Synergistic antinociceptive interaction between palmitoylethanolamide and tramadol in the mouse formalin test.

PubMed

Déciga-Campos, Myrna; Ramírez-Marín, Pamela Moncerrat; López-Muñoz, Francisco Javier

2015-10-15

Pharmacological synergism has been used to obtain a higher efficacy using drug concentrations at which side effects are minimal. In this study, the pharmacological antinociceptive interaction between N-palmitoylethanolamide (PEA) and tramadol was investigated. The individual concentration-response curves for PEA (0.1-56.2 μg/paw) and tramadol (1-56.2 μg/paw) were evaluated in mice in which nociception was induced by an intraplantar injection of 2% formalin. Isobolographic analysis was used to evaluate the pharmacological interaction between PEA (EC50=23.7±1.6 μg/paw) and tramadol (EC50=26.02±2.96 μg/paw) using the EC50 and a fixed 1:1 ratio combination. The isobologram demonstrated that the combinations investigated in this study produced a synergistic interaction; the experimental values (Zexp=9.5±0.2 μg/paw) were significantly smaller than those calculated theoretically (Zadd=24.8±0.2 μg/paw). The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-α). The sedative effect of the combination of PEA and tramadol was less than that generated by individual treatments. These findings suggest that the PEA and tramadol combination produced enhanced antinociceptive efficacy at concentrations at which side effects are minimal. Copyright © 2015 Elsevier B.V. All rights reserved.

Evolutionary Origins of a Bioactive Peptide Buried within Preproalbumin[C][W

PubMed Central

Elliott, Alysha G.; Delay, Christina; Liu, Huanle; Phua, Zaiyang; Rosengren, K. Johan; Benfield, Aurélie H.; Panero, Jose L.; Colgrave, Michelle L.; Jayasena, Achala S.; Dunse, Kerry M.; Anderson, Marilyn A.; Schilling, Edward E.; Ortiz-Barrientos, Daniel; Craik, David J.; Mylne, Joshua S.

2014-01-01

The de novo evolution of proteins is now considered a frequented route for biological innovation, but the genetic and biochemical processes that lead to each newly created protein are often poorly documented. The common sunflower (Helianthus annuus) contains the unusual gene PawS1 (Preproalbumin with SFTI-1) that encodes a precursor for seed storage albumin; however, in a region usually discarded during albumin maturation, its sequence is matured into SFTI-1, a protease-inhibiting cyclic peptide with a motif homologous to unrelated inhibitors from legumes, cereals, and frogs. To understand how PawS1 acquired this additional peptide with novel biochemical functionality, we cloned PawS1 genes and showed that this dual destiny is over 18 million years old. This new family of mostly backbone-cyclic peptides is structurally diverse, but the protease-inhibitory motif was restricted to peptides from sunflower and close relatives from its subtribe. We describe a widely distributed, potential evolutionary intermediate PawS-Like1 (PawL1), which is matured into storage albumin, but makes no stable peptide despite possessing residues essential for processing and cyclization from within PawS1. Using sequences we cloned, we retrodict the likely stepwise creation of PawS1’s additional destiny within a simple albumin precursor. We propose that relaxed selection enabled SFTI-1 to evolve its inhibitor function by converging upon a successful sequence and structure. PMID:24681618

Congenital deformity of the paw in a captive tiger: case report

PubMed Central

2012-01-01

Background The aim of this report was to describe the clinical signs, diagnostic approach, treatment and outcome in the case of a tiger with a deformity of the paw. Case presentation A 1.5-year-old tiger (Panthera tigris) was presented with lameness of the left thoracic limb. A deformity involving the first and second metacarpal bones, and a soft tissue separation between the second and third metacarpal bones of the left front paw were observed. The second digit constantly struck the ground during locomotion. Based on the physical and radiographic evaluations, a diagnosis of ectrodactyly was made. A soft tissue reconstruction of the cleft with excision of both the second digit and distal portion of the second metacarpal bone was performed. Marked improvement of the locomotion was observed after surgical treatment, although the tiger showed a low degree of lameness probably associated with the discrepancy in length between the thoracic limbs. Conclusion This report shows a rare deformity in an exotic feline that it is compatible to ectrodactyly. Reconstructive surgery of the cleft resulted in significant improvement of limb function. PMID:22747639

Health behaviors and occupational stress of Brazilian civil servants living in an urban center.

PubMed

Goston, Janaina Lavalli; Caiaffa, Waleska Teixeira; de Souza Andrade, Amanda Cristina; Vlahov, David

2013-01-01

Occupational stress and unhealthy lifestyles are common characteristics of urban workers. The association between health behaviors and job stress of urban Brazilian civil servants was studied. A cross-sectional study included 893 workers. Health markers, the dependent variables, were: Fruit/vegetable (FV) and alcohol (A) intake, physical activity (PA), including at work (PAW), smoking (S), BMI ≥ 25 Kg/m(2). Occupational stress, assessed by Job Stress Scale-Brazilian version, classified employees into: High-strain, Low-strain, Active, and Passive. Prevalence rates and multivariate Poisson models were adopted. On average, employees (mean age = 40.2 years; 69.1% female) reported healthy lifestyle factors: FV (56%); PA (59.7%); S (13.3%); however, 49.4% were overweight. Compared to low-strain, high-strain workers reported higher PAW; passive workers lesser PA and higher PAW. After adjusting for socio-demographics and work characteristics, the occupational stress dimensions were no longer associated to health behaviors. Our results do not support the hypothesis of an effect for occupational stress on urban employees' health behaviors. Copyright © 2012 Wiley Periodicals, Inc.

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

Yu, Kuang; Libisch, Florian; Carter, Emily A., E-mail: eac@princeton.edu

We report a new implementation of the density functional embedding theory (DFET) in the VASP code, using the projector-augmented-wave (PAW) formalism. Newly developed algorithms allow us to efficiently perform optimized effective potential optimizations within PAW. The new algorithm generates robust and physically correct embedding potentials, as we verified using several test systems including a covalently bound molecule, a metal surface, and bulk semiconductors. We show that with the resulting embedding potential, embedded cluster models can reproduce the electronic structure of point defects in bulk semiconductors, thereby demonstrating the validity of DFET in semiconductors for the first time. Compared to ourmore » previous version, the new implementation of DFET within VASP affords use of all features of VASP (e.g., a systematic PAW library, a wide selection of functionals, a more flexible choice of U correction formalisms, and faster computational speed) with DFET. Furthermore, our results are fairly robust with respect to both plane-wave and Gaussian type orbital basis sets in the embedded cluster calculations. This suggests that the density functional embedding method is potentially an accurate and efficient way to study properties of isolated defects in semiconductors.« less

Spatial orientation and mechanical properties of the human trachea: a computed tomography study.

PubMed

Zanella, Alberto; Cressoni, Massimo; Ferlicca, Daniela; Chiurazzi, Chiara; Epp, Myra; Rovati, Cristina; Chiumello, Davide; Pesenti, Antonio; Gattinoni, Luciano; Kolobow, Theodor

2015-04-01

The literature generally describes the trachea as oriented toward the right and back, but there is very little detailed characterization. Therefore, the aim of this study was to precisely determine the spatial orientation and to better characterize the physical properties of the human trachea. We analyzed lung computed tomography scans of 68 intubated and mechanically ventilated subjects suffering from acute lung injury/ARDS at airway pressures (Paw) of 5, 15, and 45 cm H2O. At each Paw, the inner edge of the trachea from the subglottal space to the carina was captured. Tracheal length and diameter were measured. Tracheal orientation and compliance were estimated from processing barycenter and surface tracheal sections. Tracheal orientation at a Paw of 5 cm H2O showed a 4.2 ± 5.3° angle toward the right and a 20.6 ± 6.9° angle downward toward the back, which decreased significantly while increasing Paw (19.4 ± 6.9° at 15 cm H2O and 17.1 ± 6.8° at 45 cm H2O, P < .001). Tracheal compliance was 0.0113 ± 0.0131 mL/cm H2O/cm of trachea length from 5 to 15 cm H2O and 0.004 ± 0.0041 mL/cm H2O/cm of trachea length from 15 to 45 cm H2O (P < .001). Tracheal diameter was 19.6 ± 3.4 mm on the medial-lateral axis and 21.0 ± 4.3 mm on the sternal-vertebral axis. The trachea is oriented downward toward the back at a 20.6 ± 6.9° angle and slightly toward the right at a 4.2 ± 5.3° angle. Understanding tracheal orientation may help in enhancing postural drainage and respiratory physiotherapy, and knowing the physical properties of the trachea may aid in endotracheal tube cuff design. Copyright © 2015 by Daedalus Enterprises.

Posture does not matter! Paw usage and grasping paw preference in a small-bodied rooting quadrupedal mammal.

PubMed

Joly, Marine; Scheumann, Marina; Zimmermann, Elke

2012-01-01

Recent results in birds, marsupials, rodents and nonhuman primates suggest that phylogeny and ecological factors such as body size, diet and postural habit of a species influence limb usage and the direction and strength of limb laterality. To examine to which extent these findings can be generalised to small-bodied rooting quadrupedal mammals, we studied trees shrews (Tupaia belangeri). We established a behavioural test battery for examining paw usage comparable to small-bodied primates and tested 36 Tupaia belangeri. We studied paw usage in a natural foraging situation (simple food grasping task) and measured the influence of varying postural demands (triped, biped, cling, sit) on paw preferences by applying a forced-food grasping task similar to other small-bodied primates. Our findings suggest that rooting tree shrews prefer mouth over paw usage to catch food in a natural foraging situation. Moreover, we demonstrated that despite differences in postural demand, tree shrews show a strong and consistent individual paw preference for grasping across different tasks, but no paw preference at a population level. Tree shrews showed less paw usage than small-bodied quadrupedal and arboreal primates, but the same paw preference. Our results confirm that individual paw preferences remain constant irrespective of postural demand in some small-bodied quadrupedal non primate and primate mammals which do not require fine motoric control for manipulating food items. Our findings suggest that the lack of paw/hand preference for grasping food at a population level is a universal pattern among those species and that the influence of postural demand on manual lateralisation in quadrupeds may have evolved in large-bodied species specialised in fine manipulations of food items.

Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2.

PubMed Central

Landucci, E C; Antunes, E; Donato, J L; Faro, R; Hyslop, S; Marangoni, S; Oliveira, B; Cirino, G; de Nucci, G

1995-01-01

1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7537590

Reactive radical-driven bacterial inactivation by hydrogen-peroxide-enhanced plasma-activated-water

NASA Astrophysics Data System (ADS)

Wu, Songjie; Zhang, Qian; Ma, Ruonan; Yu, Shuang; Wang, Kaile; Zhang, Jue; Fang, Jing

2017-08-01

The combined effects of plasma activated water (PAW) and hydrogen peroxide (H2O2), PAW/HP, in sterilization were investigated in this study. To assess the synergistic effects of PAW/HP, S. aureus was selected as the test microorganism to determine the inactivation efficacy. Also, the DNA/RNA and proteins released by the bacterial suspensions under different conditions were examined to confirm membrane integrity. Additionally, the intracellular pH (pHi) of S. aureus was measured in our study. Electron spin resonance spectroscopy (ESR) was employed to identify the presence of radicals. Finally, the oxidation reduction potential (ORP), conductivity and pH were measured. Our results revealed that the inactivation efficacy of PAW/HP is much greater than that of PAW, while increased H2O2 concentration result in higher inactivation potential. More importantly, as compared with PAW, the much stronger intensity ESR signals and higher ORP in PAW/HP suggests that the inactivation mechanism of the synergistic effects of PAW/HP: more reactive oxygen species (ROS) and reactive nitrogen species (RNS), especially OH and NO radicals, are generated in PAW combined with H2O2 resulting in more deaths of the bacteria.

Building a Personalized Education Portal: Get a Behind-the-Scenes Look at LSU's Award-Winning System.

ERIC Educational Resources Information Center

Ethridge, Robin R.; Hadden, Cynthia M; Smith, Michael P.

2000-01-01

Describes the Personal Access Web Services (PAWS) at Louisiana State University, a portal application which offers enterprise, workgroup, and personal services. The paper highlights: PAWS project planning; PAWS as a portal; PAWS implementation; account accreditation; user authentication; legacy integration; mapping credentials; transmission of…

Repeatability of quantitative sensory testing in healthy cats in a clinical setting with comparison to cats with osteoarthritis.

PubMed

Addison, Elena S; Clements, Dylan N

2017-12-01

Objectives The aim of this study was to evaluate the repeatability of quantitative sensory tests (QSTs) in a group of healthy untrained cats (n = 14) and to compare the results with those from cats with osteoarthritis (n = 7). Methods Peak vertical force (PVF) and vertical impulse were measured on a pressure plate system. Thermal sensitivity was assessed using a temperature-controlled plate at 7°C and 40°C. Individual paw lifts and overall duration of paw lifts were counted and measured for each limb. Paw withdrawal thresholds were measured using manual and electronic von Frey monofilaments (MVF and EVF, respectively) applied to the metacarpal or metatarsal pads. All measurements were repeated twice to assess repeatability of the tests. Results In healthy cats all tests were moderately repeatable. When compared with cats with osteoarthritis the PVF was significantly higher in healthy hindlimbs in repeat 1 but not in repeat 2. Cats with osteoarthritis of the forelimbs showed a decrease in the frequency of paw lifts on the 7°C plate compared with cats with healthy forelimbs, and the duration of paw lifts was significantly less than healthy forelimbs in the first repeat but not in the second repeat. Osteoarthritic limbs had significantly lower paw withdrawal thresholds with both MVF and EVF than healthy limbs. Conclusions and relevance QSTs are moderately repeatable in untrained cats. Kinetic gait analysis did not permit differentiation between healthy limbs and those with osteoarthritis, but thermal sensitivity testing (cold) does. Sensory threshold testing can differentiate osteoarthritic and healthy limbs, and may be useful in the diagnosis and monitoring of this condition in cats in the clinical setting.

Protective effects of radon inhalation on carrageenan-induced inflammatory paw edema in mice.

PubMed

Kataoka, Takahiro; Teraoka, Junichi; Sakoda, Akihiro; Nishiyama, Yuichi; Yamato, Keiko; Monden, Mayuko; Ishimori, Yuu; Nomura, Takaharu; Taguchi, Takehito; Yamaoka, Kiyonori

2012-04-01

We assessed whether radon inhalation inhibited carrageenan-induced inflammation in mice. Carrageenan (1% v/v) was injected subcutaneously into paws of mice that had or had not inhaled approximately 2,000 Bq/m(3) of radon for 24 h. Radon inhalation significantly increased superoxide dismutase (SOD) and catalase activities and significantly decreased lipid peroxide levels in mouse paws, indicating that radon inhalation activates antioxidative functions. Carrageenan administration induced paw edema and significantly increased tumor necrosis factor-alpha (TNF-α) and nitric oxide in serum. However, radon inhalation significantly reduced carrageenan-induced paw edema. Serum TNF-α levels were lower in the radon-treated mice than in sham-treated mice. In addition, SOD and catalase activities in paws were significantly higher in the radon-treated mice than in the sham-treated mice. These findings indicated that radon inhalation had anti-inflammatory effects and inhibited carrageenan-induced inflammatory paw edema.

Catecholamine plasma levels, IFN-γ serum levels and antibodies production induced by rabies vaccine in dogs selected for their paw preference.

PubMed

Siniscalchi, Marcello; Cirone, Francesco; Guaricci, Antonio Ciro; Quaranta, Angelo

2014-01-01

To explore the possible role of the sympathetic nervous activity in the asymmetrical crosstalk between the brain and immune system, catecholamine (E, NE) plasma levels, Interferon-γ (IFN-γ) serum levels and production of antibodies induced by rabies vaccine in dogs selected for their paw preference were measured. The results showed that the direction of behavioural lateralization influenced both epinephrine levels and immune response in dogs. A different kinetic of epinephrine levels after immunization was observed in left-pawed dogs compared to both right-pawed and ambidextrous dogs. The titers of antirabies antibodies were lower in left-pawed dogs than in right-pawed and ambidextrous dogs. Similarly, the IFN-γ serum levels were lower in left-pawed dogs than in the other two groups. Taken together, these findings showed that the left-pawed group appeared to be consistently the different group stressing the fundamental role played by the sympathetic nervous system as a mechanistic basis for the crosstalk between the brain and the immune system.

Distribution of paw preference in mongrel and tortoise-shell cats and the relation of hemispheric weight to paw preference: sexual dimorphism in paw use and its relation to hemispheric weight.

PubMed

Tan, U

1993-06-01

The distribution of the right minus left (R - L) paw use and its relation to hemispheric weight was studied in tortoise-shell cats. Paw preference was assessed by a food reaching test. All males (N = 9) were left-preferent; females (N = 13) were predominantly right-preferent. There was an inverse relationship between the degree of left-paw preference and the right-brain weight in males (no correlation with left-brain weight). In females, the R - L paw use showed a negative linear correlation with the right- and left-brain weights: the right-pawedness decreased and the left-pawedness increased as the right- and left-brain weights increased. The distributions of the R - L paw use as well as the relationships between brain-weight and pawedness exhibited sexual dimorphism. The results suggest that mainly the genetic and hormonal factors may play an important role in emergence of motor asymmetry in cats. Annett's right shift theory of handedness was also discussed in light of these results.

Short-term and long-term memory deficits in handedness learning in mice with absent corpus callosum and reduced hippocampal commissure.

PubMed

Ribeiro, Andre S; Eales, Brenda A; Biddle, Fred G

2013-05-15

The corpus callosum (CC) and hippocampal commissure (HC) are major interhemispheric connections whose role in brain function and behaviors is fascinating and contentious. Paw preference of laboratory mice is a genetically regulated, adaptive behavior, continuously shaped by training and learning. We studied variation with training in paw-preference in mice of the 9XCA/WahBid ('9XCA') recombinant inbred strain, selected for complete absence of the CC and severely reduced HC. We measured sequences of paw choices in 9XCA mice in two training sessions in unbiased test chambers, separated by one-week. We compared them with sequences of paw choices in model non-learner mice that have random unbiased paw choices and with those of C57BL/6JBid ('C57BL/6J') mice that have normal interhemispheric connections and learn a paw preference. Positive autocorrelation between successive paw choices during each session and change in paw-preference bias between sessions indicate that 9XCA mice have weak, but not null, learning skills. We tested the effect of the forebrain commissural defect on paw-preference learning with the independent BTBR T+ tf/J ('BTBR') mouse strain that has a genetically identical, non-complementing commissural trait. BTBR has weak short-term and long-term memory skills, identical to 9XCA. The results provide strong evidence that CC and HC contribute in memory function and formation of paw-preference biases. Copyright © 2013 Elsevier B.V. All rights reserved.

Noradrenaline activates the NO/cGMP/ATP-sensitive K(+) channels pathway to induce peripheral antinociception in rats.

PubMed

Romero, Thiago R L; Guzzo, Luciana S; Perez, Andrea C; Klein, André; Duarte, Igor D G

2012-03-31

Despite the classical peripheral pronociceptive effect of noradrenaline (NA), recently studies showed the involvement of NA in antinociceptive effect under immune system interaction. In addition, the participation of the NO/cGMP/KATP pathway in the peripheral antinociception has been established by our group as the molecular mechanism of another adrenoceptor agonist xylazine. Thus the aim of this study was to obtain pharmacological evidences for the involvement of the NO/cGMP/KATP pathway in the peripheral antinociceptive effect induced by exogenous noradrenaline. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E(2) (2μg/paw). All drugs were locally administered into the right hind paw of male Wistar rats. NA (5, 20 and 80ng/paw) elicited a local inhibition of hyperalgesia. The non-selective NO synthase inhibitor l-NOarg (12, 18 and 24μg/paw) antagonized the antinociception effect induced by the highest dose of NA. The soluble guanylyl cyclase inhibitor ODQ (25, 50 and 100μg/paw) antagonized the NA-induced effect; and cGMP-phosphodiesterase inhibitor zaprinast (50μg/paw) potentiated the antinociceptive effect of NA low dose (5ng/paw). In addition, the local effect of NA was antagonized by a selective blocker of an ATP-sensitive K(+) channel, glibenclamide (20, 40 and 80μg/paw). On the other hand, the specifically voltage-dependent K(+) channel blocker, tetraethylammonium (30μg/paw), Ca(2+)-activated K(+) channel blockers of small and large conductance types dequalinium (50μg/paw) and paxilline (20μg/paw), respectively, were not able to block local antinociceptive effect of NA. The results provide evidences that NA probably induces peripheral antinociceptive effects by activation of the NO/cGMP/KATP pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw.

PubMed

Srebro, Dragana P; Vučković, Sonja M; Savić Vujović, Katarina R; Prostran, Milica Š

2015-02-01

Previous studies have shown that while magnesium, an antagonist of the glutamate subtype of N-methyl-D-aspartate receptors, possesses analgesic properties, it can induce writhing in rodents. The aim of this study was to determine the effect and mechanism of action of local (intraplantar) administration of magnesium sulfate (MS) on the paw withdrawal threshold (PWT) to mechanical stimuli. The PWT was evaluated by the electronic von Frey test in male Wistar rats. Tested drugs were either co-administered intraplantarly (i.pl.) with MS or given into the contralateral paw to exclude systemic effects. MS at doses of 0.5, 1.5, 3 and 6.2 mg/paw (i.pl.) induced a statistically significant (as compared to 0.9% NaCl) and dose-dependent mechanical hyperalgesia. Only isotonic MS (250 mmol/l or 6.2% or 6.2 mg/paw) induced mechanical hyperalgesia that lasted at least six hours. Isotonic MS-induced mechanical hyperalgesia was reduced in a dose-dependent manner by co-injection of camphor, a non-selective TRPA1 antagonist (0.3, 1 and 2.5 μg/paw), MK-801, a NMDA receptor antagonist (0.001, 0.025 and 0.1 μg/paw), L-NAME, a non-selective nitric oxide (NO) synthase inhibitor (20, 50 and 100 μg/paw), ARL 17477, a selective neuronal NOS inhibitor (5.7 and 17 μg/paw), SMT, a selective inducible NOS inhibitor (1 and 2.78 μg/paw), and methylene blue, a guanylate cyclase inhibitor (5, 20 and 125 μg/paw). Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that an i.pl. injection of MS produces local peripheral mechanical hyperalgesia via activation of peripheral TRPA1 and NMDA receptors and peripheral production of NO. Copyright © 2014 Elsevier Inc. All rights reserved.

Gait changes precede overt arthritis and strongly correlate with symptoms and histopathological events in pristane-induced arthritis

PubMed Central

2010-01-01

Introduction Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed. Methods Arthritis was induced in DA.rats by injection of 150 μl 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods. Results Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis. Conclusions Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis. PMID:20222952

Ilex paraguariensis Promotes Orofacial Pain Relief After Formalin Injection: Involvement of Noradrenergic Pathway.

PubMed

de Carvalho, Eudislaine Fonseca; de Oliveira, Simone Kobe; Nardi, Viviane Koepp; Gelinski, Tathiana Carla; Bortoluzzi, Marcelo Carlos; Maraschin, Marcelo; Nardi, Geisson Marcos

2016-03-01

Drinking mate or chimarrão, a hot infusion of Ilex paraguariensis (ILEX) leaves, is a common habit in Southern South America that has a social and almost ritualistic role. It has been used as a stimulant beverage in South America and analgesic in regions of Argentina for treatment of headache and others painful inflammatory conditions such as arthritis and rheumatism. The aim of this study was to evaluate the pharmacological activity of I. paraguariensis infusion (ILEX) on orofacial nociception model induced by formalin, and study its mechanism of action. The analgesic effect of ILEX was assessed through writhing test, paw formalin test, paw edema induced by carrageenan, and orofacial pain induced by formalin. To study the action mechanism of ILEX, opioidergic, dopaminergic, nitrergic, and adrenergic pathways were investigated. The high-performance liquid chromatography analysis of ILEX infusion revealed caffeine and theobromine. The treatment with ILEX reduced the number of writhing. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan. Different from formalin paw test, ILEX was able to reduce the orofacial reactivity to formalin in 31.8% (70.4 ± 2.5 s; first phase), and 20% (127.3 ± 18.9 s; second phase). The analgesic effect of ILEX results from the modulation of noradrenergic pathways since prazosin (α1-adrenoceptor antagonist, 0.15 mg/kg; intraperitoneal) reversed the analgesic effect of ILEX. The present report demonstrates that analgesic effect of ILEX in orofacial formalin test is due mainly to modulation of noradrenergic pathways. Ilex paraguariensis (ILEX) has been used as a stimulant beverage in South America and analgesic in regions of Argentina for the treatment of headache and others painful inflammatory conditions such arthritis and rheumatism.The aim of this study was to evaluate the pharmacological activity of ILEX on orofacial nociception model induced by formalin, and study its mechanism of action.ILEX reduced the number of writhing and orofacial reactivity to formalin in mice. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan.The analgesic effect of ILEX results from the modulation of noradrenergic pathways. Abbreviation Used: ILEX: Infusion of Ilex paraguariensis, NSAIDs: Nonsteroidal anti-inflammatory drugs, L-NOARG: L-NG-nitro-arginine, UV: Ultraviolet, i.p.: Intraperitoneal, NOS: Nitric Oxide Synthase, Analysis of variance, S.E.M.: Standard error of mean, HPLC: High-performance liquid chromatography, NO: Nitric Oxide, v.o.: Oral route, DCQ: dicaffeoylquinic acid, BMS: Burning mouth syndrome, PBS: Phosphate-buffered saline.

Orbital dependent functionals: An atom projector augmented wave method implementation

NASA Astrophysics Data System (ADS)

Xu, Xiao

This thesis explores the formulation and numerical implementation of orbital dependent exchange-correlation functionals within electronic structure calculations. These orbital-dependent exchange-correlation functionals have recently received renewed attention as a means to improve the physical representation of electron interactions within electronic structure calculations. In particular, electron self-interaction terms can be avoided. In this thesis, an orbital-dependent functional is considered in the context of Hartree-Fock (HF) theory as well as the Optimized Effective Potential (OEP) method and the approximate OEP method developed by Krieger, Li, and Iafrate, known as the KLI approximation. In this thesis, the Fock exchange term is used as a simple well-defined example of an orbital-dependent functional. The Projected Augmented Wave (PAW) method developed by P. E. Blochl has proven to be accurate and efficient for electronic structure calculations for local and semi-local functions because of its accurate evaluation of interaction integrals by controlling multiple moments. We have extended the PAW method to treat orbital-dependent functionals in Hartree-Fock theory and the Optimized Effective Potential method, particularly in the KLI approximation. In the course of study we develop a frozen-core orbital approximation that accurately treats the core electron contributions for above three methods. The main part of the thesis focuses on the treatment of spherical atoms. We have investigated the behavior of PAW-Hartree Fock and PAW-KLI basis, projector, and pseudopotential functions for several elements throughout the periodic table. We have also extended the formalism to the treatment of solids in a plane wave basis and implemented PWPAW-KLI code, which will appear in future publications.

SARA - SURE/ASSIST RELIABILITY ANALYSIS WORKSTATION (VAX VMS VERSION)

NASA Technical Reports Server (NTRS)

Butler, R. W.

1994-01-01

SARA, the SURE/ASSIST Reliability Analysis Workstation, is a bundle of programs used to solve reliability problems. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. The Systems Validation Methods group at NASA Langley Research Center has created a set of four software packages that form the basis for a reliability analysis workstation, including three for use in analyzing reconfigurable, fault-tolerant systems and one for analyzing non-reconfigurable systems. The SARA bundle includes the three for reconfigurable, fault-tolerant systems: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), and PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920). As indicated by the program numbers in parentheses, each of these three packages is also available separately in two machine versions. The fourth package, which is only available separately, is FTC, the Fault Tree Compiler (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree which describes a non-reconfigurable system. PAWS/STEM and SURE are analysis programs which utilize different solution methods, but have a common input language, the SURE language. ASSIST is a preprocessor that generates SURE language from a more abstract definition. ASSIST, SURE, and PAWS/STEM are described briefly in the following paragraphs. For additional details about the individual packages, including pricing, please refer to their respective abstracts. ASSIST, the Abstract Semi-Markov Specification Interface to the SURE Tool program, allows a reliability engineer to describe the failure behavior of a fault-tolerant computer system in an abstract, high-level language. The ASSIST program then automatically generates a corresponding semi-Markov model. A one-page ASSIST-language description may result in a semi-Markov model with thousands of states and transitions. The ASSIST program also includes model-reduction techniques to facilitate efficient modeling of large systems. The semi-Markov model generated by ASSIST is in the format needed for input to SURE and PAWS/STEM. The Semi-Markov Unreliability Range Evaluator, SURE, is an analysis tool for reconfigurable, fault-tolerant systems. SURE provides an efficient means for calculating accurate upper and lower bounds for the death state probabilities for a large class of semi-Markov models, not just those which can be reduced to critical-pair architectures. The calculated bounds are close enough (usually within 5 percent of each other) for use in reliability studies of ultra-reliable computer systems. The SURE bounding theorems have algebraic solutions and are consequently computationally efficient even for large and complex systems. SURE can optionally regard a specified parameter as a variable over a range of values, enabling an automatic sensitivity analysis. SURE output is tabular. The PAWS/STEM package includes two programs for the creation and evaluation of pure Markov models describing the behavior of fault-tolerant reconfigurable computer systems: the Pade Approximation with Scaling (PAWS) and Scaled Taylor Exponential Matrix (STEM) programs. PAWS and STEM produce exact solutions for the probability of system failure and provide a conservative estimate of the number of significant digits in the solution. Markov models of fault-tolerant architectures inevitably lead to numerically stiff differential equations. Both PAWS and STEM have the capability to solve numerically stiff models. These complementary programs use separate methods to determine the matrix exponential in the solution of the model's system of differential equations. In general, PAWS is better suited to evaluate small and dense models. STEM operates at lower precision, but works faster than PAWS for larger models. The programs that comprise the SARA package were originally developed for use on DEC VAX series computers running VMS and were later ported for use on Sun series computers running SunOS. They are written in C-language, Pascal, and FORTRAN 77. An ANSI compliant C compiler is required in order to compile the C portion of the Sun version source code. The Pascal and FORTRAN code can be compiled on Sun computers using Sun Pascal and Sun Fortran. For the VMS version, VAX C, VAX PASCAL, and VAX FORTRAN can be used to recompile the source code. The standard distribution medium for the VMS version of SARA (COS-10041) is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The standard distribution medium for the Sun version of SARA (COS-10039) is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. Electronic copies of the ASSIST user's manual in TeX and PostScript formats are provided on the distribution medium. DEC, VAX, VMS, and TK50 are registered trademarks of Digital Equipment Corporation. Sun, Sun3, Sun4, and SunOS are trademarks of Sun Microsystems, Inc. TeX is a trademark of the American Mathematical Society. PostScript is a registered trademark of Adobe Systems Incorporated.

SARA - SURE/ASSIST RELIABILITY ANALYSIS WORKSTATION (UNIX VERSION)

NASA Technical Reports Server (NTRS)

Butler, R. W.

1994-01-01

SARA, the SURE/ASSIST Reliability Analysis Workstation, is a bundle of programs used to solve reliability problems. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. The Systems Validation Methods group at NASA Langley Research Center has created a set of four software packages that form the basis for a reliability analysis workstation, including three for use in analyzing reconfigurable, fault-tolerant systems and one for analyzing non-reconfigurable systems. The SARA bundle includes the three for reconfigurable, fault-tolerant systems: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), and PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920). As indicated by the program numbers in parentheses, each of these three packages is also available separately in two machine versions. The fourth package, which is only available separately, is FTC, the Fault Tree Compiler (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree which describes a non-reconfigurable system. PAWS/STEM and SURE are analysis programs which utilize different solution methods, but have a common input language, the SURE language. ASSIST is a preprocessor that generates SURE language from a more abstract definition. ASSIST, SURE, and PAWS/STEM are described briefly in the following paragraphs. For additional details about the individual packages, including pricing, please refer to their respective abstracts. ASSIST, the Abstract Semi-Markov Specification Interface to the SURE Tool program, allows a reliability engineer to describe the failure behavior of a fault-tolerant computer system in an abstract, high-level language. The ASSIST program then automatically generates a corresponding semi-Markov model. A one-page ASSIST-language description may result in a semi-Markov model with thousands of states and transitions. The ASSIST program also includes model-reduction techniques to facilitate efficient modeling of large systems. The semi-Markov model generated by ASSIST is in the format needed for input to SURE and PAWS/STEM. The Semi-Markov Unreliability Range Evaluator, SURE, is an analysis tool for reconfigurable, fault-tolerant systems. SURE provides an efficient means for calculating accurate upper and lower bounds for the death state probabilities for a large class of semi-Markov models, not just those which can be reduced to critical-pair architectures. The calculated bounds are close enough (usually within 5 percent of each other) for use in reliability studies of ultra-reliable computer systems. The SURE bounding theorems have algebraic solutions and are consequently computationally efficient even for large and complex systems. SURE can optionally regard a specified parameter as a variable over a range of values, enabling an automatic sensitivity analysis. SURE output is tabular. The PAWS/STEM package includes two programs for the creation and evaluation of pure Markov models describing the behavior of fault-tolerant reconfigurable computer systems: the Pade Approximation with Scaling (PAWS) and Scaled Taylor Exponential Matrix (STEM) programs. PAWS and STEM produce exact solutions for the probability of system failure and provide a conservative estimate of the number of significant digits in the solution. Markov models of fault-tolerant architectures inevitably lead to numerically stiff differential equations. Both PAWS and STEM have the capability to solve numerically stiff models. These complementary programs use separate methods to determine the matrix exponential in the solution of the model's system of differential equations. In general, PAWS is better suited to evaluate small and dense models. STEM operates at lower precision, but works faster than PAWS for larger models. The programs that comprise the SARA package were originally developed for use on DEC VAX series computers running VMS and were later ported for use on Sun series computers running SunOS. They are written in C-language, Pascal, and FORTRAN 77. An ANSI compliant C compiler is required in order to compile the C portion of the Sun version source code. The Pascal and FORTRAN code can be compiled on Sun computers using Sun Pascal and Sun Fortran. For the VMS version, VAX C, VAX PASCAL, and VAX FORTRAN can be used to recompile the source code. The standard distribution medium for the VMS version of SARA (COS-10041) is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The standard distribution medium for the Sun version of SARA (COS-10039) is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. Electronic copies of the ASSIST user's manual in TeX and PostScript formats are provided on the distribution medium. DEC, VAX, VMS, and TK50 are registered trademarks of Digital Equipment Corporation. Sun, Sun3, Sun4, and SunOS are trademarks of Sun Microsystems, Inc. TeX is a trademark of the American Mathematical Society. PostScript is a registered trademark of Adobe Systems Incorporated.

Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

PubMed

Guzzo, Luciana S; Perez, Andrea C; Romero, Thiago Rl; Azevedo, Adolfo O; Duarte, Igor Dg

2012-05-01

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 μg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 μg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 μg/paw) prevented the action of cafestol (80 μg/paw), whereas the aminopeptidase inhibitor bestatin (400 μg/paw) potentiated the antinociceptive effect of cafestol (40 μg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

Contribution to the Chemistry of Plasma-Activated Water

NASA Astrophysics Data System (ADS)

Julák, J.; Hujacová, A.; Scholtz, V.; Khun, J.; Holada, K.

2018-01-01

Plasma-activated water (PAW) was prepared by exposure to nonthermal plasma produced by a positive dc corona discharge in a transient spark regime. The activation of water was performed in atmosphere of various surrounding gases (air, nitrogen, carbon dioxide, and argon). This PAW retains its biological activity, measured on the mouse neuroblastoma cells culture, even after storage for more than one year. The highest hydrogen peroxide content was found for PAWs prepared in the atmospheres of argon or carbon dioxide, whereas the PAWs prepared in air and nitrogen exhibited lower hydrogen peroxide content. The acidity of PAWs mediated by nitric and nitrous acid formation displayed an opposite trend. It is concluded that the long-lasting biological effect of PAW is mediated by hydrogen peroxide in acid milieu only, whereas other possible active components decompose rapidly.

Antinociceptive and anti-inflammatory activity of the ethanolic extract of Cymbidium aloifolium (L.).

PubMed

Howlader, Md Amran; Alam, Mahmudul; Ahmed, Kh Tanvir; Khatun, Farjana; Apu, Apurba Sarker

2011-10-01

The ethanol leaf extract of Cymbidium aloifolium (L.) was evaluated for its analgesic and antiinflammatory activities. The extract, at the dose of 200 and 400 mg kg(-1) body weight, exerted the analgesic activity by observing the number of abdominal contractions and anti-inflammatory activity against Carrageenin induced paw edema in mice by measuring the paw volume. The ethanolic extract of Cymbidium aloifolium (L.) showed statistically significant (p < 0.05) reduction of percentage of writhing of 33.57 and 61.31% at 200 and 400 mg kg(-1) oral dose, respectively, when compared to negative control. The Ethanolic plant extract also showed significant (p < 0.05) dose dependent reduction of mean increase of formation of paw edema. The results of the experiment and its statistical analysis showed that the ethanolic plant extract had shown significant (p < 0.05) dose dependent analgesic and anti-inflammatory activities when compared to the control.

Two proteins for the price of one: Structural studies of the dual-destiny protein preproalbumin with sunflower trypsin inhibitor-1.

PubMed

Franke, Bastian; James, Amy M; Mobli, Mehdi; Colgrave, Michelle L; Mylne, Joshua S; Rosengren, K Johan

2017-07-28

Seed storage proteins are both an important source of nutrition for humans and essential for seedling establishment. Interestingly, unusual napin-type 2S seed storage albumin precursors in sunflowers contain a sequence that is released as a macrocyclic peptide during post-translational processing. The mechanism by which such peptides emerge from linear precursor proteins has received increased attention; however, the structural characterization of intact precursor proteins has been limited. Here, we report the 3D NMR structure of the Helianthus annuus PawS1 ( p repro a lbumin w ith s unflower trypsin inhibitor- 1 ) and provide new insights into the processing of this remarkable dual-destiny protein. In seeds, PawS1 is matured by asparaginyl endopeptidases (AEPs) into the cyclic peptide SFTI-1 ( s un f lower t rypsin i nhibitor- 1 ) and a heterodimeric 2S albumin. The structure of PawS1 revealed that SFTI-1 and the albumin are independently folded into well-defined domains separated by a flexible linker. PawS1 was cleaved in vitro with recombinant sunflower HaAEP1 and in situ using a sunflower seed extract in a way that resembled the expected in vivo cleavages. Recombinant HaAEP1 cleaved PawS1 at multiple positions, and in situ , its flexible linker was removed, yielding fully mature heterodimeric albumin. Liberation and cyclization of SFTI-1, however, was inefficient, suggesting that specific seed conditions or components may be required for in vivo biosynthesis of SFTI-1. In summary, this study has revealed the 3D structure of a macrocyclic precursor protein and provided important mechanistic insights into the maturation of sunflower proalbumins into an albumin and a macrocyclic peptide. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

UV-vis spectroscopy study of plasma-activated water: Dependence of the chemical composition on plasma exposure time and treatment distance

NASA Astrophysics Data System (ADS)

Oh, Jun-Seok; Szili, Endre J.; Ogawa, Kotaro; Short, Robert D.; Ito, Masafumi; Furuta, Hiroshi; Hatta, Akimitsu

2018-01-01

Plasma-activated water (PAW) is receiving much attention in biomedical applications because of its reported potent bactericidal properties. Reactive oxygen and nitrogen species (RONS) that are generated in water upon plasma exposure are thought to be the key components in PAW that destroy bacterial and cancer cells. In addition to developing applications for PAW, it is also necessary to better understand the RONS chemistry in PAW in order to tailor PAW to achieve a specific biological response. With this in mind, we previously developed a UV-vis spectroscopy method using an automated curve fitting routine to quantify the changes in H2O2, NO2 -, NO3 - (the major long-lived RONS in PAW), and O2 concentrations. A major advantage of UV-vis is that it can take multiple measurements during plasma activation. We used the UV-vis procedure to accurately quantify the changes in the concentrations of these RONS and O2 in PAW. However, we have not yet provided an in-depth commentary of how we perform the curve fitting procedure or its implications. Therefore, in this study, we provide greater detail of how we use the curve fitting routine to derive the RONS and O2 concentrations in PAW. PAW was generated by treatment with a helium plasma jet. In addition, we employ UV-vis to study how the plasma jet exposure time and treatment distance affect the RONS chemistry and amount of O2 dissolved in PAW. We show that the plasma jet exposure time principally affects the total RONS concentration, but not the relative ratios of RONS, whereas the treatment distance affects both the total RONS concentration and the relative RONS concentrations.

The anti-allergic activity of the acetate fraction of Schinus terebinthifolius leaves in IgE induced mice paw edema and pleurisy.

PubMed

Cavalher-Machado, Simone Campos; Rosas, Elaine Cruz; Brito, Fabiola de Almeida; Heringe, Alan Patrick; de Oliveira, Rodrigo Rodrigues; Kaplan, Maria Auxiliadora Coelho; Figueiredo, Maria Raquel; Henriques, Maria das Graças Müller de Oliveira

2008-11-01

Schinus is a genus of the Anacardiaceae family and contains Schinus terebinthifolius, the Brazilian pepper tree that is widely used in folk medicine. We investigate the anti-allergic activity of the ethyl acetate fraction of S. terebinthifolius Raddi (ST fraction). HPLC analysis reveled that gallic acid, methyl gallate and 1,2,3,4,6-pentagalloylglucose are the major aromatic components of the fraction. Oral pre-treatment with the ST fraction (100 mg/kg) significantly inhibited paw edema induced by compound 48/80 (100 ng/paw) and to a lesser extent, the allergic paw edema (OVA, 3 microg/paw). The ST fraction (100 and 200 mg/kg) also inhibited the edema induced by histamine (100 microg/paw), preventing mast cell degranulation and, consequently, histamine release in Wistar rat peritoneal mast cells induced by C 48/80 (5 microg/mL). This histamine inhibition was also observed after mast cell pre-treatment with both methyl gallate and 1,2,3,4,6-pentagalloylglucose (100 microg/mL), the isolated compounds from the ethyl acetate fraction. Pre-treatment with the ST fraction (100 mg/kg) significantly inhibited total leukocyte and eosinophil accumulation in pleural cavities 24 h after the intrathoracic injection of OVA (12.5 microg/cavity). This effect was related to the inhibition of CCL11/eotaxin and CCL5/RANTES in pleural lavage fluid. Pre-treatment with this fraction (100 mg/kg) failed to reduce the cell influx that was observed after LPS-injection into pleural cavity (250 ng/cavity). These findings demonstrate the anti-allergic effect of the ST fraction, which includes the inhibition of edema formation and histamine release caused by mast cell degranulation and eosinophil influx into the pleural cavity probably reflected by the decreased levels of chemokines in recovered pleural lavage fluid.

Automatic algorithm for monitoring systolic pressure variation and difference in pulse pressure.

PubMed

Pestel, Gunther; Fukui, Kimiko; Hartwich, Volker; Schumacher, Peter M; Vogt, Andreas; Hiltebrand, Luzius B; Kurz, Andrea; Fujita, Yoshihisa; Inderbitzin, Daniel; Leibundgut, Daniel

2009-06-01

Difference in pulse pressure (dPP) reliably predicts fluid responsiveness in patients. We have developed a respiratory variation (RV) monitoring device (RV monitor), which continuously records both airway pressure and arterial blood pressure (ABP). We compared the RV monitor measurements with manual dPP measurements. ABP and airway pressure (PAW) from 24 patients were recorded. Data were fed to the RV monitor to calculate dPP and systolic pressure variation in two different ways: (a) considering both ABP and PAW (RV algorithm) and (b) ABP only (RV(slim) algorithm). Additionally, ABP and PAW were recorded intraoperatively in 10-min intervals for later calculation of dPP by manual assessment. Interobserver variability was determined. Manual dPP assessments were used for comparison with automated measurements. To estimate the importance of the PAW signal, RV(slim) measurements were compared with RV measurements. For the 24 patients, 174 measurements (6-10 per patient) were recorded. Six observers assessed dPP manually in the first 8 patients (10-min interval, 53 measurements); no interobserver variability occurred using a computer-assisted method. Bland-Altman analysis showed acceptable bias and limits of agreement of the 2 automated methods compared with the manual method (RV: -0.33% +/- 8.72% and RV(slim): -1.74% +/- 7.97%). The difference between RV measurements and RV(slim) measurements is small (bias -1.05%, limits of agreement 5.67%). Measurements of the automated device are comparable with measurements obtained by human observers, who use a computer-assisted method. The importance of the PAW signal is questionable.

Development and validation of an automated system for detection and assessment of scratching in the rodent

PubMed Central

Marino, Marc; Huang, Polly; Malkmus, Shelle; Robertshaw, Erin; Mac, Elaine A.; Shatterman, Yuri; Yaksh, Tony L.

2012-01-01

Pruritus, the sensation of itch, which evokes reflex scratching behavior, has a diverse etiology. Because of its clinical significance, mechanisms of pruriception are an important topic. In the present work we describe and validate a paw motion detector (PMD) system. The system employs a small removable metal band placed on one hind paw that provides a signal indicative of paw movement through perturbation of an electromagnetic (EM) field. C57Bl/6 mice were fitted with a unilateral hind paw band and adapted to testing cylinders equipped with EM signal emission and detection. The following observations were made: 1) in mice, unilateral SQ injection of 48/80 into the dorsolateral aspect of the neck evoked periodic high frequency bursts of scratching at the injected site with the ipsilateral (banded) but not the contralateral (not banded) hind paw. 2) Cross correlation between PMD and human observer counts after SQ 48/80 using the specified computational algorithm revealed a highly significant correlation. 3) SQ histamine and 48/80 over a 1 hour interval produced dose dependent scratching, which diphenhydramine dose dependently reversed. Chloroquine scratching displayed an inverse u-shaped dose response curve, which was insensitive to diphenhydramine. 4) SQ 48/80 at intervals over 28 days showed no change in the scratching response within the same cohort of mice. 5) Power analysis showed 40% changes in scratching activity could be detected at the p<0.05 level with groups of 4 mice. These observations indicate that the system described can efficiently define the actions and pharmacology of pruritogenic agents. PMID:22971351

Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System.

PubMed

Ferreira, Renata Cristina Mendes; Almeida-Santos, Ana Flávia; Duarte, Igor Dimitri Gama; Aguiar, Daniele C; Moreira, Fabricio A; Romero, Thiago Roberto Lima

2017-01-01

Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E 2 (PGE 2 , 2  μ g). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE 2 injection. Aripiprazole (100  μ g/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50  μ g/paw), a nonselective opioid receptor antagonist. The role of μ -, δ -, and κ -opioid receptors was investigated using the selective antagonists, clocinnamox (40  μ g/paw), naltrindole (15, 30, and 60  μ g/paw), and nor-binaltorphimine (200  μ g/paw), respectively. The data indicated that only the δ -opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400  μ g), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25  μ g/paw) aripiprazole-induced peripheral antinociception. The results suggest the participation of the opioid system via δ -opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

Post-discharge evolution of reactive species in the water activated by a surface air plasma: a modeling study

NASA Astrophysics Data System (ADS)

Liu, Z. C.; Liu, D. X.; Chen, C.; Liu, Z. J.; Yang, A. J.; Rong, M. Z.; Chen, H. L.; Kong, M. G.

2018-05-01

Plasma-activated water (PAW) has been reported to sustain a bactericidal ability for months. However, many reactive species regarded as the main antibacterial agents in PAW have short lifetimes of less than one second. In order to explain the prolonged antibacterial ability of PAW and predict how to extend its effective time, we studied the post-discharge evolution of reactive species in PAW based on a system-level model reported previously. Three common storage conditions for PAW were considered within the post-discharge time of 14 d: (I) leaving the residual gas and PAW in the sealed reactor; (II) leaving PAW in the open air; (III) sealing the container of PAW. In comparison, storage condition III was the best condition to preserve the long-lived species including H2O2 and HNO2/, whereas storage condition I was the best method to preserve the short-lived species including OH, HO2 and ONOOH/ONOO‑. It suggests that the gas–liquid mass transfer plays an important role in the evolution of reactive species. We also found that O2NOOH/O2NOO‑ had an almost one order of magnitude higher concentration and a longer residue time than those of ONOOH/ONOO‑. This distinction suggests that the biological effect of O2NOOH/O2NOO‑ may be important.

Antinociceptive effect and interaction of uncompetitive and competitive NMDA receptor antagonists upon capsaicin and paw pressure testing in normal and monoarthritic rats.

PubMed

Pelissier, Teresa; Infante, Claudio; Constandil, Luis; Espinosa, Jeannette; Lapeyra, Carolina De; Hernández, Alejandro

2008-01-01

We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Four weeks later, the antinociceptive effect of intrathecal administration of the drugs alone or combined was evaluated by using the intraplantar capsaicin and the paw pressure tests. Ketamine (0.1, 1, 10, 30, 100, 300 and 1000 microg i.t.) and (+/-)CPP (0.125, 2.5, 7.5, 12.5, 25 and 50 microg i.t.) produced significantly greater dose-dependent antinociception in the capsaicin than in the paw pressure test. Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.

Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

PubMed

Obiri, David D; Osafo, Newman; Ayande, Patrick G; Antwi, Aaron O

2014-03-28

Xylopia aethiopica is used in a decoction of the dried fruit to treat bronchitis, asthma, arthritis, rheumatism, headache, neuralgia and colic pain. The aim of the study is to evaluate the anti-arthritic effects of a 70% aqueous ethanol extract of the fruit of Xylopia aethiopica in a chronic inflammatory model. Adjuvant arthritis was induced in Sprague-Dawley rats by intraplantar injection of Complete Freund's adjuvant into the right hind paw. Foot volume was measured by water displacement plethysmometry. The oedema component of inflammation was evaluated as the percentage change in paw swelling and the total oedema induced calculated as area under the time course curves. In addition to X-ray radiography, histopathology of ankle joints supported by haematological analysis was used to assess the anti-arthritic action of the extract of Xylopia aethiopica (XAE). Xylopia aethiopica extract (100, 300 and 600 mg kg(-1)) modified the time course curve significantly reducing hind paw oedema in the ipsilateral paw at all dose levels when administered both prophylactically and therapeutically. In addition XAE significantly suppressed the systemic spread of the arthritis from the ipsilateral to the contralateral limbs. The radiological pictures of the joints particularly metatarsal, phalanges and the ankle joint space of rats in the XAE-treated group showed protective effect against adjuvant-induced arthritis while histopathology revealed significant reduction in mononuclear infiltration, pannus formation and bone erosion. The haematological analysis in the test animals revealed significant improvement relative to the CFA model group. Xylopia aethiopica XAE suppresses joint inflammation and destruction in arthritic rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of phosphoric acid sprayed into an incinerator furnace on the flue gas pressure drop at fabric filters.

PubMed

Takahashi, Shigetoshi; Hwang, In-Hee; Matsuto, Toshihiko

2016-06-01

Fabric filters are widely used to remove dust from flue gas generated by waste incineration. However, a pressure drop occurs at the filters, caused by growth of a dust layer on the filter fabric despite regular cleaning by pulsed-jet air. The pressure drop at the fabric filters leads to energy consumption at induced draft fan to keep the incinerator on negative pressure, so that its proper control is important to operate incineration facility efficiently. The pressure drop at fabric filters decreased whenever phosphoric acid wastewater (PAW) was sprayed into an incinerator for treating industrial waste. Operational data obtained from the incineration facility were analyzed to determine the short- and long-term effects of PAW spraying on the pressure drop. For the short-term effect, it was confirmed that the pressure drop at the fabric filters always decreased to 0.3-1.2kPa within about 5h after spraying PAW. This effect was expected to be obtained by about one third of present PAW spraying amount. However, from the long-term perspective, the pressure drop showed an increase in the periods of PAW spraying compared with periods for which PAW spraying was not performed. The pressure drop increase was particularly noticeable after the initial PAW spraying, regardless of the age and type of fabric filters used. These results suggest that present PAW spraying causes a temporary pressure drop reduction, leading to short-term energy consumption savings; however, it also causes an increase of the pressure drop over the long-term, degrading the overall operating conditions. Thus, appropriate PAW spraying conditions are needed to make effective use of PAW to reduce the pressure drop at fabric filters from a short- and long-term point of view. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of long-term ketamine administration on vocalization to paw pressure and on spinal wind-up activity in monoarthritic rats.

PubMed

Pelissier, Teresa; Alvarez, Pedro; Hernández, Alejandro

2003-09-01

The antinociceptive effect of long-lasting ketamine administration (mini-osmotic pump) was studied in monoarthritic rats by using hindpaw pressure testing and wind-up measurement in a C-fiber reflex paradigm. Chronic ketamine induced antinociception in the monoarthritic paw and significantly suppressed mechanical hyperalgesia during the 14-day treatment period. The treatment also reduced C-reflex wind-up in the monoarthritic hindpaw. After pump removal, vocalization thresholds and spinal wind-up scores from the monoarthritic paw returned to control values, while hyperalgesia developed in the normal paw. Results suggest that ketamine upregulates NMDA receptors upon long-term administration, resulting in hyperalgesic response in the normal paw after drug withdrawal.

Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

PubMed Central

Ferreira, Renata Cristina Mendes; Almeida-Santos, Ana Flávia; Aguiar, Daniele C.; Moreira, Fabricio A.

2017-01-01

Background Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Methods Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2 μg). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2 injection. Results Aripiprazole (100 μg/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw), a nonselective opioid receptor antagonist. The role of μ-, δ-, and κ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw), naltrindole (15, 30, and 60 μg/paw), and nor-binaltorphimine (200 μg/paw), respectively. The data indicated that only the δ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw) aripiprazole-induced peripheral antinociception. Conclusion The results suggest the participation of the opioid system via δ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole. PMID:28758123

The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammation.

PubMed

Futaki, Nobuko; Harada, Masahiro; Sugimoto, Masanori; Hashimoto, Yuki; Honma, Yusuke; Arai, Iwao; Nakaike, Shiro; Hoshi, Keiko

2009-05-01

Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effects of lornoxicam in relation to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01-1 mg/kg), celecoxib (0.3-30 mg/kg) or loxoprofen (0.3-30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall-Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzyme-immunoassay. In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen significantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus.

Gait cycle analysis: parameters sensitive for functional evaluation of peripheral nerve recovery in rat hind limbs.

PubMed

Rui, Jing; Runge, M Brett; Spinner, Robert J; Yaszemski, Michael J; Windebank, Anthony J; Wang, Huan

2014-10-01

Video-assisted gait kinetics analysis has been a sensitive method to assess rat sciatic nerve function after injury and repair. However, in conduit repair of sciatic nerve defects, previously reported kinematic measurements failed to be a sensitive indicator because of the inferior recovery and inevitable joint contracture. This study aimed to explore the role of physiotherapy in mitigating joint contracture and to seek motion analysis indices that can sensitively reflect motor function. Data were collected from 26 rats that underwent sciatic nerve transection and conduit repair. Regular postoperative physiotherapy was applied. Parameters regarding step length, phase duration, and ankle angle were acquired and analyzed from video recording of gait kinetics preoperatively and at regular postoperative intervals. Stride length ratio (step length of uninjured foot/step length of injured foot), percent swing of the normal paw (percentage of the total stride duration when the uninjured paw is in the air), propulsion angle (toe-off angle subtracted by midstance angle), and clearance angle (ankle angle change from toe off to midswing) decreased postoperatively comparing with baseline values. The gradual recovery of these measurements had a strong correlation with the post-nerve repair time course. Ankle joint contracture persisted despite rigorous physiotherapy. Parameters acquired from a 2-dimensional motion analysis system, that is, stride length ratio, percent swing of the normal paw, propulsion angle, and clearance angle, could sensitively reflect nerve function impairment and recovery in the rat sciatic nerve conduit repair model despite the existence of joint contractures.

Mechanisms underlying the antinociceptive effect of mangiferin in the formalin test.

PubMed

Izquierdo, Teresa; Espinosa de los Monteros-Zuñiga, Antonio; Cervantes-Durán, Claudia; Lozada, María Concepción; Godínez-Chaparro, Beatriz

2013-10-15

The purpose of this study was to investigate the possible antinociceptive effect of mangiferin, a glucosylxanthone present in Mangifera indica L., in inflammatory pain. Furthermore, we sought to investigate the possible mechanisms action that contributes to these effects. The ipsilateral local peripheral (1-30 µg/paw), intrathecal (1-30 µg/rat) and oral (1-30 mg/kg) administration of mangiferin produced a dose-dependent reduction in formalin-induced nociception. The antinociceptive effect of this drug was similar to that induced by diclofenac after oral and local peripheral administration. Furthermore, mangiferin was also able to reduce 0.1% capsaicin- and serotonin-induced nociceptive behavior. The local peripheral antinociceptive effect of mangiferin in the formalin test was blocked by naloxone (50 μg/paw), naltrindole (1 μg/paw), 5-guanidinonaltrindole (5-GNTI, 1 μg/paw), N(G)-L-nitro-arginine methyl ester (L-NAME, 100 µg/paw), 1H-(1,2,4)-oxadiazolo [4,2-a]quinoxalin-1-one (ODQ, 50 µg/paw) and glibenclamide (50 μg/paw), but not by methiothepin (30 μg/paw). These results suggest that the antinociceptive effects induced by mangiferin are mediated by the peripheral opioidergic system involving the activation of δ, κ, and probably µ, receptors, but not serotonergic receptors. Data also suggests that mangiferin activates the NO-cyclic GMP-ATP-sensitive K(+) channels pathway in order to produce its local peripheral antinociceptive effect in the formalin test. Mangiferin may prove to be effective in treating inflammatory pain in humans. © 2013 Elsevier B.V. All rights reserved.

Anti-inflammatory activities of aqueous extract of Mesona procumbens in experimental mice.

PubMed

Huang, Guan-Jhong; Liao, Jung-Chun; Chiu, Chuan-Sung; Huang, Shyh-Shyun; Lin, Tsung-Hui; Deng, Jeng-Shyan

2012-04-01

Mesona procumbens is consumed as a herbal drink and jelly-type dessert in Taiwan. The aim of this study was to determine the mechanism of anti-inflammatory activities of the aqueous extract of M. procumbens (AMP) using the λ-carrageenin (Carr)-induced mouse paw oedema model. The fingerprint chromatogram of AMP was obtained by high-performance liquid chromatography (HPLC) analysis. To investigate the anti-inflammatory mechanism of AMP, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in paw oedema were monitored. Serum nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also evaluated. The fingerprint chromatogram from HPLC indicated that AMP contained protocatechuic acid, chlorogenic acid, vanillic acid and caffeic acid. In the anti-inflammatory test, AMP decreased paw oedema after Carr administration and increased the CAT, SOD and GPx activities and decreased the MDA level in paw oedema at 5 h after Carr injection. AMP also affected the serum NO, TNF-α and IL-1β levels at 5 h after Carr injection. Western blotting revealed that AMP decreased the expression of Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Mesona procumbens has the potential to provide a therapeutic approach to inflammation-associated disorders. Copyright © 2011 Society of Chemical Industry.

Novel phenanthridine (PHE-4i) derivative inhibits carrageenan-induced rat hind paw oedema through suppression of hydrogen sulfide.

PubMed

George, Leema; Ramasamy, Tamizhselvi; Manickam, Venkatraman; Iyer, Sathiyanarayanan Kulathu; Radhakrishnan, Vidya

2016-08-01

This study was conducted to assess the anti-inflammatory effect of a novel synthesized phenanthridine alkaloid (PHE-4i) and to examine the possible involvement of hydrogen sulfide (H2S) in anti-inflammatory mechanism. The synthesized phenanthridine derivative PHE-4i (2, 5, and 10 mg/kg) was administered intraperitoneally to rats. One hour following treatment, inflammation was induced by intraplantar injection of carrageenan (1 %), in the hind paw. Paw volume as the index of inflammation was measured before and after carrageenan injection. Neutrophil sequestration into the hind paw was quantified by measuring tissue myeloperoxidase (MPO) activity and was compared for the inhibition of H2S production. Pretreatment with PHE-4i significantly reduced carrageenan-induced hind paw weight, MPO activity, leukocyte infiltration, and H2S production in a dose-dependent manner (p < 0.001). These results indicate that the anti-inflammatory effect of PHE-4i on carrageenan-induced rat paw oedema could be via the inhibition of the gaseous mediator H2S.

Propolis reduces Leishmania amazonensis-induced inflammation in the liver of BALB/c mice.

PubMed

da Silva, Suelen S; Mizokami, Sandra S; Fanti, Jacqueline R; Miranda, Milena M; Kawakami, Natalia Y; Teixeira, Fernanda Humel; Araújo, Eduardo J A; Panis, Carolina; Watanabe, Maria A E; Sforcin, José M; Pavanelli, Wander R; Verri, Waldiceu A; Felipe, Ionice; Conchon-Costa, Ivete

2016-04-01

Experimental models of mouse paw infection with L. amazonensis show an induction of a strong inflammatory response in the skin, and parasitic migration may occur to secondary organs with consequent tissue injury. There are few studies focusing on the resolution of damage in secondary organs caused by Leishmania species-related cutaneous leishmaniasis. We investigated the propolis treatment effect on liver inflammation induced by Leishmania amazonensis infection in the mouse paw. BALB/c mice were infected in the hind paw with L. amazonensis (10(7)) promastigote forms. After 15 days, animals were treated daily with propolis (5 mg/kg), Glucantime (10 mg/kg), or with propolis plus Glucantime combined. After 60 days, mice were euthanized and livers were collected for inflammatory process analysis. Liver microscopic analysis showed that propolis reduced the inflammatory process compared to untreated infected control. There was a decrease of liver myeloperoxidase and N-acetyl-β-glucosaminidase activity levels, collagen fiber deposition, pro-inflammatory cytokine production, and plasma aspartate transaminase and alanine transaminase levels. Furthermore, propolis treatment enhanced anti-inflammatory cytokine levels and reversed hepatosplenomegaly. Our data demonstrated that daily low doses of Brazilian propolis reduced the secondary chronic inflammatory process in the liver caused by L. amazonensis subcutaneous infection in a susceptible mice strain.

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

PubMed

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

2016-02-01

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

Treatment with adipose derived mesenchymal stem cells and their conditioned media reverse carrageenan induced paw oedema in db/db mice.

PubMed

Shree, Nitya; Venkategowda, Sunil; Venkatranganna, M V; Bhonde, Ramesh R

2017-06-01

Mesenchymal stem cells are known for anti inflammatory and immunomodulatory activities. The aim of our study was to evaluate the effect of human adipose derived mesenchymal stem cells (hADMSCs) and its conditioned media (CM) on carrageenan induced acute inflammation in db/db mice. We injected 5×10 5 ADMSCs or the CM in the inflamed paw. We assessed the paw volume, serum IL6 levels and histopathology of the paw to reveal the anti inflammatory effect. We observed a single injection of hADMSCs or CM could reverse the inflammation within 24h as evidenced by reduction in paw volume, IL6 levels and histological examination. Our result equivocally demonstrates the role of CM in normalising the inflammation better than hADMSCs. This study will pave way for an alternative to anti inflammatory drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Microstructure and Low-Temperature Mechanical Properties of 304 Stainless Steel Joints by PAW + GTAW Combined Welding

NASA Astrophysics Data System (ADS)

Liu, Kun; Li, Yajiang; Wang, Juan

2016-10-01

The combined double-pass process of plasma arc welding (PAW) + gas tungsten arc welding (GTAW) was performed on 304 austenitic stainless steel with the thickness of 12 mm. Results indicated that two different morphologies of ferrite (e.g., lathy δ-ferrite and skeletal δ-ferrite) were formed within the austenite matrix in PAW weld metal (PAW-WM). GTAW weld metal (GTAW-WM) was mainly composed of fine austenite and skeletal δ-ferrite. In transition zone between PAW-WM and GTAW-WM, epitaxial growth contributed to cellular dendritic crystals transforming into columnar crystals. The tensile strength of joint is about 700 MPa. The impact toughness of WM varied from 281 J (20 °C) to 122 (-196 °C), while the impact toughness of heat-affected zone (HAZ) varied from 205 J (20 °C) to 112 J (-196 °C).

A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

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

Zhang, Qian; Ma, Ruonan; Tian, Ying

2013-05-20

Ar/O{sub 2} (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

PubMed

Arora, Priyanka; Mukherjee, Biswajit

2002-09-01

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

Orthogonal polynomial projectors for the Projector Augmented Wave (PAW) formalism.

NASA Astrophysics Data System (ADS)

Holzwarth, N. A. W.; Matthews, G. E.; Tackett, A. R.; Dunning, R. B.

1998-03-01

The PAW method for density functional electronic structure calculations developed by Blöchl(Phys. Rev. B 50), 17953 (1994) and also used by our group(Phys. Rev. B 55), 2005 (1997) has numerical advantages of a pseudopotential technique while retaining the physics of an all-electron formalism. We describe a new method for generating the necessary set of atom-centered projector and basis functions, based on choosing the projector functions from a set of orthogonal polynomials multiplied by a localizing weight factor. Numerical benefits of the new scheme result from having direct control of the shape of the projector functions and from the use of a simple repulsive local potential term to eliminate ``ghost state" problems, which can haunt calculations of this kind. We demonstrate the method by calculating the cohesive energies of CaF2 and Mo and the density of states of CaMoO4 which shows detailed agreement with LAPW results over a 66 eV range of energy including upper core, valence, and conduction band states.

["Animal hypnosis" and defensive dominant, behavioral aspect].

PubMed

Pavlygina, R A; Galashina, A G; Bogdanov, A V

2002-01-01

A stationary excitation focus produced in the sensorimotor cortex of a rabbit by rhythmic electrodermal paw stimulation was manifested in the reaction to a testing sound stimulus earlier indifferent for the animal. Regardless of the stimulated paw (left or right), reactions to the testing stimuli appeared approximately in the equal percent of cases (70.7% and 71.5%, respectively). After a single-trial induction of the "animal hypnosis" state, it was difficult to produce the dominant focus by simulation of the left paw, whereas the results of the right-paw stimulation did not differ from those obtained during control stimulation. Consequently, the influence of hypnosis on defensive stationary excitation foci in different hemispheres was not the same.

Fucoxanthin Inhibits the Inflammation Response in Paw Edema Model through Suppressing MAPKs, Akt, and NFκB.

PubMed

Choi, Jun-Hui; Kim, Na-Hyun; Kim, Sung-Jun; Lee, Hyo-Jeong; Kim, Seung

2016-03-01

Undaria pinnatifida is a well-known traditional Korean food with a variety of biological activities. Carrageenan (carr) is commonly used to induce paw edema in animal models. This study was designed to elucidate the processes underlying the anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U. pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly decreased carr-induced increased nitric oxide levels in the plasma of mice with carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide dismutase (SOD) activity against disruption in mice with carr-induced paw edema. In addition, fucoxanthin repressed carr-induced activation of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr-induced phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These results suggest that fucoxanthin may have therapeutic potential as a treatment for patients with inflammatory diseases. © 2015 Wiley Periodicals, Inc.

Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression

PubMed Central

Posadas, Inmaculada; Bucci, Mariarosaria; Roviezzo, Fiorentina; Rossi, Antonietta; Parente, Luca; Sautebin, Lidia; Cirino, Giuseppe

2004-01-01

Injection of carrageenan 1% (50 μl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old, weighing 32–34 g, displayed a consistent response in both phases. In 8-week-old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NOx) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E2 levels that peak in the second phase at the 72 h point. Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX-2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX-2 expression at 6 and 24 h in 3–8-week-old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age–weight of mice, as opposite to COX-2 that is present only in the second phase of the oedema and is not linked to mouse age–weight. Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX-1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX-1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is biphasic and age-weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX-1 and COX-2 in response to carrageenan injection in the two phases of the mouse paw oedema. PMID:15155540

How does the canine paw pad attenuate ground impacts? A multi-layer cushion system.

PubMed

Miao, Huaibin; Fu, Jun; Qian, Zhihui; Ren, Luquan; Ren, Lei

2017-12-15

Macroscopic mechanical properties of digitigrade paw pads, such as non-linear elastic and variable stiffness, have been investigated in previous studies; however, little is known about the micro-scale structural characteristics of digitigrade paw pads, or the relationship between these characteristics and the exceptional cushioning of the pads. The digitigrade paw pad consists of a multi-layered structure, which is mainly comprised of a stratified epithelium layer, a dermis layer and a subcutaneous layer. The stratified epithelium layer and dermal papillae constitute the epidermis layer. Finite element analyses were carried out and showed that the epidermis layer effectively attenuated the ground impact across impact velocities of 0.05-0.4 m/s, and that the von Mises stresses were uniformly distributed in this layer. The dermis layer encompassing the subcutaneous layer can be viewed as a hydrostatic system, which can store, release and dissipate impact energy. All three layers in the paw pad work as a whole to meet the biomechanical requirements of animal locomotion. These findings provide insights into the biomechanical functioning of digitigrade paw pads and could be used to facilitate bio-inspired, ground-contacting component development for robots and machines, as well as contribute to footwear design. © 2017. Published by The Company of Biologists Ltd.

Gelam Honey Attenuates Carrageenan-Induced Rat Paw Inflammation via NF-κB Pathway

PubMed Central

Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

2013-01-01

The activation of nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o.) and NSAID Indomethacin (10 mg/kg, p.o.), in two time points (1 and 7 days). Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50) and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α. PMID:24015236

The anti-inflammatory effect of diclofenac is considerably augmented by topical capsaicinoids-containing patch in carrageenan-induced paw oedema of rat.

PubMed

Ercan, Nilufer; Uludag, Mecit Orhan; Agis, Erol Rauf; Demirel-Yilmaz, Emine

2013-12-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in musculoskeletal disorders, but their systemic adverse effects limit their therapeutic benefit in local inflammation. On the other hand, topical preparations of capsaicinoids are widely used for musculoskeletal disorders as a complementary therapy. In this study, the effects of both topical capsaicinoids-containing patch and local subcutaneous capsaicin application on the anti-inflammatory action of NSAID were examined. Carrageenan-induced paw oedema of rats was used as the inflammation model. The volume and weight of the paw oedema and plasma extravasation in the paw were determined after carrageenan injection. The systemic application of diclofenac (3 mg/kg), which is an NSAID, significantly decreased the volume and weight of the paw oedema. Topical capsaicinoids-containing patch application or local capsaicin injection (2, 10, 20 μg/paw) alone did not cause any effect on oedema volume and weight. However, the combination of diclofenac with topical capsaicinoids-containing patch significantly increased the effectiveness of diclofenac on inflammation. Evans blue content of the paws that represents plasma extravasation was decreased by capsaicinoids-containing patch with and without diclofenac and diclofenac combination with the lowest dose of capsaicin injection. The results of this study indicate that topical application of capsaicinoids-containing patch enhances the anti-inflammatory effect of diclofenac and its beneficial effect may not purely relate to its capsaicin content. In the treatment of local inflammatory disorders, the combination of NSAID with topical capsaicinoids-containing patch could increase the anti-inflammatory efficiency of drug without systemic side effects.

Long thermal interactions of PAW with normal tooth structure and different dental biomaterials

NASA Astrophysics Data System (ADS)

Bostǎnaru, Andra-Cristina; Hnatiuc, Eugen; Roşca, Irina; Vasiliu, Ana Lavinia; Doroftei, Mirela; Ursu, Laura; Ailincǎi, Luminiţa Iuliana; Nǎstasǎ, Valentin; Mareş, Mihai

2016-12-01

Plasma activated water (PAW) has been widely considered to be an effective method for decontamination. Recently, numerous studies report that plasma-activated water (PAW) also has antibacterial ability to prevent or treat dental caries and periodontal related diseases. In this context, this study presents the first report to evaluate the plasma activated water effect on vital teeth enamel and different dental biomaterials. In this context, this study presents the first report to evaluate long thermal interactions of plasma activated water effect on vital teeth enamel and different dental biomaterials without organic substrate. The results suggest that the long-thermal of treatment with PAW of enamel without organic substrate can dissolve the apatite crystallites which are highly organized hierarchical structures.

Neonatal transection of the corpus callosum affects paw preference lateralization of adult Swiss mice.

PubMed

Manhães, Alex C; Krahe, Thomas E; Caparelli-Dáquer, Egas; Ribeiro-Carvalho, Anderson; Schmidt, Sergio L; Filgueiras, Cláudio C

2003-09-11

In the present work, the hypothesis that the ontogenetic development of the corpus callosum (CC) affects the establishment of behavioral lateralization was tested by studying paw preference performance in adult Swiss mice that were subjected to mid-sagittal transection of the CC on the first postnatal day. Magnitude and direction of laterality were evaluated independently. No significant differences between groups were found for the magnitude of paw preference. On the other hand, the transected group presented a significant populational bias favoring the left paw that was not present in the control groups. These results lend support to the hypothesis that the development of the CC plays a role in the establishment of the normal pattern of behavioral lateralization.

Low-cost three-dimensional gait analysis system for mice with an infrared depth sensor.

PubMed

Nakamura, Akihiro; Funaya, Hiroyuki; Uezono, Naohiro; Nakashima, Kinichi; Ishida, Yasumasa; Suzuki, Tomohiro; Wakana, Shigeharu; Shibata, Tomohiro

2015-11-01

Three-dimensional (3D) open-field gait analysis of mice is an essential procedure in genetic and nerve regeneration research. Existing gait analysis systems are generally expensive and may interfere with the natural behaviors of mice because of optical markers and transparent floors. In contrast, the proposed system captures the subjects shape from beneath using a low-cost infrared depth sensor (Microsoft Kinect) and an opaque infrared pass filter. This means that we can track footprints and 3D paw-tip positions without optical markers or a transparent floor, thereby preventing any behavioral changes. Our experimental results suggest with healthy mice that they are more active on opaque floors and spend more time in the center of the open-field, when compared with transparent floors. The proposed system detected footprints with a comparable performance to existing systems, and precisely tracked the 3D paw-tip positions in the depth image coordinates. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Gelam Honey Inhibits the Production of Proinflammatory, Mediators NO, PGE2, TNF-α, and IL-6 in Carrageenan-Induced Acute Paw Edema in Rats

PubMed Central

Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

2012-01-01

Natural honey is well known for its therapeutic value and has been used in traditional medicine of different cultures throughout the world. The aim of this study was to investigate the anti-inflammatory effect of Malaysian Gelam honey in inflammation-induced rats. Paw edema was induced by a subplantar injection of 1% carrageenan into the rat right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) Indomethacin (10 mg/kg, p.o.) or Gelam honey at different doses (1 or 2 g/kg, p.o.). The increase in footpad thickness was considered to be edema, which was measured using a dial caliper. Plasma and paw tissue were collected to analyze the production of inflammatory mediators, such as NO, PGE2, TNF-α, and IL-6, as well as iNOS and COX-2. The results showed that Gelam honey could reduce edema in a dose-dependent fashion in inflamed rat paws, decrease the production of NO, PGE2, TNF-α, and IL-6 in plasma, and suppress the expression of iNOS, COX-2, TNF-α, and IL-6 in paw tissue. Oral pretreatment of Gelam honey at 2 g/kg of body weight at two time points (1 and 7 days) showed a significantly decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory drug Indomethacin (NSAID), both in plasma and tissue. Thus, our results suggest that Gelam honey has anti-inflammatory effects by reducing the rat paw edema size and inhibiting the production of proinflammatory mediators. Gelam honey is potentially useful for treating inflammatory conditions. PMID:22919407

Antiedematogenic and antioxidant properties of high molecular weight protein sub-fraction of Calotropis procera latex in rat.

PubMed

Chaudhary, Priyanka; de Araújo Viana, Carolina; Ramos, Marcio V; Kumar, Vijay L

2015-03-01

The aim was to evaluate the effect of high molecular weight protein fraction of Calotropis procera latex on edema formation and oxidative stress in carrageenan-induced paw inflammation. A sub-plantar injection of carrageenan was given to induce edema in the hind paw of the rat. The inhibitory effect of high molecular weight protein fraction of C. procera latex was evaluated following intravenous administration (5 and 25 mg/kg body weight) and was compared with that of diclofenac given orally (5 mg/kg). The levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and myeloperoxidase (MPO) were measured in the inflamed paw tissue at the end of the study. The high molecular weight protein fraction obtained from the latex of C. procera produced a dose-dependent inhibition of edema formation that was accompanied by normalization of levels of oxidative stress markers (GSH and TBARS) and MPO, a marker for neutrophils in the paw tissue. The high molecular weight protein fraction of C. procera latex ameliorates acute inflammation in the paw through its antioxidant effect.

Arctic daily temperature and precipitation extremes: Observed and simulated physical behavior

NASA Astrophysics Data System (ADS)

Glisan, Justin Michael

Simulations using a six-member ensemble of Pan-Arctic WRF (PAW) were produced on two Arctic domains with 50-km resolution to analyze precipitation and temperature extremes for various periods. The first study used a domain developed for the Regional Arctic Climate Model (RACM). Initial simulations revealed deep atmospheric circulation biases over the northern Pacific Ocean, manifested in pressure, geopotential height, and temperature fields. Possible remedies to correct these large biases, such as modifying the physical domain or using different initial/boundary conditions, were unsuccessful. Spectral (interior) nudging was introduced as a way of constraining the model to be more consistent with observed behavior. However, such control over numerical model behavior raises concerns over how much nudging may affect unforced variability and extremes. Strong nudging may reduce or filter out extreme events, since the nudging pushes the model toward a relatively smooth, large-scale state. The question then becomes---what is the minimum spectral nudging needed to correct biases while not limiting the simulation of extreme events? To determine this, we use varying degrees of spectral nudging, using WRF's standard nudging as a reference point during January and July 2007. Results suggest that there is a marked lack of sensitivity to varying degrees of nudging. Moreover, given that nudging is an artificial forcing applied in the model, an important outcome of this work is that nudging strength apparently can be considerably smaller than WRF's standard strength and still produce reliable simulations. In the remaining studies, we used the same PAW setup to analyze daily precipitation extremes simulated over a 19-year period on the CORDEX Arctic domain for winter and summer. We defined these seasons as the three-month period leading up to and including the climatological sea ice maximum and minimum, respectively. Analysis focused on four North American regions defined using climatological records, regional weather patterns, and geographical/topographical features. We compared simulated extremes with those occurring at corresponding observing stations in the U.S. National Climate Data Center's (NCDC's) Global Summary of the Day. Our analysis focused on variations in features of the extremes such as magnitudes, spatial scales, and temporal regimes. Using composites of extreme events, we also analyzed the processes producing these extremes, comparing circulation, pressure, temperature and humidity fields from the ERA-Interim reanalysis and the model output. The analysis revealed the importance of atmospheric convection in the Arctic for some extreme precipitation events and the overall importance of topographic precipitation. The analysis established the physical credibility of the simulations for extreme behavior, laying a foundation for examining projected changes in extreme precipitation. It also highlighted the utility of the model for extracting behavior that one cannot discern directly from the observations, such as summer convective precipitation.

Xylitol and Your Dog: Danger, Paws Off

MedlinePlus

... Home For Consumers Consumer Updates Xylitol and Your Dog: Danger, Paws Off Share Tweet Linkedin Pin it ... vitamins mouthwash toothpaste Why is Xylitol Dangerous to Dogs, but Not People? In both people and dogs, ...

Anti-inflammatory effect of combined tetramethylpyrazine, resveratrol and curcumin in vivo.

PubMed

Chen, Long; Liu, Tianjun; Wang, Qiangsong; Liu, Juan

2017-04-27

Resveratrol and curcumin, as natural flavones products, have good therapeutic effect in acute and chronic inflammation; on the other hand, tetramethylpyrazine (TMP) has angiogenesis and vessel protection effect as well as anti-inflammatory function. In this paper, the anti-inflammatory effect of the tetramethylpyrazine, resveratrol and curcumin (TRC) combination in acute and chronic inflammation was reported in vivo. The dose of the combined three natural products was optimized based on the acute paw swelling mouse model with a Uniform Design methodology. The therapeutic effect of TRC combination on chronic inflammation was investigated by using the collagen-induced arthritis (CIA) rat model based upon the following indexes: the volume of paw swelling, arthritis score, serum mediators and histological examination as well as immunohistochemical staining. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were measured and the pathological sections of liver and kidney were analysed. LD 50 was measured based on the acute oral toxicity (AOT) standard method. The best formulation was the three components combined at the same mass proportion revealed by the Uniform Design methodology. This combination could significantly reduce the paw swelling in acute paw swelling mouse model, could reduce paw swelling and alleviate the damage in joint structural of ankle, cartilages and fibrous tissue in CIA rat model. The dose relationship was clear in both cases. Immunohistochemical staining of ankle tissue revealed that TRC combination was able to inhibit the expression of NF-κB p65 and TNF-α which were closely related to the inflammatory process. Analysis of serum mediators revealed TRC combination could inhibit the production of TNF-α, IL-1β, and IL-6 in the serum. Toxic study revealed this formulation was low toxic, LD 50 was larger than 5 g/kg, both the level of ALT and AST and histopathology in the liver and kidney exhibited no distinctions between the TRC combination and the blank group, no mortality occurred at the administered doses of 5 g/kg. The results showed this formulation could provide a novel potent treatment for acute and chronic inflammation (RA) without side effect like gastric injury occurring in NSAIDs.

Pharmacological and biochemical studies on protective effects of mangiferin and its interaction with nitric oxide (NO) modulators in adjuvant-induced changes in arthritic parameters, inflammatory, and oxidative biomarkers in rats.

PubMed

Pal, Rishi; Chaudhary, Manju J; Tiwari, Prafulla Chandra; Nath, Rajendra; Pant, Kamlesh Kumar

2018-06-22

Current study was designed to evaluate protective effect of mangiferin and its interaction with low dose of nitric oxide (NO) modulators in complete Freund's adjuvant (CFA) inoculated rats. Male wistar rats (200-300 g, n = 8 per group) were used in the study. On day ''0'' of study arthritis was induced in rats by injecting 0.2 ml CFA in sub-planter region of right hind paw of animals. Treatment with methotrexate (5 mg/kg), mangiferin (10-30 mg/kg) alone and in combination with NO modulators was given (i.p.) from days 14 to 28. After 28 days, blood and joint synovial fluid was collected for biochemical analysis and rat paws were excised to estimate MDA and SOD in tissue (paw) homogenates. CFA inoculation significantly increases (1) arthritic index, (2) ankle diameter, (3) paw volume, and (4) serum TNF-α, IL-6, IL-1β, and synovial TNF-α levels (p < 0.001). The serum Th 1 (IFN-γ) and Th 2 (IL-4) cytokine levels, MDA levels in rat paw tissue homogenates and serum NF-κB levels were also found significantly increased. Significant decrease in serum IL-10 levels and SOD activity was found after CFA inoculation. These CFA-induced arthritic changes, cytokine profile, and oxidative stress markers were significantly reversed by mangiferin (10-30 mg/kg) treatment alone and in combination with L-arginine and L-NAME nitric oxide modulators (p < 0.05). Treatment with methotrexate (5 mg/kg) also significantly reversed these adjuvant changes (p < 0.05). However, effect of methotrexate was less marked as compared to mangiferin (30 mg/kg) alone and in combination with L-NAME (10 mg/kg), but was comparable or slightly better than mangiferin (10 and 20 mg/kg). Thus, on the basis of our findings, we can suggest that interaction of mangiferin with nitric oxide modulators may have therapeutic value for chronic inflammatory disease such as RA.

Comparison of plasma generated nitrogen fertilizer to conventional fertilizers ammonium nitrate and sodium nitrate for pre-emergent and seedling growth

NASA Astrophysics Data System (ADS)

Andhavarapu, A.; King, W.; Lindsay, A.; Byrns, B.; Knappe, D.; Fonteno, W.; Shannon, S.

2014-10-01

Plasma source generated nitrogen fertilizer is compared to conventional nitrogen fertilizers in water for plant growth. Root, shoot sizes, and weights are used to examine differences between plant treatment groups. With a simple coaxial structure creating a large-volume atmospheric glow discharge, a 162 MHz generator drives the air plasma. The VHF plasma source emits a steady state glow; the high drive frequency is believed to inhibit the glow-to-arc transition for non-thermal discharge generation. To create the plasma activated water (PAW) solutions used for plant treatment, the discharge is held over distilled water until a 100 ppm nitrate aqueous concentration is achieved. The discharge is used to incorporate nitrogen species into aqueous solution, which is used to fertilize radishes, marigolds, and tomatoes. In a four week experiment, these plants are watered with four different solutions: tap water, dissolved ammonium nitrate DI water, dissolved sodium nitrate DI water, and PAW. Ammonium nitrate solution has the same amount of total nitrogen as PAW; sodium nitrate solution has the same amount of nitrate as PAW. T-tests are used to determine statistical significance in plant group growth differences. PAW fertilization chemical mechanisms are presented.

Non-auditory, electrophysiological potentials preceding dolphin biosonar click production.

PubMed

Finneran, James J; Mulsow, Jason; Jones, Ryan; Houser, Dorian S; Accomando, Alyssa W; Ridgway, Sam H

2018-03-01

The auditory brainstem response to a dolphin's own emitted biosonar click can be measured by averaging epochs of the instantaneous electroencephalogram (EEG) that are time-locked to the emitted click. In this study, averaged EEGs were measured using surface electrodes placed on the head in six different configurations while dolphins performed an echolocation task. Simultaneously, biosonar click emissions were measured using contact hydrophones on the melon and a hydrophone in the farfield. The averaged EEGs revealed an electrophysiological potential (the pre-auditory wave, PAW) that preceded the production of each biosonar click. The largest PAW amplitudes occurred with the non-inverting electrode just right of the midline-the apparent side of biosonar click generation-and posterior of the blowhole. Although the source of the PAW is unknown, the temporal and spatial properties rule out an auditory source. The PAW may be a neural or myogenic potential associated with click production; however, it is not known if muscles within the dolphin nasal system can be actuated at the high rates reported for dolphin click production, or if sufficiently coordinated and fast motor endplates of nasal muscles exist to produce a PAW detectable with surface electrodes.

Antihyperalgesic Effects of Indomethacin, Ketorolac, and Metamizole in Rats: Effects of Metformin.

PubMed

Guzmán-Priego, Crystell Guadalupe; Méndez-Mena, Roberto; Baños-González, Manuel Alfonso; Araiza-Saldaña, Claudia Ivonne; Castañeda-Corral, Gabriela; Torres-López, Jorge Elías

2017-03-01

Preclinical Research Metformin-dependent mechanisms have been implicated in the antinociceptive effect of some non-steroidal anti-inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan-induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia. Local peripheral or systemic administration of indomethacin, ketorolac or metamizole dose-dependently reduced carrageenan-induced thermal hyperalgesia. Local peripheral pre-treatment with metformin (800 µg/paw) partially inhibited the anti-hyperalgesic effect of indomethacin (200 µg/paw) and metamizole (200 µg/paw), but not that of ketorolac (200 µg/paw). In contrast, systemic pre-treatment with metformin (200 mg/kg) attenuated the antihyperalgesic effect of metamizole (10 mg/kg), but not that observed with either indomethacin (10 mg/kg) or ketorolac (10 mg/kg). These findings suggest that some but not all NSAIDs have effects mediated by metformin-dependent mechanisms. Drug Dev Res 78 : 98-104, 2017. ©2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of bedding material and running wheel surface on paw wounds in male and female Syrian hamsters.

PubMed

Beaulieu, A; Reebs, S G

2009-01-01

The present study investigated the effects of bedding material (pine shavings versus beta chip) and running wheel surfaces (standard metal bars versus metal bars covered with a plastic mesh) on the occurrence of wounds on the paws of male and female Syrian (golden) hamsters, Mesocricetus auratus. Four groups of 10 males and 10 females were each assigned to one of the following treatments: pine/no mesh, pine/mesh, chips/no mesh and chips/mesh. Each hamster paw was observed at 1-3-day intervals for 60 days. A total of 1-3 wounds, separate in time, developed on the paws (mostly the hind ones) of almost all animals. Wounds appeared as small pinpricks, cuts or scabs, mostly on the palms. Females ran 15% less than males, yet their front paws were more commonly affected and their wounds tended to last longer. Hamsters with plastic mesh inside their wheels took longer to develop wounds but once they appeared, the wounds were larger and lasted longer. Hamsters on pine shavings developed fewer wounds and had more wound-free days. Hamsters kept running at high levels and many wounds did not heal during the study, suggesting a need for veterinary intervention.

Evaluation of Rhodiola rosea L. extract on affective and physical signs of nicotine withdrawal in mice.

PubMed

Mattioli, Laura; Perfumi, Marina

2011-03-01

The aim of the present study was to investigate the effects of a Rhodiola rosea L. extract on the prevention of the development of nicotine dependence and for the reduction of abstinence suffering following nicotine cessation in mice. Dependence was induced in mice by subcutaneous injections of nicotine (2 mg/kg, 4 times/day) for eight days. Spontaneous abstinence syndrome was evaluated 20 h after the last nicotine administration, by analysis of withdrawal signs, as affective (anxiety-like behaviour) and physical (somatic signs and locomotor activity). Rhodiola rosea L. extract was administered orally during nicotine treatment (10, 15 and 20 mg/kg) or during nicotine withdrawal (20 mg/kg). Results show that both affective and somatic signs (head shaking, paw tremors, body tremors, ptosis, jumping, piloerection and chewing) induced by nicotine withdrawal are abolished by administration of Rhodiola rosea L. extract in a dose-dependent fashion, during both nicotine exposure and nicotine cessation. In conclusion, our data encourage additional studies to define the use of R. rosea L. as a therapeutic approach in the treatment of smoking cessation.

Preliminary analysis of variability in concentration of fine particulate matter - PM1.0, PM2.5 and PM10 in area of Poznań city

NASA Astrophysics Data System (ADS)

Sówka, Izabela; Chlebowska-Styś, Anna; Mathews, Barbara

2018-01-01

It is commonly known, that suspended particulate matter pose a threat to human life and health, negatively influence the flora, climate and also materials. Especially dangerous is the presence of high concentration of particulate matter in the area of cities, where density of population is high. The research aimed at determining the variability of suspended particulate matter concentration (PM1.0, PM2.5 and PM10) in two different thermal seasons, in the area of Poznań city. As a part of carried out work we analyzed the variability of concentrations and also performed a preliminary analysis of their correlation. Measured concentrations of particulate matter were contained within following ranges: PM10 - 8.7-69.6 μg/m3, PM2.5 - 2.2-88.5 μg/m3, PM1.0 - 2.5-22.9 μg/m3 in the winter season and 1.0-42.8 μg/m3 (PM10), 1.2-40.3 μg/m3 (PM2.5) and 2.7-10.4 (PM1.0) in the summer season. Preliminary correlative analysis indicated interdependence between the temperature of air, the speed of wind and concentration of particulate matter in selected measurement points. The values of correlation coefficients between the air temperature, speed of wind and concentrations of particulate matter were respectively equal to: for PM10: -0.59 and -0.55 (Jana Pawła II Street), -0.53 and -0.53 (Szymanowskiego Street), for PM2.5: -0.60 and -0.53 (Jana Pawła II Street) and for PM1.0 -0.40 and -0.59 (Jana Pawła II Street).

Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors

PubMed Central

Ängeby Möller, Kristina; Kinert, Susanne; Størkson, Rolf; Berge, Odd-Geir

2012-01-01

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12–8.0 mg/mL) or carrageenan (0.47–30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment. PMID:23071540

Historical analysis of Newfoundland dog fur colour genetics

PubMed Central

Bondeson, J.

2015-01-01

This article makes use of digitized historic newspapers to analyze Newfoundland dog fur colour genetics, and fur colour variations over time. The results indicate that contrary to the accepted view, the ‘Solid’ gene was introduced into the British population of Newfoundland dogs in the 1840s. Prior to that time, the dogs were white and black (Landseer) or white and brown, and thus spotted/spotted homozygotes. Due to ‘Solid’ being dominant over ‘spotted’, and selective breeding, today the majority of Newfoundland dogs are solid black. Whereas small white marks on the chest and/or paw appears to be a random event, the historical data supports the existence of an ‘Irish spotted’ fur colour pattern, with white head blaze, breast, paws and tail tip, in spotted/spotted homozygotes. PMID:26623371

Pawedness Trait Test (PaTRaT)—A New Paradigm to Evaluate Paw Preference and Dexterity in Rats

PubMed Central

Cunha, Ana M.; Esteves, Madalena; das Neves, Sofia P.; Borges, Sónia; Guimarães, Marco R.; Sousa, Nuno; Almeida, Armando; Leite-Almeida, Hugo

2017-01-01

In rodents, dexterity is commonly analyzed in preference paradigms in which animals are given the chance to use either the left or the right front paws to manipulate food. However, paw preference and dexterity at population and individual levels are controversial as results are incongruent across paradigms. We have therefore developed a semi-quantitative method—the pawdeness trait test (PaTRaT)—to evaluate paw preference degree in rats. The PaTRaT consists in a classification system, ranging from +4 to −4 where increasingly positive and negative values reflect the bias for left or right paw use, respectively. Sprague-Dawley male rats were confined into a metal rectangular mesh cylinder, from which they can see, smell and reach sugared rewards with their paws. Due to its size, the reward could only cross the mesh if aligned with its diagonal, imposing additional coordination. Animals were allowed to retrieve 10 rewards per session in a total of four sessions while their behavior was recorded. PaTRaT was repeated 4 and 8 weeks after the first evaluation. To exclude potential bias, rats were also tested for paw fine movement and general locomotion in other behavioral paradigms as well as impulsivity (variable delay-to-signal, VDS), memory and cognitive flexibility (water maze). At the population level 54% of the animals presented a rightward bias. Individually, all animals presented marked side-preferences, >2 and <−2 for left- and right-sided bias, respectively, and this preference was stable across the three evaluations. Inter-rater consistency was very high between two experienced raters and substantial when two additional inexperienced raters were included. Left- and right-biased animals presented no differences in the ability to perform fine movements with any of the forelimbs (staircase) and general locomotor performance. Additionally, these groups performed similarly in executive function and memory tasks. In conclusion, PaTRaT is able to reliably classify rats’ pawedness direction and degree. PMID:29089877

Inhibitory Effects of Medium Molecular Weight Heparinyl Amino Acid Derivatives on Ischemic Paw Edema in Mice.

PubMed

Takeda, Seiichi; Toda, Takao; Nakamura, Kazuki

2016-01-01

We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors.

PubMed

Olson, William; Abdus-Saboor, Ishmail; Cui, Lian; Burdge, Justin; Raabe, Tobias; Ma, Minghong; Luo, Wenqin

2017-10-12

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated Mrgprd CreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd + nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the "enlarged representation" of plantar paw regions in the CNS.

Angiotensin peptides attenuate platelet-activating factor-induced inflammatory activity in rats.

PubMed

Sato, Akira; Yokoyama, Izumi; Ebina, Keiichi

2015-11-01

Angiotensin (Ang)--a peptide that is part of the renin-angiotensin system-induces vasoconstriction and a subsequent increase in blood pressure; Ang peptides, especially AngII, can also act as potent pro-inflammatory mediators. Platelet-activating factor (PAF) is a potent phospholipid mediator that is implicated in many inflammatory diseases. In this study, we investigated the effects of Ang peptides (AngII, AngIII, and AngIV) on PAF-induced inflammatory activity. In experiments using a rat hind-paw oedema model, AngII markedly and dose-dependently attenuated the paw oedema induced by PAF. The inhibitory effects of AngIII and AngIV on PAF-induced paw oedema were lower than that of AngII. Two Ang receptors, the AT1 and AT2 receptors, did not affect the AngII-mediated attenuation of PAF-induced paw oedema. Moreover, intrinsic tyrosine fluorescence studies demonstrated that AngII, AngIII, and AngIV interact with PAF, and that their affinities were closely correlated with their inhibitory effects on PAF-induced rat paw oedema. Also, AngII interacted with metabolite/precursor of PAF (lyso-PAF), and an oxidized phospholipid, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), which bears a marked structural resemblance to PAF. Furthermore, POVPC dose-dependently inhibited AngII-mediated attenuation of PAF-induced paw oedema. These results suggest that Ang peptides can attenuate PAF-induced inflammatory activity through binding to PAF and lyso-PAF in rats. Therefore, Ang peptides may be closely involved in the regulation of many inflammatory diseases caused by PAF. Copyright © 2015 Elsevier Inc. All rights reserved.

The Ethanolic Stem-Bark Extract of Antrocaryon micraster Inhibits Carrageenan-Induced Pleurisy and Pedal Oedema in Murine Models of Inflammation

PubMed Central

Essel, Leslie B.; Duduyemi, Babatunde M.

2017-01-01

We investigated the antioxidant and anti-inflammatory effects of a 70% v/v ethanol extract of the stem bark of Antrocaryon micraster on murine models of carrageenan-induced pleurisy and paw oedema. Rat pleural fluid was analysed for volume, protein content, and leucocytes, while lung histology was assessed for damage. Lung tissue homogenates were assayed for glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and myeloperoxidase (MPO). Phytochemical analysis was carried out on the stem bark. Acute toxicity studies were conducted in rats. In the pleurisy model the extract (30–300 mg/kg) significantly reduced the volume and amount of proteins and leucocytes in the exudate and also protected against lung injury. Tissue level of GSH and SOD and CAT expression were increased while MDA level and MPO activity were reduced. The peak and total oedema responses were significantly suppressed when given both preemptively and curatively in the mice paw oedema test. Saponins, alkaloids, triterpenoids, and tannins were present in the stem bark. A. micraster extract exhibited no apparent acute toxicity. We conclude that the ethanolic stem-bark extract of A. micraster has antioxidant action and exhibits significant anti-inflammatory activity through suppression of pleurisy and paw oedema induced with carrageenan. PMID:28798953

Sub-Saharan Africa Report.

DTIC Science & Technology

1987-01-06

of the implementation of [words indistinct] and 1986 emergency projects. 3. Economic rehabilitation of the province including cashew nut and timber... cashew , citrus, paw- paw and pineapples. The Bantaji pilot farm (in the North) recorded an in- crease in its rice production. In the Dugusi

Histamine paw edema of mice was increased and became H[sub 2]-antagonist sensitive by co-injection of nitric oxide forming agents, but serotonin paw edema was decreased

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

Oyanagui, Yoshihiko; Sato, Sachio

1993-01-01

Nitric oxide (NO) surprisingly caused the opposite effect on histamine and serotonin edema. The local injection of acidified nitrite (0.3-30 [mu]g/paw which correspond 10 [mu]g-1mg/kg) increased histamine edema of mice up to 45[plus minus]4% and suppressed serotonin edema to 90[plus minus]3%. Other NO-generators (nitroprusside sodium and hydroxylamine) showed similar effects. These results were in accordance with previous data on endogenous NO. Methylene blue (MB, 30ng/paw which corresponds to 1 [mu]g/kg) suppressed histamine edema (62[plus minus]3%) and increased serotonin edema (43[plus minus]3%) in normal mice, being reversed by acidified nitrite. This suggests the involvement of guanosine 3[prime], 5[prime]-cyclic monophosphate (cGMP) formationmore » for the action of NO. Histamine edema became sensitive to H[sub 2]-antagonist, cimetidine, by co-injection of 30 [mu]g/paw (which corresponds to 1mg/kg) acidified nitrite (ED[sub 50] = 30 [mu]g/kg versus [much gt] 1mg/kg). NO seemed to modify the histamine receptor(s) or tautomeric form of histamine. NO, O[sup [minus

Microstructure and fatigue resistance of high strength dual phase steel welded with gas metal arc welding and plasma arc welding processes

NASA Astrophysics Data System (ADS)

Ahiale, Godwin Kwame; Oh, Yong-Jun; Choi, Won-Doo; Lee, Kwang-Bok; Jung, Jae-Gyu; Nam, Soo Woo

2013-09-01

This study presents the microstructure and high cycle fatigue performance of lap shear joints of dual phase steel (DP590) welded using gas metal arc welding (GMAW) and plasma arc welding (PAW) processes. High cycle fatigue tests were conducted on single and double lap joints under a load ratio of 0.1 and a frequency of 20 Hz. In order to establish a basis for comparison, both weldments were fabricated to have the same weld depth in the plate thickness. The PAW specimens exhibited a higher fatigue life, a gentle S-N slope, and a higher fatigue limit than the GMAW specimens. The improvement in the fatigue life of the PAW specimens was primarily attributed to the geometry effect that exhibited lower and wider beads resulting in a lower stress concentration at the weld toe where cracks initiate and propagate. Furthermore, the microstructural constituents in the heat-affected zone (HAZ) of the PAW specimens contributed to the improvement. The higher volume fraction of acicular ferrite in the HAZ beneath the weld toe enhanced the PAW specimen's resistance to fatigue crack growth. The double lap joints displayed a higher fatigue life than the single lap joints without changing the S-N slope.

Rapid ultrasonic stimulation of inflamed tissue with diagnostic intent

PubMed Central

McClintic, Abbi M.; Dickey, Trevor C.; Gofeld, Michael; Ray Illian, P.; Kliot, Michel; Kucewicz, John C.; Loeser, John D.; Richebe, Philippe G.; Mourad, Pierre D.

2013-01-01

Previous studies have observed that individual pulses of intense focused ultrasound (iFU) applied to inflamed and normal tissue can generate sensations, where inflamed tissue responds at a lower intensity than normal tissue. It was hypothesized that successively applied iFU pulses will generate sensation in inflamed tissue at a lower intensity and dose than application of a single iFU pulse. This hypothesis was tested using an animal model of chronic inflammatory pain, created by injecting an irritant into the rat hind paw. Ultrasound pulses were applied in rapid succession or individually to rats' rear paws beginning at low peak intensities and progressing to higher peak intensities, until the rats withdrew their paws immediately after iFU application. Focused ultrasound protocols consisting of successively and rapidly applied pulses elicited inflamed paw withdrawal at lower intensity and estimated tissue displacement values than single pulse protocols. However, both successively applied pulses and single pulses produced comparable threshold acoustic dose values and estimates of temperature increases. This raises the possibility that temperature increase contributed to paw withdrawal after rapid iFU stimulation. While iFU-induction of temporal summation may also play a role, electrophysiological studies are necessary to tease out these potential contributors to iFU stimulation. PMID:23927192

Development and validation of the positive affect and well-being scale for the neurology quality of life (Neuro-QOL) measurement system.

PubMed

Salsman, John M; Victorson, David; Choi, Seung W; Peterman, Amy H; Heinemann, Allen W; Nowinski, Cindy; Cella, David

2013-11-01

To develop and validate an item-response theory-based patient-reported outcomes assessment tool of positive affect and well-being (PAW). This is part of a larger NINDS-funded study to develop a health-related quality of life measurement system across major neurological disorders, called Neuro-QOL. Informed by a literature review and qualitative input from clinicians and patients, item pools were created to assess PAW concepts. Items were administered to a general population sample (N = 513) and a group of individuals with a variety of neurologic conditions (N = 581) for calibration and validation purposes, respectively. A 23-item calibrated bank and a 9-item short form of PAW was developed, reflecting components of positive affect, life satisfaction, or an overall sense of purpose and meaning. The Neuro-QOL PAW measure demonstrated sufficient unidimensionality and displayed good internal consistency, test-retest reliability, model fit, convergent and discriminant validity, and responsiveness. The Neuro-QOL PAW measure was designed to aid clinicians and researchers to better evaluate and understand the potential role of positive health processes for individuals with chronic neurological conditions. Further psychometric testing within and between neurological conditions, as well as testing in non-neurologic chronic diseases, will help evaluate the generalizability of this new tool.

The Effects of Spectral Nudging on Arctic Temperature and Precipitation Extremes as Produced by the Pan-Arctic WRF

NASA Astrophysics Data System (ADS)

Glisan, J. M.; Gutowski, W. J.; Higgins, M.; Cassano, J. J.

2011-12-01

Pan-Arctic WRF (PAW) simulations produced using the 50-km wr50a domain developed for the fully-coupled Regional Arctic Climate Model (RACM) were found to produce deep atmospheric circulation biases over the northern Pacific Ocean, manifested in pressure, geopotential height, and temperature fields. Various remedies were unsuccessfully tested to correct these large biases, such as modifying the physical domain or using different initial/boundary conditions. Spectral (interior) nudging was introduced as a way of constraining the model to be more consistent with observed behavior. However, such control over numerical model behavior raises concerns over how much nudging may affect unforced variability and extremes. Strong nudging may reduce or filter out extreme events, since the nudging pushes the model toward a relatively smooth, large-scale state. The question then becomes - what is the minimum spectral nudging needed to correct the biases occurring on the RACM domain while not limiting PAW simulation of extreme events? To determine this, case studies were devised, using a six-member PAW ensemble on the RACM grid with varying spectral nudging strength. Two simulations were run, one in the cold season (January 2007) and one in a warm season (July 2007). Precipitation and 2-m temperature fields were extracted from the output and analyzed to determine how changing spectral nudging strength impacts both temporal and spatial temperature and precipitation extremes. The maximum and minimum temperatures at each point from among the ensemble members were examined, on the 95th confidence interval. The maximum and minimums over the simulation period will also be considered. Results suggest that there is a marked lack of sensitivity to the degrees of nudging. Moreover, it appears nudging strength can be considerably smaller than the standard strength and still produce reliably good simulations.

Temperate Tree Fruits

USDA-ARS?s Scientific Manuscript database

North America has four native temperate tree fruit genera that have each played key cultural roles due to their edible fruit, medicinal uses, as well as their value as hardwood: Malus (apple), Prunus (cherry, plum, peach, etc.), Diospyros (persimmon), and Asimina (paw paw). Native North American spe...

43. CAPE COD AIR STATION PAVE PAWS FACILITY WITH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

43. CAPE COD AIR STATION PAVE PAWS FACILITY - WITH BUILDING METAL SIDING BEING APPLIED ON "C" FACE (RIGHT) AND "B" FACE BEING PREPARED FOR INSTALLATION. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

A pediatric acute wound service: a novel approach in wound management.

PubMed

Bucher, B T; Seigel, J; Rosenblum, E; Nesslein, C; Keswani, S; Foglia, R P; Dillon, P A; Warner, B W; Keller, Martin S

2010-01-01

In 2001, in response to an overwhelming increase in patient visits for various pediatric abscesses, burns, and other wounds, an ambulatory burn and procedural sedation program (Pediatric Acute Wound Service, or PAWS) was developed to minimize operating room utilization. The purpose of this study is to report our initial 7-year experience with the PAWS program. The hospital records of all children managed through PAWS from 2001 to 2007 were reviewed. Outcomes measured include patient demographics, number and location of visits per patient, procedure information, cause of wounds, and reimbursement. chi(2) test and linear regression were performed using GraphPad Prism (GraphPad Software Inc, San Diego, CA). Overall, 7620 children (age 0-18 years) received wound care through PAWS from 2001 to 2007. There were no differences in patient age, race, and sex during this time period. Between 2001 and 2007, the percentage of patients seen as outpatients increased from 51% to 68% (P < .05), and the average number of visits per patient decreased from 3.9 to 2.4 (P = .05). In, 2007, 46% of the children required only 1 visit. In 2007, 74% of the visits were for management of wound and soft tissue infections, compared with only 9% in 2001 (P < .05). The contribution margin of a PAWS visit and total contribution margin in 2007 were $1052 and $4.0 million, respectively. The creation of PAWS has allowed for the transition in management of most pediatric skin and soft tissue wounds and infections to an independent ambulatory setting, alleviating the need for operating room resources, while functioning at a profitable cost margin for the hospital. Copyright 2010 Elsevier Inc. All rights reserved.

Role of soil sorption and microbial degradation on dissipation of mesotrione in plant-available soil water.

PubMed

Shaner, Dale; Brunk, Galen; Nissen, Scott; Westra, Phil; Chen, Wenlin

2012-01-01

Mesotrione is a carotenoid biosynthesis-inhibiting herbicide labeled for pre-emergence and postemergence weed control in corn production. Understanding the factors that influence the dissipation of mesotrione in soil and in the plant-available water (PAW) is important for the environmental fate assessment and optimal weed management practices. The present research investigated the role of soil properties and microbial activities on the interrelated sorption and degradation processes of mesotrione in four soils by direct measurements of PAW. We found that mesotrione bound to the soils time dependently, with approximately 14 d to reach equilibrium. The 24-h batch-slurry equilibrium experiments provided the sorption partition coefficient ranging from 0.26 to 3.53 L kg(-1), depending on soil organic carbon and pH. The dissipation of mesotrione in the soil-bound phase was primarily attributed to desorption to the PAW. Degradation in the PAW was rapid and primarily dependent on microbial actions, with half-degradation time (DT(50)) <3 d in all four soils tested. The rapid degradation in the PAW became rate limited by sorption as more available molecules were depleted in the soil pore water, resulting in a more slowed overall process for the total soil-water system (DT(50) <26 d). The dissipation of mesotrione in the PAW was due to microbial metabolism and time-dependent sorption to the soils. A coupled kinetics model calibrated with the data from the laboratory centrifugation technique provided an effective approach to investigate the interrelated processes of sorption and degradation in realistic soil moisture conditions. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

View of the PAVE PAWS radar from approach along Spencer ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of the PAVE PAWS radar from approach along Spencer Paul Road, looking northwest - Beale Air Force Base, Perimeter Acquisition Vehicle Entry Phased-Array Warning System, End of Spencer Paul Road, north of Warren Shingle Road (14th Street), Marysville, Yuba County, CA

42. CAPE COD AIR STATION PAVE PAWS FACILITY SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

42. CAPE COD AIR STATION PAVE PAWS FACILITY - SHOWING BUILDING "RED IRON" STEEL STRUCTURE AT 46T DAY OF STEEL CONSTRUCTION. "BUILDING TOPPED OFF, 7 JULY, 1974. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

Calculation of spin-spin zero-field splitting within periodic boundary conditions: Towards all-electron accuracy

NASA Astrophysics Data System (ADS)

Biktagirov, Timur; Schmidt, Wolf Gero; Gerstmann, Uwe

2018-03-01

For high-spin centers, one of the key spectroscopic fingerprints is the zero-field splitting (ZFS) addressable by electron paramagnetic resonance. In this paper, an implementation of the spin-spin contribution to the ZFS tensor within the projector augmented-wave (PAW) formalism is reported. We use a single-determinant approach proposed by M. J. Rayson and P. R. Briddon [Phys. Rev. B 77, 035119 (2008), 10.1103/PhysRevB.77.035119], and complete it by adding a PAW reconstruction term which has not been taken into account before. We benchmark the PAW approach against a well-established all-electron method for a series of diatomic radicals and defects in diamond and cubic silicon carbide. While for some of the defect centers the PAW reconstruction is found to be almost negligible, in agreement with the common assumption, we show that in general it significantly improves the calculated ZFS towards the all-electron results.

Programmable Automated Welding System (PAWS): Control of welding through software and hardware

NASA Technical Reports Server (NTRS)

Kline, Martin D.; Doyle, Thomas E.

1994-01-01

The ATD phase of the PAWS program ended in November 1992 and the follow-on ManTech program was started in September 1993. The system will be industrially hardened during the first year of this program. Follow-on years will focus upon the transition into specific end-user sites. These implementations will also expand the system into other welding processes (e.g. FCAW, GTAW, PAW). In addition, the architecture is being developed for application to other non-welding robotic processes (e.g. inspection, surface finishing). Future development is anticipated to encompass hardening for extreme environments, expanded exception handling techniques, and application to a range of manipulators.

Programmable Automated Welding System (PAWS)

NASA Technical Reports Server (NTRS)

Kline, Martin D.

1994-01-01

An ambitious project to develop an advanced, automated welding system is being funded as part of the Navy Joining Center with Babcock & Wilcox as the prime integrator. This program, the Programmable Automated Welding System (PAWS), involves the integration of both planning and real-time control activities. Planning functions include the development of a graphical decision support system within a standard, portable environment. Real-time control functions include the development of a modular, intelligent, real-time control system and the integration of a number of welding process sensors. This paper presents each of these components of the PAWS and discusses how they can be utilized to automate the welding operation.

Automated gait analysis in the open-field test for laboratory mice.

PubMed

Leroy, Toon; Silva, Mitchell; D'Hooge, Rudi; Aerts, Jean-Marie; Berckmans, Daniel

2009-02-01

In this article, an automated and accurate mouse observation method, based on a conventional test for motor function evaluation, is outlined. The proposed measurement technique was integrated in a regular open-field test, where the trajectory and locomotion of a free-moving mouse were measured simultaneously. The system setup consisted of a transparent cage and a camera placed below it with its lens pointing upward, allowing for images to be captured from underneath the cage while the mouse was walking on the transparent cage floor. Thus, additional information was obtained about the position of the limbs of the mice for gait reconstruction. In a first step, the camera was calibrated as soon as it was fixed in place. A linear calibration factor, relating distances in image coordinates to real-world dimensions, was determined. In a second step, the mouse was located and its body contour segmented from the image by subtracting a previously taken "background" image of the empty cage from the camera image. In a third step, the movement of the mouse was analyzed and its speed estimated from its location in the past few images. If the speed was above a 1-sec threshold, the mouse was recognized to be running, and the image was further processed for footprint recognition. In a fourth step, color filtering was applied within the recovered mouse region to measure the position of the mouse's paws, which were visible in the image as small pink spots. Paws that were detected at the same location in a number of subsequent images were kept as footprints-that is, paws in contact with the cage floor. The footprints were classified by their position relative to the mouse's outline as corresponding to the front left or right paw or the hind left or right paw. Finally, eight parameters were calculated from the footprint pattern to describe the locomotion of the mouse: right/left overlap, front/hind base, right/left front limb stride, and right/left hind limb stride. As an application, the system was tested using normal mice and mice displaying pentobarbital-induced ataxia. The footprint parameters measured using the proposed system showed differences of 10% to 20% between normal and ataxic mice.

Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin

PubMed Central

Lu, Tsung-Chun; Liao, Jung-Chun; Huang, Tai-Hung; Lin, Ying-Chih; Liu, Chia-Yu; Chiu, Yung-jia; Peng, Wen-Huang

2011-01-01

Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine. PMID:19933324

Anti-Inflammatory Activities of Cinnamomum cassia Constituents In Vitro and In Vivo

PubMed Central

Liao, Jung-Chun; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Shie, Pei-Hsin; Huang, Guang-Jhong

2012-01-01

We have investigated the anti-inflammatory effects of Cinnamomum cassia constituents (cinnamic aldehyde, cinnamic alcohol, cinnamic acid, and coumarin) using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with cinnamic aldehyde together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) levels productions were detected. Western blotting revealed that cinnamic aldehyde blocked protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear transcription factor kappa B (NF-κB), and IκBα, significantly. In the anti-inflammatory test, cinnamic aldehyde decreased the paw edema after Carr administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated cinnamic aldehyde attenuated the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in the edema paw after Carr injection. Cinnamic aldehyde decreased the NO, TNF-α, and PGE2 levels on the serum level after Carr injection. Western blotting revealed that cinnamic aldehyde decreased Carr-induced iNOS, COX-2, and NF-κB expressions in the edema paw. These findings demonstrated that cinnamic aldehyde has excellent anti-inflammatory activities and thus has great potential to be used as a source for natural health products. PMID:22536283

GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

PubMed

Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2008-01-01

The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

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

Lehtomäki, Jouko; Makkonen, Ilja; Harju, Ari

We present a computational scheme for orbital-free density functional theory (OFDFT) that simultaneously provides access to all-electron values and preserves the OFDFT linear scaling as a function of the system size. Using the projector augmented-wave method (PAW) in combination with real-space methods, we overcome some obstacles faced by other available implementation schemes. Specifically, the advantages of using the PAW method are twofold. First, PAW reproduces all-electron values offering freedom in adjusting the convergence parameters and the atomic setups allow tuning the numerical accuracy per element. Second, PAW can provide a solution to some of the convergence problems exhibited in othermore » OFDFT implementations based on Kohn-Sham (KS) codes. Using PAW and real-space methods, our orbital-free results agree with the reference all-electron values with a mean absolute error of 10 meV and the number of iterations required by the self-consistent cycle is comparable to the KS method. The comparison of all-electron and pseudopotential bulk modulus and lattice constant reveal an enormous difference, demonstrating that in order to assess the performance of OFDFT functionals it is necessary to use implementations that obtain all-electron values. The proposed combination of methods is the most promising route currently available. We finally show that a parametrized kinetic energy functional can give lattice constants and bulk moduli comparable in accuracy to those obtained by the KS PBE method, exemplified with the case of diamond.« less

Antinociceptive and Anti-Inflammatory Activities of Bridelia retusa Methanolic Fruit Extract in Experimental Animals

PubMed Central

Kumar, Tekeshwar; Jain, Vishal

2014-01-01

Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (P < 0.001). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract. PMID:25506619

[Application of injection test in confirming the ideal position of esophageal balloon catheter].

PubMed

Chen, Han; Xu, Ming; Yang, Yanlin; He, Xuan; Zhou, Jianxin

2017-09-01

To evaluate the safety and feasibility of injection test which is used to locate esophageal balloon catheter. A prospective study was conducted. The patients undergoing invasive mechanical ventilation (MV) admitted to general intensive care unit (ICU) of Beijing Tiantan Hospital Affiliated to Capital Medical University from May 2015 and March 2017 were enrolled. The commercially available esophageal balloon catheter was modified to perform injection test. The catheter was withdrawn step by step and the injection test was repeated until the presence disturbance wave presented, which indicated that the balloon had just entered the esophagus. The position where disturbance wave appears was named 0 cm. End-expiratory occlusions were performed at the positions of +15, +10, +5, 0, -5, -10 and -15 cm, respectively, and the changes of esophageal pressure (Pes) and airway pressures (Paw) were measured in the spontaneous breathing and passive ventilation, and the ratio between the changes (ΔPes/ΔPaw) was calculated. A total of 20 patients were enrolled, of which 15 patients finished both the spontaneous and the passive ventilation parts, and 2 patients finished only the spontaneous part and 3 patients finished only passive part. (1) Disturbance waves could be induced by injection test in all patients. The average depth of disturbance wave in spontaneous breathing was deeper than that in passive ventilation (cm: 42.4±3.8 vs. 41.8±3.3), but there was no significant difference between the two ventilation settings (P = 0.132). No adverse events occurred during the study period. (2) Pes increased with the stepwise withdraw of esophageal catheter, reached the maximal value at +5 cm, and then decreased when the catheter was further withdrawn, no matter in the spontaneous or the passive ventilation. In spontaneous breathing, the ΔPes/ΔPaw was within the ideal range (0.8-1.2) at the positions of 0, -5 and -10 cm. The ΔPes/ΔPaw was closest to unity at the positions of 0 cm (0.98±0.15). The ΔPes/ΔPaw at -15 cm (0.66±0.26) was significantly lower than that at 0 cm (P < 0.05). For passive ventilation, the ΔPes/ΔPaw was within the ideal range at the positions of -5 cm and -10 cm, and the ΔPes/ΔPaw was closest to unity at the positions of -10 cm (0.94±0.12). The ΔPes/ΔPaw at 0 cm and -5 cm was significantly higher than that at -10 cm (1.43±0.31 and 1.12±0.14, respectively); while the ΔPes/ΔPaw at -15 cm (0.68±0.23) was significantly lower than that at -10 cm (all P < 0.01). Ideal position of the esophageal balloon catheter could be determined quickly and easily by using injection test. The method is safe and clinically feasible. Clinical Trials, NCT02446938.

Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

PubMed

Déciga-Campos, Myrna; González-Trujano, Maria Eva; Ventura-Martínez, Rosa; Montiel-Ruiz, Rosa Mariana; Ángeles-López, Guadalupe Esther; Brindis, Fernando

2016-02-01

Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia. © 2016 Wiley Periodicals, Inc.

Success Is in the Details: Publishing To Validate Elementary Authors.

ERIC Educational Resources Information Center

Chihak, Judy

1999-01-01

Describes Panther Paw Press, a school-based publishing program that is built on the efforts of teachers, parents, students, and a succession of supportive school principals. Discusses the details that make this publishing program work framed in the six goals articulated in the Panther Paw Press Handbook. (SR)

The PlayParty Project in Oberlin: A Family Affair

ERIC Educational Resources Information Center

Bennett, Peggy D.

2006-01-01

This article focuses on the PlayParty family event held by the Oberlin Conservatory of Music in Ohio. Through PlayParties, families immersed themselves in singing and playing what became traditional singing games. PlayParty songs that are frequently use include Skip to My Lou, Paw Paw Patch and Punchinella.

17. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW WITH PROJECT NEARING COMPLETION. VIEW SHOWS "A" FACE (LEFT) AND "B" FACE OF RADAR ARRAY SYSTEM. NOTE THAT NORTH IS GENERALLY TO RIGHT OF VIEW. - Cape Cod Air Station, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

47. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

47. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW OF "A" FACE (LEFT) WITH CLEANING SYSTEM INSTALLED (NOW REMOVED) AND "B" FACE (RIGHT) WITH CONSTRUCTION CRANE IN USE. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

Thermographic evaluation of hind paw skin temperature and functional recovery of locomotion after sciatic nerve crush in rats

PubMed Central

Z. Sacharuk, Viviane; A. Lovatel, Gisele; Ilha, Jocemar; Marcuzzo, Simone; Severo do Pinho, Alexandre; L. Xavier, Léder; A. Zaro, Milton; Achaval, Matilde

2011-01-01

INTRODUCTION: Peripheral nerves are often damaged by direct mechanical injury, diseases, and tumors. The peripheral nerve injuries that result from these conditions can lead to a partial or complete loss of motor, sensory, and autonomic functions, which in turn are related to changes in skin temperature, in the involved segments of the body. The aim of this study was to evaluate the changes in hind paw skin temperature after sciatic nerve crush in rats in an attempt to determine whether changes in skin temperature correlate with the functional recovery of locomotion. METHODS: Wistar rats were divided into three groups: control (n = 7), sham (n = 25), and crush (n = 25). All groups were subjected to thermographic, functional, and histological assessments. RESULTS: ΔT in the crush group was different from the control and sham groups at the 1st, 3rd and 7rd postoperative days (p<0.05). The functional recovery from the crush group returned to normal values between the 3rd and 4th week post-injury, and morphological analysis of the nerve revealed incomplete regeneration at the 4th week after injury. DISCUSSION: This study is the first demonstration that sciatic nerve crush in rats induces an increase in hind paw skin temperature and that skin temperature changes do not correlate closely with functional recovery PMID:21876984

High-resolution 3D volumetry versus conventional measuring techniques for the assessment of experimental lymphedema in the mouse hindlimb

PubMed Central

Frueh, Florian S.; Körbel, Christina; Gassert, Laura; Müller, Andreas; Gousopoulos, Epameinondas; Lindenblatt, Nicole; Giovanoli, Pietro; Laschke, Matthias W.; Menger, Michael D.

2016-01-01

Secondary lymphedema is a common complication of cancer treatment characterized by chronic limb swelling with interstitial inflammation. The rodent hindlimb is a widely used model for the evaluation of novel lymphedema treatments. However, the assessment of limb volume in small animals is challenging. Recently, high-resolution three-dimensional (3D) imaging modalities have been introduced for rodent limb volumetry. In the present study we evaluated the validity of microcomputed tomography (μCT), magnetic resonance imaging (MRI) and ultrasound in comparison to conventional measuring techniques. For this purpose, acute lymphedema was induced in the mouse hindlimb by a modified popliteal lymphadenectomy. The 4-week course of this type of lymphedema was first assessed in 6 animals. In additional 12 animals, limb volumes were analyzed by μCT, 9.4 T MRI and 30 MHz ultrasound as well as by planimetry, circumferential length and paw thickness measurements. Interobserver correlation was high for all modalities, in particular for μCT analysis (r = 0.975, p < 0.001). Importantly, caliper-measured paw thickness correlated well with μCT (r = 0.861), MRI (r = 0.821) and ultrasound (r = 0.800). Because the assessment of paw thickness represents a time- and cost-effective approach, it may be ideally suited for the quantification of rodent hindlimb lymphedema. PMID:27698469

A study of the anti-inflammatory effect of the leaves of Psidium guajava Linn. on experimental animal models

PubMed Central

Dutta, Sarmistha; Das, Swarnamoni

2010-01-01

Introduction: The aim is to study the anti-inflammatory effect of the ethanolic extract of the leaves of Psidium guajava(PGE) on experimental animal models. Materials and Methods: Fresh leaves were collected, air-dried, powdered, and percolated in 95% ethanol. Acute toxicity test was done according to OECD guidelines. Four groups of animals of either sex, weighing 150–200g of the species Rattus norvegicus were taken for the study (n = 6). Group A was taken as control (3% gum acacia in 10 mL/kg body weight), Group B as test group (PGE 250 mg/kg body weight), Group C as test group (PGE 500 mg/kg body weight), and Group D as standard (Aspirin 100 mg/kg body weight). The animals were studied for acute inflammation by Carrageenan-induced rat paw edema, subacute inflammation by Granuloma pouch method, and chronic inflammation by Freund’s adjuvant-induced arthritis method. Statistical analysis was done by one-way analysis of variance followed by multiple comparison tests. Results: In acute inflammation, there was significant inhibition of paw edema in Groups B, C, and D in comparison with Group A (P < 0.05). In subacute inflammation, there was significant inhibition of exudate formation in Groups B, C, and D in comparison to Group A (P < 0.05). In chronic inflammation, there was significant inhibition of paw edema and inhibition of weight reduction in Groups B, C, and D compared with Group A. Downregulation of arthritis index was also significant in Groups B, C, and D in comparison with Group A (P < 0.05). Conclusion: The ethanolic extract of PGE has significant anti-inflammatory activity. PMID:21589759

First characterization of bacterial pathogen, Vibrio alginolyticus, for Porites andrewsi White syndrome in the South China Sea.

PubMed

Zhenyu, Xie; Shaowen, Ke; Chaoqun, Hu; Zhixiong, Zhu; Shifeng, Wang; Yongcan, Zhou

2013-01-01

White syndrome, a term for scleractinian coral disease with progressive tissue loss, is known to cause depressed growth and increased morality of coral reefs in the major oceans around the world, and the occurrence of this disease has been frequently reported in the past few decades. Investigations during April to September in both 2010 and 2011 identified widespread Porites andrewsi White syndrome (PAWS) in Xisha Archipelago, South China Sea. However, the causes and etiology of PAWS have been unknown. A transmission experiment was performed on P. andrewsi in the Qilianyu Subgroup (QLY). The results showed that there was a significant (P ≤ 0.05) difference between test and control groups after 28 days if the invalid replicates were excluded. Rates of tissue loss ranged from 0.90-10.76 cm(2) d(-1) with a mean of 5.40 ± 3.34 cm(2) d(-1) (mean ± SD). Bacterial strains were isolated from the PAWS corals at the disease outbreak sites in QLY of the Xisha Archipelago, South China Sea, and included in laboratory-based infection trials to satisfy Koch's postulates for establishing causality. Following exposure to bacterial concentrations of 10(5) cells mL(-1), the infected colonies exhibited similar signs to those observed in the field. Using phylogenetic 16S rRNA gene analysis, classical phenotypic trait comparison, Biolog automatic identification system, MALDI-TOF mass spectrometry and MALDI Biotyper method, two pathogenic strains were identified as Vibrio alginolyticus . This is the first report of V. alginolyticus as a pathogenic agent of PAWS in the South China Sea. Our results point out an urgent need to develop sensitive detection methods for V. alginolyticus virulence strains and robust diagnostics for coral disease caused by this and Vibrio pathogenic bacterium in the South China Sea.

First Characterization of Bacterial Pathogen, Vibrio alginolyticus, for Porites andrewsi White Syndrome in the South China Sea

PubMed Central

Chaoqun, Hu; Zhixiong, Zhu; Shifeng, Wang; Yongcan, Zhou

2013-01-01

Background White syndrome, a term for scleractinian coral disease with progressive tissue loss, is known to cause depressed growth and increased morality of coral reefs in the major oceans around the world, and the occurrence of this disease has been frequently reported in the past few decades. Investigations during April to September in both 2010 and 2011 identified widespread Porites andrewsi White syndrome (PAWS) in Xisha Archipelago, South China Sea. However, the causes and etiology of PAWS have been unknown. Methodology/Principal Findings A transmission experiment was performed on P . andrewsi in the Qilianyu Subgroup (QLY). The results showed that there was a significant (P ≤ 0.05) difference between test and control groups after 28 days if the invalid replicates were excluded. Rates of tissue loss ranged from 0.90-10.76 cm2 d-1 with a mean of 5.40 ± 3.34 cm2 d-1 (mean ± SD). Bacterial strains were isolated from the PAWS corals at the disease outbreak sites in QLY of the Xisha Archipelago, South China Sea, and included in laboratory-based infection trials to satisfy Koch’s postulates for establishing causality. Following exposure to bacterial concentrations of 105 cells mL-1, the infected colonies exhibited similar signs to those observed in the field. Using phylogenetic 16S rRNA gene analysis, classical phenotypic trait comparison, Biolog automatic identification system, MALDI-TOF mass spectrometry and MALDI Biotyper method, two pathogenic strains were identified as Vibrio alginolyticus . Conclusion/Significance This is the first report of V . alginolyticus as a pathogenic agent of PAWS in the South China Sea. Our results point out an urgent need to develop sensitive detection methods for V . alginolyticus virulence strains and robust diagnostics for coral disease caused by this and Vibrio pathogenic bacterium in the South China Sea. PMID:24086529

Automatic analysis of altered gait in arylsulphatase A-deficient mice in the open field.

PubMed

Leroy, Toon; Stroobants, Stijn; Aerts, Jean-Marie; D'Hooge, Rudi; Berckmans, Daniel

2009-08-01

In current research with laboratory animals, observing their dynamic behavior or locomotion is a labor-intensive task. Automatic continuous monitoring can provide quantitative data on each animal's condition and coordination ability. The objective of the present work is to develop an automated mouse observation system integrated with a conventional open-field test for motor function evaluation. Data were acquired from 86 mice having a targeted disruption of the arylsulphatase A (ASA) gene and having lowered coordinated locomotion abilities as a symptom. The mice used were 36 heterozygotes (12 females) and 50 knockout mice (30 females) at the age of 6 months. The mice were placed one at a time into the test setup, which consisted of a Plexiglas cage (53x34.5x26 cm) and two fluorescent bulbs for proper illumination. The transparent cage allowed images to be captured from underneath the cage, so image information could be obtained about the dynamic variation of the positions of the limbs of the mice for gait reconstruction. Every mouse was recorded for 10 min. Background subtraction and color filtering were used to measure and calculate image features, which are variables that contain crucial information, such as the mouse's position, orientation, body outline, and possible locations for the mouse's paws. A set of heuristic rules was used to prune implausible paw features and label the remaining ones as front/hind and left/right. After we had pruned the implausible paw features, the paw features that were consistent over subsequent images were matched to footprints. Finally, from the measured footprint sequence, eight parameters were calculated in order to quantify the gait of the mouse. This automatic observation technique can be integrated with a regular open-field test, where the trajectory and motor function of a free-moving mouse are measured simultaneously.

Acute turpentine inflammation and kinin release in rat-paw thermic oedema.

PubMed Central

Limãos, E. A.; Borges, D. R.; Souza-Pinto, J. C.; Gordon, A. H.; Prado, J. L.

1981-01-01

Livers from rats at 2-3 days after s.c. injection of turpentine, when perfused, synthesized prekallikrein nearly 3 times faster than did livers from normal rats. On the other hand paw oedema, produced by heating to 46 degrees, in rats injured in this way was less marked. Likewise in such rats the amount of bradykinin release by 50 min. of coaxial perfusion of the paw was only 13.6 +/- 4.6 compared with 63.1 +/- 13.4 ng in normal rats. A possible explanation for the observed reduction in production of bradykinin may be inhibition of kallikrein due to an increased concentration of alpha 2-macroglobulin. PMID:6173056

University Housing | University of Wisconsin-Milwaukee

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee University Housing Powerful

Perspectives on a Whole Class Mindfulness Programme

ERIC Educational Resources Information Center

Thomas, George; Atkinson, Cathy

2017-01-01

This study sought to establish pupil and teacher views about a six-hour, whole-class mindfulness programme called Paws.b. Pupil post-intervention focus groups and teacher semi-structured interviews were used to ascertain what was interesting and useful about Paws.b, and how it could be developed. Audio recordings were transcribed and thematically…

45. CAPE COD AIR STATION PAVE PAWS FACILITY BUILDING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

45. CAPE COD AIR STATION PAVE PAWS FACILITY - BUILDING ELEVATION VIEW WITH BUILDING METAL SIDING BEING APPLIED ON "A" FACE (LEFT) AND "B" FACE (RIGHT). NOTE THAT NORTH IS GENERALLY TO RIGHT OF VIEW. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.

PubMed

Pinho-Ribeiro, Felipe A; Fattori, Victor; Zarpelon, Ana C; Borghi, Sergio M; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Alves-Filho, Jose C; Cunha, Fernando Q; Cunha, Thiago M; Casagrande, Rubia; Verri, Waldiceu A

2016-06-01

We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

Release of endogenous opioids following transcutaneous electric nerve stimulation in an experimental model of acute inflammatory pain.

PubMed

Sabino, George S; Santos, Cristiane M F; Francischi, Janetti N; de Resende, Marcos Antônio

2008-02-01

Transcutaneous electric nerve stimulation (TENS) is a noninvasive treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. The aim of the present study was to investigate the action mechanism of TENS at high (HF: 130 Hz) and low (LF: 10 Hz) frequencies in an inflammation model produced by the injection of carrageenan in rat paws (Cg; 250 microg). After carrageenan administration (0 time), either HF or LF TENS was applied to the inflamed paw of rats for 20 minutes, and hyperalgesia was assessed hourly using the modified Randall-Selitto method (1957). HF and LF TENS inhibited the carrageenan-induced hyperalgesia by 100%. Pretreatment of animals with intraplantar naltrexone (Nx; 50 microg) reversed the analgesic effect of the LF TENS but did not alter the effect of HF TENS. The application of HF and LF TENS to the contralateral paw reversed the hyperalgesia of the inflamed paw similar to that observed when TENS was applied to the inflamed paw. However, LF TENS presented a longer-lasting analgesic effect than HF TENS. Our data demonstrate that HF and LF TENS induced antihyperalgesia. We also report that the antihyperalgesia provoked by LF TENS is partially due to the local release of endogenous opioids. This study offers important information about physiotherapy practices aimed at pain relieving. TENS is a noninvasive treatment that promotes analgesia in acute and chronic inflammatory conditions. Scientists, patients, and the general population may benefit from this knowledge.

Vitex negundo inhibits cyclooxygenase-2 inflammatory cytokine-mediated inflammation on carrageenan-induced rat hind paw edema

PubMed Central

Chattopadhyay, Pronobesh; Hazarika, Soilyadhar; Dhiman, Sunil; Upadhyay, Aadesh; Pandey, Anurag; Karmakar, Sanjeev; Singh, Lokendra

2012-01-01

Background: Vitex negundo L. (Verbenaceae) is a hardy plant widely distributed in the Indian subcontinent and used for treatment of a wide spectrum of health disorders in traditional and folk medicine, some of which have been experimentally validated. In present study, we aimed to investigate the anti-inflammatory effects of V. negundo in carrageenan-induced paw edema in rats, and to investigate the probable mechanism of anti-inflammatory action. Materials and Methods: Paw edema was produced by injecting 1% solution of carrageenan, and the paw volume was measured before and after carrageenan injection up to 5 h. V. negundo leaf oil was extracted using a Clevenger apparatus and administered by a trans-dermal route to Wistar rats and the percentage of inhibition of inflammation was observed using a Plethysmometer by comparing a compound aerosol-based formulation with 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP/kg body weight served as a standard drug whereas paraffin oil served as the placebo group. After withdrawing of blood, serum was separated and cyclooxygenase (COX)-1 and COX-2 inhibitory activities were measured by the enzyme immuno assay (EIA) method by using a COX inhibitor screening assay kit. Results and Discussion: V. negundo leaf oil significantly (P < 0.05) reduced the carrageenan-induced paw edema as compared to the placebo group (paraffin oil) and 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP showed the maximum inhibition of paw edema as compared to the V. negundo leaf oil treated group and the control group. Also in the present study V. negundo leaf oil showed significantly (P < 0.05) inhibits COX-1 pathways rather than COX-2 pathways as compared to the V. negundo leaf oil treated group. Conclusion: It is suggested that the V. negundo leaf oil is a potent anti-inflammatory agent and acts via inhibition of COX-2 without much interfering COX-1 pathways. PMID:22923950

Magnetic nanogel polymer of bupivacaine for ankle block in rats.

PubMed

Nadri, Sedigheh; Mahmoudvand, Hormoz; Eatemadi, Ali

2016-11-01

In an effort of designing an alternative method for local nerve block, we demonstrated the possibility of inducing ankle block in the rat with intravenous (IV) injection of magnetic nanoparticles conjugated bupivacaine and application of a magnet at the ankle. The anaesthetic effect of magnet-directed bupivacaine-associated MNPs (NIPAAM-MAA-bupivacaine) was tested in rat using paw withdrawal latencies from thermal stimuli on the hind paw. Thirteen (13) experimental animals were grouped into two; untreated left hind paw (control group) and test group with treated right hind paw. The morphology of the synthesised nanogel was analysed using scanning electron micrograph (SEM), chemical characterisation using Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) and finally the in vivo drug release using UV spectroscopy. UV spectroscopy result show that, at 37 °C a sharp increase was observed from 24-72 h (40-75%) cumulative drug release at pH 5.3, a steady increase from 21-60% and 20-40% at pH 6.8 and 7.4m respectively. At 43 °C, a steady increase was observed at the three pH, 37-72%, 20-35% and 10-19% at pH 5.3, 6.8 and 7.4, respectively. It was shown also that drug release at higher pH (6.8 and 7.4) does not become significantly faster when temperature is high, compared to the release at a pH of 5.3. This depicts that the decreasing pH has more impact on the speed of the release of drug than increasing temperature. NMR and FTIR results displayed a comparable chemical structure as expected. The NMR peak displayed high purity of the final product. Morphology using SEM showed that the nanocomposite size is slightly greater than that of the nanogel, and the nanocomposite particles are nearly mono dispersed. Paw withdrawal latency highest peak of 15% was observed for NG/PU/30 at 40hours, and lowest peak for NG/30 at 50 h for the left paw. Group BU0.15 at 30 h shows the highest peak (20%) and NG/30 at 120 h shows the lowest peak for the right treated paw, which is significantly difference from the untreated left paw group (p< 0.0001). However, there wasn't a significant difference amongst NG/30, NG/Pub/15, or NG/Pub/60. The current study verifies the findings that we can induce ankle block in rat through IV injection administration of NIPAAM-MAA-bupivacaine complexes and the application of magnet at the ankle. We however suggest a lower temperature and pH for optimum release of this nanoanaesthetics, there is a probability of translating this mechanism to clinical practise.

The Wellness Factor: Embedding Wellness in the Curriculum at Ashley Hall

ERIC Educational Resources Information Center

Murrell, Amanda; Wood, Kelly

2013-01-01

The authors of this article describe the Personal Awareness and Wellness Seminar (PAWS) program, which they developed at Ashley Hall (South Carolina), an all-girls K-12 school. PAWS is designed to incorporate three main areas of school and personal life: academic management and study skills, general wellness and life skills, and the college search…

46. CAPE COD AIR STATION PAVE PAWS FACILITY BUILDING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

46. CAPE COD AIR STATION PAVE PAWS FACILITY - BUILDING ELEVATION VIEW WITH ALL METAL SIDING INSTALLED AND WITH EMITTER/ANTENNA ARRAY SYSTEM NEARING OCMPLETION ON "B" FACE (RIGHT). VIEW ALSO SHOWS TRAVELING "CLEANING" SYSTEM ON "B" FACE - NOW REMOVED. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

Intensive Selective Deer Browsing Favors Success of Asimina triloba (Paw Paw) a Native Tree Species

Treesearch

Mitchell A. Slater; Roger C. Anderson

2014-01-01

Although white-tailed deer (Odocoileus virginianus Zimmermann) are generalist herbivores, they can have significant effects on species composition and abundance of forest trees, especially when deer densities are high and most plant species are heavily browsed but a few are selectively avoided as browse. We evaluated effects of selective deer...

Above Ground Field Evaluation and GC-MS Analysis of Naturally Durable Wood Species

Treesearch

G.T. Kirker; A.B. Blodgett; S.T. Lebow; C.A. Clausen

2012-01-01

Nine wood species are being evaluated in above ground field studies in Mississippi and Wisconsin. Candidate naturally durable wood (NDW) species are being rated at yearly intervals for resistance to decay, cupping, and checking. Field ratings after 12 months exposure are presented. To date, Paulownia tomentosa (PAW) and southern yellow pine (SYP)...

Seasonal and interannual variability of climate and vegetation indices across the Amazon.

PubMed

Brando, Paulo M; Goetz, Scott J; Baccini, Alessandro; Nepstad, Daniel C; Beck, Pieter S A; Christman, Mary C

2010-08-17

Drought exerts a strong influence on tropical forest metabolism, carbon stocks, and ultimately the flux of carbon to the atmosphere. Satellite-based studies have suggested that Amazon forests green up during droughts because of increased sunlight, whereas field studies have reported increased tree mortality during severe droughts. In an effort to reconcile these apparently conflicting findings, we conducted an analysis of climate data, field measurements, and improved satellite-based measures of forest photosynthetic activity. Wet-season precipitation and plant-available water (PAW) decreased over the Amazon Basin from 1996-2005, and photosynthetically active radiation (PAR) and air dryness (expressed as vapor pressure deficit, VPD) increased from 2002-2005. Using improved enhanced vegetation index (EVI) measurements (2000-2008), we show that gross primary productivity (expressed as EVI) declined with VPD and PAW in regions of sparse canopy cover across a wide range of environments for each year of the study. In densely forested areas, no climatic variable adequately explained the Basin-wide interannual variability of EVI. Based on a site-specific study, we show that monthly EVI was relatively insensitive to leaf area index (LAI) but correlated positively with leaf flushing and PAR measured in the field. These findings suggest that production of new leaves, even when unaccompanied by associated changes in LAI, could play an important role in Basin-wide interannual EVI variability. Because EVI variability was greatest in regions of lower PAW, we hypothesize that drought could increase EVI by synchronizing leaf flushing via its effects on leaf bud development.

The Anti-Inflammatory and Antioxidant Potential of Pistachios (Pistacia vera L.) In Vitro and In Vivo.

PubMed

Paterniti, Irene; Impellizzeri, Daniela; Cordaro, Marika; Siracusa, Rosalba; Bisignano, Carlo; Gugliandolo, Enrico; Carughi, Arianna; Esposito, Emanuela; Mandalari, Giuseppina; Cuzzocrea, Salvatore

2017-08-22

Several reports have demonstrated the effectiveness of pistachio against oxidative stress and inflammation. In this study, we investigate if polyphenols extracts from natural raw shelled pistachios (NP) or roasted salted pistachio (RP) kernels have anti-inflammatory and antioxidant properties at lower doses than reported previously, in both in vitro and in vivo models. The monocyte/macrophage cell line J774 was used to assess the extent of protection by NP and RP pistachios against lipopolysaccharide (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR) injection in the paw. Results from the in vitro study demonstrated that pre-treatment with NP (0.01, 0.1 and 0.5 mg/mL) and RP (0.01 and 0.1 mg/mL) exerted a significant protection against LPS induced inflammation. Western blot analysis showed NP reduced the degradation of IκB-α, although not significantly, whereas both NP and RP decreased the TNF-α and IL-1β production in a dose-dependent way. A significant reduction of CAR-induced histological paw damage, neutrophil infiltration and nitrotyrosine formation was observed in the rats treated with NP. These data demonstrated that, at lower doses, polyphenols present in pistachios possess antioxidant and anti-inflammatory properties. This may contribute toward a better understanding of the beneficial health effects associated with consumption of pistachios.

The Anti-Inflammatory and Antioxidant Potential of Pistachios (Pistacia vera L.) In Vitro and In Vivo

PubMed Central

Paterniti, Irene; Impellizzeri, Daniela; Cordaro, Marika; Bisignano, Carlo; Gugliandolo, Enrico; Carughi, Arianna; Esposito, Emanuela; Mandalari, Giuseppina

2017-01-01

Several reports have demonstrated the effectiveness of pistachio against oxidative stress and inflammation. In this study, we investigate if polyphenols extracts from natural raw shelled pistachios (NP) or roasted salted pistachio (RP) kernels have anti-inflammatory and antioxidant properties at lower doses than reported previously, in both in vitro and in vivo models. The monocyte/macrophage cell line J774 was used to assess the extent of protection by NP and RP pistachios against lipopolysaccharide (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR) injection in the paw. Results from the in vitro study demonstrated that pre-treatment with NP (0.01, 0.1 and 0.5 mg/mL) and RP (0.01 and 0.1 mg/mL) exerted a significant protection against LPS induced inflammation. Western blot analysis showed NP reduced the degradation of IκB-α, although not significantly, whereas both NP and RP decreased the TNF-α and IL-1β production in a dose-dependent way. A significant reduction of CAR-induced histological paw damage, neutrophil infiltration and nitrotyrosine formation was observed in the rats treated with NP. These data demonstrated that, at lower doses, polyphenols present in pistachios possess antioxidant and anti-inflammatory properties. This may contribute toward a better understanding of the beneficial health effects associated with consumption of pistachios. PMID:28829406

Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin.

PubMed

Raju, Gayathri; Katiyar, Neeraj; Vadukumpully, Sajini; Shankarappa, Sahadev A

2018-02-01

Transdermal particulate penetration across thick-skin, such as that of palms and sole, is particularly important for drug delivery for disorders such as small fiber neuropathies. Nanoparticle-based drug delivery across skin is believed to have much translational applications, but their penetration especially through thick-skin, is not clear. This study specifically investigates the effectiveness of gold nanoparticles (AuNPs) for thick-skin penetration, especially across the stratum corneum (SC) as a function of particle size. The thick-skinned hind-paw of rat was used to characterize depth and distribution of AuNPs of varying sizes, namely, 22±3, 105±11, and 186±20nm. Epidermal penetration of AuNPs was characterized both, in harvested skin from the hind-paw using a diffusion chamber, as well as in vivo. Harvested skin segments exposed to 22nm AuNPs for only 3h demonstrated higher penetration (p<0.05) as compared to the 105 and 186nm particles. In animal studies, hind-paw skin of adult rats exposed to AuNPs solution for the same time, demonstrated nanoparticles in blood on the 4th day, and histological analysis revealed AuNPs in epidermal layers just below the SC, with no apparent tissue response. We conclude that the thick-skin allows nanoparticle penetration and acts as a depot for release of AuNPs into circulation long after the initial exposure has ceased. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Anti-inflammatory effects of Scoparia dulcis L. and betulinic acid.

PubMed

Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Tai-Hui; Lai, Shang-Chih; Lee, Chao-Ying

2011-01-01

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.

Nonlinear Inverted-U Shaped Relationship between Aging and Epidermal Innervation in the Rat Plantar Hind Paw: a Laser Scanning Confocal Microscopy Study.

PubMed

Kaliappan, Sankaranarayanan; Simone, Donald A; Banik, Ratan K

2018-04-13

The under-reporting of pain and atypical manifestations of painful syndromes within the elderly population have been well-documented, however, the specific relationship between pain and aging remains ambiguous. Previous studies have reported degenerative changes in primary afferents with aging. In this study, we questioned whether there is any change in the density of primary afferent endings within the epidermis of aged animals. Rats were categorically assessed in four age groups, each representing a key developmental stage across their life span: juvenile (2 months); adult (7 months); aged (18 months); and senescent (24-26 months). The plantar hind paw skin was removed, post-fixed, cut, and immunostained for protein gene product 9.5 and type IV collagen. Rats in the adult aged groups had significantly increased epidermal nerve densities and total lengths of immunoreactive nerve fibers, compared to both juvenile and senescent rats. However, the paw withdrawal thresholds to punctate mechanical stimulation progressively increased with age, and did not exhibit a clear relationship with epidermal innervation. We conclude a non-linear, inverted-U shaped relationship between rat plantar epidermal nerve density with aging, which does not correlate with mechanically-induced paw withdrawal behaviors. This article presents age-related decreased epidermal innervation in rat hind paw skin, which partly explains mechanisms underlying decreased pain sensitivity in aged subjects. The article may help clinicians to understand that any compromise of pain-sensing pathway can lead to under-reporting of pain, inadequate analgesia, and slower recovery from a painful condition. Copyright © 2018. Published by Elsevier Inc.

Effect of the Combined Use of Tramadol and Milnacipran on Pain Threshold in an Animal Model of Fibromyalgia

PubMed Central

Song, Junhwa; Mun, Hyunil; Park, Keon Uk

2009-01-01

Background/Aims Acidic saline injections produce mechanical hyperresponsiveness in male Sprague-Dawley rats. We investigated the effect of milnacipran in conjunction with tramadol on the pain threshold in an acidic saline animal model of pain. Methods The left gastrocnemius muscle of 20 male rats was injected with 100 µL of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Rats administered acidic saline injections were separated into four study subgroups. After determining the pre-drug pain threshold, rats were injected intraperitoneally with one of the following regimens; saline, milnacipran alone (60 mg/kg), milnacipran (40 mg/kg) plus tramadol (20 mg/kg), or milnacipran (40 mg/kg) plus tramadol (40 mg/kg). Paw withdrawal in response to pressure was measured at 30 min, 120 min, and 5 days after injection. Nociceptive thresholds, expressed in grams, were measured with a Dynamic Plantar Aesthesiometer (Ugo Basile, Italy) by applying increasing pressure to the right or left hind paw until the rat withdrew the paw. Results A potent antihyperalgesic effect was observed when tramadol and milnacipran were used in combination (injected paw, p=0.001; contralateral paw, p=0.012). This finding was observed only at 30 min after the combination treatment. Conclusions We observed potentiation of the antihyperalgesic effect when milnacipran and tramadol were administered in combination in an animal model of fibromyalgia. Further research is required to determine the efficacy of various combination treatments in fibromyalgia in humans. PMID:19543493

Taraxerol, a pentacyclic triterpene from Abroma augusta leaf, attenuates acute inflammation via inhibition of NF-κB signaling.

PubMed

Khanra, Ritu; Dewanjee, Saikat; Dua, Tarun K; Bhattacharjee, Niloy

2017-04-01

Abroma augusta L. (Malvaceae) leaf is traditionally used to treat inflammatory disorders. In our laboratory, we have scientifically validated the anti-inflammatory effect of A. augusta leaf extract. In this study, it has been aimed to evaluate in vivo anti-inflammatory effect of taraxerol isolated from the methanol extract of A. augusta leaf. It was further intended to find out the probable mechanism of anti-inflammatory effect of taraxerol. The anti-inflammatory effect of taraxerol (5 and 10mg/kg, i.p.) was measured employing carrageenan-induced paw edema model of acute inflammation. The carrageenan injection resulted significant edema formation in the right paw when compared with un-injected left paw. However, taraxerol (10mg/kg) treatment could significantly (p<0.05-0.01) attenuate carrageenan induced paw edema 2h onward. The effect of taraxerol at the dose of 5mg/kg was found to be significant (p<0.05) only after 4h of carrageenan treatment. Taraxerol (10mg/kg) treatment could significantly (p<0.01) attenuate carrageenan mediated up-regulation in the levels of IL 1β, IL 6, IL 12 and TNF α in the right paw tissues. In search of molecular mechanism, taraxerol (10mg/kg) could significantly (p<0.05-0.01) reinstate carrageenan provoked NF-κB signaling and thereby caused significant down-regulation in the expressions of COX-2 (p<0.01) and iNOS (p<0.05). In conclusion, taraxerol would attenuate acute inflammation via inhibition of NF-κB signaling. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity from Schinus molle fruits.

PubMed

Yueqin, Zeng; Recio, M Carmen; Máñez, Salvador; Giner, Rosa M; Cerdá-Nicolás, M; Ríos, José-Luis

2003-10-01

Three compounds with anti-inflammatory activity were isolated from Schinus molle fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2, and biflavanone 3 were tested on two models of mice paw inflammation: one of acute inflammation, induced by subcutaneous injection of either phospholipase A (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation in the form of eczema, provoked by repeated administration of TPA to the ears of mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 % inhibition at 60 min), whereas all compounds reduced the chronic model of inflammation (48 to 26 % of swelling reduction), but only triterpenes reduced the leukocyte infiltration, measured as tissue peroxidase activity. In the case of the carrageenan-induced mouse paw oedema, only 3 led to a reduction of the swelling 3 h after challenge (50 mg/kg, 46 % oedema inhibition). In addition, 3 inhibited the LTB (4) production in rat peritoneal polymorphonuclear leukocytes with an IC (50) value of 29.8 microM, while triterpenes showed toxicity against cells at 100 microM.

Anti-inflammatory activity of leaf essential oil from Cinnamomum longepaniculatum (Gamble) N. Chao.

PubMed

Du, Yong-Hua; Feng, Rui-Zhang; Li, Qun; Wei, Qin; Yin, Zhong-Qiong; Zhou, Li-Jun; Tao, Cui; Jia, Ren-Yong

2014-01-01

The anti-inflammatory activity of the essential oil from C. longepaniculatum was evaluated by three experimental models including the dimethyl benzene-induced ear edema in mice, the carrageenan-induced paw edema in rat and the acetic acid-induced vascular permeability in mice. The influence of the essential oil on histological changes and prostaglandin E2 (PGE2), histamine and 5-hydroxytryptamine (5-HT) production associated with carrageenan-induced rat paw edema was also investigated. The essential oil (0.5, 0.25, 0.13 ml/kg b.w.) showed significantly inhibition of inflammation along with a dose-dependent manner in the three experimental models. The anti-inflammatory activity of essential oil was occurred both in early and late phase and peaked at 4 h after carrageenan injection. The essential oil resulted in a dose dependent reduction of the paw thickness, connective tissue injury and the infiltration of inflammatory cell. The essential oil also significantly reduced the production of PGE2, histamine and 5-HT in the exudates of edema paw induced by carrageenan. Both the essential oil and indomethacin resulted relative lower percentage inhibition of histamine and 5-HT than that of PGE2 at 4 h after carrageenan injection.

Neutralization of the oedematogenic activity of Bothrops jararaca venom on the mouse paw by an antibothropic fraction isolated from opossum (Didelphis marsupialis) serum.

PubMed

Perales, J; Amorim, C Z; Rocha, S L; Domont, G B; Moussatché, H

1992-11-01

The pharmacological modulation of mice paw oedema produced by Bothrops jararaca venom (BJV) has been studied. Intraplantar injection of BJV (1-30 micrograms/paw) produced a dose- and time-related oedema, which was maximal 30 min after injection, reduced gradually thereafter and disappeared over 48 h. BJV heated at 100 degrees C for 5 or 15 min blocked local hemorrhage and caused partial inhibition of its oedematogenic activity. The BJV oedema was not inhibited by the anti-histamine meclizine, the inhibitor of histamine and serotonin, cyproheptadine, PAF-acether antagonist WEB 2170 or by the anti-leukotrienes C4/D4, LY 171883. Dexamethasone, aspirin, indomethacin, and the dual cyclooxygenase and lipoxygenase inhibitor BW 755C inhibited BJV-induced oedema indicating that arachidonic acid metabolism products via the cyclooxygenase pathway participate in its genesis and/or maintenance. The antibothropic fraction (ABF) (25-200 micrograms/paw) isolated from Didelphis marsupialis serum neutralized the oedema induced by the venom with and without heating, the hemorrhage induced by BJV and partially blocked the oedema induced by bradykinin and by cellulose sulphate. The oedema produced by histamine, serotonin, PAF-acether or leukotriene C4 was not inhibited.

Nyctanthes arbor-tristis Ameliorated FCA-Induced Experimental Arthritis: A Comparative Study among Different Extracts

PubMed Central

Uroos, Maliha; Sattar, Shumaila; Umer, Nigarish; Sharif, Ahsan

2017-01-01

Nyctanthes arbor-tristis (NAT) is commonly used traditionally for the treatment of rheumatism and inflammatory diseases. Current study evaluates the antiarthritic potential of NAT using Freund's adjuvant-induced arthritic rat model. Treatments with methanolic, ethyl acetate, and n-hexane extracts were continued for consecutive 20 days. Macroscopic arthritic scoring and water displacement plethysmometry were used to evaluate arthritic development. Hematological and biochemical parameters were investigated and ankle joints were processed for histopathological evaluation. Qualitative phytochemical analysis and GC-MS analysis were conducted for identification of constituents. NAT extracts suppressed arthritic scoring, paw edema, infiltration of inflammatory cells, pannus formation, and bone erosion. The plant extracts ameliorated total leukocytes and platelet counts and nearly normalized red blood cells (RBC) counts and hemoglobin (Hb) content. The extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea levels. Comparative analysis showed that ethyl acetate extract produced the highest inhibition of paw edema. The major constituents found in ethyl acetate extract can be classified into three major classes, that is, terpenes, terpenoids, fatty acids, and iridoid glycosides. Current study showed that Nyctanthes arbor-tristis ameliorated experimental rheumatoid arthritis and ethyl acetate extract possessed the highest inhibitory activity. PMID:28676830

1,25(OH)2D3 promotes chondrocyte apoptosis and restores physical function in rheumatoid arthritis through the NF-κB signal pathway.

PubMed

Tian, Run; Li, Xiaofang; Li, Yue; Wang, Kunzheng; Wang, Chunsheng; Yang, Pei

2018-06-26

We explored the modulatory effect of 1,25(OH) 2 D 3 on chondrocytes and physical function in rats with RA and its mechanism underlying the regulation of NF-κB signal pathway. RA patients and healthy volunteers were selected. Sprague-Dawley (SD) rats were used to establish RA models. The paw volume of rats was estimated. Chondrocytes were isolated from RA rats. The protein levels in both cartilage tissues and chondrocytes were determined using western blotting. Apoptosis was evaluated using TUNEL assay. Serum levels of IL-1β, IL-6, IL-10 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). Serum levels of 1,25(OH) 2 D 3 were lower in RA patients than in healthy volunteers. Rats in the RA + VD 3 group were lighter than those in normal and PBS groups, with an increased paw volume, severer joint swelling, higher expression levels of p-IκBα, p-p65, IL-1β, IL-6, and IL-17, and lower expression level of IL-10, while those in RA and RA + VD 3 + NF-κB group differed more significantly. In addition, by comparing RA rats and RA + NF-κB rats, we found that TNF-α stimulation exacerbated RA, increased expression levels of p-IκBα, p-p65, IL-1β, IL-6, and IL-17, and decreased the expression level of IL-10. Compared with RA chondrocytes, chondrocytes from RA + VD 3 rats exhibited lower expression levels of p-IκBα and p-p65, and had more apoptotic cells, while those from RA + NF-κB rats showed an opposite trend. Taken together, 1,25(OH) 2 D 3 accelerates chondrocyte apoptosis and improve physical function in rats with RA by the inhibition of NF-κB signal pathway. Copyright © 2018. Published by Elsevier Masson SAS.

Skin blood flow response in the rat model of wound healing: expression of vasoactive factors.

PubMed

Rendell, Marc S; Johnson, Mark L; Smith, Denae; Finney, David; Capp, Christopher; Lammers, Rebecca; Lancaster, Scott

2002-09-01

Although the microvascular blood flow response to wounding is predominantly vasodilation at skin sites with nutritive capillary perfusion (NUTR), there is a significant vasoconstrictive response at sites with high arteriovenous perfusion (AV). There may be a difference between NUTR and AV sites in the vasoactive factors which mediate the blood flow response to wounding. We measured the levels of mRNA expression of several potential mediators of the blood flow response to assess this possible difference. We measured skin blood flow at wounds placed at the back, a NUTR site, and at the paw, an AV site, in 12 Wistar Kyoto rats. Measurements were performed at baseline and then at 7 days post wounding. There was a significant increase in blood flow at back wound sites, with a rise from 4.1 +/- 0.3 ml/min/100 g to 9.8 +/- 1.9 ml/min/100 g. At the undisturbed wound perimeter, outside the zone of granulation tissue, flow rose to 7.3 +/- 1.1 ml/min/100 g. At the paw wound site, Day 0 flow was 8.8 +/- 0.8 ml/min/100 g. At 7 days, there was a significant decrease in flow at wound center to 5.5 +/- 0.5 ml/min/100 g. We measured the levels of inducible nitric oxide synthetase (iNOS), endothelin, endothelin receptor, vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF) gene mRNAs using reverse transcriptase PCR. There was a 10-fold increase in NOS mRNA in granulation tissue of both wounds on Day 7. There was a lesser but still substantial increase in the wound perimeter tissue. Levels of endothelin mRNA in the wound and wound perimeter were significantly lower at the paw than at the back. At baseline, the level of endothelin receptor B (ETrB) mRNA was greater at the back than at the paw. Wounding resulted in a substantial increase in EtrB mRNA levels in granulation tissue, reaching the same level at the back and paw wounds. There was also a substantial rise in EtrB mRNA levels at the paw wound perimeter, so that there was a reversal of the baseline condition, with paw levels actually surpassing the levels at the back perimeter. Thus, we have found significant changes in mediators both of vasoconstriction and vasodilation affecting the healing wound. These changes affect NUTR and AV sites in different ways. These results demonstrate the complexity of the regulatory processes controlling microvascular blood flow in wound healing.

Acute Radiation Sickness Amelioration Analysis

DTIC Science & Technology

1994-05-01

Emetic Drugs 16. PRICE CODE Antagonists 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19, SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF...102 UNCLASSIFIED mcuIw IA IIIcaIIin or Isis PAW CLASSFIED BY: N/A since Unclassified. DECLASSIFY ON: N/A since Unclassified. SECURITY CLASSIFICATION OF...Approximately 2000 documents relevant to the development of the candidate anti-emetic drugs ondansetron (Zofran, Glaxo Pharmaceuticals) and granisetron

Plasma ARC Welding of High-Performance-Ship Materials

DTIC Science & Technology

1979-05-01

19 REFERENCES .................. ............................ 85 iiii -. -’ - -" -. I LIST OF FIGURES Page I - Comparison of PAW and GTAW ...tungsten-arc- welding ( GTAW ) process. Both processes employ an inert-gas-shielded non- consumable tungsten electrode, as shown in Figure 1. In genernl, both...piece acts as the cathode (ground or negative). However, both PAW and GTAW can be and have been, used with direct-current reverse polarity and with

Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema.

PubMed

Maruyama, Hiroe; Sakamoto, Takashi; Araki, Yoko; Hara, Hideaki

2010-06-23

Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some of the anti-inflammatory action. The bee pollen would be beneficial not only as a dietary supplement but also as a functional food.

Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema

PubMed Central

2010-01-01

Background Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. Methods The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. Results The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. Conclusions It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some of the anti-inflammatory action. The bee pollen would be beneficial not only as a dietary supplement but also as a functional food. PMID:20573205

Polysaccharides from Arctium lappa L.: Chemical structure and biological activity.

PubMed

Carlotto, Juliane; de Souza, Lauro M; Baggio, Cristiane H; Werner, Maria Fernanda de P; Maria-Ferreira, Daniele; Sassaki, Guilherme L; Iacomini, Marcello; Cipriani, Thales R

2016-10-01

The plant Arctium lappa L. is popularly used to relieve symptoms of inflammatory disorders. A crude polysaccharide fraction (SAA) resulting of aqueous extraction of A. lappa leaves showed a dose dependent anti-edematogenic activity on carrageenan-induced paw edema, which persisted for up to 48h. Sequential fractionation by ultrafiltration at 50kDa and 30kDa cut-off membranes yielded three fractions, namely RF50, RF30, and EF30. All these maintained the anti-edematogenic effect, but RF30 showed a more potent action, inhibiting 57% of the paw edema at a dose of 4.9mg/kg. The polysaccharide RF30 contained galacturonic acid, galactose, arabinose, rhamnose, glucose, and mannose in a 7:4:2:1:2:1 ratio and had a Mw of 91,000g/mol. Methylation analysis and NMR spectroscopy indicated that RF30 is mainly constituted by a type I rhamnogalacturonan branched by side chains of types I and II arabinogalactans, and arabinan. Copyright © 2016 Elsevier B.V. All rights reserved.

Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla.

PubMed

Walker, Suellen M; Fitzgerald, Maria; Hathway, Gareth J

2015-06-01

Neonatal pain and injury can alter long-term sensory thresholds. Descending rostroventral medulla (RVM) pathways can inhibit or facilitate spinal nociceptive processing in adulthood. As these pathways undergo significant postnatal maturation, the authors evaluated long-term effects of neonatal surgical injury on RVM descending modulation. Plantar hind paw or forepaw incisions were performed in anesthetized postnatal day (P)3 Sprague-Dawley rats. Controls received anesthesia only. Hind limb mechanical and thermal withdrawal thresholds were measured to 6 weeks of age (adult). Additional groups received pre- and post-incision sciatic nerve levobupivacaine or saline. Hind paw nociceptive reflex sensitivity was quantified in anesthetized adult rats using biceps femoris electromyography, and the effect of RVM electrical stimulation (5-200 μA) measured as percentage change from baseline. In adult rats with previous neonatal incision (n = 9), all intensities of RVM stimulation decreased hind limb reflex sensitivity, in contrast to the typical bimodal pattern of facilitation and inhibition with increasing RVM stimulus intensity in controls (n = 5) (uninjured vs. neonatally incised, P < 0.001). Neonatal incision of the contralateral hind paw or forepaw also resulted in RVM inhibition of hind paw nociceptive reflexes at all stimulation intensities. Behavioral mechanical threshold (mean ± SEM, 28.1 ± 8 vs. 21.3 ± 1.2 g, P < 0.001) and thermal latency (7.1 ± 0.4 vs. 5.3 ± 0.3 s, P < 0.05) were increased in both hind paws after unilateral neonatal incision. Neonatal perioperative sciatic nerve blockade prevented injury-induced alterations in RVM descending control. Neonatal surgical injury alters the postnatal development of RVM descending control, resulting in a predominance of descending inhibition and generalized reduction in baseline reflex sensitivity. Prevention by local anesthetic blockade highlights the importance of neonatal perioperative analgesia.

Antinociceptive activity of Riparin II from Aniba riparia: Further elucidation of the possible mechanisms.

PubMed

Rodrigues de Carvalho, Alyne Mara; Vasconcelos, Leonardo Freire; Moura Rocha, Nayrton Flávio; Vasconcelos Rios, Emiliano Ricardo; Dias, Marília Leite; Maria de França Fonteles, Marta; Gaspar, Danielle Macêdo; Barbosa Filho, José Maria; Chavez Gutierrez, Stanley Juan; Florenço de Sousa, Francisca Cléa

2018-05-01

Riparin II (RipII) has an anti-inflammatory activity potentially due its ability to decrease TNF-α and IL-1β production and its histamine antagonism. The objective of this study was to evaluate the role of RipII in the pain process and the possible antinociceptive mechanisms involved, using classic models of nociception. Male Swiss mice were used in the assays. Determinate the acute toxicity according to the OECD 425 test guideline. The models used were the acetic acid-, formalin-, hot plate and glutamate-induced nociception. For evaluation of antinociceptive effect, the involvement of TRPV1, TRPA1, TRPM8, ASICS, Bradykinin, PKC and PKA were performed using the paw licking using agonists. The acute toxicity study did not detect any clinical signs or changes in behavior or mortality. RipII, administered orally (25 and 50 mg/kg) caused a reduction of nociception induced by acetic acid, formalin (on the second phase) and glutamate. In the investigation of antinociceptive mechanism, we used capsaicin (2.2 μg/paw), cinnamaldehyde (10 nmol/paw), menthol (1.2 μmol/paw), ASICS (2% acetic acid, pH 1.98) and bradykinin (10 μg/paw). The results showed that TRPV1, TRPA1, TRPM8, ASICS and bradykinin play a role in the antinociceptive effect of RipII. The results also showed that PKA is involved too. These data demonstrate that RipII has a low or not toxicity and produced an important antinociceptive effect through mechanisms that probably involve an interaction, at least in part, TRPV1, TRPA1, TRPM8, ASICS, bradykinin and PKA participate in the RipII's antinociceptive effect. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw

PubMed Central

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-01-01

Background and purpose: α-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of α-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. Experimental approach: The biological activities of α-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-κB and up-regulated expression of kinin B1 receptors. Key results: Treatment with either α-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-κB induced by LPS in the rat paw. However, only α-humulene significantly reduced the increase in TNF-α and IL-1β levels, paw oedema and the up-regulation of B1 receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Conclusions and Implications: Both α-humulene and trans-caryophyllene inhibit the LPS-induced NF-κB activation and neutrophil migration, although only α-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-α and IL-1β and the in vivo up-regulation of kinin B1 receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes α-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases. PMID:17471174

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw.

PubMed

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-07-01

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

A novel method for delivering ramped cooling reveals rat behaviours at innocuous and noxious temperatures: A comparative study of human psychophysics and rat behaviour.

PubMed

Dunham, James P; Hulse, Richard P; Donaldson, Lucy F

2015-07-15

Thermal sensory testing in rodents informs human pain research. There are important differences in the methodology for delivering thermal stimuli to humans and rodents. This is particularly true in cold pain research. These differences confound extrapolation and de-value nociceptive tests in rodents. We investigated cooling-induced behaviours in rats and psychophysical thresholds in humans using ramped cooling stimulation protocols. A Peltier device mounted upon force transducers simultaneously applied a ramped cooling stimulus whilst measuring contact with rat hind paw or human finger pad. Rat withdrawals and human detection, discomfort and pain thresholds were measured. Ramped cooling of a rat hind paw revealed two distinct responses: Brief paw removal followed by paw replacement, usually with more weight borne than prior to the removal (temperature inter-quartile range: 19.1 °C to 2.8 °C). Full withdrawal was evoked at colder temperatures (inter quartile range: -11.3 °C to -11.8 °C). The profile of human cool detection threshold and cold pain threshold were remarkably similar to that of the rat withdrawals behaviours. Previous rat cold evoked behaviours utilise static temperature stimuli. By utilising ramped cold stimuli this novel methodology better reflects thermal testing in patients. Brief paw removal in the rat is driven by non-nociceptive afferents, as is the perception of cooling in humans. This is in contrast to the nociceptor-driven withdrawal from colder temperatures. These findings have important implications for the interpretation of data generated in older cold pain models and consequently our understanding of cold perception and pain. Copyright © 2015. Published by Elsevier B.V.

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice.

PubMed

Serafim, Karla G G; Navarro, Suelen A; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Fattori, Victor; Cunha, Thiago M; Alves-Filho, Jose C; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

2015-11-01

Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

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.

Amelioration of inflammatory responses by Socheongryong-Tang, a traditional herbal medicine, in RAW 264.7 cells and rats

PubMed Central

Kim, Youn Sook; Jung, Ji Yun; Park, Chung A.; Jegal, Kyung Hwan; Ku, Sae Kwang; Kim, Jae Kwang; Lee, Chul Won; Kim, Young Woo; Cho, Il Je; An, Won G.; Kim, Sang Chan

2018-01-01

Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation in vivo and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE2 and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE2, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms. PMID:29436586

Amelioration of inflammatory responses by Socheongryong-Tang, a traditional herbal medicine, in RAW 264.7 cells and rats.

PubMed

Park, Sang Mi; Lee, Tae Hoon; Zhao, Rongjie; Kim, Youn Sook; Jung, Ji Yun; Park, Chung A; Jegal, Kyung Hwan; Ku, Sae Kwang; Kim, Jae Kwang; Lee, Chul Won; Kim, Young Woo; Cho, Il Je; An, Won G; Kim, Sang Chan

2018-05-01

Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation in vivo and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE2 and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE2, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.

Antioxidant and anti-inflammatory activities of aqueous extract of Centipeda minima.

PubMed

Huang, Shyh-Shyun; Chiu, Chuan-Sung; Lin, Tsung-Hui; Lee, Min-Min; Lee, Chao-Ying; Chang, Shu-Jen; Hou, Wen-Chi; Huang, Guan-Jhong; Deng, Jeng-Shyan

2013-05-20

Centipeda minima (L.) is traditionally used in Chinese folk medicine for the treatments of rhinitis, sinusitis, relieving pain, reducing swelling, and treating cancer for a long history in Taiwan. However, there is no scientific evidence which supports the use in the literature. The aim of this study was to evaluate the antioxidant and anti-inflammatory activities of the aqueous extract of Centipeda minima (ACM). The following activities were investigated: antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), DPPH (1,1-diphenyl-2-picrylhydrazyl)], and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigated the anti-inflammatory mechanism of ACM via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were also measured in vivo. In HPLC analysis, the fingerprint chromatogram of ACM was established. ACM showed the highest TEAC and DPPH radical scavenging activities, respectively. ACM also had highest contents of polyphenol and flavonoid contents. We evaluated that ACM and the reference compound of protocatechualdehyde and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Administration of ACM showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ACM could be via NO, TNF-α, and IL-1β suppressions and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ACM decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. Anti-inflammatory mechanisms of ACM might be correlated to the decrease in the level of Malondialdehyde (MDA), iNOS, and COX-2 via increasing the activities of CAT, SOD, and GPx in the edema paw. Overall, the results showed that ACM demonstrated antioxidant and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.

PubMed

Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Garrido-Mesa, Jose; Garrido-Mesa, Natividad; Utrilla, M Pilar; González-Tejero, M Reyes; Casares-Porcel, Manuel; Molero-Mesa, Joaquin; Del Mar Contreras, Maria; Segura-Carretero, Antonio; Pérez-Palacio, José; Diaz, Caridad; Vergara, Noemí; Vicente, Francisca; Rodriguez-Cabezas, M Elena; Galvez, Julio

2016-08-22

Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD). To test the anti-inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively. The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100µg/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg). L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti-inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition. L. dentata and L. stoechas extracts showed intestinal anti-inflammatory effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].

PubMed

Gapeev, A B; Lushnikov, K V; Shumilina, Iu V; Chemeris, N K

2006-01-01

The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity

Using an experimental model for the study of therapeutic touch.

PubMed

dos Santos, Daniella Soares; Marta, Ilda Estéfani Ribeiro; Cárnio, Evelin Capellari; de Quadros, Andreza Urba; Cunha, Thiago Mattar; de Carvalho, Emilia Campos

2013-02-01

to verify whether the Paw Edema Model can be used in investigations about the effects of Therapeutic Touch on inflammation by measuring the variables pain, edema and neutrophil migration. this is a pilot and experimental study, involving ten male mice of the same genetic strain and divided into experimental and control group, submitted to the chemical induction of local inflammation in the right back paw. The experimental group received a daily administration of Therapeutic Touch for 15 minutes during three days. the data showed statistically significant differences in the nociceptive threshold and in the paw circumference of the animals from the experimental group on the second day of the experiment. the experiment model involving animals can contribute to study the effects of Therapeutic Touch on inflammation, and adjustments are suggested in the treatment duration, number of sessions and experiment duration.

Upcoming Events

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Anti-inflammatory effect of selenium nanoparticles on the inflammation induced in irradiated rats.

PubMed

El-Ghazaly, M A; Fadel, N; Rashed, E; El-Batal, A; Kenawy, S A

2017-02-01

Selenium (Se) has been reported to possess anti-inflammatory properties, but its bioavailability and toxicity are considerable limiting factors. The present study aimed to investigate the possible anti-inflammatory and analgesic effects of selenium nanoparticles (Nano-Se) on inflammation induced in irradiated rats. Paw volume and nociceptive threshold were measured in carrageenan-induced paw edema and hyperalgesia model. Leukocytic count, tumor necrosis factor-α (TNF-α), prostaglandin E 2 (PGE 2 ), thiobarbituric acid reactive substances (TBAR), and total nitrate/nitrite (NOx) were estimated in the exudate collected from 6 day old air pouch model. Irradiated rats were exposed to 6 Gy gamma (γ)-irradiation. Nano-Se were administered orally in a dose of 2.55 mg/kg once before carrageenan injection in the first model and twice in the second model. The paw volume but not the nociceptive response produced by carrageenan in irradiated rats was higher than that induced in non-irradiated rats. Nano-Se were effective in reducing the paw volume in non-irradiated and irradiated rats but it did not alter the nociceptive threshold. The inflammation induced in irradiated rats increased all the estimated parameters in the exudate whereas; Nano-Se decreased their elevation in non-irradiated and irradiated rats. Nano-Se possess a potential anti-inflammatory activity on inflammation induced in irradiated rats.

Anti-inflammatory activity of Polygonum bistorta, Guaiacum officinale and Hamamelis virginiana in rats.

PubMed

Duwiejua, M; Zeitlin, I J; Waterman, P G; Gray, A I

1994-04-01

The aqueous ethanolic extracts of Polygonum bistorta L. Polygonaceae, Guaiacum officinale L. Zygophyllaceae and Hamamelis virginiana L. Hamamelidaceae were screened for anti-inflammatory activity. Administered (100 and 200 mg kg-1, p.o.) before the induction of carrageenan rat paw oedema, extracts of P. bistorta significantly suppressed both the maximal oedema response and the total oedema response (monitored as area under the time course curve). H. virginiana was inactive and G. officinale was only active at 200 mg kg-1. At 200 mg kg-1 administered before the induction of adjuvant arthritis, P. bistorta significantly inhibited both the acute and chronic phases of the adjuvant-induced rat paw swelling, while G. officinale and H. virginiana were only active against the chronic phase. Further studies on P. bistorta (100-800 mg kg-1) revealed a dose-dependent inhibition of the carrageenan-induced rat paw oedema over the dose range 100-400 mg kg-1, the E50 value being approximately 158.5 mg kg-1. The extract (200 mg kg-1), administered after the onset of the inflammatory responses reversed the course of both the carrageenan- and adjuvant-induced rat paw swelling. The results confirm that the extracts of P. bistorta, G. officinale and H. virginiana contain anti-inflammatory substances.

Therapeutics for Inflammatory-Related Diseases Based on Plasmon-Activated Water: A Review.

PubMed

Yang, Chih-Ping; Liu, Yu-Chuan

2018-05-28

It is recognized that the properties of liquid water can be markedly different from those of bulk one when it is in contact with hydrophobic surfaces or is confined in nano-environments. Because our knowledge regarding water structure on the molecular level of dynamic equilibrium within a picosecond time scale is far from completeness all of water's conventionally known properties are based on inert "bulk liquid water" with a tetrahedral hydrogen-bonded structure. Actually, the strength of water's hydrogen bonds (HBs) decides its properties and activities. In this review, an innovative idea on preparation of metastable plasmon-activated water (PAW) with intrinsically reduced HBs, by letting deionized (DI) water flow through gold-supported nanoparticles (AuNPs) under resonant illumination at room temperature, is reported. Compared to DI water, the created stable PAW can scavenge free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals and effectively reduce NO release from lipopolysaccharide-induced inflammatory cells. Moreover, PAW can dramatically induce a major antioxidative Nrf2 gene in human gingival fibroblasts. This further confirms its cellular antioxidative and anti-inflammatory properties. In addition, innovatively therapeutic strategy of daily drinking PAW on inflammatory-related diseases based on animal disease models is demonstrated, examples being chronic kidney disease (CKD), chronic sleep deprivation (CSD), and lung cancer.

In Vivo Evaluation of the Anti-Inflammatory Effect of Pistacia lentiscus Fruit Oil and Its Effects on Oxidative Stress

PubMed Central

Bardaa, Sana; Sahnoun, Zouheir; Rebai, Tarek

2016-01-01

In order to find new topical anti-inflammatory agents, we had recourse to a medicinal plant. This work was designed to determine the topical anti-inflammatory effect of Pistacia lentiscus fruit oil (PLFO), using carrageenan-induced paw edema rat model, and to evaluate its effects on oxidative stress. The topical anti-inflammatory activity of PLFO was compared to Inflocine® and estimated by measuring the diameter of paw edema, for 5 hours at a 1-hour interval. After that the rats were scarified and the inflamed paw tissue was removed for the exploration of some parameters of oxidative stress and histopathology. PLFO showed a significant anti-inflammatory activity in comparison with the Inflocine. The percentages of edema inhibition were 70% and % 51.5% (p < 0.01), respectively, after five hours. The treatment with PLFO and Inflocine led to significant increases (p ≤ 0.05) in the activities of CAT, SOD, and GPX and significant decreases in the MDA level and AOPP activity in the paw tissue after Carr injection, in comparison with the Carr group. Therefore, our findings demonstrate that PLFO might accelerate the development of new drugs which could be used scientifically as a source for natural health products in the treatment of topical inflammation. PMID:28070202

Proanthocyanidin-rich Pinus radiata bark extract inhibits mast cell-mediated anaphylaxis-like reactions.

PubMed

Choi, Yun Ho; Song, Chang Ho; Mun, Sung Phil

2018-02-01

Mast cells play a critical role in the effector phase of immediate hypersensitivity and allergic reactions. Pinus radiata bark extract exerts multiple biological effects and exhibits immunomodulatory and antioxidant properties. However, its role in mast cell-mediated anaphylactic reactions has not been thoroughly investigated. In this study, we examined the effects of proanthocyanidin-rich water extract (PAWE) isolated from P. radiata bark on compound 48/80-induced or antidinitrophenyl (DNP) immunoglobulin E (IgE)-mediated anaphylaxis-like reactions in vivo. In addition, we evaluated the mechanism underlying the inhibitory effect of PAWE on mast cell activation, with a specific focus on histamine release, using rat peritoneal mast cells. PAWE attenuated compound 48/80-induced or anti-DNP IgE-mediated passive cutaneous anaphylaxis-like reactions in mice, and it inhibited histamine release triggered by compound 48/80, ionophore A23187, or anti-DNP IgE in rat peritoneal mast cells in vitro. Moreover, PAWE suppressed compound 48/80-elicited calcium uptake in a concentration-dependent manner and promoted a transient increase in intracellular cyclic adenosine-3',5'-monophosphate levels. Together, these results suggest that proanthocyanidin-rich P. radiata bark extract effectively inhibits anaphylaxis-like reactions. Copyright © 2017 John Wiley & Sons, Ltd.

Seasonal and interannual variability of climate and vegetation indices across the Amazon

PubMed Central

Brando, Paulo M.; Goetz, Scott J.; Baccini, Alessandro; Nepstad, Daniel C.; Beck, Pieter S. A.; Christman, Mary C.

2010-01-01

Drought exerts a strong influence on tropical forest metabolism, carbon stocks, and ultimately the flux of carbon to the atmosphere. Satellite-based studies have suggested that Amazon forests green up during droughts because of increased sunlight, whereas field studies have reported increased tree mortality during severe droughts. In an effort to reconcile these apparently conflicting findings, we conducted an analysis of climate data, field measurements, and improved satellite-based measures of forest photosynthetic activity. Wet-season precipitation and plant-available water (PAW) decreased over the Amazon Basin from 1996−2005, and photosynthetically active radiation (PAR) and air dryness (expressed as vapor pressure deficit, VPD) increased from 2002–2005. Using improved enhanced vegetation index (EVI) measurements (2000–2008), we show that gross primary productivity (expressed as EVI) declined with VPD and PAW in regions of sparse canopy cover across a wide range of environments for each year of the study. In densely forested areas, no climatic variable adequately explained the Basin-wide interannual variability of EVI. Based on a site-specific study, we show that monthly EVI was relatively insensitive to leaf area index (LAI) but correlated positively with leaf flushing and PAR measured in the field. These findings suggest that production of new leaves, even when unaccompanied by associated changes in LAI, could play an important role in Basin-wide interannual EVI variability. Because EVI variability was greatest in regions of lower PAW, we hypothesize that drought could increase EVI by synchronizing leaf flushing via its effects on leaf bud development. PMID:20679201

Anti-inflammatory effects of essential oils from Mangifera indica.

PubMed

Oliveira, R M; Dutra, T S; Simionatto, E; Ré, N; Kassuya, C A L; Cardoso, C A L

2017-03-16

Mangifera indica is widely found in Brazil, and its leaves are used as an anti-inflammatory agent in folk medicine. The aim of this study is to perform composition analysis of essential oils from the M. indica varieties, espada (EOMIL1) and coração de boi (EOMIL2), and confirm their anti-inflammatory properties. Twenty-three volatile compounds were identified via gas chromatography-mass spectrometry (GC-MS) in two essential oils from the leaves. Paw edema and myeloperoxidase (MPO) activity were evaluated using the carrageenan-induced paw model, while leukocyte migration was analyzed using the pleurisy model. At oral doses of 100 and 300 mg/kg, the essential oils significantly reduced edema formation and the increase in MPO activity induced by carrageenan in rat paws. For a dose of 300 mg/kg EOMIL1, 62 ± 8% inhibition of edema was observed, while EOMIL2 led to 51 ± 7% inhibition of edema. At a dose of 100 mg/kg, the inhibition was 54 ± 9% for EOMIL1 and 37 ± 7% for EOMIL2. EOMIL1 and EOMIL2 significantly reduced MPO activity at doses of 100 mg/kg (47 ± 5 and 23 ± 8%, respectively) and 300 mg/kg (50 ± 9 and 31 ± 7%, respectively). In the pleurisy model, inhibitions were also observed for EOMIL1 and EOMIL2 in the leukocyte migration test. The results of the present study show that essential oils from M. indica differ in chemical composition and anti-inflammatory activity in rats.

Donate | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Alumni | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Policies | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Tutoring | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

About | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Advising | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Business | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Contact | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Procedures | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Research | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Scholarships | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Community | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

News | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

PAVE PAWS Early Warning Radar Operation Cape Cod Air Force Station, MA. Record of Decision

DTIC Science & Technology

2009-06-01

Electrical and Electronics Engineers (IEEE) C95.1-1999. Accordingly, the highest measurement was obtained directly in front of the feedhorn (i.e...waveform characterization of the Cape Cod AFS Pave PAWS radar. The data acquired during the Phase IV survey indicated that the electric fields produced...level observed among the ambient sites. During this survey, peak/average power density measurements and peak/average electric field measurements

Formulation and Characterization of Aceclofenac -Aloe vera Transemulgel.

PubMed

Raju, Y Prasanna; Haritha, K; Satyanarayana, Rao P; Vandana, K R; Bindu, D Thushara; Vinesha, V; Chowdary, V Harini

2015-01-01

The present research was aimed to formulate aceclofenac transemulgel using Aloe vera as gel base. The prepared formulations were subjected to physical characterization, in-vitro and in-vivo assessment. Aceclofenac, a hydrophobic potential non steroidal anti inflammatory drug, causes ulceration upon chronic oral administration, could be formulated into transemulgel to enhance therapeutic efficacy and to lower the unwanted side effects. The transemulgel was prepared from aqueous Aloe vera gel and aceclofenac emulsion. The prepared transemulgel was evaluated for its pH, viscosity, drug content, skin irritation, in-vitro diffusion and accelerated stability studies. The prepared aceclofenac-Aloe vera tranemulgel and commercial aceclofenac gel were subjected to pharmacodynamic studies in albino rats of Wistar strain employing carrageenan induced left hind paw edema method to assess the anti-inflammatory effect. The transemulgel showed a pH of 6.78 and viscosity of 18 cps. In-vitro diffusion data revealed better permeation characteristics. Topical application of formulation found no skin irritation. Stability study has proved the integrity of the formulation. The prepared aceclofenac Aloe vera transemulgel showed better in-vitro drug release when compared with the commercial aceclofenac gel formulation. Anti-inflammatory activity in treated rats showed the significant paw volume reduction at p<0.05 compared with that of control. Thus, it is concluded that aceclofenac, a potential non steroidal anti inflammatory drug, showed high therapeutic efficiency when formulated into transemulgel using aqueous Aloe vera as gel base.

The art of fault-tolerant system reliability modeling

NASA Technical Reports Server (NTRS)

Butler, Ricky W.; Johnson, Sally C.

1990-01-01

A step-by-step tutorial of the methods and tools used for the reliability analysis of fault-tolerant systems is presented. Emphasis is on the representation of architectural features in mathematical models. Details of the mathematical solution of complex reliability models are not presented. Instead the use of several recently developed computer programs--SURE, ASSIST, STEM, PAWS--which automate the generation and solution of these models is described.

Research Collaborations | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Center for Alternative Fuels Research Program | College of Engineering &

Science.gov Websites

Applied Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW Visit Apply Give to UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

GE Healthcare | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Software List | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Student Organizations | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Incoming Freshman | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Travel Directions | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Future Students | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Corporate Partners | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

EnQuest | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Hire a Milwaukee Engineer | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Computer Resources | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Strategic Planning | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

ANSYS Institute | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Career Fairs | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Current Students | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Foundry and Solidification Processing Laboratory | College of Engineering &

Science.gov Websites

Applied Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW Visit Apply Give to UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

April 2016 Milwaukee Engineer | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Undergraduate Curriculum | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Research Centers & Consortia | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Admissions - Graduate Students | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

FTC General Information | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Catalyst Grants: Sensing the Future | College of Engineering & Applied

Science.gov Websites

Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Center for Advanced Materials Manufacturing | College of Engineering &

Science.gov Websites

Applied Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW Visit Apply Give to UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Corporate Services | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Computer Labs | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Study Abroad | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Structures Laboratory | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Multimedia Software Laboratory | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Center for Composite Materials | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Girls Who Code Club | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Admissions - Undergraduate Students | College of Engineering & Applied

Science.gov Websites

Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

2016 Milwaukee Engineering Research Conference | College of Engineering &

Science.gov Websites

Applied Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW Visit Apply Give to UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Graduate Curriculum | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Research Labs | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Product Realization | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Fast Facts | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Strategic Plan | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

College-Wide Support | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

50th Anniversary | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

FAQ's and Deadlines | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Office of Research Support | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Department Chairs and Staff | College of Engineering & Applied Science

Science.gov Websites

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

PubMed

de Bernardis, E; Leonardi, G; Caruso, A; Cutuli, V M; Amico-Roxas, M

1994-08-01

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis

PubMed Central

Liu, Shu-Ling; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Lin, Wang-Ching; Liao, Jung-Chun; Huang, Guan-Jhong

2012-01-01

Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products. PMID:22778769

Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis.

PubMed

Liu, Shu-Ling; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Lin, Wang-Ching; Liao, Jung-Chun; Huang, Guan-Jhong

2012-01-01

Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products.

Dissemination of Clostridium difficile spores between environment and households: Dog paws and shoes.

PubMed

Janezic, Sandra; Mlakar, Sabina; Rupnik, Maja

2018-04-23

Clostridium difficile is an anaerobic, spore-forming bacterium that causes intestinal infections. Although C. difficile is still predominantly considered as a nosocomial pathogen, there has been an increase in the number of community-associated infections. Since C. difficile is ubiquitous and can be isolated from nearly any environment, one of the possibilities for community acquisition could be exposure to spores in the domestic environment. The aim of this study was to evaluate the presence of C. difficile spores on shoes, slippers and on dog paws and to explore the importance of these surfaces as vectors for the dissemination of C. difficile in a domestic environment. Overall, C. difficile was present in 14 (70%) of 20 households and in 31 of 90 (34%) collected samples. Shoes and slippers had the highest positivity rates, 19 of 44 (43%) and 6 of 21 (28%), respectively, followed by dog paws 6 of 25 (24%). Thirteen C. difficilePCR ribotypes were identified with half of the isolates belonging to ribotype 014/020, which is the predominant type circulating in human population and is also commonly found in the environment (e.g. soil and water) in Slovenia. In three households, identical PCR ribotypes were found on dog paws, shoes and slippers. To understand the fine-scale genetic relatedness of these isolates, we sequenced the genomes. Low level of single nucleotide variant (SNV) differences between isolates from the same households, consistent with a recent transmission from a common source, were seen for isolates of PCR ribotype 014/020 but not for PCR ribotype 010. Our results suggest that shoe soles and dog paws could serve for the dissemination of C. difficile spores between households and environment and could contribute to community-relevant sources for C. difficile infection in humans. © 2018 Blackwell Verlag GmbH.

Influence of several peptidase inhibitors on the pro-inflammatory effects of substance P, capsaicin and collagenase.

PubMed

Damas, J; Bourdon, V; Liégeois, J F; Simmons, W H

1996-11-01

Injection of substance P (SP) in a rat hindpaw induced extravasation of 125I-labelled albumin in both hindpaws and salivation. Intravenous injection of SP dose-dependently increased vascular permeability. This latter effect was increased in rat paws by captopril, an inhibitor of angiotensin-converting enzyme (ACE), administered locally in combination with diprotin A, an inhibitor of an dipeptidyl(amino)peptidase IV (DAP IV) or phosphoramidon, an inhibitor of neutral endopeptidase (NEP). The increase in permeability induced by SP was inhibited by RP 67580, a NK-1-receptor antagonist. Intravenous injection of capsaicin induced labelled albumin extravasation in rat paws. This effect was increased by combination of captopril with diprotin A or phosphoramidon, but not by captopril associated with amastatin, an inhibitor of aminopeptidase M (AmM). It was suppressed by RP 67580. Injection of collagenase in rat paws triggered a swelling and a local plasma exudation. These responses were reduced by RP 67580 but not by RP 68651, its inactive enantiomer. They were increased by combination of captopril with diprotin A or phosphoramidon in normal rats. The potentiating effects of captopril and diprotin A were suppressed by RP 67580 in normal rats but did not develop in kininogen-deficient rats. The oedema induced by collagenase was also increased by lisinopril, another ACE inhibitor, administered locally in combination with apstatin, an inhibitor of aminopeptidase P (AmP). In rats pretreated by methysergide, collagenase-induced oedema was reduced and can be increased by captopril, by lisinopril, administered alone or by lisinopril associated with apstatin. It is concluded that SP is mainly inactivated in rat paws by ACE, DAP IV and NEP. In collagenase-induced oedema, a low amount of SP would be released from afferent nerve terminals by bradykinin formed in low amounts. Bradykinin is inactivated in rat paws by ACE and AmP. In collagenase-oedema, the pro-inflammatory effects of bradykinin are concealed by the effects of the other mediators.

In Vivo Anti-Inflammatory, Anti-Bacterial and Anti-Diarrhoeal Activity of Ziziphus Jujuba Fruit Extract.

PubMed

Mesaik, Ahmed M; Poh, Hiap Wei; Bin, Ooi Yan; Elawad, Izzaddinn; Alsayed, Badr

2018-05-20

Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative). To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract. The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat's treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat's paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin. EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group. EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.

Efficacy of an ethanol/guar/triclosan/glycerine gel on bacteria and yeast loads in canine pododermatitis: a pilot study.

PubMed

Ortalda, C; Noli, C; Cena, T

2016-04-01

To assess efficacy of a gel compound containing guar, glycerine, triclosan and ethanol (Pawcare®, JOKER Technologies, Kerzers, Switzerland) in decreasing bacterial and yeast loads on the paws of dogs with erythematous, greasy and/or malodorous pododermatitis. In 20 dogs, each with at least two affected paws, semiquantitative Malassezia species counts were performed on 10 oil-immersion fields (range: 0 to 30) from acetate tapes pressed on the palmar/plantar surface of one paw. Half of the area was sampled before and the other half immediately after the application of Pawcare(®) . With a similar procedure, swab samples were collected from the other paw for bacterial culture, identification and evaluation of colony-forming units before and immediately after treatment. Statistical evaluation of pre- and posttreatment counts was performed with the Wilcoxon signed-rank test. Nine dogs were positive for Malassezia species Mean acetate tape preparation counts decreased significantly from 8·78 (±8·03) to 5·668 (±6·65) (P=0·0039) after treatment. Twenty-five bacterial isolates of 11 different species were cultured in 19 dogs. Posttreatment cultures were sterile in 8 dogs that had an initial zero or low number (1 to 2 log counts) of colony-forming units. In cases with a higher pre-treatment number of colony forming units (2 to 6 log counts), there was a significant decrease - by a mean of 1·16 log counts (pre 3·12 ±1·69, post 1·96 ±1·57) (P=0·0002). The findings of the present study support the use of PawCare® gel to decrease bacterial and yeast loads in dogs affected by chronic diseases involving the inter-digital spaces. © 2016 British Small Animal Veterinary Association.

Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

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

Xu, Ya-Qiong; Jin, Shao-Ju; Luohe Medical College, Luohe 462002, Henan Province

Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressuremore » and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.« less

Anti-Inflammatory and Antibothropic Properties of Jatropha Elliptica, a Plant from Brazilian Cerrado Biome

PubMed Central

Ferreira-Rodrigues, Sára Cósta; Rodrigues, Cássio Milhomens; Dos Santos, Marcio Galdino; Gautuz, Jean Antonio Abraham; Silva, Magali Glauzer; Cogo, José Carlos; Batista-Silva, Camila; Dos Santos, Cleiton Pita; Groppo, Francisco Carlos; Cogo-Müller, Karina; Oshima-Franco, Yoko

2016-01-01

Purpose: The aim of this study was to evaluate the antibothropic and anti-inflammatory properties of J. elliptica. Methods: Phytochemical screening and thin-layer chromatography (TLC) assays were performed on J. elliptica hydroalcoholic extract (TE) in order to observe its main constituents. The antibothropic activity of TE was evaluated by the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu), in a mouse phrenic nerve-diaphragm model (PND). A quantitative histological study was carried out to observe a possible protection of TE against the venom myotoxicity. The anti-inflammatory activity was also evaluated in two models, Bjssu-induced paw edema, and carrageenan-induced neutrophils migration in the peritoneal cavity. Results: TLC analysis revealed several compounds in TE, such as saponins, alkaloids, and phenolic constituents. TE was able to neutralize the blockade and the myotoxicity induced by venom, when it was pre-incubated for 30 min with venom. In addition, it showed anti-inflammatory activity, inducing less neutrophils migration and reducing paw edema. Conclusion: J. elliptica showed both antibothropic and anti-inflammatory properties. PMID:28101464

Neutrophil infiltration is implicated in the sustained thermal hyperalgesic response evoked by allergen provocation in actively sensitized rats.

PubMed

Lavich, Tatiana Ramos; Siqueira, Rodrigo de Azeredo; Farias-Filho, Francisco Alves; Cordeiro, Renato Sérgio Balão; Rodrigues e Silva, Patrícia Machado; Martins, Marco Aurélio

2006-11-01

It has been proposed that allergen provocation induces hyperalgesia but the involvement of immunoglobulin E and leukocytes remains poorly understood. Here, we have compared the profile of allergen-evoked thermal hyperalgesic response in both passively and actively sensitized rats, and investigated the role of leukocytes in allergen-evoked nociception. Wistar rats were passively sensitized with an intraplantar injection of immunoglobulin E anti-dinitrophenylated bovine serum albumin monoclonal antibody (0.5 microg/paw), and challenged with dinitrophenylated bovine serum albumin (0.5 microg/paw) 24 h later. Alternatively, the animals were actively sensitized with a mixture of Al(OH)3 and ovalbumin and challenged intraplantarly with ovalbumin (12 microg/paw) 14 days later. We found that the thermal hyperalgesic responses set in very rapidly and with comparable intensity in both passively and actively sensitized rats. However, while in the former group the response was shorter, peaking within 1 h and reducing thereafter, a marked plateau was observed from 1 to 6 h post-challenge in the latter group. Actively sensitized rats also had higher neutrophil influx in the plantar tissue, as attested by both myeloperoxidase activity and histological analysis. Treatment of actively sensitized rats with either fucoidin (10 mg/kg, i.v) or anti-rat neutrophil antiserum (i.p.) reduced neutrophil accumulation and the late hyperalgesic response noted from 3 to 6 h post-challenge. Thus, we conclude that though immunoglobulin E-mediated mechanisms can cause thermal hyperalgesia, components of the cellular immune reaction are crucial in order to amplify and sustain the immediate hyperalgesic response triggered by allergen, in a process dependent on neutrophil recruitment.

Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.

PubMed

Rodrigues, Lindaiane Bezerra; Oliveira Brito Pereira Bezerra Martins, Anita; Cesário, Francisco Rafael Alves Santana; Ferreira E Castro, Fyama; de Albuquerque, Thaís Rodrigues; Martins Fernandes, Maria Neyze; Fernandes da Silva, Bruno Anderson; Quintans Júnior, Lucindo José; da Costa, José Galberto Martins; Melo Coutinho, Henrique Douglas; Barbosa, Roseli; Alencar de Menezes, Irwin Rose

2016-09-25

The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Center for By-Products Utilization (CBU) | College of Engineering & Applied

Science.gov Websites

Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering & Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

Center for Urban Transportation Studies | College of Engineering & Applied

Science.gov Websites

Engineering of the College of Engineering and Applied Science as well as with the faculty at UW-Madison, UW Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW-System About UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College ofEngineering &

Catalyst Grants: Contributing to X-Ray History | College of Engineering &

Science.gov Websites

Applied Science A B C D E F G H I J K L M N O P Q R S T U V W X Y Z D2L PAWS Email My UW Visit Apply Give to UWM Jobs D2L PAWS Email My UW-System University of Wisconsin-Milwaukee College Olympiad Girls Who Code Club FIRST Tech Challenge NSF I-Corps Site of Southeastern Wisconsin UW-Milwaukee

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.

A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome.

PubMed

Tékus, Valéria; Hajna, Zsófia; Borbély, Éva; Markovics, Adrienn; Bagoly, Teréz; Szolcsányi, János; Thompson, Victoria; Kemény, Ágnes; Helyes, Zsuzsanna; Goebel, Andreas

2014-02-01

The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Anti-Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro-Inflammatory Mediators.

PubMed

Singh, Ajeet Kumar; Vinayak, Manjula

2016-07-01

Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti-hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c-Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL-1β, TNF-α and IL-6 as well as inflammatory enzymes COX-2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX-2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti-nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Synergistic Interaction of a Gabapentin- Mangiferin Combination in Formalin-Induced Secondary Mechanical Allodynia and Hyperalgesia in Rats Is Mediated by Activation of NO-Cyclic GMP-ATP-Sensitive K+ Channel Pathway.

PubMed

Godínez-Chaparro, Beatriz; Quiñonez-Bastidas, Geovanna Nallely; Rojas-Hernández, Isabel Rocío; Austrich-Olivares, Amaya Montserrat; Mata-Bermudez, Alfonso

2017-12-01

Preclinical Research Gabapentin is an anticonvulsant used to treat neuropathic pain. Mangiferin is an antioxidant that has antinociceptive and antiallodynic effects in inflammatory and neuropathic pain models. The purpose of this study was to determine the interaction between mangiferin and gabapentin in the development and maintenance of formalin-induced secondary allodynia and hyperalgesia in rats. Gabapentin, mangiferin, or their fixed-dose ratio combination were administrated peripherally. Isobolographic analyses was used to define the nature of the interaction of antiallodynic and/or antihyperalgesic effects of the two compounds. Theoretical ED 50 values for the combination were 74.31 µg/paw and 95.20 µg/paw for pre- and post-treatment, respectively. These values were higher than the experimental ED 50 values, 29.45 µg/paw and 37.73 µg/paw respectively, indicating a synergistic interaction in formalin-induced secondary allodynia and hyperalgesia. The antiallodynic and antihyperalgesic effect induced by the gabapentin/mangiferin combination was blocked by administration of L-NAME, the soluble guanylyl cyclase inhibitor, ODQ and glibenclamide. These data suggest that the gabapentin- mangiferin combination produces a synergistic interaction at the peripheral level. Moreover, the antiallodynic and hyperalgesic effect induced by the combination is mediated via the activation of an NO-cyclic GMP-ATP-sensitive K + channel pathway. Drug Dev Res 78 : 390-402, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Compact Cosmic Ray Telescope using Silicon Photomultipliers for use in High Schools

NASA Astrophysics Data System (ADS)

Castro, Luis; Elizondo, Leonardo; Shelor, Mark; Cervantes, Omar; Fan, Sewan; Ritt, Stefan

2016-03-01

Over the years, the QuarkNet and the LBL Cosmic Ray Project have helped trained thousands of high school students and teachers to explore cosmic ray physics. To get high school students in the Salinas, CA area also excited about cosmic rays, we constructed a cosmic ray telescope as a physics outreach apparatus. Our apparatus includes a pair of plastic scintillators coupled to silicon photomultipliers (SiPM) and a coincidence circuit board. We designed and constructed custom circuit boards for mounting the SiPM detectors, the high voltage power supplies and coincidence AND circuit. The AND logic signals can be used for triggering data acquisition devices including an oscilloscope, a waveform digitizer or an Arduino microcontroller. To properly route the circuit wire traces, the circuit boards were layout in Eagle and fabricated in-house using a circuit board maker from LPKF LASER, model Protomat E33. We used a Raspberry Pi computer to control a fast waveform sampler, the DRS4 to digitize the SiPM signal waveforms. The CERN PAW software package was used to analyze the amplitude and time distributions of SiPM detector signals. At this conference, we present our SiPM experimental setup, circuit board fabrication procedures and the data analysis work flow. AIP Megger's Award, Dept. of Ed. Title V Grant PO31S090007.

Effect of a total extract from Fraxinus ornus stem bark and esculin on zymosan- and carrageenan-induced paw oedema in mice.

PubMed

Stefanova, Z; Neychev, H; Ivanovska, N; Kostova, I

1995-05-01

This study investigates the total ethanol extract (TE) of the stem bark of Fraxinus ornus and its constituent esculin (EN). They inhibited classical pathway (CP) and alternative pathway (AP) of complement activation in mouse serum. After intraperitoneal administration the total extract displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw oedema in mice. The results suggest that the traditional use of Fraxinus ornus stem bark extracts in the treatment of inflammatory disorders is at least partially due to its coumarin constituents.

Operation of the PAVE PAWS Radar System at Beale Air Force Base, California. Part 1. Basic EIS & Appendices.

DTIC Science & Technology

1980-07-01

Middlefield Road Mail Stop 92 Menlo Park, CA 94025 U.S. Geological Survey 2800 Cottage Way Sacramento, CA 95825 State and Local Agencies Air Resources Board...RELATIONSHIP BETWEEN LOCAL SHORT-TERM USE OF MAN’S ENVIRONMT AND THE mAINUKANCE AND ENHANCEMNT OF LONG-TERM PRODUCTIVITY . . . . . . . . . . 6-1 7...Distances from Local Areas of Interest to Mt. lebo, Oregon AFS . . . .. ... 1-41 1-15 lousing Distribution of Personnel Affected by PAVS PAWS Mt.lRebo AlS

Probing HER2-PUMA and EGFR-PUMA Crosstalks in Aggressive Breast Cancer

DTIC Science & Technology

2014-09-01

observations have been published in PLoS One in 2013 [Carpenter, R. L , Han, W., Paw, I. and Lo, H.-W. PLoS ONE 9 interaction between the two...tyrosine was changed to phenylalanine (Y58F, Y152F, Y172F) or all tyrosines were mutated (triple mutant: TM). MCF- 7 cells were transfected with WT...104-115, 2012. [9] Carpenter, R. L , Han, W., Paw, I. and Lo, H.-W. HER2 phosphorylates and destabilizes proapoptotic PUMA, leading to antagonized

A Systems Analysis and Project Management Plan for the Petite Amateur Navy Satellite (PANSAT)

DTIC Science & Technology

1994-09-01

engineering is defined as a process by which a stated need (objective) is transformed into a life cycle balanced set of product and process descriptions...and rr.eseing the collection of informialtio Send comments regardmg this burden estimate or any o•her aspect of this :olleiori•t i informationt...including suggeston, for reducing this bourden, to Washington Hieadquaroers .ervin Directorate I’r Infomiation Operalions% and Repows 1211 Jefferson Paws

Gas chromatographic mass analysis and further pharmacological actions of Cymbopogon proximus essential oil.

PubMed

Al-Taweel, A M; Fawzy, G A; Perveen, S; El Tahir, K E H

2013-09-01

The present study reports Gas chromatographic mass analysis (GC-MS) as well as important biological activities of Cymbopogon proximus essential oil. The chemical composition of the essential oil of Cymbopogon proximus was investigated by GC-MS. Furthermore, the effects of Cymbopogon proximus essential oil on the cardiac parasympathetic ganglia in rats, the intra-tracheal pressure in guinea-pigs and on carrageenan-induced inflammation in the rats paw, were studied. The GC-MS study led to the identification of 22 components with Piperitone representing (73.81%), Elemol (9.32%), alpha-Eudesmol (5.21%) and alpha-Terpineol (3.01%) of the oils composition. The percentage protective effect of the oil on the vagus-induced bradycardia in rats was 90.1±3.1%, which represents a significant protection. As for the effect of Cymbopogon oil on bronchoconstrictors-induced increase in intra-tracheal pressure in guinea-pigs, the oil antagonized the actions of 5-HT and histamine by 80±3.7 and 93±8.3%, respectively. Pharmacological investigations using Cymbopogon oil revealed its inherent ability to possess a bronchodilator activity mediated via blockade of both histamine and serotonin receptors. It possessed a significant ganglionic blocking action and a limited anti-inflammatory activity that seemed to involve blockade of histamine and serotonin receptors in the rats' paws. © Georg Thieme Verlag KG Stuttgart · New York.

Low-level laser therapy (LLLT) reduces the COX-2 mRNA expression in both subplantar and total brain tissues in the model of peripheral inflammation induced by administration of carrageenan.

PubMed

Prianti, Antonio Carlos Guimarães; Silva, José Antonio; Dos Santos, Regiane Feliciano; Rosseti, Isabela Bueno; Costa, Maricilia Silva

2014-07-01

In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm(2), resulting in an energy dosage of 7.5 J/cm(2). Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS.

Functional relationship between brainstem putative pain-facilitating neurons and spinal nociceptfive neurons during development of inflammation in rats.

PubMed

Salas, Rafael; Ramirez, Karla; Tortorici, Victor; Vanegas, Horacio; Vazquez, Enrique

2018-05-01

The so-called on- and off-cells of the rostral ventromedial medulla (RVM) send their axons to the spinal dorsal horn. Activation of on-cells precedes and coincides with a facilitation, and activation of off-cells coincides with an inhibition, of withdrawal reflexes elicited by noxious agents. Considerable evidence supports the notion that on- and off-cells modulate nocifensive reflexes during opioid and non-opioid action and also during normal circumstances and during peripheral neuropathy and inflammation. Yet it is unclear whether on- and off-cells act upon sensory spinal circuits that might lead to ascending projections and the experience of pain. Here, in deeply anesthetized rats we recorded single unit discharges from pairs of one on-like or off-like cell in RVM and a nociceptive neuron in the spinal dorsal horn with input from a hind paw. Both ongoing activity and responses to a calibrated noxious stimulus applied to the paw were documented during basal conditions and during development of paw inflammation. Probably due to the strong barbiturate anesthesia, off-like cells were depressed and did not yield interpretable results. However, we showed for the first time that during the increase in neuronal activity that results from paw inflammation the activity of spinal nociceptive neurons reflects the activity of their partner on-like cells in a highly correlated manner. This implies a tight relationship between spinal sensory and RVM modulatory functions that may underlie inflammation-induced hyperreflexia and clinically relevant hyperalgesia. Copyright © 2018 Elsevier B.V. All rights reserved.

Bilobalide, a unique constituent of Ginkgo biloba, inhibits inflammatory pain in rats.

PubMed

Goldie, Michelle; Dolan, Sharron

2013-08-01

Standardized Ginkgo biloba extract EGb 761 has been shown to inhibit inflammatory hyperalgesia in rats; however, the mechanism of action is not known. This study set out to investigate the anti-inflammatory and analgesic potential of bilobalide, a unique G. biloba constituent, in three well-characterized models of acute inflammatory pain. The effect of oral, intraplantar or intrathecal administration of bilobalide or drug-vehicle (0.25% agar; 10% ethanol in H2O) on responses to noxious thermal and mechanical stimulation of the hindpaw, and paw oedema were assessed in adult male Wistar rats before and after intradermal hindpaw injection of carrageenan (3%; 50 μl) or capsaicin (10 μg; 50 μl) or after hindpaw incision (n=6-8/group). Oral administration of bilobalide (10-30 mg/kg) significantly inhibited thermal hyperalgesia in response to carrageenan, capsaicin and paw incision, independent of dose, with an efficacy similar to that of diclofenac. In the carrageenan model, mechanical hypersensitivity and paw oedema were also significantly reduced after treatment with bilobalide (10-30 mg/kg). Intrathecal administration of bilobalide (0.5-1 μg) inhibited carrageenan-induced thermal hyperalgesia, but had no effect on mechanical hypersensitivity or paw oedema (application≥2 μg induced adverse effects, precluding testing of higher doses). Intraplantar administration of bilobalide (30-100 μg) had no effect. These data show that bilobalide is a potent anti-inflammatory and antihyperalgesic agent, the therapeutic effects of which are mediated in part through a central site of action, and may account for the therapeutic action of the whole extract G. biloba.

Mild Contralesional Hypothermia Reduces Use of the Unimpaired Forelimb in a Skilled Reaching Task After Motor Cortex Injury in Rats.

PubMed

Klahr, Ana C; Fagan, Kelly; Aziz, Jasmine R; John, Roseleen; Colbourne, Frederick

2018-06-01

Therapeutic hypothermia (TH) mitigates neuronal injury in models of ischemic stroke. Although this therapy is meant for injured tissue, most protocols cool the whole body, including the contralesional hemisphere. Neuroplasticity responses within this hemisphere can affect functional outcome. Thus, cooling the contralesional hemisphere serves no clear neuroprotective function and may instead be detrimental. In this study, we cooled the contralesional hemisphere to determine whether this harms behavioral recovery after cortical injury in rats. All rats were trained on skilled reaching and walking tasks. Rats then received a motor cortex insult contralateral to their dominant paw after which they were randomly assigned to focal contralesional TH (∼33°C) for 1-48, 1-97, or 48-96 hours postinjury, or to a normothermic control group. Contralesional cooling did not impact lesion volume (p = 0.371) and had minimal impact on neurological outcome of the impaired limb. However, rats cooled early were significantly less likely to shift paw preference to the unimpaired paw (p ≤ 0.043), suggesting that cooling reduced learned nonuse. In a second experiment, we tested whether cooling impaired learning of the skilled reaching task in naive rats. Localized TH applied to the hemisphere contralateral or ipsilateral to the preferred paw did not impair learning (p ≥ 0.677) or dendritic branching/length in the motor cortex (p ≥ 0.105). In conclusion, localized TH did not impair learning or plasticity in the absence of neural injury, but contralesional TH may reduce unwanted shifts in limb preference after stroke.

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

PubMed Central

Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

2014-01-01

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

Clutch and egg allometry of the turtle Mauremys leprosa (Chelonia: Geoemydidae) from a polluted peri-urban river in west-central Morocco

USGS Publications Warehouse

Naimi, Mohamed; Znari, Mohammed; Lovich, Jeffrey E.; Feddadi, Youssef; Baamrane, Moulay Abdeljalil Ait

2012-01-01

We examined the relationships of clutch size (CS) and egg size to female body size (straight-line carapace length, CL) in a population of the turtle Mauremys leprosa from a polluted segment of oued (river) Tensift in arid west-central Morocco. Twenty-eight adult females were collected in May–July, 2009 and all were gravid. Each was weighed, measured, humanely euthanized and then dissected. Oviductal shelled eggs were removed, weighed (egg mass, EM) and measured for length (EL) and width (EW). Clutch mass (CM) was the sum of EM for a clutch. Pelvic aperture width (PAW) was measured at the widest point between the ilia bones through which eggs must pass at oviposition. The smallest gravid female had a CL of 124.0 mm. Mean CS was relatively large (9.7±2.0 eggs, range: 3–13) and may reflect high productivity associated with polluted (eutrophic) waters. Regression analyses were conducted using log-transformed data. CM increased isometrically with maternal body size. CS, EW and EM were all significantly hypoallometric in their relationship with CL. EL did not change significantly with increases in CL. EW increased at a hypoallometric rate with increasing CL but was unconstrained by PAW since the widest egg was smaller than the narrowest PAW measurement when excluding the three smallest females. Smaller females may have EW constrained by PAW. As females increase in size they increase both clutch size and egg width in contradiction to predictions of optimal egg size theory.

Using a Photon Beam for Thermal Nociceptive Threshold Experiments

NASA Astrophysics Data System (ADS)

Walker, Azida; Anderson, Jeffery; Sherwood, Spencer

In humans, risk of diabetes and diabetic complications increases with age and duration of prediabetic state. In an effort to understand the progression of this disease scientists have evaluated the deterioration of the nervous system. One of the current methods used in the evaluation of the deterioration of the nervous system is through thermal threshold experiments. An incremental Hot / Cold Plate Analgesia Meter (IITC Life Science,CA is used to linearly increase the plate temperature at a rate of 10 ºC min-1 with a cutoff temperature of 55 ºC. Hind limb heat pain threshold (HPT) will be defined as a plate temperature at which the animal abruptly withdraws either one of its hind feet from the plate surface in a sharp move, typically followed by licking of the lifted paw. One of the disadvantages of using this hot plate method is in determining the true temperature at which the paw was withdrawn. While the temperature of the plate is known the position of the paw on the surface may vary; occasionally being cupped resulting in a temperature differentiation between the plate and the paw. During experiments the rats may urine onto the plate changing the temperature of the surface again resulting in reduced accuracy as to the withdrawal threshold. We propose here a new method for nociceptive somatic experiments involving the heat pain threshold experiments. This design employs the use of a photon beam to detect thermal response from an animal model. The details of this design is presented. Funded by the Undergraduate Research Council at the University of Central Arkansas.

Mirror-image pain after nerve reconstruction in rats is related to enhanced density of epidermal peptidergic nerve fibers.

PubMed

Kambiz, S; Brakkee, E M; Duraku, L S; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

2015-05-01

Mirror-image pain is a phenomenon in which unprovoked pain is detected on the uninjured contralateral side after unilateral nerve injury. Although it has been implicated that enhanced production of nerve growth factor (NGF) in the contralateral dorsal root ganglion is important in the development of mirror-image pain, it is not known if this is related to enhanced expression of nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity in the contralateral hind paw was measured at four different time points (5, 10, 20 and 30weeks) after transection and immediate end-to-end reconstruction of the sciatic nerve in rats. These findings were compared to the density of epidermal (peptidergic and non-peptidergic) nerve fibers on the contralateral hind paw. Mechanical hypersensitivity of the contralateral hind paw was observed at 10weeks PO, a time point in which both subgroups of epidermal nerve fibers reached control values. Thermal hypersensitivity was observed with simultaneous increase in the density of epidermal peptidergic nerve fibers of the contralateral hind paw at 20weeks PO. Both thermal sensitivity and the density of epidermal nerve fibers returned to control values 30weeks PO. We conclude that changes in skin innervation and sensitivity are present on the uninjured corresponding side in a transient pain model. Therefore, the contralateral side cannot serve as control. Moreover, the current study confirms the involvement of the peripheral nervous system in the development of mirror-image pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Effective modeling and reverse-time migration for novel pure acoustic wave in arbitrary orthorhombic anisotropic media

NASA Astrophysics Data System (ADS)

Xu, Shigang; Liu, Yang

2018-03-01

The conventional pseudo-acoustic wave equations (PWEs) in arbitrary orthorhombic anisotropic (OA) media usually have coupled P- and SV-wave modes. These coupled equations may introduce strong SV-wave artifacts and numerical instabilities in P-wave simulation results and reverse-time migration (RTM) profiles. However, pure acoustic wave equations (PAWEs) completely decouple the P-wave component from the full elastic wavefield and naturally solve all the aforementioned problems. In this article, we present a novel PAWE in arbitrary OA media and compare it with the conventional coupled PWEs. Through decomposing the solution of the corresponding eigenvalue equation for the original PWE into an ellipsoidal differential operator (EDO) and an ellipsoidal scalar operator (ESO), the new PAWE in time-space domain is constructed by applying the combination of these two solvable operators and can effectively describe P-wave features in arbitrary OA media. Furthermore, we adopt the optimal finite-difference method (FDM) to solve the newly derived PAWE. In addition, the three-dimensional (3D) hybrid absorbing boundary condition (HABC) with some reasonable modifications is developed for reducing artificial edge reflections in anisotropic media. To improve computational efficiency in 3D case, we adopt graphic processing unit (GPU) with Compute Unified Device Architecture (CUDA) instead of traditional central processing unit (CPU) architecture. Several numerical experiments for arbitrary OA models confirm that the proposed schemes can produce pure, stable and accurate P-wave modeling results and RTM images with higher computational efficiency. Moreover, the 3D numerical simulations can provide us with a comprehensive and real description of wave propagation.

The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model.

PubMed

Ren, Xiaobin; Zhang, Mingzhu; Chen, Lingxiang; Zhang, Wanli; Huang, Yu; Luo, Huazhen; Li, Ling; He, Hongbing

2017-10-01

The traditional Chinese medicine Yunnan Baiyao (YNB) has been reported to possess anti‑inflammatory properties, however its mechanism of action remains unclear. It was previously reported that YNB ameliorated depression of arachidonic acid (AA) levels in a rat model of collagen-induced arthritis. In the current study, the capacity of YNB to ameliorate inflammation was compared in carrageenan‑induced and AA‑induced acute inflammation of the rat paw with celecoxib and mizolastine, respectively (n=24 per group). The capacity of YNB to affect the phospholipase A2 (PLA2)/AA pathway (using reverse transcription‑quantitative polymerase chain reaction) and release of inflammatory lipid mediators (by ELISA) were investigated. Celecoxib ameliorated carrageenan‑induced paw edema, and mizolastine ameliorated AA‑induced rat paw edema. YNB alleviated paw edema and inhibited inflammatory cell infiltration in the two models. YNB inhibited production of 5‑LOX AA metabolite leukotriene B4 (LTB4), and suppressed expression of 5‑LOX, cytosolic PLA2 (cPLA2), 5‑LOX‑activating protein, and LTB4 receptor mRNA in the AA‑induced inflammation model (P<0.05). YNB Inhibited the production of the COX‑2 AA metabolite prostaglandin E2 (PGE2) and suppressed expression of COX‑2, cPLA2, PGE2 mRNA in the carrageenan‑induced inflammation mode (P<0.05). Taken together, the data suggest that modulation of COX and LOX pathways in AA metabolism represent a novel anti-inflammatory mechanism of YNB.

Nociception and inflammatory hyperalgesia evaluated in rodents using infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion.

PubMed

Mitchell, Kendall; Lebovitz, Evan E; Keller, Jason M; Mannes, Andrew J; Nemenov, Michael I; Iadarola, Michael J

2014-04-01

TRPV1 is expressed in a subpopulation of myelinated Aδ and unmyelinated C-fibers. TRPV1+ fibers are essential for the transmission of nociceptive thermal stimuli and for the establishment and maintenance of inflammatory hyperalgesia. We have previously shown that high-power, short-duration pulses from an infrared diode laser are capable of predominantly activating cutaneous TRPV1+ Aδ-fibers. Here we show that stimulating either subtype of TRPV1+ fiber in the paw during carrageenan-induced inflammation or following hind-paw incision elicits pronounced hyperalgesic responses, including prolonged paw guarding. The ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates TRPV1+ fibers and blocks thermal nociceptive responses in baseline or inflamed conditions. Injecting sufficient doses of RTX peripherally renders animals unresponsive to laser stimulation even at the point of acute thermal skin damage. In contrast, Trpv1-/- mice, which are generally unresponsive to noxious thermal stimuli at lower power settings, exhibit withdrawal responses and inflammation-induced sensitization using high-power, short duration Aδ stimuli. In rats, systemic morphine suppresses paw withdrawal, inflammatory guarding, and hyperalgesia in a dose-dependent fashion using the same Aδ stimuli. The qualitative intensity of Aδ responses, the leftward shift of the stimulus-response curve, the increased guarding behaviors during carrageenan inflammation or after incision, and the reduction of Aδ responses with morphine suggest multiple roles for TRPV1+ Aδ fibers in nociceptive processes and their modulation of pathological pain conditions. Copyright © 2014. Published by Elsevier B.V.

Anti-inflammatory and antinociceptive activities of Croton urucurana Baillon bark.

PubMed

Cordeiro, Kátia Wolff; Felipe, Josyelen Lousada; Malange, Kauê Franco; do Prado, Pâmela Rafaela; de Oliveira Figueiredo, Patrícia; Garcez, Fernanda Rodrigues; de Cássia Freitas, Karine; Garcez, Walmir Silva; Toffoli-Kadri, Mônica Cristina

2016-05-13

Croton urucurana (Euphorbiaceae) is popularly used in Brazil to treat inflammatory processes, pain, and gastric ulcers. To evaluate the anti-inflammatory and antinociceptive properties of the methanol extract from the bark of C. urucurana (MECu) in mice and identify its chemical constituents. The extract was characterized by UHPLC-DAD-ESI-Q-TOF-MS/MS. Extract doses of 25, 100, and 400mg/kg were employed in the biological assays. Evaluation of anti-inflammatory activity was based on paw edema and leukocyte recruitment into the peritoneal cavity of mice, both induced by carrageenan. Abdominal writhing caused by acetic acid and duration of formalin-induced paw-licking were the models employed to evaluate antinociceptive activity. Ten compounds were identified in the extract: (+)-gallocatechin (1), procyanidin B3 (2), (+)-catechin (3), (-)-epicatechin (4), tembetarine (5), magnoflorine (6), taspine (7), methyl-3-oxo-12-epi-barbascoate (8), methyl-12-epi-barbascoate (9), and hardwickiic acid (10). This is the first report of compounds 2, 4, 6, 7, and 10 in C. urucurana and compound 5 in the genus Croton. In addition to inhibiting paw edema and leukocyte recruitment (particularly of polymorphonuclear cells) into the peritoneal cavity of mice, MECu reduced the number of abdominal writhings induced by acetic acid and the duration of formalin-induced paw licking. The methanol extract of C. urucurana bark exhibited anti-inflammatory and antinociceptive properties, corroborating its use in folk medicine. These effects may be related to the presence of diterpenes, alkaloids, and flavonoids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PAWS locker: a passively aligned internal wavelength locker for telecommunications lasers

NASA Astrophysics Data System (ADS)

Boye, Robert R.; Te Kolste, Robert; Kathman, Alan D.; Cruz-Cabrera, Alvaro; Knight, Douglas; Hammond, J. Barney

2003-11-01

This paper presents the passively aligned Wavesetter (PAWS) locker: a micro-optic subassembly for use as an internal wavelength locker. As the wavelength spacing in dense wavelength division multiplexing (WDM) decreases, the performance demands placed upon source lasers increase. The required wavelength stability has led to the use of external wavelength lockers utilizing air-spaced, thermally stabilized etalons. However, package constraints are forcing the integration of the wavelength locker directly into the laser module. These etalons require active tuning be done during installation of the wavelength locker as well as active temperature control (air-spaced etalons are typically too large for laser packages). A unique locking technique will be introduced that does not require an active alignment or active temperature compensation. Using the principles of phase shifting interferometry, a locking signal is derived without the inherent inflection points present in the signal of an etalon. The theoretical background of PAWS locker will be discussed as well as practical considerations for its implementation. Empirical results will be presented including wavelength accuracy, alignment sensitivity and thermal performance.

Pitavastatin is a potent anti-inflammatory agent in the rat paw model of acute inflammation.

PubMed

Qadir, Farida; Alam, Syed Mahboob; Siddiqi, Abeer Qamar; Kamran, Afshan

2014-11-01

Statins are used extensively as anti-hyperlipidemic agents. In addition to curtailing cholesterol synthesis they have been found to have multiple actions unrelated to cholesterol lowering "the pleiotropic effects," which includes inhibition of inflammation. We aimed at investigating the effect of pitavastatin a 3rd generation statin, in suppressing acute inflammation in rat paw edema model. Male Sprague-Dawley rats were randomly assigned to one of five groups (n=8): Control, indomethacin and pitavastatin (0.2mg/kg, 0.4mg/kg, 0.8mg/kg) treated. 1hour following treatment, inflammation was induced by sub-planter injection of egg albumin into the hind paw. Anti-inflammatory effect was evaluated by measurement of edema formation every half hour for three hours, assessment of polymorphonuclear leukocyte (PMNL) infiltration and measurement of tissue damage in skin biopsies. Ascending doses of pitavastatin were found to attenuate these parameters. The lowest dose of pitavastatin (0.2mg/kg) was found to significantly reduce edema volume, PMNL infiltration and tissue damage. The efficacy of the smallest dose was found comparable to indomethacin.

Participation of the nitric oxide-cyclic GMP-ATP-sensitive K(+) channel pathway in the antinociceptive action of ketorolac.

PubMed

Lázaro-Ibáñez, G G; Torres-López, J E; Granados-Soto, V

2001-08-24

The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K(+) channels in the antinociceptive effect of ketorolac was assessed using the formalin test in the rat. Local administration of ketorolac in a formalin-injured paw produced a dose-dependent antinociceptive effect due to a local action, as drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with N(G)-L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) or glibenclamide (an ATP-sensitive K(+) channel blocker) prevented ketorolac-induced antinociception. However, pretreatment with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was inactive by itself, but increased the effect of ketorolac. The present results suggest that the antinociceptive effect of ketorolac involves activation of the NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K(+) channels at the peripheral level.

Antinociceptive and pronociceptive effect of levetiracetam in tonic pain model.

PubMed

Cortes-Altamirano, José Luis; Reyes-Long, Samuel; Olmos-Hernández, Adriana; Bonilla-Jaime, Herlinda; Carrillo-Mora, Paul; Bandala, Cindy; Alfaro-Rodriguez, Alfonso

2018-04-01

Levetiracetam (LEV) is a novel anticonvulsant with proven antinociceptive properties. However, the antinociceptive and pronociceptive effect of this drug has not yet been fully elucidated in a tonic pain model. Thirty-six male rats (Wistar) were randomized into six groups and underwent the formalin test as follows: rats in the control group were administered 50μL of 1% formalin in the paw; sham-group rats were administered 50μL of saline in the paw to mimick the application of formalin; the four experimental groups were administered LEV intragastrically (ig) (50, 100, 200 and 300mg/kg), and 40min later 50μL of 1% formalin was injected in the paw. LEV exhibited antinociceptive effect in the 300mg/kg LEV group (p<0.05) and a pronociceptive effect in the 100mg/kg LEV group (p<0.05) and in the 50mg/kg LEV group (p<0.001). The antinociceptive and pronociceptive effect of LEV in a tonic pain model is dose-dependent. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Antioxidant effects of Genkwa flos flavonoids on Freund׳s adjuvant-induced rheumatoid arthritis in rats.

PubMed

Zhang, Chun-Feng; Zhang, Su-Li; He, Xin; Yang, Xiao-Lin; Wu, Hai-Tao; Lin, Bao-Qin; Jiang, Cui-Ping; Wang, Jun; Yu, Chun-Hao; Yang, Zhong-Lin; Wang, Chong-Zhi; Li, Ping; Yuan, Chun-Su

2014-05-14

Genkwa flos (Daphne genkwa Sieb. et Zucc.), a Chinese herbal medicine, has been traditionally used for over two thousand years in China for inflammation related symptoms, including joint pain. To evaluate the antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on adjuvant arthritis in rats and to identify the relationship between antioxidant potential and whole blood viscosity (WBV). FA compounds were identified using LC-MS and the content was assayed by HPLC. Arthritis was induced by an intradermal injection of Freund׳s complete adjuvant in the footpad. The effects of FA on paw volumes, secondary arthritis scores, histopathology of joints, and body and organ weights were measured. The antioxidant effects of FA and WBV were determined. LC-MS analysis showed that the FA contained four major compounds: luteolin, apigenin, hydroxygenkwanin and genkwanin. FA significantly decreased paw edema, arthritis scores, and weight loss. These observations were consistent with the reduction of oxidative stress and the improvement of the WBV. FA significantly decreased arthritis in a rat model through antioxidant and hemorheological modulatory mechanisms. The Genkwa flos flavonoids may have clinical potential for the treatment of rheumatoid arthritis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of the Aqueous Extract from Tabebuia roseoalba and Phenolic Acids on Hyperuricemia and Inflammation

PubMed Central

Ferraz-Filha, Zilma Schimith; Ferrari, Fernanda Cristina; Araújo, Marcela Carolina de Paula Michel; Bernardes, Ana Catharina Fernandes P. F.

2017-01-01

Tabebuia species (Bignoniaceae) have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL) of Tabebuia roseoalba (Ridl.) Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase) by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate) crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species. PMID:29375639

Analysis of the Exposure Levels and Potential Biologic Effects of the PAVE PAWS Radar System.

DTIC Science & Technology

1979-01-01

total body) yielded local SARs at hot spots (above the palate area and the upper part of the back of the neck) about 5 times the average values for the...increase the field intensity; whether the energy absorption is averaged over the entire body or over local areas, such as the head or particularly absorptive...animal. Full implications of the multibody effects on AAR are not completely understood, even though pilot experimental studies with anesthetized rats

Investigation on physicochemical properties of plasma-activated water for the application of medical device sterilization

NASA Astrophysics Data System (ADS)

Abuzairi, Tomy; Ramadhanty, Savira; Puspohadiningrum, Dini Fithriaty; Ratnasari, Anita; Poespawati, Nji Raden; Purnamaningsih, Retno Wigajatri

2018-02-01

Plasma activated water (PAW) is a new approach to bacterial inactivation while ensuring safety and maintaining the properties of the material sterilized. Reported research imply that PAW has been effective for inactivation of bacteria. In this paper, plasma treatment using atmospheric pressure plasma was demonstrated. Physicochemical properties such as pH, temperature, ORP, and nitrite concentration were assessed. The results suggest that plasma treatment causes acidification on water and generate reactive species, creating an environment suitable for killing bacteria. Therefore, plasma activated water is an assuring method for medical devices sterilization.

Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington's Disease: A Targeted GC-MS/MS Sterol Analysis.

PubMed

Kreilaus, Fabian; Spiro, Adena S; Hannan, Anthony J; Garner, Brett; Jenner, Andrew M

2015-01-01

Cholesterol has essential functions in neurological processes that require tight regulation of synthesis and metabolism. Perturbed cholesterol homeostasis has been demonstrated in Huntington's disease, however the exact role of these changes in disease pathogenesis is not fully understood. This study aimed to comprehensively examine changes in cholesterol biosynthetic precursors, metabolites and oxidation products in the striatum and cortex of the R6/1 transgenic mouse model of Huntington's disease. We also aimed to characterise the progression of the physical phenotype in these mice. GC-MS/MS was used to quantify a broad range of sterols in the striatum and cortex of R6/1 and wild type mice at 6, 12, 20, 24 and 28 weeks of age. Motor dysfunction was assessed over 28 weeks using the RotaRod and the hind-paw clasping tests. 24(S)-Hydroxycholesterol and 27-hydroxycholesterol were the major cholesterol metabolites that significantly changed in R6/1 mice. These changes were specifically localised to the striatum and were detected at the end stages of the disease. Cholesterol synthetic precursors (lathosterol and lanosterol) were significantly reduced in the cortex and striatum by 6 weeks of age, prior to the onset of motor dysfunction, as well as the cognitive and affective abnormalities previously reported. Elevated levels of desmosterol, a substrate of delta(24)-sterol reductase (DHCR24), were also detected in R6/1 mice at the end time-point. Female R6/1 mice exhibited a milder weight loss and hind paw clasping phenotype compared to male R6/1 mice, however, no difference in the brain sterol profile was detected between sexes. Several steps in cholesterol biosynthetic and metabolic pathways are differentially altered in the R6/1 mouse brain as the disease progresses and this is most severe in the striatum. This provides further insights into early molecular mediators of HD onset and disease progression and identifies candidate molecular targets for novel therapeutic approaches.

A report of a galactan from marine alga Gelidium crinale with in vivo anti-inflammatory and antinociceptive effects.

PubMed

de Sousa, Albertina A S; Benevides, Norma M B; de Freitas Pires, Alana; Fiúza, Felipe P; Queiroz, Maria G R; Morais, Thamires M F; Pereira, Maria G; Assreuy, Ana M S

2013-04-01

The sulfated galactan of the red marine alga Gelidium crinale (SG-Gc) was purified by ion exchange chromatography and tested by intravenous (i.v.) route in rodent experimental models of inflammation and nociception. The anti-inflammatory activity of SG-Gc (0.01, 0.1 and 1 mg/kg) was evaluated in the model of rat paw edema induced by different inflammatory stimuli, while SG-Gc (0.1, 1 and 10 mg/kg) antinociceptive effect was assessed in models of nociception/hyperalgesia elicited by chemical (formalin test), thermal (hot plate), and mechanical (von Frey) stimuli in mice. In addition, the toxicity was evaluated after rat treatment with SG-Gc (1 mg/kg; i.v.) during 10 days, followed by analysis of the wet weight of animal's body/organs and hematological/biochemical parameters. Sulfated galactan of G. crinale inhibited the time course of dextran-induced paw edema, at all doses, showing maximal effect at 1 mg/kg (42%) and that induced by carrageenan at 0.01 (18%) and 1 mg/kg (20%), but was ineffective on the edema elicited by zymosan. At the highest dose, SG-Gc also inhibited the paw edema induced by histamine (49%), compound 48/80 (32%), and phospholipase A(2) (44%). Sulfated galactan of G. crinale inhibited both neurogenic and inflammatory phases of the formalin test, at all doses, and at 10 mg/kg, the animals flinch reaction in the von Frey test in the 1st and 3rd h by 19 and 26%, respectively. Additionally, SG-Gc treatment was well tolerated by animals. In conclusion, SG-Gc presents anti-inflammatory effect involving the inhibition of histamine and arachidonic acid metabolites and also antinociceptive activity, especially the inflammatory pain with participation of the opioid system. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Differences in carbachol dose, pain condition, and sex following lateral hypothalamic stimulation.

PubMed

Holden, J E; Wang, E; Moes, J R; Wagner, M; Maduko, A; Jeong, Y

2014-06-13

Lateral hypothalamic (LH) stimulation produces antinociception in female rats in acute, nociceptive pain. Whether this effect occurs in neuropathic pain or whether male-female sex differences exist is unknown. We examined the effect of LH stimulation in male and female rats using conditions of nociceptive and neuropathic pain. Neuropathic groups received chronic constriction injury (CCI) to induce thermal hyperalgesia, a sign of neuropathic pain. Nociceptive rats were naive for CCI, but received the same thermal stimulus following LH stimulation. To demonstrate that CCI ligation produced thermal hyperalgesia, males and females received either ligation or sham surgery for control. Both males and females demonstrated significant thermal hyperalgesia following CCI ligation (p<0.05), but male sham surgery rats also showed a significant left-right difference not present in female sham rats. In the second experiment, rats randomly assigned to CCI or nociceptive groups were given one of three doses of the cholinergic agonist carbachol (125, 250, or 500 nmol) or normal saline for control, microinjected into the left LH. Paw withdrawal from a thermal stimulus (paw withdrawal latency; PWL) was measured every 5 min for 45 min. Linear mixed models analysis showed that males and females in both pain conditions demonstrated significant antinociception, with the 500-nmol dose producing the greatest effect across groups compared with controls for the left paw (p<0.05). Female CCI rats showed equivalent responses to the three doses, while male CCI rats showed more variability for dose. However, nociceptive females responded only to the 500-nmol dose, while nociceptive males responded to all doses (p<0.05). For right PWL, only nociceptive males showed a significant carbachol dose response. These findings are suggestive that LH stimulation produces antinociception in male and female rats in both nociceptive and neuropathic pain, but dose response differences exist based on sex and pain condition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Anti-inflammatory and bronchodilatory constituents of leaf extracts of Anacardium occidentale L. in animal models.

PubMed

Awakan, Oluwakemi Josephine; Malomo, Sylvia Omonirume; Adejare, Abdullahi Adeyinka; Igunnu, Adedoyin; Atolani, Olubunmi; Adebayo, Abiodun Humphrey; Owoyele, Bamidele Victor

2018-01-01

Anacardium occidentale L. leaf is useful in the treatment of inflammation and asthma, but the bioactive constituents responsible for these activities have not been characterized. Therefore, this study was aimed at identifying the bioactive constituent(s) of A. occidentale ethanolic leaf extract (AOEL) and its solvent-soluble portions, and evaluating their effects on histamine-induced paw edema and bronchoconstriction. The bronchodilatory effect was determined by measuring the percentage protection provided by plant extracts in the histamine-induced bronchoconstriction model in guinea pigs. The anti-inflammatory effect of the extracts on histamine-induced paw edema in rats was determined by measuring the increase in paw diameter, after which the percent edema inhibition was calculated. The extracts were analyzed using gas chromatography-mass spectrometry to identify the bioactive constituents. Column chromatography and Fourier transform infrared spectroscopy were used respectively to isolate and characterize the constituents. The bronchodilatory and anti-inflammatory activities of the isolated bioactive constituent were evaluated. Histamine induced bronchoconstriction in the guinea pigs and edema in the rat paw. AOEL, hexane-soluble portion of AOEL, ethyl acetate-soluble portion of AOEL, and chloroform-soluble portion of AOEL significantly increased bronchodilatory and anti-inflammatory activities (P < 0.05). Oleamide (9-octadecenamide) was identified as the most abundant compound in the extracts and was isolated. Oleamide significantly increased bronchodilatory and anti-inflammatory activities by 32.97% and 98.41%, respectively (P < 0.05). These results indicate that oleamide is one of the bioactive constituents responsible for the bronchodilatory and anti-inflammatory activity of A. occidentale leaf, and can therefore be employed in the management of bronchoconstriction and inflammation. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model.

PubMed

Wise, Laura E; Cannavacciulo, Roberta; Cravatt, Benjamin F; Martin, Billy F; Lichtman, Aron H

2008-01-01

While it has long been recognized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild-type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay.

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin.

PubMed

Liu, Yan-Li; Lin, Hai-Ming; Zou, Rong; Wu, Jun-Chao; Han, Rong; Raymond, Laurence N; Reid, Paul F; Qin, Zheng-Hong

2009-02-01

Cobratoxin (CTX), the long-chain alpha-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats. Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the alpha(7) nicotinic receptor (alpha(7)-nAChR) antagonist methyllycaconitine (MLA). CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-alpha, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 microg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-alpha, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc). These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats.

PubMed

Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M

2012-04-01

Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture.We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury.

The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats

PubMed Central

Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M

2012-01-01

Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture. We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury. PMID:22351637

Role of Trpv1 and Trpv4 in surgical incision-induced tissue swelling and Fos-like immunoreactivity in the central nervous system of mice.

PubMed

Motojima, Yasuhito; Nishimura, Haruki; Ueno, Hiromichi; Sonoda, Satomi; Nishimura, Kazuaki; Tanaka, Kentaro; Saito, Reiko; Yoshimura, Mitsuhiro; Maruyama, Takashi; Matsuura, Takanori; Suzuki, Hitoshi; Kawasaki, Makoto; Ohnishi, Hideo; Sakai, Akinori; Ueta, Yoichi

2018-06-21

Pain management remains a major concern regarding the treatment of postoperative patients. Transient receptor potential (TRP) channels are considered to be new therapeutic targets for pain control. We investigated whether the genes Trpv1 and Trpv4 are involved in hind paw swelling caused after surgical incision in mice or in incision-induced Fos-like immunoreactivity (Fos-LI) levels in the central nervous system. Mice were divided into four groups: wild-type (WT) control, WT incision, Trpv1 knockout (Trpv1 -/- ) incision, and Trpv4 knockout (Trpv4 -/- ) incision. Mice were anesthetized, and only those in the incision, and not control, groups received a surgical incision to their right plantar hind paw. Changes in paw diameter and in Fos-LI levels in the dorsal horn of the spinal cord, paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus, and central amygdala were evaluated 2 h after the incision. There was no significant difference in the paw diameter among groups. In contrast, in laminae I-II of the dorsal horn of the spinal cord and PVN, Fos-LI was significantly higher in all incision groups than in the WT control group. A significant increase in Fos-positive cells was also observed in the dorsal horn laminae III-IV in Trpv1 -/- and Trpv4 -/- incision groups compared with the WT incision group. Our results indicate that surgical incision activates the PVN and that Trpv1 and Trpv4 might be involved in neuronal activity in the dorsal horn laminae III-IV after surgical incision. Copyright © 2018 Elsevier B.V. All rights reserved.

Antinociceptive and antiedematogenic effect of pecan (Carya illinoensis) nut shell extract in mice: a possible beneficial use for a by-product of the nut industry.

PubMed

Trevisan, Gabriela; Rossato, Mateus F; Hoffmeister, Carin; Müller, Liz G; Pase, Camila; Córdova, Marina M; Rosa, Fernanda; Tonello, Raquel; Hausen, Bruna S; Boligon, Aline A; Moresco, Rafael N; Athayde, Margareth L; Burguer, Marilise E; Santos, Adair R; Ferreira, Juliano

2014-01-27

Abstract Background: Interest in pecan (Carya illinoensis) nut shells, a by-product of the nut industry, has increased due to its anti-inflammatory and antioxidant activities. The goal of this study was to evaluate the antinociceptive and antiedematogenic activity and the mechanisms of the pecan shell aqueous extract (AE). Methods: First, we performed fingerprinting of C. illinoensis AE. The antinociceptive and antiedematogenic effects of AE intragastric (i.g.) administration in mice (male Swiss mice 20-30 g) were evaluated using the acetic acid test or after subcutaneous (s.c.) paw injection of diverse transient receptor potential ankyrin 1 (TRPA1) agonists, including hydrogen peroxide (H2O2), allyl isothiocyanate, or cinnamaldehyde. We also observed AE antinociceptive and antiedematogenic effects after carrageenan s.c. paw injection and measured H2O2 production. Moreover, we observed the development of adverse effects after AE i.g. treatment. Results: The high-performance liquid chromatography fingerprinting of AE showed the presence of rutin. AE or rutin i.g. treatment produced antinociception in the acetic acid test and reduced the nociception and edema mediated by H2O2 s.c. hind paw injection or nociception induced by other TRPA1 agonists. Moreover, AE or rutin reduced the hyperalgesia, edema, and H2O2 production induced by carrageenan s.c. paw injection. No motor, gastric, or toxicological alterations were observed after AE administration. Conclusions: Collectively, the present results show that AE and its constituent rutin produced antinociceptive and antiedematogenic action in models of acute and persistent inflammatory nociception and it seems to be related to the inhibition of TRPA1 receptor activation.

The impact of early repeated pain experiences on stress responsiveness and emotionality at maturity in rats.

PubMed

Page, Gayle G; Blakely, Wendy P; Kim, Miyong

2005-01-01

The intensive care necessary for premature newborns is characterized by multiple procedures, many of which are painful. Given emerging evidence that such early pain during this time of high brain plasticity may affect long-term neurodevelopmental and social-emotional functioning, this study explored the impact of early repeated pain on emotionality and stress responsivity at maturity. From birth through postnatal day 7, Fischer 344 pups underwent either paw needle prick every day versus every other day or daily paw touch, or were left unperturbed. Each paw received the designated perturbation once per day. At maturity, some animals underwent emotionality testing: either a 4-day series of open field exposures or a single elevated plus-maze (EPM) exposure. The paw prick groups exhibited less open field habituation and occupied the EPM open arms more. Two weeks later, all animals were either subjected to forced swim or not. At 1h post-swim, animals underwent either blood withdrawal for plasma corticosterone (CS) levels and ex vivo natural killer cell activity (NKCA) or were injected intravenously with radiolabeled NK-sensitive syngeneic MADB106 tumor cells and assessed for lung tumor retention. Sex was a major factor in the manifestation of perturbation-related differences in the biologic outcomes. Whereas postnatal pain differentially affected baseline tumor retention between males and females, only males exhibited perturbation-related differences in swim stress-induced increases in tumor retention and CS. Finally, male-female differences were evident in CS, NKCA, and tumor responses to swim stress. These findings suggest that early pain affects neurodevelopmental function in the mature organism; however, these relationships are complicated by sex differences, the postnatal pain schedule, and the outcome measured.

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation

PubMed Central

Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-01-01

Introduction The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. Aim This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Materials and Methods Albino rats of either sex were divided into five groups of six rats each (Group I – Control, Group II –Gel base, Group III –P. santalinus paste, Group IV –P. santalinus gel, Group V– Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund’s Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey’s test was used for comparison among groups. Results Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Conclusion Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation. PMID:28892928

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation.

PubMed

Dhande, Priti Pravin; Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-07-01

The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Albino rats of either sex were divided into five groups of six rats each (Group I - Control, Group II -Gel base, Group III - P. santalinus paste, Group IV - P. santalinus gel, Group V- Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund's Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey's test was used for comparison among groups. Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation.

Anti-inflammatory activity of Elaeagnus angustifolia fruit extract on rat paw edema.

PubMed

Motevalian, Manijeh; Shiri, Mehdi; Shiri, Saeedeh; Shiri, Zahra; Shiri, Hadi

2017-07-26

The Elaeagnus angustifolia fruit has been traditionally used in Iranian herbal medicine to treat diarrhea and rheumatoid arthritis. In the present study, the effects of E. angustifolia fruit extract on the acute and chronic phases of formalin-induced rat paw edema were examined. The acute and chronic anti-inflammatory effects of E. angustifolia fruit extract were investigated through the subcutaneous injection of 100 μL of formalin (2.5%) into a rat's hind paw. Thirty minutes before the procedure, the experimental groups were treated intraperitoneally with hydroalcoholic fruit extracts of E. angustifolia (concentrations of 100, 300, 700, and 1000 mg/kg); sodium salicylate (SS, 400 mg/kg) and distilled water were used as positive and negative control groups, respectively. Treatment with SS and the fruit extracts were performed daily for 8 days, and the degree of edema was measured by using mercury plethysmometer and digital caliper. In the acute anti-inflammatory study, the extract showed a significant anti-inflammatory effect in a dose-dependent manner. The results of 1000 mg/kg of the extract was significantly different compared with the negative control group (p<0.05) and was comparable to sodium salicylate (p<0.05). Results from the chronic study suggested that E. angustifolia extract significantly reduced paw edema and inflammation in a dose-dependent manner. The results also showed that the measurement by digital caliper and mercury plethysmometer were both reliable and might be applied interchangeably (p<0.01). Phytochemical tests indicated that the hydroalcoholic fruit extract of E. angustifolia was positive for cardiac glycosides, flavonoids, terpenoids, and saponins. Based on our findings, the E. angustifolia fruit extract probably has acute and chronic anti-inflammatory activities to support its applications in folk medicine.

Dual effects of Rho-kinase inhibitors on a rat model of inflammatory pain.

PubMed

Paiva-Lima, Patricia; Bakhle, Y S; Francischi, Janetti Nogueira

2014-01-01

Rho-kinases (ROCKs), a family of small GTP-dependent enzymes, are involved in a range of pain models, and their inhibition typically leads to antinociceptive effects. To study the effects of inhibiting ROCKs using two known inhibitors, Y27632 and HA1077 (fasudil), administered locally, on nociception and paw edema in rats. A range of doses of Y27632 or HA1077 (2.5 μg to 1000 μg) were injected locally into rat paws alone or in combination with carrageenan, a known proinflammatory stimulus. Nociceptive responses to mechanical stimuli and increased paw volume, reflecting edema formation, were measured at 2 h and 3 h, using a Randall-Selitto apparatus and a hydroplethysmometer, respectively. Animals treated with either ROCK inhibitor showed biphasic nociceptive effects, with lower doses being associated with pronociceptive, and higher doses with antinociceptive responses. In contrast, a monophasic dose-dependent increase in edema was observed in the same animals. Local injection of 8-bromo-cyclic (c)GMP, an activator of the nitric oxide⁄cGMP⁄protein kinase G pathway, also produced biphasic effects on nociceptive responses in rat paws; however, low doses were antinociceptive and high doses were pronociceptive. Local administration of cytochalasin B, an inhibitor of actin polymerization and a downstream mediator of ROCK activity, reversed the antinociceptive effect of Y27632. The results of the present study suggest that ROCKs participate in the local mechanisms associated with nociception⁄antinociception and inflammation, with a possible involvement of the nitric oxide⁄cGMP⁄protein kinase G pathway. Also, drug effects following local administration may differ markedly from the effects following systemic administration. Finally, separate treatment of pain and edema may be needed to maximize clinical benefit in inflammatory pain.

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

PubMed

Chen, W; Marvizón, J C G

2009-06-16

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

Stepwise Evolution of a Buried Inhibitor Peptide over 45 My.

PubMed

Jayasena, Achala S; Fisher, Mark F; Panero, Jose L; Secco, David; Bernath-Levin, Kalia; Berkowitz, Oliver; Taylor, Nicolas L; Schilling, Edward E; Whelan, James; Mylne, Joshua S

2017-06-01

The de novo evolution of genes and the novel proteins they encode has stimulated much interest in the contribution such innovations make to the diversity of life. Most research on this de novo evolution focuses on transcripts, so studies on the biochemical steps that can enable completely new proteins to evolve and the time required to do so have been lacking. Sunflower Preproalbumin with SFTI-1 (PawS1) is an unusual albumin precursor because in addition to producing albumin it also yields a potent, bicyclic protease-inhibitor called SunFlower Trypsin Inhibitor-1 (SFTI-1). Here, we show how this inhibitor peptide evolved stepwise over tens of millions of years. To trace the origin of the inhibitor peptide SFTI-1, we assembled seed transcriptomes for 110 sunflower relatives whose evolution could be resolved by a chronogram, which allowed dates to be estimated for the various stages of molecular evolution. A genetic insertion event in an albumin precursor gene ∼45 Ma introduced two additional cleavage sites for protein maturation and conferred duality upon PawS1-Like genes such that they also encode a small buried macrocycle. Expansion of this region, including two Cys residues, enlarged the peptide ∼34 Ma and made the buried peptides bicyclic. Functional specialization into a protease inhibitor occurred ∼23 Ma. These findings document the evolution of a novel peptide inside a benign region of a pre-existing protein. We illustrate how a novel peptide can evolve without de novo gene evolution and, critically, without affecting the function of what becomes the protein host. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Liposomalization of oxaliplatin induces skin accumulation of it, but negligible skin toxicity.

PubMed

Nishida, Kentaro; Kashiwagi, Misaki; Shiba, Shunsuke; Muroki, Kiwamu; Ohishi, Akihiro; Doi, Yusuke; Ando, Hidenori; Ishida, Tatsuhiro; Nagasawa, Kazuki

2017-12-15

Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil ® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l-OHP promoted accumulation of platinum in rat hind paws, however, it caused negligible morphological and histological alterations on the plantar surface of the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the same distribution profile of dyes into the dermis of hind paws with DXR as in the case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty PEGylated liposomes or empty PEGylated liposomes caused migration of CD68 + macrophages into the dermis of hind paws. These findings suggest that the skin toxicity on administration of liposomalized drugs is reflected in the proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l-OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP preparation leading to an improved quality of life of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia

PubMed Central

Kumar, Vijender; Bhat, Zulfiqar Ali; Kumar, Dinesh; Khan, NA; Chashoo, IA

2012-01-01

Objective To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. Methods Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. Results The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. Conclusions The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent. PMID:23569983

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins

PubMed Central

TIAN, JINGE; YU, TINGTING; XU, YONGMING; PU, SHAOFENG; LV, YINGYING; ZHANG, XIN; DU, DONGPING

2018-01-01

ABSTRACT Introduction Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. Methods We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. Results TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Conclusions Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT. PMID:28846565

Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

PubMed

Tian, Jinge; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Lv, Yingying; Zhang, Xin; DU, Dongping

2018-01-01

Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT.

Implementation of density functional theory method on object-oriented programming (C++) to calculate energy band structure using the projector augmented wave (PAW)

NASA Astrophysics Data System (ADS)

Alfianto, E.; Rusydi, F.; Aisyah, N. D.; Fadilla, R. N.; Dipojono, H. K.; Martoprawiro, M. A.

2017-05-01

This study implemented DFT method into the C++ programming language with object-oriented programming rules (expressive software). The use of expressive software results in getting a simple programming structure, which is similar to mathematical formula. This will facilitate the scientific community to develop the software. We validate our software by calculating the energy band structure of Silica, Carbon, and Germanium with FCC structure using the Projector Augmented Wave (PAW) method then compare the results to Quantum Espresso calculation’s results. This study shows that the accuracy of the software is 85% compared to Quantum Espresso.

Anti-inflammatory activity of Pistacia lentiscus essential oil: involvement of IL-6 and TNF-alpha.

PubMed

Maxia, Andrea; Sanna, Cinzia; Frau, Maria Assunta; Piras, Alessandra; Karchuli, Manvendra Singh; Kasture, Veena

2011-10-01

The topical anti-inflammatory activity of essential oil of Pistacia lentiscus L. was studied using carrageenan induced rat paw edema and cotton pellet induced granuloma. The effect on serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats inserted with cotton pellet was also investigated. On topical application, the oil exhibited a significant decrease in paw edema. The oil also inhibited cotton pellet-induced granuloma, and reduced serum TNF-alpha and IL-6. It can be concluded that the essential oil of Pistacia lentiscus reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

Enzymologic and pharmacologic profile of loxoprofen sodium and its metabolites.

PubMed

Noguchi, Masahiro; Kimoto, Aishi; Gierse, James Kevin; Walker, Mark Crossfield; Zweifel, Ben Scott; Nozaki, Kazutoshi; Sasamata, Masao

2005-11-01

We investigated the mechanism of inhibition of loxoprofen sodium, a non-steroidal anti-inflammatory drug (NSAID), and its active metabolite (loxoprofen-SRS) on cyclooxygenase (COX). In in vitro assays, loxoprofen sodium appeared inactive against recombinant human COX-1 and COX-2, whereas loxoprofen-SRS inhibited both. In the investigation of kinetic behavior, loxoprofen-SRS showed time-dependent inhibition for both isozymes. Human whole blood assay also showed that loxoprofen-SRS possesses the profile of a non-selective inhibitor for COX. In a rat air pouch model, oral administration of loxoprofen sodium lowered prostaglandin (PG) E2 in both fluid exudates of the inflammatory pouch and stomach tissue with ED50 values of 2.0 and 2.1 mg/kg, respectively. Additionally, platelet thromboxane B2 production was also inhibited by loxoprofen sodium (ED50 of 0.34 mg/kg). In a rat carrageenan-induced paw edema model, loxoprofen sodium dose-dependently reduced the paw edema, accompanied by a decrease in PGE2 content in inflamed paw exudates. These findings suggest that the COX inhibitory activity of loxoprofen sodium is attributable to its active metabolite, loxoprofen-SRS, and that loxoprofen-SRS shows non-selective inhibition for COX.

Intrathecal oxotremorine affects formalin-induced behavior and spinal nitric oxide synthase immunoreactivity in rats.

PubMed

Przewlocka, B; Mika, J; Capone, F; Machelska, H; Pavone, F

1999-03-01

The present research was undertaken to investigate, by behavioral and immunohistochemical methods, the effects of intrathecal (i.th.) injection of the muscarinic agonist oxotremorine on the response to the long-lasting nociceptive stimulus induced by injection of formalin into the rat hind paw. Formalin injection induced a biphasic, pain-induced behavioral response (paw jerks), as well as an increase in the number of nitric oxide (NO) synthase-labeled neurons in laminae I-III, IV, and X, but not in laminae V-VI. Oxotremorine (0.1-10 ng, i.th.) inhibited paw-jerk frequency in both phases of formalin-induced behavior. The immunohistochemical results showed that i.th.-injected oxotremorine differently affected the level of NO synthase in lumbar part of the spinal cord: no change or increase after the dose of 1 ng, and a significant reduction of nitric oxide synthase neurons after the higher dose (10 ng). These results evidenced a role of cholinergic system in the modulation of tonic pain and in nitric oxide synthase expression at the spinal cord level, which further suggests that these two systems could be involved in phenomena induced by long-lasting nociceptive stimulation.

Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus

PubMed Central

Martinov, Tijana; Mack, Madison; Sykes, Akilah; Chatterjea, Devavani

2013-01-01

Measuring inflammation-induced changes in thresholds of hind paw withdrawal from mechanical pressure is a useful technique to assess changes in pain perception in rodents. Withdrawal thresholds can be measured first at baseline and then following drug, venom, injury, allergen, or otherwise evoked inflammation by applying an accurate force on very specific areas of the skin. An electronic von Frey apparatus allows precise assessment of mouse hind paw withdrawal thresholds that are not limited by the available filament sizes in contrast to classical von Frey measurements. The ease and rapidity of measurements allow for incorporation of assessment of tactile sensitivity outcomes in diverse models of rapid-onset inflammatory and neuropathic pain as multiple measurements can be taken within a short time period. Experimental measurements for individual rodent subjects can be internally controlled against individual baseline responses and exclusion criteria easily established to standardize baseline responses within and across experimental groups. Thus, measurements using an electronic von Frey apparatus represent a useful modification of the well-established classical von Frey filament-based assays for rodent mechanical allodynia that may also be applied to other nonhuman mammalian models. PMID:24378519

Antinociceptive activities of 70% methanol extract of evodiae fructus (fruit of Evodia rutaecarpa var. bodinieri) and its alkaloidal components.

PubMed

Matsuda, H; Wu, J X; Tanaka, T; Iinuma, M; Kubo, M

1997-03-01

The effects of 70% methanol extract (EA-ext) from Evodiae Fructus (EA) consisting of dried fruits of Evodia rutaecarpa var. bodinieri (Rutaceae) on nociceptive responses were investigated. Oral administration of 50 or 200 mg/kg EA-ext had the same antinociceptive effect on writhing responses as induced by acetic acid. Its major alkaloidal constituents, evodiamine and rutaecarpine also had the antinociceptive effect. EA-ext significantly decreased the frequency of licking behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. EA-ext also increased nociceptive threshold of the inflamed paw without increasing that in the non-inflamed paw in the Randall-Selitto test. Although EA-ext inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin, it was ineffective on nociceptive response in the hot plate test and on locomotor activity. These results suggest that EA possesses antinociceptive effects and its mode of action may be mediated by anti-inflammatory action, and that the antinociceptive constituents are only partially attributable to alkaloidal components mentioned above.

Decreased severity of collagen antibody and lipopolysaccharide-induced arthritis in human IL-32β overexpressed transgenic mice.

PubMed

Park, Mi Hee; Yoon, Do-Young; Ban, Jung Ok; Kim, Dae Hwan; Lee, Dong Hun; Song, Sukgil; Kim, Youngsoo; Han, Sang-Bae; Lee, Hee Pom; Hong, Jin Tae

2015-11-17

Interleukin (IL)-32, mainly produced by T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes, is dominantly known as a pro-inflammatory cytokine. However, the role of IL-32 on inflammatory disease has been doubtful according to diverse conflicting results. This study was designed to examine the role of IL-32β on the development of collagen antibody (CAIA) and lipopolysaccharide (LPS)-induced inflammatory arthritis. Our data showed that the paw swelling volume and clinical score were significantly reduced in the CAIA and LPS-treated IL-32β transgenic mice compared with non-transgenic mice. The populations of cytotoxic T, NK and dendritic cells was inhibited and NF-κB and STAT3 activities were significantly lowered in the CAIA and LPS-treated IL-32β transgenic mice. The expression of pro-inflammatory proteins was prevented in the paw tissues of CAIA and LPS-treated IL-32β transgenic mice. In addition, IL-32β altered several cytokine levels in the blood, spleen and paw joint. Our data indicates that IL-32β comprehensively inhibits the inflammation responses in the CAIA and LPS-induced inflammatory arthritis model.

Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral Paw Requires Efferent Conduction into the Contralateral Paw.

PubMed

Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin

2015-10-01

Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the 2 contralateral anesthetic procedures. These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.

Anti-Inflammatory Activities of Inotilone from Phellinus linteus through the Inhibition of MMP-9, NF-κB, and MAPK Activation In Vitro and In Vivo

PubMed Central

Huang, Guan-Jhong; Huang, Shyh-Shyun; Deng, Jeng-Shyan

2012-01-01

Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr)-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK) [extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38], and nuclear factor-κB (NF-κB), matrix-metalloproteinase (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α) levels on serum at the 5th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2), NF-κB, and MMP-9 expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the activities of CAT, SOD, and GPx in the paw edema through the suppression of TNF-α and NO. This study presents the potential utilization of inotilone, as a lead for the development of anti-inflammatory drugs. PMID:22590514

Anti-inflammatory effects of polyamines in serotonin and carrageenan paw edemata - possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radical.

PubMed

Oyanagui, Y

1984-02-01

Serotonin paw edema of mice and carrageenan paw edema of rats were inhibited by subcutaneously or orally administered certain polyamines. They must be given at least 2 h before serotonin challenge to get inhibitions which were blocked by the concomitant injections of cycloheximide. Thirty percent inhibitory dose (ID30) of polyamines (s.c.) 3 h before serotonin (s.c.) were: spermidine (8 mg/kg), spermine 28 mg/kg) and putrescine (55 mg/kg). Agmatine, cadaverine, ornithine, citrulline, lysine and arginine were not inhibitory even at 200 mg/kg. Three inhibitory polyamines were effective by oral administration but were not inhibitory by local administration into the paws. Intravenous injections of spermidine also required 2 h of lag period for inhibitions. Serotonin edema was inhibited by dexamethasone (1 mg/kg), prednisolone (1 mg/kg) or by superoxide dismutase (SOD, 5 mg/kg) in lag period requiring manner (s.c. and i.v.). High dose of cyclo-oxygenase inhibitors indomethacin and diclofenac sodium, lipo-oxygenase inhibitor BW755C (30 mg/kg s.c., respectively) and phospholipase A2 inhibitor quinacrine (100 mg/kg s.c.) failed to inhibit serotonin edema, suggesting that arachidonate metabolites are not participating in this model. ID30 of polyamines which were administered (s.c. and oral) to rats 3 h before carrageenan and determined at 3 h by paw weight were: spermidine (28 and 100 mg/kg), spermine (18 and 90 mg/kg) and putrescine (both greater than 200 mg/kg). Adrenalectomized rats responded to polyamines just as normal rats. Local vascular permeability, irritancy and acute toxicity were also tested in mice. Polyamines were proved to be glucocorticoid-type anti-inflammatory drugs. Polyamines may be mediators of glucocorticoids for the synthesis of the postulated vascular permeability inhibitory protein (called as 'vasoregulin' for convenience). Anti-inflammatory effect of glucocorticoid is recently explained by its capacity to induce phospholipase A2 inhibitory protein(s) (macrocortin or lipomodulin). However, this hypothesis has not yet been proved by in vivo experiment and our data suggest that there is induction by glucocorticoid of another kind of protein which does not inhibit phospholipase A2 activity.

The role of IL-6 and IL-1beta in painful perineural inflammatory neuritis.

PubMed

Eliav, Eli; Benoliel, Rafael; Herzberg, Uri; Kalladka, Mythili; Tal, Michael

2009-05-01

Inflammation along a nerve trunk (perineural inflammation), without detectable axonal damage, has been shown to induce transient pain in the organ supplied by the nerve. The aims of the present study were to study the role IL-6 and IL-1beta, in pain induced by perineural inflammation. IL-6 and IL-1beta secretion from rat's sciatic nerves, L-5 Dorsal Root Ganglia (DRG), and the hind paw skin, 3 and 8 days following exposure of the nerve to Complete Freund's Adjuvant (CFA), were measured using ELISA method. Hind paw tactile-allodynia, mechano-hyperalgesia, heat-allodynia and electrical detection thresholds were tested up to 8 days following the application of CFA, IL-6 or IL-1beta adjacent to the sciatic nerve trunk. Employing electrophysiological recording, saphenous nerve spontaneous activity, nerve trunk mechano-sensitivity and paw tactile detection threshold (determined by recording action potential induced by the lowest mechanical stimulus) were assessed 3 and 8 days following exposure of the nerve trunk to CFA, IL-6, or IL-1beta. IL-6 and IL-1beta secretion from the nerve was significantly elevated on the 3rd day post-operation (DPO). On the 8th DPO, IL-6 levels returned to baseline while IL-1beta levels remained significantly elevated. The DRG cytokine's level was increased on the 3rd and 8th DPOs, contralateral cytokine's level was increased on the 3rd DPO. The skin IL-6 level was increased bilaterally on the 3rd DPO and returned to baseline on the 8th DPO. IL-1beta levels increased in the affected side on the 3rd and bilaterally on the 8th DPO. Direct application of IL-6 or CFA on the sciatic nerve induced significant hind paw tactile-allodynia from the 1st to 5th DPOs, reduced electrical detection threshold from the 1st to 3rd DPOs, mechano-hyperalgesia from 3rd to 5th DPOs and heat-allodynia on the 3rd DPO. Direct application of IL-1beta induced paw tactile and heat-allodynia on the 7-8th DPOs and mechano-hyperalgesia on the 5-8th DPOs. Perineural inflammation significantly increased spontaneous activity myelinated fibres 3 and 8 days following the application. Direct application of IL-6 induced elevation of spontaneous activity on the 3rd while IL-1beta on the 8th DPO. Nerve mechano-sensitivity was significantly increased on the 3rd day following exposure to CFA and IL-6 and on the 8th following CFA application. The rat's paw lowest mechanical force necessary for induction of action potential, was significantly reduced 3 days following CFA application. IL-6 and IL-1beta play an important role in pain induced by perineural inflammation. IL-6 activity is more prominent immediately following application (2-5th DPOs), while IL-1beta, activity is more significant in a later stage (5-8th DPOs).

The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

PubMed

Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

2006-11-01

In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

Analysis of the use of fenthion via epicutaneous in dogs for Rhipicephalus sanguineus control.

PubMed

Fernandes, F de F; Freitas, E de P

2001-01-01

The action of fenthion was studied in a 15% epicutaneous formulation upon Rhipicephalus sanguineus, which may transmit pathogens to men and other animals, such as Ehrlichia, Babesia and Ricketsia. Dogs were artificially infected for the trial. The fenthion bioassays were begun four months after artificial infestation. The test group, having a mean of 186 ticks per dog, received the formulation dosage according to body weight on the neck region. Tick counts were performed, considering diameters > or = 2mm, during 11 days of treatment, in the most affected body areas: back, ears and paws. Before the application of fenthion in the dogs, it were observed an average 43.3% ticks in the ears, 38.1% in the back area and 17.6% in the paws. The number of ticks in dogs decreased by 36.2%, 63.8%, 82.7%, 67%, 40% and 4.9%, respectively on days 1, 2, 3, 5, 7, 9 and 11 after treatment. R. sanguineus anti-tick activity, lower than that officially recommended, was verified. The number of ticks increased progressively after the 5th day, demonstrating residual insecticide inefficacy. The results obtained did not indicate the use of this formulation, at the tested dosage, as an elective measure for R. sanguineus control.

Guava pomace: a new source of anti-inflammatory and analgesic bioactives

PubMed Central

2013-01-01

Background Guava pomace is an example of the processing waste generated after the manufacturing process from the juice industry that could be a source of bioactives. Thus, the present investigation was carried out in order to evaluate the anti-inflammatory and antinociceptive potential and determinate the main phenolic compounds of a guava pomace extract (GPE). Methods The anti-inflammatory activity was evaluated by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models. Acetic acid-induced abdominal writhing and formalin test were performed to investigate the antinociceptive effects. In addition, the content of total phenolic and of individual phenolic compounds was determined by GC/MS. Results GPE showed anti-inflammatory activity by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models (p < 0.05). GPE also demonstrated antinociceptive activity by acetic acid-induced abdominal writhing and formalin test (p < 0.05). The total phenolic value was 3.40 ± 0.09 mg GAE/g and epicatechin, quercetin, myricetin, isovanilic and gallic acids were identified by GC/MS analysis. Conclusions The presence of bioactive phenolic compounds as well as important effects demonstrated in animal models suggest that guava pomace could be an interesting source of anti-inflammatory and analgesic substances. PMID:24063346

Pharmacological Basis for Use of Selaginella moellendorffii in Gouty Arthritis: Antihyperuricemic, Anti-Inflammatory, and Xanthine Oxidase Inhibition

PubMed Central

Zhao, Ping; Chen, Ke-li; Zhang, Guo-li

2017-01-01

This study was aimed at evaluating the effects of Selaginella moellendorffii Hieron. (SM) on gouty arthritis and getting an insight of the possible mechanisms. HPLC method was developed for chemical analysis. The paw oedema, the neutrophil accumulation, inflammatory mediators, lipid peroxidation, and histopathological changes of the joints were analyzed in gouty arthritis rat model, and the kidney injury and serum urate were detected in hyperuricemic mice. Pharmacokinetic result demonstrated that the main apigenin glycosides might be quantitatively transformed into apigenin in the mammalian body. Among these compounds, the apigenin exhibited the strongest effect on xanthine oxidase (XOD). SM aqueous extract has proved to be active in reducing hyperuricemia in dose-dependent manner, and the levels of blood urea nitrogen (BUN) and creatinine (Cr) in high dose group were decreased significantly as compared with hyperuricemic control group (P < 0.01). The high dose of SM extract could significantly prevent the paw swelling, reduce gouty joint inflammatory features, reduce the release of IL-1β and TNF-α, lower malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and increase superoxide dismutase (SOD) level (P < 0.01). For the first time, this study provides a rational basis for the traditional use of SM aqueous extract against gout in folk medicine. PMID:28250791

Rose geranium essential oil as a source of new and safe anti-inflammatory drugs

PubMed Central

Boukhatem, Mohamed Nadjib; Kameli, Abdelkrim; Ferhat, Mohamed Amine; Saidi, Fairouz; Mekarnia, Maamar

2013-01-01

Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile. PMID:24103319

Role of phyto-stabilised silver nanoparticles in suppressing adjuvant induced arthritis in rats.

PubMed

Mani, Aparna; Vasanthi, C; Gopal, V; Chellathai, Darling

2016-12-01

The present study was aimed to evaluate the anti-arthritic effects of silver nanoparticles synthesised using Piper nigrum extract and to further establish its mechanism of action in a rat model of adjuvant induced arthritis (AA). Adjuvant arthritis was induced by injecting complete Freund's adjuvant (0.1mL) into the left hind paw of 36 albino Wistar rats (n=6). Silver nanoparticles stabilised with Piper nigrum extract (25 and 50mg/kg). Commercial silver nanoparticles (50mg/kg) and methotrexate (0.1mg/kg) were administered by intraperitoneal route from day 11 to day 22 on alternate days. It was found that treatment with silver nanoparticles stabilised with Piper nigrum (S-AgNPs) significantly reduced the paw edema and alleviated the histopathological changes of cell infiltration, synovial hyperplasia, bone and cartilage destruction. Furthermore, the phytostabilised silver nanoparticles (S-AgNPs) inhibited the protein expression of NF-kβ p65 and TNF-α as evidenced by immunohistochemistry analysis. Our current findings suggest that silver nanoparticles stabilised with Piper nigrum extract (S-AgNPs) have potent anti-arthritic activity which is mediated by inhibition of TNF-α and suppression of pro-inflammatory cytokines that are secreted in response to activated transcription factors of NF-kβ. Copyright © 2016 Elsevier B.V. All rights reserved.

Fault-Tree Compiler

NASA Technical Reports Server (NTRS)

Butler, Ricky W.; Boerschlein, David P.

1993-01-01

Fault-Tree Compiler (FTC) program, is software tool used to calculate probability of top event in fault tree. Gates of five different types allowed in fault tree: AND, OR, EXCLUSIVE OR, INVERT, and M OF N. High-level input language easy to understand and use. In addition, program supports hierarchical fault-tree definition feature, which simplifies tree-description process and reduces execution time. Set of programs created forming basis for reliability-analysis workstation: SURE, ASSIST, PAWS/STEM, and FTC fault-tree tool (LAR-14586). Written in PASCAL, ANSI-compliant C language, and FORTRAN 77. Other versions available upon request.

The effect of varying the introduction mode of reactants on electrical, physical and thermal stability properties of polypyrrole synthesized with CTAB

NASA Astrophysics Data System (ADS)

Vahidi, K.; Jalili, Y. Seyed; Salar Elahi, A.

2017-10-01

Electrical and physical properties of conducting polymers are generally enhanced via modifications in the chemical structure of the final product, there appears to be a void in facile physical means to improve the materials' properties without utilizing additives which remain in the final product as impurity. In this research, we presented the effect of altering the introduction method of reactants in emulsion polymerization of PPy with CTAB on the electrical, physical and stability properties of the final product. Three samples were prepared: one via a conventional non-emulsion polymerization method as a reference sample, the second in which the reactants were added simultaneously and the goal sample in which the monomer/surfactant mixture was allowed to be stirred separately then it was added dropwise to the oxidant solution. UV-vis, FTIR, 4-point Van Derr Paw probe, FESEM and contact angle measurements were used to investigate optical, electrical, physical, heat stability and solubility properties of the samples. The results indicate that since in the final sample a higher portion of the reaction occurred on the hydrophobic interior of the micelles, the final material had a lower number of structural and chemical defects which leads to higher conjugation lengths and thus higher properties such as a 9-fold difference in conductivity and improved solubility and thermal stability. The novelty of this work lies in the simplicity of the alterations that have been made, both in terms of optimization of the synthetic route which had been thoroughly investigated and also in terms of the differences that our work poses compared to that of the others; namely: the parameters have been thoroughly studied and analyzed but not the method of addition as in our experiments the sequence of addition and the method of addition of the reactants were altered to observe their effect on the physical and the electronic properties which has led to the conclusion that in case of drop-wise addition, a larger portion of the reaction occurs inside the micelles hence giving rise to inhibition of the defect-producing chemical bonds which is supported by the analysis in our investigations.

Anti-inflammatory activity of Achillea and Ruscus topical gel on carrageenan-induced paw edema in rats.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Naddaf, Ahmad R

2006-01-01

The anti-inflammatory activity of Achillea and Ruscus extracts was studied in comparison with diclofenac sodium topical gel (diclosal Emulgel), using the carrageenan induced paw edema model in Albino rats. Gel formulation was prepared containing 6% of each extract in gel base, namely sodium carboxymethylcellulose (NaCMC). The kinetics of drug release from the prepared formulation was studied separately in each case. Results showed that the release follows the Higuchi square root equation. The pharmacological screening revealed that the percent reduction of edema for Achillea extract and Ruscus extract were 48.1% and 18.8%, respectively, while diclosal Emulgel produced 47% reduction of edema.

Opioidergic mechanisms are not involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

PubMed

Stepanovic-Petrovic, Radica M; Tomic, M A; Vuckovic, S M; Ugresic, N D; Prostran, M S; Boskovic, B

2007-04-01

The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mg/paw) into the rat hind paw. Naloxone (3 mg/kg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine.

FTC - THE FAULT-TREE COMPILER (SUN VERSION)

NASA Technical Reports Server (NTRS)

Butler, R. W.

1994-01-01

FTC, the Fault-Tree Compiler program, is a tool used to calculate the top-event probability for a fault-tree. Five different gate types are allowed in the fault tree: AND, OR, EXCLUSIVE OR, INVERT, and M OF N. The high-level input language is easy to understand and use. In addition, the program supports a hierarchical fault tree definition feature which simplifies the tree-description process and reduces execution time. A rigorous error bound is derived for the solution technique. This bound enables the program to supply an answer precisely (within the limits of double precision floating point arithmetic) at a user-specified number of digits accuracy. The program also facilitates sensitivity analysis with respect to any specified parameter of the fault tree such as a component failure rate or a specific event probability by allowing the user to vary one failure rate or the failure probability over a range of values and plot the results. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. Although different solution techniques are utilized on different programs, it is possible to have a common input language. The Systems Validation Methods group at NASA Langley Research Center has created a set of programs that form the basis for a reliability analysis workstation. The set of programs are: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920); and the FTC fault tree tool (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree. PAWS/STEM and SURE are programs which interpret the same SURE language, but utilize different solution methods. ASSIST is a preprocessor that generates SURE language from a more abstract definition. SURE, ASSIST, and PAWS/STEM are also offered as a bundle. Please see the abstract for COS-10039/COS-10041, SARA - SURE/ASSIST Reliability Analysis Workstation, for pricing details. FTC was originally developed for DEC VAX series computers running VMS and was later ported for use on Sun computers running SunOS. The program is written in PASCAL, ANSI compliant C-language, and FORTRAN 77. The TEMPLATE graphics library is required to obtain graphical output. The standard distribution medium for the VMS version of FTC (LAR-14586) is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The standard distribution medium for the Sun version of FTC (LAR-14922) is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. FTC was developed in 1989 and last updated in 1992. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. UNIX is a registered trademark of AT&T Bell Laboratories. SunOS is a trademark of Sun Microsystems, Inc.

FTC - THE FAULT-TREE COMPILER (VAX VMS VERSION)

NASA Technical Reports Server (NTRS)

Butler, R. W.

1994-01-01

FTC, the Fault-Tree Compiler program, is a tool used to calculate the top-event probability for a fault-tree. Five different gate types are allowed in the fault tree: AND, OR, EXCLUSIVE OR, INVERT, and M OF N. The high-level input language is easy to understand and use. In addition, the program supports a hierarchical fault tree definition feature which simplifies the tree-description process and reduces execution time. A rigorous error bound is derived for the solution technique. This bound enables the program to supply an answer precisely (within the limits of double precision floating point arithmetic) at a user-specified number of digits accuracy. The program also facilitates sensitivity analysis with respect to any specified parameter of the fault tree such as a component failure rate or a specific event probability by allowing the user to vary one failure rate or the failure probability over a range of values and plot the results. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. Although different solution techniques are utilized on different programs, it is possible to have a common input language. The Systems Validation Methods group at NASA Langley Research Center has created a set of programs that form the basis for a reliability analysis workstation. The set of programs are: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920); and the FTC fault tree tool (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree. PAWS/STEM and SURE are programs which interpret the same SURE language, but utilize different solution methods. ASSIST is a preprocessor that generates SURE language from a more abstract definition. SURE, ASSIST, and PAWS/STEM are also offered as a bundle. Please see the abstract for COS-10039/COS-10041, SARA - SURE/ASSIST Reliability Analysis Workstation, for pricing details. FTC was originally developed for DEC VAX series computers running VMS and was later ported for use on Sun computers running SunOS. The program is written in PASCAL, ANSI compliant C-language, and FORTRAN 77. The TEMPLATE graphics library is required to obtain graphical output. The standard distribution medium for the VMS version of FTC (LAR-14586) is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The standard distribution medium for the Sun version of FTC (LAR-14922) is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. FTC was developed in 1989 and last updated in 1992. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. UNIX is a registered trademark of AT&T Bell Laboratories. SunOS is a trademark of Sun Microsystems, Inc.

Anti-inflammatory potential of silk sericin.

PubMed

Aramwit, Pornanong; Towiwat, Pasarapa; Srichana, Teerapol

2013-04-01

Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats' paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats' tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

Emu oil based nano-emulgel for topical delivery of curcumin.

PubMed

Jeengar, Manish Kumar; Rompicharla, Sri Vishnu Kiran; Shrivastava, Shweta; Chella, Naveen; Shastri, Nalini R; Naidu, V G M; Sistla, Ramakrishna

2016-06-15

Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis. Copyright © 2016 Elsevier B.V. All rights reserved.

VizieR Online Data Catalog: The PAWS catalogs of GMCs and islands in M51 (Colombo+, 2014)

NASA Astrophysics Data System (ADS)

Colombo, D.; Hughes, A.; Schinnerer, E.; Meidt, S. E.; Leroy, A. K.; Pety, J.; Dobbs, C. L.; Garcia-Burillo, S.; Dumas, G.; Thompson, T. A.; Schuster, K. F.; Kramer, C.

2016-08-01

The Plateau de Bure Interferometer (PdBI) Arcsecond Whirlpool Survey (PAWS; Schinnerer et al., 2013ApJ...779...42S) is a large IRAM program involving 210hr of observations with the Plateau de Bure Interferometer (PdBI) and IRAM 30m telescope to conduct a sensitive, high angular resolution (1.16''*0.97''), 12CO(1-0) survey of the inner disk of M51a (field-of-view, FoV ~270''*170''). The spatial resolution at our assumed distance to M51 of 7.6Mpc (Ciardullo et al. 2002, cat. J/ApJ/577/31) is ~40pc. The inclusion of the 30m single dish data during joint deconvolution ensures that flux information on all spatial scales is conserved. The rms of the noise fluctuations in the cube is ~0.4K per 5km/s channel. This sensitivity is sufficient to detect an object with a gas mass of 1.2*105M{Sun} at the 5σrms level. The PAWS data cube covers the LSR velocity range between 173 and 769km/s. A detailed description of the observing strategy, calibration and data reduction is presented by Pety et al. (2013ApJ...779...43P). (2 data files).

Anti-inflammatory and anti-pyretic properties of Spirulina platensis and Spirulina lonar: a comparative study.

PubMed

Somchit, Muhammad Nazrul; Mohamed, Nor Azura; Ahmad, Zuraini; Zakaria, Zainul Amiruddin; Shamsuddin, Lokman; Omar-Fauzee, Mohd Sofian; Kadir, Arifah Abdul

2014-09-01

Spirulina spp. is a blue-green algae belongs to the family of Oscillatoriaceae, which having diverse biological activity. The aim of this current study was to evaluate and compare the anti-pyretic and anti-inflammatory activity of Spirulina platensis/SP and Spirulina lonar/SL extracts. In the anti-pyretic study, the ability to reduce the rectal temperature of rats induced pyrexia with 2g/kg Brewer's Yeast (BY) was performed. Rats were dosed either 2 or 4 mg/kg SP or SL. Rectal temperature was taken every hour for 8 hours. Results shown that there were significant dose-dependent (p<0.05) reduction of both treatments. However, SP treatment revealed faster reduction in rectal temperature. For anti-inflammatory activity, the reduction in the volume of paw edema induced by Prostaglandin E2 (100 IU/rat intraplantar) was measured. Rats were dosed orally with 2 or 4 mg/kg SP or SL. The paw edema was measured every 30 minutes for 4 hours using plethysmometer. Results had shown a significant dose dependent reduction in diameter of paw edema (p<0.05). The finding suggests that SP and SL extracts have anti-pyretic and anti-inflammatory properties. However, SP was found to be more effective than SL as anti-pyretic and anti-inflammatory agent.

Effects of Koumine on Adjuvant- and Collagen-Induced Arthritis in Rats.

PubMed

Yang, Jian; Cai, Hong-Da; Zeng, Yu-Lan; Chen, Ze-Hong; Fang, Meng-Han; Su, Yan-Ping; Huang, Hui-Hui; Xu, Ying; Yu, Chang-Xi

2016-10-28

To examine the effect of koumine, a Gelsemium alkaloid, on two experimental models of rheumatoid arthritis (RA), rats with adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) were administered koumine (0.6, 3, or 15 mg/kg/day) or vehicle through gastric gavage (i.g.). Clinical evaluation was performed via measurements of hind paw volume, arthritis index (AI) score, mechanical withdrawal threshold, organ weight, and by radiographic and histological examinations. Levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and antitype II collagen (CII) antibody were also examined. In rats with AIA, koumine reduced the AI score and mechanical allodynia of the injected hind paw in a dose-dependent manner and significantly inhibited increase in thymus and liver weights. In rats with CIA, koumine inhibited increase in hind paw volume, AI score, and mechanical allodynia in a dose-dependent manner and reduced joint space narrowing. Furthermore, koumine also attenuated the increase in the expression of IL-1β and TNF-α, as well as the robust increase of serum anti-CII antibodies in response to immunization. These results suggested that koumine effectively attenuated arthritis progression in two rat models of RA and that this therapeutic effect may be associated with its immunoregulatory action.

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.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

PubMed Central

Wise, Laura E.; Cannavacciulo, Roberta; Cravatt, Benjamin F.; Martin, Billy F.; Lichtman, Aron H.

2008-01-01

While it has long been recognized that Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay. PMID:17675189

Physicochemical Properties, Antioxidant and Cytotoxic Activities of Crude Extracts and Fractions from Phyllanthus amarus

PubMed Central

Nguyen, Van Tang; Sakoff, Jennette A.; Scarlett, Christopher J.

2017-01-01

Background: Phyllanthus amarus (P. amarus) has been used as a medicinal plant for the prevention and treatment of chronic ailments such as diabetes, hepatitis, and cancer. Methods: The physicochemical properties, antioxidant and cytotoxic activities of crude extracts and fractions from P. amarus were determined using spectrophotometric method. Results: The P. amarus methanol (PAM) extract had lower levels of residual moisture (7.40%) and water activity (0.24) and higher contents of saponins, phenolics, flavonoids, and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents per g dried extract, respectively) than those of the P. amarus water (PAW) extract. The antioxidant activity of PAM extract was significantly higher (p < 0.05) than that of the PAW extract, PAM fractions, and phyllanthin (known as a major compound in the P. amarus). Higher cytotoxic activity of PAM extract based on MTT assay on different cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed in comparison to the PAW extract and PAM fractions. The cytotoxic potential of the PAW extract (200 μg/mL), based on the CCK-8 assay on a pancreatic cancer cell line (MiaCaPa2) was significantly lower (p < 0.05) than those of gemcitabine (50 nM) and a saponin-enriched extract from quillajia bark at 200 μg/mL (a commercial product), but was significantly higher than that of phyllanthin at 2 μg/mL. Conclusions: The results achieved from this study reveal that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs. PMID:28930257

Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: Involvement of calcitonin gen-related peptide.

PubMed

Arreola-Peralta, Luis D; Altamirano-Reyna, Frida; Galindo-González, Deni M; Solis-Anguiano, Jessica G; Lacivita, Enza; Leopoldo, Marcello; Terrón, José A

2018-05-03

A decrease in the activation threshold of primary sensory neurons to transient receptor potential V1 (TRPV1) stimulation by serotonin 5-HT7 receptors has been reported but no confirmation if this might translate into facilitation of neurogenic inflammation has been provided. We analysed the modulation of capsaicin (CAP)-induced neurogenic inflammation in the rat hind paw by the selective 5-HT7 receptor agonist, LP-44, and the involvement of calcitonin gen-related peptide (CGRP) in this effect. Animals received intra-plantar injections (30 μL) of vehicle, CAP (0.05%, 0.1% and 0.2%), LP-44 (7.5 and 15 nmol) and the combination of LP-44 + CAP; then, the time course of the inflammatory responses was measured. The effect of the 5-HT7 receptor antagonist, SB-269970 (3 mg/kg, s.c.), on responses produced by LP-44 alone and combined with CAP was tested. As expected, CAP produced concentration- and time-dependent inflammatory responses in the hind paw. Interestingly, LP-44 by itself also produced inflammation in a concentration- and time-dependent manner, and magnified CAP-induced responses. Systemic pre-treatment with SB-269970 significantly blunted LP-44 (15 nmol)-induced inflammation as well as magnified inflammatory responses produced by the combination of LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus confirming the involvement of 5-HT7 receptors. Finally, the non-peptide CGRP receptor antagonist, BIBN4096 (3 mg/kg, s.c.), strongly inhibited the potentiated inflammatory responses induced by LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus substantiating their neurogenic nature. Thus, sensitization of CAP-sensitive primary sensory neurons by 5-HT7 receptors may result in facilitation of neurogenic inflammation involving CGRP in the rat hind paw. Copyright © 2018. Published by Elsevier Inc.

Antinociceptive and anti-inflammatory activities of Cuscuta chinensis seeds in mice.

PubMed

Liao, Jung-Chun; Chang, Wen-Te; Lee, Meng-Shiou; Chiu, Yung-Jia; Chao, Wei-Kai; Lin, Ying-Chih; Lin, Ming-Kuem; Peng, Wen-Huang

2014-01-01

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CC MeOH ) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20-500 mg/kg of CC MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC MeOH also decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC MeOH in vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.

Central effects of ethanol interact with endogenous mu opioid activity to control isolation-induced analgesia in maternally separated infant rats

PubMed Central

Nizhnikov, Michael E.; Kozlov, Andrey P.; Kramskaya, Tatiana. A.; Varlinskaya, Elena I.; Spear, Norman E.

2014-01-01

Endogenous opioid activity plays an important role in ethanol consumption and reinforcement in infant rats. Opioid systems are also involved in mediation and regulation of stress responses. Social isolation is a stressful experience for preweanling rats and changes the effects of ethanol through opioid-dependent mechanisms. The present study assessed effects of intracisternal (i.c.) administration of a selective mu-opioid antagonist (CTOP) and i.p. administration of a nonspecific opioid antagonist (naloxone) on voluntary intake and behavior in socially isolated 12–day-old (P12) pups treated with 0.5 g/kg ethanol. Voluntary intake of 0.1% saccharin or water, locomotion, rearing activity, paw licking and grooming were assessed during short-term isolation from littermates (STSI; 8-min duration). Thermal nociceptive reactivity was measured before and after this intake test, with normalized differences between pre- and post-test latencies of paw withdrawal from a hot plate (49°C) used as an index of isolation-induced analgesia (IIA). Results indicated several effects of social isolation and ethanol mediated through the mu-opioid system. Effects of low dose ethanol (0.5 g/kg) and voluntary consumption of saccharin interacted with endogenous mu-opioid activity associated with STSI. Blockade of mu-opioid receptors on saccharin consumption and paw licking-grooming affected intoxicated animals. Low dose ethanol and ingestion of saccharin blunted effects of CTOP on rearing behavior and nociceptive reactivity. Central injections of CTOP stimulated paw licking and grooming dependent on ethanol dose and type of fluid ingested. Ethanol selectively increased saccharin intake during STSI in females, naloxone and CTOP blocked ethanol–mediated enhancement of saccharin intake. We suggest that enhancement of saccharin intake by ethanol during STSI is the product of synergism between isolation-induced mu- opioid activity that increases the pup’s sensitivity to appetitive taste stimulation and the anxiolytic effects of 0.5 g/kg ethanol that decreases behaviors otherwise competing with independent ingestive activity. PMID:24315831

Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding-Mediated Analgesic Effects in Complete Freund's Adjuvant-Induced Inflammatory Pain.

PubMed

Du, Kairong; Wang, Xue; Chi, Laiting; Li, Wenzhi

2017-08-01

The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats.

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

PubMed

Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. Georg Thieme Verlag KG Stuttgart · New York.

Owner assessment of pruritus and gastrointestinal signs in apparently healthy dogs with no history of cutaneous or noncutaneous disease.

PubMed

Stetina, Kacie M; Marks, Stanley L; Griffin, Craig E

2015-08-01

Determining the cause of pruritus relies on establishing the pattern of abnormal pruritus. The presence of gastrointestinal (GI) disease has also been helpful in determining the cause of pruritus. No study has systematically evaluated typical GI signs and pruritic behaviours in apparently healthy dogs. To evaluate owners' perceptions of pruritus and GI signs in apparently healthy dogs, and determine if age, breed, activity, diet or supplements affected these signs. Three hundred and fourteen apparently healthy dogs ≥ 12 months old with an unremarkable physical examination and no history of pruritus, otitis, skin/hair disease, metabolic or GI disease were enrolled. Thirty one veterinarians enrolled dogs after establishing their pruritus visual analog scale (PVAS) score and faecal consistency score (FCS); owners completed a comprehensive online survey regarding GI signs, possible pruritic behaviours, ear cleaning and sneezing. A PVAS score of ≤ 1.9 was recorded in 87.6% of dogs and the FCS was 2-3 in 94.9% of dogs. PVAS was positively correlated with paw licking/chewing, facial/muzzle rubbing, head shaking and sneezing. Scooting was positively correlated with sneezing. Over 96% of dogs had 1-3 bowel movements (BM) per day. Age was positively correlated with facial/muzzle rubbing, sneezing, coprophagia and borborygmi. The number of walks/day was positively correlated with paw licking/chewing, head shaking, sneezing, number of BM/day, coprophagia, belching, flatulence and borborygmi. A standard method of asking relevant questions was developed and the frequency of GI signs and many behaviours that may indicate pruritus in apparently healthy dogs was established. © 2015 ESVD and ACVD.

Understanding hydrologic budgets, dynamics in an arid basin and explore spatial scaling properties using Process-based Adaptive Watershed Simulator (PAWS)

NASA Astrophysics Data System (ADS)

Fang, K.; Shen, C.; Salve, R.

2013-12-01

The Southern California hot desert hosts a fragile ecosystem as well as a range of human economic activities, primarily mining, energy production and recreation. This inland arid landscape is characterized by occasional intensive precipitation events and year-round strong potential evapotranspiration. In this landscape, water and especially groundwater is vital for ecosystem functions and human use. However, the impact of recent development on the sustainability of groundwater resources in the area has not been thoroughly investigated. We apply an integrated, physically-based hydrologic-land surface model, the Process-based Adaptive Watershed Simulator + Community Land Model (PAWS+CLM) to evaluate the sustainability of the groundwater resources in the area. We elucidate the spatio-temporal patterns of hydrologic fluxes and budgets. The modeling results indicate that mountain front recharge is the essential recharging mechanism for the alluvial aquifer. Although pumping activities do not exceed annual-average recharge values, they are still expected to contribute significantly to groundwater drawdown in business-as-usual scenario. The impact of groundwater withdrawals is significant on the desert ecosystem. The relative importance of groundwater flow on NPP rises significantly as compared to other ecosystems. We further evaluate the fractal scaling properties of soil moisture in this very arid system and found the relationship to be much more static in time than that found in a humid continental climate system. The scaling exponents can be predicted using simple functions of the mean. Therefore, multi-scale model based on coarse-resolution surrogate model is expected to perform well in this system. The modeling result is also important for assessing the groundwater sustainability and impact of human activities in the desert environment.

Use of ethylene-vinyl alcohol copolymer as a liquid embolic agent to treat a peripheral arteriovenous malformation in a dog

PubMed Central

Culp, William T. N.; Glaiberman, Craig B.; Pollard, Rachel E.; Wisner, Erik R.

2015-01-01

Case Description An 11-year-old castrated male Tibetan Mastiff was evaluated because of a visibly enlarged blood vessel and progressively worsening swelling of the right hind limb. Clinical Findings On physical examination, the right hind limb was markedly larger than the left hind limb and the dog was minimally weight bearing on the affected limb. A bruit was auscultated over the affected region. Ultrasonography of the tarsal region of the right hind limb revealed an artery with turbulent flow that communicated with venous drainage. A CT scan confirmed the presence of an arteriovenous malformation (AVM). Treatment and Outcome Embolization of the AVM with a liquid embolic agent (ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide) was elected. An arteriogram was performed prior to treatment and delineated the vessels that were targeted for embolization. The embolic agent was infused into the AVM, and a postinjection arteriogram confirmed complete occlusion of the AVM nidus and normal arterial flow to the paw with subsequent normal venous drainage. The circumference of the abnormal paw was 51 cm before the procedure and 22.9 cm at 4 weeks after the procedure. Additionally, the gait of the dog dramatically improved. No complications associated with the procedure developed. Clinical Relevance Peripheral AVMs in dogs are uncommon, and described treatment options are limited and generally associated with serious morbidity. A liquid embolic agent, ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide, was successfully administered in this case, and no morbidity was observed secondary to the procedure. Clinical success was characterized by substantial improvement in limb swelling and marked improvement in the gait of the dog. PMID:24984133

Combined SCI and TBI: Recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement

PubMed Central

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L.; Creasey, Graham H.; Manley, Geoffrey T.; Ferguson, Adam R.; Bresnahan, Jacqueline C.; Beattie, Michael S.

2015-01-01

A significant proportion (estimates range from 16–74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI + TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6 weeks, in the paw placement test, SCI + contralateral TBI produced a profound deficit that failed to recover, but SCI + ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI + contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI + contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI. PMID:23770071

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

PubMed

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-10-01

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI. Copyright © 2013 Elsevier Inc. All rights reserved.

Opioid systems in the response to inflammatory pain: sustained blockade suggests role of kappa- but not mu-opioid receptors in the modulation of nociception, behaviour and pathology.

PubMed

Millan, M J; Colpaert, F C

1991-01-01

One day after intraplantar inoculation of Mycobacterium butyricum into the right hind-paw, unilaterally inflamed and control rats were implanted subcutaneously with osmotic mini-pumps delivering naloxone at 0.16 or 3.0 mg/kg/h or vehicle. As determined three days after implantation, 0.16 mg/kg/h of naloxone completely antagonized the antinociceptive action of the mu-agonist, morphine, but did not affect antinociception evoked by the kappa-agonist, U69,593. In contrast, at 3.0 mg/kg/h, naloxone blocked both morphine- and U69,593-induced antinociception. Thus, 0.16 mg/kg ("low dose") and 3.0 mg/kg ("high dose") of naloxone block mu, or mu- plus kappa-opioid receptors, respectively. Pumps were removed one week following their implantation. Inoculation was associated with a sustained hyperalgesia of the inflamed paw to noxious pressure, and elevation in resting core temperature, a loss of body weight, hypophagia, hypodipsia and a reduction in mobility. These parameters were differentially modified by the high as compared to the low dose of naloxone. Two days following implantation of pumps delivering the high dose of naloxone, the hyperalgesia of the inflamed paw was potentiated: by six days, this effect was lost. Further, one day after removal of pumps yielding the high dose, the inflamed paw showed a normalization of thresholds, that is a "rebound antinociception". One day later, this effect had subsided. In distinction, at no time did the low dose of naloxone modify nociceptive thresholds. The high dose of naloxone enhanced the reduction in body weight and food intake shown by unilaterally inflamed rats whereas the low dose was ineffective. Neither dose affected the reduction in water intake or hypothermia of unilaterally inflamed animals. The high dose of naloxone reduced the mobility of unilaterally inflamed rats whereas the low dose was ineffective. Finally, by 10 days following pump removal, pathology had transferred to the contralateral paw. In rats which had received the high but not the low dose, this transfer was blocked. It is concluded that blockade of kappa-opioid receptors with a high dose of naloxone experts pronounced functional effects in unilaterally inflamed rats. In distinction, selective blockade of mu-receptors with a low dose is ineffective. The changes seen include not only an enhancement of the hyperalgesia of the inflamed tissue, but also an exacerbation of variables (body weight, food intake and motility) which reflect pain states.(ABSTRACT TRUNCATED AT 400 WORDS)

Ab Initio study on structural, electronic, magnetic and dielectric properties of LSNO within Density Functional Perturbation Theory

NASA Astrophysics Data System (ADS)

Petersen, John; Bechstedt, Friedhelm; Furthmüller, Jürgen; Scolfaro, Luisa

LSNO (La2-xSrxNiO4) is of great interest due to its colossal dielectric constant (CDC) and rich underlying physics. While being an antiferromagnetic insulator, localized holes are present in the form of stripes in the Ni-O planes which are commensurate with the inverse of the Sr concentration. The stripes are a manifestation of charge density waves with period approximately 1/x and spin density waves with period approximately 2/x. Here, the spin ground state is calculated via LSDA + U with the PAW method implemented in VASP. Crystal structure and the effective Hubbard U parameter are optimized before calculating ɛ∞ within the independent particle approximation. ɛ∞ and the full static dielectric constant (including the lattice polarizability) ɛ0 are calculated within Density Functional Perturbation Theory.

Revealing anti-inflammation mechanism of water-extract and oil of forsythiae fructus on carrageenan-Induced edema rats by serum metabolomics.

PubMed

Yuan, An; Gong, Lihong; Luo, Lin; Dang, Jue; Gong, Xiaohong; Zhao, Mengjie; Li, Yan; Li, Yunxia; Peng, Cheng

2017-11-01

Forsythiae Fructus is an important Chinese medicine which shows a significant effect against inflammation. This study aimed to investigate the preventive anti-inflammation mechanism of Forsythiae Fructus by serum metabolomics strategy and compare the difference of the metabolism pathways between Forsythia extract and Forsythia oil in rat. Four groups (control group, model group, Forsythia extract group and Forsythia oil group) were orally administered 10mL/kg 0.5% Tween 80 solution, 10mL/kg 0.5% Tween 80 solution, 5g/kg Forsythia extract and 0.48mL/kg Forsythia oil respectively. 30min after drug administration, rat acute inflammation was induced by subcutaneous injection of carrageenan in the right paw in model group, Forsythia extract group and Forsythia oil group. After being administered Forsythia extract and Forsythia oil, the percentage of rat paw edema was significantly decreased (P<0.05) compared with model group. Metabolomics based on UPLC-Q-TOF-MS/MS was used to analyze the collected serum sample. Multivariate analysis was established for metabolomics analysis. According to Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) results, four groups were clearly separated. And thirteen alterative biomarkers were identified in the serum, namely PC (19:0/0:0), LysoPC (20:0), LysoPC (20:1), LysoPC (17:0), Sphingosine, Linoleic acid, 3R-hydroxy-butanoic acid (3-HB), 2-hydroxyhexadecanoic acid, Lactic acid, L-Threonine, L-Leucine, Maleic acid, Adipic acid. The change of biomarkers suggested that Forsythia extract affected Linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, Sphingolipid metabolism and Glycerophospholipid metabolism. Forsythia oil affected Sphingolipid metabolism and Glycerophospholipid metabolism. It indicated that Forsythia extract and Forsythia oil both showed significant preventive anti-inflammatory effect through acting on different metabolism pathways. Moreover, efficacy mechanism of Forsythiae Fructus could recover metabolites disturb in the body through affecting particular drug targets associated with the inflammatory pathway. Copyright © 2017. Published by Elsevier Masson SAS.

Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine to produce antihyperalgesia in rats.

PubMed

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

2013-11-01

Levetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant, are widely used against inflammatory pain. This study characterized the manner in which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and paracetamol) and caffeine to suppress hyperalgesia in a model of localized inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1 mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally), analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug combinations of levetiracetam with analgesics or caffeine were examined by a modified paw pressure test. The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold. The presented data suggest that 2-drug combinations of levetiracetam and nonsteroidal analgesics or caffeine could be useful in treatment of inflammatory pain. The efficacy and the adverse effects of those mixtures should be explored further in clinical settings. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Marine bioactive compounds: stereospecific anti-inflammatory activity of natural and synthetic cordiachromene A.

PubMed

Benslimane, A F; Pouchus, Y F; Verbist, J F; Petit, J Y; Khettab, E N; Welin, L; Brion, J D

1992-01-01

A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone.

Claustral single cell reactions to tooth pulp stimulation in cats.

PubMed

Jastreboff, P; Sikora, M; Frydrychowski, A; Słoniewski, P

1983-01-01

Single unit activity in the central region of the claustrum, evoked by electrical stimulation of tooth pulp or paws was studied on cats under chloralose anesthesia. The majority of cells responded in similar manner to stimulation of tooth pulp or paws, but there were cells with clear preference to a given type of stimulation. Latencies of reactions evoked by tooth pulp stimulation were significantly shorter than those for limb stimulation. In the former case latencies as short as 8 rns were observed. It is postulated that the central region of the claustrum receives a projection from the tooth pulp, and that in those cases with very short latency the projection is direct and does not involve the cerebral cortex.

Lymph node clearance of plutonium from subcutaneous wounds in beagles

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

Dagle, G.E.

1973-08-01

The lymph node clearance of /sup 239/Pu O/sub 2/ administered as insoluble particles from subcutaneous implants was studied in adult beagles to simulate accidental contamination of hand wounds. External scintillation data were collected from the popliteal lymph nodes of each dog after 9.2 to 39.4 mu Ci of plutonium oxide was subcutaneously implanted into the left or right hind paws. The left hind paw was armputated 4 weeks after implantation to prevent continued deposition of plutonium oxide particles in the left popliteal lymph node. Groups of 3 dogs were sacrificed 4, 8, 16, and 32 weeks after plutonium implantation formore » histopathologic, electron microscopic, and radiochemical analysis of regional lymph nodes. An additional group of dogs received treatment with the chelating agent diethyenetriaminepentaacetic acid (DTPA). Plutonium rapidly accumulated in the popliteal lymph nodes after subcutaneous injection into the hind paw, and 1 to 10% of the implant dose was present in the popliteal lymph nodes at the time of necropsy. Histopathologic changes in the popliteal lymph nodes with plutonium particles were characterized primarily by reticular cell hyperplasia, increased numbers of macrophages, necrosis, and fibroplasia. Eventually, the plutonium particles became sequestered by scar tissue that often replaced the entire architecture of the lymph node. Light microscopic autoradiographs of the popliteal lymph nodes showed a time-related increase in number of alpha tracks per plutonium source. Electron microscopy showed that the plutonium particles were aggregated in phagolysosomes of macrophages. There was slight clearance of plutonium from the popliteal lymph nodes of dogs monitored for 32 weeks. The clearance of plutonium particles from the popliteal lymph nodes was associated with necrosis of macrophages. The external iliac lymph nodes contained fewer plutonium particles than the popliteal lymph nodes and histopathologic changes were less severe. The superficial inguinal lymph nodes of one dog contained appreciable amounts of plutonium. Treatment with diethylenetriaminepentaacetic acid (DTPA) did not have a measurable effect on the clearance of plutonium from the popliteal lymph nodes. (60 references) (auth)« less

Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

PubMed

Ratheesh, M; Sandya, S; Pramod, C; Asha, S; Svenia, Jose P; Premlal, S; GrishKumar, B

2017-02-01

Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and anti-arthritic activity in experimental arthritic model. CB as an anti-arthritic drug has beneficial effect for treating inflammation, tissue damage and pain associated with arthritis.

Modeling of behavioral responses for successful selection of easy-to-train rams for semen collection with an artificial vagina.

PubMed

Ambrosi, Claudia Pamela; Rubio, Natalia; Giménez, Gustavo; Venturino, Andrés; Aisen, Eduardo Gabriel; López Armengol, María Fernanda

2018-06-01

The aim of this study was to analyze the reproductive behavioral responses in Australian Merino rams, to identify those related to a faster training for semen collection with an artificial vagina. Eight Australian Merino rams, aged 1.5 years and with no prior sexual experience, were randomly selected from an extensively grazed flock. One immobilized ewe with no hormone stimulation was used for rams to sexually interact and mount. The frequencies of approaching, sniffing, flehmen, pushing, pawing with chin resting, and tongue flicking were recorded during eight training and three post-training assessments periods. In addition, the duration of sniffing and flehmen responses, as well as the time from when the ram started to approach the ewe until the mount with ejaculation (completed mount) were recorded. Descriptive, correlation, and modeling analyses were performed. Amongst the rams, four mounted the ewe and ejaculated for the first time during the training phase, and three mounted and ejaculated for the first time after the training phase. The remaining ram mounted the ewe and ejaculated for the first time during the post-training evaluation in the following year. A great variability in the behavior repertoire was observed among rams. The correlation analysis indicated that the completed mount was associated with the behaviors during the approaching response. The expression of the sniffing response decreased between the training phase and post-training evaluation, while the responses of pushing the ewe and tongue flicking ceased to occur. Pawing the side of the ewe with the chin resting on the back of the ewe and flehmen responses, however, continued between the training and post-training phases. This led to a decrease in the time from when the ram started to approach the ewe until the completed mount. It is concluded that the responses of approaching the ewe, pawing the side of the ewe with chin resting on the ewe, and sniffing of the ewe (the latter occurring only during the training phase) are behavioral indicators that could be used for selection of easy-to-train rams for purposes of semen collection with an artificial vagina. Copyright © 2018 Elsevier B.V. All rights reserved.

Strategies for obstacle avoidance during walking in the cat.

PubMed

Chu, Kevin M I; Seto, Sandy H; Beloozerova, Irina N; Marlinski, Vladimir

2017-08-01

Avoiding obstacles is essential for successful navigation through complex environments. This study aimed to clarify what strategies are used by a typical quadruped, the cat, to avoid obstacles during walking. Four cats walked along a corridor 2.5 m long and 25 or 15 cm wide. Obstacles, small round objects 2.5 cm in diameter and 1 cm in height, were placed on the floor in various locations. Movements of the paw were recorded with a motion capture and analysis system (Visualeyez, PTI). During walking in the wide corridor, cats' preferred strategy for avoiding a single obstacle was circumvention, during which the stride direction changed while stride duration and swing-to-stride duration ratio were preserved. Another strategy, stepping over the obstacle, was used during walking in the narrow corridor, when lateral deviations of walking trajectory were restricted. Stepping over the obstacle involved changes in two consecutive strides. The stride preceding the obstacle was shortened, and swing-to-stride ratio was reduced. The obstacle was negotiated in the next stride of increased height and normal duration and swing-to-stride ratio. During walking on a surface with multiple obstacles, both strategies were used. To avoid contact with the obstacle, cats placed the paw away from the object at a distance roughly equal to the diameter of the paw. During obstacle avoidance cats prefer to alter muscle activities without altering the locomotor rhythm. We hypothesize that a choice of the strategy for obstacle avoidance is determined by minimizing the complexity of neuro-motor processes required to achieve the behavioral goal. NEW & NOTEWORTHY In a study of feline locomotor behavior we found that the preferred strategy to avoid a small obstacle is circumvention. During circumvention, stride direction changes but length and temporal structure are preserved. Another strategy, stepping over the obstacle, is used in narrow walkways. During overstepping, two strides adjust. A stride preceding the obstacle decreases in length and duration. The following stride negotiating the obstacle increases in height while retaining normal temporal structure and nearly normal length. Copyright © 2017 the American Physiological Society.

Job Aid Manuals for Phase 2-DESIGN of the Instructional Systems Development Model

DTIC Science & Technology

1980-05-01

and sources of this data should be part of the overall Job Analysis Plan. I 61 L ... ............ ..6 WHAT ARE SOME SOURCES OF JOB SIGNIFICANT DATA...SECTION II ’ f .330- S*15’- /PAW $i~ii. TEIIMTJAL IkAHIN (C 11 IVE . .... .. AA t fi -twill Ailf. fe’o- point A +o pom14 Ji - & map, cemoa9j sund...Leaqrr AIrloesr displayed by the Learnrrq Pyfamd. ,derrfie the An"lIys on Task lemei hdedarchy Olud,,iormole to rrrdleel ut skds bn k-ro edes req,.,ed l

Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

PubMed

Bernela, Manju; Ahuja, Munish; Thakur, Rajesh

2016-06-05

Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antioxidant, antibacterial, anti-inflammatory and wound healing effects of Artemisia campestris aqueous extract in rat.

PubMed

Ghlissi, Zohra; Sayari, Nadhim; Kallel, Rim; Bougatef, Ali; Sahnoun, Zouheir

2016-12-01

This study investigated some biological properties of Artemisia campestris aqueous extract (ACAE) as well its global chemical compositions. Twenty four rats were excised on the posterior neck skin area and divided into 4 groups, treated respectively with: sterile saline, glycerol, CICAFLORA and ACAE. The wound closure rate, histopathology evolution and the superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) level in skin tissue were evaluated. Anti-inflammatory activity was studied by carrageenan-induced rat paw edema. Animals were divided into 3 groups pre-treated respectively with sterile saline, acetylsalicylic acid (AA) and ACAE. The antibacterial activity was tested against six bacteria and the antioxidant activity was estimated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and β-carotene activities. Our results demonstrated a significant improvement in wound healing progression and in oxidative stress damage in the wounds tissues of ACAE-treated rats, compared to control. ACAE-treated rats revealed also a significant inhibition of carrageenan-induced hind paws edema as confirmed by the histological analysis. In addition to the antioxidant activity, ACAE showed considerable antibacterial activities. ACAE exhibited important wound healing effect probably due to the anti-inflammatory, antibacterial and antioxidant activities of its phytochemical contents. Therefore, this study confirms its popular use and highlights its promise in the development of new drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Lumbar Facet Joint Compressive Injury Induces Lasting Changes in Local Structure, Nociceptive Scores, and Inflammatory Mediators in a Novel Rat Model

PubMed Central

Henry, James L.; Yashpal, Kiran; Vernon, Howard; Kim, Jaesung; Im, Hee-Jeong

2012-01-01

Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6) facet joint was exposed and compressed to ~1 mm with modified clamps applied for three minutes; sham-operated and naïve animals were used as control groups. After five days, animals were tested for hind-paw sensitivity using von Frey filaments and axial deep tissue sensitivity by algometer on assigned days up to 28 days. Animals were sacrificed at selected times for histological and biochemical analysis. Results. Histological sections revealed site-specific loss of cartilage in model animals only. Tactile hypersensitivity was observed for the ipsi- and contralateral paws lasting 28 days. The threshold at which deep tissue pressure just elicited vocalization was obtained at three lumbar levels; sensitivity at L1 > L3/4 > L6. Biochemical analyses revealed increases in proinflammatory cytokines, especially TNF-α, IL-1α, and IL-1β. Conclusions. These data suggest that compression of a facet joint induces a novel model of local cartilage loss accompanied by increased sensitivity to mechanical stimuli and by increases in inflammatory mediators. This new model may be useful for studies on mechanisms and treatment of lumbar facet joint pain and osteoarthritis. PMID:22966427

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

PubMed

Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

2017-11-01

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systemic study on the safety of immuno-deficient nude mice treated by atmospheric plasma-activated water

NASA Astrophysics Data System (ADS)

Dehui, XU; Qingjie, CUI; Yujing, XU; Bingchuan, WANG; Miao, TIAN; Qiaosong, LI; Zhijie, LIU; Dingxin, LIU; Hailan, CHEN; Michael, G. KONG

2018-04-01

Cold atmospheric-pressure plasma is a new technology, widely used in many fields of biomedicine, especially in cancer treatment. Cold plasma can selectively kill a variety of tumor cells, and its biological safety in clinical trials is also very important. In many cases, the patient’s immune level is relatively low, so we first studied the safety assessment of plasma treatment in an immuno-compromised animal model. In this study, we examined the safety of immuno-deficient nude mice by oral lavage treatment of plasma-activated water, and studied the growth status, main organs and blood biochemical indexes. Acute toxicity test results showed that the maximum dose of plasma treatment for 15 min had no lethal effect and other acute toxicity. There were no significant changes in body weight and survival status of mice after 2 min and 4 min of plasma-activated water (PAW) treatment for 2 weeks. After treatment, the major organs, including heart, liver, spleen, lung and kidney, were not significantly changed in organ coefficient and tissue structure. Blood biochemical markers showed that blood neutrophils and mononuclear cells were slightly increased, and the others remained unchanged. Liver function, renal function, electrolytes, glucose metabolism and lipid metabolism were not affected by different doses of PAW treatment. The above results indicate that PAW treatment can be used to treat immuno-deficient nude mice without significant safety problems.

Anti-Inflammatory Effect of Supercritical-Carbon Dioxide Fluid Extract from Flowers and Buds of Chrysanthemum indicum Linnén

PubMed Central

Li, Chu-Wen; Zhang, Xiao-Jun

2013-01-01

The aim of this study was to analyze the chemical composition and investigate the anti-inflammatory property of the supercritical-carbon dioxide extract from flowers and buds of C. indicum (CISCFE). The anti-inflammatory effect was evaluated in four animal models including xylene-induced mouse ear edema, acetic acid-induced mouse vascular permeability, carrageenan-induced mouse hind paw edema, and cotton pellet-induced rat granuloma formation. The results indicated that CISCFE significantly attenuated xylene-induced ear edema, decreased acetic acid-induced capillary permeability, reduced carrageenan-induced paw, and inhibited the cotton pellet-induced granuloma formation in a dose-dependent manner. Histopathologically, CISCFE abated inflammatory response of the edema paw. Preliminary mechanistic studies demonstrated that CISCFE decreased the MDA level via increasing the activities of anti-oxidant enzymes (SOD, GPx, and GRd), attenuated the productions of NF-κB, TNF-α, IL-1β, IL-6, PGE2 and NO, and suppressed the activities of iNOS and COX-2. In phytochemical study, 35 compounds were identified by GC-MS, and 5 compounds (chlorogenic acid, luteolin-7-glucoside, linarin, luteolin and acacetin) were reconfirmed and quantitatively determined by HPLC-PAD. This paper firstly analyzed the chemical composition by combining GC-MS with HPLC-PAD and explored possible mechanisms for the anti-inflammatory effect of CISCFE. PMID:24223056

Weight bearing of the limb as a confounding factor in assessment of mechanical allodynia in the rat.

PubMed

Kauppila, T; Kontinen, V K; Pertovaara, A

1998-01-01

Effect of weight bearing of the hindlimbs on the assessment of mechanically-induced hindlimb withdrawal threshold was determined in intact rats and in rats with various pathophysiological conditions causing allodynia or hyperalgesia. Hindlimb withdrawal was elicited by applying a series of calibrated monofilaments to the plantar or the dorsal surface of the paw. During testing the rat was either in a restraint tube with hindlimbs hanging semi-extended without weight bearing or it was standing on a metal grid (bearing its own weight). In intact rats, the withdrawal thresholds were significantly lower when the stimulus site was the dorsal hairy skin rather than the plantar glabrous skin. Also, thresholds were significantly lower when the hindlimbs were not bearing weight. Following carrageenan-induced unilateral inflammation of the plantar paw or a tibial nerve cut there was a marked threshold decrease to test stimuli applied to plantar or dorsal paw, respectively, ipsilateral to the pathological condition in standing rats. However, when the hindlimbs were not weight bearing the unilateral threshold decrease was markedly attenuated (carrageenan-treated rats) or completely abolished (tibial cut). In contrast, in rats with a unilateral spinal nerve ligation the threshold decrease ipsilateral to the nerve lesion was highly significant independent of the weight bearing of the hindlimbs. The results indicate that weight bearing of hindlimbs is an important confounding factor in the assessment of tactile allodynia in rats.

Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea.

PubMed

Passos, Giselle F; Fernandes, Elizabeth S; da Cunha, Fernanda M; Ferreira, Juliano; Pianowski, Luiz F; Campos, Maria M; Calixto, João B

2007-03-21

The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageenan, bradykinin, substance P, histamine and platelet-activating factor. It also prevented carrageenan-evoked exudation and the neutrophil influx to the rat pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches. Moreover, Cordia verbenacea oil inhibited the oedema caused by Apis mellifera venom or ovalbumin in sensitized rats and ovalbumin-evoked allergic pleurisy. The essential oil significantly decreased TNFalpha, without affecting IL-1beta production, in carrageenan-injected rat paws. Neither the PGE(2) formation after intrapleural injection of carrageenan nor the COX-1 or COX-2 activities in vitro were affected by the essential oil. Of high interest, the paw edema induced by carrageenan in mice was markedly inhibited by both sesquiterpenic compounds obtained from the essential oil: alpha-humulene and trans-caryophyllene (50mg/kg, p.o.). Collectively, the present results showed marked anti-inflammatory effects for the essential oil of Cordia verbenacea and some active compounds, probably by interfering with TNFalpha production. Cordia verbenacea essential oil or its constituents might represent new therapeutic options for the treatment of inflammatory diseases.

Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response

PubMed Central

Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Cassarotti, Larissa Laila; Salvadego, Valter Eduardo Cocco; Spironello, Ricardo Alexandre; Bersani-Amado, Ciomar Aparecida

2018-01-01

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 μg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine. PMID:29743918

Potential involvement of μ-opioid receptor dysregulation on the reduced antinociception of morphine in the inflammatory pain state in mice.

PubMed

Aoki, Yuta; Mizoguchi, Hirokazu; Watanabe, Chizuko; Takeda, Kumiko; Sakurada, Tsukasa; Sakurada, Shinobu

2014-01-01

The antinociceptive effect of morphine in the inflammatory pain state was described in the von Frey filament test using the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model. After an i.pl. injection of CFA, mechanical allodynia was observed in the ipsilateral paw. The antinociceptive effect of morphine injected s.c. and i.t. against mechanical allodynia was reduced bilaterally at 1 day and 4 days after the CFA pretreatment. The expression level of mRNA for μ-opioid receptors at 1 day after the CFA pretreatment was reduced bilaterally in the lumbar spinal cord and dorsal root ganglion (DRG). In contrast, the protein level of μ-opioid receptors at 1 day after CFA pretreatment was decreased in the ipsilateral side in the DRG but not the lumbar spinal cord. Single or repeated i.t. pretreatment with the protein kinase Cα (PKCα) inhibitor Ro-32-0432 completely restored the reduced morphine antinociception in the contralateral paw but only partially restored it in the ipsilateral paw in the inflammatory pain state. In conclusion, reduced morphine antinociception against mechanical allodynia in the inflammatory pain state is mainly mediated via a decrease in μ-opioid receptors in the ipsilateral side and via the desensitization of μ-opioid receptors in the contralateral side by PKCα-induced phosphorylation.

The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction.

PubMed

Nunes-Neto, Paulo Alexandre; Peixoto-Sobrinho, Tadeu José da Silva; da Silva Júnior, Edilson Dantas; Leopoldina da Silva, Jamilka; Rodrigo da Silva Oliveira, Alisson; Pupo, André Sampaio; Araújo, Alice Valença; da Costa-Silva, João Henrique; Wanderley, Almir Gonçalves

2017-01-01

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000  µ g/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500  µ g/mL) with hydroxyzine, an H 1 -antihistamine (0.125 and 0.250  µ M), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H 1 ).

The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction

PubMed Central

Nunes-Neto, Paulo Alexandre; da Silva Júnior, Edilson Dantas; Leopoldina da Silva, Jamilka; Rodrigo da Silva Oliveira, Alisson; Pupo, André Sampaio; Araújo, Alice Valença

2017-01-01

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000 µg/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500 µg/mL) with hydroxyzine, an H1-antihistamine (0.125 and 0.250 µM), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H1). PMID:28928787

α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2.

PubMed

Li, Xiao-Jun; Yang, Yan-Jing; Li, Yu-Sang; Zhang, Wei Kevin; Tang, He-Bin

2016-02-17

Frankincense oil and water extracts (FOE, FWE) have long been used for external treatment of inflammation and pain. The present study was conducted to identify the active ingredients responsible for the anti-inflammatory and analgesic effects and to determine the underlying mechanisms. The compositions of FOE and FWE were identified and compared by GC-MS. The anti-inflammatory and analgesic activities of the two extracts and their possible active ingredients (α-pinene, linalool, and 1-octanol) were evaluated and compared in a xylene-induced ear edema model and a formalin-inflamed hind paw model. Inflammatory infiltrates and cyclooxygenase-2 (COX-2) expression in hind paw skin were investigated by histological staining. The contents of α-pinene, linalool, and 1-octanol in FOE were much higher than those in FWE. Mice treated with FOE exhibited greater and faster lessening of swelling and pain than mice treated with FWE. The combination of the three components had more potent pharmacological effects on hind paw inflammation and COX-2 overexpression than the three components used alone. These findings suggest that topical application of FOE or its active ingredients (including α-pinene, linalool, and 1-octanol) exhibit significantly anti-inflammatory and analgesic effects through inhibiting nociceptive stimulus-induced inflammatory infiltrates and COX-2 overexpression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of physical activity measures used in middle-aged women.

PubMed

Pettee Gabriel, Kelley; McClain, James J; Lee, Chong D; Swan, Pamela D; Alvar, Brent A; Mitros, Melanie R; Ainsworth, Barbara E

2009-07-01

To evaluate the reliability and validity of five commonly used physical activity questionnaires (PAQ) in women aged 45-65 yr with varying physical activity (PA) levels. Data were obtained from the Evaluation of Physical Activity Measures in Middle-aged Women (PAW) Study and included 66 women (aged 52.6 +/- 5.4 yr). PAQ evaluated include Modifiable Activity Questionnaire (past week and past month version), Nurses' Health Study PAQ, Active Australia Survey, and Women's Health Initiative PAQ. Intraclass correlation coefficients (ICC) between administrations of the PAQ were used to assess test-retest reliability. Spearman rank-order correlation coefficients were used to examine the associations of PA and physical fitness data with PAQ summary estimates. Accelerometer-determined median (25th, 75th percentiles) times (min.d) spent in moderate-lifestyle [760-1951 counts (ct)], moderate-walk (1952-5724 ct), vigorous (> or =5725 ct), and combined moderate and vigorous PA (MVPA > or = 1952 ct) during the 35 d of observation were 66.0 (51.2, 81.3), 23.1 (14.1, 34.6), 0.4 (0.0, 2.3), and 24.3 (15.9, 41.6) min, respectively. The PAQ were shown to be reproducible and relatively stable over time (ICC = 0.32 to 0.91) and were associated with total counts per day (ct.d, 0.46 to 0.60, all P < 0.001), and most were associated with many facets of physical fitness, including cardiorespiratory fitness (0.36 to 0.46, P < 0.01), body composition (-0.27 to -0.34, P < 0.05), and muscular fatigue (-0.25 to -0.44, P < 0.05). The PAQ evaluated in this study were shown to be reliable and associated with PA and physical fitness measures. Current findings support the utility of these PAQ for PA assessment in research studies of middle-aged women.

Characterization of phenotypes of immune cells and cytokines associated with chronic exposure to Premolis semirufa caterpillar bristles extract.

PubMed

Villas-Boas, Isadora Maria; Gonçalves-de-Andrade, Rute Maria; Squaiella-Baptistão, Carla Cristina; Sant'Anna, Osvaldo Augusto; Tambourgi, Denise V

2013-01-01

The Brazilian moth Premolis semirufa (Walker, 1856), usually called pararama, is a parasite of the rubber Hevea genus. Contact with the bristles causes symptoms of acute inflammation. A chronic inflammatory reaction frequently occurs in individuals after multiple contacts, and this reaction is characterised by articular synovial membrane thickening with joint deformities, common characteristics of chronic synovitis. Extract from the bristles has been shown to induce an intense inflammatory response in a murine model, and this reaction was characterised by the presence of neutrophils in the paw tissues of injected mice and a strong, specific antibody response. There is not yet an effective treatment for incidents involving contact with pararama. In this study, we evaluated the phenotype of the immunological response and cytokine production in BALB/c mice subcutaneously injected in the footpad with P. semirufa bristle extract or sterile saline (control) seven times at 15 day intervals. An analysis of cells from the draining lymph node by flow cytometry showed that the absolute numbers of TCD4, TCD8 and B lymphocytes, as well as the expression of activation molecules, were higher in the extract-treated group. Furthermore, immunohistochemistry and immunofluorescence analyses showed a mixed inflammatory infiltrate composed of neutrophils and macrophages at the inoculation site. In addition, an analysis of paw cytokines showed elevated levels of IL-6, IL-12, IL-10, IL-17 and IL-23 after the 7(th) inoculation. In conclusion, these data provide evidence of pro-inflammatory changes in the phenotypes of immune cells and cytokine production in animals subjected to injections with an extract from Premolis semirufa bristles, which may explain the intense and prolonged inflammatory response that characterises this disorder.

The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice

PubMed Central

Shiota, N; Kovanen, PT; Eklund, KK; Shibata, N; Shimoura, K; Niibayashi, T; Shimbori, C; Okunishi, H

2010-01-01

Background and purpose: Recent findings suggest the importance of mast cells in the pathogenesis of rheumatoid arthritis and their potential as a therapeutic target. Tranilast is an anti-allergic compound with a potent membrane-stabilizing effect on mast cells and a wide range of anti-inflammatory effects, thus may be advantageous in the treatment of arthritis. Here, we have evaluated the effects of tranilast on the progression of collagen-induced arthritis in mice. Experimental approach: Tranilast (400 mg·kg−1·day−1) was orally administered for 8 weeks to mice with established collagen-induced arthritis. Arthritis was assessed by clinical signs and X-ray scores. In paw tissue, the numbers of mast cells and osteoclasts were measured by histological analysis, and several inflammatory factors were assessed by RT-PCR and Western blot analysis.* Key results: TNF-α-positive mast cells were present extensively throughout the inflamed synovium of vehicle-treated arthritic mice, with some mast cells in close proximity to osteoclasts in areas of marked bone and cartilage destruction. Tranilast significantly reduced clinical and X-ray scores of arthritis and decreased numbers of TNF-α-positive mast cells and mRNA levels of TNF-α, chymase (mouse mast cell protease 4), tryptase (mouse mast cell protease 6), stem cell factor, interleukin-6, cathepsin-K, receptor activator of nuclear factor-κB, and of receptor activator of nuclear factor-κB-ligand, but increased interleukin-10 mRNA level in paws of arthritic mice. Osteoclast numbers were decreased by treatment with tranilast. Conclusions and implications: Tranilast possesses significant anti-rheumatic efficacy and, probably, this therapeutic effect is partly mediated by inhibition of mast cell activation and osteoclastogenesis. PMID:20067475

Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

PubMed

Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-04-01

Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

Anti-inflammatory activities of Aller-7, a novel polyherbal formulation for allergic rhinitis.

PubMed

Pratibha, N; Saxena, V S; Amit, A; D'Souza, P; Bagchi, M; Bagchi, D

2004-01-01

Allergic rhinitis is an immunological disorder and an inflammatory response of nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs when the body overreacts to a substance such as pollens or dust. A novel, safe polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since inflammation is an integral mechanistic component of allergy, the present study aimed to determine the anti-inflammatory activity of Aller-7 in various in vivo models. The efficacy of Aller-7 was investigated in compound 48/80-induced paw edema both in Balb/c mice and Swiss Albino mice, carrageenan-induced paw edema in Wistar Albino rats and Freund's adjuvant-induced arthritis in Wistar Albino rats. The trypsin inhibitory activity of Aller-7 was also determined and compared with ovomucoid. At a dose of 250 mg/kg, Aller-7 demonstrated 62.55% inhibition against compound 48/80-induced paw edema in Balb/c mice, while under the same conditions prednisolone at an oral dose of 14 mg/kg exhibited 44.7% inhibition. Aller-7 significantly inhibited compound 48/80-induced paw edema at all three doses of 175, 225 or 275 mg/kg in Swiss Albino mice, while the most potent effect was observed at 225 mg/kg. Aller-7 (120 mg/kg, p.o.) demonstrated 31.3% inhibition against carrageenan-induced acute inflammation in Wistar Albino rats, while ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller-7 also exhibited a dose-dependent (150-350 mg/kg) anti-inflammatory effect against Freund's adjuvant-induced arthritis in Wistar Albino rats and an approximately 63% inhibitory effect was observed at a dose of 350 mg/kg. The trypsin inhibitory activity of Aller-7 was determined, using ovomucoid as a positive control. Ovomucoid and Aller-7 demonstrated IC50 concentrations at 1.5 and 9.0 microg/ml, respectively. These results demonstrate that this novel polyherbal formulation is a potent anti-inflammatory agent that can ameliorate the symptoms of allergic rhinitis.

Caloric Restriction and Formalin-Induced Inflammation: An Experimental Study in Rat Model

PubMed Central

Nozad, Aisan; Safari, Mir Bahram; Saboory, Ehsan; Derafshpoor, Leila; Mohseni Moghaddam, Parvaneh; Ghaffari, Farzaneh; Naseri, Mohsen

2015-01-01

Background: Acute and chronic inflammations are difficult to control. Using chemical anti-inflammatory medications along with their complications considerably limit their use. According to Traditional Iranian Medicine (TIM), there is an important relation between inflammation and Imtila (food and blood accumulation in the body); food reduction or its more modern equivalent Caloric Restriction (CR) may act against both Imtila and inflammation. Objectives: This experimental study aimed to investigate the effect of 30% reduction in daily calorie intake on inflammation in rats. Materials and Methods: A total of 18 male rats (Rattus rattus) weighing 220 to 270 g were obtained. Then, the inflammation was induced by injecting formalin in their paws. Next, the rats were randomized by generating random numbers into two equal groups (9 + 9) putting on either normal diet (controls) or a similar diet with 30% reduction of calorie (cases). Paw volume changes were recorded twice per day by one observer in both groups using a standard plethysmometer for 8 consecutive days. Serum C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), complete blood count (erythrocyte, platelet, and white blood cell) and hemoglobin were compared between the groups. Results: Decline of both body weight and paw volume was significantly more prominent in the case than in the control rats within the study period (P < 0.001 and < 0.001, respectively). Paw volume decrease was more prominent after day 3. On day 8, serum CRP-positive (1 or 2 +) rats were more frequent in ad libitum fed group comparing with those received CR (33.3% vs. 11.1%). This difference, however, was insignificant (P = 0.58). At the same time, mean ESR was significantly higher in the control rats comparing with that in the case group (29.00 ± 2.89 h vs. 14.00 ± 1.55 h; P = 0.001). Other serum parameters were not significantly different between the two groups at endpoint. Conclusions: Rats fed with a 30% calorie-restricted diet in comparison with to ad libitum fed controls for 8 days had significantly more prominent regression of inflammation. PMID:26421173

Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

PubMed Central

Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

2009-01-01

Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein synthesis. We hypothesise that mTOR may be activated by excitatory neurotransmitter release acting on sensory afferent terminals as well as dorsal horn spinal neurones, which may be further amplified by descending facilitatory systems originating from higher centres in the brain. PMID:19500426

Spatial Variability of Plant Available Water, Soil Organic Carbon, and Microbial Biomass under Divergent Land Uses: A Comparison among Regression-Kriging, Cokriging, and Regression-Cokriging

NASA Astrophysics Data System (ADS)

Kiani, M.; Hernandez Ramirez, G.; Quideau, S.

2016-12-01

Improved knowledge about the spatial variability of plant available water (PAW), soil organic carbon (SOC), and microbial biomass carbon (MBC) as affected by land-use systems can underpin the identification and inventory of beneficial ecosystem good and services in both agricultural and wild lands. Little research has been done that addresses the spatial patterns of PAW, SOC, and MBC under different land use types at a field scale. Therefore, we collected 56 soil samples (5-10 cm depth increment), using a nested cyclic sampling design within both a native grassland (NG) site and an irrigated cultivated (IC) site located near Brooks, Alberta. Using classical statistical and geostatistical methods, we characterized the spatial heterogeneities of PAW, SOC, and MBC under NG and IC using several geostatistical methods such as ordinary kriging (OK), regression-kriging (RK), cokriging (COK), and regression-cokriging (RCOK). Converting the native grassland to irrigated cultivated land altered soil pore distribution by reducing macroporosity which led to lower saturated water content and half hydraulic conductivity in IC compared to NG. This conversion also decreased the relative abundance of gram-negative bacteria, while increasing both the proportion of gram-positive bacteria and MBC concentration. At both studied sites, the best fitted spatial model was Gaussian based on lower RSS and higher R2 as criteria. The IC had stronger degree of spatial dependence and longer range of spatial auto-correlation revealing a homogenization of the spatial variability of soil properties as a result of intensive, recurrent agricultural activities. Comparison of OK, RK, COK, and RCOK approaches indicated that cokriging method had the best performance demonstrating a profound improvement in the accuracy of spatial estimations of PAW, SOC, and MBC. It seems that the combination of terrain covariates such as elevation and depth-to-water with kriging techniques offers more capability for incorporating explicit ancillary information in predictive soil mapping. Overall, identification of spatial patterns of soil properties in agricultural lands gives a bird's eye view to land owners to implement and improve management practices which lead to more sustainable production.

Evaluation of immunomodulatory activity of "Shirishavaleha"-An Ayurvedic compound formulation in albino rats.

PubMed

Yadav, Shyamlal Singh; Galib; Prajapati, P K; Ashok, B K; Ravishankar, B

2011-10-01

The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity.

Evaluation of immunomodulatory activity of “Shirishavaleha”–An Ayurvedic compound formulation in albino rats

PubMed Central

Yadav, Shyamlal Singh; Galib; Prajapati, P. K.; Ashok, B. K.; Ravishankar, B.

2011-01-01

The immunomodulatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth), i.e., Twak (Bark) and Sara (Heartwood) as main ingredients was evaluated for humoral antibody formation and cell-mediated immunity in established experimental models. The study used Wistar rats of either sex weighing 200 ± 40 g, while the test drug was administered orally at a dose of 1.8 g/kg. Hemagglutination titer and body weight were recorded to assess effects on humoral immunity; immunological paw edema was assessed for cell-mediated immunity. Shirishavaleha prepared from heartwood shows significant enhancement in antibody formation, attenuation of body weight changes, and suppression of immunological paw edema, while Shirishavaleha prepared from bark shows weak immunomodulatory activity. The study therefore concludes that Shirishavaleha prepared from heartwood has significant immunomodulatory activity. PMID:22253509

Analgesic, antipyretic, anti-inflammatory effects of methanol, chloroform and ether extracts of Vernonia cinerea less leaf.

PubMed

Iwalewa, E O; Iwalewa, O J; Adeboye, J O

2003-06-01

The chloroform, methanolic and ether extracts of Vernonia cinerea (Asteraceae; Less) leaf (100, 200 and 400mg/kg intraperitoneally) were tested in: acetic acid-induced writhing in mice, carrageenin-induced oedema and brewer's yeast-induced pyrexia in rats to assess their analgesic, anti-inflammatory, antipyretic and behavioral activities, respectively. The changes in writhings and behavioural activities in mice, the pyrexia and paw volumes in rats were reduced significantly (P<0.05) compared to the control. There was an increase in pain threshold on the oedematous right hind limb paw of the rats. These results indicate that the extracts could possess analgesic, antipyretic and anti-inflammatory properties. All these effects and the changes in the behavioural activities could be suggested as contributory effects to the use of V. cinerea leaf in the treatment of malaria.

[Motor asymmetry and learning new skills in animals].

PubMed

Budilin, S Iu; Pletneva, E V; Ioffe, M E; Arsen'ev, G N

2014-01-01

The aim was to examine the relationship between the ability to learn new motor skills and preference to the right or left front paw when performing manipulation movements in rats. As a new skill used the Morris water maze, in which the animals are initially trained to detect platform hidden under water at the swim of the sector of the opposite platform, and then when sailing from sectors on the left or the right of the platform. Preference paw was determined by using the taking of animal food from a narrow horizontal tube and, accordingly, the rats were divided into left-handedness and right-handedness. We found that when changing the place of launch, that is the first voyage from the left or right of the sector, are right-handed, unlike left-handed, spent significantly more time to find the platform.

Histopathology of Lyme arthritis in LSH hamsters

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

Hejka, A.; Schmitz, J.L.; England, D.M.

1989-05-01

The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding wasmore » destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.« less

A comparative study on the transdermal penetration effect of gaseous and aqueous plasma reactive species

NASA Astrophysics Data System (ADS)

Liu, Xin; Gan, Lu; Ma, Mingyu; Zhang, Song; Liu, Jingjing; Chen, Hongxiang; Liu, Dawei; Lu, Xinpei

2018-02-01

To improve the depth of plasma active species in the skin, it is very important to develop skin disease treatment using plasma. In this article, an air plasma source was used to work directly with the skin of a mouse. A tortuous pathway, hair follicles, electroporation and a microneedle do not aid the transdermal delivery of gaseous plasma active species, therefore these gaseous plasma active species cannot penetrate mouse skin with a thickness of ~0.75 mm. The plasma activated water (PAW) produced by the air plasma source was used to study the transdermal penetration of the aqueous plasma activated species. This aqueous plasma activated species can penetrate the skin through hair follicles, intercellular and transcellular routes. The pH of the PAW did not affect the penetration efficiency of the aqueous plasma active species.

The relation between open-field and emergence tests in a hyperactive mouse model.

PubMed

Lalonde, R; Strazielle, C

2009-12-01

The relation between open-field and emergence tests was examined in mice with idiopathic hypertension. Spontaneous hypertensive mice (SHM) crossed more segments and reared more often in the open-field than normotensive controls at both age levels. In contrast, grooming episodes decreased only in the older SHM cohort. While young SHM emerged more quickly from a toy object only partially, complete emergence was faster only in the older SHM cohort. In the entire series, open-field segments were inversely correlated with 2- and 4-paw emergence latencies. There was also an inverse correlation between rears and 2-paw emergence but a positive correlation between grooming episodes and both types of emergence. In view of its association with open-field activity, the emergence test may have value in screening potential ADHD therapies.

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.

Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents

PubMed Central

Matsumoto, Misaki; Xie, Weijiao; Inoue, Makoto; Ueda, Hiroshi

2007-01-01

Background We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized. Results Here, we show that choline acetyltransferase (ChAT) signals were localized not only in outer dorsal horn fibers (lamina I–III) and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW) test, the thresholds for stimulation through C-, Aδ- and Aβ-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS)-ODN in all of these nociception tests. Conclusion These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition. PMID:18088441

Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

PubMed

Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

2008-02-01

We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

Evaluation of antinociceptive and anti-inflammatory properties of methanolic crude extract of Lophopetalum javanicum (bark).

PubMed

Ansari, Prawej; Badhan, Sanjeeda Sarmin; Azam, Shofiul; Sultana, Nasrin; Anwar, Sabbir; Mohamed Abdurahman, Mohamed Sheikh; Hannan, J M A

2016-06-01

The aim of the current study was to investigate the scientific basis of the traditional application of Lophopetalum javanicum for measuring anti-inflammatory and analgesic activity and phytochemical screening. Present study includes the preliminary screening of the phytochemical composition and in vivo analgesic and anti-inflammatory activity of methanolic extract of L. javanicum (MELJ). Hot-plate test and tail immersion method were used to investigate acute analgesic effects of L. javanicum, and the potency in inhibition of chronic inflammation in mice was tested by carrageenan-induced paw edema and formalin-induced edema method. One hour after the administration of carrageenan, rat's paw was inflamed, and after treating it with 500 mg/kg dose, increase in the significant inhibitory effect on paw was observed. At the third hour after carrageenan injection, extreme inhibition (55.61%±0.015%; p<0.001) resulted by methanolic extract. By using hot plate method, it was found that L. javanicum increases pain tolerance time up to 17.89±0.079 min, whereas the compared standard's interval was 21.48±0.397 min. In tail immersion method, the pain threshold was 3.02±0.074 (p<0.001) at 400 mg/kg by L. javanicum at 90 min of experiment. This study manifested that the methanolic extract of L. javanicum is efficient in inhibiting pain mediators to release, and conceivably, this report should get priority while searching for a new analgesic and anti-inflammatory agent.

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.

Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.

PubMed

Sanada, Luciana Sayuri; Sato, Karina Laurenti; Machado, Nathalia Leilane Berto; Carmo, Elisabete de Cássia do; Sluka, Kathleen A; Fazan, Valeria Paula Sassoli

2014-06-01

We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a.

PubMed

Lohman, Rink-Jan; Hamidon, Johan K; Reid, Robert C; Rowley, Jessica A; Yau, Mei-Kwan; Halili, Maria A; Nielsen, Daniel S; Lim, Junxian; Wu, Kai-Chen; Loh, Zhixuan; Do, Anh; Suen, Jacky Y; Iyer, Abishek; Fairlie, David P

2017-08-24

Complement C3a is an important protein in innate and adaptive immunity, but its specific roles in vivo remain uncertain because C3a degrades rapidly to form the C3a-desArg protein, which does not bind to the C3a receptor and is indistinguishable from C3a using antibodies. Here we develop the most potent, stable and highly selective small molecule modulators of C3a receptor, using a heterocyclic hinge to switch between agonist and antagonist ligand conformations. This enables characterization of C3 areceptor-selective pro- vs. anti-inflammatory actions in human mast cells and macrophages, and in rats. A C3a receptor-selective agonist induces acute rat paw inflammation by first degranulating mast cells before activating macrophages and neutrophils. An orally administered C3a receptor-selective antagonist inhibits mast cell degranulation, thereby blocking recruitment and activation of macrophages and neutrophils, expression of inflammatory mediators and inflammation in a rat paw edema model. These novel tools reveal the mechanism of C3a-induced inflammation and provide new insights to complement-based medicines.Complement C3a is an important protein in innate and adaptive immunity, but its roles in vivo are unclear. Here the authors develop novel chemical agonists and antagonists for the C3a receptor, and show that they modulate mast cell degranulation and inflammation in a rat paw edema model.

Topical Anti-Inflammatory and Analgesic Effects of Multiple Applications of S(+)-Flurbiprofen Plaster (SFPP) in a Rat Adjuvant-Induced Arthritis Model.

PubMed

Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-06-01

Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)-flurbiprofen plaster (SFPP), a novel Nonsteroidal anti-inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)-1 and COX-2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti-inflammatory effects clinically. Drug Dev Res 77 : 206-211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Topical Anti‐Inflammatory and Analgesic Effects of Multiple Applications of S(+)‐Flurbiprofen Plaster (SFPP) in a Rat Adjuvant‐Induced Arthritis Model

PubMed Central

Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-01-01

Abstract Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)‐flurbiprofen plaster (SFPP), a novel Nonsteroidal anti‐inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant‐induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)−1 and COX‐2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti‐inflammatory effects clinically. Drug Dev Res 77 : 206–211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc. PMID:27241582

Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation.

PubMed

Impellizzeri, Daniela; Di Paola, Rosanna; Cordaro, Marika; Gugliandolo, Enrico; Casili, Giovanna; Morittu, Valeria Maria; Britti, Domenico; Esposito, Emanuela; Cuzzocrea, Salvatore

2016-11-01

The aim of study was to examine the anti-inflammatory and analgesic effects of adelmidrol, an analogue of palmitoylethanolamide (PEA), in animal models of acute and chronic inflammation [carrageenan-induced paw edema (CAR) and collagen-induced arthritis (CIA)]. In order to elucidate whether the action of adelmidrol is related to activation of peroxisome proliferator-activated receptors (PPAR-α or PPAR-γ), we investigated the effects of PPAR-γ antagonist, GW9662 on adelmidrol mechanism. CAR induced paw edema, hyperalgesia and the activation of pro-inflammatory NF-κB pathway were markedly reduced by treatment with adelmidrol. GW9662, (administered prior to adelmidrol treatment), antagonized the effect of adelmidrol abolishing its positive action. On the contrary, the genetic absence of PPAR-α receptor did not modify the beneficial results of adelmidrol treatment in the acute model of inflammation. In addition, for the first time, we demonstrated that adelmidrol was able to ameliorate both the clinical signs and the histopathology of the joint and the hind paw during chronic inflammation. In particular, the degree of oxidative damage and proinflammatory cytokines and chemokines production were significantly reduced in adelmidrol-treated mice. Moreover, in CIA model, the effect of GW9662 pre-treatment on adelmidrol mechanism was also confirmed. Thus, in this study, we report that adelmidrol reduces the development of acute and chronic inflammation and could represent a novel therapeutic approach for inflammation and pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Service learning: Priority 4 Paws mobile surgical service for shelter animals.

PubMed

Freeman, Lynetta J; Ferguson, Nancy; Litster, Annette; Arighi, Mimi

2013-01-01

The increasing attention given to competencies needed to enter the workforce has revealed a need for veterinary students to gain more experience in performing small-animal elective surgery before graduation. In addition, guidelines for standards of care for shelter animals recommend that all dogs and cats should be spayed or neutered before adoption. Teaching surgical skills while serving the needs of local animal shelters represents an ideal service-learning opportunity. Following a pilot study and the benchmarking of other programs, an elective course in shelter medicine and surgery was created at Purdue University College of Veterinary Medicine (PVM) to allow senior DVM students an opportunity to spend 2 weeks on a mobile surgery unit (Priority 4 Paws) and 1 week at an animal shelter. With financial assistance from sponsors and donors, PVM purchased and equipped a mobile surgery unit, hired a full-time veterinarian and a registered veterinary technician, and established relationships with 12 animal shelters. From July 30, 2012, to March 22, 2013, 1,941 spays and neuters were performed with excellent postsurgical outcomes while training 33 veterinary students on rotation and 26 veterinary technician students. The program was well accepted by both students and the shelters being served. The Priority 4 Paws program is an example of an integrated, community-based service-learning opportunity that not only helps to improve the surgical skills of veterinary students but also helps to meet an identified community need.

Analgesic, Anti- inflammatory, Anti- lipoxygenase Activity and Characterization of Three Bioactive Compounds in the Most Active Fraction of Leptadenia reticulata (Retz.)Wight & Arn. – A Valuable Medicinal Plant

PubMed Central

Mohanty, Sudipta Kumar; Swamy, Mallappa Kumara; Middha, Sushil Kumar; Prakash, Lokesh; Subbanarashiman, Balasubramanya; Maniyam, Anuradha

2015-01-01

Leptadenia reticulata was reported to be used for several medicinal purposes. The present study was undertaken to evaluate anti-inflammatory, analgesic and lipid peroxidation inhibition activities of L. reticulata. The anti-inflammatory assay was performed by λ-carrageenan and formalin induced paw edema test. Pro inflammatory mediators (IL2, IL6, TNF-α) in serum of treated and control organism were analyzed by quantitative ELISA. Lipid peroxidation inhibition was measured by thiobarbituric acid reactive substances (TBARS) assay. Analysis of the most active fraction revealed the presence of one phenolic compound (p-coumaric acid), two flavonoids (rutin and quercetin) which also determined quantitatively. The ethyl acetate fraction at 600 mg/Kg significantly inhibited λ-carrageenan and formalin induced paw edema by 60.59% and 59.24% respectively. Notable reduction in percentage of writhing (76.25%), induced by acetic acid signifies the potent analgesic activity. Lower level of pro-inflammatory cytokines (IL-2, IL-6, TNF-α) in serum at the 4th hour of λ-Carrageenan injection indicated the inhibition of cyclooxigenase-2 (Cox-2), Nitric oxide (NO) and release of prostaglandin to prevent inflammation. The study also demonstrated the decrease in malonaldehyde (MDA) concentration which revealed the lipid peroxidation inhibition potential of the plant. Our finding provides evidence for potent biological activities in tested model which is supported by its characterized bioactive compounds and ethnomedicinal relevance. PMID:26330883

Houttuynia cordata Thunb. volatile oil exhibited anti-inflammatory effects in vivo and inhibited nitric oxide and tumor necrosis factor-α production in LPS-stimulated mouse peritoneal macrophages in vitro.

PubMed

Li, Weifeng; Fan, Ting; Zhang, Yanmin; Fan, Te; Zhou, Ping; Niu, Xiaofeng; He, Langchong

2013-11-01

Houttuynia cordata Thunb. (HC) is a medicinal herb that generally used in traditional Chinese medicine for treating allergic inflammation. The present study investigated the inhibitory effect of the volatile oil from HC Thunb. on animal models of inflammation and the production of inflammatory mediators in vivo and in vitro. In vivo, xylene-induced mouse ear edema, formaldehyde-induced paw edema and carrageenan-induced mice paw edema were significantly decreased by HC volatile oil. HC volatile oil showed pronounced inhibition of prostaglandin (PG) E2 and malondialdehyde production in the edematous exudates. In vitro exposure of mouse resident peritoneal macrophages to 1, 10, 100 and 1000 µg/mL of HC volatile oil significantly suppressed lipopolysaccharide (LPS)-stimulated production of NO and tumor necrosis factor-α (TNF-α) in a dose-dependent manner. Exposure to HC volatile oil had no effect on cell viability and systemic toxicity. Furthermore, HC volatile oil inhibited the production of NO and TNF-α by down-regulating LPS-stimulated iNOS and TNF-α mRNA expression. Western blot analysis showed that HC volatile oil attenuated LPS-stimulated synthesis of iNOS and TNF-α protein in the macrophages, in parallel. These findings add a novel aspect to the biological profile of HC and clarify its anti-inflammatory mechanism. Copyright © 2012 John Wiley & Sons, Ltd.

Contributions of structural connectivity and cerebrovascular parameters to functional magnetic resonance imaging signals in mice at rest and during sensory paw stimulation.

PubMed

Schroeter, Aileen; Grandjean, Joanes; Schlegel, Felix; Saab, Bechara J; Rudin, Markus

2017-07-01

Previously, we reported widespread bilateral increases in stimulus-evoked functional magnetic resonance imaging signals in mouse brain to unilateral sensory paw stimulation. We attributed the pattern to arousal-related cardiovascular changes overruling cerebral autoregulation thereby masking specific signal changes elicited by local neuronal activity. To rule out the possibility that interhemispheric neuronal communication might contribute to bilateral functional magnetic resonance imaging responses, we compared stimulus-evoked functional magnetic resonance imaging responses to unilateral hindpaw stimulation in acallosal I/LnJ, C57BL/6, and BALB/c mice. We found bilateral blood-oxygenation-level dependent signal changes in all three strains, ruling out a dominant contribution of transcallosal communication as reason for bilaterality. Analysis of functional connectivity derived from resting-state functional magnetic resonance imaging, revealed that bilateral cortical functional connectivity is largely abolished in I/LnJ animals. Cortical functional connectivity in all strains correlated with structural connectivity in corpus callosum as revealed by diffusion tensor imaging. Given the profound influence of systemic hemodynamics on stimulus-evoked functional magnetic resonance imaging outcomes, we evaluated whether functional connectivity data might be affected by cerebrovascular parameters, i.e. baseline cerebral blood volume, vascular reactivity, and reserve. We found that effects of cerebral hemodynamics on functional connectivity are largely outweighed by dominating contributions of structural connectivity. In contrast, contributions of transcallosal interhemispheric communication to the occurrence of ipsilateral functional magnetic resonance imaging response of equal amplitude to unilateral stimuli seem negligible.

Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model.

PubMed

Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M

2017-08-01

OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor-engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats. CONCLUSIONS The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors' knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.

Geospatial variation of grapevine water status, soil water availability, grape composition and sensory characteristics in a spatially heterogeneous premium wine grape vineyard

NASA Astrophysics Data System (ADS)

Smart, D. R.; Cosby Hess, S.; Plant, R.; Feihn, O.; Heymann, H.; Ebeler, S.

2014-11-01

The geoscience component of terroir in wine grape production continues to be criticized for its quasi-mystical nature, and lack of testable hypotheses. Nonetheless, recent relational investigations are emerging and most involve water availability as captured by available water capacity (AWC, texture) or plant available water (PAW) in the root zone of soil as being a key factor. The second finding emerging may be that the degree of microscale variability in PAW and other soil factors at the vineyard scale renders larger regional characterizations questionable. Cimatic variables like temperature are well mixed, and its influence on wine characteristic is fairly well established. The influence of mesogeology on mesoclimate factors has also been characterized to some extent. To test the hypothesis that vine water status mirrors soil water availability, and controls fruit sensory and chemical properties at the vineyard scale we examined such variables in a iconic, selectively harvested premium winegrape vineyard in the Napa Valley of California during 2007 and 2008 growing seasons. Geo-referenced data vines remained as individual study units throughout data gathering and analysis. Cartographic exercises using geographic information systems (GIS) were used to vizualize geospatial variation in soil and vine properties. Highly significant correlations (P < 0.01) emerged for pre-dawn leaf water potential (ΨPD), mid-day leaf water potential (ΨL) and PAW, with berry size, berry weight, pruning weights (canopy size) and soluble solids content (°Brix). Areas yielding grapes with perceived higher quality had vines with (1) lower leaf water potential (LWP) both pre-dawn and mid-day, (2) smaller berry diameter and weight, (3) lower pruning weights, and (4) higher °Brix. A trained sensory panel found grapes from the more water-stressed vines had significantly sweeter and softer pulp, absence of vegetal character, and browner and crunchier seeds. Metabolomic analysis of the grape skins showed significant differences in accumulation of amino acids and organic acids. Data vines were categorized as non-stressed (ΨPD ≥ -7.9 bars and ΨL ≥ -14.9 bars) and stressed (ΨPD ≤ -8.0 bars and ΨL ≤ -15.0 bars) and subjected to analysis of variance. Significant separation emerged for vines categorized as non-stressed versus stressed at véraison, which correlated to the areas described as producing higher and lower quality fruit. This report does not advocate the use of stress levels herein reported. The vineyard was planted to a vigorous, deep rooted rootstock (V. rupestris cv. St. George), and from years of management is known to be able to withstand stress levels of the magnitude we observed. Nonetheless, the results may suggest there is not a linear relationship between physiological water stress and grape sensory characteristics, but rather the presence of an inflection point controlling grape composition as well as physiological development.

Statistically designed nonionic surfactant vesicles for dermal delivery of itraconazole: characterization and in vivo evaluation using a standardized Tinea pedis infection model.

PubMed

Kumar, Neeraj; Goindi, Shishu

2014-09-10

The study aims to statistically develop a hydrogel of itraconazole loaded nonionic surfactant vesicles (NSVs) for circumventing the shortcomings and adverse effects of currently used therapies. Influential factors were screened using first-order Taguchi design, thereafter, optimization was performed via D-optimal design involving screened factors (surfactant type, content and molar ratio of cholesterol: surfactant). Response variables investigated were percent drug entrapment, vesicle size, drug skin retention and permeation in 6h. Suspensions of NSVs were gelled to improve topical applicability. Characterization of formulations was performed using vesicle shape, size, surface charge, texture analysis and rheology behavior. Ex vivo studies in rat skin depicted that optimized formulation augmented drug skin retention and permeation in 6h than conventional cream and oily solution of itraconazole. Standardized Tinea pedis model in Wistar rats exhibited in vivo antifungal efficacy of optimized formulation, observed in terms of physical manifestations, fungal-burden score and histopathological profiles. Also, a unique investigation involving studying local oxidative stress of infected paw skins as an indicator of fungal infection was performed. Rapid alleviation of infection in animals treated with optimized hydrogel was observed in comparison to commonly prescribed therapies. Therefore, the optimized NSVs may be a promising and efficient alternative to available antifungal therapies. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-inflammatory Activity of Berry Fruits in Mice Model of Inflammation is Based on Oxidative Stress Modulation

PubMed Central

Nardi, Geisson Marcos; Farias Januario, Adriana Graziele; Freire, Cassio Geremia; Megiolaro, Fernanda; Schneider, Kétlin; Perazzoli, Marlene Raimunda Andreola; Do Nascimento, Scheley Raap; Gon, Ana Cristina; Mariano, Luísa Nathália Bolda; Wagner, Glauber; Niero, Rivaldo; Locatelli, Claudriana

2016-01-01

Background: Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. Objective: The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). Materials and Methods: Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by high-performance liquid chromatography. Antioxidant activity was determine by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reducing power, lipid peroxidation thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and catalase (CAT) activity. Anti-inflammatory activity was evaluated by paw edema followed by determination of myeloperoxidase (MPO) and TBARS. Results: High amount of phenolic compounds, including rutin, were identified in all berries extracts. However, quercetin was observed only in BLUE and CRAN. GOJI presents higher scavenging activity of DPPH radical and reducing power than BLUE and CRAN. The extracts improved antioxidant status in liver; BLUE showed the largest reduction (75.3%) in TBARS when compared to CRAN (70.7%) and GOJI (65.3%). Nonetheless, CAT activity was lower in BLUE group. However, hepatic concentrations of GSH were higher in animals treated with GOJI rather than CRAN and BLUE. Despite all fruits caused a remarkable reduction in paw edema and TBARS, only BLUE and CRAN were able to reduce MPO. Conclusion: These results suggest that quercetin, rutin, or other phenolic compound found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress in paw edema model. SUMMARY Within fruits broadly consumed because of its nutraceuticals properties include, Lycium barbarum (Goji berry), Vaccinium myrtillus (Blueberry or Bilberry) and Vaccinium macrocarpon (Cranberry)The objectives of this study were the investigation and comparison of chemical composition, antioxidant activity “in vitro” and “in vivo” and anti inflammatory property of berry fruits bought dry form.In summary, two main findings can be addressed with this study: (1) Berry fruits presented antioxidant and anti inflammatory activities “in vitro” and “in vivo”; (2) the extracts of GOJI, CRAN, and BLUE modulate the inflammatory process by different mechanisms. PMID:27114691

Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats.

PubMed

Doss, Hari Madhuri; Dey, Chandrima; Sudandiradoss, C; Rasool, Mahaboob Khan

2016-03-01

The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug. Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1. In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-κB, PYCARD/ASC, and NLRP3. Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Aqueous ethanol extract of the fruit of Xylopia aethiopica (Annonaceae) exhibits anti-anaphylactic and anti-inflammatory actions in mice.

PubMed

Obiri, David D; Osafo, Newman

2013-07-30

Xylopia aethiopica has been traditionally used in the form of the dried fruit decoction to treat bronchitis, asthma, arthritis and rheumatism in Ghana, Nigeria and Cameroon. Aim of the study is to evaluate the anti-anaphylactic and anti-inflammatory effects of a 70% aqueous ethanol extract of the fruits of Xylopia aethiopica. Systemic anaphylaxis was induced by the injection of either compound 48/80 or lipopolysaccharide, LPS and survival rates of mice monitored for 1 h or 7 days respectively while IgE-mediated anaphylaxis in a local allergic reaction was studied in the pinnal inflammation model in mice. Clonidine-induced catalepsy in mice was used to evaluate the indirect antihistamine effect of Xylopia aethiopica, XAE. The effects of XAE assessed on the maximal and total oedema responses in the carrageenan-induced paw oedema in mice was used to evaluate the anti-inflammatory action of the extract. Administered at 30, 100, 300 and 1000 mg kg(-1) p.o., XAE dose dependently suppressed compound 48/80-induced mouse systemic anaphylactic shock and offered 63% protection to mice against LPS-induced endotoxic shock at a dose of 300 mg kg(-1). In addition, the extract (30-300 mg kg(-1)) in a dose dependent manner significantly inhibited by 23-62% the mouse pinnal inflammation. Clonidine-induced catalepsy in mice was significantly suppressed in a dose and time dependent manner when administered both prophylactically and therapeutically. In the same doses, when administered before the induction of the mouse carrageenan-induced paw oedema, the mean maximal swelling attained during 6 h was reduced to 41.02±6.94%, 35.61±4.30%, and 29.09±4.90% of the inflamed control response respectively and total paw swellings induced over the 6 h were also dose-dependently and significantly suppressed to 74.84±14.84%, 63.95±9.37%, and 48.13±10.90% of the inflamed control response respectively. Administered after the induction of the carrageenan paw oedema the mean maximal swelling attained during 6 h was suppressed to 49.84±3.95%, 43.62±1.01%, and 35.97±1.34% of the inflamed control response respectively while the total paw swellings induced over the 6 h were also dose-dependently and significantly suppressed at 100 and 300 mg kg(-1) to 72.39±4.38% and 60.81±3.25% of the inflamed control response respectively. These findings suggest that XAE inhibits mast cell-dependent immediate allergic reactions and exhibit anti-inflammatory actions through the inhibition of histamine release from mast cells via stabilizing the cell membrane. Our results contribute towards validation of the traditional use of Xylopia aethiopica in the treatment of bronchitis, asthma, arthritis and rheumatism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Workplace health promotion: a meta-analysis of effectiveness.

PubMed

Rongen, Anne; Robroek, Suzan J W; van Lenthe, Frank J; Burdorf, Alex

2013-04-01

An unhealthy lifestyle may contribute to ill health, absence due to sickness, productivity loss at work, and reduced ability to work. Workplace health promotion programs (WHPPs) aim to improve lifestyle and consequently improve health, work ability, and work productivity. However, systematic reviews on intervention studies have reported small effects, and the overall evaluation of effectiveness of WHPPs is hampered by a large heterogeneity in interventions and study populations. This systematic review aims to investigate the influence of population, study and intervention characteristics, and study quality on the effectiveness of workplace health promotion programs. A systematic literature search was conducted identifying RCTs, published before June 2012, evaluating the effect of a WHPP aimed at smoking cessation, physical activity, healthy nutrition, and/or obesity on self-perceived health, work absence due to sickness, work productivity, or work ability. Studies were included in the meta-analyses if quantitative information was present to calculate an effect size (ES). A meta-analysis, stratified meta-analyses, and meta-regression analyses were performed in Spring 2012 using Comprehensive Meta-analysis software 2.0 and PAWS 17.0.2. In 18 studies describing 21 interventions, the overall effect of a WHPP was small (ES=0.24, 95% CI=0.14, 0.34). The effectiveness of a WHPP was larger in younger populations, in interventions with weekly contacts, and in studies in which the control group received no health promotion. A 2.6-fold lower effectiveness was observed for studies performing an intention-to-treat analysis and a 1.7-fold lower effectiveness for studies controlling for confounders. Studies of poor methodologic quality reported a 2.9-fold higher effect size of the WHPP. The effectiveness of a WHPP is partly determined by intervention characteristics and statistical analysis. High-quality RCTs reported lower effect sizes. It is important to determine the effectiveness of WHPPs in RCTs of high quality. Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

76 FR 3153 - Endangered and Threatened Wildlife and Plants; Permit Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

... (Epioblasma torulosa rangiana), Orange-footed pimpleback pearlymussel (Plethobasus cooperianus), Pink mucket...'s paw pearlymussel, Fanshell (Cyprogenia stegaria), Fat pocketbook (Potamilus capax), Higgins' eye...: Clubshell, Northern riffleshell, Orange-footed pimpleback pearlymussel, Pink mucket pearlymussel, Rough...

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

PubMed Central

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

2013-01-01

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

Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

PubMed

González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

2017-07-04

Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

Laterality and performance of agility-trained dogs.

PubMed

Siniscalchi, Marcello; Bertino, Daniele; Quaranta, Angelo

2014-01-01

Correlations between lateralised behaviour and performance were investigated in 19 agility-trained dogs (Canis familiaris) by scoring paw preference to hold a food object and relating it to performance during typical agility obstacles (jump/A-frame and weave poles). In addition, because recent behavioural studies reported that visual stimuli of emotional valence presented to one visual hemifield at a time affect visually guided motor responses in dogs, the possibility that the position of the owner respectively in the left and in the right canine visual hemifield might be associated with quality of performance during agility was considered. Dogs' temperament was also measured by an owner-rated questionnaire. The most relevant finding was that agility-trained dogs displayed longer latencies to complete the obstacles with the owner located in their left visual hemifield compared to the right. Interestingly, the results showed that this phenomenon was significantly linked to both dogs' trainability and the strength of paw preference.

Evaluation of in vivo and in vitro biological activities of different extracts of Cuscuta arvensis.

PubMed

Koca, Ufuk; Küpeli-Akkol, Esra; Sekeroglu, Nazim

2011-10-01

In the present study, the potential effects of extracts from the whole plant of Cuscuta arvensis were studied in mice using the carrageenan-induced hind paw edema model for antiinflammatory activity and the p-benzoquinone-induced writhing reflex for the assessment of antinociceptive activity. In order to obtain the extracts, the whole plant of C. arvensis was extracted with different solvents such as n-hexane, dichloromethane, ethyl acetate, methanol and distilled water. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The methanolic and water extracts inhibited the carrageenan-induced paw edema and p-benzoquinone-induced writhing reflex, whereas the other extracts showed only mild inhibitory antinociceptive and antiinflammatory activities in these in vivo models. Additionally, the methanol and ethyl acetate extracts had higher scavenging ability then the non polar extracts.

Crocin reduces the inflammation response in rheumatoid arthritis.

PubMed

Li, Xiang; Jiang, Chao; Zhu, Wenyong

2017-05-01

This study is to determine the role and mechanism of crocin in rheumatoid arthritis (RA). Totally 60 Wistar SD rats were randomly divided into control group, RA model group, methotrexate group, crocin high dose, middle dose, and low dose groups. The paw swelling degree, arthritis score, thymus and spleen index, the mRNA and protein levels of iNOS, and the serum content of TNF-α, IL-1β, and IL-6 were evaluated. Crocin treatment significantly alleviated the paw swelling of RA rats. The arthritis score in crocin treatment groups was significantly lower than that in RA model group. Additionally, the thymus index, but not the spleen index, declined remarkably in crocin treatment groups than in RA model group. Besides, crocin administration significantly reduced the iNOS production and the serum content of TNF-α, IL-1β, and IL-6. Crocin may exert potent anti-RA effects through inhibiting cytokine.

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

Mattsson, Ann E.

Density Functional Theory (DFT) based Equation of State (EOS) construction is a prominent part of Sandia’s capabilities to support engineering sciences. This capability is based on augmenting experimental data with information gained from computational investigations, especially in those parts of the phase space where experimental data is hard, dangerous, or expensive to obtain. A key part of the success of the Sandia approach is the fundamental science work supporting the computational capability. Not only does this work enhance the capability to perform highly accurate calculations but it also provides crucial insight into the limitations of the computational tools, providing highmore » confidence in the results even where results cannot be, or have not yet been, validated by experimental data. This report concerns the key ingredient of projector augmented-wave (PAW) potentials for use in pseudo-potential computational codes. Using the tools discussed in SAND2012-7389 we assess the standard Vienna Ab-initio Simulation Package (VASP) PAWs for Molybdenum.« less

Anti-inflammatory activities of ethanolic extract of Carica papaya leaves.

PubMed

Owoyele, Bamidele V; Adebukola, Olubori M; Funmilayo, Adeoye A; Soladoye, Ayodele O

2008-08-01

The anti-inflammatory activity of an ethanolic extract of Carica papaya leaves was investigated in rats using carrageenan induced paw oedema, cotton pellet granuloma and formaldehyde induced arthritis models. Experimental animals received 25-200 mg/Kg (orally) of the extracts or saline (control group) and the reference group received 5 mg/ Kg of indomethacin. The ulcerogenic activity of the extract was also investigated. The results show that the extracts significantly (p <0.05) reduced paw oedema in the carrageenan test. Likewise the extract produced significant reduction in the amount of granuloma formed from 0.58 +/-0.07 to 0.22 +/-0.03 g. In the formaldehyde arthritis model, the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves.

Owners' direct gazes increase dogs' attention-getting behaviors.

PubMed

Ohkita, Midori; Nagasawa, Miho; Kazutaka, Mogi; Kikusui, Takefumi

2016-04-01

This study examined whether dogs gain information about human's attention via their gazes and whether they change their attention-getting behaviors (i.e., whining and whimpering, looking at their owners' faces, pawing, and approaching their owners) in response to their owners' direct gazes. The results showed that when the owners gazed at their dogs, the durations of whining and whimpering and looking at the owners' faces were longer than when the owners averted their gazes. In contrast, there were no differences in duration of pawing and likelihood of approaching the owners between the direct and averted gaze conditions. Therefore, owners' direct gazes increased the behaviors that acted as distant signals and did not necessarily involve touching the owners. We suggest that dogs are sensitive to human gazes, and this sensitivity may act as attachment signals to humans, and may contribute to close relationships between humans and dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-inflammatory effects of aqueous extract of Mangifera indica in Wistar rats.

PubMed

Oluwole, Oluwafemi Gabriel; Esume, Celestine

2015-05-01

Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract (Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound. This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation. Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours. The aqueous extract of MI (50-200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.). The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.

Modulation between high- and low-frequency transcutaneous electric nerve stimulation delays the development of analgesic tolerance in arthritic rats.

PubMed

Desantana, Josimari M; Santana-Filho, Valter J; Sluka, Kathleen A

2008-04-01

To investigate whether repeated administration of modulating frequency transcutaneous electric nerve stimulation (TENS) prevents development of analgesic tolerance. Knee joint inflammation (3% carrageenan and kaolin) was induced in rats. Either mixed or alternating frequency was administered daily (20min) for 2 weeks to the inflamed knee under light halothane anesthesia (1%-2%). Laboratory. Adult male Sprague-Dawley rats (N=36). Mixed- (4Hz and 100Hz) or alternating- (4Hz on 1 day; 100Hz on the next day) frequency TENS at sensory intensity and 100micros pulse duration. Paw and joint withdrawal thresholds to mechanical stimuli were assessed before induction of inflammation, and before and after daily application of TENS. The reduced paw and joint withdrawal thresholds that occur 24 hours after the induction of inflammation were significantly reversed by the first administration of TENS when compared with sham treatment or to the condition before TENS treatment, which was observed through day 9. By the tenth day, repeated daily administration of either mixed- or alternating-frequency TENS did not reverse the decreased paw and joint withdrawal thresholds. These data suggest that repeated administration of modulating frequency TENS leads to a development of opioid tolerance. However, this tolerance effect is delayed by approximately 5 days compared with administration of low- or high-frequency TENS independently. Clinically, we can infer that a treatment schedule of repeated daily TENS administration will result in a tolerance effect. Moreover, modulating low and high frequency TENS seems to produce a better analgesic effect and tolerance is slower to develop.

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.

PubMed

de Almeida, Antonia Amanda Cardoso; Silva, Renan Oliveira; Nicolau, Lucas Antonio Duarte; de Brito, Tarcísio Vieira; de Sousa, Damião Pergentino; Barbosa, André Luiz Dos Reis; de Freitas, Rivelilson Mendes; Lopes, Luciano da Silva; Medeiros, Jand-Venes Rolim; Ferreira, Paulo Michel Pinheiro

2017-04-01

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E 2 , and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1β levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.

Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

PubMed Central

Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

2012-01-01

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

Potentiation of the antiinflammatory effect of Anacardium occidentale (Linn.) stem-bark aqueous extract by grapefruit juice.

PubMed

Ojewole, J A O

2004-04-01

In an attempt to scientifically appraise some of the ethnomedical uses of Anacardium occidentale Linn. (family: Anacardiaceae), the present study was undertaken to examine the antiinflammatory effect of the plant's stem-bark aqueous extract in rats. Young adult male Wistar rats weighing 250-300 g were used. The antiinflammatory effect of A. occidentale stem-bark aqueous extract alone and in combination with grapefruit (Citrus paradisi Macf.) juice was investigated on fresh egg albumin-induced rat paw edema. Like diclofenac (100 mg/kg p.o.), aqueous extract of A. occidentale stem-bark (800 mg/kg p.o.) produced time-related, sustained and significant reduction (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw. However, the antiinflammatory effect of the plant extract was found to be approximately 8-15 times less than that of diclofenac. Coadministration of grapefruit juice (5 ml/kg p.o.) with A. occidentale stem-bark aqueous extract (800 mg/kg p.o.) or diclofenac (100 mg/kg p.o.) significantly potentiated (p < 0.05-0.001) the antiinflammatory effects of the crude plant extract and diclofenac on fresh egg albumin-induced rat paw edema. Although A. occidentale stem-bark aqueous extract is less potent than diclofenac as an antiinflammatory agent, the results of this experimental animal study indicate that the plant extract possesses antiinflammatory activity, and thus lend pharmacological support to the folkloric use of the plant in the management and/or control of arthritis and other inflammatory conditions among the Yoruba-speaking people of western Nigeria.

Weight bearing evaluation in inflammatory, neuropathic and cancer chronic pain in freely moving rats.

PubMed

Tétreault, Pascal; Dansereau, Marc-André; Doré-Savard, Louis; Beaudet, Nicolas; Sarret, Philippe

2011-09-01

Preclinical pain assessment remains a key step for the development of new and potent painkillers. Significant progress in pain evaluation has been achieved with the development of non-reflexive tools. Seeking efficient and clinically relevant devices for pain-related quality of life assessment, we evaluated a new Dynamic Weight Bearing (DWB) device based on pressure captors in three different preclinical chronic pain models. Inflammatory (CFA), neuropathic (CCI) and bone cancer pain (femoral tumor) models were evaluated in Sprague Dawley rats for mechanical allodynia using dynamic von Frey for pain-related behaviors and DWB for discomfort. We observed similar impairment patterns in all of the models for both von Frey (allodynia) and DWB (weight balance) during the complete observation period, starting at day 3 in CCI- and CFA-affected limbs and at day 14 in bone cancer-afflicted rats, indicating that the DWB could be a useful tool for supporting pain assessment. Interestingly, we demonstrated that the main compensation, when animals experienced pain, was seen in the forepaws, ranging from 46% to 69% of increased load compared to normal. Other pain-related coping behaviors were also measured, such as the time spent on each paw and the contact surface. Our results revealed that CFA, CCI and cancerous rats decreased the use of their ipsilateral hind paws by 30% and showed a 50% reduction in paw surface pressed against the floor. In conclusion, this new device improves methods for preclinical evaluation of discomfort and quality of life proxies and could be helpful in screening putative analgesics. Copyright © 2011 Elsevier Inc. All rights reserved.

Recruiting American Indian/Alaska Native Students to Medical School: A Multi-Institutional Alliance in the U.S. Southwest.

PubMed

Ballejos, Marlene P; Olsen, Polly; Price-Johnson, Tanisha; Garcia, Cindy; Parker, Tassy; Sapién, Robert E; Romero-Leggott, Valerie

2018-01-01

Despite national efforts to diversify the physician workforce, American Indian/Alaska Native (AI/AN) individuals have the least representation of all major racial and ethnic groups. Limited resources at state medical schools present institution-level recruitment challenges. Unified efforts to engage AI/AN students in premedical education activities are needed. The medical schools at the Universities of Arizona (Phoenix and Tucson), Colorado, New Mexico, and Utah identified a collective need to increase student diversity, particularly with regard to AI/AN students. The schools partnered with the Association of American Indian Physicians to support AI/AN students applying to medical school and to grow the overall AI/AN applicant pool. Each year from 2011 to 2016, these institutions hosted a two-day preadmissions workshop (PAW) to prepare participants for applying to medical school. From 2011 to 2016, 130 AI/AN students participated in the PAWs. Of these, 113 were first-time attendees, 15 participated on two separate occasions, and 1 participated on three separate occasions. Nineteen (21%) of the 90 first-time participants from 2011 to 2015 matriculated to a U.S. medical school in the past five years. Twenty-two of 23 participants (96% response rate) in 2016 responded to the postworkshop survey. Results indicated that interview preparation, individual consultation, and writing preparation ranked as the three most beneficial sessions/activities. Standardized evaluation of future PAWs will identify best practices for recruiting AI/AN students to medical school, and future initiatives will include more robust measures of success.

Effect of a cocoa flavonoid-enriched diet on experimental autoimmune arthritis.

PubMed

Ramos-Romero, Sara; Pérez-Cano, Francisco J; Pérez-Berezo, Teresa; Castellote, Cristina; Franch, Angels; Castell, Margarida

2012-02-01

Previously we established that a cocoa-enriched diet in young rats reduces specific antibody production and the T helper (Th) lymphocyte proportion in lymphoid tissues. The aim of the present study was to ascertain the modulatory ability of a cocoa flavonoid-enriched diet on collagen-induced arthritis (CIA), which is mediated by anti-collagen autoantibody response and Th lymphocyte activation. Female Louvain (LOU) rats were fed with a cocoa-enriched diet, beginning 2 weeks before CIA induction. Hind-paw swelling and serum cytokine and anti-collagen antibody concentrations were determined. Anti-collagen antibody-secreting cell counts and lymphocyte subset proportions were established in inguinal lymph nodes (ILN). Reactive oxygen species (ROS), nitric oxide (NO) and TNFα produced by peritoneal macrophages were determined. Although arthritic cocoa-fed rats showed a similar hind-paw swelling time course as the arthritic animals fed a standard diet, the cocoa intake was able to decrease specific IgG2a, IgG2b and IgG2c titres. Moreover, cocoa intake in CIA rats reduced ROS production, TNFα and NO release from peritoneal macrophages, and decreased the Th:cytotoxic T cell ratio in ILN. In conclusion, a cocoa flavonoid-enriched diet in LOU rats with CIA produced no effect on hind-paw swelling but was able to modulate the specific antibody response and also the Th lymphocyte proportion, as well as the synthesis of pro-inflammatory mediators from peritoneal macrophages. Therefore, a cocoa-enriched diet could be a good adjuvant therapy in disorders with oxidative stress or autoimmune pathogenesis.

Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl.

PubMed

Boonyarikpunchai, Wanvisa; Sukrong, Suchada; Towiwat, Pasarapa

2014-09-01

Rosmarinic acid (RA) was isolated from an ethanolic extract of Thunbergia laurifolia leaves. The antinociceptive activity of RA was assessed in mice using hot-plate, acetic acid-induced writhing, and formalin tests. The anti-inflammatory effects of RA were determined in two mouse models of carrageenan-induced paw edema and cotton pellet-induced granuloma formation. Orally administered RA (50, 100, and 150 mg/kg) showed significant (p<0.001) antinociceptive activity in the hot-plate test and this effect was reversed by naloxone. RA at doses of 50 and 100mg/kg significantly reduced acetic acid-induced writhing by 52% (p<0.01) and 85% (p<0.001), respectively, and RA at 100mg/kg also caused significant inhibition of formalin-induced pain in the early and late phases (p<0.01 and p<0.001, respectively). RA at 100mg/kg significantly suppressed carrageenan-induced paw edema at 3, 4, 5 and 6h after carrageenan injection (p<0.01, p<0.05 p<0.01, and p<0.05, respectively) and showed significant activity against PGE2-induced paw edema. RA at 100mg/kg also inhibited cotton pellet-induced granuloma formation in mice. Taken together, these results demonstrate that RA possesses both central and peripheral antinociceptive activities and has anti-inflammatory effects against acute and chronic inflammation. While further evaluation regarding the safety profile of RA is needed, these data may provide a basis for the rational use of RA and T. laurifolia for treatment of pain and inflammatory disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Intrathecal P/Q- and R-type calcium channel blockades on spinal substance P release and c-Fos expression

PubMed Central

Terashima, Tetsuji; Xu, Qinghao; Yamaguchi, Shigeki; Yaksh, Tony L.

2013-01-01

Intrathecal (IT) studies have shown that several voltage sensitive calcium channels (VSCCs), such as the L-, N- and T-type may play roles in nociception and that of these only the N-type regulates primary afferent substance P (SP) release. However, the actions of other VSCCs at the spinal level are not well known. We investigated the roles of spinal P/Q- and R-type VSCCs, by IT administration of R-type (SNX-482) and P/Q-type (ω-agatoxin IVA) VSCC blockers on intraplantar formalin-evoked flinching, SP release from primary afferents and c-Fos expression in spinal dorsal horn. Intraplantar injection of formalin (2.5%, 50 µL) produced an intense, characteristic biphasic paw flinching response. In rats with IT catheters, IT SNX-482 (0.5 µg) reduced formalin-evoked paw flinching in both phase 1 and 2 compared with vehicle. Intraplantar formalin caused robust neurokinin 1 receptor (NK1r) internalization (indicating SP release) and c-Fos expression in the ipsilateral dorsal horn, which were blocked by IT SNX-482. IT ω-agatoxin IVA (0.03, 0.125 and 0.5 µg) did not reduce formalin-evoked paw flinching or c-Fos expression at any doses, with higher doses resulting in motor dysfunction. Thus, we demonstrated that blockade of spinal R-type, but not P/Q type VSCCs attenuated formalin-induced pain behavior, NK1r internalization and c-Fos expression in the superficial dorsal horn. This study supports a role for Cav2.3 in presynaptic neurotransmitter release from peptidergic nociceptive afferents and pain behaviors. PMID:23810829

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

Age-Related Differences in Collagen-Induced Arthritis: Clinical and Imaging Correlations

PubMed Central

Wilson-Gerwing, Tracy D; Pratt, Isaac V; Cooper, David M L; Silver, Tawni I; Rosenberg, Alan M

2013-01-01

Arthritis is among the most common chronic diseases in both children and adults. Although intraarticular inflammation is the feature common among all patients with chronic arthritis there are, in addition to age at onset, clinical characteristics that further distinguish the disease in pediatric and adult populations. In this study, we aimed to demonstrate the utility of microCT (µCT) and ultrasonography in characterizing pathologic age-related differences in a collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult (91 d old) male Wistar rats were immunized with bovine type II collagen and incomplete Freund adjuvant to induce polyarthritis. Naïve male Wistar rats served as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws imaged by µCT and ultrasonography. Young adult rats had more severe signs of arthritis than did their juvenile counterparts. Imaging demonstrated that young adult CIA rats exhibited more widespread and severe skeletal lesions of the phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more localized and less proliferative and osteolytic damage that was confined predominantly to the phalanges and metatarsals. This report demonstrates the utility of imaging modalities to compare juvenile and young adult rats with CIA and provides evidence that disease characteristics and progression differ between the 2 age groups. Our observations indicate that the CIA model could help discern age-related pathologic processes in inflammatory joint diseases. PMID:24326225

Metformin and phenformin block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test.

PubMed

Ortiz, Mario I

2012-01-02

Recent evidence has shown that systemic administration of sulfonylureas and biguanides block the diclofenac-induced antinociception, but not the effect produced by indomethacin. However, there are no reports about the peripheral interaction between analgesics and the biguanides metformin and phenformin. Therefore, this work was undertaken to determine whether glibenclamide and glipizide and the biguanides metformin and phenformin have any effect on the peripheral antinociception induced by diclofenac and indomethacin. Diclofenac and indomethacin were administered locally in the formalin-injured rat paw, and the antinociceptive effect was evaluated using the 1% formalin test. To determine whether peripheral antinociception induced by diclofenac or indomethacin was mediated by either the ATP-sensitive K(+) channels or biguanides-induced mechanisms, the effect of pretreatment with the appropriates vehicles or glibenclamide, glipizide, metformin and phenformin on the antinociceptive effect induced by local peripheral diclofenac and indomethacin was assessed. Local peripheral injections of diclofenac (50-200 μg/paw) and indomethacin (200-800 μg/paw) produced a dose-dependent antinociception during the second phase of the test. Local pretreatment with glibenclamide, glipizide, metformin and phenformin blocked the diclofenac-induced antinociception. On the other hand, the pretreatment with glibenclamide and glipizide did not prevent the local antinociception produced by indomethacin. Nonetheless, metformin and phenformin reversed the local antinociception induced by indomethacin. Data suggest that diclofenac could activate the K(+) channels and biguanides-dependent mechanisms to produce its peripheral antinociceptive effects in the formalin test. Likewise, a biguanides-dependent mechanism could be activated by indomethacin consecutively to generate its peripheral antinociceptive effect. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of antinociceptive activity of hydromethanol extract of Cyperus rotundus in mice

PubMed Central

2014-01-01

Background Cyperus rotundus Linn. (Cyperaceae) is used to treat inflammation, pain, fever, wounds, boils and blisters in folk medicine. This study evaluated the antinociceptive effect of the hydromethanol extract of whole plant of C. rotundus (HMCR). Methods The antinociceptive activity of HMCR was investigated in thermal-induced (hot plate and tail immersion) and chemical-induced (formalin) nociception models in mice at three different doses (50, 100 and 200 mg/kg; p.o.). Morphine sulphate (5 mg/kg, i.p.) and diclofenac sodium (10 mg/kg, i.p.) were used as reference analgesic agents. Results In the hot-plate and tail-immersion tests HMCR significantly increased the latency period to the thermal stimuli at all the tested doses (50, 100 and 200 mg/kg) (p < 0.05). The significant increase in latency is clear from the observations at 60 and 90 min. In formalin-induced paw licking test oral administration of HMCR at 100 and 200 mg/kg doses decreased the licking of paw in early phase. All the tested doses (50, 100 and 200 mg/kg) significantly decreased the licking of paw in late phase of the test (p < 0.001). The dose 200 mg/kg was most effective showing maximum percentage of inhibition of licking in both early (61.60%) and late phase (87.41%). Conclusion These results indicate the antinociceptive effect of C. rotundus and suggest that this effect is mediated by both peripheral and central mechanisms. These results support the traditional use of this plant in different painful conditions. PMID:24589067

Fatty acid composition and preclinical resarches on Anthemis wiedemanniana Fisch. & Mey.: Discovery of a new anti-inflammatory agent

PubMed Central

Gönenç, Tuba Mert; Akkol, Esra Küpeli; Süntar, Ipek; Erdoğan, Tuğçe Fafal; Kıvçak, Bijen

2014-01-01

Background: Anthemis species have been used for the treatment of gastrointestinal disorders, hemorrhoid, stomachache and inflammatory diseases in Turkish folk medicine. Anthemis wiedemanniana Fisch. And Mey. is an endemic plant used as painkiller, antispasmodic, sedative and for the treatment of urinary inflammations. Objective: The objective of the present study is to evaluate the anti-inflamatory activity of the extracts of A. wiedemanniana by using in vivo methods. Materials and Methods: Carrageenan-, PGE2- and serotonin-induced hind paw edema, 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema and acetic acid-induced increase in capillary permeability models were used for the anti-inflammatory activity assessment. Moreover, the fatty acid composition of A. wiedemanniana was investigated by gas chromatography (GC). Results: n-Hexane, diethyl ether and total sesquiterpene lactone extracts exhibited significant inhibition in carrageenan-induced hind paw edema and acetic acid-induced increase in capillary permeability model. n-Hexane and total sesquiterperne lactone extracts showed anti-inflammatory activity in PGE2- and serotonin-induced hind paw edema model. However none of the extracts displayed significant activity in TPA-induced ear edema model in mice. C4:0 (Buthyric acid), C20:0 (Arachidic acid) and C16:1 (Palmitoleik acid) were found to be the major fatty acids in these species. Saturated fatty acids (SFA) were found in higher amounts than monounsaturated fatty acids and polyunsaturated fatty acids. SFAs were determined as 63.17%, UFAs as 20.89% and PuFAs as 15.95%. Conclusion: This study confirms the traditional usage of A. wiedemanniana for inflammatory diseases. PMID:24696546

Cellular prion protein protects from inflammatory and neuropathic pain

PubMed Central

2011-01-01

Cellular prion protein (PrPC) inhibits N-Methyl-D-Aspartate (NMDA) receptors. Since NMDA receptors play an important role in the transmission of pain signals in the dorsal horn of spinal cord, we thus wanted to determine if PrPC null mice show a reduced threshold for various pain behaviours. We compared nociceptive thresholds between wild type and PrPC null mice in models of inflammatory and neuropathic pain, in the presence and the absence of a NMDA receptor antagonist. 2-3 months old male PrPC null mice exhibited an MK-801 sensitive decrease in the paw withdrawal threshold in response both mechanical and thermal stimuli. PrPC null mice also exhibited significantly longer licking/biting time during both the first and second phases of formalin-induced inflammation of the paw, which was again prevented by treatment of the mice with MK-801, and responded more strongly to glutamate injection into the paw. Compared to wild type animals, PrPC null mice also exhibited a significantly greater nociceptive response (licking/biting) after intrathecal injection of NMDA. Sciatic nerve ligation resulted in MK-801 sensitive neuropathic pain in wild-type mice, but did not further augment the basal increase in pain behaviour observed in the null mice, suggesting that mice lacking PrPC may already be in a state of tonic central sensitization. Altogether, our data indicate that PrPC exerts a critical role in modulating nociceptive transmission at the spinal cord level, and fit with the concept of NMDA receptor hyperfunction in the absence of PrPC. PMID:21843375

50 CFR 17.85 - Special rules-invertebrates.

Code of Federal Regulations, 2011 CFR

2011-10-01

... florentina catspaw (purple cat's paw pearlymussel) Epioblasma obliquata obliquata clubshell Pleurobema clava... accidental and incidental to an otherwise lawful activity such as fishing, boating, commercial navigation... recreation (e.g., fishing, boating, wading, trapping, or swimming), forestry, agriculture, and other...

Intrathecal injection of fluorocitric acid inhibits the activation of glial cells causing reduced mirror pain in rats.

PubMed

Cao, Jing; Li, Zhihua; Zhang, Zhenhua; Ren, Xiuhua; Zhao, Qingzan; Shao, Jinping; Li, Ming; Wang, Jiannan; Huang, Puchao; Zang, Weidong

2014-01-01

Growing evidence has shown that unilateral nerve injury results in pain hypersensitivity in the ipsilateral and contralateral sides respective to the injury site. This phenomenon is known as mirror image pain (MIP). Glial cells have been indicated in the mechanism of MIP; however, it is not clear how glial cells are involved in MIP. To observe phenomenon MIP and the following mechanism, 20 adult male Sprague-Dawley rats (weighing 180-220 g) were separated into two groups: Sham Group (n = 10) and left L5 spinal nerve ligated and sectioned (SNL) group (n = 10). Thermal hyperalgesia and mechanical hypersensitivity were measured for both groups to determine if the SNL model had Mirror image of Pain (MIP). Nav1.7 protein expression in DRG was analyzed using immunohistochemistry and western-blotting. And then to observe the effect of fluorocitrate on MIP, 15 rats were separated into three Groups: Sham Group (n = 5); SNL + FC group: intrathecal injection of Fluorocitric acid(FC) 1 nmol/10 μL (n = 5); SNL + NS group: intrathecal injection of 0.9% Normal Saline (n = 5). Behavior testing, immunocytochemistry, and western-blotting using dorsal root ganglion (DRG) from both sides were then conducted. The results showed pain hypersensitivity in both hind-paws of the SNL animals, Mechanical tests showed the paw withdrawal threshold dropped from 13.30 ± 1.204 g to 2.57 ± 1.963 g at 14 d as will as the ipsilateral paw thermal withdrawal threshold dropped from 16.5 ± 2.236 s to 4.38 ± 2.544 s at 14 d. Mechanical tests showed the contralateral paw withdrawal threshold dropped from 14.01 ± 1.412 to 4.2 ± 1.789 g at 7d will the thermal withdrawal threshold dropped from 16.8 ± 2.176 s to 7.6 ± 1.517 s at 7d. Nav1.7 expression increased and glial cells actived in bilateral side DRG after SNL compared with sham group. After intrathecal injection of fluorocitrate, the glial cell in bilateral DRG were inhibited and the pain behavior were reversed in both hindpaws too. Fluorocitrate can inhibit the activation of glial cells in spinal cord and DRG, and reduce MIP.

Dog Mathematics: Exploring Base-4

ERIC Educational Resources Information Center

Kurz, Terri L.; Yanik, H. Bahadir; Lee, Mi Yeon

2016-01-01

Using a dog's paw as a basis for numerical representation, sixth grade students explored how to count and regroup using the dog's four digital pads. Teachers can connect these base-4 explorations to the conceptual meaning of place value and regrouping using base-10.

Characterization of a cerebral palsy-like model in rats: Analysis of gait pattern and of brain and spinal cord motor areas.

PubMed

Dos Santos, Adriana Souza; de Almeida, Wellington; Popik, Bruno; Sbardelotto, Bruno Marques; Torrejais, Márcia Miranda; de Souza, Marcelo Alves; Centenaro, Lígia Aline

2017-08-01

In an attempt to propose an animal model that reproduces in rats the phenotype of cerebral palsy, this study evaluated the effects of maternal exposure to bacterial endotoxin associated with perinatal asphyxia and sensorimotor restriction on gait pattern, brain and spinal cord morphology. Two experimental groups were used: Control Group (CTG) - offspring of rats injected with saline during pregnancy and Cerebral Palsy Group (CPG) - offspring of rats injected with lipopolysaccharide during pregnancy, submitted to perinatal asphyxia and sensorimotor restriction for 30days. At 29days of age, the CPG exhibited coordination between limbs, weight-supported dorsal steps or weight-supported plantar steps with paw rotation. At 45days of age, CPG exhibited plantar stepping with the paw rotated in the balance phase. An increase in the number of glial cells in the primary somatosensory cortex and dorsal striatum were observed in the CPG, but the corpus callosum thickness and cross-sectional area of lateral ventricle were similar between studied groups. No changes were found in the number of motoneurons, glial cells and soma area of the motoneurons in the ventral horn of spinal cord. The combination of insults in the pre, peri and postnatal periods produced changes in hindlimbs gait pattern of animals similar to those observed in diplegic patients, but motor impairments were attenuated over time. Besides, the greater number of glial cells observed seems to be related to the formation of a glial scar in important sensorimotor brain areas. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Blockade of Nogo Receptor Ligands Promotes Functional Regeneration of Sensory Axons After Dorsal Root Crush

PubMed Central

Harvey, Pamela A.; Lee, Daniel H.S.; Qian, Fang; Weinreb, Paul H.; Frank, Eric

2010-01-01

A major impediment for regeneration of axons within the central nervous system is the presence of multiple inhibitory factors associated with myelin. Three of these factors bind to the Nogo receptor, NgR, which is expressed on axons. Administration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descending axonal projections after spinal cord hemisection. A more detailed analysis of CNS regeneration can be made by examining the growth of specific classes of sensory axons into the spinal cord after dorsal root crush injury . In this study, we assessed whether administration of a soluble peptide fragment of the NgR that binds to and blocks all three NgR ligands can promote regeneration after brachial dorsal root crush in adult rats. Intraventricular infusion of sNgR for one month results in extensive regrowth of myelinated sensory axons into the white and gray matter of the dorsal spinal cord, but unmyelinated sensory afferents do not regenerate. In concert with the anatomical growth of sensory axons into the cord, there is a gradual restoration of synaptic function in the denervated region, as revealed by extracellular microelectrode recordings from the spinal gray matter in response to stimulation of peripheral nerves. These positive synaptic responses are correlated with substantial improvements in use of the forelimb, as assessed by paw preference, paw withdrawal to tactile stimuli and the ability to grasp. These results suggest that sNgR may be a potential therapy for restoring sensory function following injuries to sensory roots. PMID:19439606

Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators.

PubMed

You, Sixiang; Nakanishi, Eri; Kuwata, Hiroko; Chen, Jihua; Nakasone, Yasushi; He, Xi; He, Jianhua; Liu, Xiangxin; Zhang, Shirui; Zhang, Bin; Hou, De-Xing

2013-11-01

Garlic is used for both culinary and medicinal purposes by many cultures. The garlic organosulfur compounds (GOSCs) are thought to be bioactive components. This study aims to clarify the antiinflammatory effects and molecular mechanisms of GOSCs in both cell and animal models. RAW264.7 cells were treated with six kinds of GOSCs to screen their influence on cyclooxygenase-2 and inducible nitric oxide synthase expression by Western blotting. Prostaglandin E2 and nitrite were measured by ELISA and Griess reaction, respectively. Cytokines in culture medium were assayed by the multiplex technology. Proteins were detected by Western blotting. Mouse paw edema was induced by LPS. The results revealed that diallyl trisulfide (DATS) was a strongest inhibitor for cyclooxygenase and inducible nitric oxide synthase among GOSCs, and reduced the levels of LPS-induced IL-6, IL-10, IL-12(p70), KC, MCP-1, and TNF-α. Cellular signaling analysis revealed that DATS downregulated AKT1/TGF-β-activated kinase-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Furthermore, DATS activated Nrf2-mediated expression of HO-1 and NQO1 and reduced LPS-induced intracellular reactive oxygen species, which may contribute to suppress inflammatory mediator production. Finally, in vivo data demonstrated that DATS attenuated LPS-induced mouse paw edema. DATS as a potential inhibitor revealed antiinflammatory effect in both cell and animal models by downregulating AKT1/TGF-β-activated kinase-mediated NFκB and MAPK signaling pathways. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reliability of transpulmonary pressure-time curve profile to identify tidal recruitment/hyperinflation in experimental unilateral pleural effusion.

PubMed

Formenti, P; Umbrello, M; Graf, J; Adams, A B; Dries, D J; Marini, J J

2017-08-01

The stress index (SI) is a parameter that characterizes the shape of the airway pressure-time profile (P/t). It indicates the slope progression of the curve, reflecting both lung and chest wall properties. The presence of pleural effusion alters the mechanical properties of the respiratory system decreasing transpulmonary pressure (Ptp). We investigated whether the SI computed using Ptp tracing would provide reliable insight into tidal recruitment/overdistention during the tidal cycle in the presence of unilateral effusion. Unilateral pleural effusion was simulated in anesthetized, mechanically ventilated pigs. Respiratory system mechanics and thoracic computed tomography (CT) were studied to assess P/t curve shape and changes in global lung aeration. SI derived from airway pressure (Paw) was compared with that calculated by Ptp under the same conditions. These results were themselves compared with quantitative CT analysis as a gold standard for tidal recruitment/hyperinflation. Despite marked changes in tidal recruitment, mean values of SI computed either from Paw or Ptp were remarkably insensitive to variations of PEEP or condition. After the instillation of effusion, SI indicates a preponderant over-distension effect, not detected by CT. After the increment in PEEP level, the extent of CT-determined tidal recruitment suggest a huge recruitment effect of PEEP as reflected by lung compliance. Both SI in this case were unaffected. We showed that the ability of SI to predict tidal recruitment and overdistension was significantly reduced in a model of altered chest wall-lung relationship, even if the parameter was computed from the Ptp curve profile.

Space Shuttle Projects

NASA Image and Video Library

1994-07-01

In this photograph, astronaut Carl Walz performs the Performance Assessment Workstation (PAWS) experiment at the flight deck of the Space Shuttle Orbiter Columbia during the STS-65 mission. Present day astronauts are subject to a variety of stresses during spaceflight. These include microgravity, physical isolation, confinement, lack of privacy, fatigue, and changing work/rest cycles. The purpose of this experiment is to determine the effects of microgravity upon thinking skills critical to the success of operational tasks in space. The principle objective is to distinguish between the effects of microgravity on specific information-processing skills affecting performance and those of fatigue caused by long work periods. To measure these skills, the investigators use a set of computerized performance tests called the Performance Assessment Workstation, which is based on current theoretical models of human performance. The tests were selected by analyzing tasks related to space missions and their hypothesized sensitivity to microgravity. Multiple subjective measures of cumulative fatigue and changing mood states are also included for interpreting performance data.

STS-65 Mission Onboard Photograph

NASA Technical Reports Server (NTRS)

1994-01-01

In this photograph, astronaut Carl Walz performs the Performance Assessment Workstation (PAWS) experiment at the flight deck of the Space Shuttle Orbiter Columbia during the STS-65 mission. Present day astronauts are subject to a variety of stresses during spaceflight. These include microgravity, physical isolation, confinement, lack of privacy, fatigue, and changing work/rest cycles. The purpose of this experiment is to determine the effects of microgravity upon thinking skills critical to the success of operational tasks in space. The principle objective is to distinguish between the effects of microgravity on specific information-processing skills affecting performance and those of fatigue caused by long work periods. To measure these skills, the investigators use a set of computerized performance tests called the Performance Assessment Workstation, which is based on current theoretical models of human performance. The tests were selected by analyzing tasks related to space missions and their hypothesized sensitivity to microgravity. Multiple subjective measures of cumulative fatigue and changing mood states are also included for interpreting performance data.

Characterization of soil spatial variability for site-specific management using soil electrical conductivity and other remotely sensed data

NASA Astrophysics Data System (ADS)

Bang, Jisu

Field-scale characterization of soil spatial variability using remote sensing technology has potential for achieving the successful implementation of site-specific management (SSM). The objectives of this study were to: (i) examine the spatial relationships between apparent soil electrical conductivity (EC a) and soil chemical and physical properties to determine if EC a could be useful to characterize soil properties related to crop productivity in the Coastal Plain and Piedmont of North Carolina; (ii) evaluate the effects of in-situ soil moisture variation on ECa mapping as a basis for characterization of soil spatial variability and as a data layer in cluster analysis as a means of delineating sampling zones; (iii) evaluate clustering approaches using different variable sets for management zone delineation to characterize spatial variability in soil nutrient levels and crop yields. Studies were conducted in two fields in the Piedmont and three fields in the Coastal Plain of North Carolina. Spatial measurements of ECa via electromagnetic induction (EMI) were compared with soil chemical parameters (extractable P, K, and micronutrients; pH, cation exchange capacity [CEC], humic matter or soil organic matter; and physical parameters (percentage sand, silt, and clay; and plant-available water [PAW] content; bulk density; cone index; saturated hydraulic conductivity [Ksat] in one of the coastal plain fields) using correlation analysis across fields. We also collected ECa measurements in one coastal plain field on four days with significantly different naturally occurring soil moisture conditions measured in five increments to 0.75 m using profiling time-domain reflectometry probes to evaluate the temporal variability of ECa associated with changes in in-situ soil moisture content. Nonhierarchical k-means cluster analysis using sensor-based field attributes including vertical ECa, near-infrared (NIR) radiance of bare-soil from an aerial color infrared (CIR) image, elevation, slope, and their combinations was performed to delineate management zones. The strengths and signs of the correlations between ECa and measured soil properties varied among fields. Few strong direct correlations were found between ECa and the soil chemical and physical properties studied (r2 < 0.50), but correlations improved considerably when zone mean ECa and zone means of selected soil properties among ECa zones were compared. The results suggested that field-scale ECa survey is not able to directly predict soil nutrient levels at any specific location, but could delimit distinct zones of soil condition among which soil nutrient levels differ, providing an effective basis for soil sampling on a zone basis. (Abstract shortened by UMI.)

A combined bottom-up/top-down approach to prepare a sterile injectable nanosuspension.

PubMed

Hu, Xi; Chen, Xi; Zhang, Ling; Lin, Xia; Zhang, Yu; Tang, Xing; Wang, Yanjiao

2014-09-10

To prepare a uniform nanosuspension of strongly hydrophobic riboflavin laurate (RFL) allowing sterile filtration, physical modification (bottom-up) was combined with high-pressure homogenization (top-down) method. Unlike other bottom-up approaches, physical modification with surfactants (TPGS and PL-100) by lyophilization controlled crystallization and compensated for the poor wettability of RFL. On one hand, crystal growth and aggregation during freezing was restricted by a stabilizer-layer adsorbed on the drug surface by hydrophobic interaction. On the other hand, subsequent crystallization of drug in the sublimation process was limited to the interstitial spaces between solvent crystals. After lyophilization, modified drug with a smaller particle size and better wettability was obtained. When adding surfactant solution, water molecules passed between the hydrophilic groups of surface active molecules and activated the polymer chains allowing them to stretch into water. The coarse suspension was crushed into a nanosuspension (MP=162 nm) by high-pressure homogenization. For long term stability, lyophilization was applied again to solidify the nanosuspension (sorbitol as cryoprotectant). A slight crystal growth to about 600 nm was obtained to allow slow release for a sustained effect after muscular administration. Moreover, no paw-licking responses and very slight muscular inflammation demonstrated the excellent biocompatibility of this long-acting RFL injection. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-inflammatory effects of oxymatrine on rheumatoid arthritis in rats via regulating the imbalance between Treg and Th17 cells

PubMed Central

Ma, Ailing; Yang, Yongya; Wang, Qiuyang; Wang, Yin; Wen, Jing; Zhang, Yanli

2017-01-01

Oxymatrine (OMT), a monosomic alkaloid extracted from the Chinese herb, Sophora flavescens Ait, has long been used as a traditional Chinese medicine for the treatment of inflammatory diseases. The aim of the present study was to investigate the potential anti-inflammatory effect of OMT, and its modulation on imbalance between regulatory T (Treg) cells and T helper (Th) 17 cells in rats with collagen-induced arthritis (CIA). Sprague-Dawley rats were immunized with type II collagen and following a second collagen immunization, the rats were treated with OMT or dexamethasone (DXM) intraperitoneally once a day for 43 days. Paw swelling, arthritic score and joint histopathology were evaluated. The Treg/Th17-mediated autoreactive response was assessed by determining serum levels of inflammatory response cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-17, using an enzyme-linked immunosorbent assay. The mRNA levels of forkhead box P3 (FOXP3) and retinoic acid-related orphan receptor (ROR)γt in spleen cells stimulated with type II collagen were determined using reverse transcription-quantitative polymerase chain reaction analysis. In addition, the protein expression levels of FOXP3 and RORγt were measured using western blot analysis. The results showed that OMT treatment significantly reduced the severity of CIA, markedly abrogating paw swelling, arthritic scores and synovial hyperplasia, and the increased loss in body weight. OMT significantly reduced the production of TNF-α and IL-17A, upregulated FOXP3 and downregulated RORγt in rats with CIA. In conclusion, the present study demonstrated that OMT exhibited a protective effect on rheumatoid arthritis (RA) through the inhibition of inflammation and regulation of Treg/Th17 in the CIA rats, suggesting that OMT may be used as an immune suppressive and cartilage protective medicine in human RA. PMID:28440447

Antihyperalgesic/antinociceptive effects of ceftriaxone and its synergistic interactions with different analgesics in inflammatory pain in rodents.

PubMed

Stepanovic-Petrovic, Radica M; Micov, Ana M; Tomic, Maja A; Kovacevic, Jovana M; Boškovic, Bogdan D

2014-03-01

The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents. The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis. Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively. Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.

Garcinia morella fruit, a promising source of antioxidant and anti-inflammatory agents induces breast cancer cell death via triggering apoptotic pathway.

PubMed

Choudhury, Bhaswati; Kandimalla, Raghuram; Elancheran, R; Bharali, Rupjyoti; Kotoky, Jibon

2018-04-17

A rapid rise in cancer cases worldwide, especially breast cancer in females, instigates the need for more effective and less side effect causing drugs from natural origin. Thereby, in the present study, Garcinia morella fruit was investigated for antioxidant, anti-inflammatory and anti-breast cancer activity. Preliminary antioxidant and anticancer evaluation of different fractions and crude methanol extract of G. morella fruit suggested chloroform fraction as the bioactive fraction. Time course analysis (by 24 h, 48 h and 72 h) of the bioactive fraction (1.56-25) μg/ml treatment on breast cancer cell lines (MCF7, MDAMB231 and SKBR3) showed dose and time dependent antiproliferative responses. Further, mechanistic studies involving morphological observation and western blotting analysis, revealed its apoptosis inducing effect on breast cancer. P53 dependent up-regulation of Bax and down-regulation of Bcl X L is suggested as the possible pathway of apoptosis followed by MCF7 cells on exposure to the bioactive fraction. The anti-inflammatory assays revealed that it significantly lowered the release of nitrite and TNF-α level of LPS induced RAW 264.7 cells (p < 0.05). Moreover, pre treatment of Carrageenan induced paw edema animals with 20 mg/kg of the bioactive fraction significantly (p < 0.05) inhibited paw inflammation and controlled the cytokine and nitrite levels of the edema induced rat. Its main bioactive component was identified to be Garcinol by UHPLC and ESI-MS/MS. Thereby, this study clearly reflects that G. morella fruit is a valuable antioxidant and anti-inflammatory gift of nature with the potential to be used against breast cancer. This is also the first report of isolation of bioactive compound Garcinol from G. morella fruit. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

BIOMECHANICS AND HISTOLOGICAL ANALYSIS IN RABBIT FLEXOR TENDONS REPAIRED USING THREE SUTURE TECHNIQUES (FOUR AND SIX STRANDS) WITH EARLY ACTIVE MOBILIZATION

PubMed Central

Severo, Antônio Lourenço; Arenhart, Rodrigo; Silveira, Daniela; Ávila, Aluísio Otávio Vargas; Berral, Francisco José; Lemos, Marcelo Barreto; Piluski, Paulo César Faiad; Lech, Osvandré Luís Canfield; Fukushima, Walter Yoshinori

2015-01-01

Objective: Analyzing suture time, biomechanics (deformity between the stumps) and the histology of three groups of tendinous surgical repair: Brazil-2 (4-strands) which the end knot (core) is located outside the tendon, Indiana (4-strands) and Tsai (6-strands) with sutures technique which the end knot (core) is inner of the tendon, associated with early active mobilization. Methods: The right calcaneal tendons (plantar flexor of the hind paw) of 36 rabbits of the New Zealand breed (Oryctolagus cuniculus) were used in the analysis. This sample presents similar size to human flexor tendon that has approximately 4.5 mm (varying from 2mm). The selected sample showed the same mass (2.5 to 3kg) and were male or female adults (from 8 ½ months). For the flexor tendons of the hind paws, sterile and driven techniques were used in accordance to the Committee on Animal Research and Ethics (CETEA) of the University of the State of Santa Catarina (UDESC), municipality of Lages, in Brazil (protocol # 1.33.09). Results: In the biomechanical analysis (deformity) carried out between tendinous stumps, there was no statistically significant difference (p>0.01). There was no statistical difference in relation to surgical time in all three suture techniques with a mean of 6.0 minutes for Tsai (6- strands), 5.7 minutes for Indiana (4-strands) and 5.6 minutes for Brazil (4-strands) (p>0.01). With the early active mobility, there was qualitative and quantitative evidence of thickening of collagen in 38.9% on the 15th day and in 66.7% on the 30th day, making the biological tissue stronger and more resistant (p=0.095). Conclusion: This study demonstrated that there was no histological difference between the results achieved with an inside or outside end knot with respect to the repaired tendon and the number of strands did not affect healing, vascularization or sliding of the tendon in the osteofibrous tunnel, which are associated with early active mobility, with the repair techniques applied. PMID:27027087

Pharmacological evidence favouring the traditional use of the root bark of Condalia buxifolia Reissek in the relief of pain and inflammation in mice.

PubMed

Simões, Róli R; Coelho, Igor S; Junqueira, Stella C; Maldaner, Graciela; Morel, Ademir F; Venzke, Dalila; Ruani, Ana Paula; Pizzolatti, Moacir G; Zanchet, Eliane M; Santos, Adair R S

2015-12-04

The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and against dysentery. This study was designed to investigate whether the methanolic extract of the root bark of Condalia buxifolia (MECb) exhibits antinociceptive and anti-inflammatory effects in mice. Furthermore, also was investigated the involvement of glutamatergic and opioidergic system in the antinociceptive effect induced by MECb. The antinociceptive and anti-inflammatory effects of intra-gastric gavage (i.g.) administered MECb (10-300 mg/kg) were evaluated in mice subjected to chemical (formalin, acetic-acid, glutamate) or thermal (hot plate) models of pain. The involvement of opioid system in the antinociceptive effect of the MECb was investigated in formalin test. Furthermore, a nonspecific effect of MECb was evaluated by measuring locomotor activity and exploratory behavior in open field test. Finally, was performed a phytochemical analysis of MECb. The phytochemical analysis of MECb was performed through HPLC analysis showing that the alkaloid Condaline-A is the main constituent. The intragastric administration of MECb (100-300 mg/kg) significantly inhibited the nociception caused by acetic acid (48 ± 2%), inflammatory phase (49 ± 3%) and paw edema (32 ± 6) caused by formalin, and MECb (100mg/kg, i.g.) also inhibited nociception caused by glutamate (41 ± 7%). In addition, MECb (100-300 mg/kg, i.g.) increased the paw withdrawal latency in hot-plate test, without affecting the locomotor activity and exploratory behavior in open field test. Finally, the antinociceptive effects of MECb (100mg/kg, i.g.) were significantly reversed by naloxone (1mg/kg, i.p.) in the formalin test. These data show, for the first time, that MECb has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system and the activation of opioid mechanism, besides present central effects. These results support the use of Condalia buxifolia in traditional medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive and anti-inflammatory properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Modulation Between High- and Low-Frequency Transcutaneous Electric Nerve Stimulation Delays the Development of Analgesic Tolerance in Arthritic Rats

PubMed Central

DeSantana, Josimari M.; Santana-Filho, Valter J.; Sluka, Kathleen A.

2009-01-01

Objective To investigate whether repeated administration of modulating frequency transcutaneous electric nerve stimulation (TENS) prevents development of analgesic tolerance. Design Knee joint inflammation (3% carrageenan and kaolin) was induced in rats. Either mixed or alternating frequency was administered daily (20min) for 2 weeks to the inflamed knee under light halothane anesthesia (1%–2%). Setting Laboratory. Animals Adult male Sprague-Dawley rats (N=36). Intervention Mixed- (4Hz and 100Hz) or alternating- (4Hz on 1 day; 100Hz on the next day) frequency TENS at sensory intensity and 100μs pulse duration. Main Outcome Measures Paw and joint withdrawal thresholds to mechanical stimuli were assessed before induction of inflammation, and before and after daily application of TENS. Results The reduced paw and joint withdrawal thresholds that occur 24 hours after the induction of inflammation were significantly reversed by the first administration of TENS when compared with sham treatment or to the condition before TENS treatment, which was observed through day 9. By the tenth day, repeated daily administration of either mixed- or alternating-frequency TENS did not reverse the decreased paw and joint withdrawal thresholds. Conclusions These data suggest that repeated administration of modulating frequency TENS leads to a development of opioid tolerance. However, this tolerance effect is delayed by approximately 5 days compared with administration of low- or high-frequency TENS independently. Clinically, we can infer that a treatment schedule of repeated daily TENS administration will result in a tolerance effect. Moreover, modulating low and high frequency TENS seems to produce a better analgesic effect and tolerance is slower to develop. PMID:18374009

Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

PubMed

Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

2018-05-01

The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

Anti-nociceptive effect of methanol extract of leaves of Senna singueana in mice.

PubMed

Hishe, Hailemichael Zeru; Ambech, Tamrat Abate; Hiben, Mebrahtom Gebrelibanos; Fanta, Biruk Sintayehu

2018-05-10

Senna singueana (Del.) Lock (Fabaceae) is a shrub or tree found in Ethiopia and other African countries. It has been traditionally used for different conditions including treatment of pain conditions in humans and animals. Although various reports are available in the literature claiming different activities of the plant, scientific studies supporting analgesic potential of S. singueana are lacking and the present study aimed to investigate the antinociceptive effect of methanol extract of leaves of S. singueana in mice. Anti-nociceptive activity of S. singueana (200 mg/kg and 400 mg/kg, p.o) was investigated using acetic acid-induced writhing, formalin-induced paw licking, and hot plate tests. Acute oral toxicity was determined using a slightly modified guideline (423) of the Organization for Economic Cooperation and Development. S. singueana extract increased the percentage of inhibition of writhing response and licking response (neurogenic and inflammatory phase) in acetic acid-induced writhing and formalin-induced paw licking tests, respectively. It also significantly (p ≤ 0.05) increased the percentage of mean maximal effect (%MPE) compared to control group in the hot-plate test. In all models, the combination of S. singueana with either diclofenac or morphine produced statistically significant increase (p ≤ 0.05) in the percentage of inhibition of writhing, paw licking, and %MPE compared to single treatment groups. It was also found that the 400 mg/kg extract produced higher antinociceptive effects (p ≤ 0.05) compared to the 200 mg/kg. S. singueana leaves may have analgesic effect that is mediated through both peripheral and central mechanisms and could be used as adjuvant treatment to the modern analgesics. Copyright © 2018 Elsevier B.V. All rights reserved.

Edematogenic activity of a sulfated galactan from the red marine algae Gelidium crinale.

PubMed

Assreuy, Ana Maria Sampaio; Amorim, Renata Morais Ferreira; Brizeno, Luiz André Cavalcante; de Paulo Pereira, Lívia; de Sousa, Albertina Antonielly Sydney; Aragão, Gislei Frota; Pereira, Maria Gonçalves

2012-09-01

The red algae Gelidium crinale (Turner) Gaillon (Gelidiaceae), encountered along the Southeast and Northeast Brazilian sea coast, contains a sulfated galactan presenting a similar saccharide backbone compared to λ carrageenan. Inflammatory effects of other galactans were reported, but not for that obtained from G. crinale (SG-Gc). To investigate the in vivo edematogenic effect of SG-Gc in comparison to λ carrageenan. SG-Gc was isolated by ion exchange chromatography. Paw edema was induced by subcutaneous (s.c.) intraplantar injection of SG-Gc or λ carrageenan and evaluated by hydroplethysmometry. Data were expressed as the increase in paw volume subtracted from the basal volume or area under curve-AUC. To investigate the participation of early and late-phase inflammatory mediators, rats were treated with pyrilamine, compound 48/80, indomethacin, NG-nitro-L-arginine methyl ester (L-NAME), or pentoxifylline before SG-Gc. SG-Gc edematogenic effect was initiated at 0.5 h, peaked at 2 h (1.26 ± 0.05 mL) and lasted until 6 h (0.21 ± 0.03 mL), whereas the carrageenan-induced edema started at 1 h. The first phase (1-3 h) of SG-Gc-induced edema was 176 ± 15 (AUC) versus carrageenan (114.5 ± 14), whereas the second phase (3-5 h) was 95 ± 12 (AUC) versus carrageenan (117.5 ± 11). Treatment with compound 48/80, pyrilamine, indomethacin, L-NAME, and pentoxifylline inhibited the effect of SG-Gc by 32, 40, 69, 72, and 49%, respectively. SG-Gc and λ carrageenan induce different profile of inflammatory response in the paw edema model, that involves histamine, cytokines, prostaglandins, and nitric oxide (NO), but with different degree of participation.

Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat

PubMed Central

Wakley, Alexa A.; Wiley, Jenny L.; Craft, Rebecca M.

2014-01-01

Background Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats. Methods Cumulative dose-effect curves were obtained for THC (1.0–18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined. Results On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females, 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females. Conclusions These results demonstrate that – even when sex differences in acute THC potency are controlled for – females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure. PMID:25131716

Water-soluble phenol TS-13 combats acute but not chronic inflammation.

PubMed

Menshchikova, Elena; Tkachev, Victor; Lemza, Anna; Sharkova, Tatyana; Kandalintseva, Natalya; Vavilin, Valentin; Safronova, Olga; Zenkov, Nikolay

2014-09-01

This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation. Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis. The effects of TS-13 treatment were estimated by changes in the intensity of inflammation (paw edema, liver infiltration, animal survival, exudation, and clinical score of arthritis) and by the effects on reactive oxygen species (ROS) generation by leukocytes from peripheral blood and inflammatory exudates. We found the significant increase in expression of mRNA, content of protein and activity of a well-characterized Nrf2 target enzyme glutathione S-transferase P1, as well as nuclear extract protein binding to the ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13 markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte number and volume density of liver infiltrates in the systemic zymosan-induced inflammation model, and increased mice survival after lipopolysaccharide-induced septic shock. However, TS-13 administration did not influence cell and protein exudation into air pouches and suppressed clinical manifestation of collagen-induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the generation of ROS by leukocytes in all inflammation models. The data suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more prominent against acute innate-mediated inflammation than chronic immune inflammation. This narrows the potential therapeutic efficacy of ARE inducers in inflammation treatment.

Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice

PubMed Central

Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang

2015-01-01

Abstract In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases. PMID:25494361

Modifications of Gait as Predictors of Natural Osteoarthritis Progression in STR/Ort Mice

PubMed Central

Poulet, Blandine; de Souza, Roberto; Knights, Chancie B; Gentry, Clive; Wilson, Alan M; Bevan, Stuart; Chang, Yu-Mei; Pitsillides, Andrew A

2014-01-01

Objective Osteoarthritis (OA) is a common chronic disease for which disease-modifying therapies are not currently available. Studies to seek new targets for slowing the progress of OA rely on mouse models, but these do not allow for longitudinal monitoring of disease development. This study was undertaken to determine whether gait can be used to measure disease severity in the STR/Ort mouse model of spontaneous OA and whether gait changes are related to OA joint pain. Methods Gait was monitored using a treadmill-based video system. Correlations between OA severity and gait at 3 treadmill speeds were assessed in STR/Ort mice. Gait and pain behaviors of STR/Ort mice and control CBA mice were analyzed longitudinally, with monthly assessments. Results The best speed to identify paw area changes associated with OA severity in STR/Ort mice was found to be 17 cm · seconds−1. Paw area was modified with age in CBA and STR/Ort mice, but this began earlier in STR/Ort mice and correlated with the onset of OA at 20 weeks of age. In addition, task noncompliance appeared at 20 weeks. Surprisingly, STR/Ort mice did not show any signs of pain with OA development, even when treated with the opioid antagonist naloxone, but did exhibit normal pain behaviors in response to complete Freund's adjuvant–induced arthritis. Conclusion The present results identify an animal model in which OA severity and OA pain can be studied in isolation from one another. The findings suggest that paw area and treadmill noncompliance may be useful tools to longitudinally monitor nonpainful OA development in STR/Ort mice. This will help in providing a noninvasive means of assessing new therapies to slow the progression of OA. PMID:24623711

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

Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells.

PubMed

Ferrari, Luiz Fernando; Lotufo, Celina Monteiro; Araldi, Dionéia; Rodrigues, Marcos A; Macedo, Larissa P; Ferreira, Sérgio H; Parada, Carlos Amilcar

2014-12-23

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.

Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats.

PubMed

Refaat, Rowaida; Salama, Mona; Abdel Meguid, Elham; El Sarha, Ashgan; Gowayed, Mennatallah

2013-01-05

There is increasing body of evidence documenting the involvement of angiotensin II in inflammatory diseases. Moreover the up-regulation of angiotensin II AT(1) receptors in the synovium of rheumatoid arthritis patients has been previously described. This study aimed at investigating the anti-inflammatory effect of losartan, the selective angiotensin II AT(1) receptor blocker, and comparing the efficacy of methotrexate alone and in combination with losartan in adjuvant arthritis in rats. Twelve days post adjuvant injection, Sprague-Dawley rats were treated with methotrexate (1mg/kg/week), losartan (20mg/kg/day) and their combination for 15 days. Severity of arthritis was assessed by hind paw swelling, arthrogram scores. Serum was analyzed for measurement of albumin, C-reactive protein (CRP), nitrite/nitrate concentrations, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), aspartate transaminase (AST) and alanine transaminase (ALT). Histopathological examination was done for hind paws and livers. Methotrexate and losartan monotherapies significantly reduced all parameters of inflammation and arthritis with better results in the methotrexate group except for the transaminases where losartan caused more significant reduction in their serum levels. The combined therapy showed better results than methotrexate and losartan alone. Hind paws showed better improvement of inflammatory cell infiltration and bone resorption in the combined therapy group. Disturbances in liver architecture and fibrosis caused by adjuvant arthritis were reverted to normal status in the combined therapy group in contrast to losartan and methotrexate monotherapies. In conclusion, methotrexate and losartan combined therapy provided more effective anti-inflammatory and hepatoprotective effects than either drug alone. Copyright © 2012 Elsevier B.V. All rights reserved.

Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation.

PubMed

Rao, Sadia Saleem; Najam, Rahila

2016-01-01

Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results revealed that both coconut water possess significant anti-inflammatory activity (P < 0.001). In comparison to control, percent inhibition by young coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect.

Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats.

PubMed

Voon, Fui-Ling; Sulaiman, Mohd Roslan; Akhtar, Muhammad Nadeem; Idris, Mohamad Fauzi; Akira, Ahmad; Perimal, Enoch Kumar; Israf, Daud Ahmad; Ming-Tatt, Lee

2017-01-05

Boesenbergia rotunda (L.) Mansf. had been traditionally used as herbs to treat pain and rheumatism. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) is a compound isolated from Boesenbergia rotunda (L.) Mansf.. Previous study had shown the potential of cardamonin in inhibiting the release of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. Thus, the possible therapeutic effect of cardamonin in the rheumatoid arthritis (RA) joints is postulated. This study was performed to investigate the anti-arthritic properties of cardamonin in rat model of induced RA, particularly on the inflammatory and pain response of RA. Rheumatoid arthritis paw inflammation was induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA) in Sprague Dawley rats. Using four doses of cardamonin (0.625, 1.25, 2.5, and 5.0mg/kg), anti-arthritic activity was evaluated through the paw edema, mechanical allodynia and thermal hyperalgesia responses. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma level of TNF-α, IL-1β, and IL-6. Histological slides were prepared from the harvested rat paws to observe the arthritic changes in the joints. Behavioral, biochemical, and histological studies showed that cardamonin demonstrated significant inhibition on RA-induced inflammatory and pain responses as well as progression of joint destruction in rats. ELISA results showed that there was significant inhibition in TNF-α, IL-1β, and IL-6 levels in plasma of the cardamonin-treated RA rats. Overall, cardamonin possesses potential anti-arthritic properties in CFA-induced RA rat model. Copyright © 2016 Elsevier B.V. All rights reserved.

A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

PubMed

Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

2016-01-01

Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

PubMed Central

Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

2016-01-01

Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

Sensory nerve crush and regeneration and the receptive fields and response properties of neurons in the primary somatosensory cerebral cortex of cats.

PubMed

Brandenberg, G A; Mann, M D

1989-03-01

Extracellular recordings were made of activity evoked in neurons of the forepaw focus of somatosensory cerebral cortex by electrical stimulation of each paw in control cats and cats that had undergone crush injury of all cutaneous sensory nerves to the contralateral forepaw 31 to 63 days previously. Neurons responding only to stimulation of the contralateral forepaw were classified as sa; neurons responding to stimulation of both forepaws were classified as sb; neurons responding to stimulation of both contralateral paws were classified as sc; and neurons responding to stimulation of at least three paws were classified as m. The ratio sa:sb:sc:m neurons was 46:3:0:0 in control cats and 104:15:3:26 in cats that had undergone nerve crush 1-2 months prior to study. sa neurons from experimental cats had depth distributions similar to those in controls and responded to contralateral forepaw stimulation with more spikes per discharge, longer latency, and higher threshold than sa neurons in control cats. m neurons from experimental cats were distributed deeper in the cortex than sa neurons, and, when compared to experimental sa neurons, they responded with longer latency and poorer frequency-following ability; however, the number of spikes per discharge and threshold were not significantly different. The appearance of wide-field neurons in this tissue may be explained in terms of strengthening of previously sub-threshold inputs to neurons in the somatosensory system. If the neurons in sensory cortex play a requisite role in cutaneous sensations and if changes similar to those reported here occur and persist in human cortex after nerve crush, then "complete" recovery of sensation in such patients may occur against a background of changed cortical neuronal responsiveness.

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

PubMed Central

Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

1992-01-01

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

Antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) in Rodents: possible mechanism of actions.

PubMed

Ishola, Ismail O; Olayemi, Sunday O; Oreagba, Ibrahim A; Ifeanyi, Chikaodili I; Popoola, Temidayo O

2015-12-20

The leaves of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) is used in Traditional African medicine for the treatment of various ailments including arthritis. The present study sought to investigate the antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (HeCA). HeCA (100, 200 or 400 mg/kg, p.o.) was administered 1 h before intraplantar injection of formalin 1%v/v in saline to evaluate antinociceptive effect. Moreover, its possible mechanism of antinociceptive action was investigated through pretreatment of mice with antagonists of receptors implicated in nociception. Anti¬inflammatory effect of the extract was investigated using the carrageenan-induced paw oedema and complete Freund's adjuvant (CFA)-induced arthritis models in rats. HeCA (400 mg/kg) treatment significantly reduced the duration of paw licking/biting during both in the early (42.12%) and late (75.79%) phases of formalin-induced nociception. However, the antinociceptive effect elicited by HeCA was reverse by pretreatment of mice with naloxone, prazosin, yohimbine, ketanserin, L-arginine, and parachlorophenylalanine (PCPA). HeCA produced dose-dependent and time course decrease in carrageenan-induced paw oedema. Pre- and post-treatment of rats with HeCA ameliorated CFA-induced arthritis evidenced in the significant decrease in arthritic index comparatively similar to the effect of celecoxib. CFA- induced oxidative and nitrosative stress were attenuated by subchronic treatment with HeCA. Findings from this study shows that C. anisata possesses antinociceptive activity through possible interaction with opioidergic, noradrenergic, L-arginine-nitric oxide and serotonergic pathways as well as anti-arthritic property which could be attributed to its ability to prevent the release of inflammatory mediators and oxidative stress.

Celastrol attenuates incision-induced inflammation and pain associated with inhibition of the NF-κB signalling pathway via SARM.

PubMed

Chen, Xuhui; Zhang, Bo; Li, Jiayan; Feng, Miaomiao; Zhang, Yue; Yao, Wenlong; Zhang, Chuanhan; Wan, Li

2018-05-08

This study aimed to investigate whether celastrol (CEL) could alleviate incision-induced pain and decipher its possible mechanism. Sprague-Dawley rats were randomly divided into five groups: naïve, vehicle, CEL (5 μg/paw, 10 μg/paw and 20 μg/paw). CEL or vehicle was administered intraplantarly before plantar surgical incision. Histological examinations of skin tissues were performed after HE staining. Additionally, immunohistochemical staining, RT-PCR and western blot were performed to analyse macrophages, proinflammatory cytokines, SARM and NF-κB expression, respectively. Moreover, the previous mentioned factors were re-evaluated after suppressing SARM expression by shRNA. The plantar incision rats displayed pain-related behaviours and inflammatory infiltration in the skin. The mRNA levels of proinflammatory cytokines, such as IL-1β, IL-6, and TNFα were significantly upregulated in the skin of surgical rats. The expression of sterile α- and armadillo-motif-containing protein (SARM) was downregulated and nuclear factor kappa-B (NF-κB) was activated. Interestingly, CEL could partially restore the pain-related behavioural changes. Furthermore, molecular mechanism of CEL was explored, that included significantly reduction of proinflammatory cytokines mRNA expressions, a significant decrease of p-p65 and p65 levels and a markedly increase of SARM and IkBα expressions in skin tissues. However, supression SARM by shRNA partially eliminated those protective effect of CEL. Our data suggest that intraplantarly administration of CEL attenuates inflammatory and acute pain. This finding could be attributed to regulation of the NF-κB signalling pathway via SARM. These results provide pre-clinical evidence supporting the use of CEL in the treatment of surgical pain. Copyright © 2017. Published by Elsevier Inc.

Antinociceptive and anti-inflammatory effect of sulfated polysaccharide fractions from Sargassum wightii and Halophila ovalis in male Wistar rats

PubMed Central

Neelakandan, Yuvaraj; Venkatesan, Arul

2016-01-01

Aim: The aim of this objective is to evaluate the antinociceptive and anti-inflammatory potential of sulfated polysaccharide purified fractions isolated from brown seaweed Sargassum wightii and seagrass Halophila ovalis in male Wistar rats. Subjects and Methods: Crude sulfated polysaccharide from S. wightii and H. ovalis was subjected to anion exchange chromatography, and the chemical composition was investigated. The antinociceptive activity of purified fractions was investigated using formalin and hot plate test. Carrageenan-induced paw edema, peritonitis model, and Freund's Complete Adjuvant-induced arthritis model were employed to determine the anti-inflammatory activity. Results: In the formalin test, there was a significant reduction in licking time in both phases of the test at a dose of 10 mg/kg. In the hot plate test, the antinociceptive effect was observed only in animals treated with 5, 10 mg/kg suggesting that the analgesic effect occurs through a central action mechanism. Sw FrIV and Ho FrIV significantly inhibited paw edema induced by carrageenan, especially at 3 h after treatment and potentially decreased neutrophil migration at 10 mg/kg, respectively. In Freund's adjuvant-induced arthritic rats, a significant reduction in paw volume was observed in Sw FrIV and Ho FrIV-treated groups (10 mg/kg). Conclusion: Purified components from S. wightii and H. ovalis have strong antinociceptive and anti-inflammatory effect on animal model. However, to determine the molecular mechanism, it is necessary to investigate the effect of purified fractions on inhibition of nitric oxide synthase expression mediated by inhibiting the phosphorylation of various signal proteins in lipopolysaccharide-stimulated RAW264.7 cells. PMID:27721544

Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

PubMed Central

Rao, Sadia Saleem; Najam, Rahila

2016-01-01

Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P < 0.001). In comparison to control, percent inhibition by young coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

Long-Term Treatment by Vitamin B1 and Reduction of Serum Proinflammatory Cytokines, Hyperalgesia, and Paw Edema in Adjuvant-Induced Arthritis

PubMed Central

Zaringhalam, Jalal; Akbari, Akhtar; Zali, Alireza; Manaheji, Homa; Nazemian, Vida; Shadnoush, Mahdi; Ezzatpanah, Somayeh

2016-01-01

Introduction: Immune system is involved in the etiology and pathophysiology of inflammation and vitamins are important sources of substances inducing nonspecific immunomodulatory effects. Given the proinflammatory role of cytokines in the inflammation and pain induction, this study aimed to assess the effects of long-term administration of vitamin B1 on the proinflammatory cytokines, edema, and hyperalgesia during the acute and chronic phases of adjuvant-induced arthritis. Methods: On the first day of study, inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) in the hindpaws of rats. Vitamin B1 at doses of 100, 150, and 200 mg/kg was administrated intraperitoneally during 21 days of the study. Antinociceptive and anti-inflammatory effects of vitamin B1 were also compared to indomethacin (5 mg/kg). Inflammatory symptoms such as thermal hyperalgesia and paw edema were measured by radiant heat and plethysmometer, respectively. Serum TNF-α and IL-1β levels were checked by rat standard enzyme-linked immune sorbent assay (ELISA) specific kits. Results: The results indicated that vitamin B1(150 and 200 mg/kg) attenuated the paw edema, thermal hyperalgesia, and serum levels of TNF-α and IL-1β during both phases of CFA-induced inflammation in a dose-dependent manner. Effective dose of vitamin B1(150 mg/kg) reduced inflammatory symptoms and serum levels of TNF-α and IL-1β compare to indomethacin during the chronic phase of inflammation. Conclusion: Anti-inflammatory and antihyperalgesic effects of vitamin B1 during CFA-induced arthritis, more specifically after chronic vitamin B1 administration, suggest its therapeutic property for inflammation. PMID:27872694

Noradrenaline induces peripheral antinociception by endogenous opioid release.

PubMed

Romero, Thiago Roberto Lima; Soares Santos, Raquel Rodrigues; Castor, Marina Gomes Miranda E; Petrocchi, Júlia Alvarenga; Guzzo, Luciana Souza; Klein, Andre; Duarte, Igor Dimitri Gama

2018-02-23

The aim of this study was to investigate this involvement in not inflammatory model of pain and which opioid receptor subtype mediates noradrenaline-induced peripheral antinociception. NA is involved in the intrinsic control of pain-inducing pro-nociceptive effects in the primary afferent nociceptors. However, inflammation can induce various plastic changes in the central and peripheral noradrenergic system that, upon interaction with the immune system, may contribute, in part, to peripheral antinociception. Hyperalgesia was induced by intraplantar injection of prostaglandin E 2 (PGE 2 , 2 μg) into the plantar surface of the right hind paw and the paw pressure test to evaluated the hyperalgesia was used. Noradrenaline (NA) was administered locally into right hind paw of Wistar rat (160-200 g) alone and after either agents, α 2 -adrenoceptor antagonist yohimbine, α 1 -adrenoceptor antagonist prazosin, β-adrenoceptor antagonist propranolol, μ-opioid antagonist clocinnamox, δ-opioid antagonist naltrindole and κ-opioid antagonist nor-binaltorfimina. In addition, the enkephalinase inhibitor bestatin was administered prior to NA low dose. Intraplantar injection of NA induced peripheral antinociception against hyperalgesia induced by PGE 2 . This effect was reversed, in dose dependent manner, by intraplantar injection of yohimbine, prazosin, propranolol, clocinnamox and naltrindole. However, injection of nor-binaltorfimina did not alter antinociception of NA after PGE 2 hyperalgesia. Bestatin intensified the antinociceptive effects of low-dose of NA. Besides the α 2 -adrenoceptor, the present data provide evidence that, in absence of inflammation, NA activating α 1 and β-adrenoceptor induce endogenous opioid release to produce peripheral antinociceptive effect by μ and δ opioid receptors. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Ethnopharmacological evaluation of some Scorzonera species: in vivo anti-inflammatory and antinociceptive effects.

PubMed

Küpeli Akkol, Esra; Bahadır Acıkara, Ozlem; Süntar, Ipek; Ergene, Burçin; Saltan Çitoğlu, Gülçin

2012-03-27

Scorzonera species are mainly used against inflammation and to relieve pain in Turkish traditional medicine. Therefore, we aimed to assess in vivo anti-inflammatory and antinociceptive activities of the aerial part and root extracts of Scorzonera acuminata, Scorzonera cana var. alpina, Scorzonera cana var. jacquiniana, Scorzonera cana var. radicosa, Scorzonera cinerea, Scorzonera eriophora, Scorzonera incisa, Scorzonera laciniata ssp. laciniata, Scorzonera parviflora and Scorzonera sublanata. For the anti-inflammatory activity evaluation carrageenan, PGE(2) and serotonin-induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema models were used. p-Benzoquinone-induced abdominal constriction test was employed in mice for the assessment of antinociceptive activity. Furthermore chemical composition of the tested extracts was investigated qualitatively and quantitatively by using RP-HPLC method. Some phenolic acids and flavonoids were used as standards. Extracts prepared from the aerial parts of Scorzonera cana var. jacquiniana, Scorzonera cinerea, Scorzonera eriophora, Scorzonera incisa and Scorzonera parviflora showed significant inhibitory effect on carrageenan and PGE(2)-induced hind paw edema model as well as on p-benzoquinone-induced abdominal constriction test. The extracts did not show any remarkable activity on serotonin-induced hind paw edema and TPA-induced mouse ear edema models. Chlorogenic acid was detected as major compounds in all the species investigated. Additionally, among the tested flavonoids, luteolin-7-glucoside, hyperoside and rutin were found to be in different amounts in Scorzonera species. The experimental data revealed that Scorzonera cana var. jacquiniana, Scorzonera cinerea, Scorzonera eriophora, Scorzonera incisa and Scorzonera parviflora possess significant anti-inflammatory and antinociceptive activity. It has been suggested that flavonoids and chlorogenic acid are partly responsible for mentioned activities of Scorzonera species. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.

PubMed

Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Almon, Richard R; Jusko, William J

2008-08-01

A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.

Analgesic and anti-inflammatory effects of UP1304, a botanical composite containing standardized extracts of Curcuma longa and Morus alba.

PubMed

Yimam, Mesfin; Lee, Young-Chul; Moore, Breanna; Jiao, Ping; Hong, Mei; Nam, Jeong-Bum; Kim, Mi-Ran; Hyun, Eu-Jin; Chu, Min; Brownell, Lidia; Jia, Qi

2016-01-01

Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema. A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively. Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.

Dynamical and electronic properties of rare-earth aluminides

NASA Astrophysics Data System (ADS)

Sharma, Ramesh; Sharma, Yamini

2018-04-01

Rare-earth dialuminides belong to a large family of compounds that stabilize in cubic MgCu2 structure. A large number of these compounds are superconducting, amongst these YAl2, LaAl2 and LuAl2 have been chosen as reference materials for studying 4f-electron systems. In order to understand the role of the RE atoms, we have applied the FPLAPW and PAW methods within the density functional theory (DFT). Our results show that the contribution of RE atoms is dominant in both electronic structure and phonon dispersion. The anomalous behavior of superconducting LaAl2 is well explained from an analysis of the electron localization function (ELF), Bader charge analysis, density of electronic states as well as the dynamical phonon vibrational modes. The interaction of phonon modes contributed by low frequency vibrations of La atoms with the high density La 5d-states at EF in LaAl2 lead to strong electron-phonon coupling.

Lycopodium: Careful Harvest Fact Sheet

Treesearch

Elizabeth Nauertz

2003-01-01

Lycopodium comes from the Greek words "luko" (wolf) and "podos" (foot); thus the common name of "wolf's paw" or "Wolf's foot." Despite the common names of clubmoss, Lycopodium species are not related to mosses, but rather to ferns. They are evergreen, perennial, clonal, and rhizomatous in nature.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis.

PubMed

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions.

Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

2014-12-01

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Excavatolide B Isolated from the Culture-Type Formosan Gorgonian Briareum excavatum

PubMed Central

Lin, Yen-You; Lin, Sung-Chun; Feng, Chien-Wei; Chen, Pei-Chin; Su, Yin-Di; Li, Chi-Min; Yang, San-Nan; Jean, Yen-Hsuan; Sung, Ping-Jyun; Duh, Chang-Yih; Wen, Zhi-Hong

2015-01-01

In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue. PMID:25923315

Antioxidant and Anti-inflammatory Activities of a Commercial Noni Juice revealed by Carrageenan-induced Paw Edema.

PubMed

Yilmazer, N; Coskun, C; Gurel-Gurevin, E; Yaylim, I; Eraltan, E H; Ikitimur-Armutak, E I

2016-09-01

This study aimed to investigate antioxidant and anti-inflammatory activities of a commercial product of noni (Morinda citrifolia) juice. Carrageenan-induced rat paw edema was employed as inflammatory model. One control and three experimental groups were formed. Experimental groups were administered noni juice alone, noni juice+carrageenan, and carrageenan alone. Oxidant and antioxidant capacity were determined by d-ROMs test and BAP test, respectively. Plasma concentrations of endothelin-1 and leptin were measured by ELISA. Measurements were performed at zero time and 2nd hour of inflammation. Oxidant capacity decreased in noni-received groups at 2nd hour (p=0.019). Antioxidant capacity of the group which received noni alone was found to be higher at 2nd hour (p=0.036). Plasma concentrations of endothelin-1 and leptin were notably lower in noni-received groups (p=0.001 and p=0.021, respectively). The results show that the commercial noni juice investigated has pronounced antioxidant and anti-inflammatory activities.

Induction of lyme arthritis in LSH hamsters

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

Schmitz, J.L.; Schell, R.F.; Hejka, A.

1988-09-01

In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling weremore » dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis.« less

Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: their anti-inflammatory and anti-nociceptive activities.

PubMed

Shafi, Syed; Alam, Mohammad Mahboob; Mulakayala, Naveen; Mulakayala, Chaitanya; Vanaja, G; Kalle, Arunasree M; Pallu, Reddanna; Alam, M S

2012-03-01

A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Antinociceptive effects of radon inhalation on formalin-induced inflammatory pain in mice.

PubMed

Yamato, Keiko; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

2013-04-01

Radon therapy is clinically useful for the treatment of inflammatory diseases. The mechanisms of pain relief remain to be fully elucidated. In this study, we investigated the antinociceptive effects of radon inhalation in a mouse model of formalin-induced inflammatory pain. Immediately, after radon inhalation at a concentration of background level (ca. 19 Bq/m(3)), 1,000 or 2,000 Bq/m(3) for 24 h, 1.35 % formalin (0.5 % formaldehyde in saline, 20 μl) was subcutaneously injected into the hind paw of mice, and we measured licking response time. Radon inhalation inhibited the second phase of response in formalin test. Formalin administration induced nociception and increased tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) levels in serum and leukocyte migration in paws. Concurrently, formalin injection decreased antioxidative functions. Radon inhalation produced antinociceptive effects, i.e., lowered serum TNF-α and NO levels, and restored antioxidative functions. The results showed that radon inhalation inhibited formalin-induced inflammatory pain.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis

PubMed Central

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions. PMID:25767759

A model of peripheral microvascular injury: irreversible caudal necrosis induced in carrageenan-inflamed rats treated with anti-inflammatory drugs and mild chilling: a pluricausal thrombo-haemorrhagic phenomenon.

PubMed

Whitehouse, M W; Rainsford, K D

1985-01-01

A florid tail injury was observed in carrageenan-inflamed rats previously treated with acidic non-steroidal anti-inflammatory (NSAI) drugs to suppress paw inflammation and then exposed to mild chilling (7-10 degrees C for 10-16 h). All three treatments, i.e. NSAI drug + carrageenan paw oedema + mild chilling treatment, were required for the development of this condition. Histological observations suggest that the tissue necrosis was initiated by a primary disturbance of the peripheral vasculature. The possible involvement of suppressed prostaglandin (PG) production in the aetiology of this condition is indicated by the fact that it was totally reversed by prior treatment with PGE2. This appears to be a classical pluricausal thrombohaemorrhagic phenomenon (of Selye), with cold-stress being the sensitizer and carrageenan and NSAI drugs being the challenger. The possibilities are considered of employing this tail injury model as a convenient method of developing drugs to control microvascular disturbances in man.

Investigation of the central and peripheral analgesic and anti-inflammatory activity of Draksharishta an Indian Ayurvedic formulation

PubMed Central

Kabir, Ashraf-ul; Samad, Mehdi Bin; D′Costa, Ninadh Malrina; Hannan, Juardar Mohammad

2012-01-01

Rationale: Draksharishta (DRK) is an Ayurvedic formulation approved by the “National formulary of Ayurvedic Medicine 2011”, of Bangladesh. It is widely available in the Bangladeshi market as an effective preparation to treat lumbago, sciatia and arthritic pain of joints. But there are very scientific evidences available to support their common uses. Objectives: Our present studies make an attempt toward identifying probable antinociceptive and anti-inflammatory effect and its mechanisms of DRK. Findings: DRK, at three doses, (10 mL/kg, 20 mL/kg, and 40 mL/kg) showed no involvement of the CNS in antinociceptive activity of the test drug. Both Carrageenan-induced paw edema and acetic acid writhing tests gave significant results (P < 0.05), indicating possible peripheral analgesic and anti-inflammatory action. Formalin-induced paw- licking test showed that DRK had significant effect in suppressing inflammatory pain (P < 0.05) but not neurogenic pain. Conclusions: Hence our study shows anti-inflammatory and peripheral analgesic action for DRK. PMID:24826047

Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

PubMed

Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

2013-03-01

Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action. Georg Thieme Verlag KG Stuttgart · New York.

IN VIVO ANTI-INFLAMMATORY EFFECTS OF TARAXASTEROL AGAINST ANIMAL MODELS

PubMed Central

Wang, Ying; Li, Guan-Hao; Liu, Xin-Yu; Xu, Lu; Wang, Sha-Sha; Zhang, Xue-Mei

2017-01-01

Background: Traditional Chinese medicine Taraxacum officinale has been widely used to treat various inflammatory diseases. Taraxasterol is one of the main active components isolated from Taraxacum officinale. Recently, we have demonstrated that taraxasterol has the in vitro anti-inflammatory effects. This study aims to determine the in vivo anti-inflammatory effects of taraxasterol against animal models. Materials and Methods: Anti-inflammatory effects were assessed in four animal models by using dimethylbenzene-induced mouse ear edema, carrageenan-induced rat paw edema, acetic acid-induced mouse vascular permeability and cotton pellet-induced rat granuloma tests. Results: Our results demonstrated that taraxasterol dose-dependently attenuated dimethylbenzene-induced mouse ear edema and carrageenan-induced rat paw edema, decreased acetic acid-induced mouse vascular permeability and inhibited cotton pellet-induced rat granuloma formation. Conclusion: Our finding indicates that taraxasterol has obvious in vivo anti-inflammatory effects against animal models. It will provide experimental evidences for the traditional use of Taraxacum officinale and taraxasterol in inflammatory diseases. PMID:28480383

Resolvin D3 is dysregulated in arthritis and reduces arthritic inflammation

PubMed Central

Arnardottir, Hildur H.; Dalli, Jesmond; Norling, Lucy V.; Colas, Romain A.; Perretti, Mauro; Serhan, Charles N.

2016-01-01

Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rv) are a new family from the endogenous specialized pro-resolving lipid mediators (SPM) that actively stimulate resolution of inflammation. Herein, using lipid mediator (LM) metabololipidomics with murine joints we found a temporal regulation of endogenous SPM during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series resolvins, e.g. Resolvin (Rv) D1, RvD2, RvD3 and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared to self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis (RA) patients compared to healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores and edema. Together, these findings provide evidence for dysregulated endogenous RvD3 levels in inflamed paw joints and its potent actions in reducing murine arthritis. PMID:27534559

Techniques for modeling the reliability of fault-tolerant systems with the Markov state-space approach

NASA Technical Reports Server (NTRS)

Butler, Ricky W.; Johnson, Sally C.

1995-01-01

This paper presents a step-by-step tutorial of the methods and the tools that were used for the reliability analysis of fault-tolerant systems. The approach used in this paper is the Markov (or semi-Markov) state-space method. The paper is intended for design engineers with a basic understanding of computer architecture and fault tolerance, but little knowledge of reliability modeling. The representation of architectural features in mathematical models is emphasized. This paper does not present details of the mathematical solution of complex reliability models. Instead, it describes the use of several recently developed computer programs SURE, ASSIST, STEM, and PAWS that automate the generation and the solution of these models.

Hydrology and land use in Van Buren County, Michigan

USGS Publications Warehouse

Cummings, T.R.; Twenter, F.R.; Holtschlag, D.J.

1984-01-01

This report gives the results of an investigation to determine the chemical and physical characteristics of ground and surface water in Van Buren County and to relate these characteristics to the agricultural use of land. Chemical inputs to the hydrologic system, including those from precipitation, animal wastes, septic tanks, and fertilizers, are assessed. Land-use, geologic setting, and hydrologic conditions are given as a necessary framework for interpretations. The land surface in Van Buren county in southwestern Michigan is flat to rolling, and ranges in altitude from 580 to 1,050 feet. About 30,000 acres or 7.4 percent of land is irrigated. Annual precipitation ranges from 34 to 36 inches. Two rivers--the Paw Paw and South Branch Black--drain most of the county. During this study, the maximum discharge of the Paw Paw River was 2,500 cubic feet per second; the minimum discharge was 202 cubic feet per second. The average discharge of the South Branch Black River during a 17- year period of record has been 106 cubic feet per second. Glacial deposits are the principal source of ground-water supplies. These deposits range in thickness from 100 to 600 feet and consist of till, outwash, and materials of lacustrine and eolian origin. In places the deposits fill buried valleys that are as much as 400 feet deep. The Coldwater Shale of Mississippian age, which underlies the glacial deposits, is mostly shale and usually yields only small amounts of salty water. Of the glacial deposits, outwash is the most productive aquifer. Most domestic wells obtain water from outwash at depths ranging from 15 to 160 feet. Irrigation wells capable of yielding 1,000 gallons per minute generally are about 200 feet deep. In places in the western part of the county, glacial deposits, which are several hundred feet thick, are mostly clay and yield little or no water. Areal variations in the chemical and physical characteristics of ground and surface water are related to land use and chemical inputs to the hydrologic system. Information on fertilizer application, septic-tank discharges, animal wastes, and precipitation and dry fallout show that 72.7 percent of nitrogen input is from fertilizer, 21.3 percent from precipitation and dry fallout, 4.5 percent from animal wastes, and 1.5 percent from septic tanks.Streams and lakes generally contain a calcium bicarbonate type water. The dissolved-solids concentration of streams ranged from 56 to 749 milligrams per liter, and that of lakes, from 28 to 310 milligrams per liter. Water of streams is hard but at most locations is suitable for most uses. Total nitrogen concentrations as high as 15 milligrams per liter were found at two sites. Pesticides (Simazine and Atrazine) were detected at some sites. Relationships between land use and water quality of streams indicate that the nitrate yield of land increases as the percentage of crop land, pasture, and feeding operation increases in a drainage area. Water of lakes also is suitable for most uses, although Alachlor, Atrazine, Silvex, Simazine, Treflan, or 2,4-D were detected in 26 samples. Ground water is of a calcium bicarbonate type, although sodium, sulfate, and chloride are the predominant ions at some locations. Dissolved-solids concentrations ranged from 112 to 878 milligrams per liter; concentrations of trace metals exceeding those common in water were detected at some locations. Nitrate concentrations in the southern eight townships were generally higher than in the northern ten townships; water from 22 percent of the wells in the southern townships exceeded the 10 milligrams per liter drinking-water standard of the U.S. Environmental Protection Agency. High nitrate concentrations probably are related to fertilizer applications, but equally important seems to be the quantity of irrigation water applied. Oil-field activity in the northern part of the county seems to have increased the chloride concentrations of ground water in some places. Model simulations of the ground-water flow system matched measured conditions if hydraulic conductivities of 10 to 35 feet per day and a recharge rate of 11.8 inches per year were used. Simulations of 500 gallons per minute pumping from an unconfined aquifer indicated only 2 to 3 feet of drawdown in the vicinity of the pumping well. Similar pumping from a confined aquifer, however, produced about 10 feet of drawdown. Simulations of increased pumping for the irrigated area in the southern part of the county indicated that significant drawdown might be expected in some parts.

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

PubMed Central

2013-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Methods Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. Results CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. Conclusions TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway. PMID:23768044

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

PubMed

Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

2013-06-15

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.

Comparative Metabolic Physiology in the 'omics' Era: A Call to Arms, Paws, Flippers, and Claws

USDA-ARS?s Scientific Manuscript database

In nutrition, medicine, and animal science, metabolism research is often focused on solving questions using a single organism. Outcomes are most often linked to translational outcomes--understanding or treating a disease, optimizing nutritional status, improving select qualities of production anima...

Modeling nuclear field shift isotope fractionation in crystals

NASA Astrophysics Data System (ADS)

Schauble, E. A.

2013-12-01

In this study nuclear field shift fractionations in solids (and chemically similar liquids) are estimated using calibrated density functional theory calculations. The nuclear field shift effect is a potential driver of mass independent isotope fractionation(1,2), especially for elements with high atomic number such as Hg, Tl and U. This effect is caused by the different shapes and volumes of isotopic nuclei, and their interactions with electronic structures and energies. Nuclear field shift isotope fractionations can be estimated with first principles methods, but the calculations are computationally difficult, limiting most theoretical studies so far to small gas-phase molecules and molecular clusters. Many natural materials of interest are more complex, and it is important to develop ways to estimate field shift effects that can be applied to minerals, solutions, in biomolecules, and at mineral-solution interfaces. Plane-wave density functional theory, in combination with the projector augmented wave method (DFT-PAW), is much more readily adapted to complex materials than the relativistic all-electron calculations that have been the focus of most previous studies. DFT-PAW is a particularly effective tool for studying crystals with periodic boundary conditions, and may also be incorporated into molecular dynamics simulations of solutions and other disordered phases. Initial calibrations of DFT-PAW calculations against high-level all-electron models of field shift fractionation suggest that there may be broad applicability of this method to a variety of elements and types of materials. In addition, the close relationship between the isomer shift of Mössbauer spectroscopy and the nuclear field shift isotope effect makes it possible, at least in principle, to estimate the volume component of field shift fractionations in some species that are too complex even for DFT-PAW models, so long as there is a Mössbauer isotope for the element of interest. Initial results will be presented for calculations of liquid-vapor fractionation of cadmium and mercury, which indicate an affinity for heavy isotopes in the liquid phase. In the case of mercury the results match well with recent experiments. Mössbauer-calibrated fractionation factors will also be presented for tin and platinum species. Platinum isotope behaviour in metals appears to particularly interesting, with very distinct isotope partitioning behaviour for iron-rich alloys, relative to pure platinum metal. References: 1) Bigeleisen, J. (1996) J. Am. Chem. Soc. 118, 3676-3680. 2) Nomura, M., Higuchi, N., Fujii, Y. (1996) J. Am. Chem. Soc. 118, 9127-9130.

SURE - SEMI-MARKOV UNRELIABILITY RANGE EVALUATOR (VAX VMS VERSION)

NASA Technical Reports Server (NTRS)

Butler, R. W.

1994-01-01

The Semi-Markov Unreliability Range Evaluator, SURE, is an analysis tool for reconfigurable, fault-tolerant systems. Traditional reliability analyses are based on aggregates of fault-handling and fault-occurrence models. SURE provides an efficient means for calculating accurate upper and lower bounds for the death state probabilities for a large class of semi-Markov models, not just those which can be reduced to critical-pair architectures. The calculated bounds are close enough (usually within 5 percent of each other) for use in reliability studies of ultra-reliable computer systems. The SURE bounding theorems have algebraic solutions and are consequently computationally efficient even for large and complex systems. SURE can optionally regard a specified parameter as a variable over a range of values, enabling an automatic sensitivity analysis. Highly reliable systems employ redundancy and reconfiguration as methods of ensuring operation. When such systems are modeled stochastically, some state transitions are orders of magnitude faster than others; that is, fault recovery is usually faster than fault arrival. SURE takes these time differences into account. Slow transitions are described by exponential functions and fast transitions are modeled by either the White or Lee theorems based on means, variances, and percentiles. The user must assign identifiers to every state in the system and define all transitions in the semi-Markov model. SURE input statements are composed of variables and constants related by FORTRAN-like operators such as =, +, *, SIN, EXP, etc. There are a dozen major commands such as READ, READO, SAVE, SHOW, PRUNE, TRUNCate, CALCulator, and RUN. Once the state transitions have been defined, SURE calculates the upper and lower probability bounds for entering specified death states within a specified mission time. SURE output is tabular. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. Although different solution techniques are utilized on different programs, it is possible to have a common input language. The Systems Validation Methods group at NASA Langley Research Center has created a set of programs that form the basis for a reliability analysis workstation. The set of programs are: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920); and the FTC fault tree tool (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree. PAWS/STEM and SURE are programs which interpret the same SURE language, but utilize different solution methods. ASSIST is a preprocessor that generates SURE language from a more abstract definition. SURE, ASSIST, and PAWS/STEM are also offered as a bundle. Please see the abstract for COS-10039/COS-10041, SARA - SURE/ASSIST Reliability Analysis Workstation, for pricing details. SURE was originally developed for DEC VAX series computers running VMS and was later ported for use on Sun computers running SunOS. The VMS version (LAR13789) is written in PASCAL, C-language, and FORTRAN 77. The standard distribution medium for the VMS version of SURE is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The Sun UNIX version (LAR14921) is written in ANSI C-language and PASCAL. An ANSI compliant C compiler is required in order to compile the C portion of this package. The standard distribution medium for the Sun version of SURE is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. SURE was developed in 1988 and last updated in 1992. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. TEMPLATE is a registered trademark of Template Graphics Software, Inc. UNIX is a registered trademark of AT&T Bell Laboratories. Sun3 and Sun4 are trademarks of Sun Microsystems, Inc.

SURE - SEMI-MARKOV UNRELIABILITY RANGE EVALUATOR (SUN VERSION)

NASA Technical Reports Server (NTRS)

Butler, R. W.

1994-01-01

The Semi-Markov Unreliability Range Evaluator, SURE, is an analysis tool for reconfigurable, fault-tolerant systems. Traditional reliability analyses are based on aggregates of fault-handling and fault-occurrence models. SURE provides an efficient means for calculating accurate upper and lower bounds for the death state probabilities for a large class of semi-Markov models, not just those which can be reduced to critical-pair architectures. The calculated bounds are close enough (usually within 5 percent of each other) for use in reliability studies of ultra-reliable computer systems. The SURE bounding theorems have algebraic solutions and are consequently computationally efficient even for large and complex systems. SURE can optionally regard a specified parameter as a variable over a range of values, enabling an automatic sensitivity analysis. Highly reliable systems employ redundancy and reconfiguration as methods of ensuring operation. When such systems are modeled stochastically, some state transitions are orders of magnitude faster than others; that is, fault recovery is usually faster than fault arrival. SURE takes these time differences into account. Slow transitions are described by exponential functions and fast transitions are modeled by either the White or Lee theorems based on means, variances, and percentiles. The user must assign identifiers to every state in the system and define all transitions in the semi-Markov model. SURE input statements are composed of variables and constants related by FORTRAN-like operators such as =, +, *, SIN, EXP, etc. There are a dozen major commands such as READ, READO, SAVE, SHOW, PRUNE, TRUNCate, CALCulator, and RUN. Once the state transitions have been defined, SURE calculates the upper and lower probability bounds for entering specified death states within a specified mission time. SURE output is tabular. The mathematical approach chosen to solve a reliability problem may vary with the size and nature of the problem. Although different solution techniques are utilized on different programs, it is possible to have a common input language. The Systems Validation Methods group at NASA Langley Research Center has created a set of programs that form the basis for a reliability analysis workstation. The set of programs are: SURE reliability analysis program (COSMIC program LAR-13789, LAR-14921); the ASSIST specification interface program (LAR-14193, LAR-14923), PAWS/STEM reliability analysis programs (LAR-14165, LAR-14920); and the FTC fault tree tool (LAR-14586, LAR-14922). FTC is used to calculate the top-event probability for a fault tree. PAWS/STEM and SURE are programs which interpret the same SURE language, but utilize different solution methods. ASSIST is a preprocessor that generates SURE language from a more abstract definition. SURE, ASSIST, and PAWS/STEM are also offered as a bundle. Please see the abstract for COS-10039/COS-10041, SARA - SURE/ASSIST Reliability Analysis Workstation, for pricing details. SURE was originally developed for DEC VAX series computers running VMS and was later ported for use on Sun computers running SunOS. The VMS version (LAR13789) is written in PASCAL, C-language, and FORTRAN 77. The standard distribution medium for the VMS version of SURE is a 9-track 1600 BPI magnetic tape in VMSINSTAL format. It is also available on a TK50 tape cartridge in VMSINSTAL format. Executables are included. The Sun UNIX version (LAR14921) is written in ANSI C-language and PASCAL. An ANSI compliant C compiler is required in order to compile the C portion of this package. The standard distribution medium for the Sun version of SURE is a .25 inch streaming magnetic tape cartridge in UNIX tar format. Both Sun3 and Sun4 executables are included. SURE was developed in 1988 and last updated in 1992. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. TEMPLATE is a registered trademark of Template Graphics Software, Inc. UNIX is a registered trademark of AT&T Bell Laboratories. Sun3 and Sun4 are trademarks of Sun Microsystems, Inc.

Osthole ameliorates neurogenic and inflammatory hyperalgesia by modulation of iNOS, COX-2, and inflammatory cytokines in mice.

PubMed

Singh, Gurjit; Bhatti, Rajbir; Mannan, Rahul; Singh, Drishtant; Kesavan, Anup; Singh, Palwinder

2018-05-07

Osthole is a bioactive component reported in medicinal plants such as Angelica pubescens and Cnidium monnieri, known for analgesic activity. However, the toxicity, median effective dose (ED 50 ), and dual modulation of nitric oxide and cyclooxygenase pathways along with inflammatory cytokines of osthole are yet to be determined. The animals (mice) were assessed for general behaviour and mortality in varying doses (50, 300, and 2000 mg kg -1 ) of osthole for acute toxicity over 14 days. The analgesic activity was investigated using acetic acid and formalin-induced hyperalgesia, and anti-inflammatory activity was explored in carrageenan-induced paw oedema. ED 50 of osthole was calculated using Design Expert software. Involvement of nitric oxide and cyclooxygenase pathways was investigated by agonist challenges with L-arginine and substance P, respectively. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined in spinal sections by immunohistochemical analysis. Lipopolysaccharide (LPS) challenge was used to assess in vivo effect on inflammatory cytokines (TNFα and IL-6). Acute toxicity studies revealed no behavioural abnormality or mortality on osthole treatment and unremarkable histological findings. Osthole was found to significantly decrease acetic acid and formalin-induced hyperalgesia (ED 50  = 5.43 mg kg -1 ) and carrageenan-induced paw oedema with no toxicity symptoms. Osthole produced a marked decrease in iNOS and COX-2 expression as well as TNFα and IL-6. The findings corroborate to modulation of iNOS and COX-2 and inflammatory cytokines by osthole. This study provides promising insights and prospects for application of osthole in pain management.