Biomedical subjects

R Oishi

Publications and source records attributed to R Oishi.

At least 37 records · Page 2Linked to original sources

PubMed2000

Nitric oxide protects against contrast media-increased pulmonary vascular permeability in rats.

RATIONALE AND OBJECTIVES: Nitric oxide (NO) regulation of endothelial function is involved in the development of acute lung injury. The role of NO in contrast media-induced increases in pulmonary vascular permeability was investigated in a rat model. METHODS: Nonionic (iohexol) and ionic (ioxaglate) contrast media were intravenously injected at 1.5 mL/min in rats. Pulmonary vascular permeability was evaluated by measuring the amount of Evans blue dye uptake as a quantitative marker of albumin extravasation in lung tissue. RESULTS: Intravenous injections of contrast media at doses of 4 and 6 g I/kg induced a dose-dependent increase in pulmonary vascular permeability. L-Arginine (an NO synthase substrate) and N(G)-nitro-L-arginine (L-NNA) (an NO synthase inhibitor) prevented and aggravated, respectively, the increase in pulmonary vascular permeability induced by the contrast medium. An aggravating action of L-NNA was confirmed by morphological and histological observations, this action being blocked by L-arginine (300 mg/kg) but not by D-arginine. Isosorbide dinitrate (1-20 mg/kg), an NO donor, had a dose-dependent protective effect on ioxaglate-increased vascular permeability. CONCLUSIONS: Our experimental findings suggest that contrast media at high doses produce pulmonary edema by inhibiting endothelial NO production, and nitrovasodilators protect against this adverse effect in rats.

Animals↗

PubMed1999

Improved method of determining thiamylal enantiomers in human serum by high-performance liquid chromatography.

Thiamylal, a widely used anesthetic drug, has two enantiomers. We developed a simple and rapid method for measuring the thiamylal enantiomers in human serum. The method involves a liquid-liquid extraction procedure followed by chiral resolution using a 5 microm silica-bonded alpha1-acid glycoprotein column (Chiral-AGP). The thiamylal enantiomers and internal standard were eluted within 15 min and were well-resolved. At concentrations of 1, 5 and 20 microg ml(-1), the relative standard deviations of R(+)- and S(-)-thiamylal were 1.35-2.88% and 1.37-3.01%, respectively, for the intra-day assay, and 2.93-4.46% and 2.46-4.84%, respectively, for the inter-day assay. This method facilitates the routine monitoring and pharmacokinetic studies of thiamylal enantiomers.

Anesthetics, Intravenous↗

PubMed1999

Inhibition of GABA system involved in cyclosporine-induced convulsions.

In this study, we attempted to clarify the mechanisms mediating cyclosporine-evoked convulsions. Cyclosporine (50 mg/kg, i.p.) significantly enhanced the intensity of convulsions induced by bicuculline (GABA receptor antagonist), but not those induced by strychnine (glycine receptor antagonist), N-methyl-D-aspartic acid, quisqualic acid or kainic acid (glutamate receptor agonists). Bicuculline plus cyclosporine-induced convulsions were significantly suppressed by an activation of GABAergic transmission with diazepam, phenobarbital and valproate. The GABA turnover estimated by measuring aminooxyacetic acid-induced GABA accumulation in the mouse brain was significantly inhibited by cyclosporine (50 mg/kg, i.p.). When cultured rat cerebellar granule cells were exposed to 1 microM cyclosporine for 24 hr, the specific [3H]muscimol (10 nM) binding to intact granule cells decreased to 53% of vehicle controls. The present study provides the first evidence suggesting that cyclosporine inhibits GABAergic neural activity and binding properties of the GABAA receptor. These events are closely related to the occurrence of adverse central effects including tremors, convulsions, coma and encephalopathy under cyclosporine therapy.

Animals↗

PubMed1999

Evaluation of the in-line filters for the intravenous infusion of amphotericin B fluid.

OBJECTIVE: To evaluate the effects of four types of in-line filters on filtration rate, amphotericin B concentration and particulate matter. METHODS: Filtration rates of amphotericin B fluid through in-line filters under maximum gravity flow were examined. The concentrations of amphotericin B and the particulate matter in the non-filtered and filtered amphotericin B fluid at the flow rate of 500 ml/24 h were measured. RESULTS: Filtration through a 1.2 microm or 0.2 microm polyethersulphone (PES) filter under maximum gravity flow took less than 40 min. The 0.2 microm positively charged nylon 66 and 0.2 microm nylon 66 filters took 70 and 100 min, respectively, to filter 500 ml of amphotericin B fluid. The 0.2 microm positively charged nylon 66 filter and the 0.2 microm nylon 66 filter, but not the PES filter (1.2 and 0.2 microm), decreased the concentrations of amphotericin B in the filtered fluid by 100% within 1 h and by 66% within 24 h after the start of filtration, respectively. The particulate count in the non-filtered amphotericin B fluid was 27+/-5 particles/ml, exceeding the limit defined by USP XXIII. The 1.2 microm and 0.2 microm PES filters significantly decreased particulate matter by 83 and 97%, respectively, just after filtration. CONCLUSION: The present results indicate that the 0.2 microm PES filter is optimal for intravenous infusion of amphotericin B fluid to minimize the introduction of particulate matter, microbial contaminants and endotoxin into patients.

Amphotericin B↗

PubMed1999

Potentiation of vancomycin-induced histamine release by muscle relaxants and morphine in rats.

The intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role. These reactions are more frequently manifested when vancomycin is injected into anesthetized patients. We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats. In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced significant histamine release. Tubocurarine, vecuronium, pancuronium, succinylcholine, and morphine up to concentrations of 0.25, 1, 5, 30, and 5 mM, respectively, produced no significant histamine release. However, the nonsignificant histamine release induced by 0.5 mM vancomycin was clearly enhanced by combining vancomycin with any of these agents. In the in vivo study, the intravenous injection of vancomycin significantly increased the plasma histamine levels in rats when vancomycin was injected at 200 mg/kg of body weight (63.2 +/- 34.0 ng/ml [mean +/- standard deviation]) but not when it was injected at 100 mg/kg (30.8 +/- 20.2 ng/ml) compared with that in the saline-treated rats (22.5 +/- 11.4 ng/ml). Although the subcutaneous administration of morphine (10 mg/kg) never increased the plasma histamine levels, the intravenous injection of vancomycin (100 mg/kg) 30 min after this morphine treatment markedly increased the plasma histamine levels (56.0 +/- 26.9 ng/ml). These findings provide experimental evidence that the combination of muscle relaxants or an opioid with vancomycin may increase the risk of anaphylactoid reactions by enhancing the release of histamine.

Animals↗

PubMed1999

Contrast medium-induced pulmonary edema is aggravated by silicone contamination in rats.

PURPOSE: To examine the effect of silicone contamination, which occurs in clinical settings during vial preparation with disposable syringes, on contrast medium-induced pulmonary edema in rats. MATERIALS AND METHODS: Ioxaglate, ioversol, and iohexol, silicone-containing physiologic saline solutions, and three silicone-containing contrast media were separately, intravenously injected at 1.5 mL/min in rats. Pulmonary edema was evaluated as changes in the relative lung weight and in the water, sodium, and potassium contents of the lung. RESULTS: Intravenous injection of ioxaglate induced marked pulmonary edema, even with a dose of only 4 g of iodine per kilogram of body weight. In contrast, ioversol and iohexol induced significant pulmonary edema only after the injection of large doses (6 g of iodine per kilogram; P < .05). The injection of 4 microL/mL silicone-containing physiologic saline at a dose of 18.75 mL/kg also produced marked pulmonary edema, whereas doses of 6.25 and 12.5 mL/kg showed no significant influence. The addition of an ineffective dose (12.5 mL of physiologic saline per kilogram of body weight) of silicone in contrast medium substantially aggravated the pulmonary edema induced by the contrast medium alone; this phenomenon was also confirmed with morphologic observation. CONCLUSION: Ionic contrast media are more toxic to the endothelial cells than are nonionic contrast media. Silicone contamination might be one of the causes of pulmonary edema after intravenous injection. However, caution must be exercised in extrapolating these results to humans.

Animals↗

PubMed1999

High speed injection of radiographic contrast media induces severe particulate contamination.

In a study of exogenous particulate contamination during angiography, the effect of injection speed of four kinds of radiographic contrast media (RCM) was investigated. The particle count (> or = 10 microns) in all RCM increased in a speed-dependent manner and the increase was especially dramatic at 3 ml s-1. The extent of increase in particulate matter was higher for ioxaglate than for the other three RCM. As particulate matter is unwanted and unnecessary, to prevent the harmful effects in patients much attention should be paid to various factors generating particulate matters, such as characteristics of RCM and plastic syringe.

Angiography↗

PubMed1999

In vitro B-mode ultrasonographic criteria for diagnosing axillary lymph node metastasis of breast cancer.

Axillary lymph node status is an important factor for staging and treatment planning in breast cancer. Our study was performed in vitro on a node-by-node basis to evaluate the ability of B-mode ultrasonographic images to distinguish metastatic from nonmetastatic nodes. Immediately prior to histologic examination, individual dissected axillary nodes were scanned in a water bath using a 10 MHz B-mode ultrasonographic transducer. Four B-mode features (size, circularity, border demarcation, and internal echo) were evaluated for their ability to distinguish metastatic from nonmetastatic lymph nodes. Lymph node metastasis was indicated by (1) a large size (i.e., a length of the longest axis of 10 mm or greater); (2) a circular shape (i.e., the ratio of the shortest axis to the longest axis between 0.5 and 1.0); (3) a sharply demarcated border compared with surrounding fatty tissue; and (4) a hypoechoic internal echo, with obliteration of the fatty hilum. The sensitivity and specificity were compared for all combinations of features. We examined 84 histologically characterized axillary nodes from 27 breast cancer patients, including 64 nonmetastatic and 20 metastatic nodes. Of the criteria cited, circular shape was the best single feature for distinguishing metastatic from nonmetastatic nodes (sensitivity, 65%; specificity, 73%). The best combination of sensitivity (85%) and specificity (73%) was obtained using the criterion that a lymph node contained cancer when at least three positive features were present. The present in vitro study demonstrated that the sensitivity and specificity of B-mode ultrasonography for diagnosing lymph node metastasis were lower than 90%. Therefore, B-mode ultrasonography may not be an optimal noninvasive screening method for diagnosing axillary lymph node metastasis in breast cancer patients, particularly under in vivo clinical conditions.

Adult↗

PubMed1998

Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 showed a benefit from leucovorin (LV)-modulated 5-fluorouracil (5-FU) adjuvant therapy (5-FU + LV) in patients with Dukes' stage B or C carcinoma of the colon. Preclinical and clinical phase I/II data suggested that interferon alfa-2a (IFN) enhanced the efficacy of 5-FU therapy. Accordingly, in NSABP protocol C-05, the addition of recombinant IFN to 5-FU + LV adjuvant therapy was evaluated. METHODS: Data are presented for 2176 patients with Dukes' stage B or C cancer entered onto protocol C-05 during the period from October 1991 through February 1994. Individuals with an Eastern Cooperative Oncology Group performance status of 0-2 (ranges from fully active to ambulatory and capable of self-care but unable to work), a life expectancy of at least 10 years, and curative resection were stratified by sex, disease stage, and number of involved lymph nodes and were randomly assigned to receive either 5-FU + LV or 5-FU + LV + IFN; the mean time on the study as of June 30, 1997, was 54 months. All statistical tests were two-sided. RESULTS: There was no statistically significant difference in either disease-free survival (5-FU + LV, 69%; 5-FU + LV + IFN, 70%) or overall survival (5-FU + LV, 80%; 5-FU + LV + IFN, 81%) at 4 years of follow-up. Toxic effects of grade 3 or higher were observed in 61.8% of subjects in the group treated with 5-FU + LV and in 72.1% of subjects in the group treated with 5-FU + LV + IFN; fewer patients in the latter group completed protocol-mandated 5-FU + LV therapy than in the former group (77.1% versus 88.5%). CONCLUSION: The addition of IFN to 5-FU + LV adjuvant therapy confers no statistically significant benefit, but it does increase toxicity.

Antimetabolites, Antineoplastic↗

PubMed1998

Inhibition of neuronal dopamine uptake by some antiallergic drugs.

The effects of 10 antiallergic drugs (astemizole, azelastine, ebastine, emedastine, epinastine, ketotifen, oxatomide, terfenadine, pemirolast and tranilast) on neuronal dopamine uptake were examined. Some drugs examined showed a concentration-dependent inhibition of [3H]dopamine uptake into synaptosomal preparations of the rat striatum. The inhibition constant (Ki) values were 231-876 nM for ebastine, terfenadine, oxatomide and astemizole. The specific binding of [3H] (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) (GBR12935) to the rat striatal membranes was also inhibited by these antiallergic drugs. There was a good correlation between the degrees of inhibition of [3H]dopamine uptake and [3H]GBR12935 binding. Then, the behavioral excitement induced by L-DOPA (100 mg/kg, s.c.) plus pargyline hydrochloride (80 mg/kg, i.p.) in mice was significantly enhanced by i.p. treatment with ebastine (10 mg/kg) and astemizole (5 mg/kg). These results suggest that the neuronal dopamine uptake is inhibited by some antiallergic drugs, especially ebastine.

Animals↗

PubMed1998

Determination of salicylic acid in human serum with capillary zone electrophoresis.

The determination of salicylic acid (SA), a metabolite of aspirin, in human serum was developed using capillary zone electrophoresis (CZE) with diode array detection. The reproducibility of separation and quantification with CZE analysis of the extract of SA from human serum was appropriate for the intra- and inter-day assay coefficients. A high correlation was revealed between the serum SA levels in volunteers determined by CZE and those determined by a fluorescence polarization immunoassay (r=0.973, n = 12), although the former values were slightly higher than the latter. There were no peaks interfering with the assay of SA by internal standard method. This CZE method could provide a simple and efficient method for monitoring SA in patients.

Administration, Oral↗

PubMed1998

Enhancement of serotonergic neural activity contributes to cyclosporine-induced tremors in mice.

A single cyclosporine injection (50 mg/kg, i.p.) significantly enhanced harmine- but not oxotremorine-induced tremors in mice. This potentiation became more apparent when cyclosporine (50 mg/kg, i.p.) was administered once a day for seven days. These findings suggest an involvement of monoaminergic mechanisms in cyclosporine-induced tremors. The effects of cyclosporine were examined on the dynamics of noradrenaline, dopamine and serotonin in the mouse brain. Both single and repeated treatment with cyclosporine significantly facilitated the serotonin turnover as estimated from the probenecid-induced accumulation of 5-hydroxyindoleacetic acid, but either mode of treatment failed to change the contents of monoamines and their metabolites or the turnover of noradrenaline and dopamine. Therefore, the cyclosporine-enhanced activity of serotonin neurons may be interpreted as producing adverse central effects, including tremors.

Animals↗

PubMed1998

Capillary electrophoresis for therapeutic drug monitoring of antiepileptics.

We examined the use of capillary electrophoresis for therapeutic drug monitoring of antiepileptic drugs. Micellar electrokinetic capillary chromatography (MEKC) with a diode array detector simultaneously determined concentrations of zonisamide, a new type of antiepileptic drug, and phenobarbital, phenytoin and carbamazepine, typical antiepileptic drugs, in human serum. Zonisamide levels in human serum obtained by MEKC correlated well with levels obtained by high-performance liquid chromatography. The serum levels of phenobarbital, phenytoin and carbamazepine determined by MEKC were almost equal to those obtained by fluorescence polarization immunoassay. The reproducibility of separation and quantification with MEKC for intra- and inter-day assays were appropriate. This MEKC method could provide a simple and efficient therapeutic drug monitoring method for antiepileptic drugs, especially in patients treated with a combination of zonisamide and other antiepileptic drugs. MEKC may be an attractive method for therapeutic drug monitoring, because of its specificity of separation, automation of procedure, ease of method development, low cost, small aqueous buffer amounts, speed of analysis, small injection volume and high environment-directed performance.

Anticonvulsants↗

PubMed1998

Quality evaluation by capillary electrophoresis of amphotericin B injection after filtration through various membrane filters.

The determination of amphotericin B, an antifungal agent, was developed using micellar electrokinetic capillary chromatography (MEKC) with a diode array detector. Repeatability and intermediate precision of MEKC analysis were acceptable. A high correlation was found between amphotericin B levels in pharmaceutical solutions obtained by MEKC and those by high-performance liquid chromatography (HPLC) (r = 0.994). This MEKC method is therefore useful for the determination of amphotericin B. The concentration of amphotericin B did not significantly change after filtration through polyethersulfone (PES, 0.2 microm) and polyvinylidene difluoride (PVDF, 0.45 microm) membrane filters. When the Fungizone injection was filtered through PES (0.2 microm) and added to 5% dextrose for injection (500 mL), particulate matters larger than 10 microm decreased by 64% to a level under the standard defined by United States Pharmacopoeia (USP XXIII). PVDF filtration (0.45 microm) did not have this effect. Our results suggest that filtration of Fungizone injection through PES (0.2 microm) membrane filters is recommended for the preparation of intravenous amphotericin B fluid.

Amphotericin B↗

PubMed1998

In vitro diagnosis of axillary lymph node metastases in breast cancer by spectrum analysis of radio frequency echo signals.

Axillary lymph node status is of particular importance for staging and managing breast cancer. Currently, axillary lymph node dissection is performed routinely in cases of invasive breast cancer because of the lack of accurate noninvasive methods for diagnosing lymph node metastasis. We investigated the diagnostic ability of ultrasonic tissue characterization based on spectrum analysis of backscattered echo signals to detect axillary lymph node metastasis in breast cancer in vitro compared with in vitro B-mode imaging. Immediately after surgery, individual lymph nodes were isolated from axillary tissue. Each lymph node was scanned in a water bath using a 10-MHz instrument, and radio frequency data and B-mode images were acquired. Spectral parameter values were calculated, and discriminant analysis was performed to classify metastatic and nonmetastatic lymph nodes. Forty histologically characterized axillary lymph nodes were enrolled in this study, including 25 nonmetastatic and 15 metastatic lymph nodes. A significant difference existed in the spectral parameter values (slope and intercept) for metastatic and nonmetastatic lymph nodes. Spectral parameter-based discriminant function classification of metastatic vs. nonmetastatic lymph nodes provided a sensitivity of 93.3%, specificity of 92.0%, and overall accuracy of 92.5%. In comparison, B-mode ultrasound images of in vitro lymph nodes provided a sensitivity of 73.3%, specificity of 84.0%, and overall accuracy of 80.0%. Receiver operating characteristic (ROC) analysis comparing the efficacy of both methods gave an ROC curve area of 0.9888 for spectral methods, which was greater than the area of 0.8980 for B-mode ultrasound. Hence, this in vitro study suggests that the diagnostic ability of spectrum analysis may prove to be markedly superior to that of B-mode ultrasound in detecting axillary lymph node metastasis in breast cancer. Because of these encouraging results, we intend to conduct an investigation of the ability of spectral methods to classify metastatic axillary lymph nodes in vivo.

Adult↗

PubMed1998

Quality evaluation of radiographic contrast media in large-volume prefilled syringes and vials.

RATIONALE AND OBJECTIVES: The authors compared the particle contaminations of radiographic contrast media packaged in large-volume prefilled syringes and vials. MATERIALS AND METHODS: Particle counting was performed for four contrast media packaged in large-volume prefilled syringes (iohexol, ioversol, ioversol for angiography, and ioxaglate) and three contrast media packaged in vials (iohexol, ioversol, and ioxaglate). X-ray emission spectrometry was performed to characterize the individual particles. The amount of silicone oil in the syringe was quantified with infrared spectrophotometry. RESULTS: The particle contamination in syringes containing ioversol was higher than that in syringes containing iohexol or ioxaglate. Particle contamination in the vials was relatively low, except with ioxaglate. X-ray emission spectrometry of the components of the syringe and vial showed that the source of particles was internal material released from the rubber stopper or inner surface. CONCLUSION: The particle counts for contrast media packaged in syringes and vials varied considerably among the different contrast media and were related to the amount of silicone oil on the inner surface and rubber piston of the syringe.

Contrast Media↗

PubMed1998

Direct and continuous electrochemical measurement of noradrenaline-induced nitric oxide production in C6 glioma cells.

1. Nitric oxide (NO) production in C6 glioma cells was directly monitored in real time by electrochemical detection with a NO-specific biosensor. 2. We present here the first direct evidence that noradrenaline elicits long-lasting NO production in C6 cells pretreated with lipopolysaccharide and interferon-gamma, an effect blocked by NG-monomethyl-L-arginine, a NO synthase inhibitor. 3. This direct electrochemical measurement of glia-derived NO should facilitate our understanding of the kinetics of glial signaling in glia-glia and glia-neuron networks in the brain.

Animals↗

PubMed1997

Application of high-performance thin-layer chromatography for the detection of organophosphorus insecticides in human serum after acute poisoning.

We developed a rapid and simple method for identifying 25 commonly used organophosphorus insecticides in human serum using high-performance thin-layer chromatography (HPTLC). These organophosphates were separated on plates with three different developing systems within 6-18 min and detected by means of ultraviolet radiation and coloring reactions with 4-(4-nitrobenzyl)pyridine-tetraethylenepentamine reagent (NT reagent) or palladium chloride reagent (PdCl2 reagent). Each organophosphate was accurately identified by means of the R(F) x 100 value and the spot color in three systems. The detection limits of dichlorvos, fenitrothion, malathion, methidathion, parathion and trichlorfon in serum by the liquid-liquid extraction method were 1.1, 0.12, 0.12, 0.05, 0.6 and 0.1 microg/ml, respectively. These sensitivities may be sufficient to detect those organophosphates in patient serum after acute poisoning.

Chromatography, High Pressure Liquid↗