Status of Helminthic Infections in Residents around River Basins in the Republic of Korea for 10 Years (2011-2020)

The positive rate of Clonorchis sinensis is the highest among intestinal parasites in the Republic of Korea (Korea). More than 1.2 million people were at risk of C. sinensis infection in Korea in 2012. An intensive control program is being implemented for residents of the 5 major river basins to reduce helminthic infections, including C. sinensis infection. This study evaluated the continuous intensive control program for parasitic diseases including clonorchiasis in areas near the 5 major river basins in Korea over the past 10 years (2011-2020). A total of 335,020 fecal samples (one sample per resident) prepared by the modified sedimentation technic were microscopically examined. Those who expelled helminth eggs were treated with anthelmintics through local health centers and re-examined 3 months later. The overall positive rate of helminths egg was 7.1%. The annual positive rates were dramatically decreased from 14.4% (2011) to 5.9% (2020). The egg positive rate was highest in C. sinensis (5.3%), followed by heterophyid flukes (1.5%) and Trichuris trichiura (0.2%). The prevalence of C. sinensis was significantly higher in males (7.6%) than in females (3.7%), and the highest in the 50–59 years (7.0%) age group. Our results are beneficial to establish prevention and control policies against helminthiases including clonorchiasis in endemic areas in this country.

Cervicocerebral atherosclerosis and its hepatic and coronary risk factors in patients with liver cirrhosis

Background/Aims@#We aimed to investigate the silent atherosclerotic burden of cervicocephalic vessels in cirrhotic patients compared with the general population, as well as the relevant risk factors including coronary parameters. @*Methods@#This study included 993 stroke-free patients with liver cirrhosis (LC) who underwent magnetic resonance angiography (MRA) of the head and neck as a pre-liver transplant assessment and 6,099 health checkup participants who underwent MRA examination. The two cohorts were matched for cerebrovascular risk factors, and the prevalence of atherosclerosis in major intracranial and extracranial arteries was compared in 755 matched pairs. Moreover, traditional, hepatic, and coronary variables related to cerebral atherosclerosis were assessed in cirrhotic patients. @*Results@#Overall, intracranial atherosclerosis was significantly less prevalent in the LC group than in the matched control group (2.3% vs. 5.4%, P=0.002), whereas the prevalence of extracranial atherosclerosis was similar (4.4% vs. 5.8%, P=0.242). These results were maintained in multivariate analyses of the pooled samples, with corresponding adjusted odds ratios [ORs] of LC of 0.56 and 0.77 (95% confidence intervals [CIs], 0.36–0.88 and 0.55–1.09). In the LC group, lower platelet count was inversely correlated with intracranial atherosclerosis (adjusted OR, 0.31; 95% CI, 0.13–0.76). Coronary artery calcium (CAC) score ≥100 was the only predictive factor for both intracranial and extracranial atherosclerosis (adjusted ORs, 4.06 and 5.43, respectively). @*Conclusions@#LC confers protection against intracranial atherosclerosis, and thrombocytopenia may be involved in this protective effect. High CAC score could serve as a potential surrogate for cervicocerebral vascular screening in asymptomatic cirrhotic patients.

Characteristics of minute T1 colorectal cancer in relevance to pathology and treatment

Purpose@#Minute T1 colorectal cancer (CRC) lesions (≤5 mm) are rare; however, little is known about their characteristics and aggressiveness. In this study, we evaluated the characteristics of minute T1 CRC in relevance to pathology and treatment. @*Methods@#This retrospective study included 849 patients with T1 CRC endoscopically or surgically treated between January 2001 and December 2016. The patients were stratified into 4 groups according to tumor size; minute group (≤5 mm), small group (6–10 mm), medium group (11–20 mm), and large group (≥21 mm). Clinicopathological variables were evaluated with respect to tumor size. @*Results@#The incidence of the minute T1 CRC was 2.4% (20 of 849). Minute T1 CRC was significantly associated with flat type (minute, 25%; small, 12.6%; medium, 8.8%; large, 12.6%; P = 0.016), right-sided cancer (30%, 15.4%, 15.4%, 15.1%, P = 0.002) and the absence of background adenoma (BGA) (50%, 40.7%, 32.8%, 18.1%, P < 0.001). In patients who underwent surgery, lymph node metastasis (LNM) was significantly higher in the minute group (36.4%, 15.9%, 15.7%, 9.2%, P = 0.029). @*Conclusion@#Minute T1 CRC is significantly associated with flat type, right-sided cancers, as well as with the absence of BGA and LNM. These results suggested the minute T1 CRC lesions are often aggressive and are likely to be missed during colonoscopy.

Prognostic Value of Radiologic Extranodal Extension in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

OBJECTIVE: To determine whether radiologic extranodal extension (ENE) appearing on pretreatment CT and MRI could predict the prognosis in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: The study population was obtained from a historical cohort diagnosed with HPV-related OPSCC. A total of 134 OPSCC patients who had a metastatic lymph node on pretreatment CT or MRI were included, and radiologic ENE was evaluated by two experienced head and neck radiologists. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the impact of radiologic ENE on progression-free survival (PFS). The diagnostic performance of CT and MRI for the diagnosis of ENE was also evaluated in patients who underwent neck dissection. RESULTS: Seventy patients (52.2%) showed radiologic ENE-positive findings. Although patients showing radiologic ENE had a worse 3-year PFS (83.7% vs. 95.3%, p = 0.023), the association between radiologic ENE and PFS was not statistically significant on multivariate analysis (p = 0.141; hazard ratio, 2.68; 95% confidence interval, 0.72–9.97). CT or MRI had a sensitivity of 62%, specificity of 77.8%, and accuracy of 71.9% for predicting pathologic ENE. CONCLUSION: Radiologic ENE on CT or MRI did not predict poor PFS in patients with HPV-related OPSCC, although there was a trend towards worse PFS. Further studies are warranted to determine whether radiologic ENE is a useful imaging biomarker to risk-stratify patients with HPV-related OPSCC.

Clinical Outcomes of Totally Laparoscopic Total Gastrectomy versus Open Total Gastrectomy for Remnant Gastric Cancer

PURPOSE: This study compares the feasibility and safety of Totally Laparoscopic Total Gastrectomy (TLTG) with Open Total Gastrectomy (OTG) for Remnant Gastric Cancer (RGC) in patients who had previously undergone gastrectomy. METHODS: We retrospectively collected and analyzed the data of 139 consecutive patients who underwent OTG along with 21 patients who underwent TLTG for RGC between January 2008 and December 2016. One-to-two Propensity Score Matching (PSM) was performed to compare the age, gender, body mass index, American Society of Anesthesiologists score, clinical tumor stage, previous gastric disease, previous gastrectomy type, previous reconstruction type, history of previous upper abdominal surgery except gastrectomy, and combined major operations. A total of sixty patients (21 who underwent TLTG and 39 who underwent OTG) were matched, and surgical outcomes and survival rates were compared. RESULTS: The TLTG patients were found to recover bowel movements sooner than the OTG group (OTG 3.74±0.88 vs TLTG 3.19±0.81 days, p=0.02). Post-operative surgical outcomes, including pathological features, clinical courses, complications and survival rates did not differ between the two groups (p>0.05). CONCLUSION: Although TLTG was not found to have any definitive clinical advantage over OTG except for more rapid recovery of bowel movement, TLTG should be considered as safe and feasible surgical procedure as OTG for the treatment of RGC.

Safe Handling of Cytotoxic Drugs and Use of Personal Protective Equipment among Nurses at a Regional Cancer Center

PURPOSE: This purpose of this study was to identify the level of safe-handling of cytotoxic drugs and use of PPE (Personal Protective Equipment) among nurses at a regional cancer center in South Korea. METHODS: This was a cross-sectional descriptive study. The participants were 131 nurses who care for cancer patients undergoing chemotherapy. Demographic information, safe-handling of cytotoxic drugs and use of PPE were collected using questionnaires from May 7 to 25, 2018. RESULTS: Response rate was 98.4%. The mean age of the nurses was 28.2±4.4 years and their clinical nursing experience was 4.34±3.93 years. The mean scores out of 5 for the participants' safe handling of cytotoxic drugs was 3.73± 0.43. In use of PPE, the mean score of wearing gloves, masks, and gowns were 3.89±.77, 3.06±1.04, and 2.34±0.98, respectively. The main reason for not wearing PPE was ‘too busy’ (62.8%). The level of safe-handling of cytotoxic drugs was not significantly different according to any variables, but the use of PPE was significantly different according to age (p=.021). CONCLUSION: The findings showed that nurses had exposure to cytotoxic drugs in the processes of preparation, administration, cleaning of spills, and handling of patient waste. Education programs and continuous monitoring are needed to improve the use of PPE among nurses and trigger the appropriate motivation for consistent personal protection.

Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide population-based cohort study / 부인종양

OBJECTIVE: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. METHODS: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. RESULTS: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ≥60 years, longer duration use (≥1 year), in patients with Charlson Comorbidity Index (CCI) ≥3, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (≥180 days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (≥720 days). In multivariate Cox proportional hazards model, longer duration of BB medication (≥1 year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. CONCLUSION: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ≥3).

Effects of Atomoxetine on Height and Weight in Korean Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Retrospective Chart Review

OBJECTIVE: We aimed to investigate the long-term effects of atomoxetine on growth in Korean children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: The medical records of 82 subjects (mean age, 9.0±2.0 years; 64 boys) with ADHD treated with atomoxetine for at least 1 year at the Department of Psychiatry at Asan Medical Center were retrospectively reviewed. Height and weight data were prospectively obtained and retrospectively gathered and converted to age- and gender-corrected z scores using norms from Korean youths. Growth changes were analyzed using random coefficients models with changes in height or weight z scores as the dependent variables. RESULTS: Height z scores significantly decreased during the treatment period (β=-0.054, p=0.024). Height z scores decreased during the 1st year of treatment (β=-0.086, p=0.003), but did not change after the 1st year. Weight z scores did not change significantly during treatment (β=0.004, p=0.925). CONCLUSION: Our results suggest that long-term atomoxetine treatment may be associated with deficits in height growth in Korean youths, although this effect was minor and tended to be attenuated over the first year. Because of the limitations of this study such as retrospective design and selection bias, further prospective studies are needed.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

OBJECTIVE@#To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC).@*METHODS@#The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting.@*RESULTS@#Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment.@*CONCLUSIONS@#The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

Objective To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). Methods The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α PGE

The Association of Fever with Total Mechanical Ventilation Time in Critically Ill Patients

This research aims to investigate the impact of fever on total mechanical ventilation time (TVT) in critically ill patients. Subgroup analysis was conducted using a previous prospective, multicenter observational study. We included mechanically ventilated patients for more than 24 hours from 10 Korean and 15 Japanese intensive care units (ICU), and recorded maximal body temperature under the support of mechanical ventilation (MAX(MV)). To assess the independent association of MAX(MV) with TVT, we used propensity-matched analysis in a total of 769 survived patients with medical or surgical admission, separately. Together with multiple linear regression analysis to evaluate the association between the severity of fever and TVT, the effect of MAX(MV) on ventilator-free days was also observed by quantile regression analysis in all subjects including non-survivors. After propensity score matching, a MAX(MV) ≥ 37.5℃ was significantly associated with longer mean TVT by 5.4 days in medical admission, and by 1.2 days in surgical admission, compared to those with MAX(MV) of 36.5℃ to 37.4℃. In multivariate linear regression analysis, patients with three categories of fever (MAX(MV) of 37.5℃ to 38.4℃, 38.5℃ to 39.4℃, and ≥ 39.5℃) sustained a significantly longer duration of TVT than those with normal range of MAX(MV) in both categories of ICU admission. A significant association between MAX(MV) and mechanical ventilator-free days was also observed in all enrolled subjects. Fever may be a detrimental factor to prolong TVT in mechanically ventilated patients. These findings suggest that fever in mechanically ventilated patients might be associated with worse mechanical ventilation outcome.

Confirmation of HIF-1α Independent Pathway in the Progression of HepG2 Cells by Hypoxic Condition

BACKGROUND/AIMS: When hepatocellular carcinoma (HCC) is exposed to hypoxic condition, HIF-1α is activated and results in angiogenesis and increased tumor burden. Although inhibition of HIF-1α may reduce tumor growth, there are some limitations to control tumor growth completely. For a more effective therapy for HCC, we investigated HIF-1α independent pathway related tumor growth with angiogenesis. METHODS: We cultured HepG2 cells (HCC cell line) in both normoxia and hypoxia conditions. These cells were divided into three groups: a echinomycin treated group, a echinomycin and quinazoline treated group and a control group without any treatments. Growth morphologies of cells were observed with a microscope after 24 hours. Immunocytochemistry assay was done to detect the angiogenesis during inhibition of HIF-1α and/or NF-κB in hypoxia condition, and compared with results in normoxia condition. RESULTS: In normoxia, the expression of HIF-1α on tumor growth was not found. In hypoxia, inhibition of HIF-1α reduced the tumor growth compared to the control group. But, inhibition of both HIF-1α and NF-κB did not show apparent reduction of tumor growth as shown in HIF-1α only group. CONCLUSIONS: Signaling pathways related to cancer cell growth exist through a vast network. Inhibition of one target molecule may result in over-expression of other molecules related to the tumor growth. For an effective therapy in blocking of the tumor growth, more comprehensive understanding of the network related to signaling pathways on tumor growth is necessary.

Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells

BACKGROUNDS/AIMS: Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds. METHODS: This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days. RESULTS: Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days. CONCLUSIONS: Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial.

Association between Media Reporting and a Lower Suicide Rate in 2012 / 신경정신의학

OBJECTIVES: A recent study conducted by the Korea National Statistical Office (KNSO) reported that the suicide rate in Korea decreased in 2012. The aim of this study was to investigate the association between the decrease in suicide rate and media reporting of suicide events. METHODS: Data on suicide rates were obtained from the KNSO. Correlation between suicide rate and celebrity suicide events, number of media reports on suicide, and suicide searches was compared. Data were analyzed using Pearson's correlation coefficient. RESULTS: The number of celebrity suicide events and recognition of celebrity decreased in 2012. Pearson's correlation test showed a significant positive correlation between the monthly number of media reports on suicide and the suicide rate (daily newspaper r=0.619, p<0.001 ; broadcast r=0.393, p<0.001). The number of suicide searches showed association with celebrity suicide events. CONCLUSION: The suicide rate may be influenced by the number of media reports on suicide events. Establishing guidelines for media reporting on these events could help to decrease the suicide rates.

Psychometric Properties of the Korean Version of the Overactive Bladder Questionnaire (OAB-q) in a Korean Population / 대한배뇨장애요실금학회지

PURPOSE: Psychometric properties of the overactive bladder questionnaire (OAB-q) were recently examined. However, since the cross-cultural adaptation of a non-English version of the OAB-q has never been demonstrated, we evaluated the psychometric properties of a Korean version of the OAB-q in a Korean population with OAB. METHODS: A prospective cohort study involving 116 women with 58 OAB and 58 control subjects was performed and convergent validity was assessed. Total and subscale OAB-q scores of the control and OAB groups were compared to their sensitivity to score changes before and after administering anti-cholinergic medication for 12 weeks. Short form 36 and King's health questionnaire (KHQ) were also used for comparison or correlation. RESULTS: Assessment of face validity showed that the Korean version of the OAB-q was reasonable with OAB-q subscale scores being significantly different between the control and patient groups. Significant correlation (range, -0.29 to -0.81) was found between the OAB-q scores and KHQ results for the OAB patients. Cronbach's alpha coefficients (range, 0.77 to 0.95) indicated excellent internal consistency and test-retest analysis involving 35 OAB patients showed that each questions as well as subscale scores were reproducible. Each score of OAB-q also showed statistically significant sensitivity to changes following anti-muscarinic treatment for OAB (n=27, P<0.001 except for social, P=0.059). CONCLUSIONS: The Korean version of the OAB-q is a valid and reliable instrument to measure outcomes in Korean patients with OAB.

Immediately transcripted genes in various hepatic ischemia models / 대한외과학회지

PURPOSE: To elucidate the characteristic gene transcription profiles among various hepatic ischemia conditions, immediately transcribed genes and the degree of ischemic injury were compared among total ischemia (TI), intermittent clamping (IC), and ischemic preconditioning (IPC). METHODS: Sprague-Dawley rats were equally divided into control (C, sham-operated), TI (ischemia for 90 minutes), IC (ischemia for 15 minutes and reperfusion for 5 minutes, repeated six times), and IPC (ischemia for 15 minutes, reperfusion for 5 minutes, and ischemia again for 90 minutes) groups. A cDNA microarray analysis was performed using hepatic tissues obtained by partial hepatectomy after occluding hepatic inflow. RESULTS: The cDNA microarray revealed the following: interleukin (IL)-1beta expression was 2-fold greater in the TI group than in the C group. In the IC group, IL-1alpha/beta expression increased by 2.5-fold, and Na+/K+ ATPase beta1 expression decreased by 2.4-fold. In the IPC group, interferon regulatory factor-1, osteoprotegerin, and retinoblastoma-1 expression increased by approximately 2-fold compared to that in the C group, but the expression of Na+/K+ ATPase beta1 decreased 3-fold. CONCLUSION: The current findings revealed characteristic gene expression profiles under various ischemic conditions. However, additional studies are needed to clarify the mechanism of protection against IPC.

The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats / 대한간학회지

BACKGROUND/AIMS: Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats. METHODS: To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed. RESULTS: Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100x magnification (cells/field) were 31.8+/-24.2 in NC, 69.0+/-72.3 in TC, 80.2+/-63.1 in IP, and 21.2+/-20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400x were 3.4+/-6.0 in NC, 16.9+/-69 in TC, 17.0+/-7.8 in IP and 7.4+/-7.6 in IC (P<0.05). CONCLUSIONS: Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.

Ideal Experimental Rat Models for Liver Diseases

There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

The Factors Affecting Transplanted Hepatocytes Repopulation in Rats with Liver Fibrosis

PURPOSE: Cell therapy for various diseases has gained wide acceptance. Because most patients with chronic liver failure have mild-to-severe liver cirrhosis, there are many limitations to clinical applications. We analyzed how to increase cell engraftment in rats with liver fibrosis. METHODS: We used analbuminemic SD rats (NARs) as recipients of syngeneic CAG-EGFP SD hepatocytes obtained by the 2 perfusion method. Hepatic fibrosis was induced with thioacetamide in drinking water for 6 weeks in the recipient NARs. NARs were pre-treated with gadolinium, doxorubicin, and gliotoxin before hepatocyte transplantation. We evaluated the degree of cell engraftment by RT-PCR and immunofluorescent staining for GFP and albumin. The transplanted cells were detected by immunostaining for albumin, and serum albumin was also measured. RESULTS: Although detection of GFP by RT-PCR was variable, albumin was detected in all groups 4 wks after hepatocyte transplantation. GFP and albumin were also detected by immunofluorescent staining 1 and 4 wks after cell transplantation. In control rats, albumin production was maximal at 3 wks, and after that it rapidly decreased. In the gadolinium and doxorubicin-treated group, albumin production was increased up to 4 wks. Albumin production in the gadolinium-treated group was superior to that of the doxorubicin-treated group. CONCLUSION: Kupffer cells play the most important role in cell engraftment in hepatic fibrosis. Therefore, perturbation of kupffer cells in hepatic fibrosis is needed to increase cell engraftment.

The Factors Affecting Transplanted Hepatocytes Repopulation in Rats with Liver Fibrosis

PURPOSE: Cell therapy for various diseases has gained wide acceptance. Because most patients with chronic liver failure have mild-to-severe liver cirrhosis, there are many limitations to clinical applications. We analyzed how to increase cell engraftment in rats with liver fibrosis. METHODS: We used analbuminemic SD rats (NARs) as recipients of syngeneic CAG-EGFP SD hepatocytes obtained by the 2 perfusion method. Hepatic fibrosis was induced with thioacetamide in drinking water for 6 weeks in the recipient NARs. NARs were pre-treated with gadolinium, doxorubicin, and gliotoxin before hepatocyte transplantation. We evaluated the degree of cell engraftment by RT-PCR and immunofluorescent staining for GFP and albumin. The transplanted cells were detected by immunostaining for albumin, and serum albumin was also measured. RESULTS: Although detection of GFP by RT-PCR was variable, albumin was detected in all groups 4 wks after hepatocyte transplantation. GFP and albumin were also detected by immunofluorescent staining 1 and 4 wks after cell transplantation. In control rats, albumin production was maximal at 3 wks, and after that it rapidly decreased. In the gadolinium and doxorubicin-treated group, albumin production was increased up to 4 wks. Albumin production in the gadolinium-treated group was superior to that of the doxorubicin-treated group. CONCLUSION: Kupffer cells play the most important role in cell engraftment in hepatic fibrosis. Therefore, perturbation of kupffer cells in hepatic fibrosis is needed to increase cell engraftment.