Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

Purpose@#Since diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state. @*Materials and Methods@#The anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5'-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells. @*Results@#The protein levels of phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 μM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660. @*Conclusion@#In conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.

Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors

Background@#Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts. @*Methods@#To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity. @*Results@#Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5’-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase. @*Conclusion@#The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Acute Type A Aortic Dissection in a Patient with Situs Inversus Totalis

We describe the occurrence of acute type A aortic dissection in a patient with situs inversus totalis. A 37-year-old man presented to the emergency department with acute chest pain. Initial chest X-ray findings showed a right-sided heart and a left-sided liver. Contrast-enhanced computed tomography revealed a Stanford type A acute aortic dissection, aortic root dilatation, and situs inversus totalis. All of the thoracic structures were mirror-image reversed and an abnormal coronary artery was observed. The Bentall operation was performed. This report demonstrates that computed tomography and echocardiography were useful for understanding the anatomy and the presence or absence of concurrent anomalies in a patient with situs inversus totalis. The patient’s postoperative course was uneventful.

Extracorporeal Cardiopulmonary Resuscitation with Therapeutic Hypothermia for Prolonged Refractory In-hospital Cardiac Arrest

BACKGROUND AND OBJECTIVES: We identified the impact of extracorporeal cardiopulmonary resuscitation (ECPR) followed by therapeutic hypothermia on survival and neurologic outcome in patients with prolonged refractory in-hospital cardiac arrest (IHCA). METHODS: We enrolled 16 adult patients who underwent ECPR followed by therapeutic hypothermia between July 2011 and December 2015, for IHCA. Survival at discharge and cerebral performance category (CPC) scale were evaluated. RESULTS: All patients received bystander cardiopulmonary resuscitation (CPR); the mean CPR time was 66.5±29.9 minutes, and the minimum value was 39 minutes. Eight patients (50%) were discharged alive with favorable neurologic outcomes (CPC 1–2). The mean follow-up duration was 20.1±24.3 months, and most deaths occurred within 21 days after ECPR; thereafter, no deaths occurred within one year after the procedure. CONCLUSION: ECPR followed by therapeutic hypothermia could be considered in prolonged refractory IHCA if bystander-initiated conventional CPR is performed.

Extraskeletal Osteosarcoma Arising from the Pleura

A 37-year-old woman was referred to our institution for further management of a mass lesion located in the thoracic cavity. The mass had grown by more than 10 cm over the course of a year and was initially considered to be a scar from previous pulmonary tuberculosis at another hospital. The patient had complained of left-sided flank pain for a year and experienced dyspnea for one month. Chest radiography and chest computed tomography revealed an irregular-shaped mass in the left mid to lower pleural cavity. The mass was widely excised through left thoracotomy. Pathologic examination of the biopsy specimen revealed a malignant spindle cell tumor, which consisted of components of osteosarcoma, pleomorphic sarcoma, and leiomyosarcoma. The patient underwent adjuvant chemotherapy and has been doing well without any evidence of recurrence for 14 months.

Erratum: Funding Acknowledgment

The funding acknowledgment in this article was omitted as published.

Inhibitory effects of Capsicum annuum L. water extracts on lipoprotein lipase activity in 3T3-L1 cells

Obesity, an intractable metabolic disease, currently has no medical treatment without side effects, so studies have been actively carried out to find natural compounds that have anti-obesity activity with minimum side effects. In this study, the anti-obesity effects of water extracts of seven Capsicum annuum L. varieties being Putgochu (Pca), Oyee gochu (Oca), Kwari putgochu (Kca), Green pepper (Gca), Yellow paprika (Yca), Red paprika (Rca) and Cheongyang gochu (Cca), were examined through the evaluation of lipoprotein lipase (LPL) mRNA expression level in 3T3-L1 cells (mouse pre-adipocytes). After capsaicin elimination by chloroform defatting, freeze-dried powder of Cca was treated to 3T3-L1 cells and anti-obesity effects were examined by determining the LPL mRNA level using the RT-PCR method. Of the primary fractions, only proven fractions underwent secondary and tertiary refractionating to determine anti-obesity effects. From seven different Capsicum annuum L., there was a significant decrease of the LPL mRNA expression level of 50.9% in Cca treatment compared to the control group. A significant decrease of the LPL mRNA expression level was shown in primary fractions (Fr) 5 (36.2% decrease) and 6 (30.5% decrease) of the Cca water extracts. Due to the impurities checked by UPLC chromatography, Fr 5 and 6 were refractionated to determine the LPL mRNA expression level. Treatment of Fr 6-6 (35.8% decrease) and Fr 5-6 (35.3% decrease) showed a significant decrease in the LPL mRNA expression level. When analyzed using UPLC, major compounds of Fr 6-6 and Fr 5-6 were very similar. Subsequently, we refractionated Fr 6-6 and Fr 5-6 to isolate the major peak for structure elucidation. Treatment of Fr 5-6-1 (26.6% decrease) and Fr 6-6-1 (29.7% decrease) showed a significant decrease in the LPL mRNA expression level. Consequently, the fractions may have a possibility to ameliorate obesity through the decrease of the LPL mRNA expression level.

The Combined Effects of Ginkgo Biloba Extracts and Aspirin on Viability of SK-N-MC, Neuroblastoma Cell Line in Hypoxia and Reperfusion Condition

OBJECTIVE: The purpose of this study is to investigate the combined effects of ginkgo biloba extract, ginkgolide A and B and aspirin on SK-N-MC, human neuroblastoma cell viability and mRNA expression of growth associated protein43 (GAP43), Microtubule-associated protein 2 (MAP2), B-cell lymphoma2 (Bcl2) and protein53 (p53) gene in hypoxia and reperfusion condition. METHODS: SK-N-MC cells were cultured with Dulbecco's Modified Eagle's Medium (DMEM) media in 37degrees C, 5% CO2 incubator. The cells were cultured for 8 hours in non-glucose media and hypoxic condition and for 12 hours in normal media and O2 concentration. Cell survival rate was measured with Cell Counting Kit-8 (CCK-8) reagent assay. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to estimate mRNA levels of GAP43, MAP2, Bcl2, and p53 genes. RESULTS: The ginkgolide A and B increased viable cell number decreased in hypoxic and reperfused condition. The co-treatment of ginkgolide B with aspirin also increased the number of viable cells, however, there was no additive effect. Although there was no increase of mRNA expression of GAP43, MAP2, and Bcl2 in SK-N-MC cells with individual treatment of ginkgolide A, B or aspirin in hypoxic and reperfused condition, the co-treatment of ginkgolide A or B with aspirin significantly increased GAP43 and Bcl2 mRNA levels. In MAP2, only the co-treatment of ginkgolide A and aspirin showed increasing effect. The mRNA expression of p53 had no change in all treating conditions. CONCLUSION: This study suggests that the combined treatments of Ginkgo biloba extracts and aspirin increase the regeneration of neuroblastoma cells injured by hypoxia and reperfusion.

Cervical Esophageal Hemangioma Combined with Thyroid Cancer

Hemangiomas that arise in cervical esophagus are extremely rare, representing 3.3% of all benign esophageal tumors. Although endoscopic mucosal resection (EMR) and potassium titanyl phosphate/yttrium aluminum garnet (KTP/YAG) laser therapy have been used with success for small tumors, the safety and efficacy in the case of large tumors remains uncertain. We report the successful resection of cervical esophageal hemangioma through a cervical esophagotomy in a patient with thyroid cancer who needed a cervical collar incision.

Cervical Esophageal Hemangioma Combined with Thyroid Cancer

Hemangiomas that arise in cervical esophagus are extremely rare, representing 3.3% of all benign esophageal tumors. Although endoscopic mucosal resection (EMR) and potassium titanyl phosphate/yttrium aluminum garnet (KTP/YAG) laser therapy have been used with success for small tumors, the safety and efficacy in the case of large tumors remains uncertain. We report the successful resection of cervical esophageal hemangioma through a cervical esophagotomy in a patient with thyroid cancer who needed a cervical collar incision.

Hemopericardium Following Acupuncture

Acupuncture-related hemopericardium is a rare but potentially fatal complication. We describe a hemopericardium that occurred shortly after acupuncture in a 55-year-old woman. A chest CT scan and echocardiography revealed a hemopericardium, and pericardiocentesis was then immediately and successfully performed. Subsequently, her clinical course improved. This case increases the attention of emergency physicians for acupuncture-related complications, especially hemopericardium, and the necessity of rapid diagnosis and management.

Hemopericardium Following Acupuncture

Acupuncture-related hemopericardium is a rare but potentially fatal complication. We describe a hemopericardium that occurred shortly after acupuncture in a 55-year-old woman. A chest CT scan and echocardiography revealed a hemopericardium, and pericardiocentesis was then immediately and successfully performed. Subsequently, her clinical course improved. This case increases the attention of emergency physicians for acupuncture-related complications, especially hemopericardium, and the necessity of rapid diagnosis and management.

The Effects of TWEAK, Fn14, and TGF-beta1 on Degeneration of Human Intervertebral Disc

OBJECTIVE: The purpose of this study is to explain the effect and reciprocal action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-beta1 (TGF-beta1) on degeneration of human intervertebral disc (IVD). METHODS: Human intervertebral disc tissues and cells were cultured with Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in 37degrees C, 5% CO2 incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an antagonistic receptor for TWEAK and TGF-beta1, the level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic acid (mRNA) levels were estimated by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: When human IVD tissue was cultured for nine days, the sGAG content was elevated in proportion to culture duration. The sGAG was decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9 mRNA levels decreased with TWEAK in IVD tissue TGF-beta1 20 ng/mL elevated the sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK was increased with Fn14 or TGF-beta1 but the result was insignificant statistically. TGF-beta1 increased the Sox9 mRNA expression to 180% compared to control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK were increased with TGF-beta1 in primary cultured IVD cells, however, Fn14 did not show increasing effect on Sox9 and versican. CONCLUSION: This study suggests that TWEAK would act a role in intervertebral disc degeneration through decreasing sGAG and the mRNA level of versican and Sox9.

VATS Rib Resection in Benign Bone Tumor: A case report / 대한흉부외과학회지

A 42 year old male was admitted for a bony mass on the posterior arc of the left 6th rib, which was detected in a multiphasic health screening test. According to the chest computed tomography scan and bone scan, osteochondroma was suspected. He underwent VATS rib resection. There was no vessel or nerve injury. The patient was discharged without any complication on the 4th post operative day. The pathological diagnosis was benign fibrous histiocytoma. Generally, posterolateral thoracotomy is needed for rib resection, but we found that there was no difficulty in doing this kind of surgery under a thoracoscopic approach, which has the advantage of better cosmesis.

The Relation Between Sox9, TGF-beta1, and Proteoglycan in Human Intervertebral Disc Cells

OBJECTIVE: The aim of this study is to elucidate the effects of transforming growth factor-beta (TGF-beta)1 and L-ascorbic acid on proteoglycan synthesis, and the relationship between Sox9, proteoglycan, and TGF-beta1 in intervertebral disc cells. METHODS: Human intervertebral disc tissue was sequentially digested to 0.2% pronase and 0.025% collagenase in DMEM/F-12 media and extracted cells were cultured in 37degrees C, 5% CO2 incubator. When intervertebral disc cells were cultured with TGF-beta1 or L-ascorbic acid, the production level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay. The changes of Sox9 mRNA and protein levels via TGF-beta1 were detected by RT-PCR and Western blot analysis in each. RESULTS: The amount of sGAG was increased with the lapse of time during incubation, and sGAG content of pellet cultured cells was much larger than monolayer culture. When primary cultured intervertebral disc cells in monolayer and pellet cultures were treated by TGF-beta1 20 ng, sGAG content of experimental group was increased significantly compared to control group in both cultures. L-Ascorbic acid of serial concentrations (50-300 ug/ml) increased sGAG content of mono layer cultured intervertebral disc cells significantly in statistics. The co-treatment of TGF-beta1 and L-ascorbic acid increased more sGAG production than respective treatment. After treating with TGF-beta1, Sox9 mRNA and protein expression rates were significantly increased in disc cells compared with the control group. CONCLUSION: This study suggests that TGF-beta1 would increase sulfated glycosaminoglycan (sGAG) and other proteoglycans such as versican by elevating Sox9 mRNA and protein expressions in order.

Experience with a Safe Anastomotic Method for Ivor Lewis Operation / 대한흉부외과학회지

BACKGROUND: When it comes to esophageal cancer operations, the prevalence of anastomotic complications that adversely affect quality of life is related to the type of anastomotic procedure and the operative site. We studied outcomes related to a safe anastomotic method used in Ivor Lewis esophagogastrectomy for preventing anastomotic leakage and stricture formation. MATERIAL AND METHOD: Between May 2003 and April 2007, 18 patients with esophageal cancer underwent this type of esophagogastrectomy. Four people were lost to follow-up. There were 17 men (94.4%) and 1 woman. The mean patient age was 61 years (range, 46~73 years). RESULT: The mean follow-up period was 17.2 months (range, 1~45 months). There was no anastomotic leakage. There was one benign anastomotic stricture (5.6%) requiring esophageal balloon dilatation, which was accomplished with a 25 mm circular stapler. CONCLUSION: We experienced relatively good postoperative results using a safe anastomotic method in the Ivor Lewis operation for preventing anastomotic complications. These results suggest that this anastomotic method is effective in reducing the incidence of benign anastomotic complications.

Palliative effect of (131)I-MIBG in relapsed neuroblastoma after autologous peripheral blood stem cell transplantation / 소아과

Neuroblastoma is one of the most common extracranial solid tumor of childhood, and treatment of refractory neuroblastoma remains a significant clinical problem. Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) therapy is an alternative approach to treat stage IV neuroblastoma. We report the palliative effect of (131)I-MIBG in three cases of relapsed neuroblastoma after autologous peripheral blood stem cell transplantation. (131)I-MIBG is an effective and relatively nontoxic palliative therapy resulting in reduction of pain and prolongation of survival.

The First 20 Cases of Cardiac Surgery Using the da Vinci(TM) Surgical System: A Single Center Experience / 대한흉부외과학회지

BACKGROUND: The interest in robotic cardiac surgery has recently grown but there has not been much clinical research reported on this. The aim of this study is to examine our initial experience, since August 2007, with robotic cardiac surgery using the da Vince(TM) surgical system and to evaluate the feasibility and safety of it. MATERIAL AND METHOD: Between August and December 2007, a total of 20 patients underwent robotic cardiac surgery using the da Vinci surgical system. For mitral valve repair (n=11), tricuspid valve repair (n=1), and ASD repair (n=1), cannulation, antegrade cardioplegia and transthoracic aortic cross-clamping were conducted for the right femoral vessels and the right internal jugular vein. For minimally invasive direct CABG (MIDCAB) (n=7), the internal thoracic artery (ITA) was harvested with the da Vinci surgical system. RESULT: The mean age of the patients was 50.1 (range: 26~78) years. Three concomitant Maze procedures and one tricuspid annuloplasty were combined with mitral valve repair. The mean cardiopulmonary bypass time was 208.0+/-61.3 minutes and the aortic cross clamp time was 158.8+/-40.6 minutes. No patients showed more than mild mitral regurgitation after repair and the median hospital stay was 4 days. The robotic-harvested ITA was used for either left ITA (n=6) or bilateral ITA (n=1). The mean harvest time was 43.2+/-12.0 minutes. The harvested ITA showed good flow and it was anastomosed under direct vision after left anterolateral thoracotomy. The patency of all the grafts was 100% (18/18) in MIDCAB. CONCLUSION: Robotic cardiac surgery using the da Vinci surgical system was variously adapted to areas such as mitral and tricuspid valve repair, ASD repair and ITA harvest for MIDCAB. The early results of the robotic cardiac surgery showed its safety and feasibility. With this primary report, we anticipate that clinical applications and further studies on robotic cardiac surgery using the da Vinci surgical system will be actively conducted in Korea.

A Tension-free Herniorrhaphy Using the Prolene Hernia System: Clinical Experiences

PURPOSE: The aim of this study was to detail clinical experiences with a new type of tension-free herniorrhaphy using the Prolene Hernia System (PHS) and analyze the system' usefulness. METHODS: We reviewed 48 cases of herniorrhaphy using PHS and 45 cases of conventional herniorrhaphy retrospectively by reviewing the medical records of patients undergoing either procedure between January 2000 and February 2005. RESULTS: There was no significant difference in the operation time (P=0.054) or the length of hospital stay (P=0.138) between the groups. However, the need for analgesic therapy in the PHS group was less than in the control group (P= 0.008). There were no serious postoperative complications, but wound complications occurred more often in the PHS group (6 seromas and 2 hematomas), and urinary retention occurred more frequently in the control group. The recurrence rate in the control group was 2.2% (1/45), but there were no recurrences in the PHS group for 46 months. CONCLUSION: Herniorrhaphy using the PHS is safe and effective as conventional surgery. It can be carried out under local anesthesia more easily, and it is less painful than the conventional surgery. We suggest that the PHS be widely adopted as a method of tension-free herniorrhaphy.

The Effects of Mistletoe Extract and Anti-cancer Drugs on the Apoptosis of Gastric Cancer Cells

PURPOSE: Mistletoe extract was widely used for cancer treatment as complementary or alternative therapy in European area from early twenty century. It is currently used as alternative anti-cancer remedy by piecemeal in domestic medical group, however, the anti-cancer mechanism of mistletoe extract was not known precisely until now. In this study the effect of mistletoe extract on gastric cancer was studied vis cell line experiments. MATERIALS AND METHODS: The SNU719 gastric cancer cell line was used, and ABNOBAviscum-Q and ABNOBAviscum-F were treated to cells as mistletoe extract, or 5-FU and cisplatin were used with mistletoe extract. The cell viability and cell death rate were estimated by CCK-8 assay kit and lactate dehydrogenase (LDH) assay kit in each. Caspase 3 assay kit was used to measure caspase 3 activity. The protein expression amounts of Bcl2, p53, and PTEN were estimated through Western blot analysis. RESULTS: The co-treatments of mistletoe extract Q/F and 5-FU/cisplatin decreased lesser cell viability than only mistletoe treat. Caspase 3 activity was increased 4~6 times in co-treatment of mistletoe extracts and 5-FU than control. Bcl2 protein expression was reduced by mistletoe extracts or anti-cancer drugs, further more, the co-treatment of mistletoe extracts and 5-FU/cisplatin diminished more the expression than only mistletoe treatment. Mistletoe extracts did not affect the protein expressions of p53 and PTEN. CONCLUSION: It was concluded that the anti-cancer mechanism of mistletoe extracts was made by caspase 3 activation and lowered Bcl2 expression, and this apoptosis inducing mechanism was independent to p53.