Vascular effects of estrogen in type II diabetic postmenopausal women

AbstractOBJECTIVESWe assessed the effects of estrogen on vascular dilatory and other homeostatic functions potentially affected by nitric oxide (NO)-potentiating properties in type II diabetic postmenopausal women.BACKGROUNDThere is a higher cardiovascular risk in diabetic women than in nondiabetic women. This would suggest that women with diabetes do not have the cardioprotection associated with estrogen.METHODSWe administered placebo or conjugated equine estrogen, 0.625 mg/day for 8 weeks, to 20 type II diabetic postmenopausal women in a randomized, double-blinded, placebo-controlled, cross-over design.RESULTSCompared with placebo, estrogen tended to lower low-density lipoprotein (LDL) cholesterol levels by 15 ± 23% (p = 0.007) and increase high-density lipoprotein (HDL) cholesterol levels by 8 ± 16% (p = 0.034). Thus, the ratio of LDL to HDL cholesterol levels significantly decreased with estrogen, by 20 ± 24%, as compared with placebo (p = 0.001). Compared with placebo, estrogen tended to increase triglyceride levels by 16 ± 48% and lower glycosylated hemoglobin levels by 3 ± 13% (p = 0.295 and p = 0.199, respectively). However, estrogen did not significantly improve the percent flow-mediated dilatory response to hyperemia (17 ± 75% vs. placebo; p = 0.501). The statistical power to accept our observation was 81.5%. Compared with placebo, estrogen did not significantly change E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 or matrix metalloproteinase-9 levels. Compared with placebo, estrogen tended to decrease tissue factor antigen and increase tissue factor activity levels by 7 ± 46% and 5 ± 34%, respectively (p = 0.321 and p = 0.117, respectively) and lower plasminogen activator inhibitor-1 levels by 16 ± 31% (p = 0.043).CONCLUSIONSThe effects of estrogen on endothelial, vascular dilatory and other homeostatic functions were less apparent in type II diabetic postmenopausal women, despite the beneficial effects of estrogen on lipoprotein levels

Lack of Mitochondrial DNA Sequence Divergence between Two Subspecies of the Siberian Weasel from Korea: Mustela sibirica coreanus from the Korean Peninsula and M. s. quelpartis from Jeju Island

The objective of this study was to determine the degree of mitochondrial DNA (mtDNA) divergence between two subspecies of Mustela sibirica from Korea (M. s. coreanus on the Korean Peninsula and M. s. quelpartis on Jeju Island) and to examine the taxonomic status of M. s. quelpartis. Thus, we obtained complete sequences of mtDNA cytochrome b gene (1,140 bp) from the two subspecies, and these sequences were compared to a corresponding haplotype of M. s. coreanus, downloaded from GenBank. From this analysis, it was observed that the sequences from monogenic M. s. quelpartis on Jeju Island were identical to the sequences of four M. s. coreanus from four locations across the Korean Peninsula, and that the two subspecies formed a single clade; the average nucleotide distance between the two subspecies was 0.26% (range, 0.00 to 0.53%). We found that the subspecies quelpartis is not genetically distinct from the subspecies coreanus, and that this cytochrome b sequencing result does not support the current classification, distinguishing these two subspecies by pelage color. Further systematic analyses using morphometric characters and other DNA markers are necessary to confirm the taxonomic status of M. s. quelpartis

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4±0.14 μM (r=0.98) and 62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9±0.22 μM (r=0.98) and 195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2:1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer

A pulse of meteoric subsurface fluid discharging into the Chukchi Sea during the Early Holocene Thermal Maximum (EHTM)

This work was supported bythe Korea Ministry of Science and ICT (GP2020-038), by the Korea Ministry of Oceans and Fisheries (NP2011-040 and 1525011795), and by the Korea Polar Research Institute (Grants No. PE20350). W.-L.H. acknowledges the supports from the ArcticSGD, a project supported by the Norway Grants and the EEA Grants (2019/34/H/ST10/00645). Additional funds were contributed by the AWI Research Program PACES-II Workpackage 3.1 and 3.2.The response of Arctic Ocean biogeochemistry to subsurface flow driven by permafrost thaw is poorly understood. We present dissolved chloride and water isotopic data from the Chukchi Sea Shelf sediments that reveal the presence of a meteoric subsurface flow enriched in cations with a radiogenic Sr fingerprint. This subsurface fluid is also enriched in dissolved inorganic carbon and methane that bear isotopic compositions indicative of a carbon reservoir modified by reactions in a closed system. Such fluid characteristics are in stark contrast with those from other sites in the Chukchi Sea where the pore water composition shows no sign of meteoric input, but reflect typical biogeochemical reactions associated with early diagenetic sequences in marine sediment. The most likely source of the observed subsurface flow at the Chukchi Sea Shelf is from the degradation of permafrost that had extended to the shelf region during the Last Glacial Maximum. Our data suggest that the permafrost-driven subsurface flow most likely took place during the 2-3 oC warming in the Early Holocene Thermal Maximum (EHTM). This time scale is supported by numerical simulation of pore fluid profiles, which indicate that a minimum of several thousand years must have passed since the cessation of the subsurface methane-bearing fluid flow.Publisher PDFPeer reviewe

Sirolimus-eluting stent is superior to paclitaxel-eluting stent for coronary intervention in patients with renal insufficiency: Long-term clinical outcomes

Background: Renal insufficiency (RI) is an independent risk factor for the adverse cardiovascular events. Long-term clinical outcome of percutaneous coronary intervention (PCI) in patients with RI is unknown especially in the era of first generation drug-eluting stents (DES). This study aims at comparing clinical outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) based on large scaled registry.Methods: Patients who underwent PCI with DES from January 2004 to December 2009 in the Catholic University of Korea-PCI (COACT) registry were prospectively enrolled. A group of 1,033 patients with RI, defined as estimated glomerular filtration rate under 60 mL/min, were analyzed. Major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR) according to the type of stents were compared.Results: Median follow-up period was 810 days (interquartile range: from 361 to 1,354 days). A group of 612 (59.2%) patients were treated with SES and 421 (40.8%) patients were treated with PES. The PES vs. SES group had significantly higher rate of MACE (35.9% vs. 28.3%, p = 0.01). In multivariate Cox hazard regression analysis, PES vs. SES group had significantly higher rate of MACE (adjusted hazard ratio [AHR] 1.29, 95% confidence interval [CI] 1.02–1.64, p = 0.033), particularly pronounced by all-cause death (AHR 1.34, 95% CI 1.008–1.770; p = 0.044). In further analysis with propensity score matching, overall findings were consistent.Conclusions: In patients with RI, PCI using PES provides poorer clinical outcomes than SES in terms of MACE and all-cause death

Association between humidifier disinfectant exposure during infancy and subsequent neuropsychiatric outcomes during childhood: a nation-wide cross-sectional study

Background The purpose was to determine the association between infant exposure to humidifier disinfectant (HD) with neuropsychiatric problems in pre-school children. Methods A total of 2,150 children (age 4–11 months) were enrolled in the Panel Study of Korean Children (PSKC) study. The Korean version of the Child Behavior Checklist (CBCL) was used for assessments of neuropsychiatric problems. 1,113 children who participated in all the first to third PSKC studies and answered a question about HD exposure were finally enrolled. Results There were 717 (64.5%) children in non-HD group who were not exposed to HD and 396 (35.5%) in HD group with former exposure to HD. Exposure to HD was associated with total neuropsychiatric problems (adjusted odds ratio, aOR = 1.54, 95% CI = 1.15–2.06), being emotionally reactive (aOR = 1.55, 95% CI = 1.00–2.39), having attention problems (aOR = 1.96, 95% CI = 1.10–3.47), having oppositional defiant problems (aOR = 1.70, 95% CI = 1.07–2.71), and having attention deficit/hyperactivity problems (aOR = 11.57, 95% CI = 1.03–2.38). The risks for neuropsychiatric problems were clearly increased in boy, firstborn, and secondary smoker. Conclusions Exposure to HD during early childhood had a potential association with subsequent behavioral abnormalities.This study was supported by a grant from the Seongnam Atopy Project of the Seongnam City Government, Republic of Korea

Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies

Background/Aims: A link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations. Methods: The relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged >= 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the and, 3rd, and 4th weeks. Results: Seventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM. Conclusions: HSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.Y

«Ахеменидская Авеста» через призму античных источников

The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n=74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n=20,084) and lead dust (n=5383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects' jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20-50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation=0.79-0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in the future epidemiologic analyses