Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has various functions to affect many signalling pathways leading to cellular proliferation and differentiation and to regulate of cell migration, invasion, and angiogenesis. However, there are little reports about the relation between trophoblast stem cells and S1P. Thus, the physiologic effects of S1P on trophoblast stem (TS) cells were investigated in this study. S1P was involved in early stage development of trophoblast via upregulation of Eomesodermine mRNA expression and suppressed differentiation of TS cells through activation of extracellular-signal regulated kinase (ERK) activation. Other actions of S1P were the activation of p38 and the induction of Dlx-3 mRNA expression for angiogenesis in TS cells. Interestingly, TS cells cultured with S1P for 4 days in thrombin-fibrinogen gel culture system, specific culture system for endothelial cells, showed good healthy appearance, but TS cells cultured without S1P got severe damages. Taken together, we suggest that S1P has very important roles on placenta such as development of early stage trophoblast, suppression of differentiation, and angiogenesis on placenta.
Cell Movement ; Cell Proliferation ; Endothelial Cells ; Phosphotransferases ; Placenta ; Placentation* ; RNA, Messenger ; Stem Cells ; Trophoblasts ; Up-Regulation

Preeclampsia and fetal growth restriction are conditions associated with placental hypoperfusion and villous hypoxia. The villous response to this environment includes elevated apoptosis. Recently, trophoblast stem (TS) cells had been successfully derived. FGF-4 locates in the inner cell mass (ICM) of blastocyst and TS cells have fibroblast growth factor receptor-2 (FGFR-2). To identify whether FGF-4 protects hypoxia-induced apoptosis in TS cells, this study was carried out. TS cells were cultured up to 48 h in standard (PO2 = 20%) or hypoxic (PO2 = 3%) conditions. TS cells were very vulnerable against exposure to hypoxia for 48 h but embryonic stem (ES) cells were very resistant to hypoxiamediated apoptosis. Death of TS cells bears the typical hallmarks of apoptosis as determined by DNA laddering. FGF- 4 and epidermal growth factor (EGF) protected the hypoxia-mediated cell death of trophoblast but granulocyte-macrophage colony stimulating factor (GMSF) and transforming growth factor-beta (TGF-beta) did not protect. In conclusion, we speculate that the effects of FGF-4 on apoptosis in trophoblasts may play an important role in protecting the placenta from hypoxic injury in pregnancy related with placental hypoperfusion.
Anoxia ; Apoptosis* ; Blastocyst ; Cell Death ; Colony-Stimulating Factors ; DNA ; Epidermal Growth Factor ; Fetal Development ; Fibroblast Growth Factors ; Placenta ; Pre-Eclampsia ; Pregnancy ; Stem Cells* ; Trophoblasts*

At present, laparoscopic colon resection for benign and early malignant lesions is quite acceptable because of fast recovery and minimal morbidity. Laparoscopic curative surgery for advanced colorectal cancer, however, remains controversial because long-term oncologic outcomes are yet unavailable from multicenter randomized trials. Very recently, a timely important randomized study, focusing on the long-term survival and recurrence, was published. It showed laparoscopic resection had low risks of tumor recurrence and cancer-related death compared with open resection, especially in patients with stage III disease. The important message in this paper is not just that the laparoscopic approach is better, but that it may be better when performed by experienced hands. In this review, oncologic issues of laparoscopic cancer resection will be discussed, then the current role of laparoscopy for benign colorectal diseases will be briefly described. Finally, the proven and potential advantages of laparoscopic colectomy over open colectomy will be discussed. This article clearly reviews the current status and future perspectives of laparoscopic surgery for both benign and malignant colorectal indications.
Colectomy* ; Colon ; Colorectal Neoplasms ; Hand ; Humans ; Laparoscopy ; Recurrence

Background: Osteoporosis is a disease that affects the quality of life and imposes a high socioeconomic burden. Studies have reported that statins, a HMG CoA reductase inhibitor, have a positive or negative effect on osteoporosis. The purpose of this study was to analyze the correlation between statins and osteoporosis risk. Methods: We used the total patient sample data of the Health Insurance Review and Assessment Service (HIRA-NPS-2018). We analyzed the prevalence of osteoporosis in adult patients of Korea who were diagnosed with dyslipidemia and were prescribed statins at the same time. The odds ratio (OR) according to the intensity and type of statin was used to confirming the prevalence. Results: Among the 1,138,899 patients included in the study, 143,895 patients used statins and 27,524 patients (19.13%) were diagnosed with osteoporosis in the statin group. The OR value of statin group was 0.96 (95% CI 0.94-0.98), confirming that the prevalence of osteoporosis decreased, and a significant decrease was seen in all statin intensity. Some of the moderate-intensity statins rather increased the prevalence of osteoporosis, but atorvastatin and rosuvastatin obtained positive results at both medium- and high-intensity doses, and lovastatin, a low-intensity statin, showed the greatest reduction in the prevalence of osteoporosis. Conclusion We found that the prevalence of osteoporosis was reduced in the statin group, and there was a constant correlation regardless of gender or age. However, a large, prospective, double-blind and randomized study is needed for a long period of time to demonstrate the effectiveness of statins.

Background and Objectives: Positive airway pressure (PAP) is effective at reducing the number of complications in patients with obstructive sleep apnea (OSA). To the best of our knowledge, no cost-effectiveness analysis of PAP has been conducted in Korea. Subjects and Method: We classified subjects into two groups, those with moderate-to-severe OSA who used PAP after polysomnography (PAP treatment group) and those who did not receive a diagnosis and treatment (control group), and compared their medical expenses over a period of 10 years. The incidence rate of common complications and accidents (coronary heart disease, heart failure, stroke, depression, diabetes, vehicular accidents, and work-related accidents) with or without PAP was adopted through a literature review. The average medical expenses for treating each complication and accident were found by searching several databases. The analysis consisted of a payer’s perspective and a societal perspective. Results: The incidence of all complications was higher in the control group than in the PAP treatment group. However, since the absolute incidence rate was not high in either group and medical expenses in Korea are low, the expected treatment cost was not high. In contrast, the PAP rental fee was relatively high. To obtain 1 unit of disability-adjusted life year, it costs 40,873,288 won from the payer’s perspective and 31,791,810 won from the societal perspective. Conclusion PAP treatment reduces patient complications and extends their lifespan, but costs must be considered.

Background and Objectives: Positive airway pressure (PAP) is effective at reducing the number of complications in patients with obstructive sleep apnea (OSA). To the best of our knowledge, no cost-effectiveness analysis of PAP has been conducted in Korea. Subjects and Method: We classified subjects into two groups, those with moderate-to-severe OSA who used PAP after polysomnography (PAP treatment group) and those who did not receive a diagnosis and treatment (control group), and compared their medical expenses over a period of 10 years. The incidence rate of common complications and accidents (coronary heart disease, heart failure, stroke, depression, diabetes, vehicular accidents, and work-related accidents) with or without PAP was adopted through a literature review. The average medical expenses for treating each complication and accident were found by searching several databases. The analysis consisted of a payer’s perspective and a societal perspective. Results: The incidence of all complications was higher in the control group than in the PAP treatment group. However, since the absolute incidence rate was not high in either group and medical expenses in Korea are low, the expected treatment cost was not high. In contrast, the PAP rental fee was relatively high. To obtain 1 unit of disability-adjusted life year, it costs 40,873,288 won from the payer’s perspective and 31,791,810 won from the societal perspective. Conclusion PAP treatment reduces patient complications and extends their lifespan, but costs must be considered.

PURPOSE: Regarding laparoscopic colon cancer resection, the surgical society is currently waiting for the long-term oncologic result of multi-center randomized trials with over thousands patients. For rectal cancer surgery, however, laparoscopic approach is in much debate. The aim of this study was to evaluate the feasibility and safety of laparoscopic anterior resection for rectal cancer, based on the early results of our initial experiences. METHODS: Nineteen patients (M:F=10:9, median age 55 years) underwent laparoscopic anterior resection for rectal cancer among the 71 malignant neoplasms of the colon and rectum resected laparoscopically between October 1997 and February 2001. All clinical data were prospectively collected. During the initial period, rectosigmoid lesion was the only indication. With the development of a new roticulating stapler for distal rectal transection, the indication was extended to the lesions of the upper and middle third of the rectum. The operation parameters (operation time, blood loss), tumor parameters (stage, resection margins, and number of resected lymph nodes), and postoperative clinical course (bowel function recovery, hospital stay, and complication) were evaluated. RESULTS: The tumors located in the rectosigmoid (n=13), upper third of the rectum (n=4), and the middle third of the rectum (n=2). Four cases were converted to an open procedure. The reasons for conversion were bladder invasion (1), tumor located too low (1), inappropriate distal resection margin (1), and tumor fixation to the sacrum (1). Median operation time was 210 minutes. Median blood loss was 400 ml. Median times to passage of flatus and oral feeding were 2 days and 3 days after surgery, respectively. Median length of the distal resection margin was 3 cm. Median number of harvested lymph nodes were 22. TNM stages were as follows; 0:I:II:III:IV=1:2:6:9:1. Two anastomotic leaks occurred in the converted patients. There were no major postoperative complications in other patients. There was no operative mortality. Median time to hospital discharge was 13 days. During a median follow-up period of 15 months, one patient developed distant metastases. There were no local/port sites recurrences. CONCLUSIONS: Laparoscopic anterior resection is a safe alternative to conventional surgery for rectal cancer. Long- term follow-up is mandatory to evaluate the oncologic safety.
Anastomotic Leak ; Colon ; Colonic Neoplasms ; Flatulence ; Follow-Up Studies ; Humans ; Laparoscopy ; Length of Stay ; Lymph Nodes ; Mortality ; Neoplasm Metastasis ; Postoperative Complications ; Prospective Studies ; Recovery of Function ; Rectal Neoplasms* ; Rectum ; Recurrence ; Sacrum ; Urinary Bladder

PURPOSE: Diallyl disulfide (DADS) is a major organosulfur compound derived from garlic. It has been reported that DADS is able to inhibit the proliferation of several tumor cells. In this study, the effect of DADS was investigated in terms of the proliferation of AGS, gastric adenocarcinoma cell line at various concentrations. METHODS: The viability of cultured cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To detect the induction of apoptosis, Annexin V-FITC/propodium iodide (PI) staining assay was performed. Analysis of reactive oxygen species (ROS) and the distribution of cells in the cell cycle were measured by a flow cytometer. And using the Western blot analysis, the change of Fas, caspase-3, Bax, Bcl-2 activity was measured. RESULTS: The percentage of live AGS cells was decreased to 23% of that in the control group after 400 microM DADS treatment for 48 hours. The Annexin V positive/PI negative (apoptosis portion) area increased from low concentration of DADS to high concentration. When comparing among the DADS treatment groups, the amount of ROS production increased in a dose dependent manner. The percentage of sub-diploid DNA content increased from 8.71% at 50 microM to 25.74% at 400 microM DADS treatment group. The expressions of Fas, caspase-3, Bax were increased and that of Bcl-2 was decreased in a dose dependent manner. CONCLUSION: DADS decreases the viability of AGS cell lines and induces apoptosis in a dose-dependent manner. But the relationship of the anti-proliferative effect of DADS and related molecular changes were not clearly proportional to the concentration of DADS.
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid ; Adenocarcinoma ; Allyl Compounds ; Annexin A5 ; Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Cycle ; Cell Line ; Cells, Cultured ; Disulfides ; DNA ; Garlic ; Reactive Oxygen Species ; Stomach Neoplasms

PURPOSE: In this retrospective study, we aimed to compare the clinical characteristics of inguinal hernia developed after radical retropubic surgery for prostate cancer to the hernia without previous radical prostatectomy. METHODS: Twenty-three patients (group A) who had radical retropubic surgery for prostate cancer underwent laparoscopic or open tension-free inguinal hernia repair from March 2007 to February 2011. Nine hundred and forty patients (group B) without previous radical retropubic surgery received laparoscopic or tension-free open hernia operation. RESULTS: Group A was older than group B (mean +/- standard deviation, 69.6 +/- 7.2 vs. 54.1 +/- 16.1; P < 0.001). Right side (73.9%) and indirect type (91.3%) in group A were more prevalent than in group B (51.5% and 69.4%, respectively) with statistic significance (P = 0.020 and P = 0.023). The rate of laparoscopic surgery in group B (n = 862, 91.7%) was higher than in group A (n = 14, 64.3%, P < 0.001). In comparing perioperative variables between the two groups, operative time (49.4 +/- 23.5 minutes) and hospital stay (1.9 +/- 0.7 days) in group A were longer than in group B (38.9 +/- 16.9, 1.1 +/- 0.2; P = 0.046 and P < 0.001, respectively) and pain score at 7 days in group A was higher than in group B (3.1 +/- 0.7 vs. 2.3 +/- 1.0, P < 0.001). Postoperative recurrence rate was not significantly different between the two groups. CONCLUSION: Inguinal hernia following radical retropubic surgery for prostate cancer was predominantly right side and indirect type with statistic significance compared to hernias without previous radical prostatectomy.
Hernia ; Hernia, Inguinal ; Humans ; Laparoscopy ; Length of Stay ; Operative Time ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Recurrence ; Retrospective Studies

Purpose: This study was conducted to establish whether an ethanol extract of Lycium barbarum leaves (LLE) and an ethanol extract of Lycium barbarum leaves from which chlorophyll has been removed, denoted as LLE(Ch−), have a protective effect against hepatic fat accumulation. Methods: The inhibitory effects of LLE and LLE(Ch−) on liver fat accumulation were examined in C57BL/6 mice with non-alcoholic fatty liver disease (NAFLD) induced by an methionine and choline deficient diet and in HepG2 cells with palmitic acid-induced fat accumulation. Results: The plasma triglyceride, aspartate aminotransferase, and alanine aminotransferase levels were lower in the LLE(Ch−) group, whereas the plasma ALT activity decreased significantly in the LLE group. In both the LLE and the LLE(Ch−) groups, the triglyceride and cholesterol contents in the hepatic tissue were significantly reduced. A greater inhibitory effect on tissue fat accumulation was observed in the LLE(Ch−) group than in the LLE group. In HepG2 cells, LLE and LLE(Ch−) were non-toxic up to a concentration of 1,000 µg/mL. Compared to the control group, intracellular fat accumulation in the LLE and LLE(Ch−) groups were significantly reduced at concentrations of 200 µg/mL and 500 µg/mL, respectively. The expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated acetyl-CoA carboxylase in both LLE groups increased at the concentrations of 100 μg/mL and 500 μg/mL. The fatty acid synthase expression was suppressed in a concentration-dependent manner at 10 μg/mL. Conclusion The examined two ethanol extracts of LLE inhibit hepatic fat accumulation in NAFLD. This effect was more pronounced in the LLE(Ch−) group. Therefore, these 2 extracts have an anti-steatosis effect and can be used for NAFLD treatment.