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Biomedical subjects

R Igarashi

Publications and source records attributed to R Igarashi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Microparticle resins as a potential nasal drug delivery system for insulin.

The application of various resins for the nasal delivery of insulin was examined in rabbits. Intranasal administration of human insulin (28 U, 1 mg) mixed with fractionated sodium polystyrene sulfonate powder (an anionic resin with a particle size of 20-45 microns) caused a rapid increase of the plasma insulin level 413.0 +/- 71.7 microU/ml (mean +/- S.D.) after 15 min, while intranasal administration of insulin alone caused little increase. The blood glucose level decreased from 118.8 +/- 18.5 mg/dl to 65.8 +/- 13.8 mg/dl at 45 min after administration. These results were superior to those obtained with the unfractionated resin. Styrene-divinylbenzene copolymer (a nonionic resin; 20-45 microns fraction) showed similar enhancement of nasal insulin absorption. In contrast, polyacrylester (a nonionic resin; 20-45 microns fraction) and cholestyramine (a cationic resin) did not promote insulin absorption. These results suggest that some resins may be useful for nasal delivery of insulin.

Administration, Intranasal↗
PubMed1998

Enhancement of immune response to intranasal influenza HA vaccine by microparticle resin.

We evaluated the potential application of ion-exchange resins for the enhancement of intranasal immune response to influenza HA vaccine in mice. Female Balb/c mice were intranasally immunized with inactivated influenza HA vaccine with one of four kinds of resin microparticles: sodium polystyrene sulfonate, calcium polystyrene sulfonate, polystyrene benzyltrimetylammonium chloride, or polystyrene divinylbenzene. Haemagglutinin-inhibiting antibodies were measured in the serum and IgA antibodies in the nasal wash after 4 weeks. The results demonstrated that intranasal administration of influenza HA vaccine in combination with the 20-45 microns sized particles of sodium polystyrene sulfonate resin induced the highest levels of mucosal IgA, and enhanced systemic haemagglutinin-inhibiting antibodies. While the Th2-type cytokine IL-4 was detected in the sera after intranasal immunization with HA vaccine and sodium polystyrene sulfonate, neither IFN-gamma nor IL-2 could be detected. Furthermore, mice intranasally immunized with HA vaccine together with sodium polystyrene sulfonate resin showed higher protection against viral challenge than those that received HA vaccine alone. Intranasal administration of influenza HA vaccine with sodium polystyrene sulfonate resin might be both a safe and an effective means of immunization.

Administration, Intranasal↗
PubMed1997

Lecithinized superoxide dismutase: an inhibitor of human immunodeficiency virus replication.

Superoxide dismutase (SOD) is an enzyme used in the treatment of oxygen radical-related diseases. Lecithinization of SOD enhances its pharmacological activity. Lecithinized SOD (PC-SOD) inhibits human immunodeficiency virus (HIV) types 1 and 2 in MT-4 cells. HIV-1-infected MT-4 cells were cultured for 5 days in the presence of PC-SOD, at various concentrations. In an MTT assay, reverse transcriptase (RT) activity of the cell extract and p24 antigen production were measured. Untreated, HIV-1-infected MT-4 cells served as control. PC-SOD inhibited viral replication most effectively at 2500 U/ml, a concentration that did not affect cell viability, with an EC50 value of 718 U/ml. PC-SOD treatment inhibited RT activity and p24 production in a dose-dependent manner. Western blot analysis of the HIV-1-infected MT-4 cells treated with PC-SOD at 2500 U/ml did not detect any expression of viral proteins. Failure to inhibit virus adsorption, proviral DNA and mRNA synthesis, and RT and proteinase enzyme activity suggests that the mechanism of action of PC-SOD is entirely different from those of the currently available anti-HIV drugs. PC-SOD shows synergistic interaction with AZT, ddI, ddC, KNI-272, and dextran sulfate. PC-SOD also inhibited the oxidative stress-induced depletion of sulfhydryls, which are the cause of diminished antioxidant defenses in HIV-infected patients.

Anti-HIV Agents↗
PubMed1997

Lecithinization of IL-6 enhances its thrombopoietic activity in mice.

This study was conducted to assess the merit of lecithinization of recombinant human interleukin-6 (IL-6) as a drug delivery system. IL-6 was lecithinized by covalently binding it with a phosphatidylcholine (lecithin, PC) derivative. The in-vivo thrombopoietic potency of lecithinized IL-6 (PC-IL-6) was greater than that of native IL-6 when administered subcutaneously, although the in-vitro bioactivity of PC-IL-6 was markedly reduced by lecithinization. When PC-IL-6 and native IL-6 were given in doses that produced the same level of thrombopoietic activity, the former stimulated less production of IgG1, a marker of the adverse effects of IL-6, than did the latter. Furthermore, PC-IL-6 persisted in the blood longer than native IL-6. Based on the above, PC-IL-6 appears to be useful as a drug delivery system and may also be useful in the treatment of drug-induced thrombocytopenia.

Animals↗
PubMed1996

Characterization of T cell receptor beta chains of accumulating T cells in skin allografts in mice.

The study of T cells involved in the immune reaction that occurs in engrafted organs should provide information that would be helpful in the regulation of allograft rejection in organ transplantation. Toward this end, we focused on detection and characterization of accumulating T cells in mouse skin allografts from B10.A(4R) to C57BL/6 mice in vivo. T cell receptor beta genes were amplified by reverse transcriptase-PCR from mRNA of the skin grafts, and accumulating T cell receptor beta gene clonotypes were identified by their single strand conformation polymorphism. Their joining region usage and the amino acid sequences of the complementarity-determining region-3 were then determined. The results were as follows: (1) Distinct oligoclonal accumulation of T cells was more prevalent in the skin allografts than in the syngenic skin grafts. (2) Although the accumulating T cell clonotypes appeared to use many different variable-region gene families, preferential combinations of variable region-joining region were found. (3) Several homologous amino acid sequences were found in these accumulating TCR beta genes in allografts, suggesting that these T cells are driven by the same or similar antigens. (4) In addition, little T cell accumulation was found in spleens from the mice with allografts or syngenic skin grafts. Taken together, accumulating T cells in the skin allografts were detected in vivo, and some appeared to have characteristics in common. This may lead to T cell clonotype-specific therapy in organ transplantation.

Amino Acid Sequence↗
PubMed1994

[Development of new drugs for intractable vasculitis--lipo-PGE1 and monoclonal antibody].

"Lipo-PGE1", PGE1 incorporated into lipid microspheres (LM), has marked antiplatelet and vasodilatory actions. Since LM largely accumulate in inflamed vascular lesions, lipo-PGE1 shows a marked efficacy for treating vascular diseases such as atherosclerosis and vasculitis. Another recently developed drugs against intractable vasculitis are monoclonal antibodies to surface antigens of lymphocytes. Treatment with humanized anti-CDw52, and subsequent anti-CD4 monoclonal antibodies was reported to have brought remission up to 42 months.

Alprostadil↗
PubMed1994

Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity.

We performed the present study to clarify whether lecithinized superoxide dismutase (PC-SOD) enhanced its pharmacologic potency by increasing its cell membrane affinity. PC-SOD, in which 4 molecules of a phosphatidylcholine (PC) derivative were covalently bound to each dimer of recombinant human CuZn-SOD (rhCuZn-SOD), was shown to have a high membrane affinity using a laser confocal imaging technique. PC-SOD efficiently scavenged superoxide anion (O2-) produced by phorbol myristate acetate (PMA)-stimulated human neutrophils (IC50 0.60 U/ml), and it exerted a dose-dependent scavenging effect (IC50 1.27 U/ml) even when the neutrophils were washed after incubation with PC-SOD. In contrast, neither unmodified SOD nor polyethylene glycol-bound SOD (PEG-SOD) showed a scavenging effect for washed neutrophils, even at a high concentration (100 U/ml). PC-SOD also showed a strong protective effect against human vascular endothelial cell damage caused by O2- generated by stimulated neutrophils, and PC-SOD was approximately 100-fold more potent than unmodified SOD (in vitro IC50 100 U/ml for PC-SOD and > 10,000 U/ml for unmodified SOD). Moreover, PC-SOD (50,000 U/kg) had an inhibitory effect on ischemia-reperfusion paw edema in mice, whereas neither unmodified SOD nor PEG-SOD had any effect. These results suggest that PC-SOD (designed to target for cell membranes) exerted a far higher pharmacologic activity by increasing cell membrane affinity than unmodified SOD and may be potentially useful for various clinical applications.

Animals↗
PubMed1993

Enhanced antitumor activity and reduced toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea administered in lipid microspheres to tumor-bearing mice.

Stable lipid microspheres (LM) and lipid nanospheres (LN) with average diameters of 200 nm and 50 nm, respectively, were used to encapsulate an lipophilic antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). LM and LN containing BCNU (lipo BCNU and s-lipo BCNU, respectively) were prepared by homogenizing a soybean oil solution of BCNU with egg yolk lecithin, and their antitumor activity via the intravenous route was tested against L1210 leukemia in mice and compared with that of BCNU dissolved in saline. Both lipo-BCNU and s-lipo BCNU showed significantly enhanced antitumor activity with reduced toxicity, when compared with the corresponding doses of BCNU alone. These results suggest that LM and LN may be suitable carriers for lipophilic antitumor agents and may enhance their efficacy.

Animals↗
PubMed1993

Application of lipid microspheres to prepare a thromboxane A2 receptor antagonist aerosol for inhalation.

The methyl ester of a new thromboxane A2 receptor antagonist, (+)S-145, i.e. (1R,2S,3S,4S)-(5Z)-7-(3-phenyl-sulfonyl-aminobicyclo[2,2,1]he pt-2-yl)heptenoic acid, was incorporated into lipid microspheres (lipo S-145-Me) and its pharmacological effect and tissue distribution were examined in guinea pigs following aerosol delivery. Bronchoconstrictive responses induced by intravenous injection of U46619 or the inhalation of ovalbumin were suppressed in a dose-dependent manner by aerosol inhalation of lipo S-145-Me, which was 3-10 times more potent that the unencapsulated calcium dihydrate of the original drug (S-1452). There was no significant difference in the airway tissue distribution of labelled lipo S-145-Me versus S-1452 after 2 or 5 min of inhalation, but the encapsulated drug showed marked accumulation in the lungs after 30 min of inhalation. The in vitro uptake of lipo [14C] S-145-Me by fresh human neutrophils and an eosinophil cell line was respectively 7 times and 3.5 times higher than that of [14C] S-1452. These results suggest that lipo S-145-Me has the potential to be used as an inhalational antiasthma agent, and that its effect may be partly attributable to a for inflammatory cells which are responsible for allergic airway inflammation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Lecithinization of superoxide dismutase potentiates its protective effect against Forssman antiserum-induced elevation in guinea pig airway resistance.

We synthesized lecithinized superoxide dismutase (PC-SOD), in which a lecithin derivative was covalently bound to recombinant human SOD. We selected PC4-SOD (4 molecules of the lecithin derivative bound to each SOD dimer) and PC10-SOD (10 molecules of the derivative to each SOD dimer) for our study. Both of these PC-SOD retained SOD activity in vitro and showed delayed plasma disappearance in vivo in rats. PC-SOD also had 4 to 20 times higher affinity in vitro for several kinds of cells than that of unmodified SOD. Because Forssman antiserum is known to induce bronchial obstruction in guinea pigs via actions of O2-, we studied the effect of PC-SOD on Forssman antiserum-induced respiratory resistance. Unmodified SOD was ineffective at the doses of 1,000 to 30,000 U/kg, whereas PC-SOD showed a dose-dependent inhibitory effect over the range of 10 to 1,000 U/kg. The ED50 of PC4-SOD and PC10-SOD were 140 and 240 U/kg, respectively, at 30 min after the challenge with Forssman antiserum. These findings suggest that the pharmacological potency of PC-SOD is over 200 times more than that of unmodified SOD, and that PC-SOD may have the potential for various clinical applications.

Airway Resistance↗
PubMed1989

Two cases of hamartoangiomyomatosis with characteristic scintigraphic findings.

Hamartoangiomyomatosis is a rather rare pulmonary disease which occurs in young to middle-aged women. The chief complaint of this disease is dyspnea. The chest X-ray findings of this disease are such complicated features as reticular, reticulogranular, miliary and honeycomb-like shadow. A pulmonary perfusion scintigram was prepared with a scinticamera after intravenous injection of 10 mCi of Tc-99m MAA. The anterior image showed a remarkably reduced bilateral pulmonary blood flow, especially in the middle and lower areas of the lungs. In the upper portions, the blood flow remained relatively sufficient. The posterior and lateral images also gave similar findings. In two cases of hamartoangiomyomatosis, pulmonary perfusion scintigraphy was successful in identifying the characteristic findings of the disease.

Adult↗