a hot cautery iron. A potential consequence of tail amputation is the development of neuromas at the docking site. Neuromas have been linked to neuropathic pain, which can influence the longer-term welfare of affected individuals. To determine whether method of tail docking influences the extent of neuroma formation, 75 pigs were allocated to one of three treatments at birth: tail docked using clippers; tail docked using cautery iron; tail left intact. Tail docking was performed at 2 days of age and pigs were kept under conventional conditions until slaughter at 21 weeks of age. Tails were removed following slaughter and subjected to histological examination. Nerve histomorphology was scored according to the following scale: 1=discrete well-organised nerve bundles; 2=moderate neural proliferation and disorganisation affecting more than half of the circumference of the tail; 3=marked neural proliferation to form almost continuous disorganised bundles or non-continuous enlarged bundles compressing the surrounding connective tissue. Scores of 2 or 3 indicated neuroma formation. Scores were higher in docked pigs than undocked pigs (P<0.001), but did not differ between pigs docked using clippers and those docked using cautery (P=0.23). The results indicate that tail docking using either clippers or cautery results in neuroma formation, thus having the potential to affect long-term pig welfare.

Testing tail-mounted transmitters with Myocastor coypus (nutria)

USGS Publications Warehouse

Merino, S.; Carter, J.; Thibodeaux, G.

2007-01-01

We developed a tail-mounted radio-transmitter for Myocastor coypus (nutria) that offers a practical and efficient alternative to collar or implant methods. The mean retention time was 96 d (range 57-147 d, n = 7), making this a practical method for short-term studies. The tail-mounts were less injurious to animals than collars and easier for field researchers to implement than either collars or surgically implanted transmitters.

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…

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

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.

Efficient degradation of Acid Orange 7 in aqueous solution by iron ore tailing Fenton-like process.

PubMed

Zheng, Jianming; Gao, Zhanqi; He, Huan; Yang, Shaogui; Sun, Cheng

2016-05-01

An effective method based on iron ore tailing Fenton-like process was studied for removing an azo dye, Acid Orange 7 (AO7) in aqueous solution. Five tailings were characterized by X-ray fluorescence spectroscope (XFS), Brunner-Emmet-Teller (BET) measurement, and Scanning Electron Microscope (SEM). The result of XFS showed that Fe, Si and Ca were the most abundant elements and some toxic heavy metals were also present in the studied tailings. The result of BET analysis indicated that the studied tailings had very low surface areas (0.64-5.68 m(2) g(-1)). The degradation efficiencies of AO7 were positively correlated with the content of iron oxide and cupric oxide, and not related with the BET surface area of the tailings. The co-existing metal elements, particularly Cu, might accelerate the heterogeneous Fenton-like reaction. The effects of other parameters on heterogeneous Fenton-like degradation of AO7 by a converter slag iron tailing (tailing E) which contains highest iron oxide were also investigated. The tailing could be reused 10 times without significant decrease of the catalytic capacity. Very low amount of iron species and almost undetectable toxic elements were leached in the catalytic degradation of AO7 by the tailing E. The reaction products were identified by gas chromatography-mass spectrometry and a possible pathway of AO7 degradation was proposed. This study not only provides an effective method for removing azo dyes in polluted water by employing waste tailings as Fenton-like catalysts, but also uses waste tailings as the secondary resource. Copyright © 2016 Elsevier Ltd. All rights reserved.

Separation of Main and Tail Rotor Noise Sources from Ground-Based Acoustic Measurements Using Time-Domain De-Dopplerization

NASA Technical Reports Server (NTRS)

Greenwood, Eric II; Schmitz, Fredric H.

2009-01-01

A new method of separating the contributions of helicopter main and tail rotor noise sources is presented, making use of ground-based acoustic measurements. The method employs time-domain de-Dopplerization to transform the acoustic pressure time-history data collected from an array of ground-based microphones to the equivalent time-history signals observed by an array of virtual inflight microphones traveling with the helicopter. The now-stationary signals observed by the virtual microphones are then periodically averaged with the main and tail rotor once per revolution triggers. The averaging process suppresses noise which is not periodic with the respective rotor, allowing for the separation of main and tail rotor pressure time-histories. The averaged measurements are then interpolated across the range of directivity angles captured by the microphone array in order to generate separate acoustic hemispheres for the main and tail rotor noise sources. The new method is successfully applied to ground-based microphone measurements of a Bell 206B3 helicopter and demonstrates the strong directivity characteristics of harmonic noise radiation from both the main and tail rotors of that helicopter.

Environmental Risk Assessment System for Phosphogypsum Tailing Dams

PubMed Central

Sun, Xin; Tang, Xiaolong; Yi, Honghong; Li, Kai; Zhou, Lianbi; Xu, Xianmang

2013-01-01

This paper may be of particular interest to the readers as it provides a new environmental risk assessment system for phosphogypsum tailing dams. In this paper, we studied the phosphogypsum tailing dams which include characteristics of the pollution source, environmental risk characteristics and evaluation requirements to identify the applicable environmental risk assessment methods. Two analytical methods, that is, the analytic hierarchy process (AHP) and fuzzy logic, were used to handle the complexity of the environmental and nonquantitative data. Using our assessment method, different risk factors can be ranked according to their contributions to the environmental risk, thereby allowing the calculation of their relative priorities during decision making. Thus, environmental decision-makers can use this approach to develop alternative management strategies for proposed, ongoing, and completed PG tailing dams. PMID:24382947

Environmental risk assessment system for phosphogypsum tailing dams.

PubMed

Sun, Xin; Ning, Ping; Tang, Xiaolong; Yi, Honghong; Li, Kai; Zhou, Lianbi; Xu, Xianmang

2013-01-01

This paper may be of particular interest to the readers as it provides a new environmental risk assessment system for phosphogypsum tailing dams. In this paper, we studied the phosphogypsum tailing dams which include characteristics of the pollution source, environmental risk characteristics and evaluation requirements to identify the applicable environmental risk assessment methods. Two analytical methods, that is, the analytic hierarchy process (AHP) and fuzzy logic, were used to handle the complexity of the environmental and nonquantitative data. Using our assessment method, different risk factors can be ranked according to their contributions to the environmental risk, thereby allowing the calculation of their relative priorities during decision making. Thus, environmental decision-makers can use this approach to develop alternative management strategies for proposed, ongoing, and completed PG tailing dams.

Taguchi optimization: Case study of gold recovery from amalgamation tailing by using froth flotation method

NASA Astrophysics Data System (ADS)

Sudibyo, Aji, B. B.; Sumardi, S.; Mufakir, F. R.; Junaidi, A.; Nurjaman, F.; Karna, Aziza, Aulia

2017-01-01

Gold amalgamation process was widely used to treat gold ore. This process produces the tailing or amalgamation solid waste, which still contains gold at 8-9 ppm. Froth flotation is one of the promising methods to beneficiate gold from this tailing. However, this process requires optimal conditions which depends on the type of raw material. In this study, Taguchi method was used to optimize the optimum conditions of the froth flotation process. The Taguchi optimization shows that the gold recovery was strongly influenced by the particle size which is the best particle size at 150 mesh followed by the Potassium amyl xanthate concentration, pH and pine oil concentration at 1133.98, 4535.92 and 68.04 gr/ton amalgamation tailing, respectively.

STUDIES ON THE ANTIGENIC STRUCTURE OF SOME MAMMALIAN SPERMATOZOA

PubMed Central

Henle, Werner; Henle, Gertrude; Chambers, Leslie A.

1938-01-01

1. A method has been described for separation of heads and tails of mammalian spermatozoa. 2. By means of absorption technique applied to homologous spermatozoal sera, head-specific and tail-specific antigens could be demonstrated. Both are heat-labile. 3. A heat-stable antigen was found to be common to both heads and tails. This substance is species-specific. 4. Antibodies against the head- and tail-specific antigens led to two different types of agglutination as shown by the slide method. 5. Using heterologous antisera against spermatozoa three different cross-reacting antigens could be observed, two in the heads, one in the tails. 6. One of the head-antigens is not active in the native cell; it comes to action only after breaking the cell. Antibodies against this substance were not found in antisera against native bull spermatozoa but were formed when vibrated spermatozoa or heads were injected into rabbits. 7. The cross-reactions can be removed from an antiserum leaving the head- as well as the tail-specific reaction intact. PMID:19870792

Sulfide tails management within the framework of sustainable development in mineral sand mines--the case study of Sierra Rutile Ltd.

PubMed

Kallon, Senesie B; Jabati, Ansu M; Samura, Alusine

2011-01-01

The study discussed here assessed Sierra Rutile Ltd.'s (SRLs) water-cover sulfide tails management method. Monthly and quarterly water samples from SRLs Sulfide Tails Pond (STP), Total Tails Pond (TTP), and the Titan Domestic Pond (TDP) were analyzed for 15 months. Results indicated acceptable quality for the STP. From Student's t-test analysis, it was found that the mean pH of the TTP was significantly lower than that of the TDP (p < .05). Results did not indicate pollution of the TDP by SRLs tailings management. The water-cover method significantly suppressed sulfide oxidation in the STP. Concerns to be addressed, however, include potential overtopping of the pond, water level fluctuations, and the need for periodic reinforcement of the tailings embankments. A dedicated environmental monitoring campaign that includes other proximate water bodies is suggested; this should inform timely mitigation of any environmental contamination and promote sound environmental and public health outcomes.

Forensic species identification of elephant (Elephantidae) and giraffe (Giraffidae) tail hair using light microscopy.

PubMed

Yates, Bonnie C; Espinoza, Edgard O; Baker, Barry W

2010-09-01

Here we present methods for distinguishing tail hairs of African elephants (Loxodonta africana), Asian elephants (Elephas maximus), and giraffes (Giraffa camelopardalis) from forensic contexts. Such hairs are commonly used to manufacture jewelry artifacts that are often sold illegally in the international wildlife trade. Tail hairs from these three species are easily confused macroscopically, and morphological methods for distinguishing African and Asian tail hairs have not been published. We used cross section analysis and light microscopy to analyze the tail hair morphology of 18 individual African elephants, 18 Asian elephants, and 40 giraffes. We found that cross-sectional shape, pigment placement, and pigment density are useful morphological features for distinguishing the three species. These observations provide wildlife forensic scientists with an important analytical tool for enforcing legislation and international treaties regulating the trade in elephant parts.

Nuclear sensor signal processing circuit

DOEpatents

Kallenbach, Gene A [Bosque Farms, NM; Noda, Frank T [Albuquerque, NM; Mitchell, Dean J [Tijeras, NM; Etzkin, Joshua L [Albuquerque, NM

2007-02-20

An apparatus and method are disclosed for a compact and temperature-insensitive nuclear sensor that can be calibrated with a non-hazardous radioactive sample. The nuclear sensor includes a gamma ray sensor that generates tail pulses from radioactive samples. An analog conditioning circuit conditions the tail-pulse signals from the gamma ray sensor, and a tail-pulse simulator circuit generates a plurality of simulated tail-pulse signals. A computer system processes the tail pulses from the gamma ray sensor and the simulated tail pulses from the tail-pulse simulator circuit. The nuclear sensor is calibrated under the control of the computer. The offset is adjusted using the simulated tail pulses. Since the offset is set to zero or near zero, the sensor gain can be adjusted with a non-hazardous radioactive source such as, for example, naturally occurring radiation and potassium chloride.

Black-tailed and white-tailed jackrabbits in the American West: History, ecology, ecological significance, and survey methods

USGS Publications Warehouse

Simes, Matthew; Longshore, Kathleen M.; Nussear, Kenneth E.; Beatty, Greg L.; Brown, David E.; Esque, Todd C.

2015-01-01

Across the western United States, Leporidae are the most important prey item in the diet of Golden Eagles (Aquila chrysaetos). Leporids inhabiting the western United States include black-tailed (Lepus californicus) and white-tailed jackrabbits (Lepus townsendii) and various species of cottontail rabbit (Sylvilagus spp.). Jackrabbits (Lepus spp.) are particularly important components of the ecological and economic landscape of western North America because their abundance influences the reproductive success and population trends of predators such as coyotes (Canis latrans), bobcats (Lynx rufus), and a number of raptor species. Here, we review literature pertaining to black-tailed and white-tailed jackrabbits comprising over 170 published journal articles, notes, technical reports, conference proceedings, academic theses and dissertations, and other sources dating from the late 19th century to the present. Our goal is to present information to assist those in research and management, particularly with regard to protected raptor species (e.g., Golden Eagles), mammalian predators, and ecological monitoring. We classified literature sources as (1) general information on jackrabbit species, (2) black-tailed or (3) white-tailed jackrabbit ecology and natural history, or (4) survey methods. These categories, especially 2, 3, and 4, were further subdivided as appropriate. The review also produced several tables on population trends, food habits, densities within various habitats, and jackrabbit growth and development. Black-tailed and white-tailed jackrabbits are ecologically similar in general behaviors, use of forms, parasites, and food habits, and they are prey to similar predators; but they differ in their preferred habitats. While the black-tailed jackrabbit inhabits agricultural land, deserts, and shrublands, the white-tailed jackrabbit is associated with prairies, alpine tundra, and sagebrush-steppe. Frequently considered abundant, jackrabbit numbers in western North America fluctuate temporally and spatially. We also reviewed methods used to investigate jackrabbit populations, including spotlight line transects, flushing transects, drive counts, pellet plot counts, collections, roadside counts, mark-recapture studies, and radio-telemetry studies. Our review of jackrabbit literature illustrates a number of deficiencies in our understanding of jackrabbits in general. As an example, a detailed quantitative description of habitat preferences is lacking, as is a thorough understanding of sympatric jackrabbit species interactions. Even the existence of the oft-cited jackrabbit “cycle” is a matter of debate. Survey methods generally do not address efficacy or accuracy in measuring jackrabbit density or abundance. In addition, there is a paucity of information about jackrabbits in the Mojave Desert, with no real understanding of home ranges, habitat preferences, and population dynamics or demographics in this region.

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…

Thyroxine Induced Resorption of Xenopus Laevis Tail Tissue in Vitro.

ERIC Educational Resources Information Center

Scadding, Steven R.

1984-01-01

A simple method of studying thyroxine-induced resorption of tadpole tails in vitro is described. This procedure demonstrates that resorption is dependent on thyroxine and requires protein synthesis. It introduces students to the use of tissue culture methods. (Author)

Ethnopharmacological investigation of the aerial part of Phragmites karka (Poaceae).

PubMed

Sultan, Ramiz Ahmed; Kabir, Mohammad Shah Hafez; Uddin, Mir Muhammad Nasir; Uddin, Mohi; Mahmud, Zobaer Al; Raihan, Sheikh Zahir; Qais, Nazmul

2017-05-01

In this ethnopharmacological study, methanolic extract of the aerial plant parts of Phragmites karka (Family: Poaceae) and its petroleum ether and carbon tetrachloride fractions were investigated for bioactivities in Swiss-albino mice, namely, analgesic, central nervous system (CNS) depressant, hypoglycemic, and antidiarrheal activity. The cold methanolic extract of the aerial plant parts of Phragmites karka (MEPK) was first prepared, and it was then further fractionated as petroleum ether (PEFMEPK) and carbon tetrachloride (CTFMEPK) fractions. Analgesic activity was performed employing acidic acid-induced writhing test, central analgesic effect by radiant heat tail-flick method. CNS depressant activity was evaluated by phenobarbitone-induced sleeping time test. Hypoglycemic activity was tested by glucose tolerance test (GTT). Antidiarrheal activity was evaluated by castor oil-induced diarrhea method. For all in vivo tests, doses of 200 and 400 mg/kg body weight were used. In the mice model, the MEPK, PEFMEPK, and CTFMEPK fractions showed significant peripheral analgesic activity at a dose of 400 mg/kg body weight with percentage of inhibition of acetic acid-induced writhing 77.67 (p<0.001), 33.50 (p<0.001), and 40.29 (p<0.001), respectively, compared to the standard dichlofenac (60.68%, p<0.001) group. The hypoglycemic properties of MEPK, PEFMEPK, and CTFMEPK extracts were evaluated in normoglycemic mice where the reduction of blood glucose level after 30 min of glucose load were 69.85%, 78.91%, and 72.73%, respectively, and for standard glibenclamide, the reduction was 72.85%. All results were significant (p<0.05). In the case of the CNS depressant activity by phenobarbitone-induced sleeping time test, the crude ME significantly reduced sleep latency by 57.14% and increased the duration of sleep by 63.29% compared to the control, which were comparable to that of standard diazepam (65.71% and 77.62%, respectively). Among all the extract and fractions, methanolic extract showed the maximum antidiarrheal effect. The methanolic extract at 200 mg/kg dose induced a significant decrease in the total number of defecation in 4 h (69.05% of inhibition, p<0.001) and at 400 mg/kg dose showed 76.19% of inhibition (p<0.001). In light of the available literature, these findings represent the first experimental investigation of biological activities of P. karka in the perspective of their traditional use.

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.

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

SEARCH AND MAPPING OF THE OLD BURIED TAILINGS WITH RADIOACTIVE WASTES AT THE URBAN TERRITORY.

PubMed

Molchanov, O I; Soroka, Y N; Podrezov, A A; Soroka, M N

2017-11-01

The article presents results of investigation on search and mapping of the old buried tailings with radioactive wastes on the territory of Kamianske City. For solving the problem used complex of methods. These methods are as follows: soil-gas 222Rn measurement and measurement of 222Rn flux density from the ground surface, gamma-radiation survey, prospecting drilling, gamma-ray logging and laboratory analysis of radionuclides. The leading method in this complex was the method of soil-gas 222Rn measurement. Using this method location of the tailings has been precisely defined. The tailings boundaries have been contoured in the plan. Other methods permitted to define such parameters as thickness of the wastes, their volume (~330 000 m3), radionuclide and chemical composition. It was found that radioactive residues occur at a depth from 2 to 11 m and contain in its composition 226Ra, 210Pb and 210Po in the range from 8370 to 37 270 Bq kg-1. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Water vapour and heat combine to elicit biting and biting persistence in tsetse

PubMed Central

2013-01-01

Background Tsetse flies are obligatory blood feeders, accessing capillaries by piercing the skin of their hosts with the haustellum to suck blood. However, this behaviour presents a considerable risk as landing flies are exposed to predators as well as the host’s own defense reactions such as tail flicking. Achieving a successful blood meal within the shortest time span is therefore at a premium in tsetse, so feeding until replete normally lasts less than a minute. Biting in blood sucking insects is a multi-sensory response involving a range of physical and chemical stimuli. Here we investigated the role of heat and humidity emitted from host skin on the biting responses of Glossina pallidipes, which to our knowledge has not been fully studied in tsetse before. Methods The onset and duration of the biting response of G. pallidipes was recorded by filming movements of its haustellum in response to rapid increases in temperature and/or relative humidity (RH) following exposure of the fly to two airflows. The electrophysiological responses of hygroreceptor cells in wall-pore sensilla on the palps of G. pallidipes to drops in RH were recorded using tungsten electrodes and the ultra-structure of these sensory cells was studied by scanning and transmission electron microscopy. Results Both latency and proportion of tsetse biting are closely correlated to RH when accompanied by an increase of 13.1°C above ambient temperature but not for an increase of just 0.2°C. Biting persistence, as measured by the number of bites and the time spent biting, also increases with increasing RH accompanied by a 13.1°C increase in air temperature. Neurones in wall-pore sensilla on the palps respond to shifts in RH. Conclusions Our results show that temperature acts synergistically with humidity to increase the rapidity and frequency of the biting response in tsetse above the levels induced by increasing temperature or humidity separately. Palp sensilla housing hygroreceptor cells, described here for the first time in tsetse, are involved in the perception of differences in RH. PMID:23958224

Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

PubMed Central

Hoekman, John D.; Ho, Rodney J.Y.

2011-01-01

Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport mechanism. Conclusions Deposition of opioids to the olfactory region within the nasal cavity could have a significant impact on drug distribution and pharmacodynamic effect, and thus should be considered into account in future nasally administered opioid studies. PMID:21709146

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

Two-Dimensional Fourier Transform Analysis of Helicopter Flyover Noise

NASA Technical Reports Server (NTRS)

SantaMaria, Odilyn L.; Farassat, F.; Morris, Philip J.

1999-01-01

A method to separate main rotor and tail rotor noise from a helicopter in flight is explored. Being the sum of two periodic signals of disproportionate, or incommensurate frequencies, helicopter noise is neither periodic nor stationary. The single Fourier transform divides signal energy into frequency bins of equal size. Incommensurate frequencies are therefore not adequately represented by any one chosen data block size. A two-dimensional Fourier analysis method is used to separate main rotor and tail rotor noise. The two-dimensional spectral analysis method is first applied to simulated signals. This initial analysis gives an idea of the characteristics of the two-dimensional autocorrelations and spectra. Data from a helicopter flight test is analyzed in two dimensions. The test aircraft are a Boeing MD902 Explorer (no tail rotor) and a Sikorsky S-76 (4-bladed tail rotor). The results show that the main rotor and tail rotor signals can indeed be separated in the two-dimensional Fourier transform spectrum. The separation occurs along the diagonals associated with the frequencies of interest. These diagonals are individual spectra containing only information related to one particular frequency.

Recycling of asbestos tailings used as reinforcing fillers in polypropylene based composites.

PubMed

Zhai, Wensi; Wang, Yao; Deng, Yuan; Gao, Hongli; Lin, Zhen; Li, Mao

2014-04-15

In this work, asbestos tailings were recycled and used as reinforcing fillers to enhance the mechanical properties of polypropylene (PP). A silane coupling agent was used to chemically modify the asbestos tailings to increase the compatibility between asbestos tailings and polypropylene matrix. Both raw and chemically treated asbestos tailings with different loading levels (from 3 to 30 wt%) were utilized to fabricate composites. Mechanical properties of these composites have been investigated by dynamic mechanical analysis, tensile test and notched impact test. Results showed that hybridization of asbestos tailings in the composites enhanced the mechanical properties of neat PP evidently, and treated asbestos tailings/PP composites yielded even better mechanical properties compared with those of raw asbestos tailings/PP composites. This recycling method of asbestos tailings not only reduces disposal costs and avoids secondary pollution but also produces a new PP-based composite material with enhanced mechanical properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Confidence intervals for the between-study variance in random-effects meta-analysis using generalised heterogeneity statistics: should we use unequal tails?

PubMed

Jackson, Dan; Bowden, Jack

2016-09-07

Confidence intervals for the between study variance are useful in random-effects meta-analyses because they quantify the uncertainty in the corresponding point estimates. Methods for calculating these confidence intervals have been developed that are based on inverting hypothesis tests using generalised heterogeneity statistics. Whilst, under the random effects model, these new methods furnish confidence intervals with the correct coverage, the resulting intervals are usually very wide, making them uninformative. We discuss a simple strategy for obtaining 95 % confidence intervals for the between-study variance with a markedly reduced width, whilst retaining the nominal coverage probability. Specifically, we consider the possibility of using methods based on generalised heterogeneity statistics with unequal tail probabilities, where the tail probability used to compute the upper bound is greater than 2.5 %. This idea is assessed using four real examples and a variety of simulation studies. Supporting analytical results are also obtained. Our results provide evidence that using unequal tail probabilities can result in shorter 95 % confidence intervals for the between-study variance. We also show some further results for a real example that illustrates how shorter confidence intervals for the between-study variance can be useful when performing sensitivity analyses for the average effect, which is usually the parameter of primary interest. We conclude that using unequal tail probabilities when computing 95 % confidence intervals for the between-study variance, when using methods based on generalised heterogeneity statistics, can result in shorter confidence intervals. We suggest that those who find the case for using unequal tail probabilities convincing should use the '1-4 % split', where greater tail probability is allocated to the upper confidence bound. The 'width-optimal' interval that we present deserves further investigation.

Microbial communities in a porphyry copper tailings impoundment and their impact on the geochemical dynamics of the mine waste.

PubMed

Diaby, Nouhou; Dold, Bernhard; Pfeifer, Hans-Rudolf; Holliger, Christof; Johnson, D Barrie; Hallberg, Kevin B

2007-02-01

The distribution and diversity of acidophilic bacteria of a tailings impoundment at the La Andina copper mine, Chile, was examined. The tailings have low sulfide (1.7% pyrite equivalent) and carbonate (1.4% calcite equivalent) contents and are stratified into three distinct zones: a surface (0-70-80 cm) 'oxidation zone' characterized by low-pH (2.5-4), a 'neutralization zone' (70-80 to 300-400 cm) and an unaltered 'primary zone' below 400 cm. A combined cultivation-dependent and biomolecular approach (terminal restriction enzyme fragment length polymorphism and 16S rRNA clone library analysis) was used to characterize the indigenous prokaryotic communities in the mine tailings. Total cell counts showed that the microbial biomass was greatest in the top 125 cm of the tailings. The largest numbers of bacteria (10(9) g(-1) dry weight of tailings) were found at the oxidation front (the junction between the oxidation and neutralization zones), where sulfide minerals and oxygen were both present. The dominant iron-/sulfur-oxidizing bacteria identified at the oxidation front included bacteria of the genus Leptospirillum (detected by molecular methods), and Gram-positive iron-oxidizing acidophiles related to Sulfobacillus (identified both by molecular and cultivation methods). Acidithiobacillus ferrooxidans was also detected, albeit in relatively small numbers. Heterotrophic acidophiles related to Acidobacterium capsulatum were found by molecular methods, while another Acidobacterium-like bacterium and an Acidiphilium sp. were isolated from oxidation zone samples. A conceptual model was developed, based on microbiological and geochemical data derived from the tailings, to account for the biogeochemical evolution of the Piuquenes tailings impoundment.

Liquid Chromatographic Detection of Permethrin from Filter Paper Wipes of White-tailed Deer

USDA-ARS?s Scientific Manuscript database

A simple, small-scale method for the determination of the presence or absence of permethrin on the hair coat of white-tailed deer, Odocoileus virginianus (Zimmermann), by high performance liquid chromatography was developed. White-tailed deer in South Texas and the northeastern U.S. are routinely tr...

Ultrasound-assisted extraction for total sulphur measurement in mine tailings.

PubMed

Khan, Adnan Hossain; Shang, Julie Q; Alam, Raquibul

2012-10-15

A sample preparation method for percentage recovery of total sulphur (%S) in reactive mine tailings based on ultrasound-assisted digestion (USAD) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) was developed. The influence of various methodological factors was screened by employing a two-level and three-factor (2(3)) full factorial design and using KZK-1, a sericite schist certified reference material (CRM), to find the optimal combination of studied factors and %S. Factors such as the sonication time, temperature and acid combination were studied, with the best result identified as 20 min of sonication, 80°C temperature and 1 ml of HNO(3):1 ml of HCl, which can achieve 100% recovery for the selected CRM. Subsequently a fraction of the 2(3) full factorial design was applied to mine tailings. The percentage relative standard deviation (%RSD) for the ultrasound method is less than 3.0% for CRM and less than 6% for the mine tailings. The investigated method was verified by X-ray diffraction analysis. The USAD method compared favorably with existing methods such as hot plate assisted digestion method, X-ray fluorescence and LECO™-CNS method. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Can tail damage outbreaks in the pig be predicted by behavioural change?

PubMed

Larsen, Mona Lilian Vestbjerg; Andersen, Heidi Mai-Lis; Pedersen, Lene Juul

2016-03-01

Tail biting, resulting in outbreaks of tail damage in pigs, is a multifactorial welfare and economic problem which is usually partly prevented through tail docking. According to European Union legislation, tail docking is not allowed on a routine basis; thus there is a need for alternative preventive methods. One strategy is the surveillance of the pigs' behaviour for known preceding indicators of tail damage, which makes it possible to predict a tail damage outbreak and prevent it in proper time. This review discusses the existing literature on behavioural changes observed prior to a tail damage outbreak. Behaviours found to change prior to an outbreak include increased activity level, increased performance of enrichment object manipulation, and a changed proportion of tail posture with more tails between the legs. Monitoring these types of behaviours is also discussed for the purpose of developing an automatic warning system for tail damage outbreaks, with activity level showing promising results for being monitored automatically. Encouraging results have been found so far for the development of an automatic warning system; however, there is a need for further investigation and development, starting with the description of the temporal development of the predictive behaviour in relation to tail damage outbreaks. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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.

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

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.

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.

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.

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®

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.

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.

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.

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.

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.

(-)-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.

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.

Numerical method to compute acoustic scattering effect of a moving source.

PubMed

Song, Hao; Yi, Mingxu; Huang, Jun; Pan, Yalin; Liu, Dawei

2016-01-01

In this paper, the aerodynamic characteristic of a ducted tail rotor in hover has been numerically studied using CFD method. An analytical time domain formulation based on Ffowcs Williams-Hawkings (FW-H) equation is derived for the prediction of the acoustic velocity field and used as Neumann boundary condition on a rigid scattering surface. In order to predict the aerodynamic noise, a hybrid method combing computational aeroacoustics with an acoustic thin-body boundary element method has been proposed. The aerodynamic results and the calculated sound pressure levels (SPLs) are compared with the known method for validation. Simulation results show that the duct can change the value of SPLs and the sound directivity. Compared with the isolate tail rotor, the SPLs of the ducted tail rotor are smaller at certain azimuth.

The direct cooling tail method for X-ray burst analysis to constrain neutron star masses and radii

NASA Astrophysics Data System (ADS)

Suleimanov, Valery F.; Poutanen, Juri; Nättilä, Joonas; Kajava, Jari J. E.; Revnivtsev, Mikhail G.; Werner, Klaus

2017-04-01

Determining neutron star (NS) radii and masses can help to understand the properties of matter at supra-nuclear densities. Thermal emission during thermonuclear X-ray bursts from NSs in low-mass X-ray binaries provides a unique opportunity to study NS parameters, because of the high fluxes, large luminosity variations and the related changes in the spectral properties. The standard cooling tail method uses hot NS atmosphere models to convert the observed spectral evolution during cooling stages of X-ray bursts to the Eddington flux FEdd and the stellar angular size Ω. These are then translated to the constraints on the NS mass M and radius R. Here we present the improved, direct cooling tail method that generalizes the standard approach. First, we adjust the cooling tail method to account for the bolometric correction to the flux. Then, we fit the observed dependence of the blackbody normalization on flux with a theoretical model directly on the M-R plane by interpolating theoretical dependences to a given gravity, hence ensuring only weakly informative priors for M and R instead of FEdd and Ω. The direct cooling method is demonstrated using a photospheric radius expansion burst from SAX J1810.8-2609, which has happened when the system was in the hard state. Comparing to the standard cooling tail method, the confidence regions are shifted by 1σ towards larger radii, giving R = 11.5-13.0 km at M = 1.3-1.8 M⊙ for this NS.

Bacterial populations within copper mine tailings: long-term effects of amendment with Class A biosolids

USDA-ARS?s Scientific Manuscript database

This study evaluates the effect of surface application of dried Class A biosolids on microbial populations within copper mine tailings. Methods and Results: Mine tailing sites were established at ASARCO Mission Mine close to Sahuarita, Arizona. Site 1 (Dec. 1998) was amended with 248 tons ha-1 of C...

Mouse handling limits the impact of stress on metabolic endpoints.

PubMed

Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G; Smith, Eric P; Tong, Jenny; D'Alessio, David A; Herman, James P

2015-10-15

Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). Copyright © 2015 Elsevier Inc. All rights reserved.

Mouse Handling Limits the Impact of Stress on Metabolic Endpoints

PubMed Central

Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G.; Smith, Eric P.; Tong, Jenny; D’Alessio, David A.; Herman, James P.

2015-01-01

Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling were subjected to either a previously described “cup” handling method, or a “tail-picked” method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). PMID:26079207

Comparative sacral morphology and the reconstructed tail lengths of five extinct primates: Proconsul heseloni, Epipliopithecus vindobonensis, Archaeolemur edwardsi, Megaladapis grandidieri, and Palaeopropithecus kelyus.

PubMed

Russo, Gabrielle A

2016-01-01

This study evaluated the relationship between the morphology of the sacrum-the sole bony link between the tail or coccyx and the rest of the body-and tail length (including presence/absence) and function using a comparative sample of extant mammals spanning six orders (Primates, Carnivora, Rodentia, Diprotodontia, Pilosa, Scandentia; N = 472). Phylogenetically-informed regression methods were used to assess how tail length varied with respect to 11 external and internal (i.e., trabecular) bony sacral variables with known or suspected biomechanical significance across all mammals, only primates, and only non-primates. Sacral variables were also evaluated for primates assigned to tail categories ('tailless,' 'nonprehensile short-tailed,' 'nonprehensile long-tailed,' and 'prehensile-tailed'). Compared to primates with reduced tail lengths, primates with longer tails generally exhibited sacra having larger caudal neural openings than cranial neural openings, and last sacral vertebrae with more mediolaterally-expanded caudal articular surfaces than cranial articular surfaces, more laterally-expanded transverse processes, more dorsally-projecting spinous processes, and larger caudal articular surface areas. Observations were corroborated by the comparative sample, which showed that shorter-tailed (e.g., Lynx rufus [bobcat]) and longer-tailed (e.g., Acinonyx jubatus [cheetah]) non-primate mammals morphologically converge with shorter-tailed (e.g., Macaca nemestrina) and longer-tailed (e.g., Macaca fascicularis) primates, respectively. 'Prehensile-tailed' primates exhibited last sacral vertebrae with more laterally-expanded transverse processes and greater caudal articular surface areas than 'nonprehensile long-tailed' primates. Internal sacral variables performed poorly compared to external sacral variables in analyses of extant primates, and were thus deemed less useful for making inferences concerning tail length and function in extinct primates. The tails lengths of five extinct primates were reconstructed from the external sacral variables: Archaeolemur edwardsi had a 'nonprehensile long tail,' Megaladapis grandidieri, Palaeopropithecus kelyus, and Epipliopithecus vindobonensis probably had 'nonprehensile short tails,' and Proconsul heseloni was 'tailless.' Copyright © 2015 Elsevier Ltd. All rights reserved.

Homopolymer tail-mediated ligation PCR: a streamlined and highly efficient method for DNA cloning and library construction.

PubMed

Lazinski, David W; Camilli, Andrew

2013-01-01

The amplification of DNA fragments, cloned between user-defined 5' and 3' end sequences, is a prerequisite step in the use of many current applications including massively parallel sequencing (MPS). Here we describe an improved method, called homopolymer tail-mediated ligation PCR (HTML-PCR), that requires very little starting template, minimal hands-on effort, is cost-effective, and is suited for use in high-throughput and robotic methodologies. HTML-PCR starts with the addition of homopolymer tails of controlled lengths to the 3' termini of a double-stranded genomic template. The homopolymer tails enable the annealing-assisted ligation of a hybrid oligonucleotide to the template's recessed 5' ends. The hybrid oligonucleotide has a user-defined sequence at its 5' end. This primer, together with a second primer composed of a longer region complementary to the homopolymer tail and fused to a second 5' user-defined sequence, are used in a PCR reaction to generate the final product. The user-defined sequences can be varied to enable compatibility with a wide variety of downstream applications. We demonstrate our new method by constructing MPS libraries starting from nanogram and sub-nanogram quantities of Vibrio cholerae and Streptococcus pneumoniae genomic DNA.

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.

Robust approaches to quantification of margin and uncertainty for sparse data

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

Hund, Lauren; Schroeder, Benjamin B.; Rumsey, Kelin

Characterizing the tails of probability distributions plays a key role in quantification of margins and uncertainties (QMU), where the goal is characterization of low probability, high consequence events based on continuous measures of performance. When data are collected using physical experimentation, probability distributions are typically fit using statistical methods based on the collected data, and these parametric distributional assumptions are often used to extrapolate about the extreme tail behavior of the underlying probability distribution. In this project, we character- ize the risk associated with such tail extrapolation. Specifically, we conducted a scaling study to demonstrate the large magnitude of themore » risk; then, we developed new methods for communicat- ing risk associated with tail extrapolation from unvalidated statistical models; lastly, we proposed a Bayesian data-integration framework to mitigate tail extrapolation risk through integrating ad- ditional information. We conclude that decision-making using QMU is a complex process that cannot be achieved using statistical analyses alone.« less

Recovery of Manganese Ore Tailings by High-Gradient Magnetic Separation and Hydrometallurgical Method

NASA Astrophysics Data System (ADS)

Zhang, Xiufeng; Tan, Xiumin; Yi, Yuejun; Liu, Weizao; Li, Chun

2017-11-01

With the depletion of high-grade manganese ores, Mn ore tailings are considered valuable secondary resources. In this study, a process combining high-gradient magnetic separation (HGMS) with hydrometallurgical methods is proposed to recycle fine-grained Mn tailings. The Mn tailings were treated by HGMS at 12,500 G to obtain a Mn concentrate of 30% Mn with the recovery efficiency of 64%. The Mn concentrate could be used in the ferromanganese industry. To recover Mn further, the nonmagnetic fraction was leached by SO2 in an H2SO4 solution. Hydrogen peroxide was added to the leachate to oxidize Fe2+ to Fe3+, and the solution pH was adjusted to 5.0-5.5 with ammonia to remove Al, Fe, and Si impurities. The purified solution was reacted with NH4HCO3, and a saleable product of MnCO3 with 97.9% purity was obtained. The combined process can be applied to Mn recovery from finely dispersed weakly magnetic Mn ores or tailings.

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.

Gini estimation under infinite variance

NASA Astrophysics Data System (ADS)

Fontanari, Andrea; Taleb, Nassim Nicholas; Cirillo, Pasquale

2018-07-01

We study the problems related to the estimation of the Gini index in presence of a fat-tailed data generating process, i.e. one in the stable distribution class with finite mean but infinite variance (i.e. with tail index α ∈(1 , 2)). We show that, in such a case, the Gini coefficient cannot be reliably estimated using conventional nonparametric methods, because of a downward bias that emerges under fat tails. This has important implications for the ongoing discussion about economic inequality. We start by discussing how the nonparametric estimator of the Gini index undergoes a phase transition in the symmetry structure of its asymptotic distribution, as the data distribution shifts from the domain of attraction of a light-tailed distribution to that of a fat-tailed one, especially in the case of infinite variance. We also show how the nonparametric Gini bias increases with lower values of α. We then prove that maximum likelihood estimation outperforms nonparametric methods, requiring a much smaller sample size to reach efficiency. Finally, for fat-tailed data, we provide a simple correction mechanism to the small sample bias of the nonparametric estimator based on the distance between the mode and the mean of its asymptotic distribution.

On the statistical properties and tail risk of violent conflicts

NASA Astrophysics Data System (ADS)

Cirillo, Pasquale; Taleb, Nassim Nicholas

2016-06-01

We examine statistical pictures of violent conflicts over the last 2000 years, providing techniques for dealing with the unreliability of historical data. We make use of a novel approach to deal with fat-tailed random variables with a remote but nonetheless finite upper bound, by defining a corresponding unbounded dual distribution (given that potential war casualties are bounded by the world population). This approach can also be applied to other fields of science where power laws play a role in modeling, like geology, hydrology, statistical physics and finance. We apply methods from extreme value theory on the dual distribution and derive its tail properties. The dual method allows us to calculate the real tail mean of war casualties, which proves to be considerably larger than the corresponding sample mean for large thresholds, meaning severe underestimation of the tail risks of conflicts from naive observation. We analyze the robustness of our results to errors in historical reports. We study inter-arrival times between tail events and find that no particular trend can be asserted. All the statistical pictures obtained are at variance with the prevailing claims about ;long peace;, namely that violence has been declining over time.

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

Evaluation of pyritic mine tailings as a plant growth substrate.

PubMed

Roseby, Stuart J; Kopittke, Peter M; Mulligan, David R; Menzies, Neal W

2017-10-01

At the Kidston gold mine, Australia, the direct establishment of vegetation on tailings was considered as an alternative to the use of a waste rock cover. The tailings acid/base account was used to predict plant growth limitation by acidity, and thus methods capable of identifying tailings that would acidify to pH 4.5 or lower were sought. Total S was found to be poorly correlated with acid-generating sulfide, and total C was poorly correlated with acid-neutralizing carbonate, precluding the use of readily determined total S and C as predictors of net acid generation. Therefore, the selected approach used assessment of sulfide content as a predictor of acid generation, and carbonate content as a measure of the acid-neutralizing capacity available at pH 5 and above. Using this approach, the majority of tailings (67%) were found to be non-acid generating. However, areas of potentially acid-generating tailings were randomly distributed across the dam, and could only be located by intensive sampling. The limitations imposed by the large sample numbers, and costly analysis of sulfide and carbonate, make it impractical to identify and ameliorate acid-generating areas prior to vegetation establishment. However, as only a small proportion of the tailings will acidify, a strategy of re-treating acid areas following oxidation is suggested. The findings of the present study will assist in the selection of appropriate methods for the prediction of net acid generation, particularly where more conservative measurements are required to allow vegetation to be established directly in tailings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mobility of as, Cu, Cr, and Zn from tailings covered with sealing materials using alkaline industrial residues: a comparison between two leaching methods.

PubMed

Jia, Yu; Maurice, Christian; Öhlander, Björn

2016-01-01

Different alkaline residue materials (fly ash, green liquor dregs, and lime mud) generated from the pulp and paper industry as sealing materials were evaluated to cover aged mine waste tailings (<1% sulfur content, primarily pyrite). The mobility of four selected trace elements (Cr, Cu, Zn, and As) was compared based on batch and column leaching studies to assess the effectiveness of these alkaline materials as sealing agents. Based on the leaching results, Cr, Cu, and Zn were immobilized by the alkaline amendments. In the amended tailings in the batch system only As dramatically exceeded the limit values at L/S 10 L/kg. The leaching results showed similar patterns to the batch results, though leached Cr, Cu, and Zn showed higher levels in the column tests than in the batch tests. However, when the columns were compared with the batches, the trend for Cu was opposite for the unamended tailings. By contrast, both batch and column results showed that the amendment caused mobilization of As compared with the unamended tailings in the ash-amended tailings. The amount of As released was greatest in the ash column and decreased from the dregs to the lime columns. The leaching of As at high levels can be a potential problem whenever alkaline materials (especially for fly ash) are used as sealing materials over tailings. The column test was considered by the authors to be a more informative method in remediation of the aged tailings with low sulfur content, since it mimics better actual situation in a field.

Comparison of Vee-Type and Conventional Tail Surfaces in Combination with Fuselage and Wing in the Variable-Density Tunnel

NASA Technical Reports Server (NTRS)

Greenberg, Harry

1941-01-01

The pitching and the yawing moments of a vee-type and a conventional type of tail surface were measured. The tests were made in the presence of a fuselage and a wing-fuselage combination in such a way as to determine the moments contributed by the tail surfaces. The results showed that the vee-type tail tested, with a dihedral angle of 35.3 deg, was about 71 percent as effective in pitch as the conventional tail and had a yawing-moment to pitching-moment ratio of 0.3. The conventional tail, the panels of which were all congruent to those of the vee-type tail, had a yawing-moment to pitching-moment ratio of 0.48. These ratios are in fair agreement with values calculated by methods shown in this and previous reports. The values of the measured moments were reduced from 15 to 25 percent of the calculated value by fuselage interference.

Homopolymer tail-mediated ligation PCR: a streamlined and highly efficient method for DNA cloning and library construction

PubMed Central

Lazinski, David W.; Camilli, Andrew

2013-01-01

The amplification of DNA fragments, cloned between user-defined 5′ and 3′ end sequences, is a prerequisite step in the use of many current applications including massively parallel sequencing (MPS). Here we describe an improved method, called homopolymer tail-mediated ligation PCR (HTML-PCR), that requires very little starting template, minimal hands-on effort, is cost-effective, and is suited for use in high-throughput and robotic methodologies. HTML-PCR starts with the addition of homopolymer tails of controlled lengths to the 3′ termini of a double-stranded genomic template. The homopolymer tails enable the annealing-assisted ligation of a hybrid oligonucleotide to the template's recessed 5′ ends. The hybrid oligonucleotide has a user-defined sequence at its 5′ end. This primer, together with a second primer composed of a longer region complementary to the homopolymer tail and fused to a second 5′ user-defined sequence, are used in a PCR reaction to generate the final product. The user-defined sequences can be varied to enable compatibility with a wide variety of downstream applications. We demonstrate our new method by constructing MPS libraries starting from nanogram and sub-nanogram quantities of Vibrio cholerae and Streptococcus pneumoniae genomic DNA. PMID:23311318

Mosaic CCD method: A new technique for observing dynamics of cometary magnetospheres

NASA Technical Reports Server (NTRS)

Saito, T.; Takeuchi, H.; Kozuba, Y.; Okamura, S.; Konno, I.; Hamabe, M.; Aoki, T.; Minami, S.; Isobe, S.

1992-01-01

On April 29, 1990, the plasma tail of Comet Austin was observed with a CCD camera on the 105-cm Schmidt telescope at the Kiso Observatory of the University of Tokyo. The area of the CCD used in this observation is only about 1 sq cm. When this CCD is used on the 105-cm Schmidt telescope at the Kiso Observatory, the area corresponds to a narrow square view of 12 ft x 12 ft. By comparison with the photograph of Comet Austin taken by Numazawa (personal communication) on the same night, we see that only a small part of the plasma tail can be photographed at one time with the CCD. However, by shifting the view on the CCD after each exposure, we succeeded in imaging the entire length of the cometary magnetosphere of 1.6 x 10(exp 6) km. This new technique is called 'the mosaic CCD method'. In order to study the dynamics of cometary plasma tails, seven frames of the comet from the head to the tail region were twice imaged with the mosaic CCD method and two sets of images were obtained. Six microstructures, including arcade structures, were identified in both the images. Sketches of the plasma tail including microstructures are included.

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.

A study of bauxite tailing quality improvement by reverse flotation

NASA Astrophysics Data System (ADS)

Wulandari, W.; Purwasasmita, M.; Sanwani, E.; Malatsih, W.; Fadilla, F.

2018-01-01

The pre-treatment of bauxite ore from Tayan, West Kalimantan includes washing and screening fine bauxite particles (-2mm) prior as the feed to the Bayer process for producing alumina. These fine particles are believed to have high content of silica which is detrimental to the process. This washed bauxite tailing still has a significant amount of alumina content. Previous research has indicated that bauxite ore can be upgraded by applying reverse flotation method to reduce its silica content in the ore. Therefore, this study is aimed to utilize reverse flotation method to recover alumina content from washed bauxite tailing. The reverse flotation experiments were carried out at pH of 6 and 8; while the particle sizes were varied at - 140+270 mesh and -270 mesh, using a batch and circuit configuration. The result of this study shows that the batch reverse flotation can recover alumina in the tailing up to 81.4%, however the silica content is still significant. The complexity of silica-alumina minerals in the tailing prevents a complete separation of the ores by only using reverse flotation.

Tail Buffeting

NASA Technical Reports Server (NTRS)

Abdrashitov, G.

1943-01-01

An approximate theory of buffeting is here presented, based on the assumption of harmonic disturbing forces. Two cases of buffeting are considered: namely, for a tail angle of attack greater and less than the stalling angle, respectively. On the basis of the tests conducted and the results of foreign investigators, a general analysis is given of the nature of the forced vibrations the possible load limits on the tail, and the methods of elimination of buffeting.

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.

Study on peak shape fitting method in radon progeny measurement.

PubMed

Yang, Jinmin; Zhang, Lei; Abdumomin, Kadir; Tang, Yushi; Guo, Qiuju

2015-11-01

Alpha spectrum measurement is one of the most important methods to measure radon progeny concentration in environment. However, the accuracy of this method is affected by the peak tailing due to the energy losses of alpha particles. This article presents a peak shape fitting method that can overcome the peak tailing problem in most situations. On a typical measured alpha spectrum curve, consecutive peaks overlap even their energies are not close to each other, and it is difficult to calculate the exact count of each peak. The peak shape fitting method uses combination of Gaussian and exponential functions, which can depict features of those peaks, to fit the measured curve. It can provide net counts of each peak explicitly, which was used in the Kerr method of calculation procedure for radon progeny concentration measurement. The results show that the fitting curve fits well with the measured curve, and the influence of the peak tailing is reduced. The method was further validated by the agreement between radon equilibrium equivalent concentration based on this method and the measured values of some commercial radon monitors, such as EQF3220 and WLx. In addition, this method improves the accuracy of individual radon progeny concentration measurement. Especially for the (218)Po peak, after eliminating the peak tailing influence, the calculated result of (218)Po concentration has been reduced by 21 %. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A tail like no other. The RPC-MAG view of Rosetta's tail excursion at comet 67P/Churyumov-Gerasimenko

NASA Astrophysics Data System (ADS)

Volwerk, Martin; Goetz, Charlotte; Richter, Ingo; Delva, Magda; Ostaszewski, Katharina; Schwingenschuh, Konrad; Glassmeier, Karl-Heinz

2018-06-01

Context. The Rosetta Plasma Consortium (RPC) magnetometer (MAG) data during the tail excursion in March-April 2016 are used to investigate the magnetic structure of and activity in the tail region of the weakly outgassing comet 67P/Churyumov-Gerasimenko (67P). Aims: The goal of this study is to compare the large scale (near) tail structure with that of earlier missions to strong outgassing comets, and the small scale turbulent energy cascade (un)related to the singing comet phenomenon. Methods: The usual methods of space plasma physics are used to analyse the magnetometer data, such as minimum variance analysis, spectral analysis, and power law fitting. Also the cone angle and clock angle of the magnetic field are calculated to interpret the data. Results: It is found that comet 67P does not have a classical draped magnetic field and no bi-lobal tail structure at this late stage of the mission when the comet is already at 2.7 AU distance from the Sun. The main magnetic field direction seems to be more across the tail direction, which may implicate an asymmetric pick-up cloud. During periods of singing comet activity the propagation direction of the waves is at large angles with respect to the magnetic field and to the radial direction towards the comet. Turbulent cascade of magnetic energy from large to small scales is different in the presence of singing as without it.

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…

Lifting-surface-theory aspect-ratio corrections to the lift and hinge-moment parameters for full-span elevators on horizontal tail surfaces

NASA Technical Reports Server (NTRS)

Swanson, Robert S; Crandall, Stewart M

1948-01-01

A limited number of lifting-surface-theory solutions for wings with chordwise loadings resulting from angle of attack, parabolic-ac camber, and flap deflection are now available. These solutions were studied with the purpose of determining methods of extrapolating the results in such a way that they could be used to determine lifting-surface-theory values of the aspect-ratio corrections to the lift and hinge-moment parameters for both angle-of-attack and flap-deflection-type loading that could be used to predict the characteristics of horizontal tail surfaces from section data with sufficient accuracy for engineering purposes. Such a method was devised for horizontal tail surfaces with full-span elevators. In spite of the fact that the theory involved is rather complex, the method is simple to apply and may be applied without any knowledge of lifting-surface theory. A comparison of experimental finite-span and section value and of the estimated values of the lift and hinge-moment parameters for three horizontal tail surfaces was made to provide an experimental verification of the method suggested. (author)

Method for confining the magnetic field of the cross-tail current inside the magnetopause

NASA Technical Reports Server (NTRS)

Sotirelis, T.; Tsyganenko, N. A.; Stern, D. P.

1994-01-01

A method is presented for analytically representing the magnetic field due to the cross-tail current and its closure on the magnetopause. It is an extension of a method used by Tsyganenko (1989b) to confine the dipole field inside an ellipsoidal magnetopause using a scalar potential. Given a model of the cross-tail current, the implied net magnetic field is obtained by adding to the cross-tail current field a potential field B = - del gamma, which makes all field lines divide into two disjoint groups, separated by the magnetopause (i.e., the combined field is made to have zero normal component with the magnetopause). The magnetopause is assumed to be an ellipsoid of revolution (a prolate spheroid) as an approximation to observations (Sibeck et al., 1991). This assumption permits the potential gamma to be expressed in spheroidal coordinates, expanded in spheroidal harmonics and its terms evaluated by performing inversion integrals. Finally, the field outside the magnetopause is replaced by zero, resulting in a consistent current closure along the magnetopause. This procedure can also be used to confine the modeled field of any other interior magnetic source, though the model current must always flow in closed circuits. The method is demonstrated on the T87 cross-tail current, examples illustrate the effect of changing the size and shape of the prescribed magnetopause and a comparison is made to an independent numerical scheme based on the Biot-Savart equation.

Effect of Tail Surfaces on the Base Drag of a Body of Revolution at Mach Numbers of 1.5 and 2.0

NASA Technical Reports Server (NTRS)

Spahr, J Richard; Dickey, Robert R

1951-01-01

Wind-tunnel tests were performed at Mach numbers of 1.5 and 2.0 to investigate the influence of tail surfaces on the base drag of a body of revolution without boattailing and having a turbulent boundary layer. The tail surfaces were of rectangular plan form of aspect ratio 2.33 and has symmetrical, circular-arc airfoil section. The results of the investigation showed that the addition of these tail surfaces with the trailing edges at or near the body base incurred a large increase in the base-drag coefficient. For a cruciform tail having a 10-percent-thick airfoil section, this increase was about 70 percent at a Mach number of 1.5 and 35 percent at a Mach number of 2.0. As the trailing edge of the tail was moved forward or rearward of the base by about one tail-chord length, the base-drag increment was reduced to nearly zero. The increments in base-drag coefficient due to the presence of 10-percent-thick tail surfaces were generally twice those for 5-percent-thick surfaces. The base-drag increments due to the presence of a cruciform tail were less than twice those for a plane tail. An estimate of the change in base pressure due to the tail surfaces was made, based on a simple superposition of the airfoil-pressure field onto the base-pressure field behind the body. A comparison of the results with the experimental values indicated that in most cases the trend in the variation of the base-drag increment with changes in tail position could be predicted by this approximate method but that the quantitative agreement at most tail locations was poor.

Two-Dimensional Fourier Transform Applied to Helicopter Flyover Noise

NASA Technical Reports Server (NTRS)

Santa Maria, Odilyn L.

1999-01-01

A method to separate main rotor and tail rotor noise from a helicopter in flight is explored. Being the sum of two periodic signals of disproportionate, or incommensurate frequencies, helicopter noise is neither periodic nor stationary, but possibly harmonizable. The single Fourier transform divides signal energy into frequency bins of equal size. Incommensurate frequencies are therefore not adequately represented by any one chosen data block size. A two-dimensional Fourier analysis method is used to show helicopter noise as harmonizable. The two-dimensional spectral analysis method is first applied to simulated signals. This initial analysis gives an idea of the characteristics of the two-dimensional autocorrelations and spectra. Data from a helicopter flight test is analyzed in two dimensions. The test aircraft are a Boeing MD902 Explorer (no tail rotor) and a Sikorsky S-76 (4-bladed tail rotor). The results show that the main rotor and tail rotor signals can indeed be separated in the two-dimensional Fourier transform spectrum. The separation occurs along the diagonals associated with the frequencies of interest. These diagonals are individual spectra containing only information related to one particular frequency.

Numerical analysis of band tails in nanowires and their effects on the performance of tunneling field-effect transistors

NASA Astrophysics Data System (ADS)

Tanaka, Takahisa; Uchida, Ken

2018-06-01

Band tails in heavily doped semiconductors are one of the important parameters that determine transfer characteristics of tunneling field-effect transistors. In this study, doping concentration and doing profile dependences of band tails in heavily doped Si nanowires were analyzed by a nonequilibrium Green function method. From the calculated band tails, transfer characteristics of nanowire tunnel field-effect transistors were numerically analyzed by Wentzel–Kramer–Brillouin approximation with exponential barriers. The calculated transfer characteristics demonstrate that the band tails induced by dopants degrade the subthreshold slopes of Si nanowires from 5 to 56 mV/dec in the worst case. On the other hand, surface doping leads to a high drain current while maintaining a small subthreshold slope.

Derivation of charts for determining the horizontal tail load variation with any elevator motion

NASA Technical Reports Server (NTRS)

Pearson, Henry A

1943-01-01

The equations relating the wing and tail loads are derived for a unit elevator displacement. These equations are then converted into a nondimensional form and charts are given by which the wing- and tail-load-increment variation may be determined under dynamic conditions for any type of elevator motion and for various degrees of airplane stability. In order to illustrate the use of the charts, several examples are included in which the wing and tail loads are evaluated for a number of types of elevator motion. Methods are given for determining the necessary derivatives from results of wind-tunnel tests when such tests are available.

Tail Biting Trellis Representation of Codes: Decoding and Construction

NASA Technical Reports Server (NTRS)

Shao. Rose Y.; Lin, Shu; Fossorier, Marc

1999-01-01

This paper presents two new iterative algorithms for decoding linear codes based on their tail biting trellises, one is unidirectional and the other is bidirectional. Both algorithms are computationally efficient and achieves virtually optimum error performance with a small number of decoding iterations. They outperform all the previous suboptimal decoding algorithms. The bidirectional algorithm also reduces decoding delay. Also presented in the paper is a method for constructing tail biting trellises for linear block codes.

Method for lake restoration

DOEpatents

Dawson, Gaynor W.; Mercer, Basil W.

1979-01-01

A process for removing pollutants or minerals from lake, river or ocean sediments or from mine tailings is disclosed. Magnetically attractable collection units containing an ion exchange or sorbent media with an affinity for a chosen target substance are distributed in the sediments or tailings. After a period of time has passed sufficient for the particles to bind up the target substances, a magnet drawn through the sediments or across the tailings retrieves the units along with the target substance.

Assessing the genetic diversity of Cu resistance in mine tailings through high-throughput recovery of full-length copA genes

PubMed Central

Li, Xiaofang; Zhu, Yong-Guan; Shaban, Babak; Bruxner, Timothy J. C.; Bond, Philip L.; Huang, Longbin

2015-01-01

Characterizing the genetic diversity of microbial copper (Cu) resistance at the community level remains challenging, mainly due to the polymorphism of the core functional gene copA. In this study, a local BLASTN method using a copA database built in this study was developed to recover full-length putative copA sequences from an assembled tailings metagenome; these sequences were then screened for potentially functioning CopA using conserved metal-binding motifs, inferred by evolutionary trace analysis of CopA sequences from known Cu resistant microorganisms. In total, 99 putative copA sequences were recovered from the tailings metagenome, out of which 70 were found with high potential to be functioning in Cu resistance. Phylogenetic analysis of selected copA sequences detected in the tailings metagenome showed that topology of the copA phylogeny is largely congruent with that of the 16S-based phylogeny of the tailings microbial community obtained in our previous study, indicating that the development of copA diversity in the tailings might be mainly through vertical descent with few lateral gene transfer events. The method established here can be used to explore copA (and potentially other metal resistance genes) diversity in any metagenome and has the potential to exhaust the full-length gene sequences for downstream analyses. PMID:26286020

Enriching acid rock drainage related microbial communities from surface-deposited oil sands tailings.

PubMed

Dean, Courtney; Xiao, Yeyuan; Roberts, Deborah J

2016-10-01

Little is known about the microbial communities native to surface-deposited pyritic oil sands tailings, an environment where acid rock drainage (ARD) could occur. The goal of this study was to enrich sulfur-oxidizing organisms from these tailings and determine whether different populations exist at pH levels 7, 4.5, and 2.5. Using growth-based methods provides model organisms for use in the future to predict potential activities and limitations of these organisms and to develop possible control methods. Thiosulfate-fed enrichment cultures were monitored for approximately 1 year. The results showed that the enrichments at pH 4.5 and 7 were established quicker than at pH 2.5. Different microbial community structures were found among the 3 pH environments. The sulfur-oxidizing microorganisms identified were most closely related to Halothiobacillus neapolitanus, Achromobacter spp., and Curtobacterium spp. While microorganisms related to Chitinophagaceae and Acidocella spp. were identified as the only possible iron-oxidizing and -reducing microbes. These results contribute to the general knowledge of the relatively understudied microbial communities that exist in pyritic oil sands tailings and indicate these communities may have a potential role in ARD generation, which may have implications for future tailings management.

ArrayVigil: a methodology for statistical comparison of gene signatures using segregated-one-tailed (SOT) Wilcoxon's signed-rank test.

PubMed

Khan, Haseeb Ahmad

2005-01-28

Due to versatile diagnostic and prognostic fidelity molecular signatures or fingerprints are anticipated as the most powerful tools for cancer management in the near future. Notwithstanding the experimental advancements in microarray technology, methods for analyzing either whole arrays or gene signatures have not been firmly established. Recently, an algorithm, ArraySolver has been reported by Khan for two-group comparison of microarray gene expression data using two-tailed Wilcoxon signed-rank test. Most of the molecular signatures are composed of two sets of genes (hybrid signatures) wherein up-regulation of one set and down-regulation of the other set collectively define the purpose of a gene signature. Since the direction of a selected gene's expression (positive or negative) with respect to a particular disease condition is known, application of one-tailed statistics could be a more relevant choice. A novel method, ArrayVigil, is described for comparing hybrid signatures using segregated-one-tailed (SOT) Wilcoxon signed-rank test and the results compared with integrated-two-tailed (ITT) procedures (SPSS and ArraySolver). ArrayVigil resulted in lower P values than those obtained from ITT statistics while comparing real data from four signatures.

Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers

PubMed Central

2011-01-01

Background Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI)) exposure can cause DNA damage in electroplating workers. Methods 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%). Urinary 8-OHdG levels were measured by ELISA. Results Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L) than that in control subjects (1.54 μg/L, P < 0.001). The medians (range) of Olive tail moment, tail length and tail DNA% in exposed workers were 1.13 (0.14-6.77), 11.17 (3.46-52.19) and 3.69 (0.65-16.20), and were significantly higher than those in control subjects (0.14 (0.01-0.39), 3.26 (3.00-4.00) and 0.69 (0.04-2.74), P < 0.001). Urinary 8-OHdG concentration was 13.65 (3.08-66.30) μg/g creatinine in exposed workers and 8.31 (2.94-30.83) μg/g creatinine in control subjects (P < 0.001). The differences of urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA% between these two groups remained significant (P < 0.001) even after stratification by potential confounding factors such as age, gender, and smoking status. Chromium exposure was found to be positively associated with chromium levels in erythrocytes, urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA%. Positive dose-response associations were also found between chromium levels in erythrocytes and Olive tail moment, tail length and tail DNA%. Conclusion The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage. PMID:21481275

Probability of detecting band-tailed pigeons during call-broadcast versus auditory surveys

USGS Publications Warehouse

Kirkpatrick, C.; Conway, C.J.; Hughes, K.M.; Devos, J.C.

2007-01-01

Estimates of population trend for the interior subspecies of band-tailed pigeon (Patagioenas fasciata fasciata) are not available because no standardized survey method exists for monitoring the interior subspecies. We evaluated 2 potential band-tailed pigeon survey methods (auditory and call-broadcast surveys) from 2002 to 2004 in 5 mountain ranges in southern Arizona, USA, and in mixed-conifer forest throughout the state. Both auditory and call-broadcast surveys produced low numbers of cooing pigeons detected per survey route (x?? ??? 0.67) and had relatively high temporal variance in average number of cooing pigeons detected during replicate surveys (CV ??? 161%). However, compared to auditory surveys, use of call-broadcast increased 1) the percentage of replicate surveys on which ???1 cooing pigeon was detected by an average of 16%, and 2) the number of cooing pigeons detected per survey route by an average of 29%, with this difference being greatest during the first 45 minutes of the morning survey period. Moreover, probability of detecting a cooing pigeon was 27% greater during call-broadcast (0.80) versus auditory (0.63) surveys. We found that cooing pigeons were most common in mixed-conifer forest in southern Arizona and density of male pigeons in mixed-conifer forest throughout the state averaged 0.004 (SE = 0.001) pigeons/ha. Our results are the first to show that call-broadcast increases the probability of detecting band-tailed pigeons (or any species of Columbidae) during surveys. Call-broadcast surveys may provide a useful method for monitoring populations of the interior subspecies of band-tailed pigeon in areas where other survey methods are inappropriate.

Quantification of applied dose in irradiated citrus fruits by DNA Comet Assay together with image analysis.

PubMed

Cetinkaya, Nurcan; Ercin, Demet; Özvatan, Sümer; Erel, Yakup

2016-02-01

The experiments were conducted for quantification of applied dose for quarantine control in irradiated citrus fruits. Citrus fruits exposed to doses of 0.1 to 1.5 kGy and analyzed by DNA Comet Assay. Observed comets were evaluated by image analysis. The tail length, tail moment and tail DNA% of comets were used for the interpretation of comets. Irradiated citrus fruits showed the separated tails from the head of the comet by increasing applied doses from 0.1 to 1.5 kGy. The mean tail length and mean tail moment% levels of irradiated citrus fruits at all doses are significantly different (p < 0.01) from control even for the lowest dose at 0.1 kGy. Thus, DNA Comet Assay may be a practical quarantine control method for irradiated citrus fruits since it has been possible to estimate the applied low doses as small as 0.1 kGy when it is combined with image analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

A review on in situ phytoremediation of mine tailings.

PubMed

Wang, Li; Ji, Bin; Hu, Yuehua; Liu, Runqing; Sun, Wei

2017-10-01

Mine tailings are detrimental to natural plant growth due to their physicochemical characteristics, such as high pH, high salinity, low water retention capacity, high heavy metal concentrations, and deficiencies in soil organic matter and fertility. Thus, the remediation of mine tailings has become a key issue in environmental science and engineering. Phytoremediation, an in situ cost-effective technology, is emerging as the most promising remediation method for mine tailings by introducing tolerant plant species. It is particularly effective in dealing with large-area mine tailings with shallow contamination of organic, nutrient and metal pollutants. In this review, the background, concepts and applications of phytoremediation are comprehensively discussed. Furthermore, proper amendments used to improve the physical, chemical and biological properties of mine tailings are systematically reviewed and compared. Emphasis is placed on the types and characteristics of tolerant plants and their role in phytoremediation. Moreover, the role of microorganisms and their mechanism in phytoremediation are also discussed in-depth. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mineralogy and Geochemical Processes of Carbonate Mineral-rich Sulfide Mine Tailings, Zimapan, Mexico

NASA Astrophysics Data System (ADS)

McClure, R. J.; Deng, Y.; Loeppert, R.; Herbert, B. E.; Carrillo, R.; Gonzalez, C.

2009-12-01

Mining for silver, lead, zinc, and copper in Zimapan, Hidalgo State, Mexico has been ongoing since 1576. High concentrations of heavy metals have been found in several mine tailing heaps in the Zimapan area, with concentrations of arsenic observed as high as 28,690 mg/kg and levels of Pb as high as 2772 mg/kg. Unsecured tailings heaps and associated acid mine drainage has presented tremendous problems to revegetation, water quality, and dust emission control in the Zimapan area. Although acid mine drainage problems related to weathering of sulfide minerals have been extensively studied and are well known, the weathering products of sulfides in areas with a significant presence of carbonate minerals and their effect on the mobility of heavy metals warrant further study. Carbonate minerals are expected to neutralize sulfuric acid produced from weathering of sulfide minerals, however, in the Zimapan area localized areas of pH as low as 1.8 were observed within carbonate mineral-rich tailing heaps. The objectives of this study are to characterize (1) the heavy metal-containing sulfide minerals in the initial tailing materials, (2) the intermediate oxidation products of sulfide minerals within the carbonate-rich tailings, (3) chemical species of heavy metals within pH gradients between 1.8 and 8.2, the approximate natural pH of limestone, and (4) the mobility of soluble and colloidal heavy metals and arsenic within the carbonate-rich tailings. Representative mine tailings and their intermediate oxidation products have been sampled from the Zimapan area. Mineralogical characterization will be conducted with X-ray diffraction, infrared spectroscopy, electron microscopes and microprobes, and chemical methods. Chemical species will be extracted by selective dissolution methods. Preliminary results have identified calcite as the dominant mineral in the tailing heaps with a pH of 7, suggesting non-equilibrium with the acidic weathering products. Other minerals identified in the tailings include gypsum, quartz, pyrite, mica, talc, amphiboles, and feldspars. Oxidation products identified include copiapite as well as various iron oxides. Future results are expected to reveal most of the heavy metals to be adsorbed by or coprecipitate with iron oxides, with most of the oxidized arsenic staying in the soluble form. The mobility of the colloidal form of the oxides and associated heavy metals within the carbonate mineral-rich tailings need additional study.

Dynamics of runaway tails with time-dependent sub-Dreicer dc fields in magnetized plasmas

NASA Technical Reports Server (NTRS)

Moghaddam-Taaheri, E.; Vlahos, L.

1987-01-01

The evolution of runaway tails driven by sub-Dreicer time-dependent dc fields in a magnetized plasma are studied numerically using a quasi-linear code based on the Ritz-Galerkin method and finite elements. It is found that the runaway tail maintained a negative slope during the dc field increase. Depending on the values of the dc electric field at t = 0 and the electron gyrofrequency to the plasma frequency ratio the runaway tail became unstable to the anomalous Doppler resonance or remained stable before the saturation of the dc field at some maximum value. The systems that remained stable during this stage became unstable to the anomalous Doppler or the Cerenkov resonances when the dc field was kept at the saturation level or decreased. Once the instability is triggered, the runaway tail is isotropized.

Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling.

PubMed

Korfmacher, Walter; Luo, Yongyi; Ho, Stacy; Sun, Wei; Shen, Liduo; Wang, Jie; Wu, Zhongtao; Guo, Yang; Snow, Gregory; O'Shea, Thomas

2015-01-01

Serial sampling methods have been used for rat pharmacokinetic (PK) studies for over 20 years. Currently, it is still common to take 200-250 μL of blood at each timepoint when performing a PK study in rats and using serial sampling. While several techniques have been employed for collecting blood samples from rats, there is only limited published data to compare these methods. Recently, microsampling (≤ 50 μL) techniques have been reported as an alternative process for collecting blood samples from rats. In this report, five compounds were dosed orally into rats. For three proprietary compounds, jugular vein cannula (JVC) sampling was used to collect whole blood and plasma samples and capillary microsampling (CMS) was used to collect blood samples from the tail vein of the same animal. For the two other compounds, marketed drugs fluoxetine and glipizide, JVC sampling was used to collect both whole blood and blood CMS samples while tail-vein sampling from the same rats was also used to collect both whole blood and blood CMS samples. For the three proprietary compounds, the blood AUC as well as the blood concentration-time profile that were obtained from the tail vein were different from those obtained via JVC sampling. For fluoxetine, the blood total exposure (AUC) was not statistically different when comparing tail-vein sampling to JVC sampling, however the blood concentration-time profile that was obtained from the tail vein was different than the one obtained from JVC sampling. For glipizide, the blood AUC and concentration-time profile were not statistically different when comparing the tail-vein sampling to the JVC sampling. For both fluoxetine and glipizide, the blood concentration profiles obtained from CMS were equivalent to the blood concentration profiles obtained from the standard whole blood sampling, collected at the same sampling site. The data in this report provide strong evidence that blood CMS is a valuable small volume blood sampling approach for rats and that it provides results for test compound concentrations that are equivalent to those obtained from traditional whole blood sampling. The data also suggest that for some compounds, the concentration-time profile that is obtained for a test compound based on sampling from a rat tail vein may be different from that obtained from rat JVC sampling. In some cases, this shift in the concentration-time profile will result in different PK parameters for the test compound. Based on these observations, it is recommended that a consistent blood sampling method should be used for serial microsampling in discovery rat PK studies when testing multiple new chemical entities. If the rat tail vein sampling method is selected for PK screening, then conducting a bridging study on the lead compound is recommended to confirm that the rat PK obtained from JVC sampling is comparable to the tail-vein sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

Linear and exponential TAIL-PCR: a method for efficient and quick amplification of flanking sequences adjacent to Tn5 transposon insertion sites.

PubMed

Jia, Xianbo; Lin, Xinjian; Chen, Jichen

2017-11-02

Current genome walking methods are very time consuming, and many produce non-specific amplification products. To amplify the flanking sequences that are adjacent to Tn5 transposon insertion sites in Serratia marcescens FZSF02, we developed a genome walking method based on TAIL-PCR. This PCR method added a 20-cycle linear amplification step before the exponential amplification step to increase the concentration of the target sequences. Products of the linear amplification and the exponential amplification were diluted 100-fold to decrease the concentration of the templates that cause non-specific amplification. Fast DNA polymerase with a high extension speed was used in this method, and an amplification program was used to rapidly amplify long specific sequences. With this linear and exponential TAIL-PCR (LETAIL-PCR), we successfully obtained products larger than 2 kb from Tn5 transposon insertion mutant strains within 3 h. This method can be widely used in genome walking studies to amplify unknown sequences that are adjacent to known sequences.

Exploring the possible mechanisms of action behind the antinociceptive activity of Bacopa monniera

PubMed Central

Bhaskar, Manju; Jagtap, A. G.

2011-01-01

Aim: Earlier studies have demonstrated that Bacopa monniera (BM), a plant described in Ayurveda for many CNS actions was found to exhibit antidepressant (methanolic extract at 20mg/kg and 40mg/kg p.o.) as well as antinociceptive activity (aqueous extract (AE) at 80 mg/kg, 120 mg/kg and 160 mg/kg p.o.). The present study sought to explore the possible mechanisms of antinociceptive effects of aqueous extract of Bacopa monniera (AEBM) at 80 mg/kg, 120 mg/kg and 160 mg/kg given orally. Materials and Methods: AEBM was given singly as well as with selective α2 receptor blocker Yohimbine, selective β1 receptor blocker Atenolol, serotonin receptor antagonist Cyproheptadine and a non-selective opioid receptor antagonist naloxone in experimental groups of mice and rats under strict protocols and conditions. Results: We observed that the antinociceptive effects of AEBM in the acetic acid writhing test was prevented by prior treatment with the selective Yohimbine (1 mg/kg, i.p; 14.50 ± 2.26 and 37.17 ± 2.14 writhes in the AEBM-treated and yohimbine pre-treated AEBM groups, respectively) and selective β1 Atenolol receptor blocker (1 mg/kg, i.p; 14.50 ± 2.26 and 31.00 ± 5.44 writhes in the AEBM-treated and yohimbine pre-treated AEBM groups, respectively). In the formalin test, the reduction in licking time with AEBM was found to be reversed by prior treatment with serotonin receptor antagonist Cyproheptadine (1 mg/kg, i.p; 47.33 ± 2.25s and 113.50 ± 3.83s (during phase I i.e. 0-5 min) and 26.67 ± 3.83s and 88.17 ± 7.27s (during phase II i.e. 20-30 min) in the AEBM-treated and Cyproheptadine pre-treated AEBM groups, respectively). The % increase in tail flick latency with AEBM was prevented by prior treatment with the non-selective opioid receptor antagonist naloxone (2mg/kg, i.p; 282.35 and 107.35 in the AEBM-treated and naloxone-treated groups, respectively). Conclusions: Our results indicate, that the endogenous adrenergic, serotonergic and opioidergic systems are involved in the analgesic mechanism of action of the aqueous extract of Bacopa monniera. PMID:21897636

L-moments and TL-moments of the generalized lambda distribution

USGS Publications Warehouse

Asquith, W.H.

2007-01-01

The 4-parameter generalized lambda distribution (GLD) is a flexible distribution capable of mimicking the shapes of many distributions and data samples including those with heavy tails. The method of L-moments and the recently developed method of trimmed L-moments (TL-moments) are attractive techniques for parameter estimation for heavy-tailed distributions for which the L- and TL-moments have been defined. Analytical solutions for the first five L- and TL-moments in terms of GLD parameters are derived. Unfortunately, numerical methods are needed to compute the parameters from the L- or TL-moments. Algorithms are suggested for parameter estimation. Application of the GLD using both L- and TL-moment parameter estimates from example data is demonstrated, and comparison of the L-moment fit of the 4-parameter kappa distribution is made. A small simulation study of the 98th percentile (far-right tail) is conducted for a heavy-tail GLD with high-outlier contamination. The simulations show, with respect to estimation of the 98th-percent quantile, that TL-moments are less biased (more robost) in the presence of high-outlier contamination. However, the robustness comes at the expense of considerably more sampling variability. ?? 2006 Elsevier B.V. All rights reserved.

Assessing Risks of Mine Tailing Dam Failures

NASA Astrophysics Data System (ADS)

Concha Larrauri, P.; Lall, U.

2017-12-01

The consequences of tailings dam failures can be catastrophic for communities and ecosystems in the vicinity of the dams. The failure of the Fundão tailings dam at the Samarco mine in 2015 killed 19 people with severe consequences for the environment. The financial and legal consequences of a tailings dam failure can also be significant for the mining companies. For the Fundão tailings dam, the company had to pay 6 billion dollars in fines and twenty-one executives were charged with qualified murder. There are tenths of thousands of active, inactive, and abandoned tailings dams in the world and there is a need to better understand the hazards posed by these structures to downstream populations and ecosystems. A challenge to assess the risks of tailings dams in a large scale is that many of them are not registered in publicly available databases and there is little information about their current physical state. Additionally, hazard classifications of tailings dams - common in many countries- tend to be subjective, include vague parameter definitions, and are not always updated over time. Here we present a simple methodology to assess and rank the exposure to tailings dams using ArcGIS that removes subjective interpretations. The method uses basic information such as current dam height, storage volume, topography, population, land use, and hydrological data. A hazard rating risk was developed to compare the potential extent of the damage across dams. This assessment provides a general overview of what in the vicinity of the tailings dams could be affected in case of a failure and a way to rank tailings dams that is directly linked to the exposure at any given time. One hundred tailings dams in Minas Gerais, Brazil were used for the test case. This ranking approach could inform the risk management strategy of the tailings dams within a company, and when disclosed, it could enable shareholders and the communities to make decisions on the risks they are taking.

Leachability of Arsenic and Heavy Metals from Mine Tailings of Abandoned Metal Mines

PubMed Central

Lim, Mihee; Han, Gi-Chun; Ahn, Ji-Whan; You, Kwang-Suk; Kim, Hyung-Seok

2009-01-01

Mine tailings from an abandoned metal mine in Korea contained high concentrations of arsenic (As) and heavy metals [e.g., As: 67,336, Fe: 137,180, Cu: 764, Pb: 3,572, and Zn: 12,420 (mg/kg)]. US EPA method 6010 was an effective method for analyzing total arsenic and heavy metals concentrations. Arsenic in the mine tailings showed a high residual fraction of 89% by a sequential extraction. In Toxicity Characteristic Leaching Procedure (TCLP) and Korean Standard Leaching Test (KSLT), leaching concentrations of arsenic and heavy metals were very low [e.g., As (mg/L): 0.4 for TCLP and 0.2 for KSLT; cf. As criteria (mg/L): 5.0 for TCLP and 1.5 for KSLT]. PMID:20049231

Heavy Tail Behavior of Rainfall Extremes across Germany

NASA Astrophysics Data System (ADS)

Castellarin, A.; Kreibich, H.; Vorogushyn, S.; Merz, B.

2017-12-01

Distributions are termed heavy-tailed if extreme values are more likely than would be predicted by probability distributions that have exponential asymptotic behavior. Heavy-tail behavior often leads to surprise, because historical observations can be a poor guide for the future. Heavy-tail behavior seems to be widespread for hydro-meteorological extremes, such as extreme rainfall and flood events. To date there have been only vague hints to explain under which conditions these extremes show heavy-tail behavior. We use an observational data set consisting of 11 climate variables at 1440 stations across Germany. This homogenized, gap-free data set covers 110 years (1901-2010) at daily resolution. We estimate the upper tail behavior, including its uncertainty interval, of daily precipitation extremes for the 1,440 stations at the annual and seasonal time scales. Different tail indicators are tested, including the shape parameter of the Generalized Extreme Value distribution, the upper tail ratio and the obesity index. In a further step, we explore to which extent the tail behavior can be explained by geographical and climate factors. A large number of characteristics is derived, such as station elevation, degree of continentality, aridity, measures for quantifying the variability of humidity and wind velocity, or event-triggering large-scale atmospheric situation. The link between the upper tail behavior and these characteristics is investigated via data mining methods capable of detecting non-linear relationships in large data sets. This exceptionally rich observational data set, in terms of number of stations, length of time series and number of explaining variables, allows insights into the upper tail behavior which is rarely possible given the typical observational data sets available.

40 CFR 61.251 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following specific meanings: (a) Area means the vertical projection of the pile upon the earth's surface. (b...) Dewatered means to remove the water from recently produced tailings by mechanical or evaporative methods such that the water content of the tailings does not exceed 30 percent by weight. (d) Existing...

40 CFR 61.251 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following specific meanings: (a) Area means the vertical projection of the pile upon the earth's surface. (b...) Dewatered means to remove the water from recently produced tailings by mechanical or evaporative methods such that the water content of the tailings does not exceed 30 percent by weight. (d) Existing...

40 CFR 61.251 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... following specific meanings: (a) Area means the vertical projection of the pile upon the earth's surface. (b...) Dewatered means to remove the water from recently produced tailings by mechanical or evaporative methods such that the water content of the tailings does not exceed 30 percent by weight. (d) Existing...

40 CFR 61.251 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following specific meanings: (a) Area means the vertical projection of the pile upon the earth's surface. (b...) Dewatered means to remove the water from recently produced tailings by mechanical or evaporative methods such that the water content of the tailings does not exceed 30 percent by weight. (d) Existing...

40 CFR 61.251 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... following specific meanings: (a) Area means the vertical projection of the pile upon the earth's surface. (b...) Dewatered means to remove the water from recently produced tailings by mechanical or evaporative methods such that the water content of the tailings does not exceed 30 percent by weight. (d) Existing...

The identification of helicopter noise using a neural network

NASA Technical Reports Server (NTRS)

Cabell, Randolph H.; Fuller, Chris R.; O'Brien, Walter F.

1990-01-01

Experiments were carried out to demonstrate the ability of an artificial neural network (ANN) system to distinguish between the noise of two helicopters. The ANN is taught to identify helicopters by using two types of features: one that is associated with the ratio of the main-rotor to tail-rotor blade passage frequency (BPF), and the ohter that describes the distribution of peaks in the main-rotor spectrum, which is independent of the tail-rotor. It is shown that the ability of the ANN to identify helicopters is comparable to that of a conventional recognition system using the ratio of the main-rotor BPF to the tail-rotor BPF (when both the main- and the tail-rotor noise are present), but the performoance of ANN exceeds the conventional-method performance when the tail-rotor noise is absent. In addition, the results of ANN can be obtained as a function of propagation distance.

Removal of heavy metals from Missouri lead mill tailings by froth flotation

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

Benn, F.W.; Cornell, W.L.

Froth flotation techniques to remove heavy metals (Pb, Cu, and Zn) from southeast Missouri lead mill tailings were investigated. It has been estimated that southeast Missouri contains between 200 and 300 million st of Pb tailings stored above ground. The tailings were classified as two distinct types: (1) pre-1968 tailings from the Old Lead Belt (some more than 100 years old) and (2) post-1968 tailings from the New Lead Belt. The objectives of the investigation were to reduce the Pb remaining in the tailings to < 500 ppm (< 0.05 pct Pb) and to attempt to recover a marketable concentratemore » to offset a portion of the remediation costs. The remaining dolomite-limestone would then be used as mining backfill or agricultural limestone. Bench-scale froth flotation removed, in percent, 95 Pb, 84 Cu, and 54 Zn, leaving 94 pct of the original weight containing, in parts per million, 400 Pb, 40 Cu, and 300 Zn from the Old Lead Belt tailings. Separate flotation tests also removed, in percent, 85 Pb, 84 Cu, and 80 Zn, leaving 75 pct of the original weight containing, in parts per million, 400 Pb, 200 Cu, and 500 Zn from the New Lead Belt tailings. Concentrates recovered from the Old Lead Belt were retreated to produce a final Pb concentrate containing 72 pct Pb with a cleaner flotation recovery of 79 pct. Froth flotation proved to be a viable method to remove the heavy metals.« less

Numerical study on the power extraction performance of a flapping foil with a flexible tail

NASA Astrophysics Data System (ADS)

Wu, J.; Shu, C.; Zhao, N.; Tian, F.-B.

2015-01-01

The numerical study on the power extraction performance of a flapping foil with a flexible tail is performed in this work. A NACA0015 airfoil is arranged in a two-dimensional laminar flow and imposed with a synchronous harmonic plunge and pitch rotary motion. A flat plate that is attached to the trailing edge of the foil is utilized to model a tail, and so they are viewed as a whole for the purpose of power extraction. In addition, the tail either is rigid or can deform due to the exerted hydrodynamic forces. To implement numerical simulations, an immersed boundary-lattice Boltzmann method is employed. At a Reynolds number of 1100 and the position of the pitching axis at third chord, the influences of the mass and flexibility of the tail as well as the frequency of motion on the power extraction are systematically examined. It is found that compared to the foil with a rigid tail, the efficiency of power extraction for the foil with a deformable tail can be improved. Based on the numerical analysis, it is indicated that the enhanced plunging component of the power extraction, which is caused by the increased lift force, directly contributes to the efficiency improvement. Since a flexible tail with medium and high masses is not beneficial to the efficiency improvement, a flexible tail with low mass together with high flexibility is recommended in the flapping foil based power extraction system.

Comparative daily activity patterns of Nilgai, Boselaphus tragocamelus and white-tailed deer, Odocoileus virginianus in South Texas

USDA-ARS?s Scientific Manuscript database

Nilgai antelope, Boselaphus tragocamelus, and white-tailed deer (WTD), Odocoileus virginianus, are hosts of the cattle fever ticks, Rhipicephalus (Boophilus) microplus, and R. (B.) annulatus in south Texas. Daily activity patterns were studied to develop optimum timing for field treatment methods fo...

DETERMINATION OF GENETIC DIVERSITY AND PATERNITY IN THE GRAY-TAILED VOLE (MICROTUS CANICAUDUS) BY RAPD-PCR

EPA Science Inventory

Genetic relatedness of gray-tailed voles (Microtus canicaudus) was determined by random amplified polymorphic DNA (RAPD). This work is the first reported use of the RAPD method for pedigree analysis of M. canicaudus and demonstrates the feasibility of RAPD for assessing paternity...

Comparison of methods to estimate population densities of black-tailed prairie dogs

Treesearch

Kieth E. Severson; Glenn E. Plumb

1999-01-01

Recent reintroduction of the black-footed ferret (Mustela nigripes) in west-central South Dakota has focused new attention on black-tailed prairie dogs (Cynomys ludovicanus), because prairie dog colonies provide essential habitat for ferrets. Currently, management agencies are assessing prairie dog populations by counting active...

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.

Cartesian-Grid Simulations of a Canard-Controlled Missile with a Free-Spinning Tail

NASA Technical Reports Server (NTRS)

Murman, Scott M.; Aftosmis, Michael J.; Kwak, Dochan (Technical Monitor)

2002-01-01

The proposed paper presents a series of simulations of a geometrically complex, canard-controlled, supersonic missile with free-spinning tail fins. Time-dependent simulations were performed using an inviscid Cartesian-grid-based method with results compared to both experimental data and high-resolution Navier-Stokes computations. At fixed free stream conditions and canard deflections, the tail spin rate was iteratively determined such that the net rolling moment on the empennage is zero. This rate corresponds to the time-asymptotic rate of the free-to-spin fin system. After obtaining spin-averaged aerodynamic coefficients for the missile, the investigation seeks a fixed-tail approximation to the spin-averaged aerodynamic coefficients, and examines the validity of this approximation over a variety of freestream conditions.

Research on simulation technology of full-path infrared tail flame tracking of photoelectric theodolite in complicated environment

NASA Astrophysics Data System (ADS)

Wu, Hai-ying; Zhang, San-xi; Liu, Biao; Yue, Peng; Weng, Ying-hui

2018-02-01

The photoelectric theodolite is an important scheme to realize the tracking, detection, quantitative measurement and performance evaluation of weapon systems in ordnance test range. With the improvement of stability requirements for target tracking in complex environment, infrared scene simulation with high sense of reality and complex interference has become an indispensable technical way to evaluate the track performance of photoelectric theodolite. And the tail flame is the most important infrared radiation source of the weapon system. The dynamic tail flame with high reality is a key element for the photoelectric theodolite infrared scene simulation and imaging tracking test. In this paper, an infrared simulation method for the full-path tracking of tail flame by photoelectric theodolite is proposed aiming at the faint boundary, irregular, multi-regulated points. In this work, real tail images are employed. Simultaneously, infrared texture conversion technology is used to generate DDS texture for a particle system map. Thus, dynamic real-time tail flame simulation results with high fidelity from the theodolite perspective can be gained in the tracking process.

The effect of intact talin and talin tail fragment on actin filament dynamics and structure depends on pH and ionic strength.

PubMed

Goldmann, W H; Hess, D; Isenberg, G

1999-03-01

We employed quasi-elastic light scattering and electron microscopy to investigate the influence of intact talin and talin tail fragment on actin filament dynamics and network structure. Using these methods, we confirm previous reports that intact talin induces cross-linking as well as filament shortening on actin networks. We now show that the effect of intact talin as well as talin tail fragment on actin networks is controlled by pH and ionic strength. At pH 7.5, actin filament dynamics in the presence of intact talin and talin tail fragment are characterized by a rapid decay of the dynamic structure factor and by a square root power law for the stretched exponential decay which is in contrast with the theory for pure actin solutions. At pH 6 and low ionic strength, intact talin cross-links actin filaments more tightly than talin tail fragment. Talin head fragment showed no effect on actin networks, indicating that the actin binding sites reside probably exclusively within the tail domain.

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.

Method of making a non-lead hollow point bullet

DOEpatents

Vaughn, Norman L.; Lowden, Richard A.

2003-10-07

The method of making a non-lead hollow point bullet has the steps of a) compressing an unsintered powdered metal composite core into a jacket, b) punching a hollow cavity tip portion into the core, c) seating an insert, the insert having a hollow point tip and a tail protrusion, on top of the core such that the tail protrusion couples with the hollow cavity tip portion, and d) swaging the open tip of the jacket.

Optical properties of InGaN grown by MOCVD on sapphire and on bulk GaN

NASA Astrophysics Data System (ADS)

Osinski, Marek; Eliseev, Petr G.; Lee, Jinhyun; Smagley, Vladimir A.; Sugahara, Tamoya; Sakai, Shiro

1999-11-01

Experimental data on photoluminescence of various bulk and quantum-well epitaxial InGaN/GaN structures grown by MOCVD are interpreted in terms of a band-tail model of inhomogeneously broadened radiative recombination. The anomalous temperature-induced blue spectral is shown to result from band-tail recombination under non-degenerate conditions. Significant differences are observed between epilayers grown on sapphire substrates and on GaN substrates prepared by the sublimination method, with no apparent evidence of band tails in homoepitaxial structures, indicating their higher crystalline quality.

Lift and center of pressure of wing-body-tail combinations at subsonic, transonic, and supersonic speeds

NASA Technical Reports Server (NTRS)

Pitts, William C; Nielsen, Jack N; Kaattari, George E

1957-01-01

A method is presented for calculating the lift and centers of pressure of wing-body and wing-body-tail combinations at subsonic, transonic, and supersonic speeds. A set of design charts and a computing table are presented which reduce the computations to routine operations. Comparison between the estimated and experimental characteristics for a number of wing-body and wing-body-tail combinations shows correlation to within + or - 10 percent on lift and to within about + or - 0.02 of the body length on center of pressure.

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.

Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation.

PubMed

Pan, Yinbing; Sun, Xiaodi; Jiang, Lai; Hu, Liang; Kong, Hong; Han, Yuan; Qian, Cheng; Song, Chao; Qian, Yanning; Liu, Wentao

2016-11-17

Tolerance seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect. The present study evaluated the effects and potential mechanisms of metformin in inhibiting microglial activation and alleviating the antinociceptive tolerance of morphine. The microglial cell line BV-2 cells and mouse brain-derived endothelial cell line bEnd3 cells were used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signaling was assayed by western blot and immunohistochemistry. The antinociception and morphine tolerance were assessed in CD-1 mice using tail-flick tests. We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin. Metformin suppressed morphine-induced BV-2 cells activation through increasing AMPK phosphorylation, which was reversed by the AMPK inhibitor compound C. Additionally, in BV-2 cells, morphine did not affect the cell viability and the mRNA expression of anti-inflammatory cytokines. In bEnd3 cells, morphine did not affect the mRNA expression of interleukin-1β (IL-1β), but increased IL-6 and tumor necrosis factor-α (TNF-α) mRNA expression; the effect was inhibited by metformin. Morphine also did not affect the mRNA expression of TLR-4 and chemokine ligand 2 (CCL2). Furthermore, systemic administration of metformin significantly blocked morphine-induced microglial activation in the spinal cord and then attenuated the development of chronic morphine tolerance in mice. Metformin significantly attenuated morphine antinociceptive tolerance by suppressing morphine-induced microglial activation through increasing AMPK phosphorylation.

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.

Inducing rat brain CYP2D with nicotine increases the rate of codeine tolerance; predicting the rate of tolerance from acute analgesic response.

PubMed

McMillan, Douglas M; Tyndale, Rachel F

2017-12-01

Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC 0-60 min ; p<0.05) and the rate of loss of peak analgesia (11.42%/day versus 4.20%; p<0.006) across the first four days of codeine administration (time to negligible analgesia). Inducing brain CYP2D with nicotine did not alter acute morphine analgesia (1.03-fold; p>0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Comparison of the long-term behavioral effects of neonatal exposure to retigabine or phenobarbital in rats.

PubMed

Frankel, Sari; Medvedeva, Natalia; Gutherz, Samuel; Kulick, Catherine; Kondratyev, Alexei; Forcelli, Patrick A

2016-04-01

Anticonvulsant drugs, when given during vulnerable periods of brain development, can have long-lasting consequences on nervous system function. In rats, the second postnatal week approximately corresponds to the late third trimester of gestation/early infancy in humans. Exposure to phenobarbital during this period has been associated with deficits in learning and memory, anxiety-like behavior, and social behavior, among other domains. Phenobarbital is the most common anticonvulsant drug used in neonatology. Several other drugs, such as lamotrigine, phenytoin, and clonazepam, have also been reported to trigger behavioral changes. A new generation anticonvulsant drug, retigabine, has not previously been evaluated for long-term effects on behavior. Retigabine acts as an activator of KCNQ channels, a mechanism that is unique among anticonvulsants. Here, we examined the effects retigabine exposure from postnatal day (P)7 to P14 on behavior in adult rats. We compared these effects with those produced by phenobarbital (as a positive control) and saline (as a negative control). Motor behavior was assessed by using the open field and rotarod, anxiety-like behavior by the open field, elevated plus maze, and light-dark transition task, and learning/memory by the passive avoidance task; social interactions were assessed in same-treatment pairs, and nociceptive sensitivity was assessed via the tail-flick assay. Motor behavior was unaltered by exposure to either drug. We found that retigabine exposure and phenobarbital exposure both induced increased anxiety-like behavior in adult animals. Phenobarbital, but not retigabine, exposure impaired learning and memory. These drugs also differed in their effects on social behavior, with retigabine-exposed animals displaying greater social interaction than phenobarbital-exposed animals. These results indicate that neonatal retigabine induces a subset of behavioral alterations previously described for other anticonvulsant drugs and extend our knowledge of drug-induced behavioral teratogenesis to a new mechanism of anticonvulsant action. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of the long-term behavioral effects of neonatal exposure to retigabine or phenobarbital in rats

PubMed Central

Frankel, Sari; Medvedeva, Natalia; Gutherz, Samuel; Kulick, Catherine; Kondratyev, Alexei; Forcelli, Patrick A.

2016-01-01

Anticonvulsant drugs, when given during vulnerable periods of brain development, can have long-lasting consequences on nervous system function. In rats, the second postnatal week approximately corresponds to the late third trimester of gestation/early infancy in humans. Exposure to phenobarbital during this period has been associated with deficits in learning and memory, anxiety-like behavior, and social behavior, among other domains. Phenobarbital is the most common anticonvulsant drug used in neonatology. Several other drugs, such as lamotrigine, phenytoin, and clonazepam have also been reported to trigger behavioral changes. A new generation anticonvulsant drug, retigabine, has not previously been evaluated for long-term effects on behavior. Retigabine acts as an activator of KCNQ channels, a mechanism that is unique among anticonvulsants. Here, we examined the effects retigabine exposure from postnatal day (P)7 to P14 on behavior in adult rats. We compared these effects to those produced by phenobarbital (as a positive control) and saline (as a negative control). Motor behavior was assessed using the open field and rotarod, anxiety-like behavior by the open field, elevated plus maze, and light-dark transition task, and learning/memory by the passive avoidance task; social interactions were assessed in same-treatment pairs and nociceptive sensitivity was assessed via the tail-flick assay. Motor behavior was unaltered by exposure to either drug. We found that retigabine and phenobarbital exposure both induced increased anxiety-like behavior in adult animals. Phenobarbital, but not retigabine exposure impaired learning and memory. These drugs also differed in their effects on social behavior, with retigabine-exposed animals displaying greater social interaction than phenobarbital-exposed animals. These results indicate that neonatal retigabine induces a subset of behavioral alterations previously described for other anticonvulsant drugs, and extend our knowledge of drug-induced behavioral teratogenesis to a new mechanism of anticonvulsant action. PMID:26921596

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

PubMed

Zhai, Mei-Li; Chen, Yi; Liu, Chong; Wang, Jian-Bo; Yu, Yong-Hao

2018-05-23

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine. In the first experiment, the experimental rats were randomly divided into four groups: Control, morphine, morphine+GR antagonist mifepristone (RU38486) and morphine+GR agonist dexamethasone (Dex). Each group was treated with continuous intrathecal (IT) injection of the drugs for 6 days. The expression of GRs and MAPK 3/1 (p‑ERK 1/2) in the spinal dorsal horn was detected by western blot analysis and immunofluorescence staining. In the second experiment, the MAPK inhibitor PD98059 was added and the rats were randomly divided into four groups: Control, morphine, PD98059+morphine and PD98059+morphine+Dex. The continuous IT injection lasted for 7 days in each group. For all experiments, the tail flick test was conducted 30 min following administration every day to assess the thermal hyperalgesia of the rats. The experimental results demonstrated that there was a co‑existence of GRs and p‑ERK 1/2 in the spinal cord dorsal horn by double immunofluorescence staining. The GR antagonist RU38486 attenuated the morphine analgesia tolerance by inhibiting the expression of GR and increasing the expression of p‑ERK. The MAPK inhibitor PD98059 increased the effect of morphine tolerance and prolonged the duration of morphine tolerance. The present results suggest that spinal GRs may serve an important role in the development of morphine tolerance through the ERK signaling pathway.

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.

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

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.

Sex hormones regulate cerebral drug metabolism via brain miRNAs: down-regulation of brain CYP2D by androgens reduces the analgesic effects of tramadol

PubMed Central

Li, Jie; Xie, Mengmeng; Wang, Xiaoshuang; Ouyang, Xiufang; Wan, Yu; Dong, Guicheng; Yang, Zheqiong; Yang, Jing; Yue, Jiang

2015-01-01

Background and Purpose Brain cytochrome P450 2D (CYP2D) metabolises exogenous neurotoxins, endogenous substances and neurotransmitters. Brain CYP2D can be regulated in an organ-specific manner, but the possible regulatory mechanisms are poorly understood. We investigated the involvement of miRNAs in the selective regulation of brain CYP2D by testosterone and the corresponding alteration of the pharmacological profiles of tramadol by testosterone. Experimental Approach The regulation of CYP2D and brain-enriched miRNAs by testosterone was investigated using SH-SY5Y cells, U251 cells, and HepG2 cells as well as orchiectomized growth hormone receptor knockout (GHR-KO) mice and rats. Concentration–time curves of tramadol in rat brain were determined using a microdialysis technique. The analgesic action of tramadol was assessed by the tail-flick test in rats. Key Results miR-101 and miR-128-2 bound the 3′-untranslated region of the CYP2D6 mRNA and decreased its level. Testosterone decreased CYP2D6 catalytic function via the up-regulation of miR-101 and miR-128-2 in SH-SY5Y and U251 cells, but not in HepG2 cells. Orchiectomy decreased the levels of miR-101 and miR-128-2 in the hippocampus of male GHR-KO mice, indicating that androgens regulate miRNAs directly, not via the alteration of growth hormone secretion patterns. Changes in the pharmacokinetic and pharmacodynamic profiles of tramadol by orchiectomy was attenuated by either testosterone supplementation or a specific brain CYP2D inhibitor. Conclusions and Implications The selective regulation of brain CYP2D via brain-enriched miRNAs, following changes in androgen levels, such as in testosterone therapy, androgen deprivation therapy and/or ageing may alter the response to centrally active substances. PMID:26031356

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation.

PubMed

Bjursell, Mikael; Ryberg, Erik; Wu, Tingting; Greasley, Peter J; Bohlooly-Y, Mohammad; Hjorth, Stephan

2016-01-01

The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours.

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.

Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance.

PubMed

Wang, Zi-Long; Li, Ning; Wang, Pei; Tang, Hong-Hai; Han, Zheng-Lan; Song, Jing-Jing; Li, Xu-Hui; Yu, Hong-Ping; Zhang, Ting; Zhang, Run; Xu, Biao; Zhang, Meng-Na; Fang, Quan; Wang, Rui

2016-09-01

Mounting evidences indicate the functional interactions between neuropeptide FF (NPFF) and opioids, including the endogenous opioids. In the present work, EN-9, a chimeric peptide containing the functional domains of the endogenous opioid endomorphin-2 (EM-2) and NPFF, was synthesized and pharmacologically characterized. In vitro cAMP assay demonstrated that EN-9 was a multifunctional agonist of κ-opioid, NPFF1 and NPFF2 receptors. In the mouse tail-flick test, intracerebroventricularly (i.c.v.) administration of EN-9 produced significant antinociception with an ED50 value of 13.44 nmol, which lasted longer than that of EM-2. In addition, EN-9 induced potent antinociception after both intravenous (i.v.) and subcutaneous (s.c.) injection. Furthermore, the experiments using the antagonists of opioid and NPFF receptors indicated that the central antinociception of EN-9 was mainly mediated by κ-opioid receptor, independently on NPFF receptors. Notably, the central antinociception of EN-9 was not reduced over a period of 6 days repeated i.c.v. injection. Repeated i.c.v. administration of EN-9 with the NPFF1 and NPFF2 receptors antagonist RF9 resulted in a progressive loss of analgesic potency, consistent with the development of tolerance. Moreover, central administration of EN-9 induced the place conditioning aversion only at a high dose of 60 nmol, but not at low doses. At supraspinal level, only high dose of EN-9 (60 nmol, i.c.v.) inhibited gastrointestinal transit via NPFF receptors. Similarly, systemic administration of EN-9 also inhibited gastrointestinal transit at high doses (10 and 30 mg/kg, i.v.). Taken together, the multifunctional agonist of κ-opioid and NPFF receptors EN-9 produced a potent, non-tolerance forming antinociception with limited side effects. Copyright © 2016. Published by Elsevier Ltd.

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.

A novel polymer inclusion membrane based method for continuous clean-up of thiocyanate from gold mine tailings water.

PubMed

Cho, Youngsoo; Cattrall, Robert W; Kolev, Spas D

2018-01-05

Thiocyanate is present in gold mine tailings waters in concentrations up to 1000mgL -1 and this has a serious environmental impact by not allowing water reuse in the flotation of gold ore. This significantly increases the consumption of fresh water and the amount of wastewater discharged in tailings dams. At the same time thiocyanate in tailings waters often leads to groundwater contamination. A novel continuous membrane-based method for the complete clean-up of thiocyanate in concentrations as high as 1000mgL -1 from its aqueous solutions has been developed. It employs a flat sheet polymer inclusion membrane (PIM) of composition 70wt% PVC, 20wt% Aliquat 336 and 10wt% 1-tetradecanol which separates counter-current streams of a feed thiocyanate solution and a 1M NaNO 3 receiving solution. The PIM-based system has been operated continuously for 45days with 99% separation efficiency. The volume of the receiving solution has been drastically reduced by recirculating it and continuously removing thiocyanate by precipitating it with in-situ generated Cu(I). The newly developed PIM-based thiocyanate clean-up method is environmentally friendly in terms of reagent use and inexpensive with respect to both equipment and running costs. Copyright © 2017 Elsevier B.V. All rights reserved.

Method and apparatus for determining return stroke polarity of distant lightning

NASA Technical Reports Server (NTRS)

Blakeslee, Richard J. (Inventor); Brook, Marx (Inventor)

1992-01-01

A method is described for determining the return stroke polarity of distant lightning for distances beyond 600 km by detecting the electric field associated with a return stroke of distant lightning, and processing the electric field signal to determine the polarity of the slow tail of the VLF waveform signal associated with the detected electric field. The polarity of the return stroke of distant lightning is determined based upon the polarity of the slow tail portion of the waveform.

Determining Polarities Of Distant Lightning Strokes

NASA Technical Reports Server (NTRS)

Blakeslee, Richard J.; Brook, Marx

1990-01-01

Method for determining polarities of lightning strokes more than 400 km away. Two features of signal from each stroke correlated. New method based on fact each stroke observed thus far for which polarity determined unambiguously, initial polarity of tail same as polarity of initial deflection before initial-deflection signal altered by propagation effects. Receiving station equipped with electric-field-change antenna coupled to charge amplifier having time constant of order of 1 to 10 seconds. Output of amplifier fed to signal-processing circuitry, which determines initial polarity of tail.

Method and apparatus for determining return stroke polarity of distant lightning

NASA Technical Reports Server (NTRS)

Blakeslee, Richard J. (Inventor); Brook, Marx (Inventor)

1990-01-01

A method is described for determining the return stroke polarity of distant lightning for distances beyond 600 km by detecting the electric field associated with a return stroke of distant lightning, and processing the electric field signal to determine the polarity of the slow tail of the VLF waveform signal associated with the detected electric field. The polarity of the return stroke of distant lightning is determined based upon the polarity of the slow tail portion of the waveform.

Keyboard before Head Tracking Depresses User Success in Remote Camera Control

NASA Astrophysics Data System (ADS)

Zhu, Dingyun; Gedeon, Tom; Taylor, Ken

In remote mining, operators of complex machinery have more tasks or devices to control than they have hands. For example, operating a rock breaker requires two handed joystick control to position and fire the jackhammer, leaving the camera control to either automatic control or require the operator to switch between controls. We modelled such a teleoperated setting by performing experiments using a simple physical game analogue, being a half size table soccer game with two handles. The complex camera angles of the mining application were modelled by obscuring the direct view of the play area and the use of a Pan-Tilt-Zoom (PTZ) camera. The camera control was via either a keyboard or via head tracking using two different sets of head gestures called “head motion” and “head flicking” for turning camera motion on/off. Our results show that the head motion control was able to provide a comparable performance to using a keyboard, while head flicking was significantly worse. In addition, the sequence of use of the three control methods is highly significant. It appears that use of the keyboard first depresses successful use of the head tracking methods, with significantly better results when one of the head tracking methods was used first. Analysis of the qualitative survey data collected supports that the worst (by performance) method was disliked by participants. Surprisingly, use of that worst method as the first control method significantly enhanced performance using the other two control methods.

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).

Fractal and Chaos Analysis for Dynamics of Radon Exhalation from Uranium Mill Tailings

NASA Astrophysics Data System (ADS)

Li, Yongmei; Tan, Wanyu; Tan, Kaixuan; Liu, Zehua; Xie, Yanshi

2016-08-01

Tailings from mining and milling of uranium ores potentially are large volumes of low-level radioactive materials. A typical environmental problem associated with uranium tailings is radon exhalation, which can significantly pose risks to environment and human health. In order to reduce these risks, it is essential to study the dynamical nature and underlying mechanism of radon exhalation from uranium mill tailings. This motivates the conduction of this study, which is based on the fractal and chaotic methods (e.g. calculating the Hurst exponent, Lyapunov exponent and correlation dimension) and laboratory experiments of the radon exhalation rates. The experimental results show that the radon exhalation rate from uranium mill tailings is highly oscillated. In addition, the nonlinear analyses of the time series of radon exhalation rate demonstrate the following points: (1) the value of Hurst exponent much larger than 0.5 indicates non-random behavior of the radon time series; (2) the positive Lyapunov exponent and non-integer correlation dimension of the time series imply that the radon exhalation from uranium tailings is a chaotic dynamical process; (3) the required minimum number of variables should be five to describe the time evolution of radon exhalation. Therefore, it can be concluded that the internal factors, including heterogeneous distribution of radium, and randomness of radium decay, as well as the fractal characteristics of the tailings, can result in the chaotic evolution of radon exhalation from the tailings.

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.

Aerodynamic interference effects on tilting proprotor aircraft. [using the Green function method

NASA Technical Reports Server (NTRS)

Soohoo, P.; Morino, L.; Noll, R. B.; Ham, N. D.

1977-01-01

The Green's function method was used to study tilting proprotor aircraft aerodynamics with particular application to the problem of the mutual interference of the wing-fuselage-tail-rotor wake configuration. While the formulation is valid for fully unsteady rotor aerodynamics, attention was directed to steady state aerodynamics, which was achieved by replacing the rotor with the actuator disk approximation. The use of an actuator disk analysis introduced a mathematical singularity into the formulation; this problem was studied and resolved. The pressure distribution, lift, and pitching moment were obtained for an XV-15 wing-fuselage-tail rotor configuration at various flight conditions. For the flight configurations explored, the effects of the rotor wake interference on the XV-15 tilt rotor aircraft yielded a reduction in the total lift and an increase in the nose-down pitching moment. This method provides an analytical capability that is simple to apply and can be used to investigate fuselage-tail rotor wake interference as well as to explore other rotor design problem areas.

Determination of the proton-to-helium ratio in cosmic rays at ultra-high energies from the tail of the Xmax distribution

NASA Astrophysics Data System (ADS)

Yushkov, A.; Risse, M.; Werner, M.; Krieg, J.

2016-12-01

We present a method to determine the proton-to-helium ratio in cosmic rays at ultra-high energies. It makes use of the exponential slope, Λ, of the tail of the Xmax distribution measured by an air shower experiment. The method is quite robust with respect to uncertainties from modeling hadronic interactions and to systematic errors on Xmax and energy, and to the possible presence of primary nuclei heavier than helium. Obtaining the proton-to-helium ratio with air shower experiments would be a remarkable achievement. To quantify the applicability of a particular mass-sensitive variable for mass composition analysis despite hadronic uncertainties we introduce as a metric the 'analysis indicator' and find an improved performance of the Λ method compared to other variables currently used in the literature. The fraction of events in the tail of the Xmax distribution can provide additional information on the presence of nuclei heavier than helium in the primary beam.

The complete mitochondrial genome of the tiger tail seahorse, Hippocampus comes (Teleostei, Syngnathidae).

PubMed

Chang, Chia-Hao; Lin, Han-Yang; Jang-Liaw, Nian-Hong; Shao, Kwang-Tsao; Lin, Yeong-Shin; Ho, Hsuan-Ching

2013-06-01

The complete mitochondrial genome of the tiger tail seahorse was sequenced using a polymerase chain reaction-based method. The total length of mitochondrial DNA is 16,525 bp and includes 13 protein-coding genes, 2 ribosomal RNA, 22 transfer RNA genes, and a control region. The mitochondrial gene arrangement of the tiger tail seahorse is also matching the one observed in the most vertebrate creatures. Base composition of the genome is A (32.8%), T (29.8%), C (23.0%), and G (14.4%) with an A+T-rich hallmark as that of other vertebrate mitochondrial genomes.

Necrosis of the tail of pancreas following proximal splenic artery embolization

PubMed Central

Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

2016-01-01

The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. PMID:27177891

Solitons with Gaussian tails in dispersion-managed communication systems using gratings

NASA Astrophysics Data System (ADS)

Mezentsev, Vladimir K.; Turitsyn, Sergei K.

1997-02-01

We examine the transmission of optical pulses in fibre communication systems with dispersion management. It is shown that solitons with Gaussian tails may be formed by the adoption of gratings to periodically compensate a pulse chirp. Fast decaying Gaussian tails allow us to provide denser information packing in comparison with sech-type soliton transmission. The discovered pulse is an attractive candidate for use as information carrier in optical transmission systems with an ultra-large capacity of around 100 Gbit/s. It is shown that a variational method can be effectively used to describe the dynamics of the breathing soliton.

Head space analysis to non-invasively distinguish between vaccinated and bovine tuberculosis-infected white-tailed deer

USDA-ARS?s Scientific Manuscript database

White-tailed deer (WTD; Odocoileus virginianus) can act as a reservoir for bovine tuberculosis (bTB), caused by Mycobacterium bovis, and can be a source of infection in cattle. Presently, no method exists to noninvasively monitor the presence of bTB in wildlife. In addition, due to similarities betw...

Impact of commercial garden growth substratum and NPK-fertilizer on copper fractionation in a copper-mine tailing

NASA Astrophysics Data System (ADS)

Charles, A.; Karam, A.; Jaouich, A.

2009-04-01

Organic amendment and NPK-fertilizer could affect the distribution of copper (Cu) among Cu-mine tailing compounds and hence the availability or phytotoxicity of Cu to plants. A laboratory incubation experiment was conducted to investigate the forms of Cu in a Cu-mine tailing (pH 7.70) amended with a commercial garden growth substratum (GGS) containing peat moss and natural mycorrhizae (Glomus intraradices) in combination with a commercial NPK-fertilizer (20-20-20), by a sequential extraction method. There were eight treatments after the combination of four rates of GGS (0, 12.4, 50 and 100 g/kg tailing) and two rates of fertilizer (0 and 20 g/kg tailing). At the end of a 52-week incubation period, tailing Cu was sequentially extracted to fractionate Cu into five operationally defined geochemical forms, namely ‘water-soluble' (Cu-sol), ‘exchangeable' (Cu-exc), ‘specifically adsorbed on carbonates or carbonate-bound' (Cu-car), ‘organic-bound' (Cu-org) and ‘residual' (Cu-res) fractions. After treatments, the most labile Cu pool (Cu-sol + Cu-exc) represented about 0.94 % of the total Cu, the Cu-car and Cu-org accounted for 22.7 and 5.0% of total Cu, and the residual Cu accounted for nearly 71.3% of total Cu. Compared with the control, the application of GGS decreased Cu-car and increased CuORG whereas the addition of fertilizer increased Cu-sol + Cu-exc and decreased Cu-carb. Fertilizer-treated tailings had the highest amount of Cu-sol + Cu-exc. High rates of GGS resulted in Cu-org levels in GGS-treated tailings which were more than 2.0-2.8 times those obtained in the untreated tailing (control). The partition of Cu in GGS-treated tailings followed the order: Cu-sol + Cu-exc < Cu-car < Cu-org < Cu-res. This study suggests that NPK-fertilizer promotes the formation of labile Cu forms in the calcite-containing Cu-mine tailing. GGS in the tailing matrix acts as effective sorbent for Cu.

Noxious heat threshold temperature and pronociceptive effects of allyl isothiocyanate (mustard oil) in TRPV1 or TRPA1 gene-deleted mice.

PubMed

Tékus, Valéria; Horváth, Ádám; Hajna, Zsófia; Borbély, Éva; Bölcskei, Kata; Boros, Melinda; Pintér, Erika; Helyes, Zsuzsanna; Pethő, Gábor; Szolcsányi, János

2016-06-01

To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice. In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold. It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains. Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics. Copyright © 2016 Elsevier Inc. All rights reserved.

In vivo evaluation method of the effect of nattokinase on carrageenan-induced tail thrombosis in a rat model.

PubMed

Kamiya, Seitaro; Hagimori, Masayori; Ogasawara, Masayoshi; Arakawa, Masayuki

2010-01-01

Thrombosis is characterized by congenital and acquired procatarxis. Nattokinase inhibits thrombus formation in vitro. However, in vivo evaluation of the therapeutic efficacy of nattokinase against thrombosis remains to be conducted. Subcutaneous nattokinase injections of 1 or 2 mg/ml were administered to the tails of rats. Subsequently, κ-carrageenan was intravenously administered to the tails at 12 h after nattokinase injections. The mean length of the infarcted regions in the tails of rats was significantly shorter in rats administered 2 mg/ml of nattokinase than those in control rats. Nattokinase exhibited significant prophylactic antithrombotic effects. Previously, the in vitro efficacy of nattokinase against thrombosis had been reported; now our study has revealed the in vivo efficacy of nattokinase against thrombosis. Copyright © 2010 S. Karger AG, Basel.

Determination of primary energy in nucleus-nucleus collisions and the high P(sub)T tail of alpha-particles

NASA Technical Reports Server (NTRS)

Freier, P. S.; Atwater, T. W.

1985-01-01

A determination of primary energy is required in order to study the energy dependence of meson multiplicity in A-A collisions in cosmic rays. Various procedures which estimate the energy of a primary nucleus from its interaction were investigated. An average of two methods were used, one using the pions and wounded protons and the other using spectator protons and alpha particles. The high P sub T tail observed for Z = 2 fragments requires a modification of the latter method.

Variable Weight Fractional Collisions for Multiple Species Mixtures

DTIC Science & Technology

2017-08-28

DISTRIBUTION A: APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED; PA #17517 6 / 21 VARIABLE WEIGHTS FOR DYNAMIC RANGE Continuum to Discrete ...Representation: Many Particles →̃ Continuous Distribution Discretized VDF Yields Vlasov But Collision Integral Still a Problem Particle Methods VDF to Delta...Function Set Collisions between Discrete Velocities But Poorly Resolved Tail (Tail Critical to Inelastic Collisions) Variable Weights Permit Extra DOF in

An autonomous sperm-like propulsor in a quiescent flow

NASA Astrophysics Data System (ADS)

Kim, Boyoung; Park, Sung Goon; Sung, Hyung Jin

2016-11-01

Flapping motions of flexible fins are widespread in nature. Birds, fish, and insects use their wings, fins, or bodies to stay afloat and to advance forward in the surrounding fluids. It is important to understand the physics of the flapping motions to utilize them for the biomimetic machines. In the present study, we introduce a sperm-like propulsor that consists of a rigid head containing genetic information and a flapping flexible tail for propulsion. The head gives a sinusoidal torque to the leading edge of the tail, and the flexible tail flaps along the leading edge. In other words, the sperm-like propulsor is moved by an oscillating relative angle between the head and the leading edge of the tail. Unlike self-propelled heaving and pitching fins, the 'autonomous' sperm-like propulsor has no prescribed motion or constraint referenced from outside coordinates. The penalty method and the immersed boundary method are used to solve the autonomous sperm-like propulsor in a quiescent flow. The cruising speed and the propulsive efficiency of the propulsor are explored as a function of the head size (D/ L) , the pitching angle (θ0) , the pitching frequency (f) , and the distance from the wall (G/ L) .

Hydrophilization of Magnetic Nanoparticles with Modified Alternating Copolymers. Part 1: The Influence of the Grafting

PubMed Central

Bronstein, Lyudmila M.; Shtykova, Eleonora V.; Malyutin, Andrey; Dyke, Jason C.; Gunn, Emily; Gao, Xinfeng; Stein, Barry; Konarev, Peter V.; Dragnea, Bogdan; Svergun, Dmitri I.

2010-01-01

Iron oxide nanoparticles (NPs) with a diameter 21.6 nm were coated with poly(maleic acid-alt-1-octadecene) (PMAcOD) modified with grafted 5,000 Da poly(ethyelene glycol) (PEG) or short ethylene glycol (EG) tails. The coating procedure utilizes hydrophobic interactions of octadecene and oleic acid tails, while the hydrolysis of maleic anhydride moieties as well as the presence of hydrophilic PEG (EG) tails allows the NP hydrophilicity. The success of the NP coating was found to be independent of the degree of grafting which was varied between 20 and 80% of the –MacOD-units, but depended on the length of the grafted tail. The NP coating and hydrophilization did not occur when the modified copolymer contained 750 Da PEG tails independently of the grafting degree. To explain this phenomenon the micellization of the modified PMAcOD copolymers in water was analyzed by small angle x-ray scattering (SAXS). The PMAcOD molecules with the grafted 750 Da PEG tails form compact non-interacting disk-like micelles, whose stability apparently allows for no interactions with the NP hydrophobic shells. The PMAcOD containing the 5,000 Da PEG and EG tails form much larger aggregates capable of an efficient coating of the NPs. The coated NPs were characterized using transmission electron microscopy, dynamic light scattering, ζ-potential measurements, and thermal gravimetry analysis. The latter method demonstrated that the presence of long PEG tails in modified PMAcOD allows the attachment of fewer macromolecules (by a factor of ~20) compared to the case of non-modified or EG modified PMAcOD, emphasizing the importance of PEG tails in NP hydrophilization. The NPs coated with PMAcOD modified with 60% (towards all –MAcOD- units) of the 5,000 PEG tails bear a significant negative charge and display good stability in buffers. Such NPs can be useful as magnetic cores for virus-like particle formation. PMID:21221425

Self-consistent molecular dynamics calculation of diffusion in higher n-alkanes.

PubMed

Kondratyuk, Nikolay D; Norman, Genri E; Stegailov, Vladimir V

2016-11-28

Diffusion is one of the key subjects of molecular modeling and simulation studies. However, there is an unresolved lack of consistency between Einstein-Smoluchowski (E-S) and Green-Kubo (G-K) methods for diffusion coefficient calculations in systems of complex molecules. In this paper, we analyze this problem for the case of liquid n-triacontane. The non-conventional long-time tails of the velocity autocorrelation function (VACF) are found for this system. Temperature dependence of the VACF tail decay exponent is defined. The proper inclusion of the long-time tail contributions to the diffusion coefficient calculation results in the consistency between G-K and E-S methods. Having considered the major factors influencing the precision of the diffusion rate calculations in comparison with experimental data (system size effects and force field parameters), we point to hydrogen nuclear quantum effects as, presumably, the last obstacle to fully consistent n-alkane description.

Description of an α-cluster tail in 8Be and 20Ne: Delocalization of the α cluster by quantum penetration

NASA Astrophysics Data System (ADS)

Kanada-En'yo, Yoshiko

2014-10-01

We analyze the α-cluster wave functions in cluster states of ^8Be and ^{20}Ne by comparing the exact relative wave function obtained by the generator coordinate method (GCM) with various types of trial functions. For the trial functions, we adopt the fixed range shifted Gaussian of the Brink-Bloch (BB) wave function, the spherical Gaussian with the adjustable range parameter of the spherical Tohsaki-Horiuchi-Schuck-Röpke (sTHSR), the deformed Gaussian of the deformed THSR (dTHSR), and a function with the Yukawa tail (YT). The quality of the description of the exact wave function with a trial function is judged by the squared overlap between the trial function and the GCM wave function. A better result is obtained with the sTHSR wave function than the BB wave function, and further improvement can be made with the dTHSR wave function because these wave functions can describe the outer tail better. The YT wave function gives almost an equal quality to or even better quality than the dTHSR wave function, indicating that the outer tail of α-cluster states is characterized by the Yukawa-like tail rather than the Gaussian tail. In weakly bound α-cluster states with small α separation energy and the low centrifugal and Coulomb barriers, the outer tail part is the slowly damping function described well by the quantum penetration through the effective barrier. This outer tail characterizes the almost zero-energy free α gas behavior, i.e., the delocalization of the cluster.

Solvent extraction of Cu, Mo, V, and U from leach solutions of copper ore and flotation tailings.

PubMed

Smolinski, Tomasz; Wawszczak, Danuta; Deptula, Andrzej; Lada, Wieslawa; Olczak, Tadeusz; Rogowski, Marcin; Pyszynska, Marta; Chmielewski, Andrzej Grzegorz

2017-01-01

Flotation tailings from copper production are deposits of copper and other valuable metals, such as Mo, V and U. New hydrometallurgical technologies are more economical and open up new possibilities for metal recovery. This work presents results of the study on the extraction of copper by mixed extractant consisting p -toluidine dissolved in toluene. The possibility of simultaneous liquid-liquid extraction of molybdenum and vanadium was examined. D2EHPA solutions was used as extractant, and recovery of individual elements compared for the representative samples of ore and copper flotation tailings. Radiometric methods were applied for process optimization.

An Automated Mouse Tail Vascular Access System by Vision and Pressure Feedback.

PubMed

Chang, Yen-Chi; Berry-Pusey, Brittany; Yasin, Rashid; Vu, Nam; Maraglia, Brandon; Chatziioannou, Arion X; Tsao, Tsu-Chin

2015-08-01

This paper develops an automated vascular access system (A-VAS) with novel vision-based vein and needle detection methods and real-time pressure feedback for murine drug delivery. Mouse tail vein injection is a routine but critical step for preclinical imaging applications. Due to the small vein diameter and external disturbances such as tail hair, pigmentation, and scales, identifying vein location is difficult and manual injections usually result in poor repeatability. To improve the injection accuracy, consistency, safety, and processing time, A-VAS was developed to overcome difficulties in vein detection noise rejection, robustness in needle tracking, and visual servoing integration with the mechatronics system.

Global morphological analysis of marine viruses shows minimal regional variation and dominance of non-tailed viruses.

PubMed

Brum, Jennifer R; Schenck, Ryan O; Sullivan, Matthew B

2013-09-01

Viruses influence oceanic ecosystems by causing mortality of microorganisms, altering nutrient and organic matter flux via lysis and auxiliary metabolic gene expression and changing the trajectory of microbial evolution through horizontal gene transfer. Limited host range and differing genetic potential of individual virus types mean that investigations into the types of viruses that exist in the ocean and their spatial distribution throughout the world's oceans are critical to understanding the global impacts of marine viruses. Here we evaluate viral morphological characteristics (morphotype, capsid diameter and tail length) using a quantitative transmission electron microscopy (qTEM) method across six of the world's oceans and seas sampled through the Tara Oceans Expedition. Extensive experimental validation of the qTEM method shows that neither sample preservation nor preparation significantly alters natural viral morphological characteristics. The global sampling analysis demonstrated that morphological characteristics did not vary consistently with depth (surface versus deep chlorophyll maximum waters) or oceanic region. Instead, temperature, salinity and oxygen concentration, but not chlorophyll a concentration, were more explanatory in evaluating differences in viral assemblage morphological characteristics. Surprisingly, given that the majority of cultivated bacterial viruses are tailed, non-tailed viruses appear to numerically dominate the upper oceans as they comprised 51-92% of the viral particles observed. Together, these results document global marine viral morphological characteristics, show that their minimal variability is more explained by environmental conditions than geography and suggest that non-tailed viruses might represent the most ecologically important targets for future research.

The long-term environmental impacts of the Mount Polley mine tailings spill, British Columbia, Canada

NASA Astrophysics Data System (ADS)

Byrne, Patrick; Hudson-Edwards, Karen; Macklin, Mark; Brewer, Paul; Bird, Graham; Williams, Richard

2015-04-01

On the 4th August 2014 a tailings impoundment failure at the Mount Polley gold and copper mine in British Columbia, Canada, released approximately 25 million m3 of solid and liquid waste into Hazeltine Creek, Quesnel Lake and Polley Lake. The sheer volume of the tailings released caused Haseltine Creek channel to expand from 2m to over 25m in width and Polley Lake water level to rise by 1.7m. The spill also removed trees in a 900 km2 corridor either side of Hazeltine Creek. Local residents and government officials have expressed serious concerns regarding the potential long-term effects on regional biodiversity, water security and to the livelihoods of First Nation communities. Among impoundment failures, the Mount Polley disaster is unique in that the solid tailings contain an unusual mixture of metal contaminants (arsenic, copper, gold, manganese, nickel, lead, vanadium). As particulate matter is the principal carrier of metal contaminants, the spilled tailings may reside in the regional soils and sediments for 1000s of years serving as a secondary source of pollution. The environmental risk posed by the spilled tailings is compounded by the location of the spill in a mountainous forested catchment, affected by severe winters with prominent spring snow melts that have the potential to remobilise very large quantities of spilled tailings. No data currently exist on the short- to long-term behaviour of these tailings in soils and sediments and the effects of the clean-up operations on their behaviour in this type of river environment. In this study, we adopt a multidisciplinary approach to determine the environmental and geomorphological impacts of the tailings spill. We have two specific objectives. (1) The physicochemical speciation and geochemical stability of spilled tailings will be characterised in surface and hyporheic sediments using bulk chemistry, mineralogical (XRD and SEM) and speciation methods (sequential extractions, electron microprobe analysis, XAS). (2) Pre- and post-remediation geomorphological assessments will use unmanned aerial vehicle (UAV) photographic surveys and ground-based topographic surveys to (i) establish the efficacy of remediation efforts in stabilising Hazeltine Creek channel and (ii) quantify the physical remobilisation of tailings during the spring snowmelt.

Review of samples of water, sediment, tailings, and biota at the Little Bonanza mercury mine, San Luis Obispo County, California

USGS Publications Warehouse

Rytuba, James J.; Hothem, Roger L.; Goldstein, Daniel N.; Brussee, Brianne E.; May, Jason T.

2011-01-01

Sample Sites and Methods Samples were collected to assess the concentrations of Hg and biogeochemically relevant constituents in tailings and wasterock piles at the Little Bonanza Hg mine. Tailings are present adjacent to a three-pipe retort used to process the Hg ore. The tailings occur in the upper 15 cm of the soil adjacent to the retort and slag from the retort is present on the surface. An area of disturbed soil and rock uphill from the retort was likely formed during construction of a dam that provided water for mining activities. Wasterock in these piles was sampled. The largest amount of tailings is exposed to the west of the retort in the bank of WF Las Tablas Creek. Water, sediment, and biota were sampled from WF Las Tablas Creek, which flows through the mine area. Sample-site locations are shown in figures 10 and 11 and listed in table 1. Samples were collected when streamflow was low and no precipitation had occurred.

Identification of structural and morphogenesis genes of Pseudoalteromonas phage φRIO-1 and placement within the evolutionary history of Podoviridae.

PubMed

Hardies, Stephen C; Thomas, Julie A; Black, Lindsay; Weintraub, Susan T; Hwang, Chung Y; Cho, Byung C

2016-02-01

The virion proteins of Pseudoalteromonas phage φRIO-1 were identified and quantitated by mass spectrometry and gel densitometry. Bioinformatic methods customized to deal with extreme divergence defined a φRIO-1 tail structure homology group of phages, which was further related to T7 tail and internal virion proteins (IVPs). Similarly, homologs of tubular tail components and internal virion proteins were identified in essentially all completely sequenced podoviruses other than those in the subfamily Picovirinae. The podoviruses were subdivided into several tail structure homology groups, in addition to the RIO-1 and T7 groups. Molecular phylogeny indicated that these groups all arose about the same ancient time as the φRIO-1/T7 split. Hence, the T7-like infection mechanism involving the IVPs was an ancestral property of most podoviruses. The IVPs were found to variably host both tail lysozyme domains and domains destined for the cytoplasm, including the N4 virion RNA polymerase embedded within an IVP-D homolog. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Experimental study on acid mine drainage treatment using mine tailings of Xiangsi Valley, Tongling, China].

PubMed

Zhang, Nan; Chen, Tian-Hu; Zhou, Yue-Fei; Li, Shao-Jie; Jin, Jie; Wang, Yan-Ming

2012-04-01

Mine tailings in Xiangsi Valley, Tongling, China, is a typical skarn-type tailing with high contents of carbonates. This study designed dynamic leaching experiments to investigate the efficiency of this tailing under the acid mine drainage treatment. During 80 d trial period, the physical and chemical properties of influents were fixed and the effluents were monitored. After the trial, the speciation of Fe, Cu and Zn in solid was analyzed. The results showed that during the trial period, pH value maintained above 7.5. Moreover, the concentrations of Cu, Zn, Fe ions in effluents kept below 0.1, 0.4 and 1 mg x L(-1), respectively. In addition, the permeability coefficient of experimental column kept decreasing during the experimental period (from 0.23 cm x s(-1) to 0.10 cm x s(-1)). Five-step sequential extraction method was employed to study the distribution of elements at different depths. The results showed that Cu2+, Zn2+ were removed mainly through sorption and precipitation. This study indicates that Tongling skarn mine tailings have strong acid neutralization as well as heavy metal binding capacities. Therefore, the authors suggest that this mine tailing, which used to be waste, has a potential in AMD control and treatment.

Cell lineage tracing during Xenopus tail regeneration.

PubMed

Gargioli, Cesare; Slack, Jonathan M W

2004-06-01

The tail of the Xenopus tadpole will regenerate following amputation, and all three of the main axial structures - the spinal cord, the notochord and the segmented myotomes - are found in the regenerated tail. We have investigated the cellular origin of each of these three tissue types during regeneration. We produced Xenopus laevis embryos transgenic for the CMV (Simian Cytomegalovirus) promoter driving GFP (Green Fluorescent Protein) ubiquitously throughout the embryo. Single tissues were then specifically labelled by making grafts at the neurula stage from transgenic donors to unlabelled hosts. When the hosts have developed to tadpoles, they carry a region of the appropriate tissue labelled with GFP. These tails were amputated through the labelled region and the distribution of labelled cells in the regenerate was followed. We also labelled myofibres using the Cre-lox method. The results show that the spinal cord and the notochord regenerate from the same tissue type in the stump, with no labelling of other tissues. In the case of the muscle, we show that the myofibres of the regenerate arise from satellite cells and not from the pre-existing myofibres. This shows that metaplasia between differentiated cell types does not occur, and that the process of Xenopus tail regeneration is more akin to tissue renewal in mammals than to urodele tail regeneration.

In vivo analysis of polyadenylation in prokaryotes.

PubMed

Mohanty, Bijoy K; Kushner, Sidney R

2014-01-01

Polyadenylation at the 3' ends of mRNAs, tRNAs, rRNAs, and sRNAs plays important roles in RNA metabolism in both prokaryotes and eukaryotes. However, the nature of poly(A) tails in prokaryotes is distinct compared to their eukaryotic counterparts. Specifically, depending on the organism, eukaryotic poly(A) tails average between 50 and >200 nt and can easily be isolated by several techniques involving oligo(dT)-dependent cDNA amplification. In contrast, the bulk of the poly(A) tails present on prokaryotic transcripts is relatively short (<10 nt) and is difficult to characterize using similar techniques. This chapter describes methods that can circumvent these problems. For example, we discuss how to isolate total RNA and characterize its overall polyadenylation status employing a poly(A) sizing assay. Furthermore, we describe a technique involving RNase H treatment of total RNA followed by northern analysis in order to distinguish length of poly(A) tails on various types of transcripts. Finally, we outline a useful procedure to clone the poly(A) tails of specific transcripts using 5'-3' end-ligated RNA, which is independent of oligo(dT)-dependent cDNA amplification. These approaches are particularly helpful in analyzing transcripts with either short or long poly(A) tails both in prokaryotes and eukaryotes.

Structure of 1-alkyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide ionic liquids with linear, branched, and cyclic alkyl groups.

PubMed

Kashyap, Hemant K; Santos, Cherry S; Murthy, N Sanjeeva; Hettige, Jeevapani J; Kerr, Kijana; Ramati, Sharon; Gwon, JinHee; Gohdo, Masao; Lall-Ramnarine, Sharon I; Wishart, James F; Margulis, Claudio J; Castner, Edward W

2013-12-12

X-ray scattering and molecular dynamics simulations have been carried out to investigate structural differences and similarities in the condensed phase between pyrrolidinium-based ionic liquids paired with the bis(trifluoromethylsulfonyl)amide (NTf2(-)) anion where the cationic tail is linear, branched, or cyclic. This is important in light of the charge and polarity type alternations that have recently been shown to be present in the case of liquids with cations of moderately long linear tails. For this study, we have chosen to use the 1-alkyl-1-methylpyrrolidinium, Pyrr(1,n(+)) with n = 5 or 7, as systems with linear tails, 1-(2-ethylhexyl)-1-methylpyrrolidinium, Pyrr(1,EtHx(+)), as a system with a branched tail, and 1-(cyclohexylmethyl)-1-methylpyrrolidinium, Pyrr(1,ChxMe(+)), as a system with a cyclic tail. We put these results into context by comparing these data with recently published results for the Pyrr(1,n(+))/NTf2(-) ionic liquids with n = 4, 6, 8, and 10.1,2 General methods for interpreting the structure function S(q) in terms of q-dependent natural partitionings are described. This allows for an in-depth analysis of the scattering data based on molecular dynamics (MD) trajectories that highlight the effect of modifying the cationic tail.

Remote Sensing Extraction of Stopes and Tailings Ponds in AN Ultra-Low Iron Mining Area

NASA Astrophysics Data System (ADS)

Ma, B.; Chen, Y.; Li, X.; Wu, L.

2018-04-01

With the development of economy, global demand for steel has accelerated since 2000, and thus mining activities of iron ore have become intensive accordingly. An ultra-low-grade iron has been extracted by open-pit mining and processed massively since 2001 in Kuancheng County, Hebei Province. There are large-scale stopes and tailings ponds in this area. It is important to extract their spatial distribution information for environmental protection and disaster prevention. A remote sensing method of extracting stopes and tailings ponds is studied based on spectral characteristics by use of Landsat 8 OLI imagery and ground spectral data. The overall accuracy of extraction is 95.06 %. In addition, tailings ponds are distinguished from stopes based on thermal characteristics by use of temperature image. The results could provide decision support for environmental protection, disaster prevention, and ecological restoration in the ultra-low-grade iron ore mining area.

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.

Acetylcholinesterase activity in soleus muscle intrafusal and extrafusal fibres in tail suspended rats.

PubMed

Tang, Bin; Fan, Xiao-li; Wu, Su-di

2002-10-01

Objective. To explore the mechanisms involved in muscle atrophy and conversion of the fiber types induced by simulated weightlessness. Method. Weightlessness was simulated by tail suspension of female rats. Intrafusal and extrafusal fibers of soleus muscles in the rat were examined histochemically for their activity of acetylcholinesterase (AChE) and succinic dehydrogenase (SDH) in 7 d, 14 d, 21 d tail-suspended groups and control groups. Result. Staining for succinic dehydrogenase showed that simulated weightlessness caused obvious atrophy and change in fiber type composition in soleus muscle, with decrease of the proportion of type I fiber and increase of type II fiber. Acetylcholinesterase activities of intrafusal and extrafusal fibers were both decreased significantly after 21 d tail suspension. Conclusion. Simulated weightlessness could induce decrease of AChE activity in neuromuscular junctions, which might be linked with decrease in motor neuron activity.

Geochemical behavior and environmental risks related to the use of abandoned base-metal tailings as construction material in the upper-Moulouya district, Morocco.

PubMed

Argane, R; El Adnani, M; Benzaazoua, M; Bouzahzah, H; Khalil, A; Hakkou, R; Taha, Y

2016-01-01

In some developing countries, base-metal residues that were abandoned in tailing ponds or impoundments are increasingly used as construction material without any control, engineering basis, or environmental concern. This uncontrolled reuse of mine tailings may constitute a new form of pollution risks for humans and ecosystems through metal leaching. Therefore, the aim of the current study is to assess mine drainage, metal mobility, and geochemical behavior of two abandoned mine tailings commonly used in the upper-Moulouya region (eastern Morocco) as fine aggregates for mortar preparation. Their detailed physical, chemical, and mineralogical properties were subsequently evaluated in the context of developing appropriate alternative reuses to replace their conventional disposal and limit their weathering exposure. The obtained results showed that both tailings contain relatively high quantities of residual metals and metalloids with lead (ranging between 3610 and 5940 mg/kg) being the major pollutant. However, the mineralogical investigations revealed the presence of abundant neutralizing minerals and low sulfide content which influence mine drainage geochemistry and subsequently lower metals mobility. In fact, leachate analyses from weathering cell kinetic tests showed neutral conditions and low sulfide oxidation rates. According to these results, the tailings used as construction material in the upper-Moulouya region have very low generating potential of contaminated effluents and their reuse as aggregates may constitute a sustainable alternative method for efficient tailing management.

Quantitative Microbial Community Analysis of Three Different Sulfidic Mine Tailing Dumps Generating Acid Mine Drainage▿

PubMed Central

Kock, Dagmar; Schippers, Axel

2008-01-01

The microbial communities of three different sulfidic and acidic mine waste tailing dumps located in Botswana, Germany, and Sweden were quantitatively analyzed using quantitative real-time PCR (Q-PCR), fluorescence in situ hybridization (FISH), catalyzed reporter deposition-FISH (CARD-FISH), Sybr green II direct counting, and the most probable number (MPN) cultivation technique. Depth profiles of cell numbers showed that the compositions of the microbial communities are greatly different at the three sites and also strongly varied between zones of oxidized and unoxidized tailings. Maximum cell numbers of up to 109 cells g−1 dry weight were determined in the pyrite or pyrrhotite oxidation zones, whereas cell numbers in unoxidized tailings were significantly lower. Bacteria dominated over Archaea and Eukarya at all tailing sites. The acidophilic Fe(II)- and/or sulfur-oxidizing Acidithiobacillus spp. dominated over the acidophilic Fe(II)-oxidizing Leptospirillum spp. among the Bacteria at two sites. The two genera were equally abundant at the third site. The acidophilic Fe(II)- and sulfur-oxidizing Sulfobacillus spp. were generally less abundant. The acidophilic Fe(III)-reducing Acidiphilium spp. could be found at only one site. The neutrophilic Fe(III)-reducing Geobacteraceae as well as the dsrA gene of sulfate reducers were quantifiable at all three sites. FISH analysis provided reliable data only for tailing zones with high microbial activity, whereas CARD-FISH, Q-PCR, Sybr green II staining, and MPN were suitable methods for a quantitative microbial community analysis of tailings in general. PMID:18586975

Quantitative microbial community analysis of three different sulfidic mine tailing dumps generating acid mine drainage.

PubMed

Kock, Dagmar; Schippers, Axel

2008-08-01

The microbial communities of three different sulfidic and acidic mine waste tailing dumps located in Botswana, Germany, and Sweden were quantitatively analyzed using quantitative real-time PCR (Q-PCR), fluorescence in situ hybridization (FISH), catalyzed reporter deposition-FISH (CARD-FISH), Sybr green II direct counting, and the most probable number (MPN) cultivation technique. Depth profiles of cell numbers showed that the compositions of the microbial communities are greatly different at the three sites and also strongly varied between zones of oxidized and unoxidized tailings. Maximum cell numbers of up to 10(9) cells g(-1) dry weight were determined in the pyrite or pyrrhotite oxidation zones, whereas cell numbers in unoxidized tailings were significantly lower. Bacteria dominated over Archaea and Eukarya at all tailing sites. The acidophilic Fe(II)- and/or sulfur-oxidizing Acidithiobacillus spp. dominated over the acidophilic Fe(II)-oxidizing Leptospirillum spp. among the Bacteria at two sites. The two genera were equally abundant at the third site. The acidophilic Fe(II)- and sulfur-oxidizing Sulfobacillus spp. were generally less abundant. The acidophilic Fe(III)-reducing Acidiphilium spp. could be found at only one site. The neutrophilic Fe(III)-reducing Geobacteraceae as well as the dsrA gene of sulfate reducers were quantifiable at all three sites. FISH analysis provided reliable data only for tailing zones with high microbial activity, whereas CARD-FISH, Q-PCR, Sybr green II staining, and MPN were suitable methods for a quantitative microbial community analysis of tailings in general.

Mercury and gold concentrations of highly polluted environmental samples determined using prompt gamma-ray analysis and instrument neutron activation analysis

NASA Astrophysics Data System (ADS)

Osawa, Takahito; Hatsukawa, Yuichi; Appel, Peter W. U.; Matsue, Hideaki

2011-04-01

The authors have established a method of determining mercury and gold in severely polluted environmental samples using prompt gamma-ray analysis (PGA) and instrumental neutron activation analysis (INAA). Since large amounts of mercury are constantly being released into the environment by small-scale gold mining in many developing countries, the mercury concentration in tailings and water has to be determined to mitigate environmental pollution. Cold-vapor atomic absorption analysis, the most pervasive method of mercury analysis, is not suitable because tailings and water around mining facilities have extremely high mercury concentrations. On the other hand, PGA can determine high mercury concentrations in polluted samples as it has an appropriate level of sensitivity. Moreover, gold concentrations can be determined sequentially by using INAA after PGA. In conclusion, the analytical procedure established in this work using PGA and INAA is the best way to evaluate the degree of pollution and the tailing resource value. This method will significantly contribute to mitigating problems in the global environment.

A novel optimization algorithm for MIMO Hammerstein model identification under heavy-tailed noise.

PubMed

Jin, Qibing; Wang, Hehe; Su, Qixin; Jiang, Beiyan; Liu, Qie

2018-01-01

In this paper, we study the system identification of multi-input multi-output (MIMO) Hammerstein processes under the typical heavy-tailed noise. To the best of our knowledge, there is no general analytical method to solve this identification problem. Motivated by this, we propose a general identification method to solve this problem based on a Gaussian-Mixture Distribution intelligent optimization algorithm (GMDA). The nonlinear part of Hammerstein process is modeled by a Radial Basis Function (RBF) neural network, and the identification problem is converted to an optimization problem. To overcome the drawbacks of analytical identification method in the presence of heavy-tailed noise, a meta-heuristic optimization algorithm, Cuckoo search (CS) algorithm is used. To improve its performance for this identification problem, the Gaussian-mixture Distribution (GMD) and the GMD sequences are introduced to improve the performance of the standard CS algorithm. Numerical simulations for different MIMO Hammerstein models are carried out, and the simulation results verify the effectiveness of the proposed GMDA. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Validation of a computer code for analysis of subsonic aerodynamic performance of wings with flaps in combination with a canard or horizontal tail and an application to optimization

NASA Technical Reports Server (NTRS)

Carlson, Harry W.; Darden, Christine M.; Mann, Michael J.

1990-01-01

Extensive correlations of computer code results with experimental data are employed to illustrate the use of a linearized theory, attached flow method for the estimation and optimization of the longitudinal aerodynamic performance of wing-canard and wing-horizontal tail configurations which may employ simple hinged flap systems. Use of an attached flow method is based on the premise that high levels of aerodynamic efficiency require a flow that is as nearly attached as circumstances permit. The results indicate that linearized theory, attached flow, computer code methods (modified to include estimated attainable leading-edge thrust and an approximate representation of vortex forces) provide a rational basis for the estimation and optimization of aerodynamic performance at subsonic speeds below the drag rise Mach number. Generally, good prediction of aerodynamic performance, as measured by the suction parameter, can be expected for near optimum combinations of canard or horizontal tail incidence and leading- and trailing-edge flap deflections at a given lift coefficient (conditions which tend to produce a predominantly attached flow).

Alternative evaluation metrics for risk adjustment methods.

PubMed

Park, Sungchul; Basu, Anirban

2018-06-01

Risk adjustment is instituted to counter risk selection by accurately equating payments with expected expenditures. Traditional risk-adjustment methods are designed to estimate accurate payments at the group level. However, this generates residual risks at the individual level, especially for high-expenditure individuals, thereby inducing health plans to avoid those with high residual risks. To identify an optimal risk-adjustment method, we perform a comprehensive comparison of prediction accuracies at the group level, at the tail distributions, and at the individual level across 19 estimators: 9 parametric regression, 7 machine learning, and 3 distributional estimators. Using the 2013-2014 MarketScan database, we find that no one estimator performs best in all prediction accuracies. Generally, machine learning and distribution-based estimators achieve higher group-level prediction accuracy than parametric regression estimators. However, parametric regression estimators show higher tail distribution prediction accuracy and individual-level prediction accuracy, especially at the tails of the distribution. This suggests that there is a trade-off in selecting an appropriate risk-adjustment method between estimating accurate payments at the group level and lower residual risks at the individual level. Our results indicate that an optimal method cannot be determined solely on the basis of statistical metrics but rather needs to account for simulating plans' risk selective behaviors. Copyright © 2018 John Wiley & Sons, Ltd.

A protocol to correct for intra- and interspecific variation in tail hair growth to align isotope signatures of segmentally cut tail hair to a common time line

PubMed Central

Burnik Šturm, Martina; Pukazhenthi, Budhan; Reed, Dolores; Ganbaatar, Oyunsaikhan; Sušnik, Stane; Haymerle, Agnes; Voigt, Christian C; Kaczensky, Petra

2015-01-01

Rationale In recent years, segmental stable isotope analysis of hair has been a focus of research in animal dietary ecology and migration. To correctly assign tail hair segments to seasons or even Julian dates, information on tail hair growth rates is a key parameter, but is lacking for most species. Methods We (a) reviewed the literature on tail hair growth rates in mammals; b) made own measurements of three captive equid species; (c) measured δ2H, δ13C and δ15N values in sequentially cut tail hairs of three sympatric, free-ranging equids from the Mongolian Gobi, using isotope ratio mass spectrometry (IRMS); and (d) collected environmental background data on seasonal variation by measuring δ2H values in precipitation by IRMS and by compiling pasture productivity measured by remote sensing via the normalized difference vegetation index (NDVI). Results Tail hair growth rates showed significant inter- and intra-specific variation making temporal alignment problematic. In the Mongolian Gobi, high seasonal variation of δ2H values in precipitation results in winter lows and summer highs of δ2H values of available water sources. In water-dependent equids, this seasonality is reflected in the isotope signatures of sequentially cut tails hairs. Conclusions In regions which are subject to strong seasonal patterns we suggest identifying key isotopes which show strong seasonal variation in the environment and can be expected to be reflected in the animal tissue. The known interval between the maxima and minima of these isotope values can then be used to correctly temporally align the segmental stable isotope signature for each individual animal. © 2015 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd. PMID:26044272

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.

Microbial communities in low permeability, high pH uranium mine tailings: characterization and potential effects.

PubMed

Bondici, V F; Lawrence, J R; Khan, N H; Hill, J E; Yergeau, E; Wolfaardt, G M; Warner, J; Korber, D R

2013-06-01

To describe the diversity and metabolic potential of microbial communities in uranium mine tailings characterized by high pH, high metal concentration and low permeability. To assess microbial diversity and their potential to influence the geochemistry of uranium mine tailings using aerobic and anaerobic culture-based methods, in conjunction with next generation sequencing and clone library sequencing targeting two universal bacterial markers (the 16S rRNA and cpn60 genes). Growth assays revealed that 69% of the 59 distinct culturable isolates evaluated were multiple-metal resistant, with 15% exhibiting dual-metal hypertolerance. There was a moderately positive correlation coefficient (R = 0·43, P < 0·05) between multiple-metal resistance of the isolates and their enzyme expression profile. Of the isolates tested, 17 reduced amorphous iron, 22 reduced molybdate and seven oxidized arsenite. Based on next generation sequencing, tailings depth was shown to influence bacterial community composition, with the difference in the microbial diversity of the upper (0-20 m) and middle (20-40 m) tailings zones being highly significant (P < 0·01) from the lower zone (40-60 m) and the difference in diversity of the upper and middle tailings zone being significant (P < 0·05). Phylotypes closely related to well-known sulfate-reducing and iron-reducing bacteria were identified with low abundance, yet relatively high diversity. The presence of a population of metabolically-diverse, metal-resistant micro-organisms within the tailings environment, along with their demonstrated capacity for transforming metal elements, suggests that these organisms have the potential to influence the long-term geochemistry of the tailings. This study is the first investigation of the diversity and functional potential of micro-organisms present in low permeability, high pH uranium mine tailings. © 2013 The Society for Applied Microbiology.

Necrosis of the tail of pancreas following proximal splenic artery embolization.

PubMed

Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

2016-05-13

The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

Surficial weathering of iron sulfide mine tailings under semi-arid climate.

PubMed

Hayes, Sarah M; Root, Robert A; Perdrial, Nicolas; Maier, Raina; Chorover, Jon

2014-09-15

Mine wastes introduce anthropogenic weathering profiles to the critical zone that often remain unvegetated for decades after mining cessation. As such, they are vulnerable to wind and water dispersion of particulate matter to adjacent ecosystems and residential communities. In sulfide-rich ore tailings, propagation to depth of the oxidative weathering front controls the depth-variation in speciation of major and trace elements. Despite the prevalence of surficial mine waste deposits in arid regions of the globe, few prior studies have been conducted to resolve the near-surface profile of sulfide ore tailings weathered under semi-arid climate. We investigated relations between gossan oxidative reaction-front propagation and the molecular speciation of iron and sulfur in tailings subjected to weathering under semi-arid climate at an EPA Superfund Site in semi-arid central Arizona (USA). Here we report a multi-method data set combining wet chemical and synchrotron-based X-ray diffraction (XRD) and X-ray absorption near-edge spectroscopy (XANES) methods to resolve the tight coupling of iron (Fe) and sulfur (S) geochemical changes in the top 2 m of tailings. Despite nearly invariant Fe and S concentration with depth (130-140 and 100-120 g kg -1 , respectively), a sharp redox gradient and distinct morphological change was observed within the top 0.5 m, associated with a progressive oxidative alteration of ferrous sulfides to (oxyhydr)oxides and (hydroxy)sulfates. Transformation is nearly complete in surficial samples. Trends in molecular-scale alteration were co-located with a decrease in pH from 7.3 to 2.3, and shifts in Fe and S lability as measured via chemical extraction. Initial weathering products, ferrihydrite and gypsum, transform to schwertmannite, then jarosite-group minerals with an accompanying decrease in pH. Interestingly, thermodynamically stable phases such as goethite and hematite were not detected in any samples, but ferrihydrite was observed even in the lowest pH samples, indicating its metastable persistence in these semiarid tailings. The resulting sharp geochemical speciation gradients in close proximity to the tailings surface have important implications for plant colonization, as well as mobility and bioavailability of co-associated toxic metal(loid)s.

Surficial weathering of iron sulfide mine tailings under semi-arid climate

PubMed Central

Hayes, Sarah M.; Root, Robert A.; Perdrial, Nicolas; Maier, Raina; Chorover, Jon

2014-01-01

Mine wastes introduce anthropogenic weathering profiles to the critical zone that often remain unvegetated for decades after mining cessation. As such, they are vulnerable to wind and water dispersion of particulate matter to adjacent ecosystems and residential communities. In sulfide-rich ore tailings, propagation to depth of the oxidative weathering front controls the depth-variation in speciation of major and trace elements. Despite the prevalence of surficial mine waste deposits in arid regions of the globe, few prior studies have been conducted to resolve the near-surface profile of sulfide ore tailings weathered under semi-arid climate. We investigated relations between gossan oxidative reaction-front propagation and the molecular speciation of iron and sulfur in tailings subjected to weathering under semi-arid climate at an EPA Superfund Site in semi-arid central Arizona (USA). Here we report a multi-method data set combining wet chemical and synchrotron-based X-ray diffraction (XRD) and X-ray absorption near-edge spectroscopy (XANES) methods to resolve the tight coupling of iron (Fe) and sulfur (S) geochemical changes in the top 2 m of tailings. Despite nearly invariant Fe and S concentration with depth (130–140 and 100–120 g kg−1, respectively), a sharp redox gradient and distinct morphological change was observed within the top 0.5 m, associated with a progressive oxidative alteration of ferrous sulfides to (oxyhydr)oxides and (hydroxy)sulfates. Transformation is nearly complete in surficial samples. Trends in molecular-scale alteration were co-located with a decrease in pH from 7.3 to 2.3, and shifts in Fe and S lability as measured via chemical extraction. Initial weathering products, ferrihydrite and gypsum, transform to schwertmannite, then jarosite-group minerals with an accompanying decrease in pH. Interestingly, thermodynamically stable phases such as goethite and hematite were not detected in any samples, but ferrihydrite was observed even in the lowest pH samples, indicating its metastable persistence in these semiarid tailings. The resulting sharp geochemical speciation gradients in close proximity to the tailings surface have important implications for plant colonization, as well as mobility and bioavailability of co-associated toxic metal(loid)s. PMID:25197102

Surficial weathering of iron sulfide mine tailings under semi-arid climate

NASA Astrophysics Data System (ADS)

Hayes, Sarah M.; Root, Robert A.; Perdrial, Nicolas; Maier, Raina M.; Chorover, Jon

2014-09-01

Mine wastes introduce anthropogenic weathering profiles to the critical zone that often remain unvegetated for decades after mining cessation. As such, they are vulnerable to wind and water dispersion of particulate matter to adjacent ecosystems and residential communities. In sulfide-rich ore tailings, propagation to depth of the oxidative weathering front controls the depth-variation in speciation of major and trace elements. Despite the prevalence of surficial mine waste deposits in arid regions of the globe, few prior studies have been conducted to resolve the near-surface profile of sulfide ore tailings weathered under semi-arid climate. We investigated relations between gossan oxidative reaction-front propagation and the molecular speciation of iron and sulfur in tailings subjected to weathering in a semi-arid climate at an EPA Superfund Site in central Arizona (USA). Here we report a multi-method data set combining wet chemical and synchrotron-based X-ray diffraction (XRD) and X-ray absorption near-edge spectroscopy (XANES) methods to resolve the tight coupling of iron (Fe) and sulfur (S) geochemical changes in the top 2 m of tailings. Despite nearly invariant Fe and S concentration with depth (130-140 and 100-120 g kg-1, respectively), a sharp redox gradient and distinct morphological change was observed within the top 0.5 m, associated with a progressive oxidative alteration of ferrous sulfides to (oxyhydr)oxides and (hydroxy)sulfates. Transformation is nearly complete in surficial samples. Trends in molecular-scale alteration were co-located with a decrease in pH from 7.3 to 2.3, and shifts in Fe and S lability as measured via chemical extraction. Initial weathering products, ferrihydrite and gypsum, transform to schwertmannite, then jarosite-group minerals with an accompanying decrease in pH. Interestingly, thermodynamically stable phases such as goethite and hematite were not detected in any samples, but ferrihydrite was observed even in samples with the lowest pH, indicating its metastable persistence in these semiarid tailings. The resulting sharp geochemical speciation gradients in close proximity to the tailings surface have important implications for plant colonization, as well as mobility and bioavailability of co-associated toxic metal(loid)s.

Enigmatic human tails: A review of their history, embryology, classification, and clinical manifestations.

PubMed

Tubbs, R Shane; Malefant, Jason; Loukas, Marios; Jerry Oakes, W; Oskouian, Rod J; Fries, Fabian N

2016-05-01

The presence of a human tail is a rare and intriguing phenomenon. While cases have been reported in the literature, confusion remains with respect to the proper classification, definition, and treatment methods. We review the literature concerning this anatomical derailment. We also consider the importance of excluding underlying congenital anomalies in these patients to prevent neurological deficits and other abnormal manifestations. © 2016 Wiley Periodicals, Inc.

An improved algorithm for balanced POD through an analytic treatment of impulse response tails

NASA Astrophysics Data System (ADS)

Tu, Jonathan H.; Rowley, Clarence W.

2012-06-01

We present a modification of the balanced proper orthogonal decomposition (balanced POD) algorithm for systems with simple impulse response tails. In this new method, we use dynamic mode decomposition (DMD) to estimate the slowly decaying eigenvectors that dominate the long-time behavior of the direct and adjoint impulse responses. This is done using a new, low-memory variant of the DMD algorithm, appropriate for large datasets. We then formulate analytic expressions for the contribution of these eigenvectors to the controllability and observability Gramians. These contributions can be accounted for in the balanced POD algorithm by simply appending the impulse response snapshot matrices (direct and adjoint, respectively) with particular linear combinations of the slow eigenvectors. Aside from these additions to the snapshot matrices, the algorithm remains unchanged. By treating the tails analytically, we eliminate the need to run long impulse response simulations, lowering storage requirements and speeding up ensuing computations. To demonstrate its effectiveness, we apply this method to two examples: the linearized, complex Ginzburg-Landau equation, and the two-dimensional fluid flow past a cylinder. As expected, reduced-order models computed using an analytic tail match or exceed the accuracy of those computed using the standard balanced POD procedure, at a fraction of the cost.

Factors affecting the transformation of a pyritic tailing: scaled-up column tests.

PubMed

García, C; Ballester, A; González, F; Blázquez, M L

2005-02-14

Two different methods for predicting the quality of the water draining from a pyritic tailing are compared; for this, a static test (ABA test) and a kinetic test in large columns were chosen. The different results obtained in the two experimental set-ups show the necessity of being careful in selecting both the adequate predictive method and the conclusions and extrapolations derived from them. The tailing chosen for the weathering tests (previously tested in shake flasks and in small weathering columns) was a pyritic residue produced in a flotation plant of complex polymetallic sulphides (Huelva, Spain). The ABA test was a modification of the conventional ABA test reported in bibliography. The modification consisted in the soft conditions employed in the digestion phase. For column tests, two identical methacrylate columns (150 cm high and 15 cm diameter) were used to study the chemical and microbiological processes controlling the leaching of pyrite. The results obtained in the two tests were very different. The static test predicted a strong potential acidity for the tailing. On the contrary, pH value in the effluents draining from the columns reached values of only 5 units, being the concentration of metals (<600 mg/L) and sulphate ions (<17,000 mg/L) very small and far from the values of a typical acid mine drainage. In consequence, the static test may oversize the potential acidity of the tailing; whereas large columns may be saturated in water, displacing the oxygen and inhibiting the microbial activity necessary to catalyse mineral oxidation.

Global morphological analysis of marine viruses shows minimal regional variation and dominance of non-tailed viruses

PubMed Central

Brum, Jennifer R; Schenck, Ryan O; Sullivan, Matthew B

2013-01-01

Viruses influence oceanic ecosystems by causing mortality of microorganisms, altering nutrient and organic matter flux via lysis and auxiliary metabolic gene expression and changing the trajectory of microbial evolution through horizontal gene transfer. Limited host range and differing genetic potential of individual virus types mean that investigations into the types of viruses that exist in the ocean and their spatial distribution throughout the world's oceans are critical to understanding the global impacts of marine viruses. Here we evaluate viral morphological characteristics (morphotype, capsid diameter and tail length) using a quantitative transmission electron microscopy (qTEM) method across six of the world's oceans and seas sampled through the Tara Oceans Expedition. Extensive experimental validation of the qTEM method shows that neither sample preservation nor preparation significantly alters natural viral morphological characteristics. The global sampling analysis demonstrated that morphological characteristics did not vary consistently with depth (surface versus deep chlorophyll maximum waters) or oceanic region. Instead, temperature, salinity and oxygen concentration, but not chlorophyll a concentration, were more explanatory in evaluating differences in viral assemblage morphological characteristics. Surprisingly, given that the majority of cultivated bacterial viruses are tailed, non-tailed viruses appear to numerically dominate the upper oceans as they comprised 51–92% of the viral particles observed. Together, these results document global marine viral morphological characteristics, show that their minimal variability is more explained by environmental conditions than geography and suggest that non-tailed viruses might represent the most ecologically important targets for future research. PMID:23635867

Comparison of Two Methods Used to Model Shape Parameters of Pareto Distributions

USGS Publications Warehouse

Liu, C.; Charpentier, R.R.; Su, J.

2011-01-01

Two methods are compared for estimating the shape parameters of Pareto field-size (or pool-size) distributions for petroleum resource assessment. Both methods assume mature exploration in which most of the larger fields have been discovered. Both methods use the sizes of larger discovered fields to estimate the numbers and sizes of smaller fields: (1) the tail-truncated method uses a plot of field size versus size rank, and (2) the log-geometric method uses data binned in field-size classes and the ratios of adjacent bin counts. Simulation experiments were conducted using discovered oil and gas pool-size distributions from four petroleum systems in Alberta, Canada and using Pareto distributions generated by Monte Carlo simulation. The estimates of the shape parameters of the Pareto distributions, calculated by both the tail-truncated and log-geometric methods, generally stabilize where discovered pool numbers are greater than 100. However, with fewer than 100 discoveries, these estimates can vary greatly with each new discovery. The estimated shape parameters of the tail-truncated method are more stable and larger than those of the log-geometric method where the number of discovered pools is more than 100. Both methods, however, tend to underestimate the shape parameter. Monte Carlo simulation was also used to create sequences of discovered pool sizes by sampling from a Pareto distribution with a discovery process model using a defined exploration efficiency (in order to show how biased the sampling was in favor of larger fields being discovered first). A higher (more biased) exploration efficiency gives better estimates of the Pareto shape parameters. ?? 2011 International Association for Mathematical Geosciences.

Next-Generation Sequencing Assessment of Eukaryotic Diversity in Oil Sands Tailings Ponds Sediments and Surface Water.

PubMed

Aguilar, Maria; Richardson, Elisabeth; Tan, BoonFei; Walker, Giselle; Dunfield, Peter F; Bass, David; Nesbø, Camilla; Foght, Julia; Dacks, Joel B

2016-11-01

Tailings ponds in the Athabasca oil sands (Canada) contain fluid wastes, generated by the extraction of bitumen from oil sands ores. Although the autochthonous prokaryotic communities have been relatively well characterized, almost nothing is known about microbial eukaryotes living in the anoxic soft sediments of tailings ponds or in the thin oxic layer of water that covers them. We carried out the first next-generation sequencing study of microbial eukaryotic diversity in oil sands tailings ponds. In metagenomes prepared from tailings sediment and surface water, we detected very low numbers of sequences encoding eukaryotic small subunit ribosomal RNA representing seven major taxonomic groups of protists. We also produced and analysed three amplicon-based 18S rRNA libraries prepared from sediment samples. These revealed a more diverse set of taxa, 169 different OTUs encompassing up to eleven higher order groups of eukaryotes, according to detailed classification using homology searching and phylogenetic methods. The 10 most abundant OTUs accounted for > 90% of the total of reads, vs. large numbers of rare OTUs (< 1% abundance). Despite the anoxic and hydrocarbon-enriched nature of the environment, the tailings ponds harbour complex communities of microbial eukaryotes indicating that these organisms should be taken into account when studying the microbiology of the oil sands. © 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists.

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.

An Investigation of the Elements which Contribute to Statical and Dynamical Stability, and of the Effects of Variation in Those Elements

NASA Technical Reports Server (NTRS)

Klemin, Alexander; Warner, Edward P; Denkinger, George M

1918-01-01

Part 1 gives details of models tested and methods of testing of the Eiffel 36 wing alone and the JN2 aircraft. Characteristics and performance curves for standard JN are included. Part 2 presents a statistical analysis of the following: lift and drag contributed by body and chassis tested without wings; lift and drag contributed by tail, tested without wings; the effect on lift and drift of interference between the wings of a biplane combination; lift and drag contributed by the addition of body, chassis, and tail to a biplane combination; total parasite resistance; effect of varying size of tail, keeping angle of setting constant; effect of varying length of body and size of tail at the same time, keeping constant moment of tail surface about the center of gravity; forces on the tail and the effects of downwash; effect of size and setting of tail on statical longitudinal stability effects of length of body on stability; the effects of the various elements of an airplane on longitudinal stability and the placing of the force vectors. Part 3 presents the fundamental principals of dynamical stability; computations of resistance derivatives; solution of the stability equation; dynamical stability of the Curtiss JN2; tabulation of resistance derivatives; discussion of the resistance derivatives; formation and solution of stability equations; physical conceptions of the resistance derivatives; elements contributing to damping and an investigation of low speed conditions. Part 4 includes a summary of the results of the statistical investigation and a summary of the results for dynamic stability.

Spectral induced polarization (SIP) response of mine tailings

NASA Astrophysics Data System (ADS)

Placencia-Gómez, Edmundo; Parviainen, Annika; Slater, Lee; Leveinen, Jussi

2015-02-01

Mine tailings impoundments are a source of leachates known as acid mine drainage (AMD) which can pose a contamination risk for surrounding surface and groundwater. Methodologies which can help management of this environmental issue are needed. We carried out a laboratory study of the spectral induced polarization (SIP) response of tailings from the Haveri Au-Cu mine, SW Finland. The primary objectives were, (1) to determine possible correlations between SIP parameters and textural properties associated with oxidative-weathering mechanisms, mineralogical composition and metallic content, and (2) to evaluate the effects of the pore water chemistry on SIP parameters associated with redox-inactive and redox-active electrolytes varying in molar concentration, conductivity and pH. The Haveri tailings exhibit well defined relaxation spectra between 100 and 10,000 Hz. The relaxation magnitudes are governed by the in-situ oxidative-weathering conditions on sulphide mineral surfaces contained in the tailings, and decrease with the oxidation degree. The oxidation-driven textural variation in the tailings results in changes to the frequency peak of the phase angle, the imaginary conductivity and chargeability, when plotted versus the pore water conductivity. In contrast, the real and the formation electrical conductivity components show a single linear dependence on the pore water conductivity. The increase of the pore water conductivity (dominated by the increase of ions concentration in solution) along with a transition to acidic conditions shifts the polarization peak towards higher frequencies. These findings show the unique sensitivity of the SIP method to potentially discriminate AMD discharges from reactive oxidation zones in tailings, suggesting a significant advantage for monitoring threatened aquifers.

Application of an integrated biomarker response index to assess ground water contamination in the vicinity of a rare earth mine tailings site.

PubMed

Si, Wantong; He, Xiaoying; Li, Ailing; Liu, Li; Li, Jisheng; Gong, Donghui; Liu, Juan; Liu, Jumei; Shen, Weishou; Zhang, Xuefeng

2016-09-01

We utilized a multi-biomarker approach (Integrated Biomarker Response version 2, IBRv2) to investigate the scope and dispersion of groundwater contamination surrounding a rare earth mine tailings impoundment. Parameters of SD rat included in our IBRv2 analyses were glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase activities, total anti-oxidative capacity, chromosome aberration, and micronucleus formation. The concentration of 20 pollutants including Cl(-), SO4 (2-), Na(+), K(+), Mg(2+), Ca(2+), TH, CODMn, As, Se, TDS, Be, Mn, Co, Ni, Cu, Zn, Mo, Cd, and Pb in the groundwater were also analyzed. The results of this study indicated that groundwater polluted by tailings impoundment leakage exhibited significant ecotoxicological effects. The selected biomarkers responded sensitively to groundwater pollution. Analyses showed a significant relationship between IBRv2 values and the Nemerow composite index. IBRv2 could serve as a sensitive ecotoxicological diagnosis method for assessing groundwater contamination in the vicinity of rare earth mine tailings. According to the trend of IBRv2 value and Nemerow composite index, the maximum diffusion distance of groundwater pollutants from rare earth mine tailings was approximately 5.7 km.

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.

Response of hatchling Komodo Dragons (Varanus komodoensis) at Denver Zoo to visual and chemical cues arising from prey.

PubMed

Chiszar, David; Krauss, Susan; Shipley, Bryon; Trout, Tim; Smith, Hobart M

2009-01-01

Five hatchling Komodo Dragons (Varanus komodoensis) at Denver Zoo were observed in two experiments that studied the effects of visual and chemical cues arising from prey. Rate of tongue flicking was recorded in Experiment 1, and amount of time the lizards spent interacting with stimuli was recorded in Experiment 2. Our hypothesis was that young V. komodoensis would be more dependent upon vision than chemoreception, especially when dealing with live, moving, prey. Although visual cues, including prey motion, had a significant effect, chemical cues had a far stronger effect. Implications of this falsification of our initial hypothesis are discussed.

Pesticide Biomarker Project

EPA Pesticide Factsheets

Uploaded datasets are detailed exposure information (chemical concentrations and water quality parameters) for exposures conducted in a flow through diluter system with larval Pimephales promelas to four different pyrethroid pesticides. The GEO submission URL links to the NCBI GEO database and contains gene expression data from whole larvae exposed to different concentrations of the pyrethroids across multiple experiments.This dataset is associated with the following publication:Biales, A., M. Kostich, A. Batt, M. See, R. Flick, D. Gordon, J. Lazorchak, and D. Bencic. Initial Development of a Multigene Omics-Based Exposure Biomarker for Pyrethroid Pesticides. CRITICAL REVIEWS IN ENVIRONMENTAL SCIENCE AND TECHNOLOGY. CRC Press LLC, Boca Raton, FL, USA, 179(0): 27-35, (2016).

Radial expansion of the tail current disruption during substorms - A new approach to the substorm onset region

NASA Technical Reports Server (NTRS)

Ohtani, S.; Kokubun, S.; Russell, C. T.

1992-01-01

A new method is used to examine the radial expansion of the tail current disruption and the substorm onset region. The expansion of the disruption region is specified by examining the time sequence (phase relationship) between the north-south component and the sun-earth component. This method is tested by applying it to the March 6, 1979, event. The phase relationship indicates that the current disruption started on the earthward side of the spacecraft, and expanded tailward past the spacecraft. The method was used for 13 events selected from the ISEE magnetometer data. The results indicate that the current disruption usually starts in the near-earth magnetotail and often within 15 RE from the earth.

Aerodynamic characteristics of cruciform missiles at high angles of attack

NASA Technical Reports Server (NTRS)

Lesieutre, Daniel J.; Mendenhall, Michael R.; Nazario, Susana M.; Hemsch, Michael J.

1987-01-01

An aerodynamic prediction method for missile aerodynamic performance and preliminary design has been developed to utilize a newly available systematic fin data base and an improved equivalent angle of attack methodology. The method predicts total aerodynamic loads and individual fin forces and moments for body-tail (wing-body) and canard-body-tail configurations with cruciform fin arrangements. The data base and the prediction method are valid for angles of attack up to 45 deg, arbitrary roll angles, fin deflection angles between -40 deg and 40 deg, Mach numbers between 0.6 and 4.5, and fin aspect ratios between 0.25 and 4.0. The equivalent angle of attack concept is employed to include the effects of vorticity and geometric scaling.

The calculation of lateral stability with free controls

NASA Technical Reports Server (NTRS)

Mathias, Gotthold

1934-01-01

The discussion of the structural methods for obtaining lateral stability discloses the remarkable influence of the constant fuselage and wing proportions to the yawing moments. For the effectiveness of modifications in vertical tail surfaces and tail length, these quotas - little observed heretofore, in this connection - are decisive. This also applies to the amount of dihedral of the wing with regard to the roll stability of the complete wing already existing without angle of the dihedral.

Aircraft directional stability and vertical tail design: A review of semi-empirical methods

NASA Astrophysics Data System (ADS)

Ciliberti, Danilo; Della Vecchia, Pierluigi; Nicolosi, Fabrizio; De Marco, Agostino

2017-11-01

Aircraft directional stability and control are related to vertical tail design. The safety, performance, and flight qualities of an aircraft also depend on a correct empennage sizing. Specifically, the vertical tail is responsible for the aircraft yaw stability and control. If these characteristics are not well balanced, the entire aircraft design may fail. Stability and control are often evaluated, especially in the preliminary design phase, with semi-empirical methods, which are based on the results of experimental investigations performed in the past decades, and occasionally are merged with data provided by theoretical assumptions. This paper reviews the standard semi-empirical methods usually applied in the estimation of airplane directional stability derivatives in preliminary design, highlighting the advantages and drawbacks of these approaches that were developed from wind tunnel tests performed mainly on fighter airplane configurations of the first decades of the past century, and discussing their applicability on current transport aircraft configurations. Recent investigations made by the authors have shown the limit of these methods, proving the existence of aerodynamic interference effects in sideslip conditions which are not adequately considered in classical formulations. The article continues with a concise review of the numerical methods for aerodynamics and their applicability in aircraft design, highlighting how Reynolds-Averaged Navier-Stokes (RANS) solvers are well-suited to attain reliable results in attached flow conditions, with reasonable computational times. From the results of RANS simulations on a modular model of a representative regional turboprop airplane layout, the authors have developed a modern method to evaluate the vertical tail and fuselage contributions to aircraft directional stability. The investigation on the modular model has permitted an effective analysis of the aerodynamic interference effects by moving, changing, and expanding the available airplane components. Wind tunnel tests over a wide range of airplane configurations have been used to validate the numerical approach. The comparison between the proposed method and the standard semi-empirical methods available in literature proves the reliability of the innovative approach, according to the available experimental data collected in the wind tunnel test campaign.

Submarine and deep-sea mine tailing placements: A review of current practices, environmental issues, natural analogs and knowledge gaps in Norway and internationally.

PubMed

Ramirez-Llodra, Eva; Trannum, Hilde C; Evenset, Anita; Levin, Lisa A; Andersson, Malin; Finne, Tor Erik; Hilario, Ana; Flem, Belinda; Christensen, Guttorm; Schaanning, Morten; Vanreusel, Ann

2015-08-15

The mining sector is growing in parallel with societal demands for minerals. One of the most important environmental issues and economic burdens of industrial mining on land is the safe storage of the vast amounts of waste produced. Traditionally, tailings have been stored in land dams, but the lack of land availability, potential risk of dam failure and topography in coastal areas in certain countries results in increasing disposal of tailings into marine systems. This review describes the different submarine tailing disposal methods used in the world in general and in Norway in particular, their impact on the environment (e.g. hyper-sedimentation, toxicity, processes related to changes in grain shape and size, turbidity), current legislation and need for future research. Understanding these impacts on the habitat and biota is essential to assess potential ecosystem changes and to develop best available techniques and robust management plans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pareto-Lognormal Modeling of Known and Unknown Metal Resources. II. Method Refinement and Further Applications

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

Agterberg, Frits, E-mail: agterber@nrcan.gc.ca

Pareto-lognormal modeling of worldwide metal deposit size–frequency distributions was proposed in an earlier paper (Agterberg in Nat Resour 26:3–20, 2017). In the current paper, the approach is applied to four metals (Cu, Zn, Au and Ag) and a number of model improvements are described and illustrated in detail for copper and gold. The new approach has become possible because of the very large inventory of worldwide metal deposit data recently published by Patiño Douce (Nat Resour 25:97–124, 2016c). Worldwide metal deposits for Cu, Zn and Ag follow basic lognormal size–frequency distributions that form straight lines on lognormal Q–Q plots. Aumore » deposits show a departure from the straight-line model in the vicinity of their median size. Both largest and smallest deposits for the four metals taken as examples exhibit hyperbolic size–frequency relations and their Pareto coefficients are determined by fitting straight lines on log rank–log size plots. As originally pointed out by Patiño Douce (Nat Resour Res 25:365–387, 2016d), the upper Pareto tail cannot be distinguished clearly from the tail of what would be a secondary lognormal distribution. The method previously used in Agterberg (2017) for fitting the bridge function separating the largest deposit size–frequency Pareto tail from the basic lognormal is significantly improved in this paper. A new method is presented for estimating the approximate deposit size value at which the upper tail Pareto comes into effect. Although a theoretical explanation of the proposed Pareto-lognormal distribution model is not a required condition for its applicability, it is shown that existing double Pareto-lognormal models based on Brownian motion generalizations of the multiplicative central limit theorem are not applicable to worldwide metal deposits. Neither are various upper tail frequency amplification models in their present form. Although a physicochemical explanation remains possible, it is argued that preferential mining of the largest and smallest orebodies can have economic historical reasons. The size–frequency distribution of uranium can be regarded as lognormal without Pareto tails. At the end of the paper, it is shown that original copper deposit size data can be used for forward projection of discovery trends toward the end of this century.« less

Reducing Mouse Anxiety during Handling: Effect of Experience with Handling Tunnels

PubMed Central

Gouveia, Kelly; Hurst, Jane L.

2013-01-01

Handling stress is a well-recognised source of variation in animal studies that can also compromise the welfare of research animals. To reduce background variation and maximise welfare, methods that minimise handling stress should be developed and used wherever possible. Recent evidence has shown that handling mice by a familiar tunnel that is present in their home cage can minimise anxiety compared with standard tail handling. As yet, it is unclear whether a tunnel is required in each home cage to improve response to handling. We investigated the influence of prior experience with home tunnels among two common strains of laboratory mice: ICR(CD-1) and C57BL/6. We compared willingness to approach the handler and anxiety in an elevated plus maze test among mice picked up by the tail, by a home cage tunnel or by an external tunnel shared between cages. Willingness to interact with the handler was much greater for mice handled by a tunnel, even when this was unfamiliar, compared to mice picked up by the tail. Once habituated to handling, C57BL/6 mice were most interactive towards a familiar home tunnel, whereas the ICR strain showed strong interaction with all tunnel handling regardless of any experience of a home cage tunnel. Mice handled by a home cage or external tunnel showed less anxiety in an elevated plus maze than those picked up by the tail. This study shows that using a tunnel for routine handling reduces anxiety among mice compared to tail handling regardless of prior familiarity with tunnels. However, as home cage tunnels can further improve response to handling in some mice, we recommend that mice are handled with a tunnel provided in their home cage where possible as a simple practical method to minimise handling stress. PMID:23840458

Reducing mouse anxiety during handling: effect of experience with handling tunnels.

PubMed

Gouveia, Kelly; Hurst, Jane L

2013-01-01

Handling stress is a well-recognised source of variation in animal studies that can also compromise the welfare of research animals. To reduce background variation and maximise welfare, methods that minimise handling stress should be developed and used wherever possible. Recent evidence has shown that handling mice by a familiar tunnel that is present in their home cage can minimise anxiety compared with standard tail handling. As yet, it is unclear whether a tunnel is required in each home cage to improve response to handling. We investigated the influence of prior experience with home tunnels among two common strains of laboratory mice: ICR(CD-1) and C57BL/6. We compared willingness to approach the handler and anxiety in an elevated plus maze test among mice picked up by the tail, by a home cage tunnel or by an external tunnel shared between cages. Willingness to interact with the handler was much greater for mice handled by a tunnel, even when this was unfamiliar, compared to mice picked up by the tail. Once habituated to handling, C57BL/6 mice were most interactive towards a familiar home tunnel, whereas the ICR strain showed strong interaction with all tunnel handling regardless of any experience of a home cage tunnel. Mice handled by a home cage or external tunnel showed less anxiety in an elevated plus maze than those picked up by the tail. This study shows that using a tunnel for routine handling reduces anxiety among mice compared to tail handling regardless of prior familiarity with tunnels. However, as home cage tunnels can further improve response to handling in some mice, we recommend that mice are handled with a tunnel provided in their home cage where possible as a simple practical method to minimise handling stress.

The effect of laparotomy on hydroxyl radicals, singlet oxygen and antioxidants measured by EPR method in the tails of rats.

PubMed

Fricova, Jitka; Stopka, Pavel; Krizova, Jana; Yamamotova, Anna; Rokyta, Richard

2009-01-01

The aim of the study was to demonstrate that direct measurement of hydroxyl radicals and singlet oxygen in the tail of living rats is possible. The basic level of hydroxyl radicals and singlet oxygen were measured and the effects of antioxidants on their levels were studied in the tail of living anaesthetized rats after acute postoperative pain. Laparotomy was performed as the source of acute abdominal pain. After closure of the abdominal cavity, the animals began to awaken within 30-60 minutes. They were left to recover for 2-3 hours; then they were reanesthetized and the effect of antioxidants was measured on the numbers of hydroxyl radicals and singlet oxygen via blood in the tail. The laparotomy was preformed under general anesthesia (Xylazin and Ketamin) using Wistar rats. After recovery and several hours of consciousness they were reanaesthetized and free radicals and singlet oxygen were measured. An antioxidant mixture (vitamins A, C, D and Selenium) was administered intramuscularly prior to the laparotomy. All measurements were done on the tail of anaesthetized animals. In this particular article, the effect of antioxidants is only reported for hydroxyl radicals. After laparotomy, which represented both somatic and visceral pain, hydroxyl radicals and singlet oxygen were increased. Antioxidant application prior to laparotomy decreased the numbers of hydroxyl radicals. Results are in agreement with our previous finding regarding the increase in hydroxyl free radicals and singlet oxygen following nociceptive stimulation, in this case a combination of both somatic and visceral pain. The administered antioxidants mitigated the increase. This is further confirmation that direct measurement of free radicals and singlet oxygen represents a very useful method for the biochemical evaluation of pain and nociception.

Changes in zinc speciation with mine tailings acidification in a semi-arid weathering environment

PubMed Central

Hayes, Sarah M.; O’Day, Peggy A.; Webb, Sam M.; Maier, Raina M.; Chorover, Jon

2011-01-01

High concentrations of residual metal contaminants in mine tailings can be transported easily by wind and water, particularly when tailings remain unvegetated for decades following mining cessation, as is the case in semi-arid landscapes. Understanding the speciation and mobility of contaminant metal(loid)s, particularly in surficial tailings, is essential to controlling their phytotoxicities and to revegetating impacted sites. In prior work, we showed that surficial tailings samples from the Klondyke State Superfund Site (AZ, USA), ranging in pH from 5.4 to 2.6, represent a weathering series, with acidification resulting from sulfide mineral oxidation, long-term Fe hydrolysis, and a concurrent decrease in total (6,000 to 450 mg kg−1) and plant-available (590 to 75 mg kg−1) Zn due to leaching losses and changes in Zn speciation. Here, we used bulk and micro-focused Zn K-edge X-ray absorption spectroscopy (XAS) data and a six-step sequential extraction procedure to determine tailings solid phase Zn speciation. Bulk sample spectra were fit by linear combination using three references: Zn-rich phyllosilicate (Zn0.8talc), Zn sorbed to ferrihydrite (ZnadsFeOx), and zinc sulfate (ZnSO4·7H2O). Analyses indicate that Zn sorbed in tetrahedral coordination to poorly-crystalline Fe and Mn (oxyhydr)oxides decreases with acidification in the weathering sequence, whereas octahedral zinc in sulfate minerals and crystalline Fe oxides undergoes a relative accumulation. Micro-scale analyses identified hetaerolite (ZnMn2O4), hemimorphite (Zn4Si2O7(OH)2·H2O) and sphalerite (ZnS) as minor phases. Bulk and micro-focused spectroscopy complement the chemical extraction results and highlight the importance of using a multi-method approach to interrogate complex tailings systems. PMID:21761897