Background and Objectives: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. Methods: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. Results: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55–0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52–0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44–2.44; p=0.936). Conclusions In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell proliferation. Here, we showed that proliferation of hormone-sensitive prostate cancer cells such as LNCaP was significantly enhanced by testosterone stimulation whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not respond to testosterone stimulation. Blocking of AR using bicalutamide abolished testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR blocked testosterone-induced proliferation of LNCaP cells. Basal expression of low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP cells whereas stimulation of testosterone did not affect the expression of LRP6. However, expression of LRP6 in LNCaP cells was increased by testosterone stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced proliferation of LNCaP cells. Given these results, we suggest that androgen-dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate cancer cell proliferation.
Cell Proliferation* ; Low Density Lipoprotein Receptor-Related Protein-6* ; Prostatic Neoplasms* ; Receptors, Androgen ; Testosterone

Phosphatidylinositol 3-kinase (PI3K) is essential for both G protein-coupled receptor (GPCR)- and receptor tyrosine kinase (RTK)-mediated cancer cell migration. Here, we have shown that maximum migration is achieved by full activation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) in the presence of Gbetagamma and PI3K signaling pathways. Lysophosphatidic acid (LPA)-induced migration was higher than that of epidermal growth factor (EGF)-induced migration; however, LPA-induced activation of Akt was lower than that stimulated by EGF. LPA-induced migration was partially blocked by either Gbetagamma or RTK inhibitor and completely blocked by both inhibitors. LPA-induced migration was synergistically increased in the presence of EGF and vice versa. In correlation with these results, sphingosine-1-phosphate (S1P)-induced migration was also synergistically induced in the presence of insulin-like growth factor-1 (IGF-1). Finally, silencing of P-Rex1 abolished the synergism in migration as well as in Rac activation. Moreover, synergistic activation of MMP-2 and cancer cell invasion was attenuated by silencing of P-Rex1. Given these results, we suggest that P-Rex1 requires both Gbetagamma and PI3K signaling pathways for synergistic activation of Rac, thereby inducing maximum cancer cell migration and invasion.
Cell Line, Tumor ; *Cell Movement/drug effects ; Enzyme Activation/drug effects ; GTP-Binding Protein beta Subunits/*metabolism ; GTP-Binding Protein gamma Subunits/*metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Humans ; Lysophospholipids/pharmacology ; Neoplasms/enzymology/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction

OBJECTIVE: To investigate the lipid peroxide levels and protein carbonyls levels in the amniotic fluid of pregnant women with preterm premature rupture of membranes (PPROM). METHODS: The lipid peroxide levels in the amniotic fluid of normal pregnancy (n=20) and pregnant women with PPROM (n=20) were measured by thiobarbituric acid reaction. The protein carbonyl contents in the amniotic fluid of normal pregnancy (n=20) and pregnant women with PPROM (n=20) were determined by the 2,4-dinitrophenylhydrazine method. After amniotic fluid of them were mixed and incubated up to 5 hours with 0.2 mL of 1mM moxalactam, cefodizime, amoxacillin, erythromycin, the lipid peroxide levels and protein carbonyl contents in them were measured. RESULTS: 1. The lipid peroxide levels in the amniotic fluid of pregnant women with PPROM was significantly higher than that of normal pregnancy (9.74+/-0.48 vs. 7.20+/-0.38 nmol/mg protein, P<0.01). 2. The protein carbonyl levels in the amniotic fluid of pregnant women with PPROM was significantly higher than that of normal pregnancy (13.0+/-0.33 vs. 11.27+/-0.17 nmol/mg protein P<0.01). 3. The lipid peroxide levels and protein carbonyls formation by moxalactam in the amniotic fluid of pregnant women with PPROM was significantly higher than basal level (12.08+/-0.81 vs. 9.74+/-0.48 nmol/mg protein, 20.08+/-0.66 vs. 13.0+/-0.33 nmol/mg protein, P<0.01). 4. The lipid peroxide levels and protein carbonyls formation by cefodizime in the amniotic fluid of pregnant women with PPROM was significantly lower than basal level (5.04+/-0.33 vs. 9.74+/-0.48 nmol/mg protein, 9.76+/-0.35 vs. 13.0+/-0.33 nmol/mg protein, P<0.01). 5. There were no significant differences in the levels of lipid peroxide and protein carbonyls by amoxacillin and erythromycin in the amniotic fluid of pregnant women with PPROM between antibiotics-induced and basal levels. CONCLUSION: The lipid peroxidation and the protein carbonyls formation were increased in the amniotic fluid of pregnant women with PPROM. Antibiotics-induced lipid peroxide and protein carbonyl levels were changed in the amniotic fluid of pregnant women with PPROM. Further studies on our results may be beneficial in the selection of antibiotics for pregnant women with PPROM.
Amniotic Fluid ; Anti-Bacterial Agents ; Cefotaxime ; Erythromycin ; Female ; Humans ; Lipid Peroxidation ; Membranes ; Moxalactam ; Phenylhydrazines ; Pregnancy ; Pregnant Women ; Protein Carbonylation ; Rupture ; Thiobarbiturates

PURPOSE:To investigate the change in the antioxidant vitamin levels in maternal uterine venous plasma (MUVP), amniotic fluid (AF), and chorioamnion after vitamin C and E supplementation during pregnancy. METHODS:Thirty pregnant women who were scheduled for elective cesarean section between 37 and 39 gestational weeks were randomized in this study. Fifteen women were given a daily oral dose of vitamin C 1,000 mg and vitamin E 400 IU from 33~34 gestational weeks to delivery. The other fifteen women were not given, as a control group. Maternal uterine venous blood, AF, and chorioamnion were obtained after cesarean section. Lipid peroxides and oxygen-radical absorbance capacity value were measured by thiobarbituric acid reaction and Cao's method respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. The tissue sections of chorioamnion were stained with hematoxylin-eosin and Masson-trichrome stain, and immunohistochemical stain for collagen type IV was also performed. RESULTS:The lipid peroxide levels in MUVP of the study group were significantly lower than those of the control group but in contrast, ORAC (Oxygen-radical absorbance capacity) values were lower in the control group. The alpha-tocopherol levels in MUVP, AF, and chorioamnion study group were significantly higher than those of the control group. Amniotic membrane and subepithelial stromal tissue in the study group were thicker than those in the control group. And subchorionic type IV collagen of placenta tissue in the study group was more stained than that of the control group. CONCLUSION:Maternal vitamin C and E supplementation may be beneficial in the prevention of diseases caused by oxidative stress such as preeclampsia and PROM and in increasing fibrin and type IV collagen in chorioamnion.
alpha-Tocopherol ; Amnion ; Amniotic Fluid ; Ascorbic Acid ; beta Carotene ; Cesarean Section ; Chromatography, Liquid ; Collagen Type IV ; Female ; Fibrin ; gamma-Tocopherol ; Humans ; Lipid Peroxides ; Oxidative Stress ; Placenta ; Plasma ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Thiobarbiturates ; Uric Acid ; Vitamin A ; Vitamin E ; Vitamins

OBJECTIVE: This controlled trial investigated the effect of supplementation with vitamins C and E on the lipid peroxide, antioxidant ability, and antioxidant vitamin levels in full term maternal and umbilical venous plasma. METHODS: Forty pregnant women were randomized in this study. They were nulliparous or multiparous women with history of preeclampsia or preterm premature rupture of membranes (PPROM). Twenty women were given vitamin C (1,000 mg/day) and vitamin E (400 IU/day) from 15~20 gestational weeks to delivery. The others were not given, as a control group. Maternal venous blood was obtained before vitamin supplementation and just before delivery. Umbilical venous blood was obtained after delivery. Lipid peroxide level and oxygen-radical absorbance capacity (ORAC) were measured by thiobarbituric acid reaction and Cao's method, respectively. Ascorbic acid, uric acid, beta-carotene, retinol, alpha-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. Results: Supplementation with vitamins C and E was associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in maternal venous plasma. And it was also associated with decrease in lipid peroxide levels and increase in ORAC values and alpha-tocopherol levels in umbilical venous plasma. CONCLUSION: Supplementation with vitamins C and E may be beneficial in the prevention of oxidant-antioxidant imbalance origin diseases such as preeclampsia, PPROM. And it also may affect antioxidant ability of the fetus.
alpha-Tocopherol ; Ascorbic Acid ; beta Carotene ; Female ; Fetus ; gamma-Tocopherol ; Humans ; Membranes ; Plasma ; Pre-Eclampsia ; Pregnant Women ; Rupture ; Thiobarbiturates ; Uric Acid ; Vitamin A ; Vitamin E ; Vitamins

OBJECTIVE: To investigate and compare the amount of the lipid peroxidation and the protein carbonyls formation in maternal venous plasma of preterm premature rupture of membranes (PPROM) during antibiotics administration. METHODS: PPROM were selected between 25 and 32 weeks of gestation. Eighteen patients (group 1) were treated with amoxicillin and erythromycin for 7 day period, 18 patients (group 2) were treated with 3rd generation cephalosporin (cefodizime, cefditoren) and erythromycin for the same period. Maternal blood were obtained from the two groups before and after the antibiotics administration, day 3 and day 7. Lipid peroxidation levels and protein carbonyl contents were measured by thiobarbituric acid reaction and 2,4-dinitrophenyl hydrazine method. Other 18 women with normal pregnancy between 25 and 32 weeks of gestation of venous blood were checked same things in vitro. Interleukin (IL) -6 was measured by enzyme-linked immunosorbent assay. RESULTS: 1. The lipid peroxidation levels and protein carbonyls formation in the maternal venous plasma of PPROM was significantly higher than that of normal pregnancy (lipid peroxidation levels; 4.77+/-.36 vs 7.11+/-.41 nmol/mg protein, P<001, protein carbonyls formation; 3.55+/-.22 vs 5.69+/-.30 nmol/mg protein, P<001). 2. There were no significant differences in the lipid peroxidation levels and protein carbonyls formation of the maternal venous plasma with PPROM mixed and incubated by amoxicillin, cefodizime, cefditoren, and erythromycin (in vitro). 3. There were no significant differences in the lipid peroxidation levels and protein carbonyls formation of the venous plasma of group 1 between before and after antibiotics administration, day 3 and day 7. 4. There were no significant differences in the lipid peroxide levels of the venous plasma of group 2 between before and after antibiotics administration, day 3 and day 7. 5. The protein carbonyls formation in the venous plasma of group 2 was significantly decreased at day 3 and day 7 after antibiotics administration than that of before (6.04+/-.44 and 5.53+/-.37 vs. 7.04+/-.51 nmol/mg protein, P<005). 6. The levels of IL-6 in the venous plasma of group 2 was significantly decreased at day 7 after antibiotics administration than that of before (7.50+/-.35 vs. 3.13+/-.37 pg/mL, P<005). CONCLUSION: In the maternal venous plasma of PPROM, the lipid peroxidation levels and protein carbonyls formation were increased. The formation of protein carbonyls and IL-6 in the maternal blood of PPROM was decreased by combined treatment of 3rd generation cephalosporin and erythromycin. The results suggest that reactive oxygen species formation by inflammatory reaction is suppressed by the 3rd generation cephalosporins and erythromycin combined treatment.
Amoxicillin ; Anti-Bacterial Agents ; Cefotaxime ; Cephalosporins ; Enzyme-Linked Immunosorbent Assay ; Erythromycin ; Female ; Humans ; Hydrazines ; Interleukin-6 ; Interleukins ; Lipid Peroxidation ; Membranes ; Plasma ; Pregnancy ; Reactive Oxygen Species ; Rupture ; Thiobarbiturates

OBJECTIVE: To evaluate their roles in the pathophysiology of preterm premature rupture of membranes (PPROM), we checked interleukin (IL)-6, lipid peroxide, oxygen-radical absorbance capacity (ORAC) and antioxidant vitamin in the venous plasma and amniotic fluid of women with PPROM. METHODS: Venous plasma and amniotic fluid was taken from 20 normal pregnant women and 20 PPROM pregnancy women. IL-6 levels was determined by enzyme-linked immunosorbent assay. Lipid peroxide levels were measured by thiobarbituric acid reaction. The ORAC levels and the antioxidant levels were measured by Cao's method and by high performance liquid chromatography. RESULTS: The IL-6 levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values/lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ascorbic acid levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.05, P<0.01). CONCLUSION: This result suggest that the increased inflammatory bioactivity, increased lipid peroxidation and decreased antioxidant activity may be involved in the pathophysiology of PPROM. Low levels of ascorbic acid appears to be an important determinant of PPROM.
Amniotic Fluid ; Ascorbic Acid ; Chromatography, Liquid ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; Interleukins ; Lipid Peroxidation ; Membranes ; Plasma ; Pregnancy ; Pregnant Women ; Rupture ; Thiobarbiturates ; Vitamins

PURPOSE: The purpose of this study was to retrospectively analyze the etiologic transition of the predisposing factors and organisms for septic arthritis of the knee. MATERIALS AND METHODS: Between January 1995 and December 2006, 122 cases of septic arthritis of the knee were retrospectively evaluated for the etiologic transition and causative organism with using the patients' medical records. We researched the incidence and causative factor of septic arthritis of the knee, which was diagnosed via the patients' symptoms, physical examinations, hematologic exams, culture studies & cytology of the joint fluid. We assessed the correlation of disease with age, the year the disease happened, the causative factors and the incidence. RESULTS: Septic arthritis of the knee was increased after 40 years old, and it also increased after 1998. The most common predisposing factor was intra-articular injection of the knee joint. Even though there were no detected organisms in 79 cases (64.8%), the most common causative organism was S. aureus (20.5%). CONCLUSION: The most common etiologic factor of septic arthritis of the knee was an intra-articular injection. We should be prudent for using good aseptic technique and the correct procedure to reduce the secondary infection that's recently due to increased invasive treatment of the knee joint.
Arthritis, Infectious ; Coinfection ; Incidence ; Injections, Intra-Articular ; Joints ; Knee ; Knee Joint ; Medical Records ; Physical Examination ; Retrospective Studies