Hepatic Arterial Infusion Therapy with Cisplatin using Protein Binding Inhibition : Pharmacokinetics and Antineoplastic Effects of Cisplatin Combined with L-Cysteine in Rats

Cisplatin の蛋白結合には共有結合が関与しており、L-cysteine はcisplatin の共有結合を低下させる。そこで、この蛋白結合阻害を利用してcisplatin の肝動注療法の応用性について検討を行った。実験では、Donryu系雄性ラットにおけるL-cysteine 併用時におけるcisplatin の体内動態と抗腫瘍効果の影響について検討した。その結果、L-cysteine 併用においてcisplatin のtotal とfree 濃度に有意な差はみられなかった。また肝癌ラットを使用したin vivo 実験系において、L-cysteine を併用したcisplatin の肝動注はcisplatin のみの投与に比べ、腫瘍増殖率が抑えられる傾向であることを示した。さらに肝組織中における腫瘍部と非腫瘍部におけるcisplatin 濃度において、L-cysteine 併用により腫瘍部と非腫瘍部に有意な差を認めることができた (p<0.01)。以上の結果より、L-cysteine の併用はcisplatin の肝動注療法へ応用できると考えられる。Covalent binding is involved in the protein binding of cisplatin. L-cysteine reduces the covalent binding of cisplatin. We investigated hepatic arterial infusion therapy with cisplatin using protein binding inhibition. In the present experiment, the pharmacokinetics and antineoplastic effects of cisplatin combined with L-cysteine in male Donryu rats were investigated. As a result, no significant difference was noted in the total and free concentrations of cisplatin combined with L-cysteine. In an in vivo experiment using rats with liver cancer, the hepatic arterial infusion of cisplatin combined with L-cysteine showed that it was the tendency that tumor growth rate was inhibited in comparison with administration only for cisplatin. In addition, concentrations of cisplatin increased significantly between tumor and non-tumor regions in liver tissue when combined with L-cysteine (p<0.01). Thus, L-cysteine can be combined with cisplatin for hepatic arterial infusion therapy

Uptake of Aortic 18F-FDG Is Correlated with Low-Density Lipoprotein Cholesterol and Leptin in a General Population

Objective: This study investigated the relationship between aortic 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to atherosclerosis in a general population. Copyright:Methods: 18F-FDG uptake in the ascending aorta was measured on the positron emission tomography/computed tomography (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio (TBR) was compared with clinical and laboratory atherosclerosis findings.Results: By multivariate regression analysis adjusted for age and sex, TBR-ascending aorta (TBR-A) was significantly correlated with various clinical and laboratory parameters, such as body mass index, log visceral fat area, low-density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log homeostasis model assessment of insulin resistance, log total adiponectin and log-leptin, in all subjects. Furthermore, by multivariate linear regression analysis adjusted for confounding factors, TBR-A was significantly correlated with LDL-C (β=0.001, p=0.03) and log-leptin (β =0.336, p<0.01) in all subjects.Conclusion: TBR-A was significantly correlated with LDL-C and log-leptin independent from confounding factors. Our results suggest that aortic 18F-FDG uptake is a good marker of atherosclerosis, even in a general population

Characteristics of the Study Population.

<p>**; p<0.01, *; p<0.05.</p>a<p> body mass index, ^b blood pressure, ^c fasting plasma glucose, ^d glycosylated hemoglobin A_1c, ^e uric acid, ^f creatinine, ^g estimated glomerular filtration rate, ^h target-to-background ratio-ascending aorta, ⁱimmunoreactive insulin, ^j homeostasis model assessment of insulin resistance, ^k 1,5-anhydroglucitol, ^l high-molecular-weight adiponectin, ^m total adiponectin, ⁿ high sensitive C-reactive protein.</p><p>Characteristics of the Study Population.</p