The Effect of Preoperative Combined with Intravenous Lidocaine and Ketamine vs. Intravenous Ketamine on Pediatric Patients Undergoing Upper Gastrointestinal Endoscopy.

Background: Ketamine is widely used in pediatric sedation. New studies have recommended combination therapy to reduce the side effects of ketamine. Objectives: This study investigated the effect of adding intravenous (IV) lidocaine to ketamine on hemodynamic parameters, endoscopist satisfaction, and recovery time of children undergoing gastrointestinal endoscopy. Methods: This triple-blind, randomized, controlled clinical trial was conducted in Isfahan, Iran (2021). One hundred twenty children between the ages of 1 and 6 were enrolled. Patients were divided into 2 groups. The intervention group received 1.0 mg/kg of IV lidocaine and 1.0 mg/kg of IV ketamine, and the placebo group received 1.0 mg/kg of IV ketamine and placebo 2 minutes before entering the endoscopic room. Patients in both groups were sedated with 1.0 mg/kg of propofol, 0.1 mg/kg of midazolam, and 2.0 ug/kg of fentanyl for the procedure. The pulse rate, mean arterial pressure (MAP), respiratory rate, and oxygen saturation were recorded 1 minute before injection and every 5 minutes afterward. Results: The mean (SD) ages of the intervention and control groups were 3.4 (1.5) and 3.4 (1.7), respectively. The mean difference in hemodynamic parameters between the 2 groups was insignificant during the investigation (P > 0.05). Furthermore, no significant differences were found regarding endoscopist satisfaction scores and length of recovery room stay (P > 0.05). Conclusions: Adding low-dose IV lidocaine to ketamine for pediatric sedation does not significantly affect the hemodynamic status, endoscopist satisfaction, and recovery time.

Morphine promotes migration and lung metastasis of mouse melanoma cells.

BACKGROUND: Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. METHODS: Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 µM) or in combination with a TLR4 inhibitor (morphine10 µM +CLI-095 1µM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg-1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. RESULTS: Morphine (0.1, 1, and 10 µM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 µM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). CONCLUSION: Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

Morphine promotes migration and lung metastasis of mouse melanoma cells

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

The Inhibitory Effects of Vanillin on the Growth of Melanoma by Reducing Nuclear Factor-κB Activation.

Background: Melanoma is skin cancer, and the treatments are not efficient enough. Therefore, finding new drugs seems to be an essential need. Vanillin, which is extracted from vanilla seed, has anti-cancer effects by reducing nuclear factor-κB (NF). We explored the anti-tumor effects of vanillin in the melanoma model and its possible mechanism. Materials and Methods: In the MTT assay, mice melanoma cells (B16F10) were treated with vanillin (1, 2, 3, 4, 5 µg/mL) for 24 and 48 h. In an animal model, B16F10 was subcutaneously injected into C57BL/6 mice. After the development of tumors, the mice were treated with 50 and 100 mg/kg/day of vanillin for 10 days. The tumor size and expression level of NF-κB protein were measured. Results: In the MTT assay, vanillin in all concentrations significantly decreased B16F10 cell viability after 24 h incubation. The size of melanoma tumors was reduced in both doses 50 and 100 mg/kg/day in mice. NF-κB protein expression was decreased in the 100 mg/kg/day group in comparison with the control group. Conclusion: We found that vanillin by reducing NF-κB expression may have anti-tumor effects and reduced melanoma tumor size and cell viability.