Park, Kyung Min;Kim, Won Mi;Ahn, Su Hyun;Lee, Ha Lim;Hwang, Su Hyeon;Lee, Wonwoong;Hong, Jongki
Analytical Science and Technology
/
v.35
no.3
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pp.93-115
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2022
Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.
Kim, Jee-Hwan;Yoon, Chol-Wook;Kim, Taehyeon;Kim, Han-Sung;Woo, Dae-Gon;Lee, Keun-Woo;Shim, June-Sung
The Journal of Korean Academy of Prosthodontics
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v.52
no.4
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pp.305-311
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2014
Purpose: When the full veneer crown was treated in the tooth with abfraction lesion due to various causes, the prognosis of it may be compromised according to the location of the finish line, but there is few study about the location of its buccal finish line. The purpose of this study was to investigate the effect of location of the finish line of the full veneer crown on stress distribution of the tooth with abfraction lesion. Materials and methods: The two dimensional finite element model was developed to express tooth, surrounding tissue and full veneer crown. The stress distribution under eccentric 144 N occlusal load was analyzed using finite element analysis. The location of finish line was set just at the lower border of the lesion (Group 0), 1 mm (Group 1) and 2 mm (Group 2) below the lower border of the lesion. Results: In the Group 0, von Mises stress was concentrated at the finish line and the apex of the lesion. Also, the stress at the bucal finish line propagated to the lingual side. In the Group 1 and Group 2, stress distribution was similar each other. Stress was concentrated at the apex of lesion, but the stress at the buccal finish line did not propagate to the lingual side. That implied decrease of the possibility of horizontal crown fracture. Conclusion: Full veneer crown alleviated the stress concentrated at the apex of the abfraction lesion, when the finish line of full veneer crown was set below the lower border of abfraction lesion.
An epidemiological survey was conducted to investigate fowl typhoid outbreaks in Kyungnam province of Korea. The causative agent, salmonella gallinarum was isolated from 68 chicken samples of tentatively diagnosed fowl typhoid cases occurred during the period from January 1996 to September 1999. Comparative studies were also carried out to evaluate the diagnostic methods for detection of S gallinam The results obtained were as follows; 1. Of the 68 cases of tentatively diagnosed fowl typhoid, 56 (82%) cases were determined as fowl typhoid by biochemical test and pathological findings. The other 12 (18%) cases were determined as paratyphoid. 2. Fowl typhoid outbreaks occur continuously all seasons in the year, however the incidence was remarkably increased from May to September. 3. The frequency of incidence of fowl typhoid in terms of regional distribution was relatively high in egg-laying hens facilities, and the mode of transmission is likely to be either egg-to-egg or lateral transfer by wild birds or rats. 4. All of 18 isolates from 56 cases were identified as S gallinarum by biochemical and serological test. 5. Antimicrobial drug susceptibility test against 18 isolates showed that the isolates were highly susceptible to ASH, CZ, CF and GM (above 90%), whereas those strains were 100% resistant to EM, NA and PC. 6. S gallinarum rfbS gene was targeted to be amplified by PCR for comparative detection of S gallinarum in the experimentally infected chickens. The amplified 720bp DNA fragment, which is specific in D serogroup strains of S enterica subspecies was confirmed by agarose gel electrophoresis. 7. A comparison made between fecal culture and PCR-method revealed that later-method was relatively higher in detection rate than that of former method for S gallinarum. 8. Comparison of currently applied methods, rapid serum agglutination test (RST) and microplate agglutination test (MAT), with experimentally infected chickens were made to evaluate sensitivity of detection by neutralizing antibody titration. Both methods detected neutralizing antibodies from the challenged chickens of 5 day post infection. However, positive reactions were determined after 7 and 9 days post infection by MAT and RST, respectively.
The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits with carbon tetrachloride-induced hepatic failure. The area under the plasma concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased in severe carbon tetrachloride-induced hepatic failure rabbits ($1364.54{\pm}382.07$ ng/ml$\cdot$hr) compared to that of normal rabbits ($567.52{\pm}141.88$ ng/ml$\cdot$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($803.1{\pm}208.81$ ng/ml$\cdot$hr). The volume of distribution (Vd) (6.25$\pm$1.56 L) and the elimination rate constant($\beta$) ($0.09{\pm}0.025{\;}hr^{-1}$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were significantly (p<0.05) decreased compared to those of normal rabbits ($11.65<{\pm}2.91$L, $0.12{\pm}0.030{\;}hr^{-1}$), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($9.46{\pm}2.37$ L, $0.10{\pm}0.026{\;}hr^{-1}$). Total body clearance ($CL_t$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($0.733{\pm}0.183$ L/hr/kg) was significantly (p<0.01) decreased compared to that of normal rabbits ($1.762{\pm}0.440$ L/hr/kg), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($1.245{\pm}0.311$ L/hr/kg). The half-life(t1/2) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($7.71{\pm}2.16$ hr) was significantly (p<0.05) increased compared to that of normal rabbits ($5.75{\pm}1.44$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($6.77{\pm}1.76$hr). This results could be due to inhibition of paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially metabolized in liver. The findings suggest that the dosage regimen of paclitaxel should be adjusted when the drug would be administered in patients with liver disorder in a clinical situation.
Poly(vinyl acetate) (PVAc) nanoparticles were synthesized in oil/water miniemulsion polymerization in the presence of low amount of hexadecane as a cosurfactant. The nanoparticles were tested to apply as a drug carrier. The shape of nanoparticles was observed by scanning electron microscopy, and the average particle size and size distribution were examined by particle size analyzer. Inclusion of antibiotic drugs into the nanoparticles was confirmed by CHO, C=O, and OH peak of FT-IR. Size of the nanoparticles were adjusted between 80∼300 nm by changing the homogenization rate and amount of cosurfactant and surfactant. The monomer droplets prepared by miniemulsion method using a cosurfactant were homogeneous and stable compared with those prepared by conventional emulsion polymerization. This might be occurred due to the prevention of Ostwald ripening and coalescence between droplets by using hexadecane as a cosurfactant.
Journal of the Korean association of regional geographers
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v.13
no.4
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pp.438-453
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2007
Oriental Medicine Shopping District in Kyungdong Market developed through moving the Jongro which has been the center of oriental medicine since Joseon dynasty period. This shopping district grows up as a wholesale center based on convenient traffics. In 1994, herb clinics are major industry. But in 2007 the number of herb clinics has been reduced, while drug stores have increased. And doctors' age becomes older. Oriental Medicine Shopping District in Kyungdong Market occupies the center-stage of medicinal stuff's distribution and approximately 70% of the stuff come from other parts of the country. The district seems to be developing and modernizing comparing to the past. But it is not true. In this paper, I explain this phenomenon as "inertia about place". Oriental Medicine Shopping District in Kyungdong Market is suffering, but it tries to raise itself as the biggest oriental medicine market and new tourist site for they are designated as Hanbang Special District.
Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.
The purpose of this study was to investigate the differences of histochemical characteristics in inflammatory fibrous gingival hyperplasia (FGH), phenytoin-induced gingival hyperplasia(PIGH), idiopathic gingival hyperplasia(IDGH) and control groups (healthy and inflammatory gingiva) by immunohistochemical method with various antibodies and histomorphological analysis. In immunohistochemical finding, antibodies to inflammatory cells (T/B lymphocytes, macrophages, other monocytes), proliferating cell nuclear antigen(PCNA), epidermal growth factor(EGF), factor VIII, and type I collagen were used. 1. The inflammatory infiltrates in FGH were less than those in inflammatory gingiva. The composition of inflammatory cells of PIGH was similar with that of FGH. IDGH showed a similar histologic findings with healthy gingival tissue. 2. In FGH, the number of fibroblasts and newly-formed collagen fibers was increased. No significant increase of fibroblasts and the dense accumulation of thick collagen fibers were seen in PIGH. The increase of fibroblasts and the dense accumulation of thick collagen were seen in IDGH. 3. PCNA-positive cells were localized mainly in the area accumulated with inflammatory cells and blood vessels, significantly increased in all hyperplastic tissue groups, and distributed evenly in IDGH. 4. The distribution of EGF were not observed in healthy gingiva but detected locally in area with confluent blood vessels,without significant difference between the other tissue groups. This results suggest that inflammation plays a significant role in inducing hyperplastic change of gingival tissue. While in DIGH, drug itself as well as inflammation seems to attribute to hyperplastic change.
Bivalve samples from 30 locations Korean coastal waters were analyzed to characterize the contamination with and distribution of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). The congeners of PBDE in 30 bivalve samples were analyzed by high resolution gas chromatography with a high resolution mass detector. The levels of PBDEs in bivalve samples ranged from 0.092 to 13.5 ng/g wet weight. These values for PBDEs concentrations in bivalves from Korea were higher than or comparable to available values for bivalves from other countries. In the congener profiles, BDE-47 (mean contribution=42.2%) was predominant, followed by BDE-99 (23.1%), BDE-100 (11.9%) and BDE-154 (3.5%). Among the OCs analyzed, $\Sigma$PCBs and $\Sigma$DDTs levels were highest, followed by $\Sigma$HCHs, $\Sigma$CHLs and HCB. The wet weight based $\Sigma$PCBs and $\Sigma$DDTs ranged from 0.28 ng/g to 19.4 ng/g, and from 0.19 ng/g to 4.86 ng/g, respectively. The $\Sigma$PCBs and $\Sigma$DDT slevels in bivalves along the entire Korean coast were lower than those of the USA, and below the Food and Drug Administration (USA. FDA) limits for fish and shell fish. However, the human health criteria and wild life criteria of the USA. Environmental Protection Agency (USA. EPA) were exceeded for DDE and $\Sigma$HCHs at most of the sampling points.
Harmful environment around school area have been increased with socio-economic development in Korea. Those entertainment facilities have caused a negative effect on the learning environment in many schools. As a result of increased entertainment harmful facilities in school area, the numbers of deviant behaviors such as drinking, smoking, substance abuse and sexual activity among junior high school students have been significantly increased. Given this situation, the aim of this study was to describe the distribution of the facilities; to access applied(experience) of the facilities according to students demographic variables; and to identify the relationship between use of the facilities and students risk health behaviors such as smoking, drinking, substance abuse and sexual activity. The field theory was used to study the relationship between the use of the facilities and risk health behaviors among students. A self-administered questionnaire survey was conducted in Korea. 2,114 junior and senior high school students(middle and high school students) were recruited by the method of proportional stratified random sampling from June to July 2000. Results indicated that: 1) The rates of using game centers, PC rooms, Song rooms and comic rooms were 78.3%, 75.6%, 71.6%, and 34.3% respectively. 2) High school students visited the entertainment facilities significantly more than middle school students(p〈0.001). 3) The rates of using facilities near schools were significantly associated with parents job(p〈0.05). 4) The rates of drinking, smoking, drug abuse, and sexual activity were 21.6%, 11.9%, 4.3% and 1.6% respectively. 5) Risk health behaviors such as smoking(p〈0.001) and drinking(p〈0.001), amount of smoking and drinking(p〈0.001) and sexual activity(p〈0.05) were associated with the experience of using the facilities. Those who had drinking experience were more likely to go the facilities than those without drinking experience. Also, those who were smoker had higher probability of going using the facilities than non-smokers.
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