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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 955 records · Page 53Linked to original sources

Tandem mass spectrometry (MS/MS) utilizing electron impact ionization and multiple reaction monitoring for the rapid, sensitive, and specific identification and quantitation of morphine in whole blood.

A single step liquid-liquid extraction procedure followed by pentafluoropropionic anhydride derivatization was developed for the analysis of free morphine in blood. The specificity of the method was enhanced with the use of tandem mass spectrometry (MS/MS) using multiple reaction monitoring. Two molecular transitions were monitored. The first transition was where the first quadrupole (Q1) transmits the molecular ion of morphine-3,6-dipentafluoropropionate, 577. The 577 ion undergoes subsequent collision induced dissociation with argon and the last quadrupole (Q3) then transmits the 414 daughter ion. The second transition monitored was where Q1 transmits the 414 base peak and Q3 transmits the resultant 266 daughter ion. Deuterated morphine was included as an internal standard and analyzed similarly. Morphine was confirmed only in instances where both the m/z 577 to 414 and 414 to 266 transitions occurred simultaneously. Linear and reproducible calibration curves have been obtained for morphine at concentrations from 1.0 to 500 ng/mL achieving correlation coefficients of greater than 0.994. A signal-to-noise ratio of approximately 5:1 was observed for the 1.0-ng/mL samples.

Evaluation Studies as Topic↗

Extracorporeal hybridization of proximal renal tubular cells and an artificial membrane for the purpose of beta 2 microglobulin removal.

The present study was designed to develop a bioartificial kidney hybridized with LLC-PK1 cells for the purpose of beta 2microglobulin (B2M) removal. Cells were prepared in polystyrene culture wells; the bottom of each was covered with collagen fiber and the cells grown as monolayer cultures. Each well was inoculated with 1 ml cell suspensions with 0.0, 1.0 X 10(6), 2.0 X 10(6), or 4.0 X 10(6) cells/well. B2M was added to the culture system at a concentration of 80 micrograms/dl. Results were as follows: 1) Concentration of B2M in the supernatant of 4 X 10(6) cultivated LLC-PK1 cells was decreased from 79.32 +/- 2.41 micrograms/dl to 67.02 +/- 3.00 micrograms/dl (n = 6, p less than 0.01) at 2 hr; 2) Concentration of B2M in the supernatant of 1 X 10(6), 2 X 10(6), and 4 X 10(6) cultivated LLC-PK1 cells was 75.06 +/- 2.31 micrograms/dl (n = 6, p less than 0.05); 67.27 +/- 11.41 micrograms/dl (n = 6, p less than 0.001); and 67.02 +/- 3.00 micrograms/dl (n = 6, p less than 0.001), respectively, vs. 79.32 +/- 2.41 micrograms/dl in controls at 2 hr; 3) There was a significant positive correlation between the efficacy of B2M removal and cell number; and 4) These results suggested that it is possible to develop an artificial kidney hybridized with proximal tubular cells that possesses a high affinity for B2M removal.

Animals↗

Development of continuous recirculating peritoneal dialysis using a double lumen catheter.

Continuous recirculating peritoneal dialysis (CRPD) was newly introduced to improve solute removal efficiency in conventional dialysis therapies such as hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a part of the dialysate in the peritoneal cavity was drained through a double-lumen catheter and purified by an extracorporeal dialyzer. Urea removal characteristics in CRPD were examined in a canine study. In this study, a recirculation-dialysis experiment using a dog weighing 9.0 kg was carried out under 100 and 200 ml/min of flow for recirculating and delivered dialysates, respectively. An FB-50H (Nipro Medical Industries, Ltd., Osaka, Japan) composed of cellulose diacetate membrane with 0.5 m2 of surface area and Dianeal-1.5 (Baxter Limited Laboratories, Tokyo, Japan) containing urea were used as the extracorporeal dialyzer and dialysate. Urea peritoneal and dialyzer dialysances (DBP and DBD) were 3.05 and 33.3 ml/min by computer simulation using a compartment model for CRPD. This DBP value can be estimated as 20.3 ml/min for a 60 kg human. From this result, time-averaged value for BUN over an 8 hr/day CRPD, combined with three exchanges/day as CAPD is estimated to be 34.3 mg/dl, which is much lower than 45.2 mg/dl for a 12 hr/week HD, or 53.0 mg/dl for conventional CAPD.

Animals↗

LDL apheresis in atherosclerotic disease with hyperlipidemia.

Low density lipoprotein (LDL) apheresis was carried out in 28 atherosclerotic patients with clinical signs of poor peripheral circulation and abnormally high LDL levels. The LDL apheresis using extracorporeal adsorption with a dextran sulfate cellulose column (Liposorber, Kaneka, Japan) was done 10 times over 3 months. Hyperlipidemia was rapidly corrected after the initial two aphereses, whereas clinical signs of arteriosclerosis obliterans (ASO), such as coldness of the legs in 17 of 19 patients (89.5%), intermittent claudication in 14 of 17 patients (82.4%), foot pain at rest in 15 of 18 patients (83.3%), poor arterial pulsation in 12 of 16 patients (75.0%), and diminution of ulcer/necrosis in 3 of 5 patients (60.0%), improved in parallel. Improvement in plethysmographic and thermographic findings were observed in 10 of 10 patients (100.0%) and 13 of 14 patients (92.9%), respectively. Our tentative conclusion is that LDL apheresis using the Liposorber system was very effective in removing LDL from blood, and clinical symptoms rapidly improved in all patients concomitant with a reduction in plasma LDL levels. Hyperlipidemia may be a risk factor for symptomatic ASO in the lower extremities, and its active correction may be worth trying.

Aged↗

Heparin-free hemodialysis with an oral anti-platelet agent.

Heparin-resistant blood clotting in hemodialysis, caused mainly by platelets activated with artificial materials, was ameliorated by oral administration of a newly developed anti-platelet agent, 4-cyano-5,5-bis (4-methoxy phenyl)-4-pentenoic acid (E5510, Eisai Co. Ltd., Tokyo, Japan). Six hemodialysis patients, who were given 0.5. 1, 2, and 4 mg of E5510 orally 1 to 2 hr before starting hemodialysis, underwent hemodialysis using a hollow fiber dialyzer (PMMA or cellulose acetate). The platelet aggregation rate was depressed according to dose response, and fell to less than 30% of the initial value with 2 mg of E5510. Plasma thromboxane B2 concentration was depressed significantly. Bleeding time was mildly but not significantly prolonged. Based on these results, we tried heparin-free hemodialysis using E5510 as sole anticoagulant. Six of nine patients were successfully hemodialyzed with minimal blood clotting in the dialyzer and drip chambers. Three patients needed additional low dose heparin to prevent blood clotting in the circuit's air trap. Neither hemorrhagic complications nor other side effects were observed in these cases. E5510 is considered to be a promising oral anti-thrombogenic agent for patients with heparin-resistant blood clotting or heparin-free hemodialysis.

Administration, Oral↗

Prolongation of cardiac xenograft survival by double filtration plasmapheresis and ex vivo immunoadsorption.

A double filtration plasmapheresis (DFPP) technique and ex vivo immunoadsorption were applied to remove natural antibodies and avoid hyperacute rejection in discordant xenotransplantation. A swine heart was heterotopically transplanted into a dog's neck after DFPP and ex vivo immunoadsorption using a swine spleen or liver. Mean graft survival time was prolonged to 240 +/- 141 min in the group treated by combined DFPP and splenic adsorption, and 225 +/- 62 min in the group treated by combined DFPP and hepatic adsorption, whereas it was 9 +/- 5 min in the group without any treatment (p < 0.01). Mean removal rates of IgG and IgM were 85.5% and 93.3%, respectively. Anti-swine lymphocytotoxic antibodies and hemagglutination antibodies were also effectively removed. Deposits of canine IgM and C3 on the vascular endothelium of the graft were observed on immunofluorescence, which suggested that natural antibodies in the IgM fraction played an important role in xenohyperacute rejection.

Animals↗

Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis.

We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vasodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.

Adult↗

The significance of atherogenic indices in patients on hemodialysis.

Atherosclerotic diseases (ASD) are the major cause of mortality and morbidity in patients on hemodialysis (HD). To evaluate the significance and usefulness of atherogenic indices, we examined lipoprotein(a) (Lp(a)), remnant-like particles cholesterol (RLP.C), homocysteine (Hcy), cardiac troponin T (TnT), and ankle-arm blood pressure index (AABI) in 114 patients on HD (male 79, female 35; age 62.1 +/- 1.3 years). As a result, serum cardiac TnT and AABI levels in patients with diabetes mellitus (DM) (n = 33) were significantly higher than those in patients without DM (n = 81). In patients with cerebrovascular diseases (CVD), serum levels of both RLP.C and Hcy, and AABI levels were significantly higher than those in patients without CVD. In patients with coronary artery diseases (CAD), serum cardiac TnT and AABI levels were significantly higher than those in patients without CAD. In patients with peripheral vascular diseases (PVD), serum levels of both Hcy and cardiac TnT were significantly higher than those in patients without PVD. Multiple regression analysis did show that the presence of DM, serum Hcy levels and age were independent factors as- sociated with ASD: ASD = -0.348 + 0.426 x DM (scored: 0, absence; 1, presence) + 0.005 x Hcy (nmol/ml) + 0. 010 x Age (years) (p < 0.001). In conclusion, the presence of DM and advanced age are major determinants for atherosclerosis. In addition, serum Hcy levels are independent risk factors for atherosclerosis irrespective of the absence of DM.

Aged↗

Ultrastructure of glomerular basement membrane in active heymann nephritis rats revealed by tissue-negative staining method.

Recently, we have developed a tissue-negative staining method, and successfully visualized fine meshwork structure of the glomerular basement membrane (GBM). To clarify the mechanism of proteinuria in active Heymann nephritis, we performed tissue-negative staining and investigated the ultrastructural alterations of the GBM. Active Heymann nephritis, the animal model of human membranous nephropathy, was induced in Lewis rats by the injection of proximal tubular brush border antigen, i.e. Fx1A. Urinary protein excretion was measured and histological studies were performed over 15 weeks following the Fx1A injection. Proteinuria developed at 10 weeks after injection (38.2 +/- 7.4 mg/day) and progressively increased (160.2 +/- 20.6 mg/day at 15 weeks). Capillary fine deposits of IgG and C3 were seen by immunofluorescence, and subepithelial electron dense deposits (EDD) by transmission electron microscopy (TEM). Using the tissue-negative staining method, regular meshwork structure consisted of fine fibrils and pores (2.5 +/- 0.7 nm in short dimension) was observed in the GBM of control rats. At 10 and 15 weeks after injection, the GBM, directly facing the endothelial side of EDD, contained enlarged pores and nephrotic tunnels. Mean values of the short dimension of enlarged pores were 2.9 +/- 0.5 nm at 10 weeks and 3.1 +/- 0.4 nm at 15 weeks, which were significantly larger than that of control rats (p < 0.01). The rest area of the GBM, including newly produced GBM covering the epithelial side of EDD, had no significant difference in size of the pores from control GBM and no tunnels. Although there was no significant difference in the size of enlarged pores between 10 and 15 weeks, the percentage area of GBM with impaired size barrier increased at 15 weeks (51.4 +/- 8.1%) compared with 10 weeks (24.0 +/- 8.3%) and related to severity of proteinuria. The density of the tunnels also increased at 15 weeks. In conclusion, immune deposits may affect the GBM biosynthesis and induce the defect of size barrier of the GBM, which is responsible for proteinuria in active Heymann nephritis.

Animals↗

Self-report of ADHD symptoms in university students: cross-gender and cross-national prevalence.

Little research has examined the structure and prevalence of attention-deficit/hyperactivity disorder (ADHD) symptoms in university students, including whether symptom structure conforms to the bidimensional (i.e., inattention and hyperactivity-impulsivity) conceptualization of the Diagnostic and Statistical Manual of Mental Disorders (DSMV-IV; American Psychiatric Association, 1994) and whether self-reported symptoms vary across gender and country. A sample of 1,209 university students from three countries (Italy, New Zealand, and the United States) completed a 24-item self-report measure (the Young Adult Rating Scale) tapping ADHD symptomatology. Factor analyses within the U.S. and New Zealand samples supported a bidimensional symptom structure, whereas weaker support for this conceptualization was provided by the Italian sample. Participants did not vary significantly by gender in symptom report; however, Italian students reported significantly more inattention and hyperactivity-impulsivity symptoms than students from the United States, and students from New Zealand reported more inattention symptoms than students from the United States. The prevalence of self-reported ADHD symptoms beyond DSM-IV thresholds for diagnosis ranged from 0% (Italian women) to 8.1% (New Zealand men). The implications of these results for the use of DSM-IV criteria in identifying university students with ADHD are discussed.

Adolescent↗

Scavenger effect of elastase on calcifications in liver, kidney and central nervous system tissues of rabbits with atherosclerosis induced by cholesterol-rich diet.

The inhibitory effect of elastase on calcification in liver, kidney and the central nervous system (CNS) was studied in rabbits with atherosclerosis induced by a cholesterol-rich diet. A total of 25 male rabbits were divided into six groups. In the first three groups, rabbits received a standard diet, a 1.5% cholesterol-rich diet or a 1.5% cholesterol-rich diet with intraperitoneal elastase (450 IU/kg.day) for 3 months. In the second three groups, rabbits received a standard diet, a 0.67% cholesterol-rich diet or a 0.67% cholesterol-rich diet with intraperitoneal elastase (450 IU/kg.day) for 6 months. Tissue calcium levels were then determined by neutron activation analysis. Tissue lipid levels were also measured. Dietary cholesterol increased serum lipid levels, atherosclerotic lesions and calcium levels in the CNS, but not in the liver or kidney. Calcium levels in the cerebellum and spinal cord of rabbits receiving the 0.67% cholesterol-rich diet plus elastase were significantly lower than those of rabbits receiving the 0.67% cholesterol diet alone. Elastase had a gradual inhibitory effect on the increase in calcium levels in CNS of cholesterol-induced atherosclerotic rabbits, reduced the increase in serum lipids and decreased the incidence of atherosclerotic lesions.

Animals↗

Calcium, phosphorus and aluminium concentrations in the central nervous system, liver and kidney of rabbits with experimental atherosclerosis: preventive effects of vinpocetine on the deposition of these elements.

Calcium, phosphorus and aluminium concentrations in the central nervous system, liver and kidneys were determined in 16 rabbits with atherosclerosis experimentally induced by a cholesterol-rich diet and the protective effect of 3 or 10 mg/kg.day vinpocetine (14-ethoxycarbonyl-(3 alpha,16 alpha-ethyl)-14,15-eburnamenine) given orally on the deposition of these elements was assessed. Rabbits fed a cholesterol-rich diet developed atherosclerosis after 3 months and these rabbits possessed high concentrations of calcium, phosphorus and aluminium in the central nervous system, determined by neutron activation analysis. In atherosclerotic rabbits fed a vinpocetine supplement, there was a decrease in concentrations of these elements in tissues. It is suggested that calcium, phosphorus and aluminium may be implicated in the aetiology of atherosclerosis and that vinpocetine may have a preventive action on the deposition of these elements in central nervous tissue, liver and kidney.

Aluminum↗

Effects of ibudilast on calcium deposition in soft tissues of rabbits with atherosclerosis.

The effects of 2.5 mg/kg.day ibudilast, with or without 300 mg/kg.day nicomol, or 10 mg/kg.day ibudilast on calcium and magnesium concentrations in the central nervous system (CNS), heart, liver, kidney, skeletal muscle, abdominal aorta and bone were determined in rabbits fed a 1% cholesterol-rich diet for 3 months. Serum thromboxane B2 concentrations were reduced in rabbits treated with 10 mg/kg.day ibudilast or with 2.5 mg/kg.day ibudilast plus 300 mg/kg.day nicomol, and atherosclerotic lesions were ameliorated compared with untreated rabbits. Calcium concentrations in the frontal cortex and cerebellum were lower in ibudilast/nicomol-treated rabbits and in those fed a standard diet compared with those receiving a cholesterol-rich diet only. Calcium concentrations in the pons and abdominal aorta were also lower in ibudilast/nicomol-treated rabbits whereas the calcium concentrations in the cerebellum were lower in rabbits treated with either 2.5 or 20 mg/kg.day ibudilast. There were no significant changes in tissue magnesium concentrations after feeding a cholesterol-rich diet, with or without drug treatment. It is concluded that 2.5 mg/kg.day ibudilast plus 300 mg/kg.day nicomol or 10 mg/kg.day ibudilast produced a scavenger effect on calcium deposited in the CNS and abdominal aorta of rabbits fed a cholesterol-rich diet.

Animals↗

Effects of bifemelane on calcium and magnesium deposition in the central nervous system tissues of rats maintained on low-calcium diets.

The effects of bifemelane [4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride] on the deposition of calcium and magnesium in central nervous system (CNS) tissues, heart, liver, kidney, muscle, abdominal aorta and bones were studied in rats maintained on standard and low-calcium diets. Rats were maintained for 90 days on the following diets: standard calcium (12.5 g/kg diet); standard with 100 mg/kg bifemelane; low-calcium (30 mg/kg diet); and low-calcium with bifemelane. The presence of bifemelane did not affect blood chemistry, but the magnesium concentration in the cerebellum was significantly (P less than 0.05) higher in rats receiving standard diet after bifemelane treatment. Magnesium concentrations in the pons, cerebellum, spinal cord, heart, liver and femur of bifemelane-treated rats fed low-calcium diets were significantly (P less than 0.05) higher compared with the corresponding controls, whereas the calcium concentration in the liver was significantly (P less than 0.05) lower. In general, bifemelane tended to decrease calcium deposition in the CNS and soft tissues of rats fed standard or low-calcium diets. Bifemelane may activate cerebral metabolism and maintain magnesium concentrations in the CNS and soft tissues, and be implicated in metal metabolism in rats fed low-calcium diets.

Animals↗

Effects of bifemelane hydrochloride on atherosclerosis in aged rats fed low-calcium diets.

The preventative effects of bifemelane (4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride) on atherosclerosis in aged rats fed low-calcium diets were investigated. Male 18-month-old Wistar rats were maintained for 90 days on the following: (A) standard diet (n = 7), (B) low calcium, low magnesium, high aluminium diet (n = 8), (C) standard diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6), (D) low calcium and magnesium, high aluminium diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6). All groups were give these diets and water ad lib for 90 days, after which blood samples were taken from the abdominal aorta and samples of aorta were examined for atherosclerotic changes. The serum concentrations of the following were determined: calcium, magnesium, zinc, aluminium, inorganic phosphorus, cholesterol, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, lactate dehydrogenase, cholinesterase, creatine phosphokinase, blood urea nitrogen and N-terminal parathyroid hormone. The only significant differences between the groups in serum chemistry were reduced concentrations of cholinesterase and magnesium in groups B and D, increased aluminium in group B, and increased N-terminal parathyroid hormone in groups B and D. In groups C and D the atherosclerosis was much improved compared with that in groups A and B. It appears that bifemelane largely prevents atherosclerosis caused by calcium deposition in the arteries of rats fed low-calcium diets, due to its effect in maintaining magnesium and calcium in bones.

Aluminum↗