• Advances in Traditional Medicine
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• 제2권2호
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• pp.87-93
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• 2002

The present study was aimed to examine the role of endothelium in the relaxant effect of hawthorn fruit extract of Crataegus pinnatifida in four different types of rat arteries, posterior cerebral communicating artery, right descending coronary artery, common carotid artery, and aorta. In $9,11-dideoxy-11{\alpha}$, $9{\alpha}-epoxy-methanoprostaglandin$ $F_{2{\alpha}}$ (U46619)-preconstricted arterial rings except for aorta, the extract produced endothelium-independent relaxations with similar potency. This relaxation was unaffected by pretreatment with $100\;{\mu}M\;N^G-nitro-L-arginine$ methylester (L-NAME, the nitric oxide synthase inhibitor), $3\;{\mu}M$ 1H-[l,2,4]oxadiazolo$[4,2-{\alpha}]$quinoxalin-1-one (ODQ, the guanylate cyclase inhibitor), or $10\;{\mu}M$ indomethacin (the cyclooxygenase inhibitor). Putative $K^+$ channel blockers (charybdotoxin plus apamin or glibenclamide) did not affect the extract-induced relaxation in cerebral or coronary artery rings. In contrast, in rat aortic rings the extract produced significantly smaller relaxant response in endothelium-denuded rings than that in endothelium-intact rings. Pretreatment with L-NAME or ODQ abolished the extractinduced endothelium-dependent aortic relaxation, whilst indomethacin $(3\;{\mu}M)$ had no effect. The present results indicate that hawthorn fruit extract possesses a vasorelaxing effect in cerebral, coronary and carotid arteries and this effect is independent of the presence of a functional endothelium. However, the extract-induced endothelium-dependent relaxation in rat aorta was mediated through endothelial nitric oxide and cyclic GMP-dependent mechanisms, suggesting that active components in the extract may act on endothelium to stimulate release of nitric oxide in large conduit arteries of the rats.

• KSBB Journal
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• 제27권5호
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• pp.313-318
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• 2012

Dimethyl sulfoxide (DMSO) increased the intracellular calcium ion concentration in stably transfected Drosophila melanogaster S2 cells expressing recombinant cyclooxygenase 1 (COX-1). DMSO did not increase the Drosophila NOS (dNOS) transcript level in calcium chelator-treated cells. Expression of recombinant COX-1 due to DMSO was diminished in cells treated with calcium chelators or channel blockers. Our results indicate that an increased intracellular calcium ion concentration due to DMSO is associated with up-regulation of the dNOS gene, leading to enhanced expression of COX-1.

• Animal cells and systems
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• 제1권1호
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• pp.81-86
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• 1997

We studied the mechanism of arachidonic acid on the secretion of a neurotransmitter in rat pheochromocytoma PC12 cells. Arachidonic acid inhibited the 70 mM $K^+$-induced secretion of norepinephrine. Arachidonic acid also inhibited the 70 mM $K^+$-induced $Ca^{2+}$ mobilization which is due to the opening of the voltage-sensitive $Ca^{2+}$ channels (VSCC). Both the half maximal inhibitory concentration ($IC_{50}$) of the norepinephrine secretion and VSCC coincided at 30 uM. The major oxidized metabolites of arachidonic acid, prostaglandins did not mimic the inhibitory effect of arachidonic acid. Nordihydroguaiaretic acid (NDGA) and indomethacin which are inhibitors of lipoxygenase and cyclooxygenase, respectively, did not block the inhibitory effect of arachidonic acid. The results suggest that arachidonic acid serves as a signal itself, not in the form of metabolites. The pretreatment of various $K^+$ channel blockers such as 4-aminopyridine, tetraethylarnmonium, glipizide, or glibenclamide also did not show any effect on the inhibitory effect of arachidonic acid. Through these results we suggest that arachidonic acid regulates VSCC directly and affects the secretion of neurotransmitters.

• 대한임상독성학회지
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• 제13권1호
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• pp.1-10
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• 2015

Purpose: The purpose of this study was to evaluate the usefulness of intravenous lipid emulsion as well as adverse events in acute poisoning patients. Methods: Literature was accessed through PubMed, EMBASE, Cochrane library, Web of science, and KoreaMed. All forms of literatures relevant to human use of intravenous lipid emulsion for acute poisoning were included. Cases reports or letters without description of clinical outcomes for each case were excluded. The literature search was conducted by two investigators in March, 2015, with publication language restricted to English and Korean. The effect, onset time, and adverse event of lipid emulsion and final outcome of each case were analyzed. Results: Eighty-one published articles were included, excluding articles whose title and abstract were not relevant to this study. No articles were classified as high level of evidence. Sixty-eight case reports were identified, consisting of 25 local anesthetics and 43 other drugs, such as tricyclic antidepressants and calcium channel blockers. Although most cases described significant clinical improvements, some of them showed no beneficial effect or worsening of clinical course. Several adverse events including hyperamylasemia and laboratory interference were reported. Conclusion: Although there were many case reports illustrating successful use of lipid for various drug poisonings, the effect cannot be estimated due to significant possibility of publication bias. Therefore, lipids might be considered in severe hemodynamic instability resulting from lipophilic drug poisoning, however further studies should follow to establish the use of lipid as the standard of care.

• The Korean Journal of Physiology and Pharmacology
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• 제20권4호
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• pp.399-406
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• 2016

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.

• 한국의료질향상학회지
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• 제3권1호
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• pp.126-143
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• 1996

Background : Little work has been carried out regarding quality assessment research in a primary care setting, comparing with that of hospitals. This study aims to evaluate the process of diagnosis and management of hypertension by public health doctors on the basis of pre-established clinical guideline, and to identify several modifying factors associated with them. Methods : Hypertension was selected as the target disease, because it is a chronic disease which is of great public health importance. Self-administered questionnaires were mailed to public health doctors practicing at health centers and health subcenters across the nation. The response rate was 20.9%. The questionnaire included the diagnosis and management process such as measuring blood pressure, history taking, physical examinations, and treatment approches and potentially modifying factors such as level of training, duration of practice as a public health doctor, and education on management of hypertension. Results : Public health doctors pay little attention in measuring BP, hypertension related history taking, performing physical examination and laboratory examination. But they devoted much effort in diagnosing hypertension exactly and giving nonpharmacological treatment. Among various antihypertensive drugs, calcium-channel blockers were the most preferred agent(50.9%). Level of training, duration of practice ad a public health doctor, and education on management of hypertension made no difference on quality of care(p>0.05). Conclusion : These public health doctors showed poor compliance with the pre-established clinical guidelines, which leaves much to be desired in diagnosing and managing hypertensive patients by public health doctors. This study might be able to contribute to develop some strategies, such as educational programs, which would be able to improve the process of care in hypertensives.

• Natural Product Sciences
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• 제29권2호
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• pp.104-112
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• 2023

COVID-19 caused a catastrophe in human health. People infected with COVID-19 also suffer from various clinical illnesses during and after the infection. The Boerhavia diffusa plant is well known for its antihypertensive activity. ACE-II inhibitors and calcium channel blockers are reported as mechanisms for the antihypertensive activity of B. diffusa phytoconstituents. Various studies have said ACE-II is the virus's binding site to attack host cells. COVID-19 treatment commonly employs a variety of synthetic antiviral and steroidal drugs. As a result, other clinical illnesses, such as hypertension and hyperglycemia, emerge as serious complications. Safe and effective drug delivery is a prime objective of the drug development process. COVID-19 is treated with various herbal treatments; however, they are not widely used due to their low potency. Many herbal plants and formulations are used to treat COVID-19 infection, in which B. diffusa is the most widely used plant. The current study relies on discovering active phytoconstituents with ACE-II inhibitory activity in the B. diffusa plant. As a result, it can be used as a treatment option for patients with COVID-19 and related diseases. Different phytoconstituents of the B. diffusa plant were selected from the reported literature. The activity of phytoconstituents against ACE-II proteins has been studied. Molecular docking and ligand-protein interaction computation tools are used in the in-silico experiment. Physicochemical, drug-likeness, water solubility, lipophilicity, and pharmacokinetic parameters are used to evaluate phytoconstituents. Liriodenine has the best drug-likeness, bioactivity, and binding score characteristics among the selected ligands. The in-silico study aims to find the therapeutic potential of B. diffusa phytoconstituents against ACE-II. Targeting ACE-II also shows an effect against SARS-CoV-2. It can serve as a rationale for designing a drug for patient infected with COVID-19 and associated diseases.

• 대한수의학회지
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• 제38권4호
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• pp.712-719
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• 1998

Thyroid function is mainly regulated through cAMP and phophatidylinositol, and it is well known that TSH-stimulated thyroxine ($T_4$) release is inhibited by catecholamine from mouse thyroids via the ${\alpha}_1$-adrenoceptor stimulation. Previous study has established that the inhibition of $T_4$ release by ${\alpha}_1$-adrenoceptor stimulation results in activated protein kinase C (PKC). The purpose of this study was to determine if ion transport systems are involved in the inhibition of $T_4$ release elicited by ${\alpha}_1$-adrenergic agonist in mouse thyroids. TSH-, IBMX- and cAMP analogue-stimulated $T_4$ release were significantly inhibited by methoxamine, R59022 (diacylglycerol kinase inhibitor), and MDL (adenylate cyclase inhibitor). TSH-stimulated $T_4$ release could be inhibited by Bay K 8644 and cyclopiazoic acid, but not by verapamil and tetrodotoxin. The addition of nifedipine ($Ca^{2+}$ channel blocker), tetrodotoxin and lidocaine ($Na^+$ channel blockers), but not amiloride (EIPA) and ryanodine, completely blocked the inhibitory effects of methoxamine on $T_4$ release. TSH-stimulated $T_4$ release was also inhibited by benzamil ($Na^+-Ca^{2+}$ exchange inhibitor). TSH-, IBMX- and cAMP-stimulated $T_4$ release were inhibited by methoxamine or R59022, these effects were reversed by nifedipine. but not by verapamil. Furthermore, nifedipine reversed the inhibitory effects of benzamil and R59022 on TSH-stimulated $T_4$ release. These data suggest that the observed ${\alpha}_1$-adrenoceptor-mediated inhibition of $T_4$ release in mouse thyroids is the result of an increase in intracellular $Na^+$ or $Ca^{2+}$ effected via activation of fast $Na^+$ or nifedipine-sensitive $Ca^{2+}$ channels, and that $Na^+-Ca^{2+}$ exchange may play an important role in reducing thyroid hormone by increasing intracellular $Ca^{2+}$.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.78-83
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) has previously shown to induce neurotoxicity through intracellular $Ca^{2+}$ increase in rat neurons. In this study we investigated the role and signaling pathway of intracellular $Ca^{2+}$ in TCDD-induced inhibition of neuronal cell proliferation in SK-N-SH human neuronal cells. We found that TCDD(10nM) rapidly increased the level of intracellular $Ca^{2+}$, which was completely blocked by the extracellular $Ca^{2+}$ chelation with EGTA (1 mM) or by pretreatment of the cells with the non-selective cation channel blocker. flufenamic acid (200 ${\mu}M$). However, pretreatment of the cells with dantrolene (25 ${\mu}M$) and TMB-8(10 ${\mu}M$), intracellular $Ca^{2+}$-release blockers, or a voltage-sensitive $Ca^{2+}$ channel blocker, varapamil (100 ${\mu}M$), failed to block the TCDD-induced $Ca^{2+}$ increase in the cells. In addition, TCDD induced a rapid and transient activation of phatidvlinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2(ERK1/2), which was ingnificantly blocked by the pretreatment with BAPTA, an intracellular $Ca^{2+}$ chelator, and LY294002, a PI3K inhibitor. Furthermore, inhibitors of PI3K, ERK, or an intracellular $Ca^{2+}$ chelator further potentiated the anti-proliferative effect of TCDD in the cells. Collectively, the results suggest that intracellular $Ca^{2+}$ and PI3K-dependent activation of ERK 1/2 may be involved in the TCDD-induced inhibition of cell proliferation in SK-N-SH human neuronal cells.

• 대한수의학회지
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• 제38권2호
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• pp.280-289
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• 1998

Voltage-sensitive ion channels contribute to establishment of the cell excitablity and the generation of the cellular function. At hamster oocytes in the primitive stage during developing process, an inward current elicited by voltage pulses was found to be carried mainly by $Ca^{2+}$. Even at present, $Ca^{2+}$ channels serve as the most probable route to pass this inward current but there is no evidence of the presence of this channels in eggs. To date, both the characteristic properties and the physiological role in the early stage of development remain unclear. Here we examined the characteristic properties of the inward current and changes in this currents at unfertilized oocytes, fertilized zygotes and two-cell embryos using whole-cell voltage clamp technique. The inward current carried reportedly by $Ca^{2+}$ was remained following removing external $Ca^{2+}$ but completely abolished by further replacement of impermeants such as tetramethylammonium ion ($TMA^+$) or $choline^+$ instead of $[Na^+]_0$. Tetrodotoxin did not affect on this inward current remained at $[Ca^{2+}]_0$-free condition. Removal of $Na^+$ ion out of the experimental solution clearly decreased the current. After adding 2mM $Ca^{2+}$ to the $Na^+$-free media, the inward current was restored. Interestingly, this current carried by either $Ca^{2+}$ or $Na^+$ was decreased by the reduction of intracellular $Cl^-$ concentration, or by $Cl^-$ channel blockers such as niflumic acid, DIDS and SITS. When $Cl^-$ concentration was lowered without changes in other ionic components, this inward current was reduced. At fertilized oocytes and two-cell embryos, the inward current carried by $Ca^{2+}$ and $Na^+$ was severely reduced. Also $Cl^-$ component could not be observed. From these results, the inward current is composed of $Ca^{2+}$, $Na^+$ and $Cl^-$ component, suggesting that the channel carrying this inward current is not selective specifically to $Ca^{2+}$. During early stage of development, the voltage-sensitive ion current seems not to contribute essentially to the cell cleavage and differentiation. The loss of $Cl^-$ component after fertilization suggests that $Cl^-$ may play a role in maintaining the viability of unfertilized ova.