Rhodostomin inhibits thrombin-enhanced adhesion of ROS 17/2.8 cells through the blockade of alphavbeta3 integrin.

Osteosarcoma is a very malignant bone tumor which has a high metastatic potential and usually lead to poor prognosis. The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated the effect of thrombin on the adhesion activity of the osteosarcoma cell line, ROS 17/2.8. Incubation with the low concentrations of thrombin (0.01-5 U/ml, 5 min to 24 h) elevated the adhesion activity of ROS 17/2.8 to both human umbilical vein endothelial cells (HUVEC) and extracellular matrix, with the peak effect at the concentration of 0.5 U/ml for 30 min at 37 degrees C. The ROS 17/2.8 cells responded to thrombin by a peak effect of increased adhesion to HUVEC (5.5 folds vs. control) and fibronectin (4.8 folds) after thrombin pretreatment (0.5 U/ml, 30 min, 37 degrees C). Pretreatment with monoclonal antibodies against beta3 integrins, including anti-alphavbeta3, 10E5 and 7E3, effectively antagonized the thrombin-enhanced cell adhesion activity, whereas anti-alpha3beta1 and anti-alpha5beta1 did not antagonize the enhanced cell adhesion. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, and synthetic peptide RGDS also blocked the thrombin-enhanced ROS 17/2.8 cell adhesion. This study demonstrated that thrombin enhanced the cell adhesion of ROS 17/2.8 cells to HUVEC or ECM through an upregulation of beta3 integrins, and rhodostomin was a strong inhibitor on thrombin-enhanced cell adhesion, either to HUVEC or fibronectin substratum.     

Influence of intravenous anesthetics on neuromonitoring of the recurrent laryngeal nerve during thyroid surgery

Limited reports are available in the literature on the impact of intravenous administration of anesthetics on laryngeal electromyographic (EMG) activity. The purpose of this study was to determine the influence of the two commonly used intravenous anesthetics (propofol and thiamylal) on EMG amplitude evoked from the recurrent laryngeal nerve (RLN) during thyroid surgery. A total of 40 patients were randomized to receive a bolus of propofol (0.5 mg/kg; n = 20) or thiamylal (1.5 mg/kg; n = 20) to increase anesthetic depth when the surgeon found patient movement intraoperatively. Evoked potentials were obtained before and every 1 minute after the administration of each agent for up to 5 minutes by stimulating the RLN. The magnitude of evoked potentials at each time point and hemodynamic response were compared within groups. The mean amplitude of evoked potentials did not change significantly after administration of either propofol or thiamylal (p > 0.05 within groups). Mean arterial pressure measured from 1 minute to 5 minutes was significantly lower in the propofol group than in the thiamylal group (p < 0.05). Heart rate measured within 5 minutes did not differ significantly within groups. Low dose of propofol (0.5 mg/kg) or thiamylal (1.5 mg/kg) did not affect EMG readings during neuromonitoring of the RLN in thyroid surgery. Our results show that thiamylal provides better hemodynamic stability than propofol, and is therefore a preferable agent to increase anesthesia depth and prevent further patient movement during intraoperative neuromonitoring.     

Late Effects in Mouse Heart after 60Co γ-irradiation of the Brain: An Ultrastructural Study

Summary

A single dose of 8 or 20 Gy ⁶⁰Co γ-rays was given to C3H male mice at 4 months of age. Degenerative changes in the cardiac muscle due to brain irradiation were observed first at 6 months after irradiation, and became progressively more severe at 12–24 months. The changes seen at the ultrastructural level included myofibrillolysis, the presence of lysosomal-like bodies and interstitial fibrosis. Ultrastructural changes in the control cardiac muscle throughout the experimental period were monitored and only minor aging changes were noted. The coronary arteries of control mice began to show a slight amount of smooth muscle degeneration and fibrosis 1 year into the experiment. At 18 months the lesions became more severe, and at 24 months there was relatively less distinction between the control and the 20 Gy treated group. Degenerative changes in the coronary arteries were noticed at 6 months after irradiation, and became progressively more severe at later times (12–24 months). The major changes included smooth muscle degeneration with fibrosis and the accumulation of debris and extracellular matrix. At 18 months the medial smooth muscle showed severe damage, with accumulations of matrix material and debris. There was additional fibrosis in the adventitial layer. There were few additional changes at 24 months after 20 Gy irradiation. Quantitative analyses indicated that the average fractional volumes of degenerated smooth muscle cells were 13, 27 and 39% in the unirradiated group at 12, 18 and 24 months, respectively, and 13 and 29% in the sham-irradiated group at 12 and 18 months into the experiment, respectively. These percentages were 12, 32 and 49% (P < 0·05) after 8 Gy irradiation, and 19% (P < 0·05), 46% (P < 0·01), and 42% after 20 Gy irradiation, respectively.