• Journal of Convergence for Information Technology
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• v.12 no.4
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• pp.119-125
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• 2022

In the study, we endeavored to investigate the effect of phenylephrine, isoprenaline and prazosin on the tissue-specific vascular contractility and to determine the mechanism involved. There were few reports addressing the question whether thin or thick filament modulation is included in phenylephrine, isoprenaline and prazosin-induced regulation. We hypothesized that isoprenaline and prazosin play a role in tissue-dependent regulation of vascular contractility. Denuded arterial muscles of Sprague-Dawley male rats were suspended in organ baths and isometric tensions were transduced and recorded using isometric transducers and an automatic data acquisition system. Interestingly, sustained continuous contraction of thoracic and abdominal aorta. Furthermore, isoprenaline and prazosin together with phenylephrine inhibited transiently and persistently vasoconstriction of thoracic and abdominal aorta suggesting that additional mechanisms (e.g. decreased receptor density, chemical interaction, postreceptor signaling or distribution of agonists) might be included in the modulation of vascular contractility.

• Animal Bioscience
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• v.34 no.9
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• pp.1552-1558
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• 2021

Objective: This work was carried out to evaluate the effects of zilpaterol hydrochloride (ZH) and ractopamine hydrochloride (RH) combined with immunocastration on the welfare traits of feedlot Nellore cattle. Methods: Ninety-six Nellore males (average body weight [BW] = 409±50 kg; average 20 mo of age) were divided into two groups according to BW; half of the animals in each group received two doses of an immunocastration (ImC) vaccine in a 30 day interval, and the other half did not receive the vaccine (NoC). Afterward, the animals were housed and fed a common diet for 70 days. Then, they were split into three groups and fed one of the following diets for 30 additional days: control (CO) diet, with no β-AA; ZH diet, containing 80 mg/d ZH; and RH diet, containing 300 mg/d RH. Welfare traits were assessed by monitoring body surface temperature using infrared thermography (IRT) and plasma cortisol and temperament measurements. Results: There was no interaction between sexual condition and diet for any trait. The ImC and NoC groups did not differ in rectal and ocular temperatures. The ImC animals had higher flight speeds (p = 0.022) and tended to have higher cortisol levels (p = 0.059) than the NoC animals. Animals fed ZH and RH did not differ in cortisol levels, respiratory rate, rectal temperature, temperature measured by IRT, or temperament behaviour. Conclusion: The ImC animals showed a less stable temperament during handling practices than NoC, whereas ZH and RH supplementation had no adverse effects on animal welfare.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.337-345
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• 2007

Backgrounds: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting ${\beta}_2-agonists$ (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control. Methods: One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including $FEV_1%$ predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians. Results: The mean ACQ score decreased significantly on montelukast ($11.5{\pm}5.4$ at baseline vs. $6.7{\pm}5.0$), with a significant improvement in all individual symptom scores (p<0.01). The $FEV_1%$ predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (${\kappa}=0.85$). Conclusion: These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.

• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.261-270
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• 2002

Purpose: Nicotinic acetylcholine receptors (nAChRs), which mediate excitatory neurotransmission, are known to participate in various neurophysiological functions. Severe losses of nAChRs have been noted in Alzheimer's and Parkinson's diseases. Therefore, noninvasive and quantitative imaging of nAChRs would offer a better understanding on the function of these receptors. In this study, $2-[^{18}F]fluoro-A85380\;([^{18}F]1)$, an ${\alpha}_4{\beta}_2$ nAChRs radioligand, was prepared using one HPLC purification and evaluated in mouse brain, and the results were compared with those in the literature. Materials and Methods: $[^{18}F]1$ was prepared by $[^{18}F]$fluorination of the iodo precursor followed by acidic deprotection and then purified by HPLC. Tissue distribution studies were performed in mouse brain at the indicated time points and the result was expressed as %ID/g. Inhibition studies were also carried out with pretreatment of various ligands. Results: One HPLC purification method gave the desired product in 15-20% radiochemical yield and with high specific activity ($38-55GBq/{\mu}mol$). Tissue distribution studies showed that $[^{18}F]1$ specifically labeled nAChRs in mouse brain with a high thalamus to cerebellum uptake ratio (13.8 at 90 min). Inhibition studios demonstrated selective binding of $[^{18}F]1$ to nAChRs, blocking the uptake of the $[^{18}F]1$ in nAChR-rich legions by selective ligands such as cytisine and nicotine which are well-known nAChRs agonists. Conclusion: This study demonstrated that the $[^{18}F]1$ produced by the method using one HPLC purification gave the results similar to those reported in the literature. Therefore, this synthetic method can be readily applied to the routine preparation of $[^{18}F]1$, a PET radioligand for ${\alpha}_4{\beta}_2$ nAChRs imaging.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.287-297
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• 2001

Contraction of smooth muscle is initiated by an increase in cytosolic $Ca^{2+}$ leading to activation of $Ca^{2+}$/ calmodulin-dependnet myosin light chain (MLC) kinase and phosphorylation of MLC. The types of contraction and signaling mechanisms mediating contraction differ depending on the region. The involvement of these different mechanisms varies depending on the source of $Ca^{2+}$ and the kinetic of $Ca^{2+}$ mobilization. $Ca^{2+}$ mobilizing agonists stimulate different phospholipases $(PLC-{\beta},\;PLD\;and\;PLA_2)$ to generate one or more $Ca^{2+}$ mobilizing messengers $(IP_3\;and\;AA),$ and diacylglycerol (DAG), an activator of protein kinase C (PKC). The relative contributions of $PLC-{\beta},\;PLA_2$ and PLD to generate second messengers vary greatly between cells and types of contraction. In smooth muscle cell derived form the circular muscle layer of the intestine, preferential hydrolysis of $PIP_2$ and generation of $IP_3$ and $IP_3-dependent\;Ca^{2+}$ release initiate the contraction. In smooth muscle cells derived from longitudinal muscle layer of the intestine, preferential hydrolysis of PC by PLA2, generation of AA and AA-mediated $Ca^{2+}$ influx, cADP ribose formation and $Ca^{2+}-induced\;Ca^{2+}$ release initiate the contraction. Sustained contraction, however, in both cell types is mediated by $Ca^{2+}-independent$ mechanism involving activation of $PKC-{\varepsilon}$ by DAG derived form PLD. A functional linkage between $G_{13},$ RhoA, ROCK, $PKC-{\varepsilon},$ CPI-17 and MLC phosphorylation in sustained contraction has been implicated. Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to $M_2$ muscarinic receptors activating at least three intracellular phospholipases, i.e. phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD) and the high molecular weight (85 kDa) cytosolic phospholipase $A_2\;(cPLA_2)$ to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic $M_3$ receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the $G_{q/11}$ type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate $(PIP_2),$ producing inositol 1, 4, 5-trisphosphate $(IP_3)$ and DAG. $IP_3$ causes release of intracellular $Ca^{2+}$ and formation of a $Ca^{2+}$-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway.

• Korean Journal of Veterinary Research
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• v.43 no.3
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• pp.405-414
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• 2003

The purpose of this study was to assess the role of tachykinins (TK) in mediating nonadrenergic noncholinergic (NANC) contractions produced by electrical field stimulation (EFS) in the longitudinal muscle of the rat ileum. In the presence of atropine ($1{\mu}M$), guanethidine ($5{\mu}M$), and L-nitroarginine (L-NNA, $200{\mu}M$), EFS (0.5ms pulse duration, 120 V, 1-20 Hz for 2 min) produced a frequency-dependent slowly-developing tonic contraction with superimposed phasic contractions ('on'-contraction) followed by off slowly-decreasing tonic and superimposed phasic contractions ('off'-contraction) of mucosa-free longitudinal oriented muscle strip. These EFS induced responses were blocked by tetrotoxin. $NK_1$ receptor selective antagonist L-732,138 strongly inhibited the EFS-induced excitatory responses. However $NK_2$ receptor selective antagonist, GR 159897 and $NK_3$ receptor selective antagonist SB 222200 did not significantly inhibited the responses. $NK_1$ receptor selective agonist [$Sar^9$,$Met(O_2)^{11}$] Substance P and $NK_2$ receptor selective agonist [${\beta}-Ala^8$]-neurokinin A (4-10) induced tonic contraction with superimposed phasic contractions of longitudinal oriented muscle strip and almost blocked by selective antagonist L-732,138 and GR 159897, respectively. But $NK_3$ receptor selective agonist senktide did not showed any effect. Nifedipine ($1{\mu}M$) abolished the contraction produced either by EFS or by the TK receptor agonists [$Sar^9$,$Met(O_2)^{11}$] Substance P or [${\beta}-Ala^8$]-neurokinin A (4-10). It is concluded that, in the longitudinal muscle of rat ileum, both $NK_1$ and $NK_2$ receptors modulated the responses to exogenous tachykinins, whereas $NK_1$ is mainly involved in NANC neuromuscular contraction.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.186-186
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• 1994

Many agonists have been known to activate the hydrolysis of membrane phospholipids through the bindings with corresponding receptors on the various cells. Diacylglycerol and inositol 1,4,5-trisphosphate(IP3) generated by the action of phosphoinositide-specific phospholipase C (PI-PLC) are well known second messengers for the activation of protein kinase C and the mobilization of Ca2+ in many cells. Three types of PI-PLC isozyme (${\alpha}$,${\gamma}$, and $\delta$) and several subtrpes for each type have been identified from mammalian sources by purification of enzymes and cloning of their cDNAs. Each type PI-PLC isozyme is coupled to different receptors and mediators, for example, ${\beta}$-types are coupled to the seven-transmembrane-receptors via Gq family of G-proteins and ${\beta}$-types directly to the receptor tyrosine kinases. Specific modulators for the signaling pathway through each type of PI-PLC should be very useful as potential potential candidates for lend substances in developing novel drugs. To establish the sensitive and convenient screening systems for searching modulators on PI-PLC mediated signaling, two kinds of approaches have been tried. (1) Establishment of in vitro assay condition for each type of PI-PLC isozyme: Overexpression by using vaccinia virus and purification of each isozyme was carried out for the preparation of large amounts of enaymes. Optimum and sensitive assay condition for the measurements of PI-ELC activities were established. (2) Development of the cell lines in which each type of PI-PLC is permanently overexpressed: A fibroblast cell line (3T3${\gamma}$1-7) in which PI-PLC-${\gamma}$1 was overexpressed by using pZip-neo expression vector was developed and used for the measurement of PDGF-induced IP3 formation. The responses for IP3 formed in 3T3${\gamma}$1-7 cells by the treatment of PDGF is 8 times more sensitive than those in control cells. 3T3${\gamma}$l-7 cell is useful for the screening of the inhibitors on the PDGF-induced cellular responses from large number of samples in a small volume(50 ${\mu}$l) and short time(5-15 min). Using these systems, we screened hundreds of herb-extracts for the inhibition of PDGF-induced IP3 formation and selected several extracts that showed the inhibition as the candidates for isolation and characterization of active substances. The determination of the acting point of selected extracts or fractions in the PDGF signaling pathway has been analyzing.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.63-70
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• 1988

Alterations in splanchnic circulatory hemodynamics along with reactivities to the alpha adrenoceptor agonists were assessed in association with the preventive effects of propranolol 10 days after portal ligation. Decreases in precapillary resistance (Ra) and postcapillary resistance (Rv) along with increases in mesenteric blood flow (MBF) and capillary pressure (CP) were observed in conjunction with an increment of splenic pulp pressure (SPP). Dose-dependent increase in Rv in response to noradrenaline, increases in Ra and RV to adrenaline, and increases in superior mesenteric arterial pressure (SMAP), Ra and Rv to phenylephrine observed in sham group were significantly attenuated by portal vein stenosis. In PPL-3 group (propranolol 3 mg/kg, i.p. three times daily for 10 days), MBF was significantly decreased in association with decrease in mesenteric venous pressure (MVP) when compared with those of protal ligated (PL) group, and decreased Ra and Rv in PL group were recovered toward the values of sham group. Likewise, in PPL-1 group (propranolol 5 mg/kg, i.p. once daily for 10 days), the pressor response of Rv to adrenaline was recovered up to the level of sham group. Thus, it is suggested that decreases in Ra and Rv in association with increases in MBF and CP may have a close relevance to the increased SPP, and the changes in circulatory hemodynamics and vascular reactivities were effectively reversed by longterm propranolol treatment. Based on these results, it is concluded that these changes observed in portal hypertension are closely related with the altered functions of the adrenoceptors in the splanchnic vascular beds.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.4
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• Analytical Science and Technology
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• v.21 no.5
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• pp.412-423
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• 2008

A procedure based on solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry has been developed for the simultaneous analysis of 55 basic drugs in equine urine. The test scope covers diversified classes of drugs including some ${\beta}$-blockers, ${\beta}$-agonists, antihypotensives, CNS stimulants, sedatives, tranquilizers, antidepressants, antihypertensives and so on. LC-MS/MS separation and quantification was carried out in positive electrospray ionization and multiple reaction monitoring (MRM) mode. Four different brands of mixed mode cation exchange SPE sorbents; UCT XTRACT$^{(R)}$ XRDAH, Supelco DSC-MCAX$^{(R)}$, Varian Bond Elut Certify$^{(R)}$ and Waters Oasis$^{(R)}$ MCX were compared. The UCT XTRACT$^{(R)}$ XRDAH sorbent provided the best results in the preconcentration of samples, yielding relative recoveries higher than 80% except for terbutaline (41.3%), salbutamol (71.5%), heptaminol (70.7%), phenylpropanolamine (66.3%). Detection limits of the target drugs provided by the proposed analytical procedure were between 0.2~8.3 ng/mL.