• Title/Summary/Keyword: Kwon Young

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Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

  • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.822-835
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    • 1997
  • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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A Study on the Job Performance of Dental Coordinators and Their Perception (치과코디네이터의 업무수행 및 인식도에 관한 조사연구)

  • Kwon, Soon-Bok;Kim, Young-Nam;Moon, Hee-Jung;Shin, Myung-Suk;Han, Gyeong-Soon;Han, Su-Jin
    • Journal of dental hygiene science
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    • v.5 no.4
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    • pp.211-220
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    • 2005
  • The purpose of this study was to examine the job performance of dental coordinators and their perception of their job to lay the groundwork for utilizing dental personnels more efficiently. The subjects in this study were dental coordinators who worked at selected dental hospitals and clinics in Seoul, Gyeonggi province and Incheon. A survey was conducted to gather data from May 1 to August 8, 2005 and answer sheets from 108 respondents were analyzed. The findings of the study were as follows: 1. As for the length of service, 43.5 percent of the dental coordinators investigated had worked at dental institutes for five years or more, which was followed by less than two years(19.5%) and three years to less than five years(19.4%). Concerning the length of service as dental coordinators, 39.8 percent had served for less than two years, and 19.4 percent had worked for two years to less than three years and for five years or more respectively. Regarding the name of position, 38 percent were called team leaders, and 30.6 percent were called coordinators. As to duties, the largest group of them that stood at 30.6 percent were in charge of receiving, and in regard to department, the largest group, 57.4 percent, belonged to the treatment backup department. 2. Concerning education, the greatest number of them, 45.4 percent, had received education at private institutes, and 73.1 percent found it necessary for dental coordinators to take an authorized qualification test. 43.5 percent, the largest group, looked upon the central government as the best organization to authorize their qualifications and 70.8 percent believed that what they learned enabled them to perform their job successfully. As to the necessity of follow-up education as a means to improve job performance, 96.3 percent consented to it. As for the reason, 63.9 percent considered that necessary to enhance their own ability and 22.2 percent were in want of systematic education. Regarding educational expenses, 29.6 percent were subsidized by the dental institutes where they had worked and 25.9 percent had totally been responsible for that. Regarding a required course, medical service and marketing was most widely pointed out(66.7%), followed by theory and practice(65.7%) and introduction to dentistry(57.4%). As to what sort of education they wanted to receive more, dental service and marketing was selected the most, followed by practical health insurance(35.2%). 3. In regard to what type of job they performed as dental coordinators, 88.9 percent were in charge of appointment in the field of customer service, and 87.9 percent paid attention to having good manners as service providers in the area of self-management. In the field of hospital affairs, 81.3 percent were in charge of receiving. 4. As to their awareness of dental coordinator job, the largest group took pride in the job they performed ($3.99{\pm}0.76$), and the second largest group believed that dental coordinators made a great contribution to hospital management ($3.92{\pm}0.70$). The third largest group gave a great weight to their own job ($3.91{\pm}0.84$) in light of overall dental duties and the fourth largest group found themselves to get along with other employees regardless of position ($3.86{\pm}0.74$). The fifth largest group believed their job was of great use for promoting the oral health of patients ($3.76{\pm}0.75$), and the sixth largest group thought the future of dental coordinators was promising($3.74{\pm}0.86$). 5. In regard to their perception by age group, those who were older had a better opinion on every item of their job in general. Their age made a statistically significant difference to their view of the weight of dental coordinator job(P < 0.001) in light of overall dental duties, of being approved and trusted by managers(P < 0.01), of social awareness of dental coordinator, and of being understood and approved by other employees and dentists. Their pride in current job and their satisfaction with the name of their position were statistically significantly different according to their age as well. Besides, their age made a statistically significant difference to their opinion about whether or not there was an age limit to their occupation and about their contribution to hospital management (P < 0.05). 6. As for their perception by type of job, the dental hygienists were generally most satisfied with their job, followed by nursing aids and others. There was a statistically significant gap among their opinions about whether to make a job-related decision on their own(P < 0.001). the weight of their job in terms of overall dental duties, whether their job improved their ability, whether their job made a great contribution to enhancing the oral health of patients, whether their job was understood and approved by other employees(P < 0.01), social awareness of their job, whether they conflicted with other employees during job performance, and whether dental hospitals or clinics offered a self-development opportunity for them to take their ability to another level(P < 0.05). And their satisfaction with current pay was statistically significantly different as well.

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Studies on the Propagation of the Freshwater Prawn, Macrobrachium nipponense (De Haan) Reared in the Laboratory 2. Life History and Seedling Production (담수산 새우, Macrobrachium nipponense (De Haan)의 증${\cdot}$양식에 관한 생물학적 기초연구 2. 생활사 및 종묘생산에 관한 연구)

  • KWON Chin-Soo;LEE Bok-Kyu
    • Journal of Aquaculture
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    • v.5 no.1
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    • pp.29-67
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    • 1992
  • Life cycle and seed production of the freshwater prawn, Macrobrachium nipponense, were studied and the results are as follows : 1. Larval development : Embryos hatched out as zoea larvae of 2.06 mm in mean body length. The larvae passed through 9 zoea stages in $15{\~}20$ days and then metamorphosed into postlarvae measuring 5.68 mm in mean body length. Each zoea stage can be identified based on the shapes of the first and second antennae, exo- and endopodites of the first and second pereiopods, telson and maxillae. 2. Environmental requirements of zoea larvae : Zoea larvae grew healthy when fed with Artemia nauplii. Metamorphosing rate was $65{\~}72{\%}$ at $26{\~}28\%$ and $7.85{\~}8.28\%_{\circ}Cl.$. The relationship between the zoeal period (Y in days) and water temperature (X in $^{\circ}C$) is expressed as Y=46.0900-0.9673X. Zoeas showed best survival in a water temperature range of $26{\~}32^{\circ}C$ (optimum temperature $28^{\circ}C$), at which the metamorphosing rate into postlarvae was $54{\~}72\%$ The zoeas survived more successfully in chlorinity range of $4.12{\~}14.08{\%_{\circ}}Cl.$, (optimum chlorinity $7.6{\~}11.6\;{\%_{\circ}}Cl.$.), at which the metamorphosing rate was $42{\~}76{\%}$. The whole zoeal stages tended to be longer in proportion as the chlorinity deviated from the optimum range and particularly toward high chlorinity. Zoeas at all stages could not tolerate in the freshwater. 3. Environmental requirements of postlarvae and juveniles : Postlarvae showed normal growth at water temperatures between $24{\~}32^{\circ}C$ (optimun temperature $26{\~}28^{\circ}$. The survival rate up to the juvenile stage was $41{\~}63{\%}$. Water temperatures below $24^{\circ}C$ and above $32^{\circ}$ resulted in lower growth, and postlarvae scarcely grew at below $17^{\circ}C$. Cannibalism tended to occur more frequently under optimum range of temperatures. The range of chlorinity for normal growth of postlarvae and juveniles was from 0.00 (freshwater) to $11.24{\%_{\circ}}Cl.$, at which the survival rate was $32{\~}35\%$. The postlarvae grew more successfully in low chlorinities, and the best growth was found at $0.00\~2.21{\%_{\circ}}Cl.$. The postlarvae and juveniles showed better growth in freshwater but did not survive in normal sea water. 4. Feeding effect of diet on zoea Ilarvae : Zoea larvae were successfully survived and metamorposed into postlarvae when fed commercial artificial plankton, rotifers, and Artemia nauplii in the aquaria. However, the zoea larvae that were fed Artemia nauplii and reared in Chlorella mixed green water showed better results. The rate of metamorphosis was $68\~{\%}75$. The larvae fed cow live powder, egg powder, and Chlorella alone did not survive. 5. Diets of postlarvae, juveniles and adults : Artemia nauplii and/or copepods were good food for postlarvae. Juveniles and adults were successfully fed fish or shellfish flesh, annelids, corn grain, pelleted feed along with viscera of domestic animals or fruits. 6. Growth of postlarvae, juveniles and adults : Under favorable conditions, postlarvae molted every five or six days and attained to the juvenile stage within two months and they reached 1.78 cm in body length and 0.17 g in body weight. The juveniles grew to 3.52 cm in body length and 1.07 g in body weight in about four months. Their sexes became determinable based on the appearance of male's rudimental processes (a secondary sex character) on the endopodites of second pereiopods of males. The males commonly reached sexual maturity in seven months after attaining the postlarvae stage and they grew to 5.65 cm in body length and 3.41 g in body weight. Whereas the females attained sexual maturity within six to seven months, when they measured 4.93 cm in body length and 2.43 g in body weight. Nine or ten months after hatching, the males grew $6.62{\~}7.14$ cm in body length and $6.68{\~}8.36$ g in body weight, while females became $5.58{\~}6.08$ cm and $4.04{\~}5.54$ g. 7. Stocking density : The maximum stocking density in aquaria for successful survival and growth was $60{\~}100$ individuals/$\ell$ for zoeas in 30-days rearing (survival rate to postlarvae, $73{\~}80{\%}$) ; $100{\~}300$ individuals/$m^2$ for postlarvae of 0.57 cm in body length (survival rate for 120 days, $78{\~}85{\%}$) ; $40{\~}60$ individuals/$m^2$ for juveniles of 2.72 cm in body length (survival rate for 120 days, $63{\~}90{\%}$) : $20{\~}40$ individuals/$m^2$ for young prawns of 5.2 cm in body length (survival rate for 120 days, $62\~90{\%}$) ; and $10\~30$ individuals/$m^2$ for adults of 6.1 cm in body length (survival rate for 60 days, $73\~100{\%}$). The stocking density of juveniles, youngs and adults could be increased up to twice by providing shelters.

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The Three Types of Clinical Manifestation of Cow's Milk Allergy with Predominantly Intestinal Symptoms (위장관 증세 위주로 발현하는 영유아기 우유 알레르기 질환의 3가지 임상 유형에 관한 고찰)

  • Lee, Jeong-Jin;Lee, Eun-Joo;Kim, Hyun-Hee;Choi, Eun-Jin;Hwang, Jin-Bok;Han, Chang-Ho;Chung, Hai-Lee;Kwon, Young-Dae;Kim, Yong-Jin
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.3 no.1
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    • pp.30-40
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    • 2000
  • Purpose: During the first year of life, cow's milk protein is the major offender causing food allergy. Cow's milk allergy (CMA) affects 2~7% of infants, of which approximately one-half show predominantly gastrointestinal symptoms. We studied the clinical types of cow's milk allergy with predominantly gastrointestinal symptoms (CMA-GI) of childhood. Methods: The retrospective study was performed on 30 (male 22, female 8) patients who had diagnosed as CMA-GI during 2 years and 3 months from March 1995 to June 1997. Results: 1) Children with CMA-GI presented in the three types of clinical manifestation on the basis of time to reaction to milk ingestion: Quick (Q) onset (5 cases), Slow (S) onset (20 cases), Quick & Slow (Q&S) (5 cases). 2) Age on admission of the three groups was significantly different (p<0.05): (Q onset: $81.4{\pm}67.1$ days, S onset: $31.9{\pm}12.7$ days, Q&S: $366.0{\pm}65.0$ days). Although the body weight at birth was 10~95 percentile in all patients, body weight on admission was different: (Q onset: 10~50 percentile, S onset: below 10 percentile, Q&S: 10~25 percentile). S onset group was significantly different compared with other groups (p<0.05) and 90% of this one was failure to thrive below 3 percentile. 3) Peripheral leukocyte counts were as followings: (Q onset: $5,700{\sim}12,300/mm^3$, S onset: $10,000{\sim}33,400/mm^3$, Q&S: $5,200{\sim}14,900/mm^3$). Slow onset group was significantly different compared with other groups (p<0.05). Serum albumin levels on admission were as followings: (Q onset: $4.2{\pm}0.4\;g/dl$, S onset: $3.0{\pm}0.3\;g/dl$, Q&S: $4.0{\pm}0.3\;g/dl$). S onset group was significantly different compared with other groups (p<0.05) and 85% of this one was below 3.5 g/dl. 4) Although morphometrical analysis on small intestinal mucosa did not show enteropathy in Q onset and Q&S groups, all cases of S onset revealed enteropathy: 45% of this one showed subtotal villous atrophy, 55 % showed partial villous atrophy. 5) Allergic reaction test to other foods was not performed in S onset group because of ethical problem and high risk in general condition. In Q onset group, allergic reaction to one or two other foods: soy formula, weaning formula and eggs. Q&S goup revealed allergic reactions to several foods or to most of all foods except protein hydrolysate formula: eggs, potatos, some kinds of sea food, apples, carrots, beef and chicken. 6) Serum IgE level, peripheral eosinophil counts, milk RAST, soy RAST, skin test were not significantly different among groups. Conclusion: CMA-GI may present in three clinical ways on the basis of time to reaction to milk ingestion, typical clinical findings and morphologic changes in the small bowel mucosal biopsy specimens. This clinical subdivision might be helpful in diagnostic and therapeutic approaches in CMA-GI. Early suspicion is mandatory especially in S onset type because of high risks with malnutrition and enteropathy.

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The Legal Theory on the Civil Execution against Aircraft (항공기 집행에 관한 법리)

  • Kwon, Chang-Young
    • The Korean Journal of Air & Space Law and Policy
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    • v.30 no.2
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    • pp.83-153
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    • 2015
  • As our economy grows and the number of aircraft increase, the number of civil execution against aircraft cases are likely to increase as well in the future. The purpose of this article is to present the legal theory on the civil execution against aircrafts by drawing on the legal theory on the civil execution against vessels which constitute a relatively large number of cases thus observed. The provisions of the civil execution against immovables or vessel, shall basically apply mutatis mutandis to the civil execution against aircraft or light aircraft. The civil execution against ultra-light flying devices or a foreign aircraft shall be executed in conformity with the civil execution against movables. There are a compulsory auction, an auction to execute a security right to aircraft, and an auction under the right of retention, etc. in the civil execution against an aircraft. A compulsory execution against an aircraft means an execution carried out by a creditor against a debtor's aircraft to obtain satisfaction of claims for the purpose of payment of money. The court of execution of a compulsory execution against an aircraft shall be the district court having jurisdiction over the airport of stoppage or storage of such aircraft at the time of seizure. The forums of execution of a compulsory execution against an aircraft shall be exclusive forums. When a court has rendered an order on commencing an auction, it shall order an execution officer to receive a certificate of the aircraft's registration and other documents as required for its operation, and to submit them to the court. A court may revoke the procedures for a compulsory auction when an execution officer fails to obtain a transfer of the aircraft's registration certificate, etc. and the location of the aircraft is not evident, not later than an elapse of 2 months from the date on which an order on commencing an auction has been rendered. In the case where it is deemed that there exists a business-related need or other based on proper reasoning, the court may permit the aircraft's operation, upon the motion submitted by the debtor. In this case, there shall be a consent from the creditor, the highest bidder, the next highest bidder and successful bidder. A court may, upon a motion submitted by the creditor, make the dispositions required for observing and preserving the aircraft. When a debtor has submitted the documents under subparagraph 2 or 4 of the Article 49 of the Civil Execution Act, and furnished the guarantee equivalent to the claims of the execution creditors and the creditors demanding a distribution and to the costs for execution, before a declaration of bid, the court shall, upon request, revoke other procedures than those for distribution. The provisions of a obligatory auction against vessel or aircraft and an auction to execute a security right to real estate or vessel, shall apply mutatis mutandis to an auction to execute the security right to aircraft. In an auction to execute the security right to aircraft case, an executive title is not necessary. An executory exemplification is not necessary in an application for an auction to execute the security right to aircraft. A court should examine the existence of security right and claim secured. No order on commencing an auction procedure shall be issued with non-existence or invalidity of the security right and absence or extinguishment of the claim secured. Furthermore, these prohibitions are the reason of a decision on non-permit for sale, the court overlooked these prohibitions, and the decision on a permit for sale became final and conclusive, the successful bidder who paid the price and registered of ownership could not acquire ownership of the aircraft sold. A court may render a ruling to put plural aircrafts up for a blanket auction, only when they are in restraint and related matter (Supreme Court Order 2001Ma3688 dated on August 22, 2001). A righter of retention on aircraft may file a request for an auction against the aircraft. The provisions of an auction to execute a security right to aircraft shall apply mutatis mutandis to the formal auction. Airport facility fee and an aircraft are not in restraint and related matter, so an airport management corporation does not hold the right of retention on the aircraft (Supreme Court Decision 2011Da29291 decided on April 10, 2014). In an auction in accordance with the right of retention, all encumbrances (e.g., mortgages) on the sold aircraft shall be extinguished by a sale under the legal conditions for sale. Not only creditors who have claims for preferential payment but also general creditors could demand for distribution. The precedence of the claim of the right of retention on aircraft and that of general creditor's claims are equal.

Pharmacokinetic Study of Isoniazid and Rifampicin in Healthy Korean Volunteers (정상 한국인에서의 Isoniazid와 Rifampicin 약동학 연구)

  • Chung, Man-Pyo;Kim, Ho-Cheol;Suh, Gee-Young;Park, Jeong-Woong;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Han, Yong-Chol;Park, Hyo-Jung;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.479-492
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    • 1997
  • Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

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The Effect of Interferon-γ on Bleomycin Induced Pulmonary Fibrosis in the Rat (Interferon-γ 투여가 쥐에서의 Bleomycin 유도 폐 섬유화에 미치는 영향)

  • Yoon, Hyoung Kyu;Kim, Yong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.1
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    • pp.51-66
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    • 2004
  • Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.