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Hepatitis C virus (HCV) is the major cause of progressive liver disease such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Previously, we reported that a 29 nucleotide-long 2'-F pyrimidine modified RNA aptamer against the HCV nonstructural protein 5B efficiently inhibited HCV replication and suppressed HCV infectious virus particle formation in a cell culture system. In this study, we modified this aptamer through conjugation of cholesterol for in vivo availability. This cholesterol-conjugated aptamer (chol-aptamer) efficiently entered the cell and inhibited HCV RNA replication, without any alteration in gene expression profiling including innate immune response-related genes. Moreover, systemic administration of the chol-aptamer was well tolerated without any abnormalities in mice. To evaluate the pharmacokinetics of the chol-aptamer in vivo, dose proportionality, bioavailability, and pharmacokinetic parameters were evaluated by noncompartmental analyses in normal BALB/c mice. Population analysis was performed using nonlinear mixed effects modeling. Moreover, the pharmacokinetics of two different routes (intravenous, IV, versus intraperitoneal, IP) were compared. Cholesterol conjugation showed dose proportionality, extended the time that the aptamer was in the plasma, and enhanced aptamer exposure to the body. Noticeably, the IV route was more suitable than the IP route due to the chol-aptamer remaining in the plasma for a longer period of time.

Microemulsion propofol produced a high concentration of free propofol in the aqueous phase. For the applied dose range, microemulsion propofol showed nonlinear pharmacokinetics.

In the present study, the outbreak patterns of bovine brucellosis in Korea from 2000 to 2011 were analyzed to understand the epidemiological evolution of this disease in the country. A total of 85,521 brucella reactor animals were identified during 14,215 outbreaks over the 12-year study period. The number of bovine brucellosis cases increased after 2003 and peaked in 2006 before decreasing thereafter. The majority of the bovine brucellosis cases were Korean native cattle, Han Woo. The numbers of human brucellosis cases and cattle outbreaks increased and decreased in the same pattern. The correlation coefficient for human and bovine cases per year was 0.96 (95% confidence interval = 0.86~0.99; p < 10-3). The epidemiological characteristics of bovine brucellosis appeared to be affected by the intensity of eradication programs that mainly involved a test-and-slaughter policy. Findings from the present study were based on freely available statistics from web pages maintained by government agencies. This unlimited access to information demonstrates the usefulness of government statistics for continually monitoring the health of animal populations.

This study describes the epidemiology of hemorrhagic fever with renal syndrome (HFRS) in the past 10 yr (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) in Korea. During this period, a total of 3,953 HFRS patients and an average prevalence rate of 0.81 per 100,000 population were recorded, with a total of 40 fatal cases, corresponding to a case fatality rate of 1.01%. More HFRS cases were found in men than in women (57% vs 43%), and a higher prevalence rate of HFRS was observed in patients older than 40 yr (82.1%). The highest numbers of HFRS cases were found amongst farmers (35.6%). The majority of HFRS cases (71.3%) occurred in the last quarter of the calendar year (October to December). More HFRS cases occurred in the western part than in the eastern part of Korea (68.9% vs 31.1%). The incidence of HFRS was significantly higher (P < 0.001) in rural areas than in urban areas (80.3% vs 19.7%). HFRS still occurs commonly among men, in autumn, and in western rural area of Korea. http://dx.doi.org/10. 3346/jkms.2013.28.10.1552 • J Korean Med Sci 2013 28: 1552-1554 BRIEF COMMUNICATION Infectious Diseases, Microbiology & ParasitologyHantavirus infection induces 2 different diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), mainly in Korea, far east Russia, and China and in the United States, respectively (1, 2). The viruses are transmitted to humans by the inhalation of excreta of rodents infected with hantaviruses (3). HFRS was first recognized during the Korean War in the early 1950s, and although a hantavirus vaccine has been developed, the disease remains a serious problem in Asia and Europe (1, 4), and especially among soldiers in Korea (5, 6). A 2006 report describes HFRS epidemiology in endemic regions in Korea during a relatively short period, 1995-1998 (7); however, an updated epidemiological study is necessary to better understand the current status of HFRS in Korea. This study provides a comprehensive epidemiological overview of HFRS during the past decade in Korea.Raw data were utilized from the National Notifiable Disease Surveillance System (NNDSS) website of the Korean Center for (Table 1). The prevalence rate (PR) of HFRS per 100,000 population and case fatality rate (CFR) were estimated by the criteria established by the World Health Organization (WHO), and the upper and lower limits of the 95% confidence interval (CI) were calculated. Statistically significant differences between the epidemiological aspects were determined at P < 0.05 and P < 0.01 using the chi-square test or the paired t-test. The data analyses were carried out using the statistical system software included in Microsoft Excel 2007.As shown in Table 1, the HFRS cases were analyzed according to the PR, CFR, gender, age, and occupation of the infected individuals. There were a total of 3,953 HFRS patients with an average PR of 0.81 (95% CI, 0.79-0.85) per 100,000 population and a total of 40 fatal cases with a CFR of 1.01% (95% CI, 0.7-1.3). A significantly higher number (P <...

SUMMARY:In this study, we performed a retrospective, quantitative analysis of the epidemiological aspects and risk factors of Vibrio vulnificus infections in Korea from 2001 to 2010. In a total of 588 V. vulnificus infection cases (prevalence rate, 0.12 cases/100,000 persons), 285 were fatal (case-fatality rate [CFR], 48.5z). Males were more significantly infected by V. vulnificus than females (86.1z versus 13.9z; P º 0.01), and a higher incidence of V. vulnificus infections was observed in people aged more than 40 years (95.1z; P º 0.01). Moreover, most V. vulnificus infections occurred in the unemployed (42.0z; P º 0.01). The seasonal patterns of outbreaks revealed that most outbreaks occurred in June (early summer) throughout November (the end of autumn) (99.6z; P º 0.01), and significantly more outbreaks occurred in the southern part (65.3z) of the Korean peninsula compared with those in the northern (29.4z) and central (5.3z) parts (P º 0.01). In addition, the number of V. vulnificus infections was significantly higher in rural and coastal villages (69.9z) than in urban areas (30.1z) (P º 0.01). In conclusion, because of the rapid aggravation and high CFR of V. vulnificus infections, public health education should strongly recommend avoiding raw seafood products and limited exposure to marine water during the summer.Of all foodborne infectious diseases, Vibrio vulnificus infection is one of the most severe because the fatality rate of V. vulnificus septicemia exceeds 50z (1). V. vulnificus is a Gram-negative bacillus that only infects humans and other primates. It is a member of the same family of bacteria that cause cholera. V. vulnificus is normally found in warm seawater and is a part of a group of vibrios classified as a halophile because of their salt requirements (2). V. vulnificus was first isolated in 1976 from a series of blood culture samples submitted to the Centers for Disease Control and Prevention (CDC; Atlanta, Ga., USA) (3). In Korea, the first reported case of V. vulnificus infection was in 1982 (4); however, it was not officially reported. V. vulnificus can cause an infection in those who eat contaminated seafood or have an open wound exposed to seawater. Among healthy people, ingestion of V. vulnificus can cause vomiting, diarrhea, and abdominal pain. In immunocompromised persons, particularly those with chronic liver disease, V. vulnificus can infect the bloodstream, causing a severe and life-threatening illness characterized by fever and chills, decreased blood pressure, and blistering skin lesions (1-6). V. vulnificus is found in marine coastal waters surrounding Korea, and infection with this organism by ingestion of raw shellfish or exposure to marine water can cause necrotizing fasciitis and sepsis, which are characterized by high mortality rates and short latency periods (6,7). In Korea, V. vulnificus infection is classified as a type IV notifiable disease by the Communicable Disease Prevention Act of the Korea Center for Disease Control and Prevention (KCDC) in 2000 (7). Thereafte...

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; 25 µg/ml) and methotrexate (MTX; 50 µg/ml), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptasepolymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

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