Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.
The caving property of top coal is a key factor to the success of top coal caving mining. The influence law of cyclic loading and unloading of hydraulic support on top coal caving is of great significance to improve the recovery rate of top coal. The similar simulation methods were used to study the dynamic evolution of the top coal cracks under the multi-cycle action of the support, and the parameters of top coal cracks were analyzed quantitatively in this paper. The results show that the top coal cracks can be divided into horizontal cracks and vertical cracks under the cyclic loading and unloading of the support. With the increase of the times of the support cycles loading and unloading, the load on the support decreases, the fractal dimension of the cracks increases, the number and total length of the top coal cracks increases, and the top coal caving is getting better. With the increase of the times of multi-cycle loading and unloading, the fractal dimension, total crack length and crack rate of top coal show a trend of rapid increase first and then increase slowly. Both the total length of the top coal cracks and the crack rate basically show linear growth with the change of the fractal dimension. The top coal caving can be well improved and the coal resource recovery rate increased through the multi-cycle loading and unloading.
A shopbot is a software agent whose goal is to maximize buyer´s satisfaction through automatically gathering the price and quality information of goods as well as the services from on-line sellers. In the response to shopbots´ activities, sellers on the Internet need the agents called pricebots that can help them maximize their own profits. In this paper we adopts Q-learning, one of the model-free reinforcement learning methods as a price-setting algorithm of pricebots. A Q-learned agent increases profitability and eliminates the cyclic price wars when compared with the agents using the myoptimal (myopically optimal) pricing strategy Q-teaming needs to select a sequence of state-action fairs for the convergence of Q-teaming. When the uniform random method in selecting state-action pairs is used, the number of accesses to the Q-tables to obtain the optimal Q-values is quite large. Therefore, it is not appropriate for universal on-line learning in a real world environment. This phenomenon occurs because the uniform random selection reflects the uncertainty of exploitation for the optimal policy. In this paper, we propose a Mixed Nonstationary Policy (MNP), which consists of both the auxiliary Markov process and the original Markov process. MNP tries to keep balance of exploration and exploitation in reinforcement learning. Our experiment results show that the Q-learning agent using MNP converges to the optimal Q-values about 2.6 time faster than the uniform random selection on the average.
Anti-graffiti coatings have become more important. These layers must guarantee excellent corrosion protection properties, and graffiti must be easily removable, without reducing protection and aesthetic properties. In this study, anti-graffiti and corrosion behavior of two anti-graffiti polyurethane powder coatings were studied. These layers were deposited on aluminum substrate, with two different surface finishes, smooth, and wrinkled. The action of four different removers are investigated. Graffiti were drawn on coatings by means of red acrylic spray paint. Methyl-ethyl-ketone (MEK) and a "commercial" remover were the most effective solvents, in terms of graffiti removal capability, producing limited change in aesthetical surface aspect for smooth finishing. The wrinkled surface was less resistant. Corrosion protection properties, after removal action and contact with the remover, were evaluate by electrochemical impedance spectroscopy. After approximately 5 hours, coatings were no longer protective due to formation of defects. To simulate the weathering effect, UV-B cyclic test (4 hours of UV exposure followed by 4 hours of saturated humidity at $50^{\circ}C$) were performed for 2000 hours. Gloss and color changes were measured, and electrochemical impedance spectroscopy measurements were performed after aging and graffiti removal.
Journal of the Architectural Institute of Korea Structure & Construction
/
v.35
no.10
/
pp.155-162
/
2019
Hybrid precast concrete panel is a wall element that is able to quickly construct the core wall structure for moderate-rise modular buildings. Hybrid precast concrete panel has unique characteristics which is a pair of C-shaped steel beams combined at the top and bottom of a concrete wall, In this study, an improved anchorage detail for vertical rebar is proposed to ensure the lateral force resistance performance of hybrid precast concrete panel emulating monolithic concrete wall. Also, the structural performance of horizontal connection is investigated experimentally with the bolt spacing parameter. And the behavior of hybrid precast concrete panel with the improved detail is compared with the monolithic concrete wall tested in a previous study. Finally, the required thickness of C-shaped steel beam to eliminate or minimize the deformation in horizontal connection is calculated by prying action equation.
Cyclic adenosine 3'5'-monophosphate (cyclic AMP) has been frequently accepted as an intracellular messenger for receptor-mediated action of opioids. In this experiment, it was designed to determine the interaction of dopaminergic and opioidergic system in the mouse striatum in normal and chronic haloperidol treated groups. Haloperidol 750ug/kg I.P. for 10 days was performed for dopamine denervation. The morphine, DAGO, DPDPE, and U5O,488H inhibited the increase of haloperidol-induced cyclic AMP content in chronic haloperidol treated mouse striatum. The inhibition of DAGO and DPDPE showed significant increase compared to normal mouse striatum. Naloxone showed antagonistic effect on the morphine and U5O,488H in chronic haloperidol treated group, and showed antagonistic effect on morphine, DAGO, DPDPE, and U5O, 488H in normal mouse striatum. These findings support that there is a functional interrelationship of dopaminergic and opioidergic pathway in the striatum. This result provides an evidence that following destruction of striatal dopaminergic neuron, there are some changes of cAMP content on the ${\mu},\;{\gamma},\;and\;{\kappa}$ opioid receptor, but the ${\kappa}$ opioid receptor still has its function.
Kim, Won-Joon;Lee, Kwang-Youn;Ha, Jeoung-Hee;Kwon, Oh-Cheol
The Korean Journal of Pharmacology
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v.28
no.2
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pp.147-162
/
1992
The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.
Lee, Hyung Gon;Jeong, Chang Young;Yoon, Myung Ha;Kim, Woong Mo;Shin, Seung Heon;Kim, Yeo Ok;Huang, Lan Ji;Cui, Jin Hua
The Korean Journal of Pain
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v.20
no.1
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pp.21-25
/
2007
Background: Intrathecal sildenafil has produced antinociception by increasing the cGMP through inhibition of phosphodiesterase 5. Spinal opioid receptor has been reported to be involved in the modulation of nociceptive transmission. The aim of this study was to examine the role of opioid receptor in the effect of sildenafil on the nociception evoked by formalin injection. Methods: Rats were implanted with lumbar intrathecal catheters. Formalin testing was used as a nociceptive model. Formalin-induced nociceptive behavior (flinching response) was observed. To clarify the role of the opioid receptor for the analgesic action of sildenafil, naloxone was administered intrathecally 10 min before sildenafil delivery, and formalin was then injected 10 min later. Results: Intrathecal sildenafil produced dose-dependent suppression of flinches in both phases during the formalin test. Intrathecal naloxone reversed the analgesic effect of sildenafil in both phases. Conclusions: Sildenafil is active against the nociceptive state that's evoked by a formalin stimulus, and the opioid receptor is involved in the analgesic action of sildenafil at thespinal level.
The importance of thyroid hormones for the survival of rats in the cold is along-established fact. Hypothyroid animals are unable to survive in a cold environment. It was also reported that acute exposure of rats, guinea pigs and rabbits to cold produced an increased secretion of TSH and thereby thyroid hormone secretion within 10 to 30 min, but this increase of thyroid activity disappeared quite rapidly during warming. However, in human study no significant difference was found in the concentration of $T_4$, TSH and cortisol between summer and winter. But plasma $T_3$ concentration was increased significantly in winter in 56 adult men. On the other hand, it has been also known that catecholamines are important in the maintenance of body temperature of rat exposured to cold. Abundant evidences suggest that the sympathetic nervous system is involved in the activation of nonshivering thermogenesis and that thyroid hormone metabolism and secretion are influenced by catecholamines and consequently by the activity of the sympatheticadrenal system. Many of the metabolic effects of catecholamines are associated with an increase in the level of cAMP mediated through activation of adenylate cyclase which converts ATP to cAMP. Other studies have shown that thyroid hormones affect the amount of adenylate cyclase present in the adipose tissue. On the other hand. it was also reported that a particulate cAMP phosphodiesterase activity in fat cells was modulated by the action of thyroid hormones. The objective of the present study was to determine the interaction between thyroid activity and cyclic nucleotides during acute exposure to cold. Albino rats weighing around 200 g were used as the experimental animal. The room temperature group was kept at $25^{\circ}C$ and the cold-exposured group was kept at $4^{\circ}C$ for 1 week or 2 weeks. Each group was subdivided into three subgroups; control, KI, and MTU group. At the end of experiment the animals were etherized and blood was taken from abdominal aorta for $T_4,\;T_3$ and cyclic nucleotides. The determinations of $T_3,\;T_4$ and cyclic nucleotides were carried out with a radioimmunoassay(RIA) method. The results were summerized as followings. 1) A significant increase of thyroid weight was observed in rats exposured to cold for 2 weeks. Furthermore, in rats administered MTU while to exposure to cold the thyroid weight was also increased significantly. 2) After 2 weeks $T_3$ concentration in the plasma of cold-exposured rats was significantly increased in KI group and MTU group as well as in control group. On the contrary, after 2 weeks of cold exposure $T_4$ level was decreased in control group. 3) In the case of cyclic nucleotides, plasma cAMP was increased in the control group after 1 or 2 weeks of cold exposure. However, cAMP level in plasma was rather significantly decreased in KI group and MTU group as well as in control group.
This study was undertaken to examine the intensity of involvement of inducible nitric oxide synthase (iNOS) and cyclic GMP signal transduction pathway as one of the mechanisms of vaso-relaxative action of bacterial lipopolysaccharide (LPS) on the canine femoral artery strips. Canine femoral arteries were isolated and spiral strips of 10 mm long and 2 mm wide were made in the Tyrode solution of $0-4^{\circ}C$. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with 95% $O_2$/5% $CO_2$ at $37^{\circ}C$ and nitric oxide (NO) production was measured simulltaneously with isolated nitric oxide meter. LPS induced NO production, suppressed the phenylephrine (PE) induced contraction and enhanced the acetylcholine (ACh) induced relaxation. $N^G$-nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue, a guanylyl cyclase inhibitor, potentiated PE induced contraction and suppressed ACh induced relaxation on the LPS treated strips. The inhibitory potency of methylene blue for LPS induced vascular hyporesponsiveness was stronger than that of L-NAME. These results suggest that in canine femoral artery, both iNOS and cyclic GMP signal trnasduction pathway are related with LPS induced vascular hyporeponsiveness, but in minor with iNOS and in major with cyclic GMP signal trnasduction pathway.
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