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N Hoshino

Publications and source records attributed to N Hoshino.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relationship between area under the concentration versus time curve of cyclosporin A, creatinine clearance, hematocrit value, and other clinical factors in Japanese renal transplant patients.

We evaluated the relationship between the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) and several other clinical factors, because the clinical utility of AUC monitoring has been ambiguous. Fifty-four clinical time courses from 14 Japanese renal transplant patients during hospitalization, in the period from April 1990 to March 1997, were examined. In a bivariate regression analysis there was no correlation between the AUC and the daily dose of CsA (mg/kg/day) when the individual data or total series data were analyzed. In a chi-square test, the donor type of kidney (chi(2) = 25.254, df = 1, p = 0.0000) and renal function-related episodes, i.e. acute tubular necrosis, hemodialysis, hypertension, nephrotoxicity, or rejection (chi(2) = 13.982, df = 1, p = 0.0002) directly affected posttransplant renal function assessed by creatinine clearance, while episodes of hepatic function as assessed by the glutamate-pyruvate transaminase (GPT) activity level had no correlation with the posttransplant renal function evaluated according to creatinine clearance. In contrast, the renal function-related episodes significantly affected the AUC after renal transplantation (chi(2) = 4.934, df = 1, p = 0.0263), while hepatic function assessed by GPT did not. In a multivariate analysis, the creatinine clearance and obesity had significant positive correlations with the AUC, whereas the hematocrit had a significant negative correlation with the AUC. From these observations, we concluded that the dosage adjustment of CsA cannot be performed using the linear relationship between the daily oral dose and the AUC, and that renal function, obesity, and the CsA blood distribution properties affect the CsA pharmacokinetics after renal transplantation. Posttransplant renal function as well as obesity and CsA blood distribution properties are important factors to be considered when therapeutic monitoring is performed.

Adult↗
PubMed1997

Relationship between erythrocyte-to-plasma distribution ratio of cyclosporin and lymphocyte proliferation in renal transplant patients.

OBJECTIVE: The aim of this study was to examine the relationship between erythrocyte-to-plasma distribution ratio of cyclosporin (CsA-EP) and lymphocyte proliferation as an indicator of immunosuppressive activity in renal transplant patients. METHODS: A total of 113 whole blood samples obtained from 6 inpatients with renal transplantation were analysed. CsA concentrations in blood and plasma at trough were measured by fluorescence polarization immunoassay using monoclonal antibody, lymphocyte proliferation in response to phytohaemagglutinin was evaluated by the fluorimetric derivatization method using ethidium bromide and the stimulation index (SI) was calculated. RESULTS: There was no correlation between CsA dose and trough levels (vs blood CsA, r2 = 0.052; vs plasma CsA, r2 = 0.054, n = 113). A significant negative correlation between the SI and the CsA-EP was found in individual or all samples (r2 = 0.224, p < 0.0001, n = 113), whereas CsA trough levels in blood or plasma had no correlation with the SI. CONCLUSION: Although the degree of contribution of CsA-EP to the SI was 22%, the CsA-EP is a more useful predictor of changes in immunosuppressive response than CsA concentration in blood or plasma. The adoption of the CsA-EP as a monitoring index could be helpful in assessing the appropriateness of CsA immunosuppressive therapy.

Adult↗
PubMed1997

A predictive model for area under the concentration versus time curve of cyclosporin A using several routine monitoring results in renal transplant patients.

We created a predictive model for the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) using routine monitoring results, and examined its clinical utility. Based on 48 clinical time courses accumulated from renal transplant patients, the AUC predictive model was created. An estimate of the AUC0-8 (integrated from time zero to 8 h) was then given as follows: AUC0-8 = 5673.1 x log(TL) + 9342.8 x log(OB) + 64.1 x Dprd x 869.4 x DTK - 168.9 x HCT - 161.2 x SCr - 11.3 x GPT + 3.0 x PL - 588.6 x SEX - 24794.5. In this model, the AUC0-8(ng.h/ml) is given as a function of the CsA through levels (TL, ng/ml), obesity (OB, %), daily dose of prednisolone (Dprd, mg/d), donor type of kidney (DTK), hematocrit (HCT, %), serum creatinine (SCr, mg/dl), glutamate-pyruvate transaminase activity (GPT, IU/l), plasma lipids (PL, mg/dl) and sex distinction (SEX). The Statistical significance of the multiple regression was p < 0.00001 (R2 = 0.862, n = 48), and the day after transplantation, neither the administered oral dose of CsA, or the patient's age had any contribution to the regression. The predictive performance of this model was almost equal to that of the existing method which used 3-point data on the concentration versus time curve. In clinical adaptation for renal transplant patients, the steady-state concentration of CsA (Css) based on the AUC0-8 predictive model was significantly decreased during acute gastroenteritis or before acute rejection, whereas nephrotoxicity was increased, even though CsA trough levels were within a normal therapeutic range (100-200 ng/ml). These findings suggest that the created AUC0-8 predictive model using routine monitoring results, i.e., the trough level of CsA, biochemical tests, a daily dose of predorinsolone (PRD), and basic patient information, is convenient as a monitoring device for CsA therapy, and is satisfactory in clinical practice.

Adult↗
PubMed1995

A nomogram for predicting optimal dosage of cyclosporine in renal transplant patients: taking physiological factors into consideration for regimen during immunosuppressive therapy.

We constructed a nomogram for determining the optimal regimen of cyclosporine (CyA), based on physiological changes that occur during immunosuppressive therapy. The nomogram consists of a fixed model and a variable model. In the fixed model, the oral dose of CyA (D, mg/kg) is given by the multiple linear function of logarithmic CyA trough level (TL, ng/ml), the surrogate apparent total body clearance of CyA (CL/fsu, l/h/kg, being equal to D/TL/12), and the erythrocyte-to-plasma distribution ratio of CyA (CyA-EP), as defined by: D = 4.938 x log(TL) + 1.5037 x CL/fsu - 0.0326 x CyA-EP - 10.7156. In the variable model, the CL/fsu is given by the CyA-EP and the patient's intrinsic parameters (P1, P2), using a nonlinear equation: CL/fsu = P1 x exp(P2 x CyA-EP)/CyA-EP. An optimal CyA dose to maintain a desired trough level was calculated, and the validity of the nomogram was found satisfactory for clinical use. This offers a very concise and practical method for the therapeutic monitoring of CyA. Because the pharmacokinetics of CyA depends on physiological changes due to several disease states, and because the CyA-EP reflects the pharmacokinetics of CyA and the patient's disease state, the proposed nomogram is believed to provide an optimal dosage adjustment, taking physiological factors into consideration.

Adolescent↗
PubMed1992

New screening system for simultaneous determination of two marker proteins by homogeneous enzyme immunoassay.

AIMS: To save time and labour in mass screening, by detecting two marker proteins on one specimen using only one test. METHODS: alpha Fetoprotein and ferritin were chosen to demonstrate the principal of this system. The assay reagents were horseradish peroxidase (HRP)-labelled anti-alpha fetoprotein and HRP-labelled anti-ferritin antibodies. After the serum sample had been incubated with these reagents the substrate for HRP was added and the absorbance measured. An absorbance value below the cutoff point indicated that both parameters were within normal limits; a value above the cutoff point indicated that at least one of the two parameters was abnormally high. RESULTS: Fifty sera from healthy Japanese subjects were assayed by the simultaneous assay method. All samples gave absorbancy values below the cutoff point. Fifty serum samples from patients with high alpha fetoprotein concentrations (over 20 ng/ml) and 50 samples with high ferritin concentrations (over 200 ng/ml) were also assayed. The absorbancy values of all samples with high alpha fetoprotein concentrations, and all but one sample with high ferritin concentrations gave values above the cutoff point. CONCLUSIONS: Although this homogeneous enzyme assay method was applied to the combination of alpha fetoprotein and ferritin, it could be used in mass screening for any other combination of two markers.

Biomarkers↗
PubMed1990

Cysteamine-induced duodenal ulcer and the hepatoduodenal branch of the vagus nerve.

We investigated the role of the autonomic nervous system in gastric acid secretion, somatostatin concentration and PAS-positive mucus production in Brunner's glands in cysteamine-induced duodenal ulcer. Vagotomized rats were used. No ulcers occurred in the groups with vagotomies of the hepatoduodenal, truncal or gastric branches after cysteamine administration. However, in the hepatoduodenal branch vagotomized group, there was an increase in gastric acid secretion after cysteamine administration. A similar increase was observed in the control group, but the decreases in somatostatin concentration and PAS-positive mucus seen in the control group were not found in the hepatoduodenal vagotomized group. These results suggest that the hepatoduodenal branch of the vagus nerve might play an important role in the ulcerogenic process of cysteamine-induced duodenal ulcer.

Animals↗
PubMed1989

Ozagrel hydrochloride monohydrate, a thromboxane synthase inhibitor, and its metabolites as inhibitors of hepatic microsomal drug metabolism.

The change in the hepatic oxidative drug-metabolizing capacity in humans treated with ozagrel hydrochloride monohydrate (OZA), an imidazole derivative and a new thromboxane A2 synthase inhibitor, was studied and the inhibitory potencies of the metabolites of OZA (M-1 and M-2) on the mouse hepatic microsomal monooxygenase system in vitro were compared with that of OZA. In vitro, M-1 and M-2, which are the beta-oxidized form and the reduced form of OZA, respectively, inhibited aminopyrine N-demethylation, aniline hydroxylation and testosterone hydroxylations in mouse hepatic microsomes and produced type II difference spectra in the same manner as OZA. The kinetic data indicated that the inhibitory potencies and the affinities of these compounds for cytochrome P-450 were decreased in the order of M-2 greater than OZA greater than M-1. The ratio of 6 beta-hydroxycortisol (6 beta-OHF) to cortisol (F) in urine, used as an indicator of oxidative drug-metabolizing capacity in humans, did not change significantly during oral treatment with 400 mg/d of OZA, while the ratio decreased to 80-85% of the original level during treatment with 800 mg/d of OZA. Although the participation of the metabolites of OZA in the reduction of drug-metabolizing capacity in vivo is not yet clear, the results suggest that hepatic oxidative drug-metabolizing enzyme activities in humans are inhibited by treatment with a relatively high dose of OZA.

Acrylates↗
PubMed1989

Diabetic state-induced activation of calcium-activated neutral proteinase in mouse skeletal muscle.

The effect of a diabetic state in the diabetic KK-CAy mouse on calcium activated neutral proteinase (CANP) of hind-limb skeletal muscles was investigated. In the diabetic state, there was an increased sensitivity to activation of CANP by calcium (Ca). In addition, there was an enhancement of maximal activity of the enzyme. The effect was induced by secondary modification of the diabetic state, but not genetical factors. Several lines of evidence suggest that the CANP is responsible for 92 K dalton protein in diabetic skeletal muscles. Among the evidence are the following: a) The 92 K band in the diabetic muscles was lower than in the prediabetic mouse and restored by the addition of 2 mM EDTA and 2 mM EGTA. b) The band was reduced by increasing the Ca content and neutral pH in the non-diabetic normal muscles. c) E-64-C, a CANP inhibitor, restored the 92 K component reduced by the diabetic state. Since the band in denervated muscles was not changed by the Ca chelating agents, the reduction of the band in the diabetic muscles is related with musculotrophic factors, not diabetic neuropathy. These results suggest that diabetic amyotrophy may be regarded as a phenomenon linked to an increase in intracellular Ca ions and an increase in CANP activity.

Actinin↗
PubMed1988

Diabetic state-induced modifications of succinylcholine binding mode in the microsomal fractions of mouse skeletal muscles.

The skeletal muscles of alloxan-induced diabetic mice and genetically diabetic KK-CAY mice are hypersensitive to a depolarizing blocker, succinylcholine (SuCh) but not to the competitive antagonist, d-tubocurarine (d-TC). The mechanism by which the action of the depolarizing blocker is modified in the diabetic state was investigated on the binding of 14C-SuCh to the microsomal fraction isolated from mouse skeletal muscles. The Scatchard plot of microsomal preparations from normal ddY mice showed positive cooperativity in SuCh binding, whereas that of the preparations from alloxan-induced diabetic mice as well as genetically diabetic KK-CAY mice lost the positive cooperative interactions. The dissociation constant (Kd) of high affinity site in diabetic muscles was significantly lower than that in non-diabetic ddY muscle. The microsomal fractions from denervated muscles of normal ddY mice maintained weakly positive cooperativity in SuCh binding, and the affinity of SuCh binding in denervated muscles was lower than that of non-denervated muscles. In conclusion, the diabetic state selectively altered the SuCh binding mode. This alteration seems to be closely correlated with the pharmacological hypersensitivity to SuCh.

Alloxan↗
PubMed1988

Protein C in human plasma determined by homogeneous enzyme immunoassay with use of a centrifugal analyzer.

We describe the simple and rapid enzyme immunoassay of protein C in human plasma with use of a Cobas Fara centrifugal analyzer. The antibody, labeled with horseradish peroxidase, is reacted with antigen (protein C) for 15 min. The peroxidase activity of the resulting antigen-antibody conjugate is measured at 500 nm for 5 min in the presence of excess H2O2, phenol, and 4-aminoantipyrine, as compared with that of free conjugates. Results are calculated from a stored standard curve and expressed as a percentage of the value determined for a pooled specimen of normal adult plasma. The standard curve is linear from 0% to 200%. The CV is generally less than 4% for different concentrations of protein C. In liver cirrhosis, hepatocellular carcinoma, therapy with warfarin, thrombosis, and disseminated intravascular coagulation, protein C concentrations are about 40-70% of normal. Results obtained with the present homogeneous enzyme immunoassay correlated well with those by enzyme-labeled immunosorbent assay (r = 0.97).

Adult↗
PubMed1987

The effect of polymerization of horseradish peroxidase on the peroxidase activity in the presence of excess H2O2: a background for a homogeneous enzyme immunoassay.

The phenol oxidation catalyzed by horseradish peroxidase (HRP) is slowed down by the presence of excess H2O2. This inhibition is due to accumulation of Compound III, which is a catalytically sluggish form of HRP. When HRP is polymerized through covalent bonds, Compound III becomes unstable and the peroxidase activity is less sensitive to excess H2O2. Under suitable experimental conditions, the phenol oxidation is increased by about 20-fold upon polymerization of the enzyme. This fact represents the principle of a homogeneous enzyme immunoassay reported by Hoshino et al. (J. Biochem. 97, 113-118 (1985)). The ratio of the peroxidase activities of monomeric and polymerized HRPs is 1 : 4 when phenol is replaced by resorcinol, and the difference is no larger when guaiacol and catechol are used as electron donors.

Horseradish Peroxidase↗
PubMed1987

Thyroxine-induced molting and gonadal function of laying hens.

Twenty laying hens, 238 days of age, were divided into four groups which received daily intramuscular injections of L-thyroxine (T4) (0, 20, 100, or 500 micrograms/kg body weight per day) for 4 weeks. There was no change in body weight or egg production rate of the control (0 microgram T4) or of 20 and 100-micrograms T4 groups over time. Body weight and egg production of the 500 micrograms T4 group decreased markedly and molting started 10 days after T4 injection. Circulating iodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) of the 500-micrograms T4 group increased markedly (30 to 150 times those of the control group) whereas serum luteinizing hormone and progesterone declined after one week and estradiol after two weeks. We concluded that a large dose of T4 (500 micrograms T4/kg, body weight per day) induced an increase in circulating iodothyronine levels, decreased secretion of gonadotropin and sex steroid hormones, and induced molting.

Animals↗
PubMed1987

Nutritional implications of high-iodine egg diet in rats: effects on lipid metabolism and thyroid function.

The effects of a diet including high-iodine eggs, containing much higher amounts of iodine than ordinary eggs, were investigated on lipid metabolism and thyroid function in rats. To a non-purified diet was added at the 1% (w/w) level ordinary egg power (OE diet: 35 micrograms iodine/100 g diet) or high-iodine egg powder (IE diet: 392 micrograms iodine/100 g diet). At 7 months and 19 months, feeding of the IE diet resulted in a lowered serum triacylglycerol level, elevated tissue lipoprotein lipase activity and a lowered lipid peroxide level in the brain. Although the serum total iodine level was 5 times higher in animals given the IE diet than in those given the OE diet, serum levels of thyroid-related hormones (TSH, T3 and T4) were not affected by feeding of the IE diet. In animals exposed to cold and given antithyroid drug treatment, the IE diet seemed to improve age-related defects in thermogenic and thyroid hormone responses to cold, and also to confer resistance to the antithyroid drug. These results suggest that iodine ingestion through high-iodine eggs modulates both lipid metabolism and thyroid function in rats.

Animal Nutritional Physiological Phenomena↗