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Biomedical subjects

A Otsuka

Publications and source records attributed to A Otsuka.

At least 55 records · Page 3Linked to original sources
PubMed1991

Dissolution of solid dosage form. II. Equations for the dissolution of nondisintegrating tablet under the sink condition.

An equation for dissolution from the whole surface of a nondisintegrating single component tablet under the sink condition was derived. Also, equations for several dissolution manners of the tablet under the sink condition were derived in the postulation of the dominant dissolution rate constant which determines the dissolution manner. The applicability or validity of these equations were examined by the dissolution measurements with nondisintegrating single component tablets. About one-tenth the amount of the amount needed to saturate the solution was used to prepare a tablet, and dissolution measurements were carried out with the tablet whose flat or side surface was masked with an adhesive tape in accordance with the conditions for derivation of equations. Among the derived equations, dissolution from the whole surface of a tablet was expressed by a form similar to the cube root law equation for particles. Hence, a single component tablet compressed by the use of a suitable amount was thought to behave like a single crystal. Also, equations derived for several dissolution manners were thought to be applicable for the dissolution of a nonspherical particle and crystal concerning the crystal's habit and its dissolution property, and the extended applicability was examined by converting the crystal into a simplified or idealized form, i.e., rectangle or plate.

Mathematics↗
PubMed1991

Nicotinamide and 3-aminobenzamide reduce interferon-gamma-induced class II MHC (HLA-DR and -DP) molecule expression on cultured human endothelial cells and fibroblasts.

We investigated the effects of nicotinamide and 3-aminobenzamide, known as inhibitors of poly (ADP-ribose) synthetase, on the expression of interferon- gamma (IFN-gamma)-induced class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF). Indirect immunofluorescent staining on HUVEC and HDF was performed using monoclonal antibodies against class I MHC (HLA-A,B,C) and class II MHC (HLA-DR, HLA-DP and HLA-DQ) molecules, and then the expression of these molecules was determined using a fluorescence flow cytometry. Human recombinant IFN-gamma (100 U/ml) increased the expression of HLA-A,B,C molecules, and induced the expression of HLA-DR molecules and, to a lesser extent, of HLA-DP on both HUVEC and HDF. HLA-DQ molecules were not induced by IFN-gamma on either cell type. Nicotinamide and 3-aminobenzamide in the concentration greater than or equal to 1 mM reduced the IFN- gamma -induced expression of HLA-DR and HLA-DP on both HUVEC and HDF, whereas neither agent in the concentration of up to 10 mM affected the IFN- gamma -induced increase in HLA-A,B,C molecule expression. These data suggest that nicotinamide and 3-aminobenzamide suppress antigen presenting function of class II MHC positive endothelial cells and fibroblasts at the site of tissue inflammation.

Animals↗
PubMed1991

Lipopolysaccharide augments HLA-A,B,C molecule expression but inhibits interferon-gamma-induced HLA-DR molecule expression on cultured human endothelial cells.

The effect of bacterial lipopolysaccharide (LPS) on the expression of class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) was determined by indirect immunofluorescent staining followed by flow cytometric analysis. LPS at concentrations higher than 0.01 micrograms/ml augmented class I MHC (HLA-A,B,C) expression on HUVEC in a concentration-dependent manner. Optimal augmentation, approximately sixfold compared with control, was seen with 10 micrograms/ml of LPS. Time-course experiments indicated that the augmentation was maximal on Day 4. In contrast, LPS had no effect on the induction of class II MHC (HLA-DR) molecules and at concentrations higher than 0.01 micrograms/ml inhibited the interferon-gamma(IFN-gamma)-induced class II MHC expression. The inhibition was about 60% at the concentration of 100 micrograms/ml of LPS. Interleukin-1 (IL-1) had a similar effect as LPS on class I and II MHC expression. However, LPS appeared to affect MHC expression directly and not through production of IL-1 or cyclo-oxygenase pathway products, since anti-IL-1 antibodies or an inhibitor of cyclo-oxygenase pathway products, indomethacin, failed to reverse the effects of LPS. These data stress the role of LPS as a direct modulatory factor of class I and II MHC expression on endothelial cells during the development of immune and inflammatory response against Gram-negative bacteria.

Antibodies↗
PubMed1991

Importance of the sympathetic nervous system in blood pressure elevation by subpressor intraventricular NaCl and angiotensin II in the rat.

The present study was performed to examine the effect of chemical sympathectomy with guanethidine on the BP change and humoral factors in rats which received continuous and concomitant infusion of i.c.v. hypertonic NaCl with i.v. Ang II, both at subpressor doses for 7 days. Male rats were divided into 3 groups which received the following infusions using an osmotic minipump at a rate of 1 microliter/min: Group 1 (n = 11), 0.15 M NaCl i.c.v. and Ang II (5.4 pmol/kg/min) i.v.; Group 2 (n = 9), 0.8 M NaCl i.c.v. and Ang II i.v.; Group 3 (n = 5), 0.8 M NaCl i.c.v. and Ang II i.v. with daily i.p. injection of guanethidine (40 mg/kg). Significant increase in BP was observed only in Group 2 (from 103 +/- 3 mmHg to 132 +/- 5 mmHg on day 7, p less than 0.001). Addition of i.p. guanethidine to i.c.v. infusion of 0.8 M NaCl and the subpressor dose of Ang II completely prevented increase in the BP, suggesting that the presence of the intact sympathetic nervous system is necessary for the development of BP elevation in response to i.c.v. hypertonic NaCl plus i.v. Ang II. Thus, the sodium status in the central nervous system is important in the regulation of BP and is closely related to the activity of the sympathetic nervous system.

Angiotensin II↗
PubMed1990

No beneficial effect of splenectomy in hereditary high red cell membrane phosphatidylcholine hemolytic anemia: clinical and membrane studies of 20 patients.

The clinical features and red cell membrane characteristics of 20 patients with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) were studied in relation to the effect of splenectomy. After splenectomy, anemia worsened and the extent of increased hemolysis in these patients was unchanged, indicating a contraindication for splenectomy. Concomitant with these results in clinical hematology, marked stomatocytic changes, increased red cell phosphatidylcholine content, and enhanced sodium transport, which were observed before splenectomy, were not improved by splenectomy.

Adolescent↗
PubMed1990

Preventive effect of a new immunosuppressant FK-506 on insulitis and diabetes in non-obese diabetic mice.

We investigated the effect of an immunosuppressant FK-506 on histological change of islets, the onset of diabetes, and the change of spleen cell subsets in female non-obese diabetic mice. Mice administered intraperitoneally with FK-506 from 5 to 20 weeks of age showed marked suppression of mononuclear cell infiltration (insulitis) at 10 weeks of age. Among the subsets of the spleen cells, a significant decrease in the population of Thyl.2-positive T cells (pan-T), L3T4-positive T cells (mainly helper/inducer), and Lyt2-positive T cells (mainly suppressor/cytotoxic) was observed in FK-506-treated mice. Furthermore, glucose tolerance of the mice at 15 weeks of age was clearly improved. Cumulative incidence observed up to 40 weeks of age was 86% in control mice and 23% in FK-506-treated mice (p less than 0.01). These data indicate that FK-506 has a preventive effect on insulitis and diabetes by the suppression of cell-mediated autoimmunity in non-obese diabetic mice.

Animals↗
PubMed1990

Differential blood pressure responses to oral and central salt administration in two substrains of Dahl rats.

Studies were made on whether oral or intraventricular (icv) NaCl had different effects on the blood pressure (BP) of Dahl rats. Five groups of each strain of Dahl rats, salt-sensitive (S) and salt-resistant (R) rats, were given, respectively, a diet containing 0.3% and icv infusion of 0.15 mol/L NaCl (group 1, control group) or 0.8 mol/L NaCl (group 2), a diet containing 8% NaCl and icv infusion of 0.15 mol/L (group 3) or 0.8 mol/L NaCl (group 4) for 12 days, or an 8% NaCl diet and icv infusion of 5% glucose (group 5). The icv infusions were made into the third cerebral ventricle with an osmotic minipump. In the control group of S rats (group 1) the BP was 120 +/- 4 mm Hg, whereas the BP in groups 3, 4 and 5 were 154 +/- 4, 161 +/- 5 and 153 +/- 3 mm Hg, respectively, and that in group 2 was 142 +/- 3 mm Hg on day 12. In the R rat, group 2 and group 4 showed a significant increase in BP over that of the control group. Multivariate analysis (quantification I) of these data confirmed that the BP of S rats was more sensitive to oral salt loading and that of the R rat was more strongly influenced by central salt administration. These results indicate that the two substrains of Dahl rats show different BP responses to oral and central administrations of NaCl.

Animals↗
PubMed1990

Haemodynamic effect of endothelin, a novel potent vasoconstrictor in dogs.

1. The effects of endothelin (40 and 400 pmol/kg, intravenous (i.v.), a novel vasoconstrictor, on haemodynamics were evaluated in normal dogs and dogs treated with hexamethonium. 2. The lower dose of endothelin caused no significant changes in mean blood pressure (MBP), heart rate (HR), cardiac output (CO), or total peripheral resistance (TPR) in normal dogs. In dogs treated with hexamethonium MBP decreased transiently associated with decrease in TPR. 3. In both dogs, the higher dose of endothelin caused MBP increase with CO increase in an early phase, and with TPR increase in a later phase. In normal dogs, the CO decreased 60 min after endothelin, but in dogs treated with hexamethonium the decrease in CO was not significant. 4. Electrocardiograms showed ST changes and arrhythmias. 5. Thus, endothelin has dual effects on both the vasculature and the heart, its effect depending on its dose and the time after its administration: initial vasodilation followed by prolonged vasoconstriction, and cardiostimulation followed by cardiosuppression. The cardiosuppression appears to be mediated in part by a neural mechanism.

Animals↗
PubMed1990

Absence of nocturnal fall in blood pressure in elderly persons with Alzheimer-type dementia.

Circadian changes of the blood pressure and heart rate in elderly normotensive bedridden patients with severe dementia of the Alzheimer type (group D) were compared with those in elderly normotensive bedridden patients without dementia (group R), normotensive subjects with normal daily activity (group N), and hypertensive patients with normal daily activity (group H). In groups R, N, and H, the blood pressure increased in the afternoon and decreased at midnight; in group D, however, although it increased in the afternoon, it did not decrease at night. The circadian changes of the heart rate were similar in all four groups, showing maxima in the afternoon and minima at midnight. Thus, a specific alteration was found in the circadian rhythm of the blood pressure in patients with Alzheimer-type dementia.

Activities of Daily Living↗
PubMed1990

Interferon-gamma reduces actin filaments and inhibits thyroid-stimulating hormone-induced formation of microvilli and pseudopods in mouse monolayer thyrocytes.

To study the role of interferon-gamma (IFN gamma), which is released from activated lymphocytes in the development of lymphocytic thyroiditis, we investigated the effects of IFN gamma on the morphology of mouse thyrocytes, using scanning electron microscopy. Thyrocytes were cultured in monolayers for 5-7 days and incubated with TSH (10 mU/ml) for 1 h before fixation. IFN gamma (200 U/ml) was added to the culture medium for 1 h to 5 days before TSH stimulation. Coculture of thyrocytes with IFN gamma for more than 24 h inhibited TSH-induced morphological changes in the thyrocytes; IFN gamma inhibited the increase in the number of and elongation of microvilli and the appearance of pseudopods. IFN gamma also reduced the number of actin filaments in thyrocytes, as confirmed by immunofluorescence photometry. These results suggest that IFN gamma inhibits the morphological response of thyrocytes to TSH stimulation by the reduction of actin filaments.

Actins↗
PubMed1990

[Circadian changes of blood pressure in the elderly with Alzheimer's type dementia].

We evaluated the circadian changes of blood pressure in the elderly with Alzheimer's type dementia with ambulatory blood pressure monitoring (ABPM-630, Nihon Colin, Aichi, Japan). Blood pressure and heart rate were high in the daytime and low in the nighttime in the elderly without dementia. Blood pressure did not decrease in the nighttime in the elderly with dementia, although heart rate decreased. Thus, the circadian rhythm of blood pressure was selectively impaired in the elderly with Alzheimer's type dementia.

Aged↗
PubMed1990

Increased plasma level of endothelin with vasoconstriction after dextran infusion.

Our previous study demonstrated that volume expansion with dextran produced blood pressure elevation due to vasoconstriction 3 hours after the cessation of infusion. To examine whether endogenous endothelin contributes to this vasoconstriction, we measured plasma level of endothelin before, immediately after, and 3 hours after the administration of dextran. Plasma level of endothelin decreased immediately after the administration (from 1.5 +/- 0.3 pg/ml to 1.1 +/- 0.2 pg/ml, P less than 0.05), and increased 3 hours after the administration (2.1 +/- 0.3 pg/ml, P less than 0.05). However, the changes in the plasma level of endothelin did not significantly correlated with those in blood pressure or total peripheral resistance. Thus, vasoconstriction after dextran infusion was accompanied by an increase in the plasma level of endothelin, but further evaluation is needed for the direct role of this peptide in the vasoconstrictive blood pressure elevation.

Animals↗
PubMed1990

Effect of aspirin on the pressor activity of endothelin.

To examine the inhibition of prostaglandins to the pressor activity of endothelin, hemodynamic changes of dogs pretreated with aspirin in response to endothelin were compared with those of control. In control dogs, endothelin rose blood pressure due to vasoconstriction, with a transient vasodilation in some dogs in the initial phase. In dogs treated with aspirin, the initial vasodilation and the subsequent vasoconstriction were also noted, but the zenith of the total peripheral resistance was observed earlier, compared with control dogs. Thus, prostaglandins do not appear to have a role in the initial vasodilatory action of endothelin, but may modify the long lasting vasoconstriction in the late phase.

Animals↗
PubMed1990

Effect of the calcium antagonist nicardipine on the pressor action of endothelin.

To evaluate hemodynamic actions of endothelin, anesthetized normal dogs and dogs with two doses of nicardipine received endothelin (400 pmol/kg, i.v.). Normal dogs showed an increase in blood pressure (BP) associated with an early (5 min) increase in cardiac output (CO) and a later (60 min) increase in total peripheral resistance (TPR). The lower dose of nicardipine (0.01 mg/kg/h) abolished the latter vasoconstrictive BP elevation. Dogs with the higher dose of nicardipine (0.1 mg/kg/h) did not show any changes in BP, CO or TPR. Thus, endothelin has both cardiostimulatory and vasoconstrictive actions, depending on the degree of calcium influx.

Animals↗
PubMed1989

Increase in the blood pressure and decrease in the norepinephrine release in the ventrolateral medulla during intraventricular administration of hypertonic NaCl.

Norepinephrine (NE) release in the ventrolateral medulla (VLM) was serially measured in anesthetized male Wistar rats during the rise in the blood pressure (BP) produced by acute intraventricular (ICV) administration of hypertonic (1.5 M) NaCl. Catecholamine release was determined by a brain microdialysis method using high performance liquid chromatography and electrochemical detector. The release of NE in the VLM was significantly decreased after ICV 1.5 M NaCl. In another set of rats, the pressor response to acute ICV 1.5 M NaCl was attenuated by selective administration of NE to the VLM using the microdialysis method. Chronic and continuous ICV infusion of 1.5 M NaCl to conscious rats caused an increase in BP on day 10 which was associated with a decrease in NE release in the VLM; concomitant ICV infusion of NE or of a synthetic NE precursor, L-threo-3,4-dihydroxyphenylserine (L-DOPS) prevented the rise in BP as well as the reduction in NE release. These results suggest that a decrease in the NE release of the VLM may contribute to the change in BP induced by ICV infusion of hypertonic saline.

Animals↗
PubMed1989

Effect of volume expansion on hemodynamic variables in nephrectomized dogs.

We have previously demonstrated that blood pressure elevation by acute blood volume expansion is volume-dependent during the infusion period and resistance-dependent in the post-infusion period in normal anesthetized dogs, and that such an increase in blood pressure is associated with a potentiation of the pressor response to norepinephrine. To evaluate the possible renal contribution to these hemodynamic changes, blood volume expansion was performed for 1 h with dextran dissolved in lactated Ringer's solution (20 ml/kg) in 15 nephrectomized dogs. The mean blood pressure, cardiac output and total peripheral resistance at the end of infusion were 126%, 225% and 60%, respectively; 3 h after volume expansion they were 126%, 151%, and 92% respectively. However, in 4 dogs, there was an increase in mean blood pressure (138%) 3 h after volume expansion. This was thought to result from an increase in the total peripheral resistance (133%) associated with the recovery of cardiac output (106%). The pressor response to norepinephrine (0.5 microgram/kg) was potentiated after volume expansion. These results indicate that the handling of volume by the kidney contributed to the maintenance of an elevated level of cardiac output. However, nephrectomy did not seem to interfere with the hemodynamic switching of the causative factor for blood pressure elevation from increased cardiac output to increased total peripheral resistance. Neither was the potentiation of pressor response to norepinephrine affected.

Animals↗
PubMed1989

Effects of the baroreceptor reflex system on atrial natriuretic factor secretion during volume expansion in dogs.

1. The purpose of this study was to determine whether the baroreceptor reflex system affects the secretion of atrial natriuretic factor directly or indirectly during acute volume expansion. 2. Lactated Ringer's solution containing low mol. wt. dextran was infused at 20 ml/kg for 1 h into dogs in which baroreceptors had been denervated surgically (Vx), dogs in which the autonomic system had been blocked with hexamethonium (Hx) and control dogs. 3. The plasma noradrenaline level was significantly higher in the Vx group and lower in the Hx group than in the control group throughout the experiment. The plasma levels of arginine vasopressin in the Vx and Hx groups were significantly higher than in the control group. 4. The plasma atrial natriuretic factor levels in the three groups showed similar increases during and after volume expansion. 5. The plasma atrial natriuretic factor level was significantly correlated with the right atrial pressure during volume expansion. 6. From these results, it seems unlikely that changes in the plasma level of atrial natriuretic factor during volume expansion are regulated by the baroreceptor reflex directly or indirectly by systemic changes in the sympathetic nervous system or arginine vasopressin secretion.

Animals↗