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Biomedical subjects

M Terasawa

Publications and source records attributed to M Terasawa.

108 records · Page 6Linked to original sources

[Effect of Y-12, 141 on immune response of dd mice. Studies on anti-allergic agents, V. (author's transl)].

Mice were immunized with sheep red blood cells (SRBC) at day 0, and hemagglutinin (HA) titer of the serum, hemolytic plaque forming cells (HPFC) in the spleen cells and rosette forming cells (RFC) in both the spleen and thymus cells were assayed at day 5. The immune responses in the mice immunized with 1 X 10(8) SRBC intravenously were not affected by Y-12, 141 given orally for 5 days (0 approximately 4 days) at doses of 30 approximately 100 mg/kg, but were suppressed by cyclophosphamide (10 approximately 30 mg/kg p.o.) and D-penicillamine (100 mg/kg p.o.). The treatment of the mice with levamisole (1 approximately 30 mg/kg p.o.) resulted in the increase of RFC number in the spleen. Levamisole increased the number of RFC in the mice immunized with 5 X 10(6) approximately 10(8) SRBC. On the other hand, Y-12,141 (10 approximately 30 mg/kg p.o.) increased spleen RFC number in the mice immunized with 5 approximately 10 X 10(6) SRBC. Y-12,141 and levamisole given orally on day 0, 1 or 2 increased spleen RFC number in the mice immunized with 5 X 10(6) SRBC. D-Penicillamine given orally for 3 days (-2 approximately 0 days) also potentiated spleen rosette formation. The decreased number of RFC in the spleen and thymus by cyclophosphamide given orally in a dose of 20 mg/kg was restored by the treatment with Y-12,141 (3 approximately 30 mg/kg) and levamisole (1 approximately 30 mg/kg). In addition, these agents suppressed 19S HA titer, and elevated 7S HA titer in the cyclophosphamide-treated mice. Prednisolone given orally in a dose of 30 mg/kg also decreased the number of RFC in the spleen. This decrease was restored by the treatment with Y-12,141 and levamisole. These findings suggest that Y-12,141 has a capacity to potentiate the immune response in mice immunized with low doses of SRBC and to restore the decrease of immune response caused by immunosuppressive drugs such as cyclophosphamide and prendisolone.

Adjuvants, Immunologic↗

Anti-inflammatory activity of an imidazopyridine derivative (miroprofen).

Anti-inflammatory activity of 2-[p-(2-imidazo[1,2-a]pyridyl) phenyl]propionic acid (Y-9213, miroprofen) was studied on various experimental models. Miroprofen was found to be as active as indomethacin against the exudative inflammation such as pleuritis in rats induced by Evans blue-carrageenin and the peritonitis in mice induced by acetic acid, and against the local Shwartzman reaction in rabbits. Miroprofen also inhibited the formation of edema induced by carrageenin or kaolin in rats' paws at lower doses. Against the proliferation of connective tissues, miroprofen showed the inhibitory action at higher doses. The ulcerogenic activity of miroprofen in rats was less potent than that of indomethacin, and as active as that of phenylbutazone. These findings indicate that miroprofen may be more effective in suppressing pain responses and acute inflammation accompanied with increased vascular permeability.

Animals↗

Immunochemical studies of the turnover of delta-aminolevulinate synthase in rat liver mitochondria and the effect of hemin on it.

The half-life of delta-aminolevulinate (ALA) synthase in the liver mitochondria of allylisopropylacetamide-treated rats was estimated to be about 35 min, taking advantage of the observation that hemin strongly inhibits the translocation of ALA synthase from the liver cytosol into the mitochondria. ALA synthase accumulating in the liver cytosol in allylisopropylacetamide-treated rats is rapidly translocated into mitochondria with a half-disappearance time of about 20 min, but does not appear to undergo degradation until it is translocated into mitochondria. A study with an ALA synthase-specific IgG revealed that the decrease in the ALA synthase activity in the liver mitochondria observed after the administration of cycloheximide or hemin effectively paralleled the decrease in the amount of immunologically reactive protein, providing further evidence that ALA synthase is rapidly degraded in the mitochondria.

5-Aminolevulinate Synthetase↗

Effects of hemin on the synthesis and intracellular translocation of delta-aminolevulinate synthase in the liver of rats treated with 3,5-dicarbethoxy-1,4-dihydrocollidine.

The administration of hemin to rats which had been treated with 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) brought about a rapid decrease of the delta-aminolevulinate (ALA) synthase activity in the mitochondria and an appreciable increase of the enzyme activity in the cytosol in the liver. In DDC-treated rats, however, the degree of accumulation of ALA synthase in the liver cytosol resulting from the hemin administration was relatively small and the total ALA synthase activity in the liver was considerably decreased after the hemin administration; these results are in contrast with those for allylisopropylacetamide-treated rats. Further studies by combined use of [3H]leucine and an anti-ALA synthase IgG revealed that incorporation of [3H]leucine into the mitochondrial ALA synthase was greatly reduced in hemin-injected rats and that incorporation of [3H]leucine into total ALA synthase in the liver (the sum of radioactivity incorporated into the mitochondrial enzyme and the cytosolic enzyme) was also decreased to a considerable extent in these rats; this decrease in incorporation of [3H]leucine appeared to occur immediately after the administration of hemin. It was concluded that hemin actually inhibits the translocation of ALA synthase from the cytosol into the mitochondria and that hemin also inhibits de novo synthesis of ALA synthase, possibly at a post-transcriptional level in DDC-treated rats.

5-Aminolevulinate Synthetase↗

Effects of oral befunolol on heart rate and systolic blood pressure during submaximal exercise in man.

For the purpose of determining exercise intensity required for evaluating the effect of beta-blocking agents, the multi-stage treadmill exercise was carried out up to intensity of 85% of maximal oxygen intake (VO2max) after administration of beta-blocking agents in 7 healthy men. To obtain a stable dose response in the inhibitory effect of beta-blocking agents on heart rate (HR) and systolic blood pressure (S-BP), the exercise intensity more than 65% of VO2max (75% of maximal heart rate) was needed. In order to evaluate the effect of befunolol (BFE), a submaximal treadmill exercise of 75% of the age adjusted predicted maximal heart rate was loaded in 6 healthy men at 1.5, 4, and 8 hours following a single oral administration of 10 mg, 20 mg or 40 mg of BFE and 20 mg or 40 mg of propranolol. Simultaneously, the plasma concentration of BFE was determined 1.5, 4, 6 and 8 hours after the administration of BFE at each dose. In human serum, BFE was detected together with its metabolite, revealing a significant correlation between BFE and metabolite (r = 0.94, p < 0.001). Almost a certain rate of metabolite (4--5 times) was detected against BFE. As for the biological half life, it was 1.79 +/- 0.13 hours with BFE and 3.67 +/- 1.33 hours with metabolite. The inhibitory effect of BFE on HR and S-BP during exercise exhibited a dose response with the oral dose and its plasma concentration, and was almost twice as much as that of propranolol at the same dose. Accordingly, the myocardial oxygen consumption which may be represented as rate pressure product was inhibited twice as much as propranolol. BFE is characteristic of its more rapid elimination of its effect compared to the other beta-blocking agents. The decrease in the inhibitory effect of BFE or HR during exercise was about 1.8 times quicker than that of propranolol.

Administration, Oral↗

Anti-anaphylactic activities of a new benzopyranopyridine derivative Y-12,141 in rats and guinea pigs.

The active anaphylactic bronchoconstriction of rats mediated by IgE-like antibody against DNP-Ascaris was inhibited by intravenous and intratracheal treatment with Y-12,141 in a dose-dependent manner. In both routes, the inhibitory effect of Y-12,141 on this response was more potent than that of disodium cromoglycate (DSCG). The oral administration of Y-12,141 also produced a similar inhibition of the response. The passive anaphylactic bronchoconstriction of guinea pigs mediated by IgG-like antibody against egg albumin was also prevented dose-dependently by treatment with Y-12,141 given intravenously, but not with DSCG. The present results suggest that Y-12,141 may be effective for the treatment of allergic bronchial asthma.

Anaphylaxis↗

Anti-allergic activities of a new benzopyranopyridine derivative Y-12,141 in rats.

Passive cutaneous anaphylaxis (PCA) mediated in rats by IgE-like antibodies against egg albumin or the benzylpenicilloyl determinant was inhibited in a dose-dependent manner by intravenous treatment with Y-12,141; the ED50 was 0.09--0.2 mg/kg. The inhibitory effect of Y-12,141 ON PCA was about 5 times as potent as that of disodium cromoglycate (DSCG). Oral treatment with Y-12,141 resulted in the inhibition of PCA, showing an ED50 of 2.5 mg/kg. This action of Y-12,141 on PCA was considered to be due to the inhibition of the release of allergic mediatros from mast cells in a manner similar to DSCG. The results suggest that Y-12,141 may have an anti-allergic activity.

Animals↗

[Anti-allergic activity of 7-acetyl-5-oxo-5H-[1] benzopyrano (2,3-b] pyridine (Y-9000) (author's transl)].

The IgE mediated reactions such as 48 hr homologous passive cutaneous anaphylaxis (PCA) and active anaphylactic bronchoconstriction in rats were inhibited in a dose dependent manner by treatment with 7-acetyl-5-oxo-5H-[1]benzopyranol[2,3-b] pyridine (Y-9000) and disodium cromoglycate (DSCG) given intraperitoneally. The inhibitory activity of Y-9000 was to the same extent as that seen with DSCG. The IgE mediated reactions were also inhibited by oral treatment with Y-9000 but not with DSCG. In addition, the treatment with Y-9000 resulted in inhibition of IgG mediated reaction such as anaphylactic asthma in the passively sensitized guinea pigs and 4 hr heterologous PCA in rats. However, DSCG failed to prevent these reactions. Y-9000 also inhibited the active systemic anaphylaxis of the mouse and non-immunological reactions in rats such as histamine release after an intraperitoneal injection of dextran, anaphylactoid reaction and paw edema induced by the dextran, egg white or carrageenin. This agent had a stimulating effect on the adrenals, and showed glucocorticoid like activity, but bronchodilator and antagonistic activities on chemical mediators were nil. These results suggest that the anti-allergic activities of Y-9000 are elicited by inhibiting the release of allergic mediators in a manner similar to DSCG, and are partially mediated by stressor activity.

Anaphylaxis↗

[Pharmacological studies of 2-(5H-(1)benzopyrano(2,3-b)pyridin-7-yl)propionic acid (Y-8004). (I) Anti-inflammatory, analgesic and antipyretic actions].

A newly synthesized anti-inflammatory agent, Y-8004 demonstrated a greater inhibition than did indomethacin (IM). on inflammatory response such as ultraviolet erythema in guinea pigs, carrageenin edema, evans blue and carrageenin-induced pleuritis and acetic acid-induced peritonitis in rats. On the other hand, the inhibition of Y-8004 was to the same extent as IM regarding granuloma formation around cotton pellet and the development of adjuvant arthritis in rats, however, Y-8004 was only half as effective as IM regarding exudation in granuloma pouch. In addition, the agent was effective in alleviating established adjuvant arthritis, the anti-inflammatory activity was not mediated by stimulation of the adrenals, and glucocorticoid-like activity could not be demonstrated. Furthermore, analgesic and antipyretic activities were to the degree as seen with IM, and the analgesic property of Y-8004 was considered to be peripheral as is the case with IM. The ulcerogenic activity of Y-8004 was observed to be mainly in the jejunum and ileum of the rat, but compared to IM, there were considerable differences between the ulcerogenic and the effective doses. As Y-8004 has a wider therapeutic margin than IM, this non-steroidal anti-inflammatory agent should be quite applicable for clinical purposes.

Adrenal Cortex↗

Effect of a potent PAF antagonist, Y-24180, on an allergen-induced late asthmatic response in guinea-pigs.

The effect of Y-24180, a potent and specific PAF antagonist, on the antigen-induced late asthmatic response in guinea-pigs was investigated. We used an asthmatic guinea-pig model which had a high incidence of dual-phase reaction and high reproducibility. Y-24180 (1 mg/kg, p.o.) had a significant inhibitory effect on the late asthmatic response and eosinophil infiltration in bronchoalveolar lavage fluid. These results suggest that PAF may play, at least partially, an important role in the development of the late asthmatic response. Thus, Y-24180 may be useful for the treatment of asthma.

Allergens↗

Nondestructive evaluation by x-ray computed tomography of dialysate flow patterns in capillary dialyzers.

It is hard to evaluate dialysate flow patterns inside the fiber bundle of capillary dialyzers. The current study describes a novel determination of dialysate flow by x-ray computed tomography. The authors did steady and nonsteady state tracer experiments with adipiodone to observe the dialysate flow pattern in capillary dialyzers held vertically and horizontally. The hollow fibers were filled with paraffin to avoid permeation of adipiodone from the dialysate to blood compartment. In steady state tracer experiments, adipiodone solution (50 vol%) was injected into the dialysate compartment at a flow rate of 1.5 ml/min. Horizontal sectional dialysate flow patterns were observed every 2 cm from the point of the adipiodone injection. Adipiodone solution flowed along broken and twisted fiber bundles at dialysate flow rates ranging from 200 to 600 ml/min. In nonsteady state tracer experiments, dialysate was switched from pure water to adipiodone solution by solenoid-controlled valves after a steady state was reached, and adipiodone solution (2.4 vol%) was infused into the dialysate compartment for 30 sec at a flow rate of 500 ml/min. Vertical sectional dialysate flow patterns were observed every 2 sec after the start of adipiodone infusion. Values for dialysate flow velocity at the outer and inner regions of the fiber bundle were 3.5 and 0.6 cm/sec for the CA-170, and 1.4 and 0.7 cm/sec for the HF-200 capillary dialyzer, respectively. This study demonstrates the usefulness of x-ray computed tomography in visually and quantitatively determining dialysate flow patterns in capillary dialyzers.

Iodipamide↗