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Studies for Antibiotic Free Chicken Production Using Water Extracts from Artemisia capillaris and Camellia sinensis (인진쑥 및 녹차 추출물을 이용한 무항생제 닭고기 생산 연구)

  • Kim, Dong-Wook;Kim, Ji-Hyuk;Kang, Geun-Ho;Kang, Hwan-Ku;Park, Sung-Bok;Park, Jae-Hong;Bang, Han-Tae;Kim, Min-Ji;Na, Jae-Cheon;Chae, Hyun-Suk;Choi, Hee-Chul;Suh, Ok-Suk;Kim, Sang-Ho;Kang, Chang-Won
    • Food Science of Animal Resources
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    • v.30 no.6
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    • pp.975-988
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    • 2010
  • Two experiments were conducted to determine whether water extracts from Artemisia capillaries (A. capillaries) and Camellia sinensis (C. sinensis) could be used as alternatives to antibiotic growth promoters in broiler feed. The experiment 1 was verified their chemical composition, extracts yields, total phenolic compounds concentration, antioxidant activity, antimicrobial activity, and chicken splenocytes proliferation through in vitro test. The extract yields of A. capillaries and C. sinensis were 26.5 and 16.8%, respectively. Total phenolic compounds concentrations of them expressed as gallic acid equivalent were 15.28 and 26.74 mg/mL, respectively. Electron donating abilities of them expressed as $SC_{50}$ showing 50% DPPH radical scavenging were 0.30 and 0.06 mg, respectively. Bacterial inhibitory rates of them against Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium were ranged from 42.1 to 52.3% and from 21.6 to 33.7%, respectively. And, these extracts increased proliferation of chicken splenocytes. Especially, A. capillaris was more excellent than Echinacea and Concanavalin A known as T-cell stimulator. The experiment 2 was investigated their effects on growth performance, relative organ weight, cecal microflora, blood biochemical parameters, and splenic cytokines mRNA expression in broiler chicks. Four hundred eighty 1-day-old male broiler chicks (Ross 308) were divided in to 4 treatment groups with 4 replicates of 30 birds in each group: NC (control, no antibiotics), PC (avilamycin, 10 ppm; salinomycin, 60 ppm), AC (A. capillaries, 100 ppm), and CS (C. sinensis, 100 ppm); treatments were administered through water supplementation. Final body weight was significantly higher in all treated groups than in NC (p<0.05). Cecal Salmonella numbers were significantly or somewhat decreased in all treated groups than in NC (p<0.05). The relative weights and lengths of the small intestine were more significantly decreased in the PC and AC groups than in the other groups. Cecal Salmonella numbers were significantly or somewhat decreased in all treated groups than in the NC group (p<0.05). The contents of total cholesterol, aspatate aminotransferase, and alanine aminotransferase in blood serum were more significantly decreased in all treated groups than in NC (p<0.05). In conclusion, these results suggested the possibility that these extracts could serve as alternatives for antibiotic growth promoters.

Mineralogy and Biogeochemistry of Intertidal Flat Sediment, Muan, Chonnam, Korea (전남 무안 갯벌 퇴적물에 관한 광물학적 및 생지화학적 연구)

  • Park, Byung-No;Lee, Je-Hyun;Oh, Jong-Min;Lee, Seuug-Hee;Han, Ji-Hee;Kim, Yu-Mi;Seo, Hyun-Hee;Roh, Yul
    • Journal of the Mineralogical Society of Korea
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    • v.20 no.1 s.51
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    • pp.47-60
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    • 2007
  • While sedimentological researches on Western coastal tidal flats of Korea have been much pelformed previously, mineralogical and biogeochemical studies are beginning to be studied. The objectives of this study were to investigate mineralogical characteritics of the inter-tidal flat sediments and to explore phase transformation of iron(oxyhydr)oxides and biomineralization by metal-reducing bacteria enriched from the inter-tidal flat sediments from Muan, Jeollanam-do, Korea. Inter-tidal flat sediment samples were collected in Chungkye-myun and Haeje-myun, Muan-gun, Jeollanam-do. Particle size analyses were performed using the pipette method and sedimentation method. The separates including sand, silt and clay fractions were examined by scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis, transmission electron microscopy (TEM), and X-ray diffiaction (XRD). After enriching the metal-.educing bacteria from the into,-tidal flat sediments, the bacteria were used to study phase transformation of the synthesized iron (oxyhydr)oxides and iron biomineralization using lactate or glucose as the electron donors and Fe(III)-containing iron oxides as the electron accepters. Mineralogical studies showed that the sediments of tidal flats in Chung]rye-myun and Haeje-myun consist of quartz, plagioclase, microcline, biotite, kaolinite and illite. Biogeochemical researches showed that the metal-reducing bacteria enriched from the inter-tidal flat sediments reduced reddish brown akaganeite and mineralized nanometer-sized black magnetite. The bacteria also reduced the reddish brown ferrihydrite into black amorphous phases and reduced the yellowish goethite into greenish with formation of nm-sized phases. These results indicate that microbial Fe(III) reduction may play one of important roles in iron and carbon biogeochemistry as well as iron biomineralization in subsurface environments.

An Analysis of the Psychiatric Characteristics of the Alopecia Areata in Female (여성 탈모증의 정신의학적 특성 분석)

  • Lee, Kil-Hong;Na, Chul;Lee, Young-Sik;Lee, Chang-Hoon;No, Byung-In;Hong, Chang-Kwon
    • Korean Journal of Psychosomatic Medicine
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    • v.8 no.1
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    • pp.31-45
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    • 2000
  • Objectives : The present study was performed to reveal differences between female and male cases of alopecia in their alopecia related variables such as patterns of hair loss, psychiatric characteristics, associate illnesses, and methods of treatment, and to use them as basic materials for proper management and early prevention of the alopecia prone cases. Methods : In order to analysis the gender difference in hair losses, the subjects were divided into two subgroups as the 51 cases of female alopecia and the 42 cases of male alopecia, who had visited to the department of psychiatry consulted from the department of dermatology, Yongsan hopital, ChungAng University, Seoul, Korea, from January 1998 to December 1998. In data analysis, the subjects were statistically assesed by chi-squre test and analysis of varaiance, through SPSS-$PC^+$ 9.0V. Results : 1) Female subjects were more likely showed lower socio-economical level including lower eonomical level, lower educational level, or lower occupational level in their parent's job, were more likely to have larger number of siblings and to have many sisters comparison to the male cases. 2) Female subjects were more likely visited to the department of dermatology, more history of alopecia in their female family members, lesser history of alopecia in their male family members, more loss of hairs in vertex or frontal region of scalp, lesser loss of hairs in occipital region, and lesser nail changes in comparison to the male cases. 3) Female subjects were more suffered from intra-familial conflicts and economical changes, or their introverted personality makeup, lesser likely suffered from changes of business and health changes, and showed lesser conflicts related with poorer adaptaion in their job life. 4) Female subjects were more likely diagnosed as depression or conversion disorders, more frequently complaint anxiety symptoms or depressive symptoms, higher level of anxiety index, lesser complaint somatization or obsessive compulsive symptoms, and lesser diagnosed as anxiety disorder in comparison to the male cases. 5) Female subjects were more likely tended to show personality makeup such as the introverted, the lie, the repressed, or the feminine trends than the male cases. 6) Female subjects were more significantly treated by antianxiety drug such as etizolam and dermatological therapies include tretinoin, and lesser treated by clotiazepam and prednicarbonate in comparison to the male cases. Conclusion : From the facts that The most important factors in developing hair loss in the female subjects in comparison to the male cases seems to be closely correlated with the serious psychopathology such as the presence of mental disorders including depression, the presence of complaining anxiety or depressive symptomatology, the presence of stressful life events such as intrafamilial life changes, and the presence of personality makeup such as the introverted, the lie, the repressed, or the feminine trends, the authors confirmed that dermatologists act as the primary care physician are in a unique position to recognize psychiatric comorbidity and execute meaningful intervention for female patients with the alopecia with psychiatrists.

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The Obligation of Return Unjust Enrichment or Compensation for the Use of Flight Safety Zone -Seoul High Court Judgment 2018Na2034474, decided on 2018. 10. 11.- (비행안전구역의 사용에 대한 부당이득반환·손실 보상 의무의 존부 -서울고등법원 2018. 10. 11. 선고 2018나2034474 판결-)

  • Kwon, Chang-Young;Park, Soo-Jin
    • The Korean Journal of Air & Space Law and Policy
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    • v.35 no.1
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    • pp.63-101
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    • 2020
  • 'Flight safety zone' means a zone that the Minister of National Defense designates under Articles 4 and 6 of the Protection of Military Bases and Installations Act (hereinafter 'PMBIA') for the safety of flight during takeoff and landing of military aircrafts. The purpose of flight safety zone is to contribute to the national security by providing necessary measures for the protection of military bases and installations and smooth conduct of military operations. In this case, when the state set and used the flight safety zone, the landowner claimed restitution of unjust enrichment against the country. This article is an analysis based on the existing legal theory regarding the legitimacy of plaintiff's claim, and the summary of the discussion is as follows. A person who without any legal ground derives a benefit from the property or services of another and thereby causes loss to the latter shall be bound to return such benefit (Article 741 of the Civil Act). Since the subject matter is an infringing profit, the defendant must prove that he has a legitimate right to retain the profit. The State reserves the right to use over the land designated as a flight safety zone in accordance with legitimate procedures established by the PMBIA for the safe takeoff and landing of military aircrafts. Therefore, it cannot be said that the State gained an unjust enrichment equivalent to the rent over the land without legal cause. Expropriation, use or restriction of private property from public necessity and compensation therefor shall be governed by Act: provided, that in such a case, just compensation shall be paid (Article 23 (1) of the Constitution of The Republic of KOREA). Since there is not any provision in the PMBIA for loss compensation for the case where a flight safety zone is set over land as in this case, next question would be whether or not it is unconstitutional. Even if it is designated as a flight safety zone and the use and profits of the land are limited, the justification of the purpose of the flight safety zone system, the appropriateness of the means, the minimization of infringement, and the balance of legal interests are still recognized; thus just not having any loss compensation clause does not make the act unconstitutional. In conclusion, plaintiff's claim for loss compensation based on the 'Act on Acquisition of and Compensation for land, etc. for Public Works Projects', which has no provision for loss compensation due to public limits, is unjust.

The Usefulness of Noninvasive Positive Pressure Ventilation in Patients With Acute Respiratory Failure after Extubation (기관내 관 제거 후 발생한 급성 호흡부전에서 비침습적 양압 환기법의 유용성)

  • Na, Joo-Ock;Lim, Chae-Man;Shim, Tae-Sun;Park, Joo-Hun;Lee, Ki-Man;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Koh, Youn-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.3
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    • pp.350-362
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    • 1999
  • Background: Acute Respiratory failure which is developed after extubation in the weaning process from mechanical ventilation is an important cause of weaning failure. Once it was developed, endotracheal reintubation has been done for respiratory support. Noninvasive Positive Pressure Ventilation (NIPPV) has been used in the management of acute or chronic respiratory failure, as an alternative to endotracheal intubation, using via nasal or facial mask. In this study, we evaluated the usefulness of NIPPV as an alternative method of reintubation in patients who developed acute respiratory failure after extubation. Method: We retrospectively analyzed thirty one patients(eighteen males and thirteen females, mean ages $63\pm13.2$ years) who were developed acute respiratory failure within forty eight hours after extubation, or were extubated unintentionally at medical intensive care unit(MICU) of Asan Medical Center. NIPPV was applied to the patients. Ventilatory mode of NIPPV, level of ventilatory support and inspiratory oxygen concentration were adjusted according to the patient condition and results of blood gas analysis by the attending doctors at MICU. NIPPV was completely weaned when the patients maintained stable clinical condition under 8 $cmH_2O$ of pressure support level. Weaning success was defined as maintenance of stable spontaneous breathing more than forty eight hours after discontinuation of NIPPV. Respiratory rate, heart rate, arterial blood gas analysis, level of pressure support, and level of PEEP were monitored just before extubation, at thirty minutes, six hours, twenty four hours after initiation of NIPPV. They were also measured at just before weaning from NIPPV in success group, and just before reintubation in failure group. Results: NIPPV was successfully applied to thirty-one patients of thirty-two trials and one patient could not tolerated NIPPV longer than thirty minutes. Endotracheal reintubation was successfully obviated in fourteen patients (45%) among them. There was no difference in age, sex, APACHE III score on admission at MICU, duration of intubation, interval from extubation to initiation of NIPPV, baseline heart rate, respiratory rate, arterial blood gas, and $PaO_2/FiO_2$ between the success and the failure group. Heart rate and respiration rate were significantly decreased with increase $SaO_2$ after thirty minutes of NIPPV in both groups(p<0.05). However, in the patients of failure group, heart rate and respiratory rate were increased again with decrease in $SaO_2$ leading to endotracheal reintubation. The success rate of NIPPV treatment was significantly higher in the patients with COPD compared to other diseases(62% vs 39%) (p=0.007). The causes of failure were deterioration of arterial blood gas without aggravation of underlying disease(n=9), aggravation of undelying disease(n=5), mask intolerance(n=2), and retained airway secretion(n=l). Conclusion: NIPPV would be a useful therapeutic alternative which can avoid reintubation in patient who developed acute respiratory failure after extubation.

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The Research on Recommender for New Customers Using Collaborative Filtering and Social Network Analysis (협력필터링과 사회연결망을 이용한 신규고객 추천방법에 대한 연구)

  • Shin, Chang-Hoon;Lee, Ji-Won;Yang, Han-Na;Choi, Il Young
    • Journal of Intelligence and Information Systems
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    • v.18 no.4
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    • pp.19-42
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    • 2012
  • Consumer consumption patterns are shifting rapidly as buyers migrate from offline markets to e-commerce routes, such as shopping channels on TV and internet shopping malls. In the offline markets consumers go shopping, see the shopping items, and choose from them. Recently consumers tend towards buying at shopping sites free from time and place. However, as e-commerce markets continue to expand, customers are complaining that it is becoming a bigger hassle to shop online. In the online shopping, shoppers have very limited information on the products. The delivered products can be different from what they have wanted. This case results to purchase cancellation. Because these things happen frequently, they are likely to refer to the consumer reviews and companies should be concerned about consumer's voice. E-commerce is a very important marketing tool for suppliers. It can recommend products to customers and connect them directly with suppliers with just a click of a button. The recommender system is being studied in various ways. Some of the more prominent ones include recommendation based on best-seller and demographics, contents filtering, and collaborative filtering. However, these systems all share two weaknesses : they cannot recommend products to consumers on a personal level, and they cannot recommend products to new consumers with no buying history. To fix these problems, we can use the information which has been collected from the questionnaires about their demographics and preference ratings. But, consumers feel these questionnaires are a burden and are unlikely to provide correct information. This study investigates combining collaborative filtering with the centrality of social network analysis. This centrality measure provides the information to infer the preference of new consumers from the shopping history of existing and previous ones. While the past researches had focused on the existing consumers with similar shopping patterns, this study tried to improve the accuracy of recommendation with all shopping information, which included not only similar shopping patterns but also dissimilar ones. Data used in this study, Movie Lens' data, was made by Group Lens research Project Team at University of Minnesota to recommend movies with a collaborative filtering technique. This data was built from the questionnaires of 943 respondents which gave the information on the preference ratings on 1,684 movies. Total data of 100,000 was organized by time, with initial data of 50,000 being existing customers and the latter 50,000 being new customers. The proposed recommender system consists of three systems : [+] group recommender system, [-] group recommender system, and integrated recommender system. [+] group recommender system looks at customers with similar buying patterns as 'neighbors', whereas [-] group recommender system looks at customers with opposite buying patterns as 'contraries'. Integrated recommender system uses both of the aforementioned recommender systems to recommend movies that both recommender systems pick. The study of three systems allows us to find the most suitable recommender system that will optimize accuracy and customer satisfaction. Our analysis showed that integrated recommender system is the best solution among the three systems studied, followed by [-] group recommended system and [+] group recommender system. This result conforms to the intuition that the accuracy of recommendation can be improved using all the relevant information. We provided contour maps and graphs to easily compare the accuracy of each recommender system. Although we saw improvement on accuracy with the integrated recommender system, we must remember that this research is based on static data with no live customers. In other words, consumers did not see the movies actually recommended from the system. Also, this recommendation system may not work well with products other than movies. Thus, it is important to note that recommendation systems need particular calibration for specific product/customer types.

A Study Concerning Health Needs in Rural Korea (농촌(農村) 주민(住民)들의 의료필요도(醫療必要度)에 관(關)한 연구(硏究))

  • Lee, Sung-Kwan;Kim, Doo-Hie;Jung, Jong-Hak;Chunge, Keuk-Soo;Park, Sang-Bin;Choy, Chung-Hun;Heng, Sun-Ho;Rah, Jin-Hoon
    • Journal of Preventive Medicine and Public Health
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    • v.7 no.1
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    • pp.29-94
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    • 1974
  • Today most developed countries provide modern medical care for most of the population. The rural area is the more neglected area in the medical and health field. In public health, the philosophy is that medical care for in maintenance of health is a basic right of man; it should not be discriminated against racial, environmental or financial situations. The deficiency of the medical care system, cultural bias, economic development, and ignorance of the residents about health care brought about the shortage of medical personnel and facilities on the rural areas. Moreover, medical students and physicians have been taught less about rural health care than about urban health care. Medical care, therefore, is insufficient in terms of health care personnel/and facilities in rural areas. Under such a situation, there is growing concern about the health problems among the rural population. The findings presented in this report are useful measures of the major health problems and even more important, as a guide to planning for improved medical care systems. It is hoped that findings from this study will be useful to those responsible for improving the delivery of health service for the rural population. Objectives: -to determine the health status of the residents in the rural areas. -to assess the rural population's needs in terms of health and medical care. -to make recommendations concerning improvement in the delivery of health and medical care for the rural population. Procedures: For the sampling design, the ideal would be to sample according to the proportion of the composition age-groups. As the health problems would be different by group, the sample was divided into 10 different age-groups. If the sample were allocated by proportion of composition of each age group, some age groups would be too small to estimate the health problem. The sample size of each age-group population was 100 people/age-groups. Personal interviews were conducted by specially trained medical students. The interviews dealt at length with current health status, medical care problems, utilization of medical services, medical cost paid for medical care and attitudes toward health. In addition, more information was gained from the public health field, including environmental sanitation, maternal and child health, family planning, tuberculosis control, and dental health. The sample Sample size was one fourth of total population: 1,438 The aged 10-14 years showed the largest number of 254 and the aged under one year was the smallest number of 81. Participation in examination Examination sessions usually were held in the morning every Tuesday, Wenesday, and Thursday for 3 hours at each session at the Namchun Health station. In general, the rate of participation in medical examination was low especially in ages between 10-19 years old. The highest rate of participation among are groups was the under one year age-group by 100 percent. The lowest use rate as low as 3% of those in the age-groups 10-19 years who are attending junior and senior high school in Taegu city so the time was not convenient for them to recieve examinations. Among the over 20 years old group, the rate of participation of female was higher than that of males. The results are as follows: A. Publie health problems Population: The number of pre-school age group who required child health was 724, among them infants numbered 96. Number of eligible women aged 15-44 years was 1,279, and women with husband who need maternal health numbered 700. The age-group of 65 years or older was 201 needed more health care and 65 of them had disabilities. (Table 2). Environmental sanitation: Seventy-nine percent of the residents relied upon well water as a primary source of dringking water. Ninety-three percent of the drinking water supply was rated as unfited quality for drinking. More than 90% of latrines were unhygienic, in structure design and sanitation (Table 15). Maternal and child health: Maternal health Average number of pregnancies of eligible women was 4 times. There was almost no pre- and post-natal care. Pregnancy wastage Still births was 33 per 1,000 live births. Spontaneous abortion was 156 per 1,000 live births. Induced abortion was 137 per 1,000 live births. Delivery condition More than 90 percent of deliveries were conducted at home. Attendants at last delivery were laymen by 76% and delivery without attendants was 14%. The rate of non-sterilized scissors as an instrument used to cut the umbilical cord was as high as 54% and of sickles was 14%. The rate of difficult delivery counted for 3%. Maternal death rate estimates about 35 per 10,000 live births. Child health Consultation rate for child health was almost non existant. In general, vaccination rate of children was low; vaccination rates for children aged 0-5 years with BCG and small pox were 34 and 28 percent respectively. The rate of vaccination with DPT and Polio were 23 and 25% respectively but the rate of the complete three injections were as low as 5 and 3% respectively. The number of dead children was 280 per 1,000 living children. Infants death rate was 45 per 1,000 live births (Table 16), Family planning: Approval rate of married women for family planning was as high as 86%. The rate of experiences of contraception in the past was 51%. The current rate of contraception was 37%. Willingness to use contraception in the future was as high as 86% (Table 17). Tuberculosis control: Number of registration patients at the health center currently was 25. The number indicates one eighth of estimate number of tuberculosis in the area. Number of discharged cases in the past accounted for 79 which showed 50% of active cases when discharged time. Rate of complete treatment among reasons of discharge in the past as low as 28%. There needs to be a follow up observation of the discharged cases (Table 18). Dental problems: More than 50% of the total population have at least one or more dental problems. (Table 19) B. Medical care problems Incidence rate: 1. In one month Incidence rate of medical care problems during one month was 19.6 percent. Among these health problems which required rest at home were 11.8 percent. The estimated number of patients in the total population is 1,206. The health problems reported most frequently in interviews during one month are: GI trouble, respiratory disease, neuralgia, skin disease, and communicable disease-in that order, The rate of health problems by age groups was highest in the 1-4 age group and in the 60 years or over age group, the lowest rate was the 10-14 year age group. In general, 0-29 year age group except the 1-4 year age group was low incidence rate. After 30 years old the rate of health problems increases gradually with aging. Eighty-three percent of health problems that occured during one month were solved by primary medical care procedures. Seventeen percent of health problems needed secondary care. Days rested at home because of illness during one month were 0.7 days per interviewee and 8days per patient and it accounts for 2,161 days for the total productive population in the area. (Table 20) 2. In a year The incidence rate of medical care problems during a year was 74.8%, among them health problems which required rest at home was 37 percent. Estimated number of patients in the total population during a year was 4,600. The health problems that occured most frequently among the interviewees during a year were: Cold (30%), GI trouble (18), respiratory disease (11), anemia (10), diarrhea (10), neuralgia (10), parasite disease (9), ENT (7), skin (7), headache (7), trauma (4), communicable disease (3), and circulatory disease (3) -in that order. The rate of health problems by age groups was highest in the infants group, thereafter the rate decreased gradually until the age 15-19 year age group which showed the lowest, and then the rate increased gradually with aging. Eighty-seven percent of health problems during a year were solved by primary medical care. Thirteen percent of them needed secondary medical care procedures. Days rested at home because of illness during a year were 16 days per interviewee and 44 days per patient and it accounted for 57,335 days lost among productive age group in the area (Table 21). Among those given medical examination, the conditions observed most frequently were respiratory disease, GI trouble, parasite disease, neuralgia, skin disease, trauma, tuberculosis, anemia, chronic obstructive lung disease, eye disorders-in that order (Table 22). The main health problems required secondary medical care are as fellows: (previous page). Utilization of medical care (treatment) The rate of treatment by various medical facilities for all health problems during one month was 73 percent. The rate of receiving of medical care of those who have health problems which required rest at home was 52% while the rate of those who have health problems which did not required rest was 61 percent (Table 23). The rate of receiving of medical care for all health problems during a year was 67 percent. The rate of receiving of medical care of those who have health problems which required rest at home was 82 percent while the rate of those who have health problems which did not required rest was as low as 53 percent (Table 24). Types of medical facilitied used were as follows: Hospital and clinics: 32-35% Herb clinics: 9-10% Drugstore: 53-58% Hospitalization Rate of hospitalization was 1.7% and the estimate number of hospitalizations among the total population during a year will be 107 persons (Table 25). Medical cost: Average medical cost per person during one month and a year were 171 and 2,800 won respectively. Average medical cost per patient during one month and a year were 1,109 and 3,740 won respectively. Average cost per household during a year was 15,800 won (Table 26, 27). Solution measures for health and medical care problems in rural area: A. Health problems which could be solved by paramedical workers such as nurses, midwives and aid nurses etc. are as follows: 1. Improvement of environmental sanitation 2. MCH except medical care problems 3. Family planning except surgical intervention 4. Tuberculosis control except diagnosis and prescription 5. Dental care except operational intervention 6. Health education for residents for improvement of utilization of medical facilities and early diagnosis etc. B. Medical care problems 1. Eighty-five percent of health problems could be solved by primary care procedures by general practitioners. 2. Fifteen percent of health problems need secondary medical procedures by a specialist. C. Medical cost Concidering the economic situation in rural area the amount of 2,062 won per residents during a year will be burdensome, so financial assistance is needed gorvernment to solve health and medical care problems for rural people.

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Combined Effect of Ganciclovir and Vidarabine on the Replication, DNA Synthesis, and Gene Expression of Acyclovir-resistant Herpes Simplex Virus (Acyclovir저항성 Herpes Simplex Virus의 복제, DNA합성 및 형질 발현에 미치는 Ganciclovir 및 Vidarabine의 병용효과에 관한 연구)

  • Yang, Young-Tai;Cheong, Dong-Kyun;Mori, Masakazu
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.115-134
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    • 1989
  • Combined effects of ganciclovir (GCV) and vidarabine (ara-A) on the replication, DNA synthesis, and gene expression of wild type-1 herpes simplex virus (HSV-1) and three acyclovir (ACV)-resistant HSV-1 mutants were studied. These mutants include a virus expressing no thymidine kinase $(ACV^r)$, a virus expressing thymidine kinase with altered substrate specificity $(IUdR^r)$, and a mutant expressing altered DNA polymerase $(PAA^r5)$. GCV, an agent activated by herpesvirus specific thymidine kinase, showed potent antiviral activity against the wild type HSV-1(KOS) and DNA polymerase mutant $(PAA^r5)$. The ACV-resistant mutants with thymidine kinase gene $(ACV^r\;and\;IUdR^r)$ were resistant to GCV. All tested wild type HSV-1 or ACV-resistant HSV-1 mutants did not display resistance to vidarabine (are-A). Combined GCV and ara-A showed potentiating synergistic antiviral activity against wild type KOS and $PAA^r5$, and showed subadditive combnined ativiral activity against thymidine kinase mutants. Combined GCV and ara-A more significantly inhibited the viral DNA synthesis in wild type KOS and $PAA^r5-infected$ cells to a greater extent than either agent alone, but the synergism was not determined in $ACV^r$ or $IUdR^r-infected$ cells. These data clearly indicate that combined GCV and ara-A therapy might be useful for the treatment of infections caused by wild type HSV-1 or ACV-resistant HSV-1 with DNA polymerase mutation. ACV-resistant viruses with the mutation in thymidine kinase gene are also, resistant to GCV, but susecptible to ara-A, indicating that ara-A would the drug of choice for the treatment of ACV-resistant HSV-1 which does not express thymidine kinase or expresses thymidine kinase with altered substrate specificity. While the synthesis of viral ${\alpha}-proteins$ of wild type HSV-1 was not affected by ACV, GCV, ara-A, or combined GCV and ara-A, the synthesis of ${\beta}-proteins$ was slightly but significantly increased at the later stage of viral infection by the antiviral agents. The synthesis of ${\gamma}-proteins$ of wild type HSV- 1 was significantly inhibited by ACV, GCV, ara-A, and combined GCV and ara-A. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ also significantly altered the expression of viral ${\beta}-and$ ${\gamma}-proteins$, of which efffct was similar to that of GCV $(10-{\mu}M)$ alone. Although ACV at the concentration of $10-{\mu}M$ did not alter the expression of ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ of ACV-resistant $PAA^r5$, GCV and ara-A significantly alter the epression of ${\beta}-and$ ${\gamma}-proteins$, not ${\alpha}-protein$, as same manner as they altered the expression of those proteins in cells inffcted with wild type HSV-1. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ altered the expression ${\beta}-and$ ${\gamma}-proteins$ in $PAA^r5$ infected cells, and the effect of combined regimen was comparable of that of GCV $(10-{\mu}M)$. These data indicate that the alteration in the expression of ${\beta}-and$ ${\gamma}-proteins$ in wild type HSV-1 or $PAA^r5$ infected cells could be more significantly affected by combined GCV and are-A than individual GCV or ara-A. In view of the fact that (a) viral ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ are synthesized in a cascade manner; (b) ${\beta}-proteins$ are essential for the synthesis of viral DNA; (c) the synthesis of ${\beta}-proteins$ are inhibited by ${\gamma}-proteins$; and (d) most ${\gamma}-proteins$ are made from the newly synthesized progeny virus, it is suggested that GCV and ara-A, alone or in combination, primarily inhibit the synthesis of viral DNA, and by doing so might exhibit their antiherpetic activity. The alteration in viral protein synthesis in the presence of tested antiviral agents could result from the alteration in viral DNA synthesis. From the present study, it can be concluded that (a) combined GCV and ara-A therapy would be beneficial for the control of inffctions caused by wild type HSV-1 or ACV-resistant DNA polymerase mutants; (b) the combined synergistic activity of GCV and ara-A is due to further decrease in the viral DNA by the combined regimen; (c) ara-A is the drug of choice for the infection caused by ACV-resistant HSV-1 with thymidine kinase mutation; and (d) the alteration in viral protein synthesis by GCV and ars-A, alone or in combination, is mostly due to the decreased synthesis of viral DAN.

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