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Biomedical subjects

M Yanaka

Publications and source records attributed to M Yanaka.

15 recordsLinked to original sources

Determination of the bioavailability of intranasal elcatonin in humans: development of a sandwich transfer enzyme immunoassay for elcatonin.

A sandwich transfer enzyme immunoassay for elcatonin (ECT) and its usability for the pharmacokinetic study are described. The anti-salmon calcitonin (SCT) antibody was used for the present assay. The assay procedure consisted of the reaction of ECT with 2,4-dinitrophenylbiotinyl anti-SCT IgG and anti-SCT Fab'-beta-D-galactosidase conjugate, trapping onto (anti-2,4-dinitrophenyl bovine serum albumin) IgG-coated polystyrene balls, eluting with epsilonN-2,4-dinitrophenyl-L-lysine and transferring to streptavidin-coated polystyrene balls and fluorometric detection of beta-D-galactosidase activity. The practical detection limit of ECT was 0.15 pg (44 amol)/50 microl of sample and 3 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of ECT dosed intranasaly at a therapeutic level (100 IU, 17 microg) for its anti-osteoporotic effect as compared to an intramuscular dose (40 IU, 6.7 microg). The pharmacokinetic parameters of the intranasal ECT (n = 6) thus estimated were as follows: the area underthe serum concentration-time curve (AUC) = 2,570 +/- 1,650 (SD) pg x min/ml, and the maximal concentration (Cmax) = 60 +/- 25 (SD) pg/ml with the maximal time (Tmax) = 17.5 +/- 6.9 (SD) min, when the AUC for the intramuscular ECT (n = 9) = 9,460 +/- 5,870 (SD) pg x min/ml and the Cmax = 165 +/- 79 (SD) pg/ml with the Tmax = 16.1 +/- 4.2 (SD) min.

Administration, Intranasal↗

Effect of blood filling in intramyocardial vessels on coronary arterial inflow.

The influence of the filling condition of the unstressed volume (UV) of intramyocardial vessels on the diastolic coronary arterial pressure-flow relationship was analyzed. UV is defined as the blood volume at zero transmural pressure. In seven anesthetized, paced dogs with induced heart block, coronary artery inflow was occluded so that blood in the UV was displaced into the coronary vein by myocardial contraction. After pacing was turned off, coronary perfusion pressure was increased stepwise to seven target pressures (20-90 mmHg). After reperfusion, left anterior descending coronary arterial (LAD) flow reached an initial quasi-steady level, but great cardiac venous (GCV) flow was absent (UV-unfilled phase). With reappearance of the GCV flow (UV-filled phase), LAD flow decreased to a final steady level. Pressure-flow relationships during both phases were linear (r = 0.97-0.99). The inverse of the slope of the pressure-flow relationship during the UV-filled phase, 0.69 +/- 0.08 mmHg.min.ml-1, was significantly higher than that during the UV-unfilled phase, 0.55 +/- 0.06 mmHg.min.ml-1 (P less than 0.01), although the zero-flow pressure intercepts were similar (18.9 +/- 1.8 mmHg for UV filled vs. 19.9 +/- 2.2 for UV unfilled). These results indicate that diastolic coronary arterial inflow is impeded by a blood volume within intramyocardial vessels that exceeds the UV.

Animals↗

Analysis of the characteristics of the flow velocity waveforms in left atrial small arteries and veins in the dog.

To clarify the characteristics of the phasic blood velocity pattern in small arteries and veins on the left atrial surface, we used our newly developed fiber-optic laser Doppler velocimeter. We intended particularly to examine the influence of atrial contraction and relaxation on velocity waveforms to obtain some insight into the nature of the mechanical force acting on the atrial intramyocardial vascular beds. In 14 anesthetized open-chest dogs, the left atrial appendage was gently displaced to expose small branches of the artery and vein. Vessels with an outer diameter of about 150-500 microns were chosen for the measurements because their walls are transparent to laser light. The fiber tip (velocity sensor) was fixed on the vessel surface with a drop of cyanoacrylate when good-quality Doppler signals were consistently observed. Additional experiments with three dogs were performed to observe the blood velocities in the atrial artery and vein during arrhythmia. The blood velocity waveform in the artery was similar to the pattern of aortic pressure during ventricular ejection (peak velocity, 18.8 +/- 7.8 cm/sec) but was characterized by a pronounced dip during atrial contraction. The temporal coincidence between the dip formation and atrial contraction was confirmed during atrial flutter with an atrioventricular block. After isoproterenol administration (2 micrograms i.v.), the acceleration rate of the forward flow velocity increased by 176% (p less than 0.05), and reverse flow appeared during atrial contraction in five cases out of eight (p = 0.013). The blood flow velocity in atrial small veins, on the other hand, was predominant during atrial contraction (peak velocity, 15.6 +/- 5.8 cm/sec). Isoproterenol increased the acceleration rate of this forward flow velocity by 121% (p less than 0.01). Nitroglycerin did not change the blood velocity waveform significantly in atrial arteries or in veins. The phase opposition between arterial inflow into and venous outflow from the atrial myocardium indicates that a large portion of the coronary inflow to the atrial myocardium may be stored due to the presence of atrial myocardial vascular capacitance. We conclude that atrial myocardial contraction impedes atrial inflow and promotes venous outflow from atrial capacitance vessels.

Animals↗

Effects of dietary protein level and ascorbic acid supplementation on the contents of tyrosine metabolites in droppings and plasma of chicks fed a diet containing excess tyrosine.

A study on chickens was conducted to investigate whether or not: a) excess dietary tyrosine increases the content of tyrosine metabolites in plasma and excreta, b) these elevations of tyrosine metabolites are presented by increasing dietary protein level or supplementing with ascorbic acid (AA), and c) urine is a major excretory route of tyrosine metabolites. Chicks fed a 10% protein diet with excess tyrosine developed external foot lesions accompanied by retarded growth and depressed feed intake. These adverse effects were alleviated by elevating dietary protein level or supplementing with AA. Excreta and plasma of chicks fed the 10% protein diet contained small or undetectable amounts of free tyrosine, 4-hydroxyphenylpyruvate (4-HPP), 4-hydroxyphenylacetate (4-HPL), and 4-hydroxyphenylacetate (4-HPA), while these metabolites were markedly increased by the addition of excess tyrosine to the 10% protein diet. From the results with colostomized cocks, the major source of 4-HPP, 4-HPL, and 4-HPA excreted by chicks fed a tyrosine excess diet was considered more likely to be of urinary than fecal origin. Elevated contents of tyrosine and its metabolites in plasma were partially counteracted by increasing dietary protein level or AA supplementation. In excreta, elevated contents of tyrosine and its metabolites caused by excess tyrosine were reduced by increasing dietary protein level and supplementing with AA when expressed in the proportion of tyrosine intake. These results suggest that the beneficial effects of increased dietary protein level and supplementation with AA are related to enhanced ability of chicks to degrade excessively ingested tyrosine.

Animals↗

Influence of ascorbic acid on the adverse effect of feeding a diet containing excess tyrosine to chicks.

1. The effects of dietary or parenteral administration of ascorbic acid on the adverse effects of excess tyrosine were investigated with young male White Leghorn chicks in a 2-week experiment. 2. Addition of 10 g ascorbic acid/kg to the control diet (without excess tyrosine) produced no beneficial effects on performance. Excess dietary tyrosine caused depressions in all measures of performance. 3. Adding 0.1, 1, 10 or 20 g ascorbic acid/kg to the diet containing excess tyrosine tended to improve performance. 4. Subcutaneous injection of 50 mg ascorbic acid/bird d to chicks receiving excess tyrosine brought about a significant improvement in body-weight gain. 5. The elevation of plasma free tyrosine caused by excess dietary tyrosine decreased as dietary ascorbic acid increased. 6. Ascorbic acid can alleviate, though not completely counteract, the adverse effect of excess dietary tyrosine.

Animals↗

Effects of dietary excess tyrosine and level of feed intake on nitrogen and energy utilization in chicks.

The present study using 8-day-old White Leghorn male chicks, was made to determine whether retarded growth of chicks fed a tyrosine excess (Tx) diet ad lib was due to the depression in feed intake or the reduced efficiency of feed utilization. A Tx diet was prepared by supplementing a 20% crude protein basal diet with 5% L-tyrosine. The levels of feed intake prepared for 10 days were as follows: 160 (corresponding to the amounts of the basal diet the chick would consume ad lib), 140, 120 (corresponding to the amounts of the Tx diet the chick would consume ad lib), 100, and 80 g per bird. Body weight gain, gain:feed ratio, and energy retention rate of chicks fed the basal or Tx diet decreased proportionally as the level of feed intake was decreased. The addition of Tx to the basal diet significantly reduced the body weight gain, gain:feed ratio, metabolizable energy (ME) value, and nitrogen and energy retention rates at all levels of feed intake. Body composition was not significantly affected by the addition of Tx to the basal diet at all levels of feed intake. The plasma free tyrosine concentration was markedly increased by the addition of Tx to the basal diet and also with increments in feed intake. Dietary Tx per se had a decreasing effect on body weight gain, efficiencies of dietary nitrogen, energy utilization, and ME value. The growth retardation of chicks fed a Tx diet ad lib was due to the combined effects of the depression in feed intake and the reduced efficiency of feed utilization.

Amino Acids↗

Plasma cell granuloma (inflammatory pseudotumor) of the spinal cord meninges: report of a case.

A case of plasma cell granuloma (inflammatory pseudotumor) arising in the meninges of cervical spinal cord of a 37-year-old Japanese man is presented. The diagnosis was made by analogy with the similar lesions known in the lung. Its histology was characterized by infiltration of three kinds of cells; histiocytes with slight epithelioid appearance, plasma cells with numerous Russell bodies, and lymphocytes. Electron microscopy of the formalin-fixed tissue was useful for the identification of these cells, particularly of histiocytes. Although extrapulmonary plasma cell granulomas have been reported, this is the first case, to our knowledge, of this type "tumor" in the spinal cord meninges. Differential diagnoses have been briefly discussed.

Adult↗