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71.
Hidetoshi Kawashima Toshiji Igarashi Yoshikage Nakajima Yasuhiro Akiyama Kazuyasu Usuki Shinzaburo Ohtake 《Naunyn-Schmiedeberg's archives of pharmacology》1978,305(2):123-126
Summary An intravenous injection of 40 or 65 mg/kg streptozotocin induced not only diabetes but also severe hypertension in rats. Whereas the hyperglycemia developed fully within a few days after the injection of streptozotocin, the hypertension progressively advanced and reached maximum level several weeks after the treatment and lasted more than 20 weeks. Twenty mg/kg streptozotocin did not induce hyperglycemia but significantly increased blood pressure several weeks after the treatment. Arrest of growth, polyuria, glycosuria, hyperlipemia and lenticular cataracts developed in the animals treated with 40 or 65 mg/kg streptozotocin, but in none of the animals treated with 20 mg/kg. In histological examinations in the 24th week after the treatment, degranulation and necrosis in the pancreatic -cells, and vacuolization and deposition of PAS-positive materials in the renal proximal tubules were found in the animals treated with 40 or 65 mg/kg streptozotocin. 相似文献
72.
73.
OBJECTIVE: To evaluate the efficacy of intranasal desmopressin (DDAVP) and retention control training (RCT) for monosymptomatic nocturnal enuresis in childhood and to assess the predictive value of daytime functional bladder capacity for both methods. MATERIALS AND METHODS: A total of 114 children with monosymptomatic nocturnal enuresis, of whom 99 (86.8%) wetted the bed every night, were treated with 1 of the 2 methods: intranasal DDAVP in 54 and RCT in 60 subjects. RESULTS: Twenty-one of 54 patients (38.9%) and 14 of 60 patients (23.3%) in the DDAVP group and the RCT group, respectively, achieved strong improvement (p = 0.061). Forty-five of 54 (90.0%) in the DDAVP and 35 of 60 (58.3%) in the RCT group had a more than 50% decrease in wet nights (p = 0.004). In the DDAVP group, the functional bladder capacities at baseline in responders and nonresponders were 82+/-22% and 56+/-20% of the predicted bladder capacity for their age (p<0.001). In the RCT group, responders and nonresponders did not differ in functional bladder capacity at baseline. CONCLUSION: DDAVP treatment is more effective than RCT in decreasing the number of wet nights in childhood nocturnal enuresis, but not so effective in children with a low functional bladder capacity. Daytime functional bladder capacity is a valuable predictor of response to DDAVP, but not so to RCT. 相似文献
74.
75.
Tomoko Ohtsu Hirofumi Fujii Hisashi Wakita Tadahiko Igarashi Kuniaki Itoh Shigeru Imoto Masahiro Kohagura Yasutsuna Sasaki 《Cancer chemotherapy and pharmacology》1998,42(1):1-8
The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA)
as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and
14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition,
multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured
by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day
1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax),
area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more
frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital,
dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations
were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present
we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view.
Received: 2 May 1997 / Accepted: 13 October 1997 相似文献
76.
Yamamoto K Miyagawa J Waguri M Sasada R Igarashi K Li M Nammo T Moriwaki M Imagawa A Yamagata K Nakajima H Namba M Tochino Y Hanafusa T Matsuzawa Y 《Diabetes》2000,49(12):2021-2027
Betacellulin (BTC), a member of the epidermal growth factor family, is expressed predominantly in the human pancreas and induces the differentiation of a pancreatic acinar cell line (AR42J) into insulin-secreting cells, suggesting that BTC has a physiologically important role in the endocrine pancreas. In this study, we examined the in vivo effect of recombinant human BTC (rhBTC) on glucose intolerance and pancreatic morphology using a new mouse model with glucose intolerance induced by selective alloxan perfusion. RhBTC (1 microg/g body wt) or saline was injected subcutaneously every day from the day after alloxan treatment. The intraperitoneal glucose tolerance test revealed no difference between rhBTC-treated and rhBTC-untreated glucose-intolerant mice at 2-4 weeks. However, glucose tolerance was significantly improved and body weight was significantly increased in rhBTC-treated mice compared with untreated mice at 8 weeks. Islet-like cell clusters, consisting mainly of beta-cells, were increased in the pancreas and were localized in contact with the ductal lining cells and sometimes with acinar cells. In conclusion, administration of rhBTC improved glucose tolerance in this mouse model by increasing beta-cell volume, primarily through accelerated neogenesis from ductal lining cells. 相似文献
77.
Hatano T Igarashi H Nakada J Oishi Y Yanada S Furuta A Takizawa A Iwamuro S Tashiro K 《Nihon Hinyōkika Gakkai zasshi. The japanese journal of urology》2000,91(6):542-546
BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers. RESULTS: The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer. 相似文献
78.
M Hosoya Y Kawasaki M Katayose H Sakuma M Watanabe E Igarashi M Aoyama H Nunoi H Suzuki 《Archives of disease in childhood》2006,91(6):469-472
AIMS: To evaluate the prognostic predictive values of cytochrome c, cytokines, and other laboratory measurements in serum collected during neurological onset in acute encephalopathy with multiple organ failure. METHODS: In addition to general laboratory examinations, the concentrations of cytochrome c (apoptosis marker) and cytokines (inflammatory markers) were measured in serum samples collected at the initial phase in 29 patients with acute encephalopathy. The obtained values were evaluated as predictors for the development of severe encephalopathy. RESULTS: Cytochrome c, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF-receptor 1 (sTNF-R1), and aspartate aminotransferase (AST) concentrations at the initial phase were high and correlated well with patient outcome. High concentrations of serum cytochrome c (>45 ng/ml), sTNF-R1 (>2000 pg/ml), AST (>58 IU/dl), IL-6 (>60 pg/ml), and TNF-alpha (>15 pg/ml) predicted an unfavourable prognosis (sequelae and death) at 93%, 79%, 82%, 77%, and 60%, respectively. The specificity of those markers was 100%, 89%, 83%, 100%, and 100%, respectively. CONCLUSIONS: Serum cytochrome c is the most sensitive and specific predictor for the development of severe encephalopathy at the initial phase. Results suggest that this marker might be used to guide decisions regarding the start of the initial treatment and further intensive care. 相似文献
79.
Naoki Ishiguro Takashi Nozawa Akiko Tsujihata Asami Saito Wataru Kishimoto Kazutoshi Yokoyama Takafumi Yotsumoto Kenji Sakai Takashi Igarashi Ikumi Tamai 《Drug metabolism and disposition》2004,32(5):519-524
We investigated influx and efflux transporters involved in blood-brain barrier transport of the nonsedative H1-antagonist epinastine. The basal-to-apical transport of [14C]epinastine was markedly higher than that in the opposite direction in LLC-GA5-COL150 cells stably transfected with human multidrug resistance (MDR)1 gene. The brain-to-plasma concentration ratio of [14C]epinastine in mdr1a/b(-/-) mice was 3.2 times higher than that in wild-type mice. The uptake of both [3H]mepyramine and [14C]epinastine into immortalized rat brain capillary endothelial cells (RBEC)1 showed temperature and concentration dependence. The kinetic parameters, K(m), V(max), and uptake clearance (V(max)/K(m)), of the initial uptake of [3H]mepyramine and [14C]epinastine by RBEC1 were 150 microM, 41.8 nmol/min/mg protein, and 279 microl/min/mg protein for mepyramine and 10.0 mM, 339 nmol/min/mg protein, and 33.9 microl/min/mg protein for epinastine, respectively. The uptake of [3H]mepyramine and [14C]epinastine by RBEC1 was inhibited by organic cations such as quinidine, amantadine, and verapamil, but not by other organic cations, tetraethyl ammonium, guanidine, and carnitine. Organic anions such as benzoic acid, estrone-3-sulfate, taurocholate, and neutral digoxin were not inhibitory. Furthermore, some cationic H1 antagonists (chlorpheniramine, cyproheptadine, ketotifen, and desloratadine) inhibited the [3H]mepyramine and [14C]epinastine uptake into RBEC1. In conclusion, the present study demonstrated that the combination of efficient efflux transport by P-glycoprotein and poor uptake by the influx transporter, which is identical with that responsible for the uptake of mepyramine, account for the low brain distribution of epinastine. 相似文献