Parecoxib expresses anti-metastasis effect through inhibition of epithelial-mesenchymal transition and the Wnt/ß-catenin signaling pathway in human colon cancer DLD-1 cell line.

Colorectal cancer is the third leading cause of cancer death in Taiwan. Current treatments involve combination of surgical resection, radiation, and chemotherapy. These treatments have demonstrated to increased five-year survival of a patient with colorectal cancer. However, metastasis is a major capability of cancer cells that causes poor prognosis, recurrence, and even death. Epidemiological and clinical studies have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) as an effective class of compounds to prevent colon cancer. Parecoxib is an NSAID and the only parenterally administered selective cyclooxygenase (COX)-2 inhibitor. In this study, we evaluated whether parecoxib inhibits the metastasis of DLD-1 human colon cancer cells, a COX-2 null cell line, and the underlying mechanism. Cell migration of the DLD-1 cells was significantly inhibited by parecoxib treatment as shown by the Transwell migration assay. This enhanced anti-migration effect was correlated with the attenuated phosphorylation of Akt, expression of vimentin (a mesenchymal marker), and ß-catenin, and corresponded with the upregulated GSK3ß and E-cadherin (an epithelial marker). These findings suggested that parecoxib could inhibit the epithelial-mesenchymal transition (EMT) and metastasis in human colon cancer cells by downregulating ß-catenin. Thus, parecoxib could provide a novel prospective strategy for a combination treatment with chemotherapeutic drugs against metastasis of human colon cancer.

Correction: Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

[This corrects the article DOI: 10.1371/journal.pone.0186784.].

Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model.

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1ß) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1ß while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

A comparison of three types of postoperative pain control after posterior lumbar spinal surgery.

STUDY DESIGN: Retrospective, nonrandomized, comparative study. OBJECTIVE: This study compared the early postoperative analgesic effects and the postoperative nausea and vomiting (PONV) associated with three methods of pain control after posterior lumbar spinal surgery. SUMMARY OF BACKGROUND DATA: The use of opioids for postoperative pain control is common after spinal surgery; however, PONV is the most frequently encountered side effect, and it is yet to be overcome. The effectiveness of the use of an absorbable low-dose morphine-soaked microfibrillar collagen hemostatic sponge placed on the surface of the dural sac (epidural MMCHS) was compared to patient-controlled analgesia (PCA) and intermittent intramuscular bolus injection of meperidine for postoperative pain control after spine surgery. METHODS: One hundred sixty-five patients who underwent short-segment posterior lumbar spinal decompression and fusion surgery between January 2007 and July 2007 in the orthopedic department of a medical center were enrolled. For postoperative pain control, 40 patients received epidural MMCHS, 48 patients received PCA, and 77 patients received meperidine injection. Patient ratings of pain intensity (visual analog scale score from 0 [no pain] to 10 [most severe pain]), nausea (from 0 [no nausea] to 5 [severe nausea]), and vomiting (from 0 [no vomiting] to 5 [severe vomiting]) were recorded at 4 hours postoperation and on postoperative days 1, 2, and 3. RESULTS: The analgesic effect was enhanced significantly in both epidural MMCHS group and the PCA group as compared with the meperidine group on postoperative days 1 and 2 (P < 0.05). On postoperative days 1, 2, and 3, PONV was more severe in the PCA group than in the other two groups (P < 0.05). The side effects of epidural MMCHS were nausea (25%), pruritus (12.5%), vomiting (5%), and hypotension (2.5%). CONCLUSION: A single low-dose epidural MMCHS is effective for postoperative pain control and minimizes the occurrence of PONV after posterior lumbar spinal surgery.

Synergistic anti-cancer effect of baicalein and silymarin on human hepatoma HepG2 Cells.

This study investigated the effect of baicalein, silymarin, and their combination, on two human liver-derived cell lines, HepG2 (hepatocellular carcinoma) and Chang liver (non-tumor liver cells). It was found that 6.75 microg/ml baicalein or 100 microg/ml silymarin alone significantly inhibited the growth of HepG2. When baicalein was used in combination with silymarin on HepG2, an additive effect at 24 h and a synergistic effect at 48 h were observed. The viability at 48 h was 85.62% from 6.75 microg/ml baicalein treatment; but the viability reduced to 49.67%, 38.56%, and 19.61% when 25, 50, and 100 microg/ml silymarin respectively, was added to the treatment. By contrast, each treatment had little or no effect on Chang liver. Compared to treatment of baicalein or silymarin alone on HepG2, combination of both drugs synergistically increased the percentages of cells in G0/G1 phase and decreased those in S-phase, which were associated with up-regulation of Rb, p53, p21(Cip1) and p27(Kip1) and down-regulation of cyclin D1, cyclin E, CDK4 and phospho-Rb. The results indicate that the combination of baicalein and silymarin eradicates tumor cells efficiently, has minimal deleterious effects to the surrounding normal cells, and offers mechanistic insight for further exploitation of HCC treatment.

The efficacy of protective effects of tannic acid, gallic acid, ellagic acid, and propyl gallate against hydrogen peroxide-induced oxidative stress and DNA damages in IMR-90 cells.

There is increasing evidence that reactive oxygen species (ROS) are intimately involved in the oxidative damage of tissues for a wide variety of pulmonary diseases. Thus, it is desirable to search for chemopreventive agents that can counteract ROS-mediated injury to the pulmonary tissues. Using a human lung fibroblast IMR-90 cells as the experimental model, we first demonstrated that nearly 90% of intracellular ROS could be removed when H(2)O(2)-treated cells (200 microM) simultaneously incubated with 10 microg/mL of tannic acid (TA), gallic acid (GA), ellagic acid (EA), and propyl gallate (PA). Using C(11)-BODIPY(581/591 )as a lipid peroxidation probe, we also attested that all these compounds examined (10 microg/mL) could alleviate H(2)O(2)-evoked lipid peroxidation phenomena. Next, we examined the protective effects of these compounds on the depletion of intracellular glutathione (iGSH) in H(2)O(2)-treated cells using CMF-DA probe. Interestingly, PA was demonstrated to be the only compound that could effectively protect the integrity of iGSH from being depleted by this system. Finally, the protective effects of these compounds against oxidative DNA damage were evaluated using 8-oxoguanine formation as a marker. Our data indicated that all four compounds suppressed the formation of 8-oxoguanine effectively. Taken together, our data suggested that TA, GA, EA, and PA can protect cells from oxidative stress.

Cytotoxic constituents of the stems of Cinnamomum subavenium.

The aim of this study was to evaluate the cytotoxic effects of three new butanolides, subamolides A - C (1-3), and a new secobutanolide, secosubamolide (4), on the human colorectal cancer cell line SW480. Compounds 1-4 are new and were isolated from the stems of Cinnamomum subavenium, along with 17 known compounds. The structures of 1-4 were determined by spectroscopic analysis. Propidium iodide staining and flow cytometry were used to evaluate DNA damage of the treated SW480 cells, and it was found that 1-4 caused DNA damage in a dose-dependent manner after 24 h of treatment.

Dexamethasone effectively reduces postoperative nausea and vomiting in a general surgical adult patient population.

BACKGROUND: Postoperative nausea and vomiting (PONV) is still a common and major complication for surgical patients, which may delay post-anesthetic care unit discharge, prolong hospital stay and thus increase the cost of hospitalization. It is understood that PONV is a multi-factorial outcome and occurs more often with general anesthesia than with other anesthetic methods. Prophylactic administration of antihistamines, antidopaminergics, anticholinergics, phenothiazines, serotonin antagonist, steroids and even acupuncture has been shown to be effective. However, expenses and side effects of these agents have also been a concern for clinical doctors. The aim for this prospective study was to find an agent that is cost effective and side effect free (or at least with a low incidence of side effects) for the prevention of PONV. METHODS: A total of 700 adult surgical patients who planned to have surgery under general anesthesia were enrolled in this double-blinded, randomized and placebo-controlled study. Group P received the placebo (0.9% normal saline 2 ml) and Group D received 10 mg dexamethasone intravenously right before the induction of anesthesia. RESULTS: We found that during the postoperative period of 1-8 h, patients in Group D reported a lower incidence of PONV (24%) than those in Group P (39%, p < 0.001). Patients in Group D also requested less rescue anti-emetic (17%) than those in Group P (30%, p < 0.05). The same phenomenon was also noted in the 8-to-24-hour interval (PONV 4% vs. 12%, p < 0.05 and rescue anti-emetic 3% vs. 9%, p < 0.05 in Group D vs. Group P, respectively.) CONCLUSIONS: We conclude that the prophylactic intravenous administration of 10 mg dexamethasone immediately before the induction of anesthesia is effective in preventing PONV in the general surgical adult patient population.

Sevoflurane-induced oxidative stress and cellular injury in human peripheral polymorphonuclear neutrophils.

Sevoflurane is an inhalation anesthetic used for general anesthesia. Several studies have demonstrated that reactive oxygen species (ROS) exist in cardioprotection when preconditioned with sevoflurane. Moreover, sevoflurane can also directly trigger the formation of peroxynitrite. Up to now, information pertinent to the effect of sevoflurane on cellular injuries in human polymorphonuclear neutrophils (PMN) is scant. In this study, we demonstrated that sevoflurane significantly increases intracellular H2O2 and/or peroxide, superoxide, and nitric oxide (NO) in PMN within 1h treatment. Intensification of intracellular glutathione (GSH) depletion in PMN has been demonstrated with the presence of sevoflurane. Inhibition of sevoflurane-mediated intracellular H2O2 and/or peroxide in PMN by catalase, mannitol, dexamethasone, N-acetylcysteine (NAC) and trolox, but not superoxide dismutase (SOD) pretreatment, was observed. Among them, catalase has the best effect scavenging intracellular H2O2 and/or peroxide, suggesting that H2O2 is the major ROS during sevoflurane treatment. Two apoptotic critical factors-lowering of the mitochondrial transmembrane potential (DeltaPsim) and activation of caspase 3/7-were significantly increased after 1h of sevoflurane treatment. Apoptosis of PMN were determined by comet assay and flow cytometric analysis of annexin V-FITV protein binding to the cell surface. Exposure of PMN to sevoflurane markedly increased apoptosis in a dose-dependent manner. In summary, these results are important for demonstrating the oxidative stress and cellular injury on sevoflurane-treated human PMN.

Anesthesia for pediatric patients with Prader-Willi syndrome: report of two cases.

Prader-Willi syndrome (PWS) is a sporadic disorder of chromosome abnormalities with an estimated prevalence of 1 in 15,000. It mainly affects the central nervous system, and often involves the hypothalamus. Both general and regional anesthesia for these patients is difficult mainly due to morbid obesity. Other common problems include hypotonia, disturbance in thermoregulation, arrhythmia, cor pulmonale, diabetes mellitus, behavior problems, and convulsions. We report on 2 pediatric patients with PWS receiving general anesthesia. The first patient experienced life-threatening episodes of severe hypoxemia in the postanesthesia care unit (PACU) as well as in the pediatric intensive care unit (PICU). Nasal continuous positive airway pressure (CPAP) was suggested by the pediatric pulmonary medicine specialist, and thereafter the patient's condition improved. The clinical course of the second patient was uneventful except for transient intermittent episodes of bronchospasms during emergence. In addition, we discuss differences between these 2 cases and our strategy for the prevention of perioperative complications for PWS patients in the future.

Reproducible hepatic dysfunction following separate anesthesia with sevoflurane and desflurane.

Both desflurane and sevoflurane have individually been reported to induce hepatic dysfunction; however hepatic dysfunction after administration of both of them separately in a single patient has not previously been reported. As their metabolites differ in nature, we considered that it would be unlikely that their combined use would cause sensitization and induce hepatic dysfunction. We report on the first patient with reproducible liver dysfunction after sevoflurane and desflurane. This 54-year-old man sequentially received 3 anesthetics over a 1-year period. The first anesthetic was isoflurane, and the course was uneventful. The second anesthetic was sevoflurane, and this resulted in fever with chills and elevated aspartate aminotransferase (543 U/l) 17 days later. The third anesthetic was desflurane which resulted in a similar clinical picture after 17 days. The symptoms improved, and the serum transaminase level returned to normal after conservative therapy. The similar time interval between the operation date and the onset of hepatic dysfunction, after excluding other possibilities, made us highly suspicious that the hepatic dysfunction was induced by sevoflurane on 1 occasion and desflurane on the other. We suggest that inhaled anesthetics should be totally replaced by intravenous anesthetics for future operations in patients with such a diagnosis.

Delayed hypoxemia after bone cement insertion during total hip replacement under spinal anesthesia--a case report.

We report a case of delayed hypoxemia in an aged healthy male patient, which developed 2 hours after cementation of the prosthesis in total hip replacement (THR) under spinal anesthesia. The patient was doing well throughout the operation but unfortunately, progressive tachypnea was noted 1 h after he was transferred to the recovery room (i.e. 2 h after the application of bone cement into the femur). An hour further, distinct wheeze was heard bilaterally on auscultation, which signified bronchospasm. Arterial blood gases analysis revealed a low PaO2 of 71 mmHg and a decrease of oxygen saturation to 91% with supplement of fractional oxygen of 35%. Aerosolization of bronchodilator with terbutaline was administered and supplemental fractional oxygen was increased to 50%. Although wheezing soon subsided, tachypnea and desaturation persisted. He was then transferred to the surgical intensive care unit for further management. Ventilation-perfusion lung scan was performed, which was suggestive of multiple pulmonary embolism.