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Isoprostanes are a novel class of eicosanoids primarily formed by peroxidation of arachidonic acid. Because of their potential as inflammatory and/or hyperalgesic agents whose formation is largely independent of cyclooxygenases, we examined whether 8-iso prostaglandin E(2) (8-iso PGE(2)) or 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)) reduces mechanical and thermal withdrawal threshold in rats, and whether they sensitize rat sensory neurons. Injection of 1 microg of 8-iso PGE(2) (in 2.5 microl) into the hindpaw of rats significantly reduced mechanical and thermal withdrawal thresholds, whereas 1 microg of 8-iso PGF(2alpha) elicited a transient decrease in only the mechanical withdrawal threshold. Both isoprostanes enhanced the firing of C-nociceptors in a concentration-dependent manner when injected into peripheral receptive fields. Exposing sensory neurons grown in culture to 1 microM 8-iso PGE(2) or 8-iso PGF(2alpha) augmented the number of action potentials elicited by a ramp of depolarizing current. In contrast, 8-iso PGE(2) but not 8-iso PGF(2alpha) enhanced the release of substance P- and calcitonin gene-related peptide-like immunoreactivity from isolated sensory neurons. Ten micromolar 8-iso PGE(2) stimulated peptide release directly, whereas treatment with 1 microM 8-iso PGE(2) augmented the release evoked by either bradykinin or capsaicin. Pretreating neuronal cultures with the nonsteroidal anti-inflammatory drug ketorolac did not alter the sensitizing action of 8-iso PGE(2) on peptide release, suggesting that this action of the isoprostane was not secondary to the production of prostaglandins via the cyclooxygenase pathway. These data support the notion that isoprostanes are an important class of inflammatory mediators that augment nociception.

[3H]5-HT revealed the presence of serotonin receptors in cultured rat sensory neurons. [3H]5-CT binding was inhibited by cyanopindolol with an IC50 of 0.87 +/- 0.30 nM, suggesting the expression of the 5-HT1B receptor in these neurons. The presence of 5-HT1B receptors was confirmed by the displacement of [125I]Iodocyanopindolol binding by cyanopindolol with an IC50 of 2.43 +/- 0.81 nM. 5-HT1B receptors are the predominant type of serotonin receptors labeled by [3H]5-HT in cultured DRG neurons, representing approximately 60% of the specific [3H]5-HT binding sites. In addition, 5-HT1D and 5-HT2A receptor binding was also found in these neurons. RT-PCR analysis of RNA isolated from embryonic sensory neurons in culture confirmed the expression of 5-HT1B, 5-HT1D and 5-HT2A receptor mRNA. It also demonstrated the presence of 5-HT1F, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT5B receptor mRNA and the absence of 5-HT1A, 5-HT1E, 5-HT2B, 5-HT6 and 5-HT7 mRNA. The identification of multiple subtypes of serotonin receptors expressed in cultured embryonic sensory neurons suggests that DRG neuronal cultures may be an excellent model to examine the direct effects of serotonin on the activity of these sensory neurons.

The thermoelastic properties of polymer networks are usually obtained by studying the effect of temperature on the magnitude of the stress of samples subjected to uniaxial elongation. It is assumed that polymer networks are in the region of small elongation characterized by reversible deformation, and that the results obtained represent equilibrium values. The method makes it possible to characterize the network by a series of thermodynamic parameters, of which the ratio fu/f is used most frequently. This ratio, fu/f, expresses the ratio between the energetic component fu and the total elastic force f. The values of fu/f are technically important parameters which may serve as a measure of the "ideality" of an elastomer. For an ideal elastic polymer, i.e., the polymer the elasticity of which is entirely entropic in origin, it can be written fu/f = 0. The significance of thermoelasticity was markedly increased when the phenome-nological parameter fu/f was shown to be interpretable on the molecular level as a consequence of conformational changes in macro-molecular chains. By refinement of the molecular theory of rubberlike elasticity, a relation between fu /f and the temperature coefficient of the unperturbed dimensions of the chains d In r02/dT (TCUD) was established [l, 2]

To determine whether opioid receptors in sensory neurons are regulated by chronic exposure to opioids, we assessed the binding of various opioid ligands to membranes derived from isolated rat dorsal root ganglia neurons grown in culture. Equilibrium binding of [3H]diprenorphine onto membranes from cells grown for 13-15 days revealed a saturable binding site with a Kd value of 0.3 +/- 0.2 nM and an approximate Bmax value of 1300 +/- 200 fmol/mg of protein. [3H]Diprenorphine binding increased 3-fold from 1-15 days in culture. The mu receptors represent approximately 70 +/- 11% of the [3H]diprenorphine binding sites, as indicated by saturation binding of [3H]DAMGO. The kappa and delta receptors represent approximately 10 +/- 3% and approximately 5 +/- 2% of the [3H]diprenorphine binding sites, respectively. Preexposure of neurons to 10 microM naloxone for 48 hr up-regulated the receptors by 40%, whereas incubation with 100 nM to 10 microM DAMGO for 48 hr resulted in a significant decrease in the Bmax value of opioid receptors, with a maximum reduction of 70%. The identification of a high level of opioid receptors expressed in isolated sensory neurons and their modulation by opioids demonstrates that cultured sensory neurons are an excellent model with which to study opioid receptor regulation.

The development of tolerance to the depressant and stimulant actions of morphine on locomotor activity and brain acetylcholine (ACh) utilization (indirect turnover) was investigated in the rat. When administered to nontolerant rats, 1.0 mg/ kg s.c. of morphine produced an increase in locomotor activity and a concomitant increase in ACh utilization. Larger doses produced biphasic effects on locomotor activity, but only 10 mg/kg s.c. resulted in both an initial decrease and subsequent increase in ACh utilization in whole rat brain. The depressant and stimulant actions of morphine on both endpoints were antagonized by 1.0 mg/kg i.p. of naloxone administered 30 min before the maximum effect. Tolerance to morphine was produced by t.i.d. injections of increasing doses. Rapid tolerance developed to the locomotor depressant actions of morphine and to the decrease in brain ACh utilization. Tolerance to the depressant effects resulted in an enhanced stimulant action. Tolerance also developed to the stimulant actions of morphine but only when large doses of drug were administered daily. Biphasic effects of 10 mg/kg of morphine on brain ACh utilization were also observed in the hippocampus, thalamus and hypothalamus. Only a decrease in ACh utilization was observed in the caudate nucleus. Tolerance developed to the decreases and increases in ACh utilization in these discrete brain regions. This study demonstrates that tolerance development to the depressant and stimulant actions of morphine is complex and involves different dose and time schedules. It is not possible therefore to study tolerance to the actions or morphine without specifying the precise endpoint studied and the tolerance schedule utilized.

Our study focuses on the numerical solution of the stochastic vibration of elastic-plastic mechanical systems with Gaussian random excitations. It's realized the short review about linearization techniques in stochastic dynamics mainly with application in area of elastic-plastic finite element modelling using BW (Bouc-Wen) differential mathematical model. The presented methods of statistical linearization, Hurtado-Barbat's modification of statistical linearization, statistical quadratization and Monte Carlo approach are applied to numerical testing.

Modern transfer system device is used in industrial automatization and it ensures a smooth transfer of material along the tracks. The transfer system model was created in CAD system. Finite-element and modal analysis was created in Ansys Workbench software. The system consists of aluminium profiles from Bosh Rexroth firm, and it contains electric, pneumatic and control elements.

The paper presents an analysis of the stress state in the tensile test sample. The test sample has a hardened surface layer with chemic heat treatment - cementation. The analysis was carried out for various thicknesses of the reinforced cemented layer. If the whole thickness of the material is not cemented, the fracture is near the grip section of the specimen. The analysis results explain the cause of this fracture.

Additive manufacturing is process of joining material, bringing many benefits such as customization and low production cost. Markforged developed Continuous fiber fabrication technology, which allows to print continuous fiber reinforced thermoplastic (CFRTP) composites. Although printed CFRTP parts achieve mechanical properties better than another 3D printed counterparts, there is demand to gain suitable mechanical properties comparable with conventionally manufactured parts using improvements in printing parameters and fiber deposition. In this paper, the main goal is analyzing of geometry constraints of fiber deposition and modeling options in FEM program ADINA. Additionally, stress distribution analysis with regard to stresses in matrix and fibers will be performed.