In Situ Cross-Linkable Hydrogels as a Dynamic Matrix for Tissue Regenerative Medicine

BACKGROUND: Polymeric hydrogels are extensively used as promising biomaterials in a broad range of biomedical applications, including tissue engineering, regenerative medicine, and drug delivery. These materials have advantages such as structural similarity to the native extracellular matrix (ECM), multi-tunable physicochemical and biological properties, and biocompatibility. METHODS: In situ forming hydrogels show a phase transition from a solution to a gel state through various physical and chemical cross-linking reactions. These advanced hydrogel materials have been widely used for tissue regenerative medicine because of the ease of encapsulating therapeutic agents, such as cells, drugs, proteins, and genes. RESULTS: With advances in biomaterials engineering, these hydrogel materials have been utilized as either artificial cellular microenvironments to create engineered tissue constructs or as bioactive acellular matrices to stimulate the native ECM for enhanced tissue regeneration and restoration. CONCLUSION: In this review, we discuss the use of in situ cross-linkable hydrogels in tissue engineering and regenerative medicine applications. In particular, we focus on emerging technologies as a powerful therapeutic tool for tissue regenerative medicine applications.

Adenovirus adenine nucleotide translocator-2 shRNA effectively induces apoptosis and enhances chemosensitivity by the down-regulation of ABCG2 in breast cancer stem-like cells

Cancer stem cells (CSCs) are resistant to chemo- and radio-therapy, and can survive to regenerate new tumors. This is an important reason why various anti-cancer therapies often fail to completely control tumors, although they kill and eliminate the bulk of cancer cells. In this study, we determined whether or not adenine nucleotide translocator-2 (ANT2) suppression could also be effective in inducing cell death of breast cancer stem-like cells. A sub-population (SP; CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. We utilized the adeno-ANT2 shRNA virus to inhibit ANT2 expression and then observed the treatment effect in a SP of breast cancer cell line. In this study, MCF7, MDA-MB-231 cells, and breast epithelial cells (MCF10A) mesenchymally-transdifferentiated through E-cadherin knockdown were used. ANT2 expression was high in both stem-like cells and non-stem-like cells of MCF7 and MDA-MB-231 cells, and was induced and up-regulated by mesenchymal transdifferentiation in MCF10A cells (MCF10AEMT). Knockdown of ANT2 by adeno-shRNA virus efficiently induced apoptotic cell death in the stem-like cells of MCF7 and MDA-MB-231 cells, and MCF10AEMT. Stem-like cells of MCF7 and MDA-MB-231, and MCF10AEMT cells exhibited increased drug (doxorubicin) resistance, and expressed a multi-drug resistant related molecule, ABCG2, at a high level. Adeno-ANT2 shRNA virus markedly sensitized the stem-like cells of MCF7 and MDA-MB-231, and the MCF10AEMT cells to doxorubicin, which was accompanied by down-regulation of ABCG2. Our results suggest that ANT2 suppression by adeno-shRNA virus is an effective strategy to induce cell death and increase the chemosensitivity of stem-like cells in breast cancer.

A Nationwide Survey on the Hand Washing Behavior and Awareness / 예방의학회지

OBJECTIVES: This study was conducted to evaluate the public's awareness of the importance of hand washing and to compare perceptions on the habit of hand washing with actual hand washing behavior. METHODS: Data were collected by observing 2,800 participants washing their hands after using public restrooms in seven cities nationwide and by surveying 1,000 respondents (age > 14 years) through telephone interviews using a structured questionnaire. RESULTS: Although 94% of the survey respondents claimed to mostly or always wash their hands after using public restrooms, only 63.4% of the observed participants did wash their hands after using public restrooms. Significant factors related to increased adherence to hand washing were female gender, approximate ages of 20 to 39 years by their appearance, and the presence of other people from the observation. About 79% of the survey respondents always washed their hands after using bathrooms at home, 73% washed their hands before handling food, and 67% washed their hands upon returning to their home. However, 93.2% and 86.3% of the survey respondents did not wash their hands after coughing or sneezing and after handling money, respectively. Although most of the survey respondents (77.6%) were aware that hand washing is helpful in preventing communicable diseases, 39.6% of the survey respondents did not do so because they were 'not accustomed' to washing their hands and 30.2% thought that washing their hands is 'annoying'. CONCLUSIONS: This is the first comprehensive report on hand washing behavior and awareness of the general population in Korea. The result of this study in terms of individual behavior and awareness of hand washing are comparable with similar studies conducted in other countries. However adherence to hand washing is still low and needs to be increased. The results of this study can be used as a baseline in setting up strategies and activities to Bpromote adherence to hand washing.

Reemerging vivax malaria: changing patterns of annual incidence and control programs in the Republic of Korea

Changing patterns of the reemerging Plasmodium vivax malaria in the Republic of Korea (South Korea) during the period 1993 to 2005 are briefly analyzed with emphasis on the control measures used and the effects of meteorological and entomological factors. Data were obtained from the Communicable Diseases Monthly Reports published by the Korea Center for Disease Control and Prevention, and webpages of World Health Organization and United Nations. Meteorological data of Kangwon-do (Province) were obtained from local weather stations. After its first reemergence in 1993, the prevalence of malaria increased exponentially, peaking in 2000, and then decreased. In total, 21,419 cases were reported between 1993 and 2005 in South Korea. In North Korea, a total of 916,225 cases were reported between 1999 and 2004. The occurrence of malaria in high risk areas of South Korea was significantly (P<0.05) correlated with the mosquito population but not with temperature and rainfall. Control programs, including early case detection and treatment, mass chemoprophylaxis of soldiers, and international financial aids to North Korea for malaria control have been instituted. The situation of the reemerging vivax malaria in the Republic of Korea is remarkably improving during the recent years, at least in part, due to the control activities undertaken in South and North Korea.

Introduction of zoonses in Korea / 한국역학회지

Many new human pathogens that have emerged or reemerged worldwide originated from animals or from products of animal origin. Many animal species as well as categories of agents have been involved in the emergence of diseases. Nearly all of these emergent disease episodes have involved zoonotic infectious agents; that is, they have involved the transmission of the etiologic agent to humans from an ongoing reservoir life cycle in animals or arthropods. Control of zooneses depends on attempts to reduce vector populations of limit contact with reservior species. But in most instances, the control efforts require environmental or human behavioral modification in addition to direct efforts at vector population reduction. We described the general ecological characteristics of zoonses and epidemiologic features of 7 important zoonoses in Korea-anthrax, brucellosis, rabies, E. coli O157 infection, japanese B encephalitis, bovine spongiform encephalitis and variant Creutzfelt-Jacob diseases, and high pathogenic avian influenza. We have made some suggestions in this article. First the network of medical field and veterinary field(including experts and governmental organization) should be systematically organized in zoonosis surveillance, epidemic investigation, outbreak control and so forth. Second, we should practically prepare the new emerging epidemics-including pandemic and bioterrorism in connection with zoonoses control. Third, we need ecological and epidemiological basic studies on zoonoses in Korea, and finally, the zoonoses control policy should be connected food safety.

Revision of International Health Regulation and Task of Improving Communicable Disease Control and Quarantine System in the Republic of Korea

No abstract available.

Possibility of Novel Influenza Pandemic and Preparedness Plan

No abstract available.

Development of New Coronary Stent-Grafts using Surface-Modified Polymers

BACKGROUND AND OBJECTIVE: The purpose of this study was to develop a new type of coronary stent-graft, using surface modification of polymeric synthetic graft materials, to improve biocompatibility. MATERIALS AND METHODS: Three different polymers, Dacron, GoreTex and Teflon were tested. During the surface-modification process, hydroxybutyl acrylate (HBA) choline, an excellent blood-compatible phospholipid, was stably grafted onto the polymer surface. The optimal conditions for maximizing the amount of HBA choline grafted onto the polymeric surface were determined by quantitative analysis. The surface-modified polymers were then tested for their biocompatibility using an in vitro platelet adhesion test. Thereafter, stent-grafts were constructed with each of three different types of surface-modified polymer and implanted in porcine coronary arteries to compare their biocompatibility in vivo. RESULTS: In the platelet adhesion test, all the surface-modified polymers showed better biocompatibility than the control polymers. The in vitro biocompatibility correlated positively with the increasing quantity of grafted HBA choline. In the animal experiment, the surface-modified Teflon stent-graft showed the best biocompatibility. Whereas, all pigs implanted with the modified Dacron and GoreTex stent-grafts died within 48 hours of the implantation, five out of the six pigs with the Teflon stent-grafts remained alive at after the 4th week. In four of the five surviving pigs, angiography, intravascular ultrasound (IVUS) and histological evaluations demonstrated the patency of the stent-grafts, with a uniform neointima formation covering the entire stent-graft, without stent thrombosis or chronic inflammatory cells. CONCLUSION: The surface-modified Teflon coronary stent-grafts showed good in vitro and in vivo biocompatibility. Further animal and clinical studies will be required to validate the efficacy of the surface-modified polymer stent-grafts.

A Study on the Potential of Hydroxyapatite Based Bioactive Bone Cement / 대한정형외과연구학회지

Study on the Potential of Hydroxapatite Based Bioactive Bone Cement PURPOSE: The purpose of this study is to propose a new bioactive bone cement (BBC) composed of bone powder (hydroxyapatite; HA), chitosan powder, and currently available polymethylmethacrylate (PMMA) bone cement for use in orthopaedic surgeries such as vertebroplasty or bone filler. MATERIALS AND METHODS: Three types of proposed BBCs and a currently available commercial PMMA were tested. In vitro studies the surface morphology, chemical composition, changes in pH value along the time, exothermic temperatures, intrusion and cellular responses were investigated. SEM, radiological and histological examinations were performed in animal studies. RESULTS: The major components of BBCs were C, O, Ca, P, Cl, Si, S, Ba and Mg. The pH values in BBCs decreased after 1 day, however they eventually reached 7.2-7.4. The water absorbency, weight loss, and porosity in BBCs increased more than PMMA more than during degradation (p<0.05). However, the compressive Young's moduli and ultimate compressive strength (UCS) of BBCs were lower than those of PMMA (<0.05). The exothermic temperatures of the BBCs were considerably lower than that of PMMA (p<0.05). In view of setting time, it takes relatively longer for BBCII and III to be solidified than PMMA (p<0.05). The intrusion tests showed that the BBCs were more intrusive than PMMA (p<0.05). The cell proliferation test on BBCII showed that the BBCII was more preferable than the PMMA. No cytotoxic characteristics were found in all BBCs. In the animal test, BBC II was more biocompatible as well as osteoconductible than the PMMA. CONCLUSION: The results of in vitro and animal studies indicated that the proposed BBCs have a potential of clinical application as replacement of the current PMMA bone cements.

The Biomechanical Responses of Intervertebral Disc due to Degenerative Change in Porcine Lumbar Spine / 대한정형외과연구학회지

PURPOSE: The biomechanical responses of degenerative porcine intervertebral disc were compared with those MATERIALS AND METHODS: Two groups were set; Group A (44.0+/-2.8 months old, female) and Group B (6.2 +/-1.3 months old, female). Histological (H&E stain) observations were carried out to see the degeneration for both groups. Then biomechanical responses were investigated by measuring height changes in disc, intradiscal pressure values and relaxation time for each specimen under axial compressive loads. RESULTS: Degenerative changes were confirmed through H&E staining in Group A. The ratios of the nucleus pulposus area to total area were 14.7+/-4.5% and 29.2+/-6.0% in Group A and B, respectively (p=0.000). The decrease rates in disc height were 12.1+/-3.3% and 21.6+/-7.6%, in Group A and B, respectively under the axial compression of 740 N (p=0.000). No significant difference in intradiscal pressure measured in anterior zone between-groups except at axial load of 740N (p> 0.05). However, significant difference in pressure was found in posterolateral zone when the load was 542 N and higher (542 N: p=0.015, 740 N: p=0.010). The average relaxation time for Group A was significantly longer than that for Group B at 740N, i.e., at maximum load (anterior: p=0.010, posterolateral: p=0.014). CONCLUSION: Different biomechanical responses in degenerative disc were confirmed. They are 1) less flexible, 2) slower in energy relaxation under axial loading, and 3) larger portion of the external load were taken up at posterior part of annulus fibrous, especially in degenerative disc.

Primary Care Physician in Korea

No abstract available.

Tuberculosis Management of Private Health Care Institution: Current Situation and Task / 결핵

Since the inception of the National Tuberculosis Control Program in 1962, the incidence of tuberculosis and its associated mortality has declined dramatically due to effective anti-tuberculosis drugs and a systematic control program. The prevalence of radiographically active tuberculosis has fallen from 5.1% in 1965 to 1.0 in 1995.However, tuberculosis is still a major problem, as the mortality rate is still higher compared to other developed countries. Furthermore, tuberculosis is currently re-emerging in HIV/AIDS epidemic countries.In order to lower the tuberculosis death rate to the levels of developed countries, the tuberculosis control efforts in private healthcare institutions and the national tuberculosis control program in the public sector, need to work together more effectively adn efficiently.In this paper, the quthor reviewed te current situation regarding tuberculosis management in private healthcare institutions of Korea based on the literature and the National Health Insurance Claim data, and the future tasks of tuberculosis management are suggested.

Tuberculosis Management of Private Health Care Institution: Current Situation and Task / 결핵

Since the inception of the National Tuberculosis Control Program in 1962, the incidence of tuberculosis and its associated mortality has declined dramatically due to effective anti-tuberculosis drugs and a systematic control program. The prevalence of radiographically active tuberculosis has fallen from 5.1% in 1965 to 1.0 in 1995.However, tuberculosis is still a major problem, as the mortality rate is still higher compared to other developed countries. Furthermore, tuberculosis is currently re-emerging in HIV/AIDS epidemic countries.In order to lower the tuberculosis death rate to the levels of developed countries, the tuberculosis control efforts in private healthcare institutions and the national tuberculosis control program in the public sector, need to work together more effectively adn efficiently.In this paper, the quthor reviewed te current situation regarding tuberculosis management in private healthcare institutions of Korea based on the literature and the National Health Insurance Claim data, and the future tasks of tuberculosis management are suggested.

Study for the Ureteral Reconstruction with Tissue Engineering Using Poly (glycolide/epsilon-caprolactone) Scaffold-1 / 대한비뇨기과학회지

PURPOSE: Transplantation is one modality saving human life. But not only lack of the living or cadaveric human organs but also immunologic problems or some ethical situations limit transplantation in terminal stage patients. Recent research for escaping from those problems resulted in the reconstruction of the artificial organ using patients' own cells with tissue engineering. The goal of this study is, for the better reconstruction of urinary system using tissue engineering, to perform basic researches on techniques related with seeding and viability of cells. MATERIALS AND METHODS: We used 16 adult dogs, 4 female and 12 male, for primary culture of the dog bladder mucosal cell and muscle cell. The scaffold we used was made of absorbable substance polyglycolide/epsilon-caprolactone (GL/CL) in thin sponge like shape. Fibroblast 3T3 cell was used for control and 16 primary cultured mucosal cell and smooth muscle cells were used. For dynamic culture, rocker was adapted with for 5 hours. Attached cells were evaluated by 562nm ELISA reader using BCA method and scanning electron microscope. RESULTS: Successful primary culture was achieved with cells from dog bladder, and results were much better by using male dog. The dynamic culture increased attachment of the cell in scaffold and the cell attached at deeper portion of the scaffold. Long term culture showed formation of the cellular sheets on the surface of scaffold preventing inner passage of the suggesting disadvantageous condition for cells in core of the scaffold. CONCLUSIONS: We conclude that for the better attachment of the cultured cells on scaffolds, dynamic culture would be desirable. And for the better in vivo reconstruction of the organ with primary cultured cell attached scaffold, evaluation of culture state with repeated in vitro experiments are necessary.

Tissue engineering of urinary organs

Tissue engineering can serve as an alternative treatment for a malfunctioning or lost organ. Isolated and expanded cells adhere to a temporary scaffold, proliferate, and secrete their own extracellular matrices (ECM) replacing the biodegrading scaffold. The genitourinary system, composed of the kidney, ureter, bladder, urethra, and genital organs, is exposed to a variety of possible injury sites from the time of fetal development. All the urinary organs are mainly composed of smooth muscle and uroepithelial cells and which may be approached by tissue engineering techniques. A large number of materials, including naturally-derived and synthetic polymers have been utilized to fabricate prostheses for the genitourinary system. Usually, whenever there is a lack of native urologic tissue, reconstruction is considered with native non-urologic tissue, such as, gastrointestinal segments, or skin or mucosa from multiple body sites. Engineering tissues using selective cell transplantation may provide a means to create functional new genitourinary tissues. This review concerns urinary tissues reconstructed with bladder uroepithelial cells and smooth muscle cells (SMCs) implanted on biodegradable polymer matrices.

Effect of Poly Ethylene GlycolPEGGraft Polymerization onto Polymethy lmethacrylatePMMAon Cultured Keratocyte Adhesion

In this study, the effect of surface modification of polymethylmethacry-late[PMMA]by grafting of poly[ethylene glycol][PEG]on cell adhesion was investigated. PMMA surface was treated with ozone and then PEG-acry-late[PEGA]was graft-polymerized. Ozone treatment of the surface was car-ried out at room temperature by applying constant flow of oxygen[4.5liter/min]and 1 bar pressure. After ozone treatment, PMMA was immersed immediately in 20 wt%aq. PEG-acrylate solutions in glass ampoules. After degassing, the ampoule was sealed and kept at 60 degrees C for 24 hours to complete the graft polymerization. PMMA surface grafted with PEG revealed the enhanced oxygen content at ESCA analysis and the decreased dynamic receding contact angles. The adhesion of keratocytes onto modified PMMA was investigated. Keratocytes[4 x105cells/milliliter ]were layered on each PMMA discs which were glued to the bottom of 24-well culture plates, and cultured in a CO2 incubator for 24 hours. The adherent cells onto the surfaces were harvested by trypsinization and counted. The mean numbers of keratocytes on untreated PMMA, PEG-grafted PMMA with 1hour ozone treatment and PEG-grafted PMMA with 2 hour were 72.5 x104 and 6.5 x104 and 7.6 x104cells respectively, and there was a significant statistical difference [p=0.002], irrespective of ozone treatment period. This result suggests that surface modification of PMMA using PEG grafting may reduce etroprosthetic membrane formation of artificial cornea.

Serological Immunity to Diphtheria among Korean Population / 감염

BACKGROUND: Diphtheria epidemics in Russia have spread to all the other independent states of the former Soviet Union and East European countries around 1990s. One of the most important measures in preventing diphtheria is to maintain high levels of immunity in the population. We studied the diphtheria antibody levels of 1,086 participants to investigate herd immunity in Korea. METHODS: The tested 1,086 serum specimens were collected from healthy individuals from September 1995 to March 1996. Diphtheria antitoxin titers were measured by a micro cell culture method using Vero cells. Antibody titer of 0.01 IU/ml to neutralize diphtheria toxin is an internationally accepted protective level. RESULTS: We studied the diphtheria antitoxin titer levels of 1,086 cases consisting of 579 males and 507 females. The proportion of protective antitoxin level to diphtheria is 69.2%. Diphtheria antitoxin levels showed no significant difference between males and females. The highest seropositive rate was observed in the 5 to 9-year old age group(95.8%). The seropositivity rate declined with age. The lowest seropositive rate was observed in the 20~39 years of age, maximally 43.4 %. Over 40 years of age, the seropositive rates increased again. CONCLUSION: The antibody titers in the Korean population declined from 95.8% to below 50% with age in the 1~39 year-old age group. To maintain the rate of population with protective antibodies to diphtheria, we recommend Td booster immunization to adults with low antitoxin titers and continuous survey for antitoxin titers.

Estimation of Disease Code Accuracy of National Medical Insurance Data and the Related Factors / 예방의학회지

This study was undertaken in order to estimate the accuracy of disease code of the Korean National Medical Insurance Data and disease the characteristics related to the accuracy. To accomplish these objectives, 2,431 cases coded as notifiable acute communicable diseases (NACD) were randomly selected from 1994 National Medical Insurance data file and family medicine specialists reviewed the medical records to confirm the diagnostic accuracy and investigate the related factors. Major findings obtained from this study are as follows: 1. The accuracy rate of disease code of NACD in National Medical Insurance data was very low, 10.1% (95% C.I.: 8.8-11.4). 2. The reasons of inaccuracy in disease code were 1) claiming process related administrative error by physician and non-physician personnel in medical institutions (47.0%), 2) input error of claims data by key punchers of National Medical Insurer (31.3%) and 3) diagnostic error by physicians (21.7%). 3. Characteristics significantly related with lowering the accuracy of disease code were location and level of the medical institutions in multiple logistic regression analysis. Medical institutions in Seoul showed lower accuracy than those in Kyonngi, and so did general hospitals, hospitals and clinics than tertiary hospitals. Physician related characteristics significantly lowering disease code accuracy of insurance data were sex, age group and specialty. Male physicians showed significantly lower accuracy than female physicians; thirties and forties age group also showed significantly lower accuracy than twenties, and so did general physicians and other specialists than internal medicine/pediatric specialists. This study strongly suggests that a series of policies like 1) establishment of peer review organization of National Medical Insurance data, 2) prompt nation-wide expansion of computerized claiming network of National Medical Insurance and 3) establishment and distribution of objective diagnostic criteria to physicians are necessary to set up a national disease surveillance system utilizing National Medical Insurance claims data.

The amendment tendency analysis of the Korean Infectious Disease Prevention Act and a recommendation for the next amendment / 예방의학회지

This Study has been carried out to make a recommendation for the next amendment of the Infectious Disease Prevention Act with a specific focus on the kind of notifiable disease. Korean, Japanese, German, U.S, English and French acts on infectious diseases prevention were reviewed, compared with and analyzed in regards of numbers and kinds of notifiable infectious diseases and their tendency of amendments. An criteria was designed to assess the level of validity of diseases to be designated in the act. Four items, the fatality (greater than 10% or not), the possibility to make a big epidemic, the availability of efficient vaccination and the usefulness of isolation, are used in the assessment. This index is applied to the diseases in Korean and other countries' Infectious Disease Prevention Acts. Results are as follows : 1. The Korean Infectious Disease Prevention Act has a unique way of classifying the notifiable infectious disease, that is, the first, the second and the third class. But the author cannot find the basis of classification. No other countries reviewed have the similar classification. 2. The ten diseases, cholera, plague, yellow fever, diphtheria, typhoid fever, poliomyelitis, rabies, tetanus, malaria, and meningococcal meningitis are designated as the notifiable diseases not only in Korea but also in Japan, Germany, United States, England and France. 3. Thirty seven diseases including small pox, Lassa fever, anthrax, influenza, German measles, Legionellosis, infection with E. coli O157:H7, Q-fever, brucellosis, Lyme disease are designated as legal disease at least one of the above mentioned countries. 4. The Korea has been coped with the change of the infectious disease occurrence for last fifty years in amendment of the Infectious Disease Prevention Act. 5. Japan has a special infectious surveillance system composed of 3,880 clinics throughout the whole country. 6. Germany has classified infectious diseases in five categories which are based on seriousness of disease. Any confirmed death, cases and suspected cases in class I should be reported within 24 hours. But only confirmed death and cases in class II, but not suspected cases, are repotable in Germany. 7. Plague, bacillary dysentery, pertussis, mumps, Japanese encephaltis and Korean hemorrhagic fevers are diseases with high credits validity index among Korean legal disease. 8. German measles, anthrax, E. coli O157:H7 infection, Lassa fever, Q-fever, brucellosis are high in validity index among those which are not designated in Korea but designated in other countries. In conclusion, the Korean Infectious Disease Prevention Act has well been coped with the changes of infectious disease occurrence for last fifty years, but the classification basis and the validity of diseases to be designated as legal diseases is worth reevaluating.