BACKGROUND: Native low-density lipoprotein (nLDL) was one of the modifiable risk factors contributed directly to cardiovascular diseases development. We investigated that nLDL stimulation induced NADPH oxidase activation and superoxide production that was an important factor on human aortic smooth muscle cells (hAoSMC) proliferation. METHODS: Superoxide generation was recorded with fluorescent-staining of dihydroethidine or by measuring lucigenin-induced chemiluminescence for 5 minutes. We examined cell proliferation with 4[-3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) reagent and analyzed the change of gene expression by northern blot analysis. RESULTS: nLDL stimulation increased superoxide anion production in hAoSMC that confirmed through dihydroethidine staining and lucigenin-induced chemiluminescence methods. nLDL-induced proliferation abolished with preincubation of superoxide scavengers or NADPH oxidase inhibitor. NADPH as a substrate of NADPH oxidase increased superoxide generation in both nLDL-stimulated and unstimulated cell homogenate, which was completely blocked at the diphenylene iodinium (DPI)- or apocynin-pretreated hAoSMC homogenates. Furthermore, superoxide generation was only observed at the fraction of cellular precipitate, but not in soluble fraction. Expression of p22phox in mRNA level increased with nLDL treatment as early as 30 minutes and transfection of anti-sense oligonucleotide of p22phox completely abolished nLDL-induced proliferation of hAoSMC. CONCLUSIONS: The above results have shown that nLDL-induced proliferation in hAoSMC depends on superoxide production through NADPH oxidase activation.
Blotting, Northern ; Cardiovascular Diseases ; Cell Proliferation ; Dicarbethoxydihydrocollidine ; Gene Expression ; Humans ; Lipoproteins ; Luminescence ; Muscle, Smooth ; Myocytes, Smooth Muscle ; NADP ; NADPH Oxidase ; Risk Factors ; RNA, Messenger ; Superoxides ; Transfection

The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Aging ; Animals ; Aorta/enzymology/physiopathology ; Arginase/genetics/*metabolism ; Endothelium, Vascular/*enzymology/physiopathology ; Enzyme Induction ; Gene Knockdown Techniques ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/*metabolism ; RNA, Small Interfering/genetics ; Reactive Oxygen Species/metabolism ; Up-Regulation ; Vasoconstriction/drug effects

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.
Animals ; Aorta ; Arginase ; Atherosclerosis ; Blood Circulation ; Caesalpinia ; Cardiovascular Diseases ; Endothelium ; Kidney ; Mass Screening ; Mice ; Nitric Oxide ; Nitric Oxide Synthase Type III ; Plants, Medicinal ; Superoxides

OBJECTIVES: Biliary tract cancers (BTCs) are rare but highly fatal. Although the etiology of BTC is poorly understood, gallstones are proposed to be a major risk factor. We conducted a systematic review and meta-analysis to examine the associations between gallstone characteristics and BTC risk. METHODS: We searched the MEDLINE, Embase, and Cochrane Central databases and systematically reviewed cohort and case-control studies published before April 9, 2018. All the included studies reported appropriate risk estimates and confidence intervals (CIs) for associations between the presence, size, number, or duration of gallstones and the risk of BTC, including gallbladder cancer (GBC), extrahepatic bile duct cancer (EBDC), and ampulla of Vater cancer (AOVC). Summary odds ratios (ORs) and their 95% CIs were calculated using a random-effects model in the meta-analysis. Subgroup analyses were conducted to inspect sources of potential heterogeneity, and the Egger test was performed to assess publication bias. RESULTS: Seven cohort studies and 23 case-control studies in Asian, European, and American populations were included. The presence of gallstones was associated with an increased risk of BTC (OR, 4.38; 95% CI, 3.23 to 5.93; I2=91.2%), GBC (OR, 7.26; 95% CI, 4.33 to 12.18), EBDC (OR, 3.17; 95% CI, 2.24 to 4.50), and AOVC (OR, 3.28; 95% CI, 1.33 to 8.11). Gallstone size (>1 vs. <1 cm; OR, 1.88; 95% CI, 1.10 to 3.22) was significantly associated with the risk of GBC. CONCLUSIONS Gallstone characteristics, such as presence, size, and number, are associated with an increased risk of BTC. However, significantly high heterogeneity in the meta-analyses is a limitation of this study.

OBJECTIVES: Biliary tract cancers (BTCs) are rare but highly fatal. Although the etiology of BTC is poorly understood, gallstones are proposed to be a major risk factor. We conducted a systematic review and meta-analysis to examine the associations between gallstone characteristics and BTC risk. METHODS: We searched the MEDLINE, Embase, and Cochrane Central databases and systematically reviewed cohort and case-control studies published before April 9, 2018. All the included studies reported appropriate risk estimates and confidence intervals (CIs) for associations between the presence, size, number, or duration of gallstones and the risk of BTC, including gallbladder cancer (GBC), extrahepatic bile duct cancer (EBDC), and ampulla of Vater cancer (AOVC). Summary odds ratios (ORs) and their 95% CIs were calculated using a random-effects model in the meta-analysis. Subgroup analyses were conducted to inspect sources of potential heterogeneity, and the Egger test was performed to assess publication bias. RESULTS: Seven cohort studies and 23 case-control studies in Asian, European, and American populations were included. The presence of gallstones was associated with an increased risk of BTC (OR, 4.38; 95% CI, 3.23 to 5.93; I2=91.2%), GBC (OR, 7.26; 95% CI, 4.33 to 12.18), EBDC (OR, 3.17; 95% CI, 2.24 to 4.50), and AOVC (OR, 3.28; 95% CI, 1.33 to 8.11). Gallstone size (>1 vs. <1 cm; OR, 1.88; 95% CI, 1.10 to 3.22) was significantly associated with the risk of GBC. CONCLUSIONS Gallstone characteristics, such as presence, size, and number, are associated with an increased risk of BTC. However, significantly high heterogeneity in the meta-analyses is a limitation of this study.

Objective: Arterial blood gas analysis (ABGA) is routinely performed in hyperventilation syndrome (HVS) patients in the emergency department (ED). We tried to substitute end-tidal carbon dioxide (ETCO2) for arterial partial pressure of carbon dioxide (PaCO2) in HVS patients in ED. Methods: It was a prospective observational cohort study of HVS patients from May 2019 to March 2020. Data of age, sex, vital sign, ETCO2 and ABGA were collected. We compared the Pearson correlation between ETCO2 and PaCO2. Results: A total of 135 HVS patients were included in the study. The average value for ETCO2 was 24.9±7.2. It showed a significant linear between ETCO2 and PaCO2. The Pearson correlation coefficient was 0.893 (P<0.001). The linear correlation coefficients of ETCO2 <20 mmHg and ETCO2 20-35 mmHg groups were 0.513 and 0.827, respectively (P<0.001). Conclusion We suggest that ABGA can be replaced by ETCO2 in HVS patients in ED.

As of September 2020, SARS-CoV-2 has infected over 30 million people worldwide, and the death toll has now risen to 950,000. Given that Povidone-iodine (PVP-I) had consistently been showing the virucidal efficacy against various types of viruses, such as SARS-CoV, MERS-CoV, and Ebola, we conducted this study to figure out the virucidal effect against SARS-CoV-2 by using a viral plaque assay. We performed Kill-Time assays to assess the viral inactivation of SARS-CoV-2 contaminants after the application of the PVP-I product (Betadine® Throat Spray, PVP-I 0.45%). This test consisted of clean and dirty conditions and was designed to check the viral titers at a contact time of 60 seconds, which were evaluated by plaque-reduction rates in Vero cells. This PVP-I product fully achieved ≥4 log 10 reductions in viral titers under both clean and dirty conditions. This level of reduction, ≥4 log 10 (99.99%), in viral titers presented to be effective in terms of virucidal efficacy, according to the European standards, EN14476. This study revealed the virucidal efficacy of Betadine® Throat Spray against SARS-CoV-2 virus. Given that the convenience and availability of this product, we think that it may contribute to inhibit viral infection and transmissibility as an active type of personal protective equipment (PPE) by managing the hygiene of patients and medical professionals.

OBJECTIVE: The purpose of this study was to report the authors' preliminary experience using the Amplatzer Vascular Plug (AVP) (St. Jude Medical, Plymouth, MN, USA) for parent artery occlusion of the internal carotid artery (ICA) or vertebral artery (VA). MATERIALS AND METHODS: Between September 2008 and December 2015, we performed 52 therapeutic parent artery occlusions (PAOs) by an endovascular technique. Among them, 10 patients underwent PAO of the carotid or vertebral arteries using AVPs. Clinical and radiographic data of these patients were retrospectively reviewed. RESULTS: The devices were used for VA dissection that presented with subarachnoid hemorrhage (SAH) in five patients, traumatic arteriovenous fistula (AVF) in two patients, spontaneous AVF in one patient, recurrence of carotid-cavernous fistula (CCF) in one patient, and symptomatic unruptured giant ICA aneurysm in one patient. The devices were used in conjunction with detachable and/or pushable coils and in the extracranial segments of the ICA or VA. Complete occlusion of the parent artery was achieved in all patients. There was one intra-procedural rupture of the VA dissection during coiling prior to using the device. CONCLUSION: Results from the current series suggest that the AVP might be used for therapeutic PAO in the extracranial segments of the ICA or VA.
Aneurysm ; Arteries* ; Arteriovenous Fistula ; Carotid Artery, Internal ; Endovascular Procedures ; Fistula ; Humans ; Parents* ; Recurrence ; Retrospective Studies ; Rupture ; Subarachnoid Hemorrhage ; Vertebral Artery*

PURPOSE: Endoscopic thyroidectomy using a cervico-axillary approach (CAA) provides optimal visualization with a smaller dissection plane. Despite the excellent cosmetic results and high patient satisfaction, the surgical and oncologic safety of CAA endoscopic surgery has not been fully established. The present study evaluated the feasibility, safety, and surgical outcomes of CAA endoscopic thyroidectomy. METHODS: From October 2009 to April 2012, 100 patients with papillary thyroid cancer underwent CAA endoscopic thyroidectomy. Patient demographics, pathologic features, and surgical outcomes including complications and recurrence were collected. RESULTS: CAA endoscopic thyroidectomy was successful in all patients, and none required conversion to open thyroidectomy. All patients underwent ipsilateral thyroid lobectomy with or without central compartment neck dissection. The mean tumor size was 1.0±0.6 cm (range, 0.5~1.6), and 35.0% of tumors showed extrathyroidal extension. The mean number of harvested lymph nodes was 4.1±4.4, and metastasis was found in 12.0% of patients. The mean surgical time was 175.2±50.4 min, mean intraoperative blood loss was 42.5±69.2 ml, and the mean hospital stay was 3.3±0.6 days. There were five cases of postoperative transient hypocalcemia and eight cases of vocal cord palsy. No permanent complication or postoperative bleeding was observed. Patients continued to be seen for a median period of 63.7 months, and no recurrence of thyroid cancer was seen. CONCLUSION: CAA endoscopic thyroidectomy is a feasible and safe procedure for low-risk thyroid cancer, with excellent cosmesis. It can be recommended as an alternative option for selected patients with low-risk thyroid cancer.
Demography ; Hemorrhage ; Humans ; Hypocalcemia ; Length of Stay ; Lymph Nodes ; Neck Dissection ; Neoplasm Metastasis ; Operative Time ; Patient Satisfaction ; Recurrence ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy* ; Vocal Cord Paralysis

OBJECTIVE: The aim of this study was to validate the Glasgow-Blatchford score (GBS), Pre-Rockall score (PRS), and AIMS65 score to predict active bleeding in patients with normotension and upper gastrointestinal bleeding (UGIB), and analyze the variables that can predict active bleeding to help develop new predictive factors. METHODS: Data were collected retrospectively from January 2015 to December 2017. A systolic blood pressure ≥90 mmHg were defined as normotension, and the patients were divided into active bleeding and not-active bleeding groups based on an esophagogastroduodenoscopy and levin-tube irrigation. The GBS, PRS, and AIMS65 of each group were calculated. The receiver operator characteristic (ROC) curve and area under the curve (AUC) were also calculated to obtain the predictive power for active bleeding. Furthermore, the factors that can predict active bleeding were analyzed by multivariate logistic regression. The ROC curve and AUC were calculated using the variables that were adopted as useful factors. RESULTS: Of the 250 patients included, 85 were active bleeding and 165 were not-active bleeding. The ROC curve showed GBS (AUC, 0.54; 95% confidence interval [CI], 0.47–0.61), PRS (AUC, 0.58; 95% CI, 0.50–0.65), and AIMS65 (AUC, 0.51; 95% CI, 0.43–0.59) to have low predictive power for active bleeding. Multivariate logistic regression revealed the lactate (odds ratio [OR], 1.10; 95% CI, 1.01–1.20) and shock indices (OR, 4.15; 95% CI, 1.12–15.40) to be significant predictors of active bleeding. When calculating the probability of predicting active bleeding through these variables, AUC 0.64 (95% CI, 0.57–0.71) showed higher prediction power than the previous scores. CONCLUSION: The conventional scoring systems that predict the prognosis of UGIB showed low predictability in predicting active bleeding in UGIB patients with a systolic blood pressure ≥90 mmHg. Further study suggests the development of new score using factors, such as the lactate and shock indices.
Area Under Curve ; Blood Pressure ; Emergency Medicine ; Endoscopy, Digestive System ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Lactic Acid ; Logistic Models ; Prognosis ; Retrospective Studies ; ROC Curve ; Shock