It has been reported that activation of metabotropic glutamate receptor 1 (mGluR1) can mediate endocannabinoid-induced short-term depression of synaptic transmission in cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse. mGluR1 has signaling pathways involved in intracellular calcium increase which may contribute to endocannabinoid release. Two major mGluR1-evoked calcium signaling pathways are known: (1) slow-kinetic inward current carried by transient receptor potential canonical (TRPC) channel which is permeable to $Ca^{2+}$; (2) $IP_3$-induced calcium release from intracellular calcium store. However, it is unclear how much each calcium source contributes to endocannabinoid signaling. Here, we investigated whether calcium influx through mGluR1-evoked TRPC channel contributes to endocannabinoid signaling in cerebellar Purkinje cells. At first, we applied SKF96365 to inhibit TRPC, which blocked endocannabinoid-induced short-term depression completely. However, an alternative TRP channel inhibitor, BTP2 did not affect endocannabinoid-induced short-term depression although it blocked mGluR1-evoked TRPC currents. Endocannabinoid signaling occurred normally even though the TRPC current was mostly blocked by BTP2. Our data imply that TRPC current does not play an important role in endocannabinoid signaling. We also suggest precaution in applying SKF96365 to inhibit TRP channels and propose BTP2 as an alternative TRPC inhibitor.
Natural products are one of the useful source of cardiovascular drugs, in particular, when they have antioxidant activity. Gagaminine, an alkaloid isolated from the roots of Cynanchum wilfordi Hemsley, has been reported to potently inhibit the aldehyde oxidase activity ({TEX}$IC_{50}${/TEX}=0.8$\mu$M) and reduce lipid peroxidation. However, the effect of gagaminine on vascular smooth muscle has not yet been investigated. In the present study, we examined whether gagaminine relaxes vascular smooth muscle by isometric tension study. In order to observe its relaxation effect on the arteries, conductivel vessel (rat thoracic aorta) and resistance vessel (pig coronary artery) were purposely used. Results indicated that gagaminine relaxed in a concentration-dependent manner $\alpha$-adrenoceptor agonist, phenylephrine (PE)-induced contraction of rat aorta. Pretreatment with gagaminine inhibited PE-induced contraction, noncompetitively. {TEX}$Ca^{2+}${/TEX}-induced contraction was significantly diminished by gagaminine. In pig coronary artery, gagaminine relaxed thromboxane receptor (U 46619)-mediated contraction in dose-dependent manner. Pretreatment with gagaminine also reduced the maximum contraction induced by KCl. These observations strongly suggest that agagminnine relaxes vascular smooth muscle, irrespective of both resistance and conductive artery. We demonstrate that gagaminine, a potent natural antioxidant, has a significant vasodilatory effect and its action mechanism van be ascribed at least in part to {TEX}$Ca^{2+}${/TEX} antagonistic action as evidenced by inhibition {TEX}$Ca^{2+}${/TEX}-induced contraction (rat aorta) and KCl-induced contraction (porcine artery). Furthermore, neither $\alpha$ -adrenoceptor nor thromboxane receptor seems responsible for the relaxation of gagaminine.
Yahi, Dauda;Ojo, Nicholas Adetayo;Mshelia, Gideon Dauda
Journal of Animal Science and Technology
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v.59
no.5
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pp.12.1-12.7
/
2017
Background: Despite the widespread use of dexamethasone in veterinary and human medicine, it is reported to cause some severe pregnancy related side effects like abortion in some animals. The mechanism of the response is not clear but seems to be related to interspecies and/or breed difference in response which may involve alterations in the concentrations of some reproductive hormones. Methods: Twenty Sahel goats comprising 18 does and 2 bucks were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injections were given at 0.25 mg/kg body weight. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested at days 28 and day 78 of gestation through caesarean section for immunohistochemical analysis using 3 pregnant does randomly selected from each group at each instant. Data were expressed as Means ${\pm}$ Standard Deviations and analyzed using statistical soft ware package, GraphPad Instant, version 3.0 (2003) and progesterone receptor (PR) were scored semi-quantitatively. Results: Dexamethasone treatments had no significant (p > 0.05) effect on progesterone and estrogen concentrations in pregnant Sahel goats but up regulated PR from 2+ to 3+ in second trimester. Conclusion: As dexamethasone adverse effect on placenta is an established fact, the lack of effect on progesterone level in this study may be due to the fact that unlike other species whose progesterone production during pregnancy is placenta - dependent, in goats is corpus luteum - dependent. Consequently dexamethasone adverse effect on placenta reported in literatures did not influence progesterone levels during pregnancy in Sahel goat. The up regulation of progesterone receptor (PR) in Sahel goat gravid uterus is a beneficial effects and that dexamethasone can safely be used in corpus luteum - dependent progesterone secreting pregnant animal species like Sahel goat and camel. Therefore source of progesterone secretions during pregnancy should be considered in clinical application of dexamethasone in pregnancy.
Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.
An, Geon-Ho;Suh, Young-Bae;Son, Kun-Ho;Chang, Il-Moo;Mar, Woong-Chon
Natural Product Sciences
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v.3
no.1
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pp.29-37
/
1997
Protein Kinase C (PKC) is generally believed to play a central role in signal transduction, cellular growth control, gene expression, and tumor promotion. And it has been suggested that inhibitors of PKC might play important roles for the prevention and treatment of cancer. In order to investigate the possible inhibitors of PKC from natural products, PKC receptor binding assay was performed using bovine brain particulate as a source of PKC and the amount of $[^3H]Phorbol$ 12,13-dibutyrate (PDBu) bound to PKC was measured in the presence of test materials. Total methanol extracts from 100 kinds of natural products were partitioned into 3 fractions (n-hexane, ethyl acetate and aqueous layer) and their binding ability to the regulatory domain of PKC was evaluated. The ethyl acetate fractions of Morus alba $(roots,\;IC_{50}:\;156.6\;{\mu}g/ml)$, Rehmannia glutinosa $(roots,\;IC_{50}:\;134.3\;{\mu}g/ml)$, Lysimachia foenum-graecum $(roots,\;IC_{50}:\;167.8\;{\mu}g/ml)$, Polygonum cuspidata $(roots,\;IC_{50}:\;157.3\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;IC_{50}:\;145.2\;{\mu}g/ml)$, and the hexane $(IC_{50}:\;179.3\;{\mu}g/ml)$ and the EtOAc fraction of Symplocarpus nipponicus $(roots,\;IC_{50}:\;155.9\;{\mu}g/ml)$ showed inhibitory activity of $[^3H]PDBu$ binding to PKC.
Source contribution for VOCs collected in Seoul metropolitan area was conducted using PAMs (Photochemical assessment monitoring system) data and CMB(Chemical Mass Balance) model8.0, in order to estimate spatial and temporal variations of VOCs source contribution in that area, and also to compare with corresponding emission inventory. VOCs data used in model calculation were collected at 6 different sites of PAMs(Seokmori, Guwoldong, Simgokdong, Bulgwangdong, Jeongdong and Yangpyeong) and 22 out of 56 VOCs species were analyzed from June 2002 to march 2003 and used for CMB model estimation. The result showed that vehicle exhaust, coating and energy combustion were important sources of VOCs in Seoul metropolitan area, averaging 32.6%, 25.5% and 25.1%, respectively. In this study as well as other references, it was revealed that vehicle exhaust is the main contributor of urban area VOCs, but there is remarkable contrast between emission inventory and model estimation. Vehicle exhaust portion is seriously underestimated while coating is usually overestimated in emission estimates, compared to CMB results. Therefore, it is considered to assert and confirm the uncertainty of emission estimates and clarify the distinction between two other source apportionment methods.
Journal of Korean Society for Atmospheric Environment
/
v.25
no.3
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pp.219-236
/
2009
Particle-phase organic tracers (molecular markers) have been shown to be an effective method to assess and quantify the impact of sources of carbonaceous aerosols. These molecular markers have been used in chemical mass balance (CMB) models to apportion primary sources of organic aerosols in regions where the major organic aerosol source categories have been identified. As in the case of all CMB models, all important sources of the tracer compounds must be included in a Molecular Marker CMB (MM-CMB) model or the MMCMB model can be subject to biases. To this end, the application of the MM-CMB models to locations where reasonably accurate emissions inventory of organic aerosols are not available, should be performed with extreme caution. Of great concern is the potential presence of industrial point sources that emit carbonaceous aerosols and have not been well characterized or inventoried. The current study demonstrates that emissions from industrial point sources in the St. Louis, Missouri area can greatly bias molecular marker CMB models if their emissions are not correctly addressed. At a sampling site in the greater St. Louis Area, carbonaceous aerosols from industrial point sources were found to be important source of carbonaceous aerosols during specific time periods in addition to common urban sources (i.e. mobile sources, wood burning, and road dust). Since source profiles for these industrial sources have not been properly characterized, method to identify time periods when point sources are impacting a sampling site, needs to avoid obtaining biases source apportionment results. The use of real time air pollution measurements, along with molecular marker measurements, as a screening tool to identify when point sources are impacting a receptor site is presented.
The purpose of this study was to investigate the effects of neurotransmitters and the source of $Ca^{2+}$ in the effects of neurotransmitters on the motility of pig oviductal isthmic smooth muscle. The motility of the isolated smooth muscle was recorded by using physiological recording system. The results were summarized as follows; Acetylcholine, norepinephrine, histamine and prostaglandin $F_{2{\alpha}}(PGF_{2{\alpha}})$ caused the contraction and the contractile responses were increased in a dose-dependent manner from the concentration of $10^{-7}$ to $10^{-4}M$. The maximum contractility of acetylcholine, norepinephrine, histamine and $PGF_{2{\alpha}}$ was 65.99, 28.66, 83.99 and 47.33% of 100 mM K contraction, respectively. The contractile response induced by acetylcholine$(10^{-6}M)$ was completely blocked by the pretreatment with cholinergic receptor blocker, atropine$(10^{-6}M)$, the contractile response induced by norepinephrine$(10^{-5}M)$ was blocked by the pretreatment with ${\alpha}$-adrenergic receptor blocker, phentolamine$(10^{-6}M)$ but was not blocked and rather increased by the pretreatment with ${\beta}$-adrenergic receptor blocker. propranolol$(10^{-6}M)$, the contractile response induced by histamine$(10^{-6}M)$ was completely blocked by the pretreatment with $H_1$-histaminergic receptor blocker, pyrilamine$(10^{-6}M)$ but was increased by the pretreatment with $H_2$-histaminergic receptor blocker, cimetidine$(10^{-6}M)$. The contractile response induced by acetylcholine$(10^{-6}M)$, norepinephrine$(10^{-5}M)$ and histamine$(10^{-6}M)$ was weakly contracted response in $Ca^{2+}$-free medium, but the contractile response induced by $PGF_{2{\alpha}}(10^{-6}M)$ was disappeared. The contractile response induced by acetylcholine$(10^{-6}M)$, norepinephrine$(10^{-5}M)$ and histamine$(10^{-6}M)$ was powerfully depressed by the pretreatment with $Ca^{2+}$-channel blocker, verapamil$(10^{-5}M)$ but the contractile response induced by $PGF_{2{\alpha}}(10^{-6}M)$ was completely inhibited.
In this study, CALPUFF modeling was performed, using a real surface and upper air meterological data to predict trustworthy modeling-results. Pollutant-releases from windscreen chambers of enclosed poultry farms, P1 and P2, and from a open poultry farm, P3, and their diffusing behavior were modeled by CALPUFF modeling with volume sources as well as by finally-adjusted CALPUFF modeling where a linear velocity of upward-exit gas averaged with the weight of each directional-emitting area was applied as a model-linear velocity ($u^M_y$) at a stack, with point sources. In addition, based upon the scenario of poultry farm-releasing odor and particulate matter (PM) removal efficiencies of 0, 20, 50 and 80% or their corresponding emission rates of 100, 80, 50 and 20%, respectively, CALPUFF modeling was performed and concentrations of odor and PM were predicted at the region as a discrete receptor where civil complaints had been frequently filed. The predicted concentrations of ammonia, hydrogen sulfide, $PM_{2.5}$ and $PM_{10}$ were compared with those required to meet according to the offensive odor control law or the atmospheric environmental law. Subsequently their required removal efficiencies at poultry farms of P1, P2 and P3 were estimated. As a result, a priori assumption that pollutant concentrations at their discrete receptors are reduced by the same fraction as pollutant concentrations at P1, P2 and P3 as volume source or point source, were controlled and reduced, was proven applicable in this study. In case of volume source-adopted CALPUFF modeling, its required removal efficiencies of P1 compared with those of point source-adopted CALPUFF modeling, were predicted similar each other. However, In case of volume source-adopted CALPUFF modeling, its required removal efficiencies of both ammonia and $PM_{10}$ at not only P2 but also P3 were predicted higher than those of point source-adopted CALPUFF modeling. Nonetheless, the volume source-adopted CALPUFF modeling was preferred as a safe approach to resolve civil complaints. Accordingly, the required degrees of pollution prevention against ammonia, hydrogen sulfide, $PM_{2.5}$ and $PM_{10}$ at P1 and P2, were estimated in a proper manner.
Journal of Korean Society for Atmospheric Environment
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v.31
no.5
/
pp.437-448
/
2015
The purpose of this study is to present the source contribution of the fine particles ($PM_{2.5}$) in Chungju area using the CMB (chemical mass balance) method throughout the four seasons in Korea. The Chungju's annual average level of $PM_{2.5}$ was $48.2{\mu}g/m^3$, which exceeded two times higher than standard air quality. Among these particles, the soluble ionic compounds represent 54.2% of fine particle mass. Additionally, the OC concentration in Chungju stayed similar to other domestic cities, while the EC concentration decreased significantly compared to other domestic/international cities. The concentration of sulfur represented the highest composition (8%) among the fine particle compounds. According to the CMB results, the general trend of the $PM_{2.5}$ mass contributors was the following: secondary aerosols (50.5%: ammonium sulfate 26.5% and ammonium nitrate 24.0%) > gasoline vehicle (18.3%) > biomass burning (11.0%) > industrial boiler (6.0%) > diesel vehicles (4.4%). The contribution of the secondary aerosols was the main cause than others. This impact is assumed to be emitted from air pollutants of urban cities or neighbor countries such as China.
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