• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.99-109
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• 2005

It has been focused on the importance of the host inflammatory response in periodontal pathogenesis and progression, treatment has been introduced to control the host response and the method, which diminishes production and activity of MMP by doxycycline, has been used in periodontal field. MMP is a proteolytic enzyme which plays a major role in tissue destruction and MMP-1 is secreted in the periodontally healthy tissue, while MMP-8, 9, 13, etc in the inflammatory state. Among these, MMP-13 has been discovered lately and reported to degrade primarily type II collagen. Periodontal ligament (PDL) cell plays a role in destruction of periodontal tissue. This study was to evaluate the effect of doxycycline and mefenamic acid, non-steroidal antiinflammatory drug on MMP-13 mRNA expression in the rat PDL cell. Doxycycline concentration of $1{\sim}100\;{\mu}g/ml$ was added rat PDL cell and cell activity was measured by MIT assay at day 1 and 3. MMP-13 gene expression was evaluated by RT-PCR after PDL cells were pre-treated for 1hour with doxycycline (50 ${\mu}g/ml$) alone or with mefenamic acid ($10^{-6}M$), then added $IL-1{\beta}$(1.0 ng/ml) and incubated for 16-18 hours. The results are as follows: 1. Cell activity decreased Significantly at 24 and 72 hours in 100 ${\mu}g/ml$ (p<0.05). 2. Level of MMP-13 mRNA was in 20.2% increase by $IL-1{\beta}$ and in pre-treating doxycycline group, expression of $IL-1{\beta}$ induced MMP-13 mRNA was inhibited by 31% than $IL-1{\beta}$ treated only. 3. Mefenamic acid did not inhibit on the expression of $IL-1{\beta}$ induced MMP-13 mRNA, while mefenamic acid in combination with doxycycline inhibited the expression by 41% compared to only $IL-1{\beta}$ stimulation. These results suggest that doxycycline synergistically inhibit the expression of $IL-1{\beta}$ induced MMP-13 mRNA in combination with mefenamic acid.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.233-239
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• 2001

Local drug delivery by using biocompatible polymers has been developed in the treatment of periodontitis for many years. In the field of dental therapy, doxycycline is usually a first choice because of its broad-spectrum antibiotic activity. The strip releases antibiotics for a week, and the polymer should be degradable after a week. In this study, we prepared and evaluated the chitosan strips and nanoparticle strips containing doxycycline hydrochloride, and studied their antiacterial activity, dissoultion, and degrability in vitro. The weight of cast strip containing a 5 mg of doxycycline hydrochloride and a 45 mg of chitosan polymer was $57.67{\pm}0.17\;mg$. The release rate of doxycycline hydrochloride from the strip was measured by HPLC. The drug released from chitosan strip and nanoparticle strip was shown to be $50\;{\mu}g/mL$ in first 24 hours. In antibacterial test showed growth inhibitory activity after 24 hrs anaerobic incubation. In vitro degradability showed demolished weight of $93.74{\pm}0.08%$ chitosan strip, $82.48{\pm}1.29%$ chitosan nanoparticle strip, $2.47{\pm}1.99%$ polycarprolactione strip (control). These results showed that, with this doxycycline hydrochloride strip, it is feasible to obtain a sustained release of the drug within the periodontal pocket for seven days which may be improve for local drug delivery system for treatment of periodontal disease.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.531-536
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• 1994

Background: The intrapleural instillation of tetracycline for pleural sclerosis had been most commonly used in patients with symptomatic malignant pleural effusion or recurrent pneumothorax for a long time. Unfortunately, at a time of expanding use of this agent, the production of injectable tetracycline hydrochloride used for pleurodesis was discontinued by its sole manufacturer in mid-1991 because the manufacturer was unable to meet US Food and Drug Administration purity standards. So we performed a preliminary study of doxycycline, as a alternative pleural sclerosant on rabbit pleura and compared its efficacy with that of tetracycline. Method: Eighteen New Zealand white rabbits weighing 2 to 3kg(mean 2.6kg) were devided into three groups. In each groups, one tetracycline(20 mg/ml/kg) and two doxycycline solutions(7 mg/ml/kg and 20 mg/ml/kg) instillated into the right pleural space through an 18-gauge angiocath with care to prevent pneumothorax. All rabbits were sacrificed after 28 days. Results: 1) In the group of tetracycline 20 mg/ml/kg(six rabbits), five rabbits showed partial pleural symphysis with several fibrous bands, and one rabbit died on 22th day. 2) In the group of doxycycline 7 mg/ml/kg(six rabbits), three rabbits showed partial pleural symphysis and the other three rabbits showed complete pleural symphysis without necrosis of underlying parenchymal lung tissue. 3) In the group of doxycycline 20 mg/ml/kg(six rabbits), two rabbits showed complete pleural symphysis without lung necrosis, another two rabbits showed complete pleural symphysis with lung necrosis, and the other two rabbits died on 4th and 13th day, respectively. Conclusion: We concluded that doxycycline is a highly effective sclerosing agent having stronger pleurodesis effect with that of tetracycline by dose base and its optimal dosage was considered as 7 mg/ml/kg with minimal complications.

• Journal of Yeungnam Medical Science
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• v.37 no.2
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• pp.112-121
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• 2020

Background: Vancomycin-resistant Enterococcus (VRE) has become more common in nosocomial infections, especially in urine samples. However, until now, no treatment regimen has been proven to effectively eradicate urine VRE colonization. Therefore, to evaluate the efficacy of doxycycline in eradicating urine VRE and shortening VRE isolation period, we compared VRE colony detection period between doxycycline-treated and untreated patients. Methods: A retrospective cohort study of 83 patients with VRE colonization in urine cultures was conducted at a tertiary academic hospital from January 2011 to February 2018. Kaplan-Meier survival analysis was used to evaluate eradication rates in the treatment and non-treatment groups. Factors affecting urine VRE colonization persistence were analyzed by multiple logistic regression analysis. Results: The overall rate of VRE eradication during the entire hospital stay was higher in the doxycycline treatment group (90.5%) than in the non-treatment group (58.1%, p=0.014). Survival analysis showed that the 5-, 10-, and 20-day cumulative eradication rates were 78.3%, 100%, and 100% in the doxycycline treatment group, and 18.5%, 45.7%, and 67.8% in the non-treatment group, respectively, thereby indicating that eradication rates were higher in the doxycycline treatment group than in the non-treatment group (p<0.001). Only doxycycline treatment was shown to affect urine VRE colonization persistence in multivariate logistic regression analysis. Conclusion: Doxycycline treatment enhanced the eradication rate of urine VRE colonization and appeared to be useful in shortening VRE isolation period.

• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.11-15
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• 2004

Embryonic stem (ES) cells are derived from the inner cell mass of the blastocyst-stage embryos that can be propagated indefinitely and, at the same time, can be differentiated into all the cell types that constitute the body. Current research using ES cells is mainly focused on the efficient generation of specific cell types by employing optimal differentiation conditions, which often requires the genetic manipulation of ES cells. As a way of developing an efficient system to regulate foreign gene expression in ES cells, we have inserted the gene encoding Corynebacterium diphtheria toxin-A (DTA) into an autonomously induced plasmid under positive doxycycline control ('Tet-on' system). In this study, we demonstrate that this system can lead to the cell death of mouse ES cells by the induction of DTA expression when exposed to the tetracycline derivative, doxycycline. MTT assay showed that this induction resulted in the apoptosis of ES cells.

• Environmental Analysis Health and Toxicology
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• v.4 no.1_2
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• pp.1-10
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• 1989

Experiments were performed on mice to investigate the influences of doxycycine and ethanol on the immune responses. Doxycycline was injected intraperitoneally and ethanol was administered in the drinking water. Mice were sensitized and challenged with sheep red blood cells. Immune responses were evaluated by humoral immunity, cellular immunity, peripheral circulating white blood cell and phagocyte activity. Pathotoxicological influences were measured by serum protein and albumin. The weight of spleen, thymus and liver were measured. Doxycline and ethanol combined administration decreased the weight of thymus and spleen. Humoral and cellular immune response were reduced by doxycycline administration. Especially ethanol combined administration significantly reduced humoral and cellular immune response. Phagocyte activity was increased by ethanol combined administration and peripheral circulating white blood cell was significantly increased by ethanol adminstration. Ethanol combined administration decreased serum A/G ratio.

• The Journal of Korean Medicine
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• v.21 no.4
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• pp.292-299
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• 2000

We experienced two cases of Tsutsugamushi disease which occurred in October, 2000. The patients, who were over 70 years old and living in a rural area, visited Wonkwang University Oriental Chonju Medicine Hospital because of suffering fever, chill, skin rash, abdominal discomfort, and general weakness for a duration of seven days. The diagnosis was confmned as Tsutsugamushi disease by clinical findings such as eschar and high antibody titers on Reverse Passive Hemagglutination(RPHA). As for treatment, we used Sengmagalgentang-gamibang during the acute and Chojungikitang during convalescent phases of the illness. The patients were treated with Doxycycline of western medicine. The patients improved within 3 days of admission and were discharged within one week.

• Journal of Chest Surgery
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• v.29 no.1
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• pp.59-62
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• 1996

Chemical pleurodesis with doxycycline has been used during video-assisted thoracoscopic surgery (VATS) as an auxiliary method to enhance therapeutic goal in patients with pneumothorax. However, the therapeutic effect of doxycycline pleurodesis (DP) has not been clearly defined yet. To evaluate the effect of DP, we compared two groups of patients who were given VATS bullectomy from October 1993 to June 1995. Group I composed of 21 patients who received DP and group II composed of 20 patients who did not received DP Doxycycline 500mg with saline 200ml were instilled into the pleural cavity upon a completion of bullec omy, and retained there for 0.5-1 hour and then drained out. The age of group I was 30.9 $\pm$ 20.0 and that of group II was 24.3 $\pm$ 9.49 years. Male to female ratio was 20: I in group I and 20 : 0 in group II. The postoperative indwelling time of chest tube was 5.86 $\pm$ 4.69 days in group I and 3.80 $\pm$ 2.28 days in group II. Seven patients had more than 100m1/day of chest tube drainage on the postoperative third day in group I compared to one patient in group II. Five patients had postoperative indwelling time of chest tube greater than 7 days in group I compared to two in group II. The number of patients who had postoperative fever were 3 in both group, analgesic requirements were 2.19 $\pm$ 2.77 amples in group I and 2.30 $\pm$ 1.95 ambles in group II. Follow-up was done from 2 months to 16 months after surgery. During the follow up periods, four patients had recurrence 2 (9.5%) in group I and 2 (10%) in group II. We conclude that concomitant doxycycline pleurodesis with video-assisted thor coscopic bullectomy In patients with pneumothorax is not necessary.

• Journal of Periodontal and Implant Science
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• v.30 no.2
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• pp.335-347
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• 2000

치주질환의 진행에 따른 치주조직파괴에 있어 치주조직내 다양한 세포외기질성분을 분해하는 matrix metalloproteinase-3(MMP-3)는 염증반응에 관여하는 세포들로부터 분비된 interleukin-$1{\beta}$(IL-$1{\beta}$)에 의해 유도될 수 있다. 이전 연구에서 치주인대세포에서의 MMP-3 생성이 tetracycline 및 tetracycline 유도체에 의하여 억제될 수 있음이 보고되었다. 이 연구의 목적은 metronidazole 및 doxycycline-HCl을 적용한 후 치은섬유아세포에 IL $1{\beta}$를 적용하여 MMP-3의 생성을 유도한 후 이들 약물들이 치은섬유아세포의 MMP-3 생성에 미치는 영향을 조사하기 위한 것이다. 건강한 성인으로부터 치주질환이 이환되지않은 상악 제2대구치 후방의 건강한 치은결합 조직을 절취하여 치은섬유아세포를 배양한 후 다양한 농도의 metronidazole (10-$200{\mu}g/m{\ell}$) 및 doxycyline-HCl(10-$200{\mu}g/m{\ell}$)을 각각 적용하여 1시간 배양하고 proMMP-3의 활성화를 유도하기 위하여 25ng/ml의 IL-$1{\beta}$을 투여한 후 24시간 배양하여 배양된 세포의 상층 배양액을 추출하고 proMMP-3 ELISA kit를 이용하여 비색정량하였다. 비색정량을 통하여 얻어진 자료들은 독립 t-test와 일원분산분석(ANOVA) 및 사후검정으로 Duncan test를 시행하여 다음과 같은 결과를 얻었다. 1. Metronidazole 경우 10-$200{\mu}g/ml$의 모든 농도군에서 proMMP-3의 활성도가 억제되었다(p<0.05). 2. Doxycycline-HCl의 경우 $100{\mu}g/ml$ 이하의 농도군에서는 proMMP-3의 활성도가 억제되었으나(p<0.05), $200{\mu}g/ml$ 농도에서는 proMMP-3의 활성도가 상승되었다(p<0.05). 3. Metronidazole과 doxycycline-HCl의 대조군에 대한 각 실험농도군의 proMMP-3 생성의 감소비율 비교시 모든 농도군에서 metronidazole이 doxycycline-HCl보다 더 높은 감소율을 보였다. 이상과 같은 결과는 metronidazole(10-$200{\mu}g/ml$)이 doxycycline-HCl($100{\mu}g/ml$ 이하) 보다 더 광범위한 혈중농도에서 IL-$1{\beta}$의한 인체치은섬유아세포내 MMP-3의 활성도를 효과적으로 억제할 수 있음을 시사하였다.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.701-722
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• 1997

It was reported that low dose doxycycline(LDD) regimen could inhibit pathologically elevated collagenase activity in the gingival crevicular fluid of petients with adult periodontitis without producing typical antibiotic side effects. The purpose of this study was to evaluate the effects of LDD regimen(20mg) administered during non-surgical therapy on clinical index and gingival crevicular fluid enzyme activity in diabetics who are at high risk for periodontal disease. Forty-nine subjects having at least two sites with probing pocket depths greater than 4mm were selected. In this double-blind, placebo-controlled study, the patients were administered 20 mg doxycycline capsule or placebo capsule b.i.d. for 2 weeks. Clinical parameters of dental plaque, gingival inflammation, probing pocket depth and probing attachment level were assessed at week 0, 2, 4, and 8. Gingival crevicular fluid samples were collected at the same time to evaluate the activities of collagenase and elastase. Clinical parameters and elastase activity were significantly reduced in all groups compared to the baseline value after treatment. Significantly greater reduction in pocket depth and gain in attachment level was shown in the LDD-administered group compared to placebo group in both adult periodontitis and diabetic patients. Total collagenase activity was also reduced significantly in all groups after treatment, but the greater reduction was seen in the LDD-administered diabetics group compared to relevant placebo group(at 4, 8week). Significantly greater reduction in active collagenase activity was also seen in the LDD-administered group compared to placebo group in diabetic patients(at 2, 4, 8week). These results indicated that use of low dose doxycycline could be aueseful adjunct to instrumentation therapy in the management of diabetic patient with periodontitis as well as adult periodontitis patient.