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141.
In vitro drug-drug interactions with perospirone and concomitantly administered drugs in human liver microsomes. 总被引:3,自引:0,他引:3
Jin Shimakura Naoko Tani Yoshiko Mizuno Setsuko Komuro Hiroshi Kanamaru 《European journal of drug metabolism and pharmacokinetics》2003,28(1):67-72
In vitro metabolism studies were conducted to assess drug-drug interactions between perospirone, an antipsychotic agent, and concomitantly administered drugs--biperiden, flunitrazepam, haloperidol, and diazepam--using human liver microsomes. The metabolism of perospirone in the presence of 100 microg/ml drugs was decreased to 45-73% of that in their absence, whereas no effects were observed with any of the drugs at 1 microg/ml or lower. The effects of perospirone on the metabolism of concomitantly administered drugs were also assessed, and no inhibitory effect was observed. Thus, the metabolism of perospirone and concomitantly administered drugs did not demonstrate any marked mutual inhibition in the human liver microsomes. On the other hand, the perospirone metabolism was markedly reduced by ketoconazole indicating a major role for CYP 3A4. Based on the inhibition constant (Ki) for perospirone metabolism and the plasma unbound concentration of ketoconazole, in vivo perospirone clearance was estimated to be reduced to 64-90% of the control level. Thus careful attention should be paid to the possibility of increase in unchanged perospirone concentration when perospirone is co-administered with drugs that are known as CYP3A4 inhibitors, including macrolide antibiotics and other imidazole antifungals. 相似文献
142.
Yoshihide Kii Katsuyoshi Nakatsuji Isamu Nose Masafumi Yabuuchi Michiaki Matsuda Tsugutaka Ito 《Drug development research》2003,58(2):209-217
The purpose of this study was to evaluate the effects of ebastine and terfenadine on the electrocardiogram of conscious dogs and cats. In dogs, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the electrocardiographic QT interval and the corrected QT (QTc) interval on the seventh day, whereas the drug did not affect these parameters on the first day. Plasma concentrations of terfenadine and its active metabolite, fexofenadine, reached 306 and 8,541 ng/mL, respectively, on the seventh day. Ebastine at oral doses of 30 and 100 mg/kg once a day for 7 days was without effect on the QT and QTc intervals, whereas the drug slightly shortened the RR interval. On the seventh day following the dose of 100 mg/kg, plasma concentrations of ebastine and its active metabolite, carebastine, reached 36 and 1,939 ng/mL, respectively. In conscious cats, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the QT and QTc intervals, QRS duration, JT and the corrected JT intervals. Unexpectedly, terfenadine induced ventricular tachyarrhythmia and premature beats. On the other hand, ebastine at oral doses of 100 mg/kg once a day for 7 days was without effect on the electrocardiographic parameters in cats. These results suggest that the electrocardiographic changes indicative of the proarrhythmic potential of terfenadine can be evaluated in conscious dogs and especially in conscious cats by repeated oral administration, and that ebastine does not induce such changes. 58:209–217, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
143.
Recently we found that the carboxyl-terminal propeptide of type I collagen (c-propeptide) is a major secretory protein of
osteoblasts. Mature osteoblasts secreted 64 nM c-propeptide, and it was reported that 40 nM c-propeptide inhibited collagen
synthesis at 80% of the control level. In this study, we investigated the effect of c-propeptide on collagen synthesis of
preosteoblasts and osteoblasts, and found that preosteoblasts downregulated collagen synthesis by 40 nM c-propeptide, but
osteoblasts were not affected by the same condition. When the binding activities of c-propeptide for preosteoblasts and osteoblasts
were compared, osteoblasts showed weak affinity to c-propeptide compared with preosteoblasts, and the number of receptors
for c-propeptide decreased in osteoblasts. These results imply that a decrease of receptors in osteoblasts might reduce the
sensitivity of osteoblasts to c-propeptide.
Received: 6 August 1999 / Accepted: 9 May 2000 / Online publication: 22 September 2000 相似文献
144.
Nishikawa T Iguchi T Honda H Harada T Kurosaka M Mizuno K 《Journal of spinal disorders》2000,13(4):360-364
Two case reports of femoral bone lesions simulating lumbar spinal disease are presented. Physical examination and case history were strongly suggestive of lumbar spinal pathology. In case 1, surgical resection of a venous hemangioma in the lumbar epidural space was performed but did not relieve pain. In case 2, conservative treatments for a protruded disk were performed for 3 months before an accurate diagnosis was made. After correct diagnoses were made, excision of the femoral tumors brought rapid relief of all abnormal findings in both cases. Compared with other causes of sciatica, femoral bone tumors are rare. However, careful attention should be paid to rule out these lesions if the diagnosis of a lumbar spinal disease is uncertain. Bone scintigraphy seems to be a sensitive diagnostic method to detect extraspinal osseous lesions. 相似文献
145.
Significant antitumoral activity of cationic multilamellar liposomes containing human IFN-beta gene against human renal cell carcinoma. 总被引:3,自引:0,他引:3
Hiroyuki Nakanishi Yoichi Mizutani Akihiro Kawauchi Osamu Ukimura Takumi Shiraishi Manabu Hatano Masaaki Mizuno Jun Yoshida Tsuneharu Miki 《Clinical cancer research》2003,9(3):1129-1135
PURPOSE: Immunotherapy is the most effective treatment against metastatic renal cell carcinoma (RCC). However, the response rate is approximately 15%. More effective therapy is, therefore, needed for patients with metastatic RCC. We then examined the antitumor effect of cationic multilamellar liposome containing human IFN-beta (huIFN-beta) gene (IAB-1) against RCC. EXPERIMENTAL DESIGN: Concentrations of huIFN-beta protein were measured by ELISA. The cytotoxicity of IAB-1 against human RCC (NC65, ACHN, and freshly isolated RCC cells), prostate and bladder cancer cell lines, and renal proximal tubule endothelial cells (RPTEC5899) was examined by the colorimetric method using tetrazolium salt. Apoptosis was assessed by the acridine-orange staining. For in vivo study, we used NC65 cells inoculated into severe combined immunodeficiency mouse. RESULTS: The RCC cells treated with IAB-1 secreted significant amounts of huIFN-beta protein continuously. Drastic in vitro cytotoxic effect of IAB-1 against RCC was observed. In contrast, treatment with 1000 IU/ml recombinant huIFN-beta protein resulted in weak cytotoxicity. The cytotoxic effect against prostate and bladder cancer cell lines was less than that against RCC. Furthermore, no significant cytotoxicity was observed in RPTEC5899 cells. Apoptosis was observed in the cells treated with IAB-1, but recombinant huIFN-beta failed to induce apoptosis. The size of NC65 tumors transfected with IAB-1 in mice was significantly smaller than that receiving injection of empty liposome or recombinant huIFN-beta protein. CONCLUSION: These findings indicate that IAB-1 may have an antitumor activity against human RCC by inducing apoptosis, suggesting its potential clinical application for gene therapy against RCC. 相似文献
146.
147.
148.
Juxta-articular hemangioma of long bone 总被引:1,自引:0,他引:1
We report on a rare case of an intraosseous hemangioma involving the proximal tibia in a 70-year-old man. Radiographically,
the lesion was a well-defined osteolytic lesion with marginal sclerosis. The CT images demonstrated a well-defined osteolytic
lesion with partial cortical breakthrough. T1-weighted MR images showed a hypointense lesion, while T2-weighted images revealed
hyperintense areas, with internal, hypointense septa. Gadolinium-enhanced T1-weighted images showed lattice-like enhancement
of the lesion.
Received: 28 December 1999 Revision requested: 3 March 2000 Revision received: 23 May 2000 Accepted: 26 May 2000 相似文献
149.
In order to address an age-dependent alteration in the concentration of beta-amyloid polypeptides (Abetas) within the central nervous system and its probable predisposition to amyloidgenesis in Alzheimer's disease (AD), we measured two species of soluble Abetas, Abeta40 and Abeta42, in cerebrospinal fluids (CSF) from randomly selected Japanese control subjects at various ages (n = 33) and then compared these data with those of probable Japanese AD patients (n = 23). CSF concentrations of Abeta40 and Abeta42 peptides were age-dependent (ANOVA, Bonferroni's multiple comparison; p < 0.01 and p < 0.05, respectively) and were lower in the infant than in adults. From mid-20, the Abeta40 concentrations were decreasing while Abeta42 were rather stable. Abetas in CSF from AD patients (n = 23), whose epsilon4 allele frequency of the apolipoprotein E gene was higher than in controls (n = 83, p < 0.03), were not statistically different from those of age-matched controls (n = 13). A linear relationship was detected between the Abeta40 concentration and the Mini-Mental State Examination score (p < 0.05). The ratio of the Abeta42 to the Abeta40 level measured in the AD CSF samples was approximately 38% decreased compared to age-matched controls (p < 0. 05). These data suggest that the physiological metabolism of soluble Abetas in the brain is regulated in an age-dependent manner, and that the ratio of Abeta42 to Abeta40 level in the CSF would be a useful marker for monitoring progression of AD. 相似文献
150.
In order to address the significance of apolipoprotein E (apoE) in the pathogenesis as well as the clinical diagnosis of Alzheimer's disease (AD), we measured its level in cerebrospinal fluid (CSF) from randomly selected Japanese control subjects at various ages (n = 36), which included 14 age-matched controls, and from AD patients including early-onset (n = 11, EOAD) and late-onset (n = 14, LOAD) cases. The CSF apoE level in controls linearly decreased during aging to over 80 years (r(2) = 0.323, p < 0.0001). The CSF apoE level in AD patients was 31.9% elevated compared to the age-matched controls (n = 14, p < 0.05) and linearly increased with a decrement of the patients' Mini Mental State Examination scores. Moreover, the CSF apoE level of EOAD patients (n = 11) was higher than that of LOAD patients (n = 14, p < 0.05), whose APOE epsilon4 allele frequency was significantly higher than that of controls (chi(2) = 7. 16, p < 0.03). Two-dimensional gel electrophoretic analysis of the heparin-Mn(2+)-precipitable lipoprotein fraction in CSFs showed that the ratio between the level of CSF apoA-I and that of CSF apoE of controls was significantly higher than those of all AD and LOAD subjects (p < 0.01, p < 0.05), while the CSF apoA-I-to-apoE ratios of the two AD groups were not significantly different. These results suggest that overproduction of apoE protein may be a consequence of astroglial response to neurodegeneration in AD and that the determination of CSF apoliprotein levels serves as a clinical marker for monitoring the progression of AD. 相似文献