Thiamylal sodium increased inflammation and the proliferation of vascular smooth muscle cells / 대한마취과학회지

BACKGROUND: Thiamylal sodium is a common anesthetic barbiturate prepared in alkaline solution for clinical use. There is no previously reported study on the effects of barbiturates on the inflammation and proliferation of vascular smooth muscle cells (VSMCs). Here, we examined the effects of clinical-grade thiamylal sodium solution (TSS) on the inflammation and proliferation of rat VSMCs. METHODS: Expression levels of interleukin (IL)-1α, IL-1β, IL-6, and toll-like receptors in rat VSMCs were detected by quantitative reverse transcription-polymerase chain reaction and microarray analyses. The production of IL-6 by cultured VSMCs or ex vivo-cultured rat aortic segments was detected in supernatants by enzyme-linked immunosorbent assay. VSMC proliferation and viability were determined by the water-soluble tetrazolium-1 assay and trypan blue staining, respectively. RESULTS: TSS increased expression of IL-1α, IL-6, and TLR4 in VSMCs in a dose-dependent manner, and reduced IL-1β expression. Ex vivo TSS stimulation of rat aorta also increased IL-6. Low concentrations of TSS enhanced VSMC proliferation, while high concentrations reduced both cell proliferation and viability. Expression of IL-1 receptor antagonist, which regulates cell proliferation, was not increased by TSS stimulation. Exposure of cells to the TSS additive, sodium carbonate, resulted in significant upregulation of IL-1α and IL-6 mRNA levels, to a greater extent than TSS. CONCLUSIONS: TSS-induced proinflammatory cytokine production by VSMCs is caused by sodium carbonate. However, pure thiamylal sodium has an anti-inflammatory effect in VSMCs. TSS exposure to VSMCs may promote vascular inflammation, leading to the progression of atherosclerosis or in-stent restenosis, resulting in vessel bypass graft failure.

Usefulness of high capacity acetaminophen suppository in cancer pain patients

<b>Purpose</b>: In Japan, the daily dosage limit of acetaminophen is considered to be 1500mg: however, in Europe and the USA, the daily dosage limit of acetaminophen for patients with cancer pain is 4000 mg. In Japan, only 100 mg and 200 mg acetaminophen suppositories are available, which means that cancer pain patients may need to insert up to 3 - 4 acetaminophen suppositories at the same time. Therefore, in this study, we examined the efficacy of 600 and 800 mg suppositories prepared at our hospital. <b>Methods</b>: We measured the serum concentrations of acetaminophen in cancer pain patients prescribed either oral or the rectal formulation of acetaminophen, and examined the side effects of the drug. <b>Results</b>: Our results revealed similar mean blood concentrations of acetaminophen in both the oral and rectal group of patients, and the serum AST, ALT and total bilirubin levels were within normal range in all the cancer pain patients prescribed acetaminophen. <b>Conclusion</b>: Our results suggest good bioavailability of acetaminophen from the acetaminophen suppositories in our cancer pain patients.