• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.193-200
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• 2016

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has been reported to lead to cardiac toxicity even at therapeutic doses including sudden cardiac death and ventricular arrhythmia. And in a SSRI-independent manner, sertraline has been known to inhibit various voltage-dependent channels, which play an important role in regulation of cardiovascular system. In the present study, we investigated the action of sertraline on Kv1.5, which is one of cardiac ion channels. The effect of sertraline on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Sertraline reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $0.71{\mu}M$ and 1.29, respectively. Sertraline accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -20 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +10 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance ${\delta}$ of 0.16. Sertraline slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of sertraline, were superimposed. Inhibition of Kv1.5 by sertraline was use-dependent. The present results suggest that sertraline acts on Kv1.5 currents as an open-channel blocker.

• 대한치과마취과학회지
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• 제1권1호
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• pp.26-31
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• 2001

The wide deep penetrating wound of maxillofacial region should be early closed under emergency general anesthesia for the prevention of complications of bleeding, infection, shock & residual scars. But, if the emergency general anesthesia wound be impossible because of pneumoconiosis, obstructive pulmonary disease & hypovolemic shock, early primary closure should be done under local anesthesia by use of much amount of the anesthetic solution. The maximum dose of dental lidocaine (2% lidocaine with 1 : 100,000 epinephrine) is reported to 7 mg/kg under 500 mg (13.8 ampules) in normal adult. But the maximum permissible dose of dental lidocaine can be changed owing to the general health, rapidity of injection, resorption, distribution & excretion of the drug. The blood level of overdose toxicity is above $4.0{\mu}g/ml$ in central nervous & cardiovascular system. The injection of dental lidocaine 1-4 ampules is attained to the blood level of $1{\mu}g/ml$ in normal healthy adult. The duration of anesthetic action in the dental 2% lidocaine hydrochloride with 1 : 100.000 epinephrine is 45 to 75 minutes and the period to elimination is about 2 to 4 hours. Therefore, authors selected the following anesthetic methods that the first injection of 6 ampules is applied into the deeper periosteal layer for anesthetic action during 1 hour, the second injection into the deeper muscle & fascial layer, the third injection into the superficial muscle and fascial layer, the fourth injection into the proximal skin & subcutaneous tissue and the fifth final injection into the distal skin & subcutaneous tissue. The total 26-28 ampules of dental lidocaine were injected into the wound as the regular time interval during 5-6 hours, but there were no systemic complications, such as, agitation, talkativeness, convulsion and specific change of vital signs and consciousness.

• 대한예방한의학회지
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• 제15권2호
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• pp.69-99
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• 2011

Objective : Scutellaria baicalensis is one of the most popular and multi-purpose herb in traditional medicine. It is also useful for its practicability to cultivate in Korea. The purpose of this study is to contribute to researches and applications of scutellaria baicalensis by analyzing and reviewing international researches on the compositions and the effects of scutellaria baicalensis. Methods : This study analyzed 146 articles from PubMed by searching with the keyword "Scutellaria baicalensis", "Huang quin", "Baical Skullcap", "Huang qin", "baical skullcap root", "ogon", "Hwanggeum" and "Hwangkeum", published within the last 10 years(from 2000 to 2009). We reviewed the 146 articles on Scutellaria baicalensis and its active constituents in terms of 'Active constituents', 'Experimental studies', 'Clinical studies', 'Drug interaction', 'Side Effects/Toxicity' and 'Pharmacokinetics'. Results : The active constituents of Scutellaria baicalensis are flavonoids such as baicalein, baicalin, wogonin and oroxylin-A. It is reported that scutellaria baicalensis and its active compounds have antiinflammatory activity, antitumor activity, antioxidant activity, antiviral and antibiotic activity, neuroprotective effects, hepatoprotective effects and cardiovascular effect. Conclusions : This study is aimed to summarize the results obtained within the last 10 years and to contribute to following researches and applications of Scutellaria baicalensis.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.112-112
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• 2003

Voltage-gated $K^{+}$ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. These channels play an important role in determining the length of the cardiac action potential and are the targets for antiarrhythmic drugs. Many $K^{+}$ channel genes have been cloned from human myocardium and functionally contribute to its electrical activity. One of these channels, Kv1.5, is one of the more cardiovascular-specific $K^{+}$ channel isoforms identified to date and forms the molecular basis for an ultra-rapid delayed rectifier $K^{＋}$ current found in human atrium. Thus, the blocker of hKv1.5 is expected to be an ideal antiarrhythmic drug for atrial fibrillation. Chelidonine was isolated from Chelidonium majus L. We examined the effect of chelidonine on the hKv1.5 current expressed in Ltk-cells using whole cell mode of patch clamp techniques. Chelidonine selectively inhibited the hKv1.5 current expressed in Ltk-cells in a concentration-dependent manner, whereas did not affect the HERG current expressed in HEK-293 cells. Additionally, chelidonine reduced the tail current amplitude recorded at -50 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a 'crossover' phenomenon when the tail currents recorded under control conditions and in the presence of chelidonine were superimposed. We found that chelidonine also inhibited the $K^{+}$ current in isolated human atrial myocytes where hKv1.5 channels were predominantly expressed. Furthermore, we examined the effects of chelidonine on the action potentials in rabbit hearts using conventional microelectrode technique. Chelidonine prolonged the action potential durations (APD) of atrial, ventricular myocytes and Purkinje fibers in a dose-dependent manner. However, the effect of chelidonine on atrial APD was frequency-dependent whereas the effect of chelidonine on the APDs of ventricular myocytes and Purkinje fibers was not frequency- dependent. Also, the selective action of chelidonine on heart was more potent than dofetilide, $K^{+}$ channel blocker.

• 동의생리병리학회지
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• 제25권1호
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• pp.92-99
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• 2011

Topical natural antioxidants are a useful strategy for the prevention of oxidative stress mediated cardiovascular disease including atherosclerosis. From the viewpoint of this underlying principle, the screening of natural plant extracts with scavenging activity for pro-oxidant reactive species is a primary requirement for the development of new topical antioxidant formulations. Euryale ferox Salisbury (EF) is botanical name and it's pharmaceutical name is EURYALES SEMEN (ES). The stems and branchs of EF have been used as a traditional herbal medicine for the treatment of dysentery, diarrhea, leucorrhoea, incontinence and paralysis of joint. In this study, the antioxidant activity of extract from EF was studied in vitro methods by measuring the antioxidant activity and free radical scavenging activity by TEAC and DPPH, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$-induced human LDL oxidation. The EF extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation. In conclusion, the EF extracts have antioxidative effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and chronic degenerative disease such as atherosclerosis.

• Journal of Chest Surgery
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• 제34권7호
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• pp.539-546
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• 2001

배경: 면역저하 환자에게 발생하는 폐 합병증은 흔히 치명적이다. 폐생검술과 같은 침습적인 진단 술기의 위험도 때문에 일반적으로 임상 양상과 방사선 영상 소견에 근거하여 경험적인 치료가 적용된다. 그러나 최근 수술 술기와 수술 전후의 환자 관리의 발전으로 인해 술기와 연관된 위험도는 줄어든 실정이다. 이에 폐합병증을 동반한 심한 면역저하 환자에서 시행된 폐생검술의 위험성 및 유효성에 대하여 전향적으로 분석하였다. 대상 및 방법: 1996년 6월부터 1999년 12월까지 폐합병증을 동반한 면역저하 환자 42명에서 43례의 폐생검술을 실시하였다. 면역저하는 다음과 같이 정의하였고(1, 혈액학적인 질환으로 인해 화학요법이나 다른 치료를 동반하여 받은 경우, 2. 이식 수술 후 면역 억제제를 복용하는 경우, 3. 1 개월 이상의 스테로이드 복용, 4. 원발성 면역결핍 질환), 이상의 면역저하 환자에서 새로운 폐합병증을 동반하고 1 주간의 경험적 치료에 호전이 없거나 급속하게 진행되는 경우를 대상으로 하였다 기저 질환은 혈액학적 질환(31명), 이식 수술 환자(3명), 고형암으로 인한 화학요법(2명)등이었으며 수술은 개흉술이나 video-aided thoracoscopic surgery (VATS)를 통하여 이루어 졌다.

• 대한한의학회지
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• 제32권4호
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• pp.1-24
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• 2011

Backgrounds: Danggui, one of the major herbs in Korean traditional medicine consists of three species: Angelica gigas of Korea, Angelica sinensis of China, and Angelica acutiloba of Japan. Despite its importance in Korean traditional medicine, recognition of the clinical differences between its three species is insufficient. Objectives: The purpose of the present review is to suggest evidence in using Angelica gigas, Angelica sinensis, and Angelica acutiloba distinctively in clinic, by comparing their pharmacological effects and bioactive compounds. Methods: We searched articles published from 2000 to 2009 in Pubmed, EMbase, and RISS. The search keywords were "Angelica gigas", "Angelica sinensis", "Angelica acutiloba", "dongquei", "toki", "Angelicae Radix", "Archangelica officinalis Hoffm.", "Garden Angelica", "Chinese angelica root", "tangkuei", and "danggui". 861 articles were searched. Among them, we selected 143 articles which met our inclusion criteria. Results: This review summarizes active constituents, experimental studies, clinical studies, pharmacokinetics, side effects and toxicity, drug interaction, and industrial use of Angelica gigas, Angelica sinensis, and Angelica acutiloba. Conclusions: While Angelica sinensis and Angelica acutiloba are relatively similar, Angelica gigas is quite different from the others in main active constituents and genetic form. The main experimental studies of Danggui are cardiovascular studies, central nervous system studies and anti-cancer activity. Even though there were cases in which the three species show similar pharmacological effects, the mechanism was not always shared. Therefore, distinguished use of Angelica gigas, Angelica sinensis and Angelica acutiloba is needed.

• 동의생리병리학회지
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• 제22권5호
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• pp.1152-1157
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• 2008

Hyperlipidemia has been treated as one of the most important etiological cause factor in 21th century. The cortex and root of Acanthopanax sessiliflorus (AR), a herbal medicine, have been used for several diseases including cardiovascular diseases in Oriental countries. Recently, we reported that AR has anti-hyperlipidemic action. BS-01 was made using extract from AR. For these reasons, we investigated the effects of BS-01 as anti-hyperlipidemic drug through measurement of body weights, cholesterol levels, total lipid, phospholipid in serum. In our results, mice induced by high fat diet elevated body weight level compared to naive group. And total lipid in serum was also elevated by induction of hyperlipidemia. In BS-01 group, body weight of mice was lowered significantly compared to that of control group. Oral administration of BS-01 decreased total cholesterol and triglyceride level back to that of naive mice. HDL and LDL cholesterol levels were not affected by BS-01. In addition, total lipid level, which elevated by induction of hyperlipidemia was also lowered by oral administration of BS-01. Finally, free fatty acid level was lowered in BS-01 group. These results demonstrate that BS-01 lowered body weight and titers involved in hyperlipdemia such as total cholesterol, triglyceride, free fatty acid and total lipid. In these results, we demonstrate that BS-01 has anti-hyperlipidemic action.

• Journal of Chest Surgery
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• 제25권12호
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• pp.1508-1515
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• 1992

Between 1975 and 1992, forty five patients with trachea stenosis received tracheoplasty for relief of obstruction. The causes of airway problem are brain contusion[19 cases, 40%], cerebrovascular disease[3 cases, 7%], drug intoxication[8 cases, 18%], psychotic problem[2 cases, 4%], trachea tumor[3 cases, 7%], adult respiratory distress syndrome[9 cases, 20%] and direct trauma[1 case, 2%]. Direct causes of trachea stenosis were complications of tracheostomy[36 cases, 80%], complications of nasotracheal intubation[5 cases, 11%], tumor[3 cases, 6%] and trauma[1 case, 2%]. Thirty one patients underwent the sleeve resection and end-to-end anastomosis. Five patients performed a wedge resection and end-to-end anastomosis. Forteen patients received the Montgomery T-tube for relief of airway obstruction. Four patients have done simple excision of granulation tissue. Two, subglottic stenosis patients were received Rethi procedure[anterior division of cricoid cartilage, wedge partial resection of lower thyroid cartilage and Montgomery T-tube molding] and the other subglottic stenosis patient underwent permanent trachea fenestration. Including cervical flexion in all patients postoperatively, additional surgical techniques for obtain tension-free anastomosis were hyoid bone release technique in two cases, and hilar mobilization, division of inferior pulmonary ligament and mobilization of pulmonary vessel at the pericardium were performed in one case. Cervical approach was used in 39 cases, cervicomediastinal in 12 cases and transthoracic in one case. Complications of tracheoplasty were formation of granulation tissue at the anastomosis site[3 cases], restenosis[9 cases], trachea-innominate artery fistula[2 cases], wound infection[2 cases], separation of anastomosis[2 cases], air leakage[3 cases], injury to a recurrent laryngeal nerve[temporary 8 cases, permanent 2 cases] and hypoxemia[1 case]. Surgical mortality for resection with primary reconstruction was 6.7%, with one death due to postoperative respiratory failure and two deaths due to tracheo-innominate artery fistula.

• Journal of Chest Surgery
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• 제22권6호
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• pp.914-920
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• 1989

Bleomycin and cyclophosphamide are widely used and effective anti-cancer agents for treatment of various forms of cancer. Bleomycin has no myelotoxicity, but because of potential risk of pulmonary complications including interstitial pneumonitis and idiopathic interstitial pulmonary fibrosis, it has been limited in use. Some investigator has also suggested that cyclophosphamide can induce pulmonary toxicity like bleomycin. Recently, The combination chemotherapy including bleomycin and cyclophosphamide has been adopted effectively in some types of cancer. But there are no available literatures for synergistic effect of pulmonary toxicity in combination chemotherapy including these two drugs. We tried this study to observe synergism of pulmonary toxicity using these two drugs in rats. The animals were divided into five groups: group 1 received intra-peritoneal injection of saline, group 2-a received only bleomycin 0.1 mg [0.4 mg/kg] by intra-peritoneal injection twice a week, group 2-b received only bleomycin 0.5 mg [2 mg/kg] by intra-peritoneal injection twice a week, group 3-a received bleomycin 0.1 mg [0.4 mg/kg] twice a week +cyclophosphamide 5 mg [20 mg/kg] two weeks interval by intra-peritoneal injection, group 3-b received bleomycin 0.5 mg [2 mg/kg] twice a week + cyclophosphamide 5 mg[20 mg/kg] two weeks interval by intra-peritoneal injection. The animals were sacrificed at 2 and 4 weeks later. Lung tissues were obtained and observed by light microscope. The results are as follows: 1. The pathologic findings of group 1 were normal without change. 2. There was no difference between group 2-a and group 3-a at 2 weeks later, group 3-a, however, revealed more severe change in lung tissue at 4 weeks later compared with group 2-a. 3. In group 3-b there was more severe pulmonary injury compared with group 2-b at 2 and 4 weeks later. We conclude that the combined administration of bleomycin and cyclophosphamide induce more severe pulmonary toxic effect than bleomycin administration alone and the combination chemotherapy including these two drugs will be require special attention to selection of the dose of each drug.