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Biomedical subjects

K Hosoya

Publications and source records attributed to K Hosoya.

At least 55 records · Page 3Linked to original sources

Enalapril and losartan reduced cardiac mass and improved coronary hemodynamics in SHR.

Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.

Angiotensin Receptor Antagonists↗

Myocardial contractility of the canine left ventricle during unsynchronized dual chamber pacing.

The influence of changes of left ventricular (LV) myocardial contractility on the decrease of cardiac output during atrial fibrillation was investigated in dogs using the slope (Ec) and the length intercept (Lo) of the LV end-systolic force-length relationship. The hearts of nine healthy adult mongrel dogs were instrumented with ultrasonic crystals and a micromanometer, after which pharmacologic autonomic blockade was instituted. The LV diameter and pressure data were recorded during inferior vena caval occlusion. Hemodynamic parameters were measured during pacing from the right atrial appendage at a pacing rate 30 beat/min greater than the natural heart rate using a cardiac stimulator (atrial pacing), and during simultaneous pacing from the right atrial appendage and right ventricular apex at the same rate (unsynchronized dual chamber pacing). Cardiac hemodynamics in the absence of synchronized left atrial contraction were simulated by unsynchronized pacing. During atrial pacing, the cardiac output (1.68 +/- 0.25 vs 1.57 +/- 0.21 l/min, p < 0.005) and Ec (110.1 +/- 58.5 vs 81.8 +/- 30.8 g/cm, p < 0.05) were significantly greater than during normal sinus rhythm, whereas the stroke volume (12.4 +/- 2.4 vs 15.1 +/- 3.1 ml, p < 0.005) and LV end-diastolic volume (16.6 +/- 2.7 vs 19.5 +/- 3.4 ml, p < 0.005) were significantly smaller. Lo did not change during pacing. During unsynchronized dual chamber pacing, cardiac output (1.46 +/- 0.17 vs 1.68 +/- 0.25 l/min, p < 0.005), stroke volume (10.8 +/- 1.7 vs 12.4 +/- 2.4 ml, p < 0.005), and LV end-diastolic volume (15.0 +/- 2.0 vs 16.6 +/- 2.7 ml, p < 0.05) were significantly smaller than during atrial pacing. However, Ec and Lo were similar during both types of pacing. These findings suggest that the decrease of cardiac output and stroke volume during atrial fibrillation is chiefly due to the decrease of LV end-diastolic volume through loss of left atrial contraction, and is not due to a change of LV myocardial contractility.

Animals↗

Contribution of Na(+)-glucose cotransport to the short-circuit current in the pigmented rabbit conjunctiva.

The objective of this study was to determine whether Na(+)-glucose cotransport contributed to the residual short-circuit current (Isc) in the pigmented rabbit conjunctiva not accounted for by Cl- secretion. The Isc of the pigmented rabbit conjunctiva was measured following exposure of its mucosal or serosal side to varying concentrations of D-glucose or phloridzin in a glutathione-bicarbonated Ringer's solution (GBR). Addition of D-glucose to the mucosal side of the conjunctiva bathed in glucose-free GBR elevated Isc up to 26 +/- 6% in a dose-dependent manner (K0.5 = 1.2 mM), while mucosal (but not serosal) addition of phloridzin reduced the Isc (IC50 = 0.05 mM) of the conjunctiva bathed in regular GBR. In a mucosal Na(+)-free medium, neither 20 mM D-glucose nor 0.5 mM phloridzin was effective. In a mucosal glucose-containing medium, deletion of Na+ reduced Isc up to 27 +/- 4%. It was, however, restored to its initial value upon the addition of 17.5-141 mM Na+ to a medium containing 5 mM D-glucose. Hill plot analysis of Isc elevation at 141 mM Na+ in the presence of varying D-glucose concentrations in the mucosal bathing fluid yielded a Hill coefficient of 0.86. There is, therefore, evidence for the apical localization of phloridzin-sensitive Na(+)-coupled D-glucose transport that exhibits apparent 1:1 stoichiometry, being responsible for the maximal 26% increase in the Isc.

Animals↗

Temperature-controlled high-performance liquid chromatography using a uniformly sized temperature-responsive polymer-based packing material.

Uniformly sized polymer-based packing materials modified with a temperature-responsive polymeric selector, poly(N-isopropylacrylamide), on either the internal or the external surface were prepared by an in situ surface-selective modification method. These packing materials were utilized as stationary phases in reversed-phase high-performance liquid chromatography to evaluate their ability to thermally control chromatographic separation selectivity. A packing material having a modified internal surface showed temperature-dependent separation selectivity in drug separation. Drugs that could not be separated below the phase transition temperature of the poly(N-isopropylacrylamide) selector were separated faster and with much better resolution above the phase transition temperature, while the unmodified base packing material afforded worse resolution of the drugs above the phase transition temperature due to the peak overlapping resulting from faster elution of all the solutes employed. In addition, a packing material modified on the external surface showed a temperature-responsive shift of the elution region for a polypeptide such as BSA, which was thought to be useful in direct injection of a serum sample.

Acrylic Resins↗

Uniform-size hydrophobic polymer-based separation media selectively modified with a hydrophilic external polymeric layer.

A simple procedure for the preparation of macroporous hydrophobic styrene-divinylbenzene polymeric separation media with a hydrophilic outer surface has been developed. A hydrophilic monomer and water-soluble polymerization initiator are added to the reaction mixture during the final polymerization step of the preparation of size-monodisperse particles. Because the hydrophobic styrene-divinylbenzene framework of the beads is already formed, and the hydrophilic monomer does not penetrate the pores of the beads that are filled with a hydrophobic porogen, the hydrophilic layer is formed only at the surface of the beads. The hydrophilic monomers used included glycerol monomethacrylate and glycerol dimethacrylate and toluene was used as the porogen for the poly(styrene-co-divinylbenzene) beads. Comparative experiments involving beads with or without a hydrophilic medium showed that the separation selectivity of the media towards hydrophobic solutes remains unchanged. However, the modified medium with a hydrophilic layer could be used to analyse mixtures that also contained large peptide molecules as these do not adsorb at its surface as is the case with the unmodified hydrophobic beads.

Chromatography, Liquid↗

Photodecomposition of 1,2,3,4- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in water-alcohol media on a solid support.

We used a hydrophobic solid support, octadecylsilylated silica gel (C18), packed in a quartz column as a reaction medium for the photolysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD). When we exposed the column to a 450 W UV lamp, the adsorbed 1,2,3,4-TCDD or 2,3,7,8-TCDD in 10% 2-propanol/water decomposed completely in 20 minutes and 5 minutes, respectively. The large estimated partition coefficient of 1,2,3,4-TCDD in 10% 2-propanol/water (> 1000) indicates that on the C18 stationary phase, both the saturated hydrocarbon chains and the absorbed 2-propanol may act as proton donors and accelerate the photolysis. In direct sunlight, the adsorbed 1,2,3,4-TCDD in 10% 2-propanol/water decomposed much faster than in a nonaqueous solvent (50% 2-propanol/methanol). This solvent effect is advantageous for the practical use of the C18 photolysis process in aqueous waste treatment. We have demonstrated that complete C18 trapping with continuous photodecomposition of TCDD contained in an aqueous alcohol waste is possible.

Adsorption↗

Cross-bridge activation rate constant determined from systolic time intervals in patients with systemic lupus erythematosus.

Cardiac adrenergic activity was investigated in 38 patients with systemic lupus erythematosus (SLE) who were not receiving cardiovascular agents using a new index of the adrenergic tone of the working left ventricular (LV) myocardium and using the heart rate to represent sinus node adrenergic tone. According to the active cross-bridge model employed in this study, the cross-bridge activation rate constant (Ka) of the LV myocardium, corresponding to the rate constant for the binding of Ca2+ to troponin C, can be approximately expressed as Ka = 3/electromechanical systole (sec-1). The Ka value corrected for heart rate (Kac) remains nearly constant in normal individuals, but is increased without change of the heart rate by dobutamine infusion. Fifty patients who fulfilled the American Rheumatism Association criteria for SLE underwent echocardiography, as well as simultaneous recording of the electrocardiogram, phonocardiogram, and carotid pulse wave tracing. Kac was calculated from the interval between the onset of the QRS complex to the second heart sound (QS2 interval) and the heart rate (HR) as follows: Kac = 3/QS2 + 0.0249 (66-HR). The 38 SLE patients were divided into a normal Kac group (n = 26, 6.9 < Kac < 8.3 sec-1) and a high Kac group (n = 12, Kac > or = 8.3 sec-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of sodium taurodihydrofusidate on nasal drug delivery: differences in its concentration and penetrant molecular weight.

The effect of sodium taurodihydrofusidate (STDHF) on drug permeation across nasal mucosa was studied in vitro using Ussing type diffusion chamber. Disodium cromoglicate (DSCG, M.W. 512.3) and fluorescein isothiocyanate-dextran (FD) of different molecular weights (M.W. 4400-71200) were used as model drugs. Permeation profiles of DSCG and FDs showed a typical pseudo steady-state curve with short lag time. The permeability coefficient of FD (M.W. 9400) sigmodially increased with increasing STDHF concentration. It also enhanced the DSCG permeation. Interestingly the enhancement efficacy was independent of molecular weight of penetrants.

Adjuvants, Pharmaceutic↗

Evaluation of enhancers to increase nasal absorption using Ussing chamber technique.

The effects of eight prospective absorption enhancers on the nasal mucosa in rabbit have been assessed using an in vitro Ussing chamber technique. Sodium taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl ether (BL-9), lysophosphatidylcholine (LPC) and sodium dodecyl sulfate (SDS) were found to possess relatively high protein leaching activity, while sodium glycocholate (GC), sodium taurocholate (TC) and EDTA had relatively low activity. The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a model drug across the nasal mucosa was found to be greater in the presence of these enhancers. Their enhancement ratio was found to be in the order of BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein leaching activity. The differences in protein leaching and enhancement ratio dependent on the magnitude of change of membrane resistance (delta Rm), indicating that these enhancers damaged the membrane and increased FD permeation. delta Rm thus appears to be a useful indicator by which one can estimate nasal mucosa damage by the enhancers.

Absorption↗

The structural barrier of absorptive mucosae: site difference of the permeability of fluorescein isothiocyanate-labelled dextran in rabbits.

The permeability of fluorescein isothiocyanate-labelled dextran (FD, M.W. 4400-71,200) across nasal, buccal, duodenal, jejunal, ileal, colonic, and rectal mucosae excised from rabbits has been measured to estimate the structural barrier of absorptive mucosae using Ussing-type diffusion chambers. The permeability coefficient of FD in all these mucosae decreased with increasing molecular weight. The rank order of FD permeability did not always correlate with the electrical resistance of the mucosae. Among components of the small intestine (duodenum, jejunum, ileum) and the large intestine (colon, rectum), however, the rank order of FD permeability corresponded to the magnitude of the electrical resistance in each instance; the upper colonic mucosa showed the highest permeability, especially in FD of low molecular weight, and permeability of the rectal mucosa was lowest except for the duodenal mucosa. The nasal mucosa showed the lowest electrical resistance and the highest permeability of those studied, suggesting that it has a leaky structural barrier.

Animals↗

New interpretation of systolic time intervals from active cross-bridge model.

Using an active cross-bridge model proposed by the authors, it has been established theoretically that cross-bridge activation rate (Ka) of the left ventricular myocardium, which might correspond to the rate of binding of Ca2+ with troponin C, is approximately expressed as a simple formula: Ka = 3/electromechanical systole (sec-1), although no definitive biological proof has yet been provided for the equation. One hundred eighteen patients without significant cardiac disease and 6 patients who had atrioventricular block with a permanent pacemaker were evaluated to determine the Ka value of the normal human left ventricular myocardium (test 1), and to examine the effect of changes in heart rate (test 2) as well as afterloading (test 3) or dobutamine infusion (test 4) on Ka. The pacing rate was increased from 50 to 110 beats/min at 20-beat increments in test 2. Arterial pressure was elevated by angiotensin II infusion in test 3, and 7 subjects received a continuous dobutamine infusion in test 4. The Ka value was found to be related to heart rate, to be increased by dobutamine infusion, and to be decreased by myocardial lengthening due to afterloading. Dependence of Ka on heart rate appeared to result from changes in myocardial length. The Ka value corrected for heart rate (Kac) had an average variation of only 4.6%, and was unrelated to age or myocardial length in individual subjects. Thus, the Kac value of normal human left ventricular myocardium appears to be nearly constant between individuals but to be increased by catecholamine infusion or myocardial shortening.

Adult↗

Polymeric porogens used in the preparation of novel monodispersed macroporous polymeric separation media for high-performance liquid chromatography.

A novel approach to monosized macroporous polymeric separation media with vastly enhanced pore size distributions and chromatographic properties has been developed. Key to this approach is the combined use of monodispersed polymeric particles and suitable solvents as porogens in the copolymerization of styrene and divinylbenzene. Following polymerization, the polymeric porogen is dissolved, leaving behind the monosized beads with a controlled pore structure. The exact pore size and pore size distribution of the final beads are largely controlled by the amount of soluble polymer in the polymerizing mixture: the larger the proportion of soluble polymer in the system, the larger the pores. The uniformly sized macroporous beads prepared with an optimized ratio of polymeric and low molecular weight porogens proved to be very efficient even in short columns for the separation of polystyrene standards in the SEC mode and the separation of proteins in the reversed-phase mode. The relationship between pore size and specific surface area, on one hand, and chromatographic properties of the stationary phase, on the other, have been clearly documented.

Chromatography, High Pressure Liquid↗

Mechanism of skin penetration-enhancing effect by laurocapram.

In order to clarify the mechanism of action of laurocapram (Azone) on the skin permeation of drugs, the following experiments were done. First, the effect of Azone on the skin components was compared with that of other penetration enhancers. Azone markedly fluidized liposomal lipids (as a model lipid system) compared with other enhancers. Ethanol extracted large amounts of the stratum corneum lipids, whereas Azone did not. These results suggest that the effect of Azone on the lipids in the stratum corneum is not the same as that of ethanol. In addition, ethanol increased the amount of free sulfhydryl (SH) group of keratin in the stratum corneum, whereas Azone did not directly affect the stratum corneum protein. Azone increased water content in the stratum corneum, as measured by skin conductance. This effect might be a reason for the action of Azone. For further understanding, the enhancing effects of Azone on the skin permeation of several model compounds (alcohols, sugars, and inorganic ions) were compared with the effects of pretreatment with distilled water, which was thought to increase water-holding capacity, and pretreatment with ethanol, which was thought to affect the lipids and protein in the skin barrier (i.e., stratum corneum). Pretreatment with water or ethanol enhanced skin permeation of hydrophilic compounds, whereas they decreased that of octanol, a hydrophobic compound. The tendency of Azone to increase or decrease the skin permeation rate of most compounds was similar to that of pretreatment with water or ethanol. However, the effect of Azone on the skin permeation of inorganic ions was relatively low, whereas that of pretreatment with water or ethanol was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗

Performance of wide-pore silica- and polymer-based packing materials in polypeptide separation: effect of pore size and alkyl chain length.

The effects of pore size and alkyl chain length of silica- and polymer-based packing materials in the elution of polypeptides with an acetonitrile gradient in the presence of trifluoroacetic acid were studied. Considerable differences were found in the performance of alkylsilylated phases prepared from various wide-pore silica particles assumed to have 30-50-nm pores. The pore size of such silica gels was found to be the critical factor in determining the efficiency for high-molecular-weight polypeptides. Silica C18 phases having small pore volumes below 20 nm pore diameter showed comparable performances to C4 and C8 phases for polypeptides with molecular weights of up to 80,000, and were more stable. Polymer-based packing materials with adequate pore size provided excellent column efficiencies and recoveries for polypeptides with higher chemical stabilities than silica-based materials.

Acetonitriles↗

Primary structure of an alkaline ribonuclease from bovine liver.

A pyrimidine base specific and most basic alkaline RNase named RNase BL4 was isolated from bovine liver as a protein showing a single band on slab gel-electrophoresis. The enzyme is most active at pH 7.5. The enzyme was immunologically distinguishable from the known bovine RNases such as pancreatic RNase (RNase A), seminal RNase, kidney non-secretory RNase (RNase K2), and brain RNase (RNase BRb). The primary structure of this pyrimidine base-specific RNase was determined to be less than EDRMYQRFLRQHVDPDETG- GNDSYCNLMMQRRKMTSHQCKRFNTFIHEDLWNIRSICSTTNIQCKNGQMNCHEGVVRV- TDCRETGSSRAPNCRYRAKASTRRVVIACEGNPEVPVHFDK. It consists of 119 amino acid residues, and is 5 amino acid residues shorter than RNase A. The sequence homology of RNase BL4 with RNase A is 46.2%, and optimal alignment of RNase A and RNase BL4 requires five deletions, one at the 24th position, two at the 75th and 76th positions, and two at the C-terminus in RNase BL4. The RNase BL4 was highly homologous with a porcine liver RNase (RNase PL3, 94.1% homology) studied by Hofsteenge et al. (personal communication from Hofsteenge, J., Matthies, R., and Stones, S.R.).

Amino Acid Sequence↗

[New method to detect late potential with fast Fourier transform analysis].

We compared a new method to detect late potential applied fast Fourier transform (FFT-LP) with the prior method of Simson (S-LP). We investigated 159 consecutive pts excluding atrial fibrillation, 102 pts with old myocardial infarction (MI) without bundle branch block (BBB), 10 pts with dilated cardiomyopathy (DCM) without BBB, normal 17 pts without BBB, 15 MI pts with BBB, 3 DCM pts with BBB, and normal 12 pts with BBB. And 102 MI pts without BBB were divided into 3 groups by S-LP, group 1 was 12 pts, of which 2 or 3 parameters of S-LP were positive, group 2 was 5 pts, of which 1 parameter of S-LP was positive, and the 3rd group was 85 pts, of which all parameters of S-LP were negative. FFT was performed in the segment from terminal 40 mesc of QRS complex to ST segment, then, the area under the curve between 20 and 50 Hz was divided by the area under the curve between 0 and 20 Hz. We called this ratio "area ratio (AR)", and examined it in each group. When the value of AR was over 20, defined as FFT-LP positive, the positive ratio was 75% (group 1), 20% (group 2), 11.9% (group 3), 0% (normal pts without BBB), 40% (MI with BBB), 8.3% (normal with BBB).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Association of various cardiac parameters and signal-averaged electrocardiographic late potentials in patients with myocardial infarction].

UNLABELLED: After the amplification and filtration of the surface ECG, late potential signal (LP) in QRS termination was determined. Subjects were 52 patients who experienced acute myocardial infarction within 5 years and measurement was undertaken 70 times. 271 pulses (average) were measured using the Model 101 PC system (ART Co, Ltd) with 40-250 Hz filter. Relationship of LPs and ventricular tachyarrhythmia, LPs and left ventricular function were studied according to the ejection fraction (EF) of left ventricle (= index of left ventricular function) and maximum value of CPK (CPKmax) in acute phase. The patients with bundle branch block, atrial fibrillation and noise above 1.0 microV were excluded. RESULTS: (1) Higher incidence of LP was shown in patients with triplet or more runs of ventricular tachycardias. (2) Higher incidence of LP was shown in patients with lower EF and higher CPKmax. Above results showed that non-invasive and simple recording of LPs in patients with myocardial infarction was useful in the discrimination of the patients with ventricular arrhythmia and presumption of left ventricular function.

Adult↗