• Title/Summary/Keyword: diclofenac

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Effects of Calcium Citrate Isolated from Oyster Shell on Papain-induced Osteoarthritis in C57BL/6J Mice (굴 패각 구연산칼슘이 Papain으로 유도된 골관절염 C57BL/6J Mice에 미치는 영향)

  • Choi, Eun-Young;Kim, Hak-Ju;Han, Ji-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.10
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    • pp.1510-1518
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    • 2014
  • This study investigated the effects of calcium citrate on papain-induced osteoarthritis in C57BL/6J mice. Osteoarthritis was induced by injecting $6{\mu}L$ of papain into the knee joints of mice. Calcium citrate was made by crushing the centrifuged precipitate after reacting 0.5 M citric acid with 1 kg of oyster shell extract. The mice were divided into five groups (n=8). The normal group was untreated, whereas the papain group was induced to have osteoarthritis and treated with $200{\mu}L$ of water per day. The papain+DS group was treated with diclofenac sodium. The papain+calcium citrate groups were treated with calcium citrate at 150 and 300 mg/kg/bw for 28 days. Proteoglycan contents in articular cartilages were measured by safranin O/fast green staining and hematoxylin & eosin staining. Histopathological changes in cartilages were analyzed by the Rudolphi score approach. Contents of pro-inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in plasma, were measured by the ELISA method. Body weights among the treated groups were not significantly different compared with that of the normal group. Cartilage loss and joint instability in the calcium citrate group improved significantly (P<0.05) in a dose-dependent manner compared with the papain group. Further, proteoglycan content of the calcium citrate group was considerably (P<0.05) higher than that of the papain group. Osteoarthritis scores in the calcium citrate group were considerably (P<0.05) reduced compared with the papain group. In the group treated with calcium citrate, contents of TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in plasma were significantly (P<0.05) reduced in a dose-dependent manner in comparison with the normal group. Based on these results, we suggest that calcium citrate is effective for treatment of osteoarthritis.

Effects of Oyster Shell Extract on Papain-induced Osteoarthritis in C57BL/6J Mice (굴 패각 추출물이 Papain으로 유도된 골관절염 C57BL/6J Mice에 미치는 영향)

  • Lee, Se-Young;Kim, Hak-Ju;Han, Ji-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.8
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    • pp.1183-1189
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    • 2013
  • We investigated the effects of oyster shell extract (OSE) on papain-induced osteoarthritis in C57BL/6J mice. Osteoarthritis was induced in mice by a papain injection into the knee joint. The mice were divided into a total of five groups (n=8). The normal group was untreated, whereas the papain group (negative control) was induced with osteoarthritis and treated with water daily. The papain+DS group (positive control) was treated with diclofenac sodium. Papain+OSE groups were treated with OSE concentrations of 100 and 200 mg/kg/bw for 20 days. Proteoglycan content in articular cartilage was analyzed through safranine-O fast green staining and H&E staining. The histopathological changes in cartilage were measured by the Rudolphi score approach. The contents of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 in plasma were analyzed by the ELISA method. After experiments, body weights of the treated groups were not significantly different compared with the normal group. Cartilage loss and joint instability significantly improved in a dose-dependent manner in the OSE-treated group compared with the papain group (P<0.05). Proteoglycan content was significantly higher in the OSE-treated group than the papain group (P<0.05). Osteoarthritis scores of the OSE-treated group were significantly decreased compared with the papain group (P<0.05). TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 content in the plasma of the papain+OSE treated groups significantly decreased in a dose-dependent manner compared with the papain group (P<0.05). These results suggest that OSE treatment might have anti-arthritic effects on papain-induced osteoarthritis in C57BL/6J mice.

Ecological Risk Assessment of Pharmaceuticals in the Surface Water Near a Pharmaceutical Manufacturing Complex in Korea (제약단지 인접 지역 지표수의 잔류 의약물질 생태위해성평가)

  • Park, Suhyun;Kang, Habyeong;Shin, Hyesoo;Ryoo, Ilhan;Choi, Kyungho;Kho, Younglim;Park, Kyunghwa;Kim, Kyungtae;Ji, Kyunghee
    • Journal of Environmental Health Sciences
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    • v.46 no.1
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    • pp.45-64
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    • 2020
  • Objectives: Limited information is available on the presence and associated ecological risks of pharmaceutical residues in aquatic environments near pharmaceutical manufacturing areas in Korea. In this study, we investigated the current state of pharmaceutical contamination and its associated ecological risks in streams near a pharmaceutical manufacturing complex. Methods: Seven pharmaceuticals (acetaminophen, clarithromycin, diclofenac, diphenhydramine, ibuprofen, mefenamic acid and roxithromycin) were measured in water samples collected from the streams near a pharmaceutical manufacturing complex. A predicted no-effect concentration (PNEC) was derived using either the assessment factor method or species sensitivity distribution method. In addition, a hazard quotient for each pharmaceutical was calculated by dividing its measured environmental concentration by its PNEC. Results: Samples collected downstream from the wastewater treatment plant (WWTP) had higher concentrations of pharmaceuticals than those collected from the reference site (upstream). Moreover, pharmaceutical concentrations were greater in ambient water than in the final effluent from the WWTP, which suggested that non-point sources were contributing to the contamination of the ambient water environment. Some of the target pharmaceuticals exhibited a hazard quotient >1, indicating that their potential ecological effects on the aquatic environment near the pharmaceutical industrial area should not be ignored. Conclusion: This study demonstrated that the pharmaceutical manufacturing area was contaminated with residual drugs, and that there was a possible non-point source near the WWTP effluent discharge area. The results of this study will aid in the development of management plans for pharmaceuticals, particularly in hotspots such as pharmaceutical industrial sites and their vicinities.

Formulation and Skin Penetration Characteristics of Aceclofenac Plaster for Transdermal Delivery (아세클로페낙의 경피 제제설계 및 피부투과 특성)

  • Chung, Jong-Keun;Lee, Min-Suk;Park, Jeong-Hwa;Lee, Jang-Won;Kim, Ha-Hyung;Choi, Young-Wook;Lee, Kwang-Pyo
    • Journal of Pharmaceutical Investigation
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    • v.29 no.1
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    • pp.29-36
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    • 1999
  • Aceclofenac is an non-steroidal antiinflammatory drug which has been used in the treatment of rheumatoidal rthritis and osteo-arthritis. In order to decrease the gastric ulcerogenic effects and contol the plasma level of aceclofenac, we have developed the transdermal delivery system of aceclofenac plaster, which were formulated employing matrix polymers of acrylates and penetration-enhancers such as $Lauroglycol^{\circledR}$, $Transcutol^{\circledR}$, oleic acid and linoleic acid. Using Franz diffusion cells mounted with a rat skin, transdermal penetration characteristics of the formulations were evaluated by the HPLC assay of aceclofenac and diclofenac, an active metabolite, in the receptor compartment of pH 7.2 phosphate buffered solution. Skin penetration was increased when the content of aceclofenac increased, showing the flux $(J,\;{\mu}g/cm^2/hr)$ of 0.37 and 2.50 for 2% and 6.75% of the content, respectively. The flux$(J,\;{\mu}g/cm^2/hr)$ from plasters made of $Durotak^{\circledR}$ 87-2074, $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 were 2.50, 2.77 and 4.39, respectively. $Durotak^{\circledR}$ 87-2074 showed the lowest penetration due to the carboxylic acid group in the polymer, which might form a strong hydrogen bonding with a secondary amine of aceclofenac. Although both $Durotak^{\circledR}$ 87-2510 and $Durotak^{\circledR}$ 87-2097 are amine-resistant adhesives, $Durotak^{\circledR}$ 872510 showed lower penetration than $Durotak^{\circledR}$ 87-2097 because of the hydroxyl group in $Durotak^{\circledR}$ 87-2510, which might form a weak hydrogen bonding with aceclofenac. These results reveal that the functional group in acrylic polymers would greatly affect the release of aceclofenac from the matrix, which is the rate-limiting step in the penetration of aceclofenac through rat skins. The penetration of aceclofenac from plasters using different penetration-enhancers increased in the following order: Transcutol < linoleic acid < oleic acid. And the flux from the plasters containing oleic acid as a penetrationenhancer was 2.22 times greater than that of creams, which suggest that a newly deveolped aceclofenac plaster could be used in the treatment of rheumatoidal arthritis and osteo-arthritis as an advanced transdermal delivery system.

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Rejection rate and mechanisms of drugs in drinking water by nanofiltration technology

  • Ge, Sijie;Feng, Li;Zhang, Liqiu;Xu, Qiang;Yang, Yifei;Wang, Ziyuan;Kim, Ki-Hyun
    • Environmental Engineering Research
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    • v.22 no.3
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    • pp.329-338
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    • 2017
  • Nanofiltration (NF) technology is a membrane-based separation process, which has been pervasively used as the high-effective technology for drinking water treatment. In this study, a kind of composite polyamide NF thin film is selected to investigate the removal efficiencies and mechanisms of 14 trace drugs, which are commonly and frequently detected in the drinking water. The results show that the removal efficiencies of most drugs are quite high, indicating the NF is an effective technology to improve the quality of drinking water. The removal efficiencies of carbamazepine, acetaminophen, estradiol, antipyrine and isopropyl-antipyrine in ultrapure water are $78.8{\pm}0.8%$, $16.4{\pm}0.5%$, $65.4{\pm}1.8%$, $71.1{\pm}1.5%$ and $89.8{\pm}0.38%$, respectively. Their rejection rates increase with the increasing of their three-dimensional sizes, which indicates that the steric exclusion plays a significant role in removal of these five drugs. The adsorption of estradiol with the strongest hydrophobicity has been studied, which indicates that adsorption is not negligible in terms of removing this kind of hydrophobic neutral drugs by NF technology. The removal efficiencies of indomethacin, diclofenac, naproxen, ketoprofen, ibuprofen, clofibric acid, sulfamethoxazole, amoxicillin and bezafibrate in ultrapure water are $81{\pm}0.3%$, $86.3{\pm}0.5%$, $85.7{\pm}0.4%$, $93.3{\pm}0.3%$, $86.6{\pm}2.5%$, $90.6{\pm}0.4%$, $59.7{\pm}1.7%$, $80.3{\pm}1.4%$ and $80{\pm}0.5%$, respectively. For these nine drugs, their rejection rates are better than the above five drugs because they are negatively charged in ultrapure water. Meanwhile, the membrane surface presents the negative charge. Therefore, both electrostatic repulsion and steric exclusion are indispensable in removing these negatively charged drugs. This study provides helpful and scientific support of a highly effective water treatment method for removing drugs pollutants from drinking water.

Anti-arthritic Effect of a New Diet-Supplement Containing Red Ginseng Extract and Glucosamine Complex (홍삼추출물과 글루코사민 복합제제의 관절염에 미치는 영향)

  • Jeong, Choon-Sik;Hyun, Jin-Ee;Kang, Min-Hee;Sim, Joon-Soo;Son, Mi-Jin;Jung, Sang-Hoon;Kim, Jong-Hoon;Lee, Kwang-Seong;Kim, Yeong-Shik
    • Korean Journal of Pharmacognosy
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    • v.34 no.4 s.135
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    • pp.327-334
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    • 2003
  • We evaluated the anti-arthritic effect of a new diet-supplement product containing red ginseng, glucosamine, shark cartilage, ascorbic acid and manganese chloride for the relieving arthritic symptoms. Anti-inflammatory activities of the aqueous extract of red ginseng (250 and 500 mg/kg), glucosamine (240 mg/kg) and shark cartilage (240 mg/kg) were tested individually on vascular permeability and carrageenan-induced paw edema. Glucosamine and shark cartilage showed the inhibition of vascular permeability by 29.6 and 32.9%, respectively. Red ginseng (500 mg/kg) and shark cartilage showed the inhibition of carrageenan-induced paw edema at 0.5, 1, 2 and 3 hr. The supplement (red ginseng mixture: RGM) composed of red ginseng (43.5%), glucosamine (25.0%), shark cartilage (25.0%), ascorbic acid (5.0%) and manganese chloride (1.5%) was prepared and its inhibitory activities including vascular permeability and carrageenan-induced paw edema were comparable to anti-inflammatory drugs such as diclofenac and ibuprofen. It was also tested on adjuvant-induced arthritis in rats as one of chronic arthritic tests and Randall-Selitto assay as an analgesic test. RGM showed the inhibition against the swelling of rat paws induced by Mycobacterium tuberculosis at a dose of 1,500 mg/kg. Determination of cytokines of the sera sampled from arthritis-induced animals indicated that RGM increased the levels of $interferon-{\gamma}$ and interleukin-6, representing the immunostimulatory effect by red ginseng. RGM treatment moderately reduced the production of NO in RAW 264.7 cells in a dose-dependent manner. Taken together, these results support that RGM can be applicable for the improvement of arthritic as a new diet-supplement.

Reduced Port Surgery for Prostate Cancer is Feasible: Comparative Study of 2-port Laparoendoscopic and Conventional 5-port Laparoscopic Radical Prostatectomy

  • Akita, Hidetoshi;Nakane, Akihiro;Ando, Ryosuke;Yamada, Kenji;Kobayashi, Takahiro;Okamura, Takehiko;Kohri, Kejiro
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6311-6314
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    • 2013
  • Background: While 5-port laparoendoscopic radical prostatectomy is standard practice, efforts have been focused in developing a single port surgery for cosmetic reasons. However, this is still in the pioneering stage considering the challenging nature of the surgical procedures. We have therefore focused on reduced port surgery, using only 2-ports. In this study, we compared 2-port laparoendoscopic radical prostatectomy (2-port RP) and conventional 5-port laparoscopic radical prostatectomy (LRP) for clinically localized prostate carcinoma and evaluated the potential advantages of each. Materials and Methods: From January 2010 to December 2010, all 23 patients with clinically localized prostate cancer underwent LRP. Starting November, 2010, when we introduced the reduced port approach, we performed this procedure for 22 consecutive patients diagnosed with early-stage prostate cancer (cT1c, cT2N0). The patients were matched 1:1 to 2-port RP or LRP for age, preoperative serum PSA level, clinical stage, biopsy and pathological Gleason grade, surgical margin status, pad-free rates and post-operative pain. Results: There was a significant difference in operative time between the 2-port RP and LRP groups ($286.5{\pm}63.3$ and $351.8{\pm}72.4$ min: p=0.0019, without any variation in blood loss (including urine) ($945.1{\pm}479.6$ vs $1271.1{\pm}871.8ml$: p=0.13). The Foley catheter indwelling period was shorter in the 2 port RP group, but without significance ($5.6{\pm}1.8$ vs $8.0{\pm}5.6$ days: p=0.057) and the total perioperative complication rates for 2 port RP and LRP were comparable at 4.5% and 8.7% (p=0.58). There was an improvement in pad-free rates up to 6 months follow-up (p=0.090), and significantly improvement at 1 year (p=0.040). PSA recurrence was 1 (4.5%) in 2-port RP and 2 (8.7%) in LRP. Continuous epidural anesthesia was used in most of LRP patients (95.7%) and in early 2-port RP patients (40.9%). In these patients, average total amount of Diclofenac sodium was 27.8mg/patient in 2-port RP and 50.0mg/patient in LRP. Conclusions: Thus the reduced port approach is as efficacious as LRP in terms of many outcome measures, with significant cosmetic advantages and reduction in post surgical pain. This method can be readily performed safely and therefore can be recommended as a standard laparoscopic surgery for prostate cancer in the future.

Effect of Beta-Glucan on the Collagen-Induced Rheumatoid Arthritis (콜라겐유발 관절염에서 폴리칸의 효과)

  • Kim, Joo-Wan;Cho, Hyung-Rea;Kim, Ki-Yung;Ku, Sae-Kwang;Lee, Hyeung-Sik
    • Journal of Veterinary Clinics
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    • v.27 no.4
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    • pp.315-324
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    • 2010
  • The effect of beta-glucan ($Polycan^{TM}$) derived from Aureobasidium pullulans SM-2001 were observed on, collagen-induced rheumatoid arthritis (RA) in DBA mice. Six week-old male DBA/1J mice were immunized by the intradermal injection of $200\;{\mu}g$ of bovine type II collagen with the equal volume of complete Freund's adjuvant at the tail base on day 1. On day 21, the mice were boosted by the intradermal injection of $200\;{\mu}g$ of bovine type II collagen with incomplete Freund's adjuvant. From the first immunization, mice had been administered $Polycan^{TM}$ (21.25, 42.5 and 85 mg/kg), diclofenac and vehicle once a day for 4 weeks, respectively. Collagen-induced hyperimmunities and arthritis signs were markedly and dose-dependently inhibited by treatment of $Polycan^{TM}$ compared with RA control except for tibial cartilages of $Polycan^{TM}$ 21.25 group. $Polycan^{TM}$ effectively inhibited the histopathological changes of collagen-induced arthritis and hyper-immunities.

Clinical Efficacy of Transdermal Clonidine (St 155 BS) for Anesthetic Management in Hypertensive Patients (고혈압 환자 마취시 Transdermal Clonidine (St 155 BS)의 임상적 유용성)

  • Lee, Hyun-Hwa;Kim, Dong-Ok;Kim, Keon-Sik;Choi, Young-Kyoo;Shin, Ok-Young;Kwon, Moo-Il;Lee, Doo-Ik
    • The Korean Journal of Pain
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    • v.6 no.2
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    • pp.231-236
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    • 1993
  • Clonidine, a centrally-acting antihypertensive agent known to reduce central sympathetic outflow and modulate presynaptic transmitter's release, has shown to suppress central noradrenergic hyperactivity induced by immobilization stress in animals, by decreasing the MAC of halothane and the dose of narcotics required to prevent reflex cardiovascular response to noxious stimuli, and to have potent analgesic properties in humans. These characteristics suggest that clonidine might be a useful adjunct to the anesthetic management of patients with preexisting hypertension. Accordingly, we determined the clinical efficacy and safety on analgesia, sedation and hemodynamic stability in the perioperative period. Thirty patients(ASA physical status II-III) with a history of arterial hypertension, scheduled for elective orthopedic surgery were randomly assigned to two groups. We applied CPA-clonidine patch($6.9\;mg/cm^2$, 0.2 mg delivered daily) or placebo patch to each groups, 48 hours prior to induction of anesthesia. Antihypertensive medication was continued until the morning of the scheduled surgery. All patients received premedication of atropine and lorazepam, and induced anesthesia with thiopental and succinylcholine, and maintained with enflurane and 50% nitrous oxide, while sustaining the BP and pulse rate at acceptable range. For the relief of pain postoperatively, diclofenac and fentanyl were administered intramuscularly on demand. The results were as follows: 1) The change of hemodynamic responses in clonidine group was less compared to the placebo group. 2) Intraoperative anesthetic requirement for enflurane in clonidine group were significantly lower than placebo group. 3) Postoperative analgetic requirement in clonidine group were significantly lower than placebo group. In clonidine group, 5 cases out of 15 cases were required no analgetics, and the incidence of administration of additional fentanyl was decreased to 5 cases, comparing with 10 cases in placebo group.

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Effect of TSHAC on Human Cytochrome P450 Activity, and Transport Mediated by P-Glycoprotein

  • Im, Yelim;Kim, Yang-Weon;Song, Im-Sook;Joo, Jeongmin;Shin, Jung-Hoon;Wu, Zhexue;Lee, Hye Suk;Park, Ki Hun;Liu, Kwang-Hyeon
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1659-1664
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    • 2012
  • TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.