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Preliminary Mechanistic Study on the Trachea Smooth Muscle Relaxant Activity of Aqueous Leaf Extract of Tridax Procumbens in Male Wistar Rats

  • Salami, Shakiru Ademola;Salahdeen, Hussein Mofomosara;Anidu, Babatunde Shuaib;Murtala, Babatunde Adekunle;Alada, AbdulRasak Akinola
    • Journal of Pharmacopuncture
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    • v.25 no.3
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    • pp.209-215
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    • 2022
  • Objectives: Aqueous leaf extract of Tridax procumbens (ALETP) has potent relaxant activity. However, this relaxant activity in respiratory smooth muscle remains uninvestigated. This study investigates the effect of ALETP on the contractile activity of tracheal smooth muscle (TSM) in adult male Wistar rats. Methods: Twelve male Wistar rats divided into 2 groups and were treated with either 100 mg/kg of ALETP (ALETP treatment group) or vehicle (distilled water; control group) through oral gavage for 4 weeks. Dose responses of TSM from the 2 groups to acetylcholine (10-9 to 10-5 M), phenylephrine (10-9 to 10-5 M), and potassium chloride (KCl; 10-9 to 10-4 M) were determined cumulatively. Furthermore, cumulative dose responses to acetylcholine (10-9 to 10-5 M) after pre-incubation of TSM with atropine (10-5 M), L-NAME (10-4 M), indomethacin (10-4 M), and nifedipine (10-4 M), were determined. Results: Treatment with ALETP substantially inhibited TSM contraction stimulated by cumulative doses of acetylcholine, phenylephrine, and KCl. Furthermore, preincubation of TSM from the 2 groups in atropine significantly inhibited contractility in TSM. Incubation in L-NAME and indomethacin also significantly inhibited contractility in TSM of ALETP-treated rats compared to that of controls. Contractile activity of the TSM was also inhibited significantly with incubation in nifedipine in ALETP-treated rats. Conclusion: ALETP enhanced relaxant activity in rat TSM primarily by blocking the L-type calcium channel and promoting endothelial nitric oxide release. ALETP contains agents that may be useful in disorders of the respiratory tract.

HMGB1 increases RAGE expression in vascular smooth muscle cells via ERK and p-38 MAPK-dependent pathways

  • Jang, Eun Jeong;Kim, Heejeong;Baek, Seung Eun;Jeon, Eun Yeong;Kim, Ji Won;Kim, Ju Yeon;Kim, Chi Dae
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.5
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    • pp.389-396
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    • 2022
  • The increased expression of receptors for advanced glycation end-product (RAGE) is known as a key player in the progression of vascular remodeling. However, the precise signal pathways regulating RAGE expression in vascular smooth muscle cells (VSMCs) in the injured vasculatures are unclear. Given the importance of mitogen-activated protein kinase (MAPK) signaling in cell proliferation, we investigated the importance of MAPK signaling in high-mobility group box 1 (HMGB1)-induced RAGE expression in VSMCs. In HMGB1 (100 ng/ml)-stimulated human VSMCs, the expression of RAGE mRNA and protein was increased in association with an increase in AGE-induced VSMC proliferation. The HMGB1-induced RAGE expression was attenuated in cells pretreated with inhibitors for ERK (PD98059, 10 μM) and p38 MAPK (SB203580, 10 μM) as well as in cells deficient in ERK and p38 MAPK using siRNAs, but not in cells deficient of JNK signaling. In cells stimulated with HMGB1, the phosphorylation of ERK, JNK, and p38 MAPK was increased. This increase in ERK and p38 MAPK phosphorylation was inhibited by p38 MAPK and ERK inhibitors, respectively, but not by JNK inhibitor. Moreover, AGE-induced VSMC proliferation in HMGB1-stimulated cells was attenuated in cells treated with ERK and p38 MAPK inhibitors. Taken together, our results indicate that ERK and p38 MAPK signaling are involved in RAGE expression in HMGB1-stimulated VSMCs. Thus, the ERK/p38 MAPK-RAGE signaling axis in VSMCs was suggested as a potential therapeutic target for vascular remodeling in the injured vasculatures.

Utilization of Piper betle L. Extract for Inactivating Foodborne Bacterial Biofilms on Pitted and Smooth Stainless Steel Surfaces

  • Songsirin Ruengvisesh;Pattarapong Wenbap;Peetitas Damrongsaktrakul;Suchanya Santiakachai;Warisara Kasemsukwimol;Sirilak Chitvittaya;Yossakorn Painsawat;Isaratat Phung-on;Pravate Tuitemwong
    • Journal of Microbiology and Biotechnology
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    • v.33 no.6
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    • pp.771-779
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    • 2023
  • Biofilms are a significant concern in the food industry. The utilization of plant-derived compounds to inactivate biofilms on food contact surfaces has not been widely reported. Also, the increasing negative perception of consumers against synthetic sanitizers has encouraged the hunt for natural compounds as alternatives. Therefore, in this study we evaluated the antimicrobial activities of ethanol extracts, acetone extracts, and essential oils (EOs) of seven culinary herbs against Salmonella enterica serotype Typhimurium and Listeria innocua using the broth microdilution assay. Among all tested extracts and EOs, the ethanol extract of Piper betle L. exhibited the most efficient antimicrobial activities. To evaluate the biofilm inactivation effect, S. Typhimurium and L. innocua biofilms on pitted and smooth stainless steel (SS) coupons were exposed to P. betle ethanol extract (12.5 mg/ml), sodium hypochlorite (NaClO; 200 ppm), hydrogen peroxide (HP; 1100 ppm), and benzalkonium chloride (BKC; 400 ppm) for 15 min. Results showed that, for the untreated controls, higher sessile cell counts were observed on pitted SS versus smooth SS coupons. Overall, biofilm inactivation efficacies of the tested sanitizers followed the trend of P. betle extract ≥ BKC > NaClO > HP. The surface condition of SS did not affect the biofilm inactivation effect of each tested sanitizer. The contact angle results revealed P. betle ethanol extract could increase the surface wettability of SS coupons. This research suggests P. betle extract might be utilized as an alternative sanitizer in food processing facilities.

Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells

  • Hongliang Li;Yue Zhou;Yongqi Yang;Yiwen Zha;Bingqian Ye;Seo-Yeong Mun;Wenwen Zhuang;Jingyan Liang;Won Sun Park
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.399-406
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    • 2023
  • Voltage-dependent K+ (Kv) channels are widely expressed on vascular smooth muscle cells and regulate vascular tone. Here, we explored the inhibitory effect of encainide, a class Ic anti-arrhythmic agent, on Kv channels of vascular smooth muscle from rabbit coronary arteries. Encainide inhibited Kv channels in a concentration-dependent manner with an IC50 value of 8.91 ± 1.75 μM and Hill coefficient of 0.72 ± 0.06. The application of encainide shifted the activation curve toward a more positive potential without modifying the inactivation curve, suggesting that encainide inhibited Kv channels by altering the gating property of channel activation. The inhibition by encainide was not significantly affected by train pulses (1 and 2 Hz), indicating that the inhibition is not use (state)-dependent. The inhibitory effect of encainide was reduced by pretreatment with the Kv1.5 subtype inhibitor. However, pretreatment with the Kv2.1 subtype inhibitor did not alter the inhibitory effects of encainide on Kv currents. Based on these results, encainide inhibits vascular Kv channels in a concentration-dependent and use (state)-independent manner by altering the voltage sensor of the channels. Furthermore, Kv1.5 is the main Kv subtype involved in the effect of encainide.

Biophysically stressed vascular smooth muscle cells express MCP-1 via a PDGFR-β-HMGB1 signaling pathway

  • Ji Won Kim;Ju Yeon Kim;Hee Eun Bae;Chi Dae Kim
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.5
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    • pp.449-456
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    • 2024
  • Vascular smooth muscle cells (VSMCs) under biophysical stress play an active role in the progression of vascular inflammation, but the precise mechanisms are unclear. This study examined the cellular expression of monocyte chemoattractant protein 1 (MCP-1) and its related mechanisms using cultured rat aortic VSMCs stimulated with mechanical stretch (MS, equibiaxial cyclic stretch, 60 cycles/min). When the cells were stimulated with 10% MS, MCP-1 expression was markedly increased compared to those in the cells stimulated with low MS intensity (3% or 5%). An enzyme-linked immunosorbent assay revealed an increase in HMGB1 released into culture media from the cells stimulated with 10% MS compared to those stimulated with 3% MS. A pretreatment with glycyrrhizin, a HMGB1 inhibitor, resulted in the marked attenuation of MCP-1 expression in the cells stimulated with 10% MS, suggesting a key role of HMGB1 on MCP-1 expression. Western blot analysis revealed higher PDGFR-α and PDGFR-β expression in the cells stimulated with 10% MS than 3% MS-stimulated cells. In the cells deficient of PDGFR-β using siRNA, but not PDGFR-α, HMGB1 released into culture media was significantly attenuated in the 10% MS-stimulated cells. Similarly, MCP-1 expression induced in 10% MS-stimulated cells was also attenuated in cells deficient of PDGFR-β. Overall, the PDGFR-β signaling plays a pivotal role in the increased expression of MCP-1 in VSMCs stressed with 10% MS. Therefore, targeting PDGFR-β signaling in VSMCs might be a promising therapeutic strategy for vascular complications in the vasculatures under excessive biophysical stress.

Does oral ciprofloxacin affect the structure of thoracic aorta in adult and senile male albino rats? A clue to fluoroquinolones-induced risk of aortic dissection

  • Ahmed Farid Al-Neklawy;Nagwa Ebrahim El-Nefiawy;Hagar Yousry Rady
    • Anatomy and Cell Biology
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    • v.55 no.1
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    • pp.79-91
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    • 2022
  • In this study, the effect of oral ciprofloxacin on the structure of the thoracic aorta in rats was investigated. Twenty four male albino rats were divided into 4 groups (6 rats/group): group I (adult control), group II (adult rats treated with ciprofloxacin), group III (senile control), and group IV (senile rats treated with ciprofloxacin). Rats in groups II and IV received ciprofloxacin via oral gavage in a daily dose of 3.5 mg/kg/d for 14 days, while control rats received equivalent amount of distilled water used to dissolve the drug. After 2 weeks, all rats were sacrificed, thoracic aortae were dissected, and half of the specimens were processed for paraffin sections and examined by light microscopy. The other half of the specimens were prepared for scanning electron microscopy. Sections from rats treated with ciprofloxacin showed evident damaging effect on aortic wall particularly in (group IV). Aortic intima showed, focal desquamation of the lining epithelium. Tunica media exhibited loss of the normal concentric arrangement and degeneration of the smooth muscle cells. Immune staining for alpha smooth muscle actin showed muscle damage. Interestingly, some sections in (group IV) showed out-pouch (aneurysm like) of the aortic wall. There was dense collagen fibers deposition. Scanning electron microscopic observations of (group IV) revealed uneven intima, adherent blood cells and fibrin filaments to damaged intima, and out-pouch formation. It was concluded that oral ciprofloxacin caused deleterious structural changes in the thoracic aortic wall of rats explaining clinical observations of fluoroquinolones induced risk of aortic dissection and aneurysm.

Study on the improvement for envelopment curve of probable maximum precipitation (가능최대강수량 포락곡선 개선방안 연구)

  • Beck, Yoohyun;Ahn, Jaehyun;Cho, Hyonkook
    • Journal of Korea Water Resources Association
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    • v.57 no.10
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    • pp.725-739
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    • 2024
  • In Korea, the national PMP map is used to calculate the Probable Maximum Precipitation (PMP) but the intercept adjustments are necessary to obtain uniform PMP envelopment results. The Box-Cox and cubic Spline methods to get the PMP envelopment modeling were proposed by the past studies.. However there has been no significant progress in the study of PMP envelopment modeling since then. This study, which focused on the last step of PMP estimation process in Korea, used the Monotone Cubic Spline (MCS) and compared with existing methods. As a result, the intercept adjustments involving the engineer's subjectivity were necessary to obtain smooth envelopment curves in case of using the existing method such as the cubic spline. However, a smooth envelopment curves were obtained without intercept adjustment in case of using MCS method. Therefore, using the MCS method for dam-related new projects can get smooth and consistent envelopment results without intercept adjustment for PMP calculation in Korea.

Evaluation to Obtain the Image According to the Spatial Domain Filtering of Various Convolution Kernels in the Multi-Detector Row Computed Tomography (MDCT에서의 Convolution Kernel 종류에 따른 공간 영역 필터링의 영상 평가)

  • Lee, Hoo-Min;Yoo, Beong-Gyu;Kweon, Dae-Cheol
    • Journal of radiological science and technology
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    • v.31 no.1
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    • pp.71-81
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    • 2008
  • Our objective was to evaluate the image of spatial domain filtering as an alternative to additional image reconstruction using different kernels in MDCT. Derived from thin collimated source images were generated using water phantom and abdomen B10(very smooth), B20(smooth), B30(medium smooth), B40 (medium), B50(medium sharp), B60(sharp), B70(very sharp) and B80(ultra sharp) kernels. MTF and spatial resolution measured with various convolution kernels. Quantitative CT attenuation coefficient and noise measurements provided comparable HU(Hounsfield) units in this respect. CT attenuation coefficient(mean HU) values in the water were values in the water were $1.1{\sim}1.8\;HU$, air($-998{\sim}-1000\;HU$) and noise in the water($5.4{\sim}44.8\;HU$), air($3.6{\sim}31.4\;HU$). In the abdominal fat a CT attenuation coefficient($-2.2{\sim}0.8\;HU$) and noise($10.1{\sim}82.4\;HU$) was measured. In the abdominal was CT attenuation coefficient($53.3{\sim}54.3\;HU$) and noise($10.4{\sim}70.7\;HU$) in the muscle and in the liver parenchyma of CT attenuation coefficient($60.4{\sim}62.2\;HU$) and noise ($7.6{\sim}63.8\;HU$) in the liver parenchyma. Image reconstructed with a convolution kernel led to an increase in noise, whereas the results for CT attenuation coefficient were comparable. Image scanned with a high convolution kernel(B80) led to an increase in noise, whereas the results for CT attenuation coefficient were comparable. Image medications of image sharpness and noise eliminate the need for reconstruction using different kernels in the future. Adjusting CT various kernels, which should be adjusted to take into account the kernels of the CT undergoing the examination, may control CT images increase the diagnostic accuracy.

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Effects of Bombesin on Electrical and Mechanical Activities of Gastric Smooth Muscle Strips of Cats (적출한 고양이 위(胃) 평활근 절편의 전기적 및 기계적 활동에 미치는 Bombesin의 영향과 그 작용기전)

  • Park, Hyoung-Jin;Kwon, Hyeok-Yil;Suh, Sang-Won;Kim, Jeong-Mi;Lee, Tae-Hyung
    • The Korean Journal of Physiology
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    • v.24 no.1
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    • pp.39-49
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    • 1990
  • It has been reported that bombesin induces contraction of the smooth muscle of the gastrointestinal tract. Thus, the present investigation was undertaken to see an influence of bombesin on electrical activity of the gastric smooth muscle, since electrical activity is associated with contractile activity in the smooth muscle of the stomach. Smooth muscle strips $(5\;{\times}\;1.5\;cm)$ that included the corpus and antrum were prepared from the ventral and dorsal portion of the feline stomach along the greater curvature. Circular muscle strips $(1\;{\times}\;0.3\;cm)$ of the corpus were also obtained. Electrical activity of the corpus and antrum of the muscle strip was monophasically recorded by using Ag-AgCl capillary electrodes placed on the circular muscle layer. Contractile activity of the circular muscle strip was also recorded. The recordings were performed in Krebs-Ringer solution that was continuously aerated with $O_{2}$ containing 5% $Co_{2}$, and kept at $36^{\circ}C$. Dose-related responses of electrical activity and contractility to bombesin was studied after frequency of slow waves and contraction of each strip reached to a steady state. An action of $D-leu^{13}-{\psi}\;(CH_{2}NH)-D-leu^{14}-bombesin,\;D-pro^{2}-D-trp^{7,9}-substance\;P$, tetrodotoxin, hexamethonium, atropine, phentolamine or propranolol on the effect of bombesin was also observed. 1) Bombesin increased frequency of slow waves and contractions dose-dependently at concentrations from $10^{-9}\;M\;to\;3\;{\times}\;10^{-8}\;M$. 2) The bombesin analogue at a concentration of $3\;{\times}\;10^{-7}\;M$ antagonized the effect of bombesin on frequency of slow waves. 3) The effect of bombesin on frequency of slow waves was inhibited by tetrodotoxin $(10^{-6}\;M)$ and hexamethonium $(10^{-3}\;M)$ but unaffected by atropine $(10^{-6}\;M)$, phentolamine $(10^{-5}\;M)$ and propranolol $(10^{-5}\;M)$. 4) The effect of bombesin on frequency of slow waves was blocked by the substance P analogue at a concentration of $10^{-5}\;M$. 5) Substance P at a concentration of $10^{-5}\;M$ failed to change frequency of slow waves. It is concluded from the above results that bombesin increases the frequency of slow waves as well as contractions of the smooth muscle strip from the feline stomach, and the effect of bombesin might be mediated by non-cholinergic or non-adrenergic mechanism at neuromuscular junction. However, enteric nerves that have substance P as a neurotransmitter do not appear to participate in the action of bombesin on frequency of slow waves.

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Effect of pH Change on Vascular Smooth Muscle Contractility in Rat Superior Mesenteric Artery and Its Branches (쥐 상장간막 동맥과 그 분지에서 pH 변화가 혈관평활근 수축성에 미치는 영향)

  • Choi, Soo-Seung
    • Journal of Chest Surgery
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    • v.43 no.4
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    • pp.345-355
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    • 2010
  • Background: Extracellular and intracellular pH ($pH_o$ and $pH_i$), which can be changed in various pathological conditions such as hypoxia, affects vascular contractility. To elucidate the mechanism to alter vascular contractility by pH, the effects of pH on reactivity to vasocontracting agents, intracellular $Ca^{2+}$ influx, and $Ca^{2+}$ sensitivity in vascular smooth muscle were examined. Material and Method: Isometric contractions in rat superior mesenteric arteries (SMA) were observed. Intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) was recorded by microfluorometer using Fura-2/acetoxylmethyl ester in muscle cells. $pH_o$ was increased from 7.4 to 7.8 or decreased to 6.9 or 6.4. $pH_i$ was decreased by applying $NH_4^+$ or propionic acid or modulated by changing $pH_o$ after increasing membrane permeability using $\beta$-escin. Result: Decreases in $pH_o$ from 7.4 to 6.9 or 6.4 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the right and significantly increased half maximal effective concentration (EC50) to NE or SE. Increase in $pH_o$ from 7.4 to 7.8 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the left and significantly reduced EC50 to NE or SE. NE increased $[Ca^{2+}]_i$ in cultured smooth muscle cells from SMA and the increased $[Ca^{2+}]_i$ was reduced by decreases in $pH_o$. NE-induced contraction was inhibited by $NH_4^+$, whereas the resting tension was increased by $NH_4^+$ or propionic acid. When the cell membrane of SMA was permeabilized using ${\beta}$-escin, SMA was contracted by increasing extracellular $Ca^{2+}$ concentration from 0 to $10{\mu}M$ and the magnitude of contraction was decreased by a decrease in $pH_o$ and vice versa. Conclusion: From these results, it can be concluded that a decrease in $pH_o$ might inhibit vascular contraction by reducing the reactivity of vascular smooth muscle to vasoactive agents, $Ca^{2+}$ influx and the sensitivity of vascular smooth muscle to $Ca^{2+}$.