Ultrasonographic Carotid Artery Flow Measurements as Predictors of Spinal Anesthesia-Induced Hypotension in Elderly Patients: A Prospective Observational Study.

BACKGROUND In elderly patients, spinal anesthesia-induced hypotension (SAH) can be frequently caused by reduced preload and stiff ventricles. The primary purpose of this study was to investigate the ability of ultrasonographic carotid artery flow measurements during the passive leg raise (PLR) test to predict SAH in elderly patients. The correlation between preoperative transthoracic echocardiography (TTE) measurements and SAH was also investigated. MATERIAL AND METHODS The patients aged over 65 years scheduled for elective surgery under spinal anesthesia were recruited. Preoperative TTE was performed in all patients. Corrected carotid flow time and carotid blood flow were measured in the supine, semirecumbent, and PLR positions. Ultrasonographic carotid artery flow and preoperative TTE measurements were compared between patients who developed SAH and those who did not. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to test the association with SAH. RESULTS SAH occurred in 17 of 50 patients. Carotid blood flow in the semirecumbent position and preoperative mitral inflow E velocity could predict SAH, showing an area under the ROC curve of 0.754 (95% CI, 0.612-0.865) and 0.775 (95% CI, 0.634-0.881), respectively. However, according to the multivariate analysis, the independent risk factor for SAH was mitral inflow E velocity (OR 0.918, 95% CI 0.858-0.982, P=0.013). CONCLUSIONS In elderly patients, ultrasonographic carotid artery flow measurements failed to predict the occurrence of SAH. Only preoperative mitral inflow E velocity of TTE was selected as an independent risk factor for SAH.

Physician-Customized Strategies for Reducing Outpatient Waiting Time in South Korea Using Queueing Theory and Probabilistic Metamodels.

The time a patient spends waiting to be seen by a healthcare professional is an important determinant of patient satisfaction in outpatient care. Hence, it is crucial to identify parameters that affect the waiting time and optimize it accordingly. First, statistical analysis was used to validate the effective parameters. However, no parameters were found to have significant effects with respect to the entire outpatient department or to each department. Therefore, we studied the improvement of patient waiting times by analyzing and optimizing effective parameters for each physician. Queueing theory was used to calculate the probability that patients would wait for more than 30 min for a consultation session. Using this result, we built metamodels for each physician, formulated an effective method to optimize the problem, and found a solution to minimize waiting time using a non-dominated sorting genetic algorithm (NSGA-II). On average, we obtained a 30% decrease in the probability that patients would wait for a long period. This study shows the importance of customized improvement strategies for each physician.

Astaxanthin induces NADPH oxidase activation and receptor­interacting protein kinase 1­mediated necroptosis in gastric cancer AGS cells.

Astaxanthin (ASX), a red­colored xanthophyll carotenoid, functions as an antioxidant or pro­oxidant. ASX displays anticancer effects by reducing or increasing oxidative stress. Reactive oxygen species (ROS) promote cancer cell death by necroptosis mediated by receptor­interacting protein kinase 1 (RIP1) and RIP3. NADPH oxidase is a major source of ROS that may promote necroptosis in some cancer cells. The present study aimed to investigate whether ASX induces necroptosis by increasing NADPH oxidase activity and ROS levels in gastric cancer AGS cells. AGS cells were treated with ASX with or without ML171 (NADPH oxidase 1 specific inhibitor), N­acetyl cysteine (NAC; antioxidant), z­VAD (pan­caspase inhibitor) or Necrostatin­1 (Nec­1; a specific inhibitor of RIP1). As a result, ASX increased NADPH oxidase activity, ROS levels and cell death, and these effects were suppressed by ML171 and NAC. Furthermore, ASX induced RIP1 and RIP3 activation, ultimately inducing mixed lineage kinase domain­like protein (MLKL) activation, lactate dehydrogenase (LDH) release and cell death. Moreover, the ASX­induced decrease in cell viability was reversed by Nec­1 treatment and RIP1 siRNA transfection, but not by z­VAD. ASX did not increase the ratio of apoptotic Bax/anti­apoptotic Bcl­2, the number of Annexin V­positive cells, or caspase­9 activation, which are apoptosis indices. In conclusion, ASX induced necroptotic cell death by increasing NADPH oxidase activity, ROS levels, LDH release and the number of propidium iodide­positive cells, as well as activating necroptosis­regulating proteins, RIP1/RIP3/MLKL, in gastric cancer AGS cells. The results of this study demonstrated the necroptotic effect of ASX on gastric cancer AGS cells, which required NADPH oxidase activation and RIP1/RIP3/MLKL signaling in vitro.

Effect of Astaxanthin on Activation of Autophagy and Inhibition of Apoptosis in Helicobacter pylori-Infected Gastric Epithelial Cell Line AGS.

Helicobacter pylori (H. pylori) infection leads to the massive apoptosis of the gastric epithelial cells, causing gastric ulcers, gastritis, and gastric adenocarcinoma. Autophagy is a cellular recycling process that plays important roles in cell death decisions and can protect cells by preventing apoptosis. Upon the induction of autophagy, the level of the autophagy substrate p62 is reduced and the autophagy-related ratio of microtubule-associated proteins 1A/1B light chain 3B (LC3B)-II/LC3B-I is heightened. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are involved in the regulation of autophagy. Astaxanthin (AST) is a potent anti-oxidant that plays anti-inflammatory and anti-cancer roles in various cells. In the present study, we examined whether AST inhibits H. pylori-induced apoptosis through AMPK-mediated autophagy in the human gastric epithelial cell line AGS (adenocarcinoma gastric) in vitro. In this study, H. pylori induced apoptosis. Compound C, an AMPK inhibitor, enhanced the H. pylori-induced apoptosis of AGS cells. In contrast, metformin, an AMPK activator, suppressed H. pylori-induced apoptosis, showing that AMPK activation inhibits H. pylori-induced apoptosis. AST inhibited H. pylori-induced apoptosis by increasing the phosphorylation of AMPK and decreasing the phosphorylation of RAC-alpha serine/threonine-protein kinase (Akt) and mTOR in H. pylori-stimulated cells. The number of LC3B puncta in H. pylori-stimulated cells increased with AST. These results suggest that AST suppresses the H. pylori-induced apoptosis of AGS cells by inducing autophagy through the activation of AMPK and the downregulation of its downstream target, mTOR. In conclusion, AST may inhibit gastric diseases associated with H. pylori infection by increasing autophagy through the activation of the AMPK pathway.

Inhibitory Effect of ß-Carotene on Helicobacter pylori-Induced TRAF Expression and Hyper-Proliferation in Gastric Epithelial Cells.

Helicobacter pylori infection causes the hyper-proliferation of gastric epithelial cells that leads to the development of gastric cancer. Overexpression of tumor necrosis factor receptor associated factor (TRAF) is shown in gastric cancer cells. The dietary antioxidant ß-carotene has been shown to counter hyper-proliferation in H. pylori-infected gastric epithelial cells. The present study was carried out to examine the ß-carotene mechanism of action. We first showed that H. pylori infection decreases cellular IBα levels while increasing cell viability, NADPH oxidase activity, reactive oxygen species production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) activation, and TRAF1 and TRAF2 gene expression, as well as protein-protein interaction in gastric epithelial AGS cells. We then demonstrated that pretreatment of cells with ß-carotene significantly attenuates these effects. Our findings support the proposal that ß-carotene has anti-cancer activity by reducing NADPH oxidase-mediated production of ROS, NF-B activation and NF-B-regulated TRAF1 and TRAF2 gene expression, and hyper-proliferation in AGS cells. We suggest that the consumption of ß-carotene-enriched foods could decrease the incidence of H. pylori-associated gastric disorders.

Propofol attenuates osteoclastogenesis by lowering RANKL/OPG ratio in mouse osteoblasts.

Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis.

The effect of tulobuterol patches on the respiratory system after endotracheal intubation.

BACKGROUND: Endotracheal intubation during anesthesia induction may increase airway resistance (Raw) and decrease dynamic lung compliance (Cdyn). We hypothesized that prophylactic treatment with a transdermal ß2-agonist tulobuterol patch (TP) would help to reduce the risk of bronchospasm after placement of the endotracheal tube. METHODS: Eighty-two American Society of Anesthesiologists (ASA) category I or II adult patients showing obstructive patterns were divided randomly into a control and a TP group (n = 41 each). The night before surgery, a 2-mg TP was applied to patients in the TP group. Standard monitors were recorded, and target controlled infusion (TCI) with propofol and remifentanil was used for anesthesia induction and maintenance. Simultaneously, end-tidal carbon dioxide, Raw, and Cdyn were determined at 5, 10, and 15 min intervals after endotracheal intubation. RESULTS: There was no significant difference in demographic data between the two groups. The TP group was associated with a lower Raw and a higher Cdyn, as compared to the control group. Raw was significantly lower at 10 min (P < 0.05) and 15 min (P < 0.01), and Cdyn was significantly higher at 5 min (P < 0.05) and 15 min (P < 0.01) in the TP group. A trend towards a lower Raw was observed showing a statistically significant difference 5 min after endotracheal intubation (P < 0.01) in each group. CONCLUSIONS: Prophylactic treatment with TP showed a bronchodilatory effect through suppressing an increase in Raw and a decrease in Cdyn after anesthesia induction without severe adverse effects.

Correlation between Sorangium cellulosum subgroups and their potential for secondary metabolite production.

Phylogenetic analysis of the groEL1 and xynB1 gene sequences from Sorangium cellulosum strains isolated in Korea previously revealed the existence of at least 5 subgroups (A-E). In the present study, we used sequence analysis of polymerase chain reaction-amplified biosynthetic genes of strains from the 5 subgroups to indicate correlations between S. cellulosum subgroups and their secondary metabolic gene categories. We detected putative biosynthetic genes for disorazol, epothilone, ambruticin, and soraphen in group A, group C, group D, and group E strains, respectively. With the exception of KYC3204, culture extracts from group A, group B, and group C strains exhibited no noticeable antimicrobial inhibitory activities. By contrast, culture extracts from group D strains inhibited the growth of Candida albicans, whereas culture extracts from group E strains inhibited the growth of C. albicans and Staphylococcus aureus. High performance liquid chromatography analysis of the culture extracts from the strains of each subgroup revealed unique peak patterns. Our findings indicate the existence of at least 5 subgroups of S. cellulosum strains, each of which has the potential to produce a unique set of secondary metabolites.