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Thermal Stimulus (thermal + stimulus)

Distribution by Scientific Domains

Medical Sciences	66%

Selected Abstracts

Multiphysics Modelling of Volume Phase Transition of Ionic Hydrogels Responsive to Thermal Stimulus

MACROMOLECULAR BIOSCIENCE, Issue 9 2005
Hua Li
Abstract Summary: This paper presents the analysis of the volume phase transition of ionic thermo-sensitive hydrogels to thermal stimulus through mathematical modelling. The model is termed the multi-effect-coupling thermal-stimulus (MECtherm) model and it considers the effects of multi-phases and multi-physics. Its application to steady-state analysis of the hydrogels in swelling equilibrium is validated against available experimental data for the relation between volume swelling ratio and temperature, in which very good agreement is achieved. The phenomenon of volume phase transition is studied for the thermal-stimulus responsive hydrogel. The numerical studies predict well the influences of initially fixed charge density and initial volume fraction of polymeric network on the swelling equilibrium of the hydrogels. Comparison of numerical simulations with the experimental swelling data for the thermo-sensitive PNIPA hydrogels in pure water. [source]

Comparison of Analgesic Effects of Khat (Catha edulis Forsk) Extract, D-Amphetamine and Ibuprofen in Mice

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2000
JOHN CONNOR
We have compared the analgesic properties of khat (Catha edulis Forsk) extract, amphetamine and ibuprofen in mice. After intragastric administration of the drugs analgesia was measured relative to water-injected controls using the hot-plate, the tail-flick, and abdominal-constriction tests. At the highest doses examined (amphetamine 1.8 mg kg,1, ibuprofen 90 mg kg,1, khat extract 1800 mg kg,1), all three substances produced analgesia, but the order of efficacy varied with the test. Khat and ibuprofen were significantly different from the control in the hot-plate assay at three or more time points post-injection. In the tail-flick test, khat and amphetamine were efficacious; ibuprofen means were somewhat lower but still significantly different from control. Higher doses of the drugs decreased the number of responses in the acetic acid-induced abdominal-constriction assay. We conclude that khat, like amphetamine and ibuprofen, can relieve pain. Differences in assay results may reflect differences in modes and sites of action, as well as in the type of pain generated by the chemical and thermal stimuli for nociception. [source]

Sporadic onset of erythermalgia: A gain-of-function mutation in Nav1.7

ANNALS OF NEUROLOGY, Issue 3 2006
Chongyang Han BS
Objective Inherited erythermalgia (erythromelalgia) is an autosomal dominant disorder in which patients experience severe burning pain in the extremities, in response to mild thermal stimuli and exercise. Although mutations in sodium channel Nav1.7 have been shown to underlie erythermalgia in several multigeneration families with the disease that have been investigated to date, the molecular basis of erythermalgia in sporadic cases is enigmatic. We investigated the role of Nav1.7 in a sporadic case of erythermalgia in a Chinese family. Methods Genomic DNA from patients and their asymptomatic family members were sequenced to identify mutations in Nav1.7. Whole-cell patch clamp analysis was used to characterize biophysical properties of wild-type and mutant Nav1.7 channels in mammalian cells. Results A single amino acid substitution in the DIIS4-S5 linker of Nav1.7 was present in two children whose parents were asymptomatic. The asymptomatic father was genetically mosaic for the mutation. This mutation produces a hyperpolarizing shift in channel activation and an increase in amplitude of the response to slow, small depolarizations. Interpretation Founder mutations in Nav1.7, which can confer hyperexcitability on peripheral sensory neurons, can underlie sporadic erythermalgia. Ann Neurol 2006 [source]

A Shuttling Molecular Machine with Reversible Brake Function

CHEMISTRY - A EUROPEAN JOURNAL, Issue 11 2008
Keiji Hirose Dr.
Abstract Design, synthesis, and demonstration of a prototype of a shuttling molecular machine with a reversible brake function are reported. It is a photochemically and thermally reactive rotaxane composed of a dianthrylethane-based macrocycle as the ring component and a dumbbell shaped molecular unit with two, secondary ammonium stations separated by a phenylene spacer as the axle component. The rate of shuttling motion was shown to be reduced to less than 1,% (from 340 to <2.5,s,1) by reducing the size of the ring component from 30-crown-8 to 24-crown-8 macrocycles upon photoirradiation. The ring component was turned back to 30-crown-8 by thermal ring opening, thus establishing a reversible brake function that works in response to photochemical and thermal stimuli. [source]

Does aerobic fitness influence microvascular function in healthy adults at risk of developing Type 2 diabetes?

DIABETIC MEDICINE, Issue 4 2005
A. R. Middlebrooke
Abstract Aim To investigate whether aerobic fitness is associated with skin microvascular function in healthy adults with an increased risk of developing Type 2 diabetes. Methods Twenty-seven healthy normal glucose-tolerant humans with either a previous diagnosis of gestational diabetes or having two parents with Type 2 diabetes and 27 healthy adults who had no history of diabetes were recruited. Maximal oxygen uptake was assessed using an incremental exercise test to exhaustion. Skin microvascular function was assessed using laser Doppler techniques as the maximum skin hyperaemic response to a thermal stimulus (maximum hyperaemia) and the forearm skin blood flow response to the iontophoretic application of acetylcholine (ACh) and sodium nitroprusside. Results Maximal oxygen uptake was not significantly different in the ,at-risk' group compared with healthy controls. Maximum hyperaemia was reduced in those ,at risk' (1.29 ± 0.30 vs. 1.46 ± 0.33 V, P = 0.047); however, the peak response to acetylcholine or sodium nitroprusside did not differ in the two groups. A significant positive correlation was demonstrated between maximal oxygen uptake and maximum hyperaemia (r = 0.52, P = 0.006 l/min and r = 0.60, P = 0.001 ml/kg/min) and peak ACh response (r = 0.40, P = 0.04 l/min and r = 0.47, P = 0.013 ml/kg/min) in the ,at-risk' group when expressed in absolute (l/min) or body mass-related (ml/kg/min) terms. No significant correlations were found in the control group. Conclusions In this ,at-risk' group with skin microvascular dysfunction maximal oxygen uptake was not reduced compared with healthy controls. However, in the ,at-risk' group alone, individuals with higher levels of aerobic fitness also had better microvascular and endothelial responsiveness. [source]

CNS response to a thermal stressor in human volunteers and rats may predict the clinical utility of analgesics

DRUG DEVELOPMENT RESEARCH, Issue 1 2007
David Borsook
Abstract fMRI was used to test the hypothesis that global brain activation following a stressor (a thermal stimulus) that activates multiple brain circuits in healthy subjects can predict which drugs have higher potential for clinical utility for neuropathic pain. The rationale is that a drug will modulate multiple neural circuits that are activated by the system-specific stressor (e.g., pain). In neuropathic pain, some brain circuits have altered function, but most brain systems are "normal." Thus, the manner in which a drug effect on neural circuits is modulated by the stressor may provide insight into the clinical utility based on the readout of brain activation in response to the stimulus. Six drugs with known clinical efficacy (or lack thereof) in treating neuropathic pain were selected and the CNS response to each drug in the presence or absence of a pain stimulus was examined. The present results suggest that it is possible to identify potentially effective drugs based on patterns of brain activation in healthy human subjects and indicate that CNS activity is a more sensitive measure of drug action than standard psychophysical measures of pain intensity. This approach was repeated in rats and showed that a similar fMRI paradigm segregates these drugs in a similar manner suggesting a potential "translational tool" in evaluating drug efficacy for neuropathic pain. The sensitivity of this paradigm using fMRI allows clinical screening in small groups of healthy subjects, suggesting it could become a useful tool for drug development as well as for elucidating the mechanisms of neuropathic disease and therapy. Drug Dev. Res. 68:23,41, 2007. © 2007 Wiley-Liss, Inc. [source]

Multiphysics Modelling of Volume Phase Transition of Ionic Hydrogels Responsive to Thermal Stimulus

Triggering of proteinase-activated receptor 4 leads to joint pain and inflammation in mice

ARTHRITIS & RHEUMATISM, Issue 3 2009
Jason J. McDougall
Objective To investigate the role of proteinase-activated receptor 4 (PAR-4) in mediating joint inflammation and pain in mice. Methods Knee joint blood flow, edema, and pain sensitivity (as induced by thermal and mechanical stimuli) were assessed in C57BL/6 mice following intraarticular injection of either the selective PAR-4 agonist AYPGKF-NH2 or the inactive control peptide YAPGKF-NH2. The mechanism of action of AYPGKF-NH2 was examined by pretreatment of each mouse with either the PAR-4 antagonist pepducin P4pal-10 or the bradykinin antagonist HOE 140. Finally, the role of PAR-4 in mediating joint inflammation was tested by pretreating mice with acutely inflamed knees with pepducin P4pal-10. Results PAR-4 activation caused a long-lasting increase in joint blood flow and edema formation, which was not seen following injection of the control peptide. The PAR-4,activating peptide was also found to be pronociceptive in the joint, where it enhanced sensitivity to a noxious thermal stimulus and caused mechanical allodynia and hyperalgesia. The proinflammatory and pronociceptive effects of AYPGKF-NH2 could be inhibited by pepducin P4pal-10 and HOE 140. Finally, pepducin P4pal-10 ameliorated the clinical and physiologic signs of acute joint inflammation. Conclusion This study demonstrates that local activation of PAR-4 leads to proinflammatory changes in the knee joint that are dependent on the kallikrein,kinin system. We also show for the first time that PARs are involved in the modulation of joint pain, with PAR-4 being pronociceptive in this tissue. Thus, blockade of articular PAR-4 may be a useful means of controlling joint inflammation and pain. [source]

Pharmacokinetic,pharmacodynamic modelling of the analgesic effects of lumiracoxib, a selective inhibitor of cyclooxygenase-2, in rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010
DA Vásquez-Bahena
Background and purpose:, This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats. Experimental approach:, Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg,1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg,1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI. Results:, A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT0/(1 +MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL,1. Conclusions:, The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. [source]