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991.
Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats. 总被引:15,自引:2,他引:13 下载免费PDF全文
M Takemoto K Egashira M Usui K Numaguchi H Tomita H Tsutsui H Shimokawa K Sueishi A Takeshita 《The Journal of clinical investigation》1997,99(2):278-287
The long-term administration of N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, produces coronary vascular remodeling and myocardial hypertrophy in animals. This study used a rat model to investigate the role of angiotensin I converting enzyme (ACE) in the pathogenesis of such changes. We studied the following groups, all of which received drug treatment in their drinking water: untreated controls, and those administered L-NAME, L-NAME, and an ACE inhibitor (ACEI), and L-NAME and hydralazine. Cardiovascular structural changes and tissue ACE activities were evaluated after the first, fourth, and eighth week of treatment. In rats treated with L-NAME alone, vascular remodeling was evident at the fourth and eighth week, and myocardial hypertrophy was present at the eighth week of treatment. The vascular and myocardial remodeling were characterized by increased tissue ACE activities and immunodetectable ACE in those tissues. These changes were markedly reduced by ACEI, but not by hydralazine treatment. Increased local ACE expression may thus be important in the pathogenesis of cardiovascular remodeling in this model. 相似文献
992.
M Takeda T Sasagawa K Saito T Tsutsui H Takahashi H Go T Nishiyama A Hatano R Watanabe T Saito 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》1992,83(5):605-610
The effect of double Malecot type polyurethane intraurethral catheter (IUC) was examined in 17 benign prostatic hypertrophy patients who were unfit for operation and suffered from urinary retention. Patients were aged 68 to 90 (mean 80.5) years old and the causes of IUC insertion were cardiac, cerebrovascular, respiratory and gastrointestinal diseases, diabetes mellitus and aging. IUC was selected among three types (55, 60, 65 mm) according to the length of prostatic urethra. Insertion of IUC was carried out easily under fluoroscopic guidance without endoscopy. All patients could void by themselves just after insertion of IUC and the longest indwelling period was 10 months. The length of IUC need not be longer than that of prostatic urethra and patients with normal or hypertonic bladder could void better than those with atonic bladder. Urinary tract infection did not get worse in any patients with indwelling IUC. Double Malecot type polyurethane IUC is a safe and an effective alternative method in place of urethral balloon catheter for inoperable prostatic hypertrophy patients in urinary retention. 相似文献
993.
T Haruta T Tsutsui S Kuroki H Nigami Y Kobayashi 《The Japanese journal of antibiotics》1989,42(9):2016-2022
The clinical effectiveness of cefteram pivoxil (CFTM-PI) granule, a new oral cephalosporin, was studied in pediatric patients. The results are summarized as follows. 1. CFTM-PI was given orally to 17 children in daily doses of 9.5 to 31.8 mg/kg in 3 to 4 divided portions for 2 to 10 days. Clinical evaluations were made on 14 patients. Clinical effects of CFTM-PI were excellent in 4, good in 5 of 9 patients with tonsillitis or pharyngitis, excellent in all cases of 2 patients with pneumonia, 1 patient with scarlet fever and 1 patient with pyelonephritis, and fair in 1 patient with purulent cervical lymphadenitis. Overall clinical effects were excellent in 8, good in 5, and fair in 1 with an efficacy rate of 92.9%. 2. No side effects were observed in any of the 17 patients. Hematological tests showed a slight elevation of blood platelet counts in 1 patient. 3. The taste and odor of CFTM-PI granule were well accepted by the children. 4. CFTM-PI is a useful oral antibiotic for the treatment of bacterial infections in pediatrics. 相似文献
994.
H. Nakasa H. Nakamura S. Ono M. Tsutsui M. Kiuchi S. Ohmori M. Kitada 《European journal of clinical pharmacology》1998,54(2):177-183
Objective: The purposes of this study were to identify the P450 enzyme (CYP) responsible for zonisamide metabolism in humans by using
expressed human CYPs and to predict drug interaction of zonisamide in vivo from in vitro data. Methods: Ten expressed human CYPs and human liver microsomes were used in the experiments for the identification of enzymes responsible
for zonisamide metabolism and for the prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro
data, respectively. Two-sulfamoylacetyl phenol, a reductive metabolite of zonisamide, was measured by the HPLC method. Results: From the experiments using ten expressed human CYPs, CYP2C19, CYP3A4 and CYP3A5 were shown to be capable of catalyzing zonisamide
reduction. However, an intrinsic clearance, Vmax/kM, of CYP3A4 was much higher than those of CYP2C19 and CYP3A5. From the point of view of enzyme amount in human liver CYPs
isoform and their intrinsic clearance, it was suggested that CYP3A4 is mainly responsible for zonisamide metabolism in human
CYPs. Zonisamide metabolism in human liver microsomes was markedly inhibited by cyclosporin A, dihydroergotamine, ketoconazole,
itraconazole, miconazole and triazolam. We estimated the possibility and degree of change of zonisamide clearance in vivo
in clinical dose range from in vitro inhibition constant of other drugs against zonisamide metabolism (Ki) and unbound inhibitor
concentration in blood (Iu) in clinical usage. Clearance of zonisamide was maximally estimated to decrease by 31%, 23% and
17% of the clearance without inhibitors i.e. ketoconazole, cyclospolin A and miconazole, respectively. Fluconazole and carbamazepine
are estimated to decrease by 5–6% of the clearance of zonisamide. On the other hand, there may be lack of interaction of zonisamide
metabolism by dihydroergotamine, itraconazole and triazolam in clinical dose range. Conclusion: We demonstrated that: (1) zonisamide is metabolized by recombinant CYP3A4, CYP2C19 and CYP3A5, (2) the metabolism is inhibited
to a variable extent by known CYP3A4/5 substrates and/or inhibitors in human liver microsomes, and (3) in vitro-in vivo predictive
calculations suggest that several compounds demonstrating CYP3A4-affinity might cause in vivo drug-drug interactions with
zonisamide.
Received: 12 June 1997 / Accepted in revised form: 17 November 1997 相似文献
995.
996.
Y Kobayashi T Haruta S Kuroki K Okura S Tsuji T Tsutsui 《The Japanese journal of antibiotics》1983,36(4):849-854
T-1982 (cefbuperazone), a new injectable cephamycin antibiotic, was employed for bacterial infections in children, and the following results were obtained. 1. When administered intravenously at a dose of 20 mg/kg to a 6-year-old female child, serum levels were 62 micrograms/ml at 30 minutes, 39 micrograms/ml at 1 hour, 17.6 micrograms/ml at 2 hours, 6.8 micrograms/ml at 4 hours and 2.9 micrograms/ml at 6 hours with serum half-life (T 1/2) of 76 minutes. Urinary excretion rates were 41.0, 5.3% and 2.4% respectively at 0-2, 2-4 hours and 4-6 hours, and urinary levels were 820 micrograms/ml, 182 micrograms/ml and 310 micrograms/ml, respectively. The total urinary recovery within 6 hours was 48.7%. 2. A total of 11 cases of pediatric infections was treated with T-1982. The clinical efficacy evaluated for 9 cases, excluding 2 cases of non-bacterial infections, was as follows; excellent in 4, good in 1 out of 5 cases of pneumonia, good in 1 case of cervical purulent lymphadenitis, and excellent in 1, good in 1, poor in 1 out of 3 cases of urinary tract infection. 3. As side effect, mild diarrhea in 1 case and slight elevation of GOT, GPT in 2 cases were observed. 4. These results suggest that T-1982 is of good use for bacterial infections in children and the expected efficacy is obtained at a dose of 20 mg/kg 3 times a day. 相似文献
997.
T. Takahiro Tsukamoto K. Morita M. Naya C. Katoh Y. Kuge H. Okamoto H. Tsutsui N. Tamaki M. Mehdi Namdar P. T. Siegrist P. Koepfli P. Tschuetscher T. F. Hany C. A. Wyss P. A. Kaufmann R. Riikka Lautamäki K. E. J. Airaksinen M. Seppänen J. Toikka M. Luotolahti E. Ball R. Härkönen J. Knuuti M. Stewart P. Nuutila H. Hamid Ghanbari B. Hassunizadeh F. Williams D. Cunningham S. Agrawal C. Machado S. Saba Y. Tekabe A. Abu-Taha L. Johnson B. A. Ban-AN Khaw G. L. Gavin Noble R. ElKoustaf S. M. Navare J. Lundbye D. Katten M. Platt A. Ahlberg G. V. Heller 《Journal of nuclear cardiology》2005,12(2):S18-S19
998.
K Sasai K Ono M Hiraoka K Tsutsui Y Shibamoto M Takahashi J Hamakawa C Nadai M Abe 《International journal of radiation oncology, biology, physics》1989,16(6):1477-1481
Anemia is believed to be an important prognostic factor in treating cancer patients by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be of more importance than the hemoglobin (Hb) level. This study shows the relationship between the CaO2 and tumor response to radiation therapy. Forty-two patients with epidermoid bronchogenic carcinoma, treated by irradiation alone between April 1982 and March 1986, were reviewed. Regression of the tumor after radiation therapy was calculated as a percent change in the tumor area. Arterial oxygen partial pressure (PaO2), Hb level, and percent oxygen saturation of Hb in arterial blood (SaO2) were measured within 2 weeks of commencement of radiation therapy and the CaO2 was calculated. The rank correlation coefficients between the maximum percent regression of the tumor and the PaO2, the Hb level and the CaO2 were 0.36, 0.34, and 0.46, respectively. Statistical analyses of the data indicate that the group of patients with CaO2 over 14.5 ml/dl exhibited greater tumor regression and longer survival periods than the group of patients with CaO2 below 14.5 ml/dl. Similarly patients with PaO2 over 90 mmHg or Hb level over 11 g/dl, exhibited significantly greater tumor regression and longer survival periods than those with PaO2 below 90 mmHg and Hb level below 11 g/dl. There were no significant differences in the length of survival periods with respect solely to the Hb level or the PaO2. It was concluded that the CaO2 is more important than the Hb level in determining tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors. 相似文献
999.
1000.
The adenylate cyclase system of FRSK cells, a cultured cell line of fetal rat epidermal keratinocytes, and SV40-transformed human keratinocytes was investigated. Stimulators of the human epidermal adenylate cyclase, epinephrine, adenosine, and prostaglandin E2 increased cyclic AMP levels of these cells. There were marked differences in the stimulatory effects; while epinephrine revealed a much stronger effect than the other stimulators in FRSK cells, epinephrine and prostaglandin E2 revealed similarly marked effects in SV40-transformed cells. Histamine had little or only slight effect on the cyclic AMP levels of these cells. Cholera toxin and forskolin, which work on the stimulatory guanine nucleotide binding protein (Gs) and the catalytic component of adenylate cyclase, respectively, also increased cyclic AMP levels. Northern blot hybridization analysis revealed that both FRSK cells and SV40-transformed human keratinocytes express mRNAs for the beta 2-adrenergic receptor, as well as the stimulatory and inhibitory guanine nucleotide binding proteins (Gs and Gi, respectively). The presence of Gs as well as Gi were confirmed by cholera toxin-, and pertussis toxin (IAP)-induced ADP-ribosylation of membranous proteins of these cells. Our results indicate that both FRSK cells and SV40-transformed human keratinocytes express the fundamental components of the adenylate cyclase system. These cell lines might be useful tools for the analysis of the adenylate cyclase system in epidermal keratinocytes. 相似文献