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Biomedical subjects

M Masada

Publications and source records attributed to M Masada.

At least 37 records · Page 2Linked to original sources
PubMed1994

Improvement of the rectal bioavailability of latamoxef sodium by adjuvants following administration of a suppository.

The absorption of an antibiotic, latamoxef sodium (LMOX), following the rectal administration of a suppository containing adjuvants was investigated. A lipophilic base (Witepsol H15) was used. The rectal absorption of LMOX following the administration of a suppository without adjuvants was very low. Diclofenac sodium (DF) was used as an absorption promoter; it enhances rectal membrane permeability. The blood level of LMOX following the addition of DF(10 mg) to the base was increased only about 1.3-fold compared with that achieved with LMOX alone (difference not significant); even with a higher dose of DF, the absorption of LMOX was not sufficient. The release rate of LMOX from the base was slow. When Tween 80, a non-ionic surfactant, was added to improve the release rate of LMOX, the rate was sufficiently increased. The rectal absorption of LMOX on the addition of both Tween 80 and DF was markedly increased compared to that achieved with LMOX alone or with DF. These results indicate that the rectal absorption of LMOX after administration by a suppository was sufficiently improved by enhancing both the release rate from the base and the membrane permeability of the rectum. Lymphatic uptake and blood levels of LMOX were also investigated after the rectal administration of the LMOX preparation containing both Tween 80 and DF; the lymphatic uptake of LMOX was significantly enhanced compared with the LMOX preparation in which only DF was used as an adjuvant. The mechanism whereby adjuvants lead to the absorption of a non-absorbable drug, and the subsequent drug transportation routes through the membrane are discussed.

Adjuvants, Pharmaceutic↗
PubMed1993

Determination of human immunoglobulin A and secretory immunoglobulin A in bronchoalveolar lavage fluids by solid phase enzyme immunoassay.

Solid phase enzyme immunoassay methods for the determination of secretory immunoglobulin A (IgA) and the total amount of serum and secretory IgA in bronchoalveolar lavage fluids (BALF) were developed. The solid phase was prepared by immobilizing rabbit anti-human IgA. Horseradish peroxidase-conjugated goat anti-secretory component or horseradish peroxidase-conjugated goat anti-human IgA (Fc) were used as labeled antibodies. The minimum detectable amounts of secretory IgA and total IgA were 2 and 0.5 ng/well, respectively. These assay methods were successfully applied to the determination of secretory and total IgA levels in BALF samples obtained from 44 subjects including healthy non-smokers, smokers and patients with the following lung diseases: idiopathic pulmonary fibrosis, sarcoidosis and hypersensitivity pneumonitis. The secretory and total IgA levels in BALF collected from healthy non-smokers (n = 9) were 10.5 +/- 3.6 and 25.4 +/- 15.5 (S.D.) micrograms/ml, respectively. In healthy smokers, the secretory IgA concentration was significantly decreased and in idiopathic pulmonary fibrosis, the total IgA was increased. These results indicate that the quantitation of secretory and total IgA may be useful for the investigation of lung disease.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Effect of cyclodextrins on biological membrane. II. Mechanism of enhancement on the intestinal absorption of non-absorbable drug by cyclodextrins.

The effects of two kinds of cyclodextrins (CyDs), alpha- and beta-CyD, on biological membranes were investigated by measuring changes in the absorption of a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine, using in situ and in vitro experiments. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), only beta-CyD increased the absorption of SA significantly compared to the absorption without pretreatment. The mechanism of the enhancing effect of CyDs on the absorption of SA was discussed. Almost no morphological change in the small intestine was observed by pretreatment with N-Ac alone, N-Ac or alpha- or beta-CyD combinations. The liberation of membrane components differed among the CyDs, e.g., alpha-CyD selectively released phospholipid while beta-CyD released mainly cholesterol from the intestinal membrane. It is suggested that the interaction of membrane components with CyDs may be at least partly responsible for the enhanced absorption of SA. Moreover it was found from in vitro electrophysiological experiment, that the alteration in enhanced permeability caused by beta-CyD occurred primarily in the transcellular pathways, rather than in the paracellular pathways of the small intestine. These results suggest that the enhancement of intestinal absorption by beta-CyD, after removal of the mucin layer from the intestinal surface, is due to the interaction between the membrane components and CyD. This interaction would induce disorder in cell membrane lipid, resulting in the increased permeability of the transcellular route.

Animals↗
PubMed1990

Effect of adjuvants on charge-selective permeability and electrical resistance of rat jejunal membrane.

Effects of disodium ethylenediaminetetraacetate (EDTA) and bile salts on the ion-selective permeability and electrical resistance (Rm) of rat jejunal membrane were investigated in vitro to characterize the enhanced permeability to drugs by these adjuvants. Ion-selective permeability was estimated from diffusion potentials across the membrane and expressed as permeability ratios for ions (Pcl/PNa, PK/PNa). Pretreatment of the mucosal membrane with EDTA increased PCl/PNa and decreased Rm. At the same time, the mucosal-to-serosal flux rate of sulfanilic acid (SA), a model of polar drugs, was enhanced. The relationship between Pcl/PNa and SA flux rate after pretreatment with EDTA was demonstrated to yield a curve asymptotic to the free mobility ratio of those ions. When bile salts were used as the pretreatment agent, instead of EDTA, similar results to the case of EDTA were obtained. Assuming that EDTA interacts with the tight junctional portion of the mucosal membrane to enhance the paracellular permeability to drugs selectively, as demonstrated in many other reports, changes in PCl/PNa and Rm were assumed to correspond to structural change in the tight junction. Consequently, we suggest that these factors can be useful parameters when considering the mechanism of enhanced permeability of the intestinal membrane by several adjuvants.

Adjuvants, Pharmaceutic↗
PubMed1990

Improvement by adjuvants on the rectal bioavailability of non-absorbable drugs following administration of suppository.

The influence of suppository bases and adjuvants on the release rate of drugs and the absorption of non-absorbable drugs such as sulfanilic acid (SA) and sulfaguanidine (SG), was investigated following the rectal administration of suppositories. The suppository bases used were lipophilic bases such as Witepsol W 35, H 15, S 55, E 75 and hydrophilic base such as macrogol. SA was rapidly released from macrogol, W 35, H 15 and S 55, except E 75. On the other hand, SG was rapidly released from macrogol, whereas the release of SG from lipophilic bases was slow. Rectal absorption of SA and SG following administration of each drug alone in suppository form was slight. On the addition of diclofenac sodium (DF) as absorption promoter the blood levels of SA and SG released from all suppositories increased by about two to four fold compared with those suppositories containing only SA or SG, respectively. However, the absorption of SG still did not attain sufficient levels by the administration of DF only. The rectal absorption of SG was markedly increased by the release rate of the drug from the suppository. These results indicate that after administration of these suppositories the bioavailability of non-absorbable drugs was sufficiently improved by enhancing both the release rate from the suppositories and the rectal membrane permeability.

Adjuvants, Pharmaceutic↗
PubMed1990

Glucuronate-modified liposomes with prolonged circulation time.

For the purpose of obtaining liposomes with long circulation time in blood, we synthesized 1-O-palmityl-D-glucuronic acid (PGlcUA) and incorporated it into the liposomal membranes. The clearance of the PGlcUA-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and PGlcUA (40:40:20 as a molar ratio) from blood and their tissue distribution were compared with those of dipalmitoylphosphatidylglycerol (DPPG)-liposomes (DPPC/cholesterol/DPPG = 40:40:20). When [3H]inulin-loaded PGlcUA-liposomes and DPPG-liposomes were intravenously injected into rats, the half-life of the PGlcUA-liposomes in the blood appeared to be 1.7-fold longer than that of DPPG-liposomes. Radioactivities present in plasma and various tissues were measured 22 h after administration of these liposomes, and radioactivity remaining in the plasma was 2.5-fold greater when PGlcUA-liposomes were injected. The distribution pattern of [3H]inulin in PGlcUA-liposomes was similar to that in DPPG-liposomes. The radioactivity recovered in urine was 25% lower in rats treated with PGlcUA-liposomes than in those treated with DPPG-liposomes. Since both PGlcUA- and DPPG-liposomes exhibited similar size distribution and zeta-potential, glucuronic acid, rather than negative charge, on the liposomal surface appears to endow liposomes with a longer circulation time in the bloodstream.

Animals↗
PubMed1990

Effect of cyclodextrins on biological membrane. I. Effect of cyclodextrins on the absorption of a non-absorbable drug from rat small intestine and rectum.

The effects of three kinds of cyclodextrins (CyDs), alpha-, beta- and gamma-CyD on biological membranes were investigated by changes in absorption of a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine and rectum using an in situ perfusion technique. The absorption of SA from the intestine was slight and was not affected by the addition of CyDs. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), the absorption of SA was increased compared with SA alone in the presence of only beta-CyD. Similar treatment with sodium deoxycholate (SDC) and sodium lauryl sulfate (SLS) to gastro-intestinal membrane showed the enhanced absorption of SA by the addition of beta-CyD. The mucin layer on the surface of the gastro-intestinal membrane may play an important role in the absorption of drugs. On the other hand, enhanced absorption of SA from the rat rectum was not induced by beta-CyD with or without pretreatment with N-Ac, SDC or SLS. Simultaneously, the release of neutral sugars in the perfusate after treatment with adjuvants was also observed with N-Ac, SDC and SLS. These results indicate that the mucin layer works as a barrier to the increased absorption of SA by beta-CyD.

Animals↗
PubMed1989

Effect of the interaction of drug-beta-cyclodextrin complex with bile salts on the drug absorption from rat small intestinal lumen.

This investigation was concerned with the change of the bioavailability of a drug owing to the interaction of the drug-beta-cyclodextrin complex with bile salts in rat intestinal lumen. The absorption of sulfamethizole (SMZ) from rat intestinal lumen after administration of SMZ-beta-cyclodextrin complex was determined by a closed-loop method in the presence or absence of bile. The blood level of SMZ after administration of SMZ-beta-cyclodextrin complex was significantly decreased in comparison with that after administration of SMZ alone in bile duct-ligated rats. On the other hand, the blood level of SMZ after SMZ-beta-cyclodextrin administration in intact rats (bile duct non-ligated) or on the addition of sodium cholate was similar to the level in the case of SMZ alone. Thus, bile salts were found to act as a competing agent in the gastrointestinal tract.

Animals↗
PubMed1989

5-Fluorouracil derivatives with serum protein binding potencies.

To develop an optimal delivery system for 5-fluorouracil (5FU) using serum protein as a drug carrier, a series of its benzyl derivatives was synthesized. Then their binding to the serum protein was investigated by equilibrium dialysis. The benzyl derivatives of 5FU were strongly bound to rat plasma protein or human serum albumin. The bound percentage increased with increasing hydrophobicity. It was suggested that the benzyl derivative of 5FU existed in the blood as a complex with serum albumin and circulated for a long time as a polymeric drug does.

Animals↗
PubMed1987

Effects of diclofenac sodium and disodium ethylenediaminetetraacetate on electrical parameters of the mucosal membrane and their relation to the permeability enhancing effects in the rat jejunum.

The effects of diclofenac sodium and disodium ethylenediaminetetraacetate (EDTA) on electrical parameters of rat jejunal membrane were investigated, together with measurement of the mucosal-to-serosal flux of sulphanilic acid or L-phenylalanine. Both adjuvants increased the flux rate of sulphanilic acid to a similar extent when added to the mucosal solution at 10 mM, but there were apparent differences in their effects on the electrical parameters. The addition of EDTA induced the gradual reduction in the membrane resistance (Rm) by 6-8 ohm cm-2, while the effect of diclofenac on Rm was complicated and concentration-dependent. The short circuit current (Isc) was reduced rapidly to the level of 30-40 microA cm-2 by the addition of diclofenac, but was less affected by EDTA. The flux rate of L-phenylalanine was decreased extensively by diclofenac or the 10 mM concentration of EDTA, suggesting an inhibition of carrier-mediated transport systems in the membrane. Together with our preceding communication (Yamashita et al 1985, J. Pharm. Pharmacol. 37: 512-513), it became obvious that the sites of action of diclofenac and EDTA were different, the former directly interacting with the epithelial cell to alter the permeability and functions of the cell membrane, while the primary effect of EDTA could be at the intercellular junctions.

Animals↗
PubMed1986

A sensitive assay of GTP cyclohydrolase I activity in rat and human tissues using radioimmunoassay of neopterin.

A highly sensitive and simple assay for the activity of GTP cyclohydrolase I (EC 3.5.4.16) was established using a newly developed radioimmunoassay. D-erythro-7,8-Dihydroneopterin triphosphate formed from GTP by GTP cyclohydrolase I was oxidized by iodine and dephosphorylated by alkaline phosphatase to D-erythro-neopterin, and quantified by a radioimmunoassay for D-erythro-neopterin. This method was highly sensitive and required only 0.2 mg of rat liver tissues for the measurement of the activity. It was reproducible and can be applied for the simultaneous assay of many samples. The activity of GTP cyclohydrolase I was measured in several rat tissues. For example, the enzyme activity in rat striatum (n = 5) was 13.7 +/- 1.5 pmol/mg protein per hour (mean +/- SE), and agreed well with those obtained by high-performance liquid chromatography with fluorescence detection. The activity in the autopsy human brains (caudate nucleus) was measured by this new method for the first time. The activity in the caudate nucleus from parkinsonian patients (n = 6) was 0.82 +/- 0.56 pmol/mg protein per hour which was significantly lower than the control value, 4.22 +/- 0.43 pmol/mg protein per hour (n = 10).

Aminohydrolases↗
PubMed1986

Investigations of influx and accumulation processes of beta-lactam antibiotics and their role in the transmural transfer across rat jejunum.

The transport characteristics of beta-lactam antibiotics was investigated in rat jejunum using the Ussing-type chambers in vitro. Not only the transmural flux rate, but also the influx rate and accumulation into the mucosal epithelium were measured to clarify the sequential processes of drug transport. beta-Lactam antibiotics examined were cephalexin (CEX), cephradine (CED), ampicillin (AB-PC) and cefazolin (CEZ). The transport characteristics of these drugs were compared with that of L-phenylalanine (L-Phe). The results suggested that specialized transport systems are involved in all processes of mucosal-to-serosal transport for CEX and CED. From the kinetical analysis, it was demonstrated that these two drugs have similar capacity and affinity to carriers in the influx process or components which contribute to the cellular accumulation, while their transmural flux rates were different from each other. L-Phe was shown to have a much greater activity, affinity and capacity in the intestinal transport process than those of CEX, CED, AB-PC and CEZ.

Animals↗