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Regulation of Tumor Neceosis Factor-${\alpha}$ Receptors and Signal Transduction Pathways

  • Han, Hyung-Mee
    • Toxicological Research
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    • v.8 no.2
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    • pp.343-357
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    • 1992
  • Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

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Effects of Post Individualities on Treatability of Small Diameter Japanese Larch (Larix Leptolepis) with ACQ and CCA (낙엽송 원주상 소경목의 원목성상과 방부 처리성)

  • Kim, Yeong-Suk;Hong, Soon-Il;Yun, Jeong-Hee
    • Journal of the Korean Wood Science and Technology
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    • v.34 no.1
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    • pp.52-60
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    • 2006
  • This study investigated how wood properties (i.e., annual rings, sapwood, heartwood, and cracks) might affect preservative treatment in Japanese larch (Larix leptolepis) round-wood product. We specially focused on small-diameter (~10 cm diameter) wood that is commercially sold in market. Among 100 wood samples, the groups of sample with 13~16, 17~20 annual rings represented 33 and 27 in each frequency, while 2~3 and 4~5 mm annual ring width accounted for 72 and 68 in frequency. More than a half (54%) of wood samples contained a mix of heartwood and sapwood in its surface. The rest (46%) had only heartwood exposed in the wood surface. A wide range of checks were showed in the wood samples, but the highest frequency was observed in samples with 1~6 surface (1~14 mm in size) checks and 1~4 end-grain (8~14 mm in size) checks in each round-wood sample. Pressure treatment resulted in a wide range of penetration of ACQ (Alkaline Copper Quat) into the wood, showing $4.3{\pm}4.19mm$ penetration in the wood samples contained a mix of heartwood and sapwood in its surface. However preservative treatment was much less effective for the heartwood only wood samples, ranging average 1.3 mm with ACQ and 1.1 mm with CCA (Chromated Copper Arsenate). These penetration results shown in heartwood samples did not meet the penetration standard that is required for H3 by the Korean Forest Service in relation to wood preservation treatment. These low penetration results were not significantly improved even if we incised wood samples to improve treatment effect, showing only small increase of 0.7 mm with ACQ and 0.6 mm with CCA. When preservative treatment was tested with heartwood, penetration of preservatives decrease with increase of annual rings per a cross-section area (r=0.5345). We also found that the length and number of check had no effect on preservative treatment, showing r=0.1301 and r=0.1802, respectively.

Effect of Ischemic Preconditioning on Myocardial Protection - A Comparative Study between Normothermic and Moderate Hypothermic Ischemic Hearts Induced by Cardioplegia in Rats - (허혈 전처치가 심근보호에 미치는 영향 - 적출 쥐 심장에서 상온에서의 심근허혈과 중등도 저체온하에서 심근정지액 사용 시의 비교 연구 -)

  • 조성준;황재준;김학제
    • Journal of Chest Surgery
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    • v.36 no.5
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    • pp.242-254
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    • 2003
  • Background: Most of the studies conducted have investigated the beneficial effects of ischemic preconditioning on normothermic myocardial ischemia. However, the effect of preconditioning could be attenuated through the use of multidose cold cardioplegia as practiced in contemporary clinical heart surgical procedures. The purpose of this study was to investigate whether preconditioning improves postischemic cardiac function in a model of $25^{\circ}C$ moderate hypothermic ischemic heart induced by cold cardioplegia in isolated rat hearts. Material and Method: The isolated Sprague-Dawley rat hearts were randomly assigned to four groups All hearts were perfused at 37$^{\circ}C$ for 20 minutes with Krebs-Henseleit solution before the baseline hemodynamic data were obtained, Group 1 consisted of preconditioned hearts that received 3 minutes of global ischemic preconditioning at 37$^{\circ}C$, followed by 5 minutes of reperfusion before 120 minutes of cardioplegic arrest (n=6). Cold (4$^{\circ}C$) St. Thomas Hospital cardioplegia solution was infused to induce cardioplegic arrest. Maintaining the heart at $25^{\circ}C$, infusion of the cardioplegia solution was repeated every 20 minutes throughout the 120 minutes of ischemic period. Group 2 consisted of control hearts that underwent no manipulations between the periods of equilibrium and 120 minutes of cardioplegic arrest (n=6). After 2 hours of cardioplegic arrest, Krebs solution was infused and hemodynamic data were obtained for 30 minuts (group 1, 2: cold cardioplegia group). Group 3 received two episodes of ischemic preconditioning before 30 min of 37$^{\circ}C$ normothermic ischemia and 30 minutes of reperfusion (n=6) Group 4 soloed as ischemic controls for group 3 (group 3, 4: warm ischemia group). Result: Preconditioning did not influence parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and left ventricular dp/dt (LV dp/dt) in the cold cardioplegia group. (p=NS) However, preconditioning before warm ischemia attenuated the ischemia induced cardiac dysfunction, Improving the LVSP, LVEDP, RPP, and LV dp/dt. Less leakage of CPK and LDH were observed in the ischemic preconditioning group compared to the control group (p<0.05). Conclusion: Ischemic preconditioning improved postischemic cardiac function after warm ischemia, but did not protect cold cardioplegic hearts.

Dry Matter, Nitrogen Distribution and Organic Reserves Accumulation as Affected by Nitrate Supply Level in Alfalfa (Medicago sativa L.) (질산태 질소의 공급수준에 따른 알팔파의 건물, 질소의 분포 및 저장영양소의 축적)

  • Kim, Tae-Hwan;Jung, Woo-Jin;Lee, Bok-Rye;Kim, Dae-Hyun;Kim, Kil-Yong
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.22 no.3
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    • pp.153-160
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    • 2002
  • To investigate the effects of the exogenous N $O_3$$^{[-10]}$ supply level on the nitrate assimilation and growth during the vegetative growth stage, and on the accumulation of organic reserves during the successive regrowth period, dry matter (DM), the amount of nitrogenous compounds, total N and starch in alfalfa plants grown hydroponically with 0.2, 1.0 and 3.0 mM KN $O_3$ was estimated, respectively, during vegetative growth period and two cycle of regrowth. When compared with DMs and N contents in various N compounds in the organs grown with 1.0 mM N $O_3$$^{[-10]}$ , N starvation symptoms were found in 0.2 mM and a depressive effect was observed in 3.0 mM after 10 weeks of vegetative growth. Total starch content in root system gown with 0.2, 1.0 and 3.0 mM N $O_3$$^{[-10]}$ during the first regrowth was 50.96, 15.47 and 6.37 mg plant$^{-1}$, respectively. Starch was contained mainly in taproots. The starch content was not significantly changed by 24 days of the second regrowth with 1.0 mM N $H_4$N0$_3$. Total nitrogen content in root system grown with 0.2, 1.0 and 3.0 mM N $O_3$$^{[-10]}$ during the first regrowth was 6.66, 8.43 and 11.09 mg plant$^{-1}$ , respectively. Nitrogen was contained mainly in lateral roots; 80% (in 0.2 mM), 74% (1.0 mM) and 76% (3.0 mM) of total nitrogen in root system. Total N content in root system at the end of the second regrowth also closely affected by the N $O_3$$^{[-10]}$ supply level during the first regrowth. These results suggest that the level of N $O_3$$^{[-10]}$ may strongly influence the accumulation of organic reserves in root system, and that the initial level of organic reserves for the successive regrowth was one of the determinants for shoot regrowth.

Studies on Application of Organic-Compound Fertilizer on Hilly Mixed Sward I. Effect of organic-compound fertilizer application on dry matter yield and botanical composition of grass-clover mixtures (산지초지에 의한 유기질복합비료의 시용에 관한 연구 I. 유기질 복합비료의 시용이 혼파목초의 건물수량과 식생변화에 미치는 영향)

  • 박근제;이혁호;신재순;이종열
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.8 no.3
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    • pp.92-98
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    • 1988
  • With a purpose of finding out the effects of magnesium and boron enriched organic-compound fertilizer application on the dry matter yield, yield components and changes in the botanical composition on the hilly pasture, a field experiment was arranged with five different treatments as a randomized block design and lasted from September, 1984 to the end of growing season in 1986. The results obtained are summarized as follows : 1. As a early plant growth and development, winter hardiness, growth vigour and coverage of grasses at the plots with organic-compound fertilizer application were better comparing to single dressing. 2. Average dry matter yields for two years were shown significantly high due to increasing amount of fertilizer. This trend was same both single and organic-compound fertilizer. And dry matter yields with organic-compound fertilizer application of low (8, 693.1 kg/ha) and conventional level (12, 758.7 kg/ha) were appeared to increase by 10 and 15% than those of single dressing of Low (7, 930.6 kg/ha) and conventional level (11, 122.6 kg/ha), respectively. But it was not significant difference. 3. Dry matter yield of grasses was significantly gained by increasing amount of fertilizer. The yield of legumes at the plot without fertilization was significant higher comparing to fertilizing plots, but it was not different between low and conventional dressing levels. However, at the plots with organic-compound fertilizer application the yields of grasses were a little more increased by 8-14%, and legumes were much more gained by 26-29% than those of the same species groups with single dressing, but it was not significant between the different kinds of fertilizer in the same fertilizing level. 4. At the grassland management, the rate of legumes tended to dominate at the plot without fertilization gradually. On the other hand, the botanical compositions and the rates of grasses were much better maintained at the plots with fertilization. But the rates of legumes with organic-compound fertilizer application tended to increase a little more than those of single dressing gradually.

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Quality of Life Changes in Patients Admitted to the Hospice Unit (호스피스 병동 입원 환자의 삶의 질 변화)

  • Park, Theresia;Song, Hae-Hiang;Seo, In-Ok;Cho, Young-Yee;Park, Myung-Hee;Heo, Jeong-Hee;Kim, Eun-Kyung;Park, Sun-Ju;Ra, Jeong-Ran
    • Journal of Hospice and Palliative Care
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    • v.3 no.1
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    • pp.18-27
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    • 2000
  • Purpose : This study aims to find out the quality of life of patients admitted to the hospice unit at Kangnam St. Mary's Hospital, at admission and after weeks hospice service and to assess the effects of hospice service on the quality of life of terminal cancer patients. Methods : This study subjects were 100 patients admitted to the hospice unit at Kangnam St. Mary's Hospital, Catholic University between October 1999 and March 2000, and their primary caregivers. Quality of life data were collected using a questionnaire revised by the authors and were analyzed by means of repeated measures ANOVA. Results : 1) Patient's quality of life as perceived by the primary caregiver was significantly improved and the mean score was 3.31, 3.68, 3.56, 3.73, 3.75 at admission and week 1, 2, 3, 4. With the detailed item analysis, the following items were shown to be significantly improved: "clean bodies"(F=6.50, P=0.0001) "pain control"(F=18.01, P=0.0001) constipate"(F=2.96, P=0.0237) "sleep"(F=3.99, P=0.0048) "nausea/vomiting"(F=4.50, P=0.0022) "medical team's comfortable care" (F=3.95, P=0.0051) "family's care"(F=2.76, P=0.0317) "anxiety" (F=3.14, P=0.0177) "comfort"(F=3.63, P=0.0085) "treat with dignity"(F=3.32, P=0.0136). The item of "death is not the end of life rather the beginning" was significantly decreased(F=2.54, P=0.0450). 2) Patient's quality of life as perceived by the patient showed an improvement but statistically insignificant and the mean score was 3.63 and 3.83 at admission and week 1. With the detailed item analysis, the item of "pain control" was shown to be significantly improved(F=9.19, P=0.0251). 3) The quality of score in the last week of life of patient were 3.48, 3.51, 3.44, 3.46, 3.50, respectively, from 5 week prior to 1 week prior to death and these changes were insignificant. Conclusion : The findings of this study showed a positive effect of hospice service on quality of life of the terminal cancer patients admitted to the hospice unit. To improve the quality of life, we need first of all to develop hospice interventions with a particular emphasis on the spiritual aspect of patient. Secondly, measurement instruments need to be developed to collect the quality of life of the hospice patients who become weakened especially in the last weeks of their life and with this effort more representative data of hospice patients may be collected.

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Estrus Induction Rates and Conception Rates by MGA Feeding System in Hanwoo (MGA Feeding System에 의한 발정 동기화 방법이 한우의 발정 발현율과 수태율에 미치는 영향)

  • Lee, M.S.;Jung, Y.H.;Park, S.B.;Im, S.K.;Park, J.J.;Jung, J.K.;Moon, S.J.;Kim, C.K.
    • Journal of Embryo Transfer
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    • v.21 no.3
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    • pp.177-182
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    • 2006
  • This study was conducted to investigate the effects of melengesterol acetate (MGA) and $PGF_{2{\alpha}}$ administrations on serum progesterone level, synchrony of estrus and conception rates in Han-woo. Firstly, ten heifers and one freematin were fed 0.5 mg MGA/day for 14 days in a grain carrier, and after 19 days of MGA feeding, a single injection of 25 mg $PGF_{2{\alpha}}$ were treated. Blood samples were collected to evaluate serum progesterone concentrations from the start of feeding of MGA until the end of feeding and subsequent estrous detection and artificial insemination (AI) at 3 days intervals, and on days of $PGF_{2{\alpha}}$ injection, estrous detection, AI, and 15th and 60th days after AI. The level of progesterone in the blood began to increase from 7 days after MGA feeding, and 9 days after feeding it became 5.4 ng/ml and maintained that level thereafter. On the 33th day when the $PGF_{2{\alpha}}$ was injected, it reached the peak level of 7.6 ng/ml. However, 2-3 days after $PGF_{2{\alpha}}$ injection, it dropped to 1.4 ng/ml drastically (p<0.05). Secondly, one hundred and ninety four Hanwoo heifers or cows were divided into two groups to compare estrous induction and conception rates: the one treated with MGA and $PGF_{2{\alpha}}$, (n=104) and the other with $PGF_{2{\alpha}}$ treatment (two injections at 11 days interval, n=90). The heifers or cows treated with MGA and $PGF_{2{\alpha}}$ were identical to those used as above. The percentages of heifers or cows showed estrus were higher in the $MGA+PGF_{2{\alpha}}$ treatment (91.3%) than in the $PGF_{2{\alpha}}$ treatment (72.2%, p<0.05). Conception rates were also higher in the $MGA+PGF_{2{\alpha}}$ treatment (94.2%) than in the $PGF_{2{\alpha}}$ treatment (88.9%, p<0.05). The results of this experiment indicate that estrus synchronization using $MGA+PGF_{2{\alpha}}$ is more effective than that using $PGF_{2{\alpha}}$ (two injections) in Hanwoo.

Industrial potential of domestic Zanthoxylum piperitum and Zanthoxylum schinifolium: Protective effect of both extracts on high glucose-induced neurotoxicity (국내산 초피와 산초의 산업적 활용 가능성: 고당으로 유도된 뇌신경세포 독성에 대한 추출물의 보호 효과)

  • Han, Hye Ju;Park, Seon Kyeong;Kim, Min Ji;An, Jun Woo;Lee, Se Jin;Kang, Jin Yong;Kim, Jong Min;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.274-283
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    • 2020
  • This study focused on the in vitro investigation of antioxidant and anti-diabetic activities, along with neuroprotection against high glucose-induced cytotoxicity, in order to evaluate the physiological effects of Zanthoxylum piperitum and Zanthoxylum schinifolium. The highest total phenolic content was measured in the 40% ethanolic extracts of Zanthoxylum piperitum (EZP) and Zanthoxylum schinifolium (EZS). The in vitro EZP antioxidant activity showed a relatively higher ABTS/DPPH radical scavenging activity and malondialdehyde inhibitory effect than that of EZS. The EZP inhibited carbohydrate hydrolysis (α-glucosidase and α-amylase) more efficiently than EZS in anti-diabetic tests. However, EZS showed a more efficient inhibition of advanced glycation end-products formation than EZP. In addition, both EZP and EZS effectively protected human-derived neuronal cells from high glucose-induced cytotoxicity. Finally, the physiological compounds were analyzed using UPLC IMS-QTOF/MSE, and the main EZP (quercetin-3-O-glucoside and 3-caffeoylquinic acid) and EZS (5-caffeoylquinic acid) compounds were identified as phenolic compounds.

Anti-Obesity Effect of Crataegus Fructus Extract from Chinese Cultivation (중국산 산사자 추출물의 항비만 효과)

  • Gal, Sang-Wan;Choi, Young-Jae;Cho, Soo-Jeong
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1586-1591
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    • 2011
  • This study was carried out to evaluate the antiobesity effects of Crataegus fructus in 3T3-L1 adipocytes and mice fed a high fat diet (high fat 45% cal). The inhibitory effect of methanol extract from Crataegus fructus on lipid accumulation in 3T3-L1 adipocytes was quantified using Oil red O staining. Compared with the control, lipid accumulation was significantly decreased by 10-25% with treatment with Crataegus fructus extract at a concentration of 600-2,000 ug/ml. Three-week old ICR mice (n=24) were randomly divided into four groups (T0: normal diet, T1: high fat diet, T2: high fat diet and 50 ug of Crataegus fructus extract, T3: high fat diet and 100 ug of Crataegus fructus extract) and were fed an experimental diet for 5 weeks. At the end of the experiment, body weight gain in the T1 group (3.9${\pm}$0.24 g) was higher than that in the T0 group (2.56${\pm}$0.14 g), while body weight gain in the T2 (3.02${\pm}$0.25 g) and T3 (2.58${\pm}$0.16 g) groups was significantly reduced as compared with that of the T1 group. Moreover, liver weight in the T1 (4.8${\pm}$0.17 g) and T2 (4.8${\pm}$0.16 g) groups was significantly higher than that of the T0 (4.05${\pm}$0.16 g) and T3 (4.57${\pm}$0.10 g) groups, while kidney weight was significantly lower than that of the T0 and T3 groups (p<0.05). The levels of total cholesterol and triglyceride in serum in the T2 and T3 groups were significantly decreased compared to the T1 group. These results suggest that Crataegus fructus can be used as functional materials in food and medicine.

Variables Affecting Long-Term Compliance of Oral Appliance for Snoring (코골이 치료용 구강장치의 지속적 사용에 영향을 주는 요인의 분석)

  • Lee, Jun-Youp;Hur, Yun-Kyung;Choi, Jae-Kap
    • Journal of Oral Medicine and Pain
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    • v.33 no.4
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    • pp.305-316
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    • 2008
  • The mandibular advancement device(MAD) has been used to help manage snoring and obstructive sleep apnea. The aims of this study were to specify the demographic and clinical characteristics of the patients receiving long-term treatment with MAD and to quantify the compliance with and side effects of the use of the device. Of 103 patients who were treated with MAD for at least one full year after delivery date, 49 were able to be contacted with telephone and complete follow-up questionnaires were obtainable. They were telephoned to determine whether they were still using the device. If not, they were asked when and why they stopped using it. Patients were also asked how much effectiveness of the MAD in decreasing snoring and how much they and their bed-partners were satisfied with the MAD therapy. The initial respiratory disturbance indices and pre-treatment snoring frequency and intensity were obtained from the medical records of initial visit. All the data were compared between users and nonusers. The results were as follows: 1. Of 49 patients 25 are still using the device, but 24 stopped using it. Among nonusers nobody stopped wearing the device within first 1 month, but 37.5% of nonusers stopped wearing it in the following 6 months, and another 4.2% before the end of the first year. 2. The one-year compliance of the MAD therapy was 79.59%. 3. There were no significant differences in mean age, mean body mass index, and gender distribution between users group and nonusers group. 4. There was no significant difference in mean respiratory disturbance index at initial visit between users group and nonusers group. 5. There was no significant difference in pre-treatment snoring frequency and intensity between users group and nonusers group. 6. The degree of decrease in snoring with use of MAD was significantly higher in the users when compared to nonusers. 7. Patient's overall satisfaction with treatment outcome was significantly higher in the users when compared to nonusers. 8. Bed partner's satisfaction with treatment outcome tended to be higher in the users when compared to nonusers. 9. The most frequent reasons why patients discontinued wearing the MAD were: jaw pain(25%), dental pain(20.83%), broken appliance(20.83%), hassle using(16.67%), lost weight(8.3%), dental work(8.3%), no or little effect(4.17%), sleep disturbance(4.27).