• Title/Summary/Keyword: Cardiovascular drug

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Oxidized LDL Accelerates Cartilage Destruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway

  • Jeong Su Lee;Yun Hwan Kim;JooYeon Jhun;Hyun Sik Na;In Gyu Um;Jeong Won Choi;Jin Seok Woo;Seung Hyo Kim;Asode Ananthram Shetty;Seok Jung Kim;Mi-La Cho
    • IMMUNE NETWORK
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    • v.24 no.3
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    • pp.15.1-15.18
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    • 2024
  • Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

Isolated Lung Perfusion with Cisplatin in Rabbit - evaluation of pharmacokinetics and long term pathologic changes of the lung- (가토에서 Cisplatin을 사용한 분리 폐 관류 -약리학적 변화 및 폐의 장기적 병리학적 변화에 관한 연구-)

  • 김관민;김진국;한정호
    • Journal of Chest Surgery
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    • v.32 no.7
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    • pp.613-620
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    • 1999
  • Background: Recently, regional or isolated organ perfusion is being studied again as a drug administration modality which is able to reduce systemic toxicity while delivering high-dose chemotherapeutic agents. This research was planned to evaluate the pharmacokinetics and long-term pathologic changes of the lung in isolated lung perfusion (ILP) with cisplatin. Material and Method: Twenty-five New Zealand white rabbits were divided into 2 groups (Group I: 10, Group II: 15). The groups were then subdivided into 2 and 3 subgroups of 5 rabbits. In group I, tissue samples of the lung and kidney, and systemic blood for platinum concentration measurement were taken 30 minutes after systemic intravenous infusion of cisplatin (5 mg/kg) and isolated lung perfusion in each 5 rabbits. In 2 subgroups of group II, lung tissues for pathologic exams were taken 30 minutes and 1 week after ILP in each 5 rabbits, which received 10% pentastarch solution only and cisplatin, respectively. In the other subgroups, lung biopsy was undertaken 4 weeks after ILP with cisplatin. Result: When cisplatin was infused via systemic vein, the platinum concentration in the lung, kidney and plasma were 1.50${\pm}$0.43 $\mu\textrm{g}$/g, 7.65${\pm}$2.49 $\mu\textrm{g}$/g, 1.19${\pm}$0.03 $\mu\textrm{g}$/ml, respectively. However, the platinum concentration in the lung was about 50 times higher (75.43${\pm}$11.47 $\mu\textrm{g}$/g) than that of intravenous infusion group, and those in the kidney and plasma were decreased (1.30${\pm}$ 0.35 $\mu\textrm{g}$/g, 0.13${\pm}$0.02 $\mu\textrm{g}$/ml) when cisplatin was introduced through ILP. Pathologic change in the treated lung with ILP was characterized by the medial hypertrophy of the pulmonary arterioles and interstitial eosinophilic infiltration, which was not dependent on cisplatin

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Analysis of stress distribution of tooth restored with metal-ceramic crown covering abfraction lesion according to its finish line location under occlusal load (금속도재관으로 수복된 Abfraction lesion이 있는 치아에 가해지는 교합력의 응력 분포 분석)

  • Kim, Jee-Hwan;Yoon, Chol-Wook;Kim, Taehyeon;Kim, Han-Sung;Woo, Dae-Gon;Lee, Keun-Woo;Shim, June-Sung
    • The Journal of Korean Academy of Prosthodontics
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    • v.52 no.4
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    • pp.305-311
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    • 2014
  • Purpose: When the full veneer crown was treated in the tooth with abfraction lesion due to various causes, the prognosis of it may be compromised according to the location of the finish line, but there is few study about the location of its buccal finish line. The purpose of this study was to investigate the effect of location of the finish line of the full veneer crown on stress distribution of the tooth with abfraction lesion. Materials and methods: The two dimensional finite element model was developed to express tooth, surrounding tissue and full veneer crown. The stress distribution under eccentric 144 N occlusal load was analyzed using finite element analysis. The location of finish line was set just at the lower border of the lesion (Group 0), 1 mm (Group 1) and 2 mm (Group 2) below the lower border of the lesion. Results: In the Group 0, von Mises stress was concentrated at the finish line and the apex of the lesion. Also, the stress at the bucal finish line propagated to the lingual side. In the Group 1 and Group 2, stress distribution was similar each other. Stress was concentrated at the apex of lesion, but the stress at the buccal finish line did not propagate to the lingual side. That implied decrease of the possibility of horizontal crown fracture. Conclusion: Full veneer crown alleviated the stress concentrated at the apex of the abfraction lesion, when the finish line of full veneer crown was set below the lower border of abfraction lesion.

The Association of Blood Concentrations of Healvy Metals and Blood Pressure in Residents Living Near Janghang Copper Smelter in Korea (제련소 주변 지역 주민들의 혈중 중금속 농도와 혈압과의 관련성)

  • Eom, Sang-Yong;Yim, Dong-Hyuk;Moon, Sun-In;Ochirpurev, Bolormaa;Choi, Young-Sook;Park, Choong-Hee;Kim, Guen-Bae;Yu, Seung-Do;Choi, Byung-Sun;Park, Jung-Duck;Kim, Yong-Dae;Kim, Heon
    • Journal of agricultural medicine and community health
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    • v.42 no.1
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    • pp.13-23
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    • 2017
  • Objectives: This study was conducted to evaluate a relationship between the blood concentrations of toxic metals and the blood pressure in people living near the copper smelter. Methods: The study included 570 adults living within 4km of the smelter. We compared systolic and diastolic blood pressure between tertiary groups for blood cadmium, mercury and lead levels, respectively. Multiple regression analysis was performed to identify risk factors affecting systolic and diastolic blood pressures. Results: In male subjects, there is a significant difference in the mean of systolic and diastolic blood pressure between tertiary groups of blood cadmium and mercury levels, but in women, there was no significant difference in the mean systolic and diastolic blood pressures in all tertiary groups of heavy metals. The results of multiple regression analysis showed that age, BMI, and cadmium concentration in men were risk factors for blood pressure. In women, age and BMI, drinking and smoking, and blood mercury were significantly influenced to blood pressure. Conclusions: Residents living near the Janghang smelter showed high concentrations of blood lead and cadmium, suggesting that they were exposed to high concentrations of heavy metals released from the smelter in the past. Such exposure may have caused some blood pressure increase. Especially, the concentration of cadmium in the case of men and the concentration of mercury in blood in the case of women were found to be significantly related to the increase of blood pressure. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize cardiovascular disease, and to pay close attention to any health problems possibly related to toxic metal exposure.

Aprotinin Therapy for Cardiac Operation in Adult -Full dose regimen- (개심술에서 아프로티닌의 효과 (고용량 요법))

  • 장운하;오태윤;김미혜
    • Journal of Chest Surgery
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    • v.32 no.4
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    • pp.358-363
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    • 1999
  • Background: Recently, many cardiac centers have been using aprotinin to reduce operative bleeding in cardiac operations using cardiopulmonary bypass. A variety of reports have confirmed the effectiveness of the drug in cardiac operations. In addition to the operations which could be considered to cause severe operative bleeding such as redo operation, long cardiopulmonary bypass operation and etc, the use of aprotinin is increasing in the field of primary cardiac operations. Varying doses of regimen have been introduced since the first report by Royston et al, and also various opinions on the effectiveness and safeness of the each regimen have been reported. We reviewed our own experience of the full dose aprotinin regimen(Hammersmith regimen) retrospectively. Material and Method: From October 1994 to February 1998, 40 cases of cardiac operative patients were randomized into two groups: aprotinin group(20 patients) which received a full dose aprotinin regimen and control group(20 patients) which did not receive aprotinin. To evaluate the degree of bleeding decrease, we analysed and compared the amount of postoperative 6 hours and 24 hours bleeding in the each group. To confirm the renal dysfunction, we measured the postoperative creatinine level. Result: In the amount of postoperative 6 hours bleeding, a statistically significant bleeding decrease was demonstrated in the aprotinin group compared to the control group(aprotinin group: 186${\pm}$40cc, control group:409${\pm}$69cc, P=0.010). Similar result was observed in the postoperative 24 hours(aprotinin group:317${\pm}$53cc, control group: 671${\pm}$133cc, P=0.024). Conclusion: We concluded that full dose regimen of aprotinin can remarkably reduce postoperative bleeding in cardiac operations without significant renal dysfunctions.

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A Study on Pulmonary Toxic Effect of High-Dose Cisplatin Administered by Isolated Lung Perfusion in Dogs (잡견에서 분리폐관류 방법으로 투여된 고농도 cisplatin의 페독성에 관한 연구)

  • 김관민;한정호;김주현
    • Journal of Chest Surgery
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    • v.33 no.9
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    • pp.697-706
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    • 2000
  • Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

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Heart Transplantation: the Seiong General Hospital Experience (심장이식 환자의 임상적 고찰)

  • 박국양;박철현
    • Journal of Chest Surgery
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    • v.29 no.6
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    • pp.606-613
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    • 1996
  • Cardiac transplantation has been the treatment of patients with end-stage heart disease since it was first performed in 1967. In Korea the first case was performed in 1992 and 42 patients underwent heart trans- plantation so far. The purpose of this article is to report short-term result of cardiac transplantation at our center. Between April 1994 and September 1995, 14 patients had undergone orthotopic heart transplantations. There was 12 male and 2 female patients. Mea recipient age was 34 years(range 11 to 54 years) and mean donor age was 28.4 years(16 to 50 years). Mean graft ischemic time was 120.7minutes(80 to 280 minutes). The follow-up period after transplantation was 11 months(3 to 17 months). Recipient diagnosis included dilated cardiomyopathy in 10, ischemic cardiomyopathy in 2, valvular cardiomyopathy in 1, congenital complex heart disease in 1 patient. The preoperative status of the recipients were state I (50%) and ll (50%) by UNOS classification and class 111 (5 patients) and class IV (9) by NYHA functional class. All patients were treated with triple-drug immunosuppression (cyclosporine, azathioprine, steroid) and induction with RATG. The rejection episodes were 5 times in 3 patients during the follow-up. Causes of infection were aspergillosis (2), and hepes zoster (1), CMV pneumonitis (1). Permanent pace- maker was inserted in 1 patient. Currently 9 patients are alive with seven patients in WYHA functional class I and two in class l . The ejection fraction increased from preoperative value of 19.9 $\pm$ 3.4% to postoperative value of 69.0 $\pm$ 5.6%. The causes of death were cellular rejection (1),chronic graft failure due to size-mismatching (1),respirat- oxy insufficiency due to asthma attack (1), subarachnoid hemorrhage (1), and RIO humoral rejection (1).

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Optimization of Interesterification Reaction for the Continuous Production of trans-Free Fat in a Packed Bed Enzyme Bioreactor with Immobilized Lipase (고정화 리파제를 이용한 충진형 효소생물반응기 내에서의 무-트랜스 유지 연속 생산을 위한 에스테르 교환 반응의 최적화)

  • Kim, Sang-Woo;Park, Kyung-Min;Ha, Jae-Uk;Lee, Jae-Hwan;Chang, Pahn-Shick
    • Korean Journal of Food Science and Technology
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    • v.41 no.2
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    • pp.173-178
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    • 2009
  • Epidemiological studies showed that high trans-fat consumption is closely associated with getting the risks of cardiovascular disease. The objective of this study was to produce trans-free fat through lipase-catalyzed interesterification, as a substitute for the cream margarine commonly used in industry. Optimum conditions for interesterification in a packed bed enzyme bioreactor (PBEB) were determined using response surface methodology (RSM) based on central composite design. Three kinds of reaction variables were chosen, such as substrate flow rate (0.4-1.2 mL/min), reaction temperature (60-70$^{\circ}C$), and ratio of fully hydrogenated canola oil (FHCO, 35-45%) to evaluate their effects on the degree of interesterification. Optimum conditions from the standpoint of solid fat content (SFC) were found to be as follows: 0.4 mL/min flow rate, 64.7$^{\circ}C$ reaction temperate, and 42.8% (w/w) ratio of FHCO, respectively. The half-life of immobilized lipase in PBEB with two stages at 60$^{\circ}C$ ($1^{st}$ stage) and 55$^{\circ}C$ ($2^{nd}$ stage) was about more than 30 days as estimated by extrapolating the incubation time course of tristearoyl glycerol (TS) conversion, whereas the half-life of the enzyme in PBEB with single stage at 65$^{\circ}C$ was only about 15 days. Finally, the results from SFC analysis suggest that trans-free fat produced in this study seems to be a suitable substitute for the cream margarine commonly used in industry.

Plasma Levels of High Molecular Weight Adiponectin are Associated with Cardiometabolic Risks in Patients with Hypertension (고혈압 환자에서 혈장 고분자량 아디포넥틴 농도와 심장-대사위험인자와의 관련성 연구)

  • Chung, Hye-Kyung;Shin, Min-Jeong
    • Journal of Nutrition and Health
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    • v.41 no.8
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    • pp.733-741
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    • 2008
  • In the present study, we comprehensively examined the associations of plasma levels of total adiponectin and high molecular weight (HMW) adiponectin with the features of cardiometabolic risks including body fat distribution, dyslipidemia, insulin resistance and inflammatory markers in a cross-sectional study of 110 treated hypertensive patients. Blood lipid profiles, high sensitivity C-reactive protein (hsCRP) and homeostasis model assessment of insulin resistance (HOMA- IR) derived from fasting glucose and insulin concentrations were determined. Plasma levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were analyzed using ELISA. The results showed that plasma levels of HMW-adiponectin were negatively associated with body mass index (BMI, r = - 0.203, p < 0.05) and waist circumference (r = -0.307, p < 0.01), which was not shown in total adiponectin. Plasma levels of HMW-adiponectin were negatively associated with triglyceride (r = -0.223, p < 0.05) and positively associated with HDL-cholesterol (r = 0.228, p < 0.05). Plasma levels of adiponectin were positively associated with HDL-cholesterol (r = 0.224, p < 0.05). Plasma levels of HMW-adiponectin were negatively associated with hsCRP (r = -0.276, p < 0.01) and IL-6 (r = -0.272, p < 0.01). In addition, there were weak associations between plasma levels of HMWadiponectin and TNF-${\alpha}$ (r = -0.163, p = 0.07) and ICAM-1 (r = -0.158, p = 0.09). However, there were no significant associations of total adiponectin with inflammatory markers except hsCRP (r = -0.203, p < 0.05). Stepwise multiple linear regression analysis showed that only plasma levels of HMW-adiponectin was an independent factor influencing serum levels of hsCRP, a marker of systemic low grade inflammation, after adjusting for age, gender, BMI, waist circumference, alcohol intake, smoking status, blood lipids, total adiponectin and drug use (p < 0.01). These results suggest that HMW-adiponectin, rather than total adiponectin, is likely to be closely associated with the features of cardiometabolic risks in treated hypertensive patients and might be effective biomarker for the prediction of cardiovascular disease.

Analgesic Effect of Hippophae rhamnoides Extract in Orofacial Pain in Rats (구강안면통증모델에서 산자나무 추출물의 진통효과)

  • Kim, Yun-Kyung;Choi, Ja-Hyeong;Kim, Hee-Jin;Yoon, Hyun-Seo;Hyun, Kyung-Yae;Lee, Min-Kyung
    • Journal of dental hygiene science
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    • v.17 no.6
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    • pp.495-500
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    • 2017
  • Hippophae rhamnoides L. (sea buckthorn) is a shrub wood that belongs to the bamboo tree family, and is rich in vitamin C, D, and E; it is referred to as a vitamin tree. It is mainly grown in the high mountains of Europe and Central Asia, and has been widely used in China and Russia as natural medicine. Recent studies have shown that it is effective in the treatment of cancer, liver diseases, cardiovascular diseases, and gastrointestinal diseases. However, results of studies on its effect on the regulation of pain are insufficient. In this study, we investigated the effect of sea buckthorn on the development and control of pain in two facial areas. The experimental animals included 7- to 8-week-old Sprague-Dawley rats (240~260 g). Formalin (5%), which is known as an inflammation inducer, was injected into the vibrissa pad or temporomandibular joints to induce orofacial acute pain. Rubbing or scraping of the region injected with formalin was regarded as a pain index, and the behavioral response was observed for 45 minutes after the injection. Sea buckthorn extract diluted to 150, 300 mg/kg (in 1 ml of distilled water) was orally administered 30 minutes prior to the acute pain. The facial pain behavior was effectively reduced in the 300 mg/kg group when compared to the control group (vehicle). Likewise, in an experiment in which formalin was injected into the temporomandibular joints, effective pain alleviation was confirmed at the same drug concentration. These results suggest that sea buckthorn extract may be useful in the development of therapeutic agents for acute inflammatory pain in the orofacial area and for controlling temporomandibular joint pain.