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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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Eri Inoue-Matsuhisa Sayoko E Moroi Hisashi Takenaka Shunji Sogo Tomiya Mano 《Journal of ocular pharmacology and therapeutics》2003,19(1):55-62
The serotonin 2 (5-HT(2)) receptor antagonists, MCI-9042 (Anplag) and ketanserin, have been shown to lower intraocular pressure in rabbits (1) and humans (2). The mechanism of action of these drugs has not been determined, but it is hypothesized that 5-HT(2) receptors, and possibly alpha-adrenergic receptors, (3) may regulate in part aqueous humor production via an intracellular signal transduction pathway in the ciliary body. We therefore examined whether 5-HT(2) receptors were coupled to phosphoinositide hydrolysis in an organ culture system of isolated bovine ciliary epithelium. 5-HT stimulated [(3)H]inositol phosphates ([(3)H]InsPs) accumulation in a dose-dependent manner with a maximum increase approximately twice over the basal level. The mean EC(50) value was 1.1 microM, which was calculated from four dose-response curves. The 5-HT stimulated accumulation of [(3)H]InsPs was inhibited by spiperone (5-HT(2A/1A) and dopamine 2 (D(2)) antagonists), M-1 (a major metabolite of MCI-9042), ketanserin (5-HT(2A) antagonist), SB-206553 (5- HT(2B/2C) antagonist), and mesulergine (5-HT(2C) antagonist and D(2) agonist). It was not inhibited by chlorpromazine, which is a D(2) receptor antagonist. Accordingly, our study demonstrates that 5-HT(2) receptors are coupled to phospholipase C in bovine ciliary epithelium. 相似文献
5.
Eri Ogawa Yuichiro Otsubo Norihiro Taira Nihal S. Agar 《Comparative clinical pathology》2005,13(3):137-141
Uptake of dehydroascorbic acid (DHA) was studied in two types of dog erythrocytes with high GSH and normal GSH levels. Compared with ascorbic acid uptake, DHA produced a much greater ascorbic acid accumulation in dog erythrocytes. Both dog erythrocytes showed a concentration dependence of DHA uptake, and cellular ascorbic acid concentrations were significantly higher in high-GSH cells than in normal-GSH cells. Glucose and cytochalasin B inhibited DHA uptake. This suggests that DHA enters dog erythrocytes predominantly by the facilitated glucose transporter, particularly by the Glut 1 glucose transporter. The rate of glucose uptake was quite similar in the two types of cells. Compared with normal-GSH cells, high-GSH cells were more resistant to oxidative stress induced by high concentration of DHA. As a rapid entry of DHA inflicts on cells a heavy demand for GSH for its reduction to ascorbic acid, high-GSH cells containing a larger reserve of GSH have an advantage over normal-GSH cells in both ascorbic acid accumulation and resisting oxidative stress produced by DHA. 相似文献
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Kazuki Hotta 《Ophthalmic surgery, lasers & imaging》2007,38(4):336-338
To determine postoperative refractive errors of secondary intraocular lens (IOL) implantation, this study was performed in 42 eyes of 42 patients following secondary IOL implantation fixed in the sulcus after simultaneous vitrectomy and phacoemulsification and aspiration. Controls were 138 eyes of 124 patients with cataract who underwent phacoemulsification and aspiration and IOL implantation. The spread between expected and actual refraction (actual - expected) was -0.81 +/- 0.86 diopters (average +/- standard deviation) in the study group and 0.01 +/- 0.91 diopters in the control group (statistically significant, P < .001, Student's t test). The actual refractive errors in the study subjects were shifted toward myopia compared with the controls. 相似文献
8.
Long-term lithium treatment causes serotonin receptor down-regulation via serotonergic presynapses in rat brain 总被引:2,自引:0,他引:2
The effects of lithium treatment on serotonin (5-HT) receptors in rat frontal cortex and hippocampus were investigated. Long-term lithium treatment strongly blocked 5-hydroxytryptophan-induced head twitches, while acute lithium administration by itself induced head twitches in rats, and ketanserin blocked this acute lithium action. Long-term administration of lithium decreased the number of not only 5-HT2 receptors in the frontal cortex but also 5-HT1 and 5-HT2 receptors in the hippocampus in rats. Decreases in 3H-5-HT binding to hippocampal 5-HT1 receptors and 3H-spiperone binding to frontal cortical 5-HT2 receptors, caused by chronic lithium treatment, were abolished by co-administration of p-chlorophenylalanine, and were enhanced by co-administration with methiothepin. The turnover of 5-HT in either frontal cortex or hippocampus was facilitated by lithium, and co-administered methiothepin enhanced this facilitation. These results suggest that long-term lithium treatment causes the down-regulation of postsynaptic 5-HT1 and 5-HT2 receptors, in part probably through its action on presynaptic nerve terminals. 相似文献
9.
Alexia with agraphia is very rare symptom in multiple sclerosis. We present a patient of opticospinal multiple sclerosis with kanji-predominant alexia with agraphia. A 55-year-old, right-handed man was admitted to our hospital because of difficulty in reading and writing in August 2001. The patient had been diagnosed as having relapsing-remitting opticospinal multiple sclerosis eight years prior to admission. Language examination showed alexia with agraphia predominantly affecting kanji and also mild naming difficulties, but a good comprehension and a normal repetition. T2-weighted MRI demonstrated hyperintensity area in the left temporo-parietal lobe, involving the white matter beneath the postero-inferior temporal lobe and inferior parietal lobule. On brain SPECT, low blood perfusion was observed in the left temporo-parietal regions. Although agraphia for kana and alexia for both kana and kanji improved after steroid therapy, agraphia for kanji did not improve. After the treatment, high intensity area of inferior parietal lobule was disappeared on MRI, and the hypoperfusion of inferior parietal lobule on brain SPECT was also improved, but the lesion of left postero-inferior temporal lobe did not show any remarkable changes. We considered that the kanji-predominant alexia with agraphia was due to the lesions of left inferior parietal lobule and postero-inferior temporal lobe, and agraphia for kanji was due to the lesion of left postero-inferior temporal lobe. 相似文献
10.
Soichi Hotta Hiromasa Kashimura Shinji Hirai Akira Nakahara Hisayuki Fukutomi Toshiaki Osuga Yasuo Uchiyama 《Lasers in surgery and medicine》1995,16(3):262-271
Background and Objective: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. Study Design/Materials and Methods: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. Results: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. Conclusion: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH. 相似文献