Effect of 5-aminoimidazole-4-formamide Ribonucleotide Combined with Interferon on Chronic Myeloid Leukemia K562 Cells / 中国实验血液学杂志

OBJECTIVE@#To study the effect of 5-aminoimidazole-4-formamide ribonucleotide (AICAR) combined with interferon (IFN-α-2b) on the proliferation and apoptosis of chronic myeloid leukemia K562 cells, and explore its possible mechanism.@*METHODS@#CCK-8 method was used to detect the inhibition of cell proliferation. Wright Giemsa method was used to stain and cell morphology was observed by light microscopy. FITC Annexin V/PI double staining method was used to analyze the change of apoptosis rate. Immunocytochemistry method was used to detect the expression of wild-type P53 protein.@*RESULTS@#Different concentration of AICAR was inhibitory effect on K562 cells at different time point of action for 24 h, 48 h, and 72 h, and the inhibition was time and dose-dependent (r=0.71, r=0.84). The combination of AICAR and IFN-α-2b could effectively inhibit the proliferation and promote apoptosis of K562 cells. The inhibition rate of K562 cells was (45.26±2.54)%, and the early apoptosis rate was (33.72±0.23)%, which was statistically significantly different from the control group, AICAR or IFN-ɑ-2b alone (P<0.05). The combination of two drugs promoted the expression of wild-type p53 protein.@*CONCLUSION@#AICAR and/or IFN-ɑ-2b can inhibit the cell proliferation and promote the apoptosis of K562 cells. The combination of two drugs shows synergistic antitumor effect, and its mechanism may be related to the promotion of high expression of wild-type p53 protein.

AMP-activated protein kinase activation regulates adhesion of monocytes to vascular endothelial cells and the underlying mechanism / 生理学报

The present study was aimed to explore the effect of AMP-activated protein kinase (AMPK) on monocyte adhesion to vascular endothelial cells and underlying molecular mechanism. Tumor necrosis factor α (TNFα)-activated human aortic endothelial cells (HAECs) were treated with different concentrations of AMPK agonist 5-Aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR) or AMPK inhibitor compound C. And other HAECs were overexpressed with constitutive active or dominant negative AMPK protein and then treated with TNFα. The rates of monocytes adhering to endothelial cells were detected by fluorescent staining. Intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA levels and protein secretions were detected by quantitative PCR and ELISA, respectively. Acetylation of NF-κB p65 at lysine 221 site was assessed by Western blot. NF-κB p65 DNA binding activity was analyzed by an ELISA-based method. By using small interfering RNA based strategy, p300 expression in HAECs was down-regulated and then cells were incubated with TNFα. NF-κB p65 DNA binding activity, ICAM-1 and VCAM-1 expressions and adhesion rates were detected, respectively. The activity of p300 was also detected by ELISA. The results showed that AICAR treatment significantly reduced monocyte-endothelial adhesion rate, as well as ICAM-1 and VCAM-1 mRNA levels and protein secretions, in TNFα-activated HAECs. Moreover, transfection of constitutive active AMPKα but not dominant negative AMPKα strongly diminished TNFα-induced upregulation of ICAM-1 and VCAM-1 mRNA expressions and secretions, as well as monocyte-endothelial adhesion. Furthermore, AMPK activation decreased TNFα-mediated acetylation of NF-κB p65 at Lys221 site and reduced NF-κB p65 DNA binding activity. Silencing p300 by siRNA significantly abolished the effect of TNFα- induced adhesion molecules expression and monocyte-endothelial adhesion. Blocking AMPK activation by compound C almost completely reversed the effect of AICAR exerted on HAECs. These results suggest AMPK activation suppresses monocyte-endothelial adhesion, and the underlying mechanism is relevant to the inhibition of p300 activity and NF-κB p65 transcriptional activity.

Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase

Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.

Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

The effect of 5-aminoimidazole-4-carboxamide-ribonucleoside was mediated by p38 mitogen activated protein kinase signaling pathway in FRO thyroid cancer cells

BACKGROUND/AIMS: 5'-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cellular energy sensor that monitors intracellular AMP/adenosine triphosphate (ATP) ratios and is a key regulator of the proliferation and survival of diverse malignant cell types. In the present study, we investigated the effect of activating AMPK by 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR) in thyroid cancer cells. METHODS: We used FRO thyroid cancer cells harboring the BRAF(V600E) mutation to examine the effect of AICAR on cell proliferation and cell survival. We also evaluated the involvement of mitogen-activated protein kinase (MAPK) pathways in this effect. RESULTS: We found that AICAR treatment promoted AMPK activation and suppressed cell proliferation and survival by inducing p21 accumulation and activating caspase-3. AICAR significantly induced activation of p38 MAPK, and pretreatment with SB203580, a specific inhibitor of the p38 MAPK pathway, partially but significantly rescued cell survival. Furthermore, small interfering RNA targeting AMPK-alpha1 abolished AICAR-induced activation of p38 MAPK, p21 accumulation, and activation of caspase-3. CONCLUSIONS: Our findings demonstrate that AMPK activation using AICAR inhibited cell proliferation and survival by activating p38 MAPK and proapoptotic molecules in FRO thyroid cancer cells. These results suggest that the AMPK and p38 MAPK signaling pathways may be useful therapeutic targets to treat thyroid cancer.

Effect of AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleoside on proliferation, differentiation and apoptosis in U937 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on proliferation, differentiation and apoptosis of U937 cells and explore its possible mechanism.</p><p><b>METHODS</b>U937 cells were cultured with different concentrations of AICAR for 24 h and 48 h. Cell proliferation was evaluated. Cell growth curve was analyzed by CCK-8; cell apoptosis was analyzed by cell morphology, Annexin V/7-AAD double labeling. The differentiation of U937 cells was evaluated by expression of CD11b. The Bcl-xL, Bax, Bim, caspase-3 mRNA expressions of U937 cells were determined by real time PCR.</p><p><b>RESULTS</b>AICAR significantly inhibited the growth of U937 cells in a time-and dose-dependent manner, with a 24 h IC50 value of 1.1 mmol/L and 48 h of 0.9 mmol/L. 1.0 mmol/L AICAR didn't induce differentiation of U937 cells with the increase of CD11b expression for 24 h (P > 0.05). The U937 cells apoptosis was confirmed by cell morphology and Annexin V/7-AAD labeling. AICAR induced apoptosis of U937 cells and the apoptosis rate was (6.81 ± 1.16)% at 1 mmol/L AICAR higher than control group (2.74 ± 0.32)% without AICAR for 24 h treatment (P < 0.05). The real time PCR assay revealed that as compared with control group, the expression of Bim and caspase-3 mRNA were increased, while Bcl-xL and Bax were unchanged on the AICAR treatment.</p><p><b>CONCLUSION</b>AICAR can effectively inhibit proliferation and induce apoptosis of U937 cells. However, it has no significant effect on differentiation of U937 cells. The mechanism may be related with up-regulating Bim and Caspase-3.</p>

Efficacy of Prophylactic Antibiotics in Spinal Surgery

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: The aim of this study was to compare the efficacy of prophylactic antibiotics in spinal surgery for the occurrence of postoperative surgical site infection (SSI) and host immune reactions depending on various administration regimens and protocols. SUMMARY OF LITERATURE REVIEW: The superiority of one regimen or protocol of prophylactic antibiotics over others for SSI in spinal surgery has not been clearly demonstrated. We designed a controlled clinical trial to compare the occurrence of SSI with the changes of hematologic results depending on prophylaxis regimens and protocols. MATERIALS AND METHODS: Between January 2007 and February 2011, two hundred consecutive patients who had undergone thoracolumbar/lumbar surgery for degenerative or traumatic disease were included. Postoperative protocol was altered for each group of fifty consecutive patients; 1st generation cephalosporins for 5-days (group A), 2nd generation cephalosporins for 5-days (group B), 1st generation cephalosporins for 3-days (group C), and 2nd generation cephalosporins for 3-days (group D). Preoperative antibiotic prophylaxis was administrated within 1 hour prior to surgical incision with the same trial antibiotics. Intraoperative bacterial culture was performed from the surgical site. The occurrences of SSI were evaluated as either incisional or organ/space SSI. Serial changes in hematologic inflammatory markers (WBC, ESR, CRP) and DIC markers (fibrinogen, FDP, D-dimer) were compared until postoperative 2 weeks. RESULTS: The study groups were homogeneous regarding age, sex, body mass index, estimated blood loss, diabetes mellitus, smoking, diagnosis, baseline laboratory values, and type of surgery including instrumentation. Overall, 13 cases of incisional SSI (6.5%) and 3 cases (1.5%) of organ/space SSI occurred. There was no difference in the occurrence of incisional and organ/space SSI among the 4 groups (P=0.690, 0.799). Laboratory results revealed that postoperative changes in hematologic inflammatory markers and DIC markers were not influenced by prophylaxis regimens and protocols (all P>0.05). CONCLUSIONS: The occurrences of SSI and host immune responses were not influenced by postoperative antibiotics regimens and protocols. Hematologic investigation revealed that host immune responses did not depend on the type of prophylactic antibiotics.

Evaluation of the Nanopia P-FDP Reagent Kit for Use in the STA-R EVOLUTION Automated Blood Coagulation Analyzer / 임상검사와정도관리

BACKGROUND: In this study on fibrinogen/fibrin degradation products (FDPs), we evaluated the performance of a quantitative immunoturbidimetric assay (ITA) using the new Nanopia P-FDP reagent kit (Sekisui Medical Co., Japan) in comparison with a semiquantitative latex agglutination assay (LA) currently performed using the FDP PLASMA kit (Diagnostica Stago SAS, France). METHODS: The quantitative Nanopia P-FDP method using the STA-R EVOLUTION automated coagulation analyzer (Diagnostica Stago SAS) was evaluated with respect to precision, linearity, carryover, and reference interval. The correlations were measured for each of the 145 samples by using the Nanopia P-FDP method and the semiquantitative FDP PLASMA method. RESULTS: The coefficients of variation with regard to precision in low and high control concentrations were 2.97% and 5.77%, respectively. The correlation coefficient of linearity (r) was 0.990 in the measurement range of 2.4-122.8 microg/mL. The level of carryover was 0.83%, while the reference interval range was 0.22-4.32 microg/mL. The results of FDP assay showed an acceptable accord in 115 samples (79%) among the 145 samples by both LA method and ITA method. Seventeen samples (12%) showed relatively lower FDP values in the LA method than those in the ITA method. Thirteen cases (9%) showed relatively higher FDP values in the LA method than those in the ITA method. CONCLUSIONS: The quantitative Nanopia P-FDP method showed good precision, linearity, carryover, reference interval, and an acceptable concordance rate with the semiquantitative FDP PLASMA method. Thus, the Nanopia P-FDP reagent using the STA-R EVOLUTION automated coagulation analyzer can replace the FDP PLASMA reagent for the quantitative analysis of FDPs.

Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor alpha (TNFalpha) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNFalpha production in vitro and in vivo, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNFalpha mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP-activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNFalpha production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The in vivo effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNFalpha mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNFalpha production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNFalpha production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNFalpha production by cilostazol.

Flexor Tenorrhaphy Using Absorbable Suture Materials

BACKGROUND: Nonabsorbable sutures are favorable for repairing flexor tendons. However, absorbable sutures have performed favorably in an animal model. METHODS: Two-strand sutures using the interlocking modified Kessler method with polydioxanone absorbable sutures 4-0 were used to repair completely ruptured flexor tendons in 55 fingers from 41 consecutive patients. The medical records of average 42 follow up weeks were analyzed retrospectively. The data analyzed using the chi-squared test, and Fisher's exact test was used for postoperative complications. The results were compared with those of other studies. RESULTS: Among the index, middle, ring, and little fingers were injured in 9, 17, 16, and 13 fingers, respectively. The injury levels varied from zone 1 to 5. Of the 55 digits in our study, there were 26 (47%) isolated flexor digitorum profundus (FDP) injuries and 29 (53%) combined FDP and with flexor digitorum superficialis injuries. Pulley repair was also conducted. Concomitant injuries of blood vessels and nerves were found in 17 patients (23 fingers); nerve injuries occurred in 5 patients (10 fingers). Two patients had ruptures (3.6%), and one patient had two adhesions (3.6%). Using the original Strickland criteria, all the patients were assessed to be excellent or good. Also, fibrosis and long-term foreign body tissue reactions such as stitch granuloma were less likely occurred in our study. Compared to the Cullen's report that used nonabsorbable sutures, there was no significant difference in the rupture or adhesion rates. CONCLUSIONS: Therefore, this study suggests that appropriate absorbable core sutures can be used safely for flexor tendon repairs.

A Case of Paratesticular Leiomyosarcoma Successfully Treated with Orchiectomy and Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

A 50-year-old male patient presented with a right scrotal mass that had been growing rapidly for more than one year. A heterogeneous enhancing right scrotal mass (12x9 cm) with para-aortic and peri-caval lymphadenopathies was found on abdominal computed tomography (CT). Right orchiectomy was performed and the gross finding had shown intact testis with a well-defined, huge, whitish solid mass adjacent to the testis. According to pathology, the mass was characterized as a leiomyosarcoma, grade 3 (by National Cancer Instituted [NCI] system). Therefore, the diagnosis was stage III, grade 3 paratesticular leiomyosarcoma. The patient underwent additional systemic chemotherapy using ifosfamide and adriamycin. After nine cycles of chemotherapy, positron emission tomography-CT was performed and no FDP uptake was observed. The patient has been followed up for 12 months after systemic chemotherapy, and he has maintained a complete response. We report here on a rare case of paratesticular leiomyosarcoma treated successfully with orichiectomy and additional systemic chemotherapy.

Beneficial effects of metformin on primary cardiomyocytes via activation of adenosine monophosphate-activated protein kinase / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Metformin has become a cornerstone in the treatment of patients with type-2 diabetes. Accumulated evidence suggests that metformin supports direct cardiovascular effects. The present study aimed to investigate if metformin has beneficial effects on primary cardiomyocytes damaged by H2O2, and reveal the potential mechanism of action of metformin.</p><p><b>METHODS</b>Cardiomyocytes were incubated in the presence of 100 µmol/L H2O2 for 12 hours. Cardiomyocytes were pretreated with metformin at different concentrations and time and with aminoimidazole carboxamide ribonucleotide (AICAR) (500 µmol/L), an adenosine monophophate (AMP)-activated protein kinase (AMPK) agonist for 60 minutes before the addition of H2O2. Other cells were preincubated with compound C (an AMPK antagonist, 20 µmol/L) for 4 hours. The viability and apoptosis of cells were analyzed. AMPK, endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-β1 were analyzed using immunblotting.</p><p><b>RESULTS</b>Metformin had antagonistic effects on the influences of H2O2 on cell viability and attenuated oxidative stress-induced apoptosis. Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-β1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-α.</p><p><b>CONCLUSIONS</b>Metformin has beneficial effects on cardiomyocytes, and this effect involves activation of the AMPK-eNOS pathway. Metformin may be potentially beneficial for the treatment of heart disease.</p>

Globular adiponectin protects human umbilical vein endothelial cells against apoptosis through adiponectin receptor 1/adenosine monophosphate-activated protein kinase pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endothelial dysfunction is a key event in the onset and progression of atherosclerosis in diabetic patients. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. However, no study has addressed apoptosis in human umbilical vein endothelial cells (HUVECs) induced by an intermittent high-glucose media and its association with adiponectin receptor 1 (adipoR1), adipoR2, or adenosine monophosphate (AMP)-activated protein kinase (AMPK).</p><p><b>METHODS</b>HUVECs were cultured in continuous normal glucose (5.5 mmol/L), continuous high glucose (25 mmol/L), alternating normal and high glucose and mannitol. In the alternating normal and high-glucose media, HUVECs were treated under different conditions. First, cells were transfected with the adipoR1-specific small-interfering RNA (siRNA) and then stimulated with globular adiponectin (gAD). Second, cells were cultured in both gAD and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). Third, cells were cultured in the AMPK inhibitor adenine-9-β-D-arabino-furanoside (araA), gAD, and in AICAR.</p><p><b>RESULTS</b>HUVEC apoptosis increased more significantly in an intermittent high-glucose medium than in a constant high-glucose medium. HUVEC apoptosis induced by an intermittent high-glucose medium was inhibited when the cells were pretreated with 3 µg/ml gAD, which rapidly activated AMPK and adipoR1 in HUVECs. However, adipoR2 was not activated.</p><p><b>CONCLUSIONS</b>We found that adipoR1, not adipoR2, is involved in mediating intermittent high-concentration glucose-evoked apoptosis in endothelial cells. gAD activated AMPK through adipoR1, leads to the partial inhibition of HUVEC apoptosis. A fluctuating glucose medium is more harmful than a constant high-glucose medium to endothelial cells.</p>

Marginal fit of three-unit zirconia anterior fixed dental prostheses fabricated using CAD/CAM and MAD/MAM system / 대한치과보철학회지

PURPOSE: The purpose of this study was to compare the marginal fit of three-unit zirconia fixed dental prostheses (FDPs) fabricated using CAD/CAM and MAD/MAM system. MATERIALS AND METHODS: Dentiform maxillary central and lateral incisor were prepared for 3-unit FDP and fixed in yellow stone. This model was duplicated to epoxy resin die. On the resin die, fifteen 3-unit FDPs were fabricated. Metal-ceramic group was three-unit metal-ceramic FDPs, Everest(R) group was zirconia three-unit FDPs fabricated using the Everest(R) system (Kavo Dental GmbH, Biberach, Germany) and Rainbow(TM) group was zirconia three-unit FDPs fabricated using the Rainbow(TM) system (Dentium Co. Inc., Seoul, South Korea). They were cemented to resin dies with adhesive resin cement. After removing pontics, each retainers were separated and observed under measuring machine (Presize 440C) and analyzed through one-way ANOVA and Duncan test (alpha= .05). RESULTS: Mean values and standard deviations of marginal gap dimensions in each group for three-unit FDPs were 78.5 +/- 11.05 microm for the metal-ceramic group, 59.30 +/- 11.63 microm for the Everest(R) group and 70.34 +/- 13.98 microm for the Rainbow(TM) group. CONCLUSION: 1. The Everest(R) group in comparison with metal-ceramic group showed better marginal fit, which had significant differences (P.05). 3. The mean marginal gap values between Rainbow(TM) group and metal-ceramic group did not showed significant differences (P>.05). 4. The mean marginal gaps of each group were within clinically acceptable range (120 microm).

Risk Factors and Control Strategies for the Rapidly Rising Rate of Breast Cancer in Korea / 한국유방암학회지

Due to the aging population and tremendous changes in life style over the past decades, cancer has been the leading cause of death in Korea. The incidence rate of breast cancer is the second highest in Korea, and it has shown an annual increase of 6.8% for the past 6 years. The major risk factors of breast cancer in Korean women are as follows: Early menarche, late menopause, late full-term pregnancy (FTP), and low numbers of FTP. Height and body mass index increased the risk of breast cancer in postmenopausal women only. There are ethnic variations in breast cancer due to the differences in genetic susceptibility or exposure to etiologic agent. With the epidemiological evidences on the possibility of further increase of breast cancer in Korea, the Korean Government began implementing the National Cancer Screening Program against breast cancer in 2002. Five-year survival rates for female breast cancer have improved significantly from 78.0% in early 1993-1995 to 90.0% in 2004-2008. This data indicate that improvement of the survival rate may be partially due to the early diagnosis of breast cancer as well as the increased public awareness about the significance of early detection and organized cancer screening program. The current primary prevention programs are geared towards strengthening national prevention campaigns. In accordance with the improvement in 5-year survival rate, the overall cancer mortality has started to decrease. However, breast cancer death rate and incidence rates are still increasing, which need further organized effort by the Korean Government.

Chronic ethanol feeding impairs AMPK and MEF2 expression and is associated with GLUT4 decrease in rat myocardium

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg(-1)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-1).d(-1)) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKalpha subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFalpha levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKalpha1 and alpha2, the protein levels of total- and phospho-AMPKalpha in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKalpha and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFalpha level. Taken together, chronic ethanol exposure decreases the expression of AMPKalpha and MEF2, and is associated with GLUT4 decline in rat myocardium.

Effects of AMPK on the transcriptional activity of FOXO1 and ubiquitin ligase MuRF1 expression in rat cardiomyocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of AICAR on the activity of transcription factor FOXO1 and expression of ubiquitin ligase MuRF1 in rat cardiomyocytes, and explore the possible role of AMP-activated protein kinase (AMPK) in proteolysis pathways.</p><p><b>METHODS</b>In vitro cultured neonatal rat cardiac myocytes were treated with AICAR, and Western blotting was used to detect the phosphorylation of FOXO1 and expression of MuRF1 in the cells.</p><p><b>RESULTS</b>AICAR activated AMPK in rat cardiac myocytes. Activated AMPK significantly inhibited the phosphorylation of FOXO1 and increased MuRF1 protein expression.</p><p><b>CONCLUSION</b>AMPK may regulate proteolysis by activating FOXO1 transcription factor and up-regulating MuRF1 expression.</p>

Usefulness of Venous Graft in Hand Injury

PURPOSE: In hand injury, pedicle is usually damaged by avulsion injury or crushing injury. Because of postoperative pedicle obliteration, it is often hard to save the injured hand and fingers, even after successful replantation. The author introduces three cases of extensive hand injury, and successful results after applicatoin of multiple venous grafts to these patients. METHODS: In all cases there was no circulation in any finger. In the first case, some vessels were extracted, so venous graft was applied to two sites of severely damaged venous sites. In the second case, venous grafts were applied to all four digital arteries of all fingers except thumb which got severely crushed, and two sites of dorsal veins. In the third case, venous graft was applied to all four digital arteries of all five fingers, and two sites of dorsal veins and palmar veins each. RESULTS: In all cases, survival of hands and fingers was successful. In the second case, however, amputation in thumb and little finger at DIP joint level was inevitable, because of its severe damage, and the large dorsal defect on index finger was filled with DIEP free flap. Thumb was reconstructed with toe-to-thumb free flap, and additional debulking procedures and contracture release is furtherly needed. In the first case, additional surgery was done, as FDP tendon got re-ruptured, but in long term follow-up, satisfactory range of motion was attained. In the third case, FTSG on dorsal skin region was planned. as flap on dorsal area got partial necrosis. CONCLUSION: In hand injury, there are many structures to be repaired, but sometimes venous graft is avoided for its long operating time. Even though the length of damaged vessel is enough for anastomosis, the endothelium is often damaged(zone of injury). In extensive hand injury, successful reconstruction would be possible with active venous graft to all vessels suspicious for damage.

Loop Suture Technique for Flexor Digitorum Profundus Tendon Repair in the Insertion Site

PURPOSE: In the case of repair for far distal parts of FDP (Flexor digitorum profundus) division, the method of either pull-out suture or fixation of tendon to the distal phalanx is preferred. In this paper, the results of a modified loop suture technique used for the complete division of FDP from both zone 1a and distal parts of zone 1b in Moiemen classification are presented. METHODS: From July 2006 to July 2009, the modified loop suture technique was used for the 10 cases of FDP in complete division from zone 1a and distal parts of zone 1b, especially where insertion sites were less than 1 cm apart from a tendon of a stump. In a suture technique, a loop is applied to each distal and proximal parts of tendon respectively. Core suture of 2-strand and epitendinous suture are done with PDS 4-0. Out of 10 patients, the study was done on 6 patients who were available for the follow-up. The average age of the patients was 49.1 years (in the range from 26 to 67). 5 males and 1 female patients were involved in this study. There were 3 cases with zone 1a and distal parts of zone 1b. The average distance to the distal tendon end was 0.6 cm. There were 5 cases underwent microsurgical repair where both artery and nerve divided. One case of only tendon displacement was presented. The dorsal protective splint was kept for 5 weeks on average. The results of the following tests were measured: active & passive range of motion, grip strength test, key pinch and pulp pinch test. RESULTS: The follow-up period on average was 11 months, in the range from 2 to 20 months. There was no case of re-rupture, but tenolysis was performed in 1 cases. In all 6 cases, the average active range of motion of distal interphalangeal joint was 50.8 degree. The grip strength (ipsilateral/contralateral) was measured as 88.7% and the pulp pinch test was 79.2% as those of contralateral side. Flexion contracture was presented in 2 cases (15 degree on average) and there was no quadrigia effect found. CONCLUSION: Despite short length of tendon from the insertion site in FDS rupture in zone 1a and distal parts of zone 1b, sufficient functional recovery could be expected with the tendon to tendon repair using the modified loop suture technique.

Aceptabilidad de sopas deshidratadas de leguminosas adicionadas de realzadores del sabor (UMAMI) / Acceptability of dehydrated legume soups with the addition of flavor enhancers (UMAMI)

The enhancer effect of glutamate monosodium (MSG) flavor was evaluated and its synergistic action with 5'-ribonucleotides: ionone rib nucleotides 5'-monophosphate (IMP) and guano sine monophosphate (GMP) in dehydrated soups consisting of lentils and peas. Four formulations were developed for both soups: the first was the target with the original level of MSG, the following had different concentrations and mixtures of these enhancers (6 percent MSG; 6 percent MSG and 0.26 percent IMP; 0.6 MSG and 0.12 percent IMP-GMP). A five-.point Graphic Hedonic Scale test was used, where 1 represented the most upset face and 5 represented the happiest face. The most accepted soup was selected by thirty elderly adults. The lentils soup with 0,6 MSG and 0J2 percent IMP-GMP and the pea's soup with 6 percent MSG and 0.26 percent IMP obtained the greatest level of acceptance. So, the effectiveness of the synergistic action between the MSG and 5'-ribonucleotides was demonstrated, because they can improve the acceptance of the evaluated formulation.

Se evaluó el efecto realzador del sabor del glutamato monosódico (GMS) y su acción sinergista con 5'-ribonucleótidos: inosinato monofosfato (IMP) y guanilato monofosfato (GMP), cuando se adicionaron a sopas deshidratadas de lentejas y arvejas. Se elaboraron 4 formulaciones para cada sopa, la primera formulación correspondió al control con su nivel de GMS original, las siguientes formulaciones contaron con distintas concentraciones y mezclas de estos realzadores (6 por ciento GMS; 6 por ciento GMS mas 0,26 por ciento IMP y 0,6 GMS mas 0,12 por ciento IMP-GMP). Se utilizó la evaluación sensorial de Escala Hedónica Gráfica, con una escala de 1 al 5, donde 1: representa "la carita más disgustada" y 5: "la más feliz". Treinta adultos mayores determinaron la formulación más aceptada. La sopa de lentejas con 6 por ciento de GMS mas 0,12 por ciento de IMP-GMP fue la que tuvo mayor aceptación, mientras que para la sopa de arvejas fue aquella que contenía 6 por ciento de GMS más 0,26 por ciento de IMP. Por tanto, se pudo demostrar la efectividad de la acción sinergista entre el GMS y los 5'-ribonucleótidos, al mejorar las aceptación de las formulaciones evaluadas.