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1.
Keiko Goto Yutaka Fujiwara Takeshi Isobe Naoko Chayahara Naomi Kiyota Toru Mukohara Yukari Tsubata Takamasa Hotta Kenji Tamura Noboru Yamamoto Hironobu Minami 《Cancer science》2019,110(6):1987-1994
Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m2), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m2), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe. 相似文献
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Yoshiki Imamura Takahiro Shinozaki Akiko Okada‐Ogawa Noboru Noma Masahiro Shinoda Koichi Iwata Akihiko Wada Osamu Abe Kelun Wang Peter Svensson 《Journal of oral rehabilitation》2019,46(6):574-587
Burning mouth syndrome (BMS) is a chronic oro‐facial pain disorder of unknown cause. It is more common in peri‐ and post‐menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line–derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network–related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first‐line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well‐designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands. 相似文献
4.
Kazunori Aizawa Takeshi Hanaoka Hiroki Kasai Kaoru Kogashi Setsuo Kumazaki Jun Koyama Hiroshi Tsutsui Yoshikazu Yazaki Noboru Watanabe Osamu Kinoshita Uichi Ikeda 《Hypertension research》2006,29(2):123-128
The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH. 相似文献
5.
Masahiro Yamauchi Hiroko Kusano Etsuko Saito Takeshi Iwata Masashi Nakakura Yasuki Kato Takaaki Uochi Shiro Akinaga Noboru Aoki 《Journal of controlled release》2006,114(2):268-275
Previously, we demonstrated that wrapping dextran fluorescein anionic/cationic lipid complexes with neutral lipids produced a stable formulation that markedly increased the duration of the compound in plasma after intravenous administration to rats. The improved drug-delivery properties of the wrapped liposomes (WL) relative to other formulations suggested that this technology could offer important advantages for the administration of other polyanionic drugs, including antisense oligodeoxynucleotides (ODN). In the present study, we investigated the value of WL for formulating fluorescence-labeled phosphorothioated ODN (F-ODN). WL encapsulating F-ODN/cationic lipid complexes were prepared efficiently using similar methodology to that used in our earlier study. Studies confirmed that these WL were stable in vitro. Following intravenous administration to mice, free F-ODN and naked F-ODN/cationic lipid complexes were rapidly eliminated whereas administration of the WL resulted in high blood concentrations of drug that were maintained for several hours. Additional studies were conducted in mice that were inoculated with tumor cells (Caki-1 xenograft model, human kidney); in these experiments, intravenous administration of WL delivered 13 times more F-ODN to the tumor site than achieved after injection of free F-ODN. 相似文献
6.
Mamoru Uemura MD Masahiko Higashiyama MD Jiro Okami MD Kazuyuki Oda MD Koji Takami MD Ken Kodama MD 《General thoracic and cardiovascular surgery》2006,54(2):289-292
We present a case of intrapulmonary metastasis developing 18 years after complete resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted on chest X-ray in a 76-year-old woman who had undergone complete resection of Masaoka’s stage II thymoma 18 years earlier. Since the nodule grew to 17 mm during a 2-year follow-up, wedge resection was performed. The lesion was histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely late recurrence after complete resection of thymoma is discussed. 相似文献
7.
Katsuo Kamata Ayako Makino Noriyasu Kanie Shu-ichi Oda Takayuki Matsumoto Tsuneo Kobayashi Toyohiko Kikuchi Masato Nishimura Toshio Honda 《Journal of Smooth Muscle Research》2006,42(2-3):75-88
Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders. 相似文献
8.
T Oda N Yoshizawa S Oshima A Takeuchi T Kubota S Kondo Y Oshikawa Y Akashi Y Suzuki H Niwa 《Nihon Jinzo Gakkai shi》1990,32(6):631-641
To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis. 相似文献
9.
H Murakami M Togawa S Takahashi N Kasahara J Yamamoto N Matsuura Y Koshiyama Y Ino M Oda 《Arzneimittel-Forschung》1990,40(12):1352-1358
The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis. 相似文献
10.