Biomedical subjects

M Iwaki

Publications and source records attributed to M Iwaki.

At least 127 records · Page 7Linked to original sources

PubMed1992

Percutaneous absorption of pindolol and pharmacokinetic analysis of the plasma concentration.

The percutaneous (p.c.) absorption of pindolol, a beta-blocker, through rabbit skin was examined by in vitro and in vivo studies. Additionally, for practical use of the transdermal system (TTS), a trial for sustaining a suitable plasma concentration of pindolol by using a rate-controlling membrane and for describing plasma drug levels after p.c. application by using a simple pharmacokinetic model was tested. As a result, the drug penetrated through rabbit skin in vitro at a zero-order rate. In vivo, the drug was also absorbed through the skin from a gel base with or without enhancers. The gel preparation with Azone (Rp. 2) gave high plasma levels of pindolol. The transdermal system produced with Rp. 2 and a rate-controlling membrane (Hipore 4050) provided relatively constant plasma levels for 48 h. The model presented could describe the time course of plasma pindolol concentrations following p.c. application of the systems.

Administration, Cutaneous↗

PubMed1992

Growth factor-dependent phosphorylation of membrane proteins in cultured human retinal pigment epithelial cells.

Recently, growth factors are known to phosphorylate tyrosine residues of proteins to regulate cellular functions. We investigated growth factor-dependent phosphorylation of membrane proteins in cultured human retinal pigment epithelial (RPE) cells. The phosphorylation experiments were done in membrane preparations of cultured RPE cell and the reaction was started by applying [32P]adenosine 5'-triphosphate (ATP) at 0 degrees C, and terminated after 0, 1, 5, 15, and 30 min. The samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and were analyzed by autoradiography. Many proteins showed time-dependent phosphorylation. Among them, a 170 kDa protein showed platelet-derived growth factor (PDGF)-specific phosphorylation with both time- (up to 30 min) and dose-(maximal effect at 50 ng/ml) dependence. On the other hand, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) showed no specific phosphorylation. Phosphoaminoacids of the 170 kDa protein were analyzed by thin layer chromatography and autoradiography. Phosphotyrosine showed much higher radioactivity than phosphoserine or phosphothreonine. Consequently, PDGF induced phosphorylation of the 170 kDa protein which mainly consisted of phosphotyrosine. The data suggest that tyrosine phosphorylation of membrane protein is involved in signal transduction of PDGF in human RPE cells.

Adenosine Triphosphate↗

PubMed1992

Is a trypsin-like protease of mites a Der f III allergen?

A trypsin-like protease was purified from mite (Dermatophagoides farinae) fecal extract. In SDS-PAGE, the mite trypsin-like protease showed a single band at 34 kD. The purified trypsin-like protease possessed potent allergenic activity. Both the twenty N-terminal amino acid sequence and the amino acid composition of the purified protease were very similar to those of Der f III. These data strongly suggest that the trypsin-like protease in the mite is a Der f III allergen.

Allergens↗

PubMed1991

Full replacement of the function of the secondary electron acceptor phylloquinone(= vitamin K1) by non-quinone carbonyl compounds in green plant photosystem I photosynthetic reaction centers.

One-carbonyl quinonoid compounds, fluorenone (fluoren-9-one), anthrone, and their derivatives are introduced into spinach photosystem (PS) I reaction centers in place of the intrinsic secondary electron acceptor phylloquinone (= vitamin K1). Anthrone and 2-nitrofluorenone fully mediated the electron-transfer reaction between the reduced primary electron acceptor chlorophyll A0- and the tertiary electron acceptor iron-sulfur centers. It is concluded that the PS I phylloquinone-binding site has a structure that enables various compounds with different molecular structures to function as the secondary acceptor and that the reactions of incorporated compounds are mainly determined by their redox properties rather than by their molecular structure. Carbonyl groups increase the binding affinity of the quinone/quinonoid compounds but do not seem to be essential to their function. The quinonoid compounds as well as quinones incorporated into the PS I phylloquinone-binding sites are estimated to function at redox potentials more negative than in organic solvents.

Anthracenes↗

PubMed1991

Structure of the phylloquinone-binding (Q phi) site in green plant photosystem I reaction centers: the affinity of quinones and quinonoid compounds for the Q phi site.

The dissociation constants (Kd) between the phylloquinone-binding site (designated as the Q phi site) and 23 quinones and 2 quinonoid compounds were measured in spinach photosystem I reaction centers. Kd values were calculated from the dependency of the recovery of the flash-induced stable oxidation of the primary donor chlorophyll P700 in the phylloquinone-extracted reaction center on the concentration of added compounds. The binding free energy, calculated from the Kd value of quinones with nonpolar substituted groups, linearly depended on their partition coefficients between water and cyclohexane, but only if their molecular sizes are smaller than anthraquinone. The quinones with larger molecular sizes showed a lower affinity than expected from their hydrophobicities. This suggests that the quinone-binding domain is hydrophobic and that its size is similar to that of anthraquinone. The interaction other than the hydrophobic one was also estimated to stabilize the binding by -5.7 kcal/mol for alkylated quinones. Deletion of one of the carbonyls of p-quinones significantly decreased the binding affinity. This suggests a hydrogen bond or a pi-pi electronic interaction between quinone and the Q phi site. Effects of halogens and amino substitutions on the binding affinity were also studied. The structure of the quinone-binding site in the photosystem I reaction center is deduced from these results.

Anthracenes↗

PubMed1991

Scanning electron microscopy of eggs of Mansonia uniformis, Ma. indiana, Ma. annulifera, and Ma. annulata (Diptera: Culicidae).

The eggs of Mansonia uniformis, Ma. indiana, Ma. annulifera, and Ma. annulata are described with the aid of scanning electron micrographs. Comparisons of egg structure among the four species showed that the eggs differed discernibly with respect to the outer chorionic tubercles on the anterior tube, the spines surrounding the raised central micropyle within the anterior cup, and the outer chorionic tubercles in the posterior region. Attempts to produce a key for identification of these eggs under scanning electron microscopy are discussed.

Animals↗

PubMed1991

Isolation of cysteine protease in the crude mite extract, Dermatophagoides farinae.

In order to study the relationship between cysteine protease and Der f I, which is one of the major allergens in the mite, Dermatophagoides farinae, isolation of cysteine protease was attempted using various column chromatographies. Both the potent cysteine protease activity and the allergenic activity were detected in the same fractions by anion exchange chromatography on a DEAE-Sephacel, gel chromatographies and chelating Sepharose 6B chromatography. In the double immunodiffusion test, the finally isolated fraction and rabbit anti-Der f I sera reacted to give a single precipitation line which fused completely with the precipitation line formed by Der f I and anti-Der f I sera. Sequence analysis for the first 10 N-terminal amino acids from cysteine protease and Der f I were identical. These results strongly suggest that cysteine protease of mites may be Der f I allergen and that measuring cysteine protease activity may possibly become a beneficial method for detecting Der f I allergens.

Allergens↗

PubMed1991

Treatment of pars planitis with cryotherapy.

Cryotherapy was performed on 28 eyes exhibiting massive exudates (snowbank) over the pars plana and the ora serrata. Twenty-six patients ranging in age from 8 to 52 years were treated and then followed up for a median of 34 months. Eleven eyes needed repeat cryotherapy. After cryotherapy, retinal vasculitis and vitreous opacities decreased in most eyes. Although only 3 of 5 eyes with a snowbank greater than 90 degrees and treated over 1 year from the onset achieved visual acuity of 20/25 or better, all 12 eyes with a snowbank smaller than 60 degrees and treated within 3 months after the onset maintained a visual acuity of 20/25 or better. The prognosis was not different from the 20 eyes that received systemic steroid treatment and the 8 eyes that received no systemic steroids. We recommend cryotherapy as the primary treatment for pars planitis with a snowbank.

Adolescent↗

PubMed1991

Enhancement by fatty acids of the rectal absorption of propranolol: in vitro evaluation in the rat.

The effects of a series of fatty acids on the rectal absorption of propranolol (PL) were examined in vitro, using macrogol 1500 base and rat rectal tissue. Lauric acid, at a fatty acid: PL molar ratio of 1:1, produced the largest increase in permeation rate (Js), penetration coefficient and partition coefficient of PL. PL flux was increased 2.5-fold in the presence of lauric acid compared to that without the fatty acid. However, the Js value of PL was decreased at increased molar ratios (e.g., 3:1) of lauric acid. The permeation rate of lauric acid across the rectal membrane was much larger than that of PL. Furthermore, the apparent partition coefficient of PL in an n-octanol/buffer system was significantly increased at a 1:1 molar ratio to lauric acid compared with that of PL alone. These results suggest that a complex-mediated mechanism facilitates PL transport, thereby partially contributing to the enhancement of PL rectal absorption. A similar mechanism is applicable to percutaneous drug absorption, as reported previously. Thus, a portion of PL, after first forming a complex with fatty acids, may rapidly permeate across rectal membranes.

Animals↗

PubMed1991

Drug interaction between cyproheptadine and tipepidine. Effect of single and repeated administrations.

In order to elucidate the interaction between cyproheptadine (CPH) and tipepidine (TP), the disposition of CPH and its metabolites from plasma and the hepatic drug metabolizing enzyme activities in rats dosed singly or repeatedly were investigated. The elimination of CPH and its metabolites, desmethylCPH (DMCPH) and DMCPH-epoxide (DMCPHEPO), from plasma after a single intravenous (i.v.) administration of both CPH and TP was not significantly altered compared with that after CPH alone, although the i.v. administration of DMCPH and TP enhanced the plasma levels of DMCPHEPO. The elimination of TP from plasma was not affected by the coadministration with CPH. The single oral administration of both CPH and TP (50 mg/kg) significantly enhanced the plasma levels of CPH and DMCPH compared with those after CPH alone, consequently resulting in their delayed elimination. However, the coadministration with TP at a low dose (5 mg/kg) hardly affected the plasma decay of CPH and its metabolites. The repeated dosing of them for 7 d obscured the interactive effect. The hepatic drug-metabolizing enzyme activities, cytochrome P-450 and aminopyrine demethylase activity, were greatly increased after the repeated administration of CPH, especially showing much more increased activities after the coadministration with TP. These results suggest that the competition of hepatic oxidative metabolism between CPH or its metabolites and TP based on the depletion of the enzymes might largely be involved in the drug interaction on a single dosing of them and that the repeated dosing of them would dissolve the depletion due to their strongly inductive effect.

Administration, Oral↗

PubMed1991

Percutaneous absorption of bromhexine in rats.

The percutaneous absorption of bromhexine (BH), an expectorant drug, through rat skin was examined in vitro and in vivo. BH in free base form penetrated better than the hydrochloride through the skin. When the in vitro penetration of BH was compared using Plastibase, macrogol and sucrose ester of fatty acid F-160 (DK-ester) formulations, the DK-ester formulation showed the best penetration of BH of the three. The addition of Azone (3%) or lauric acid (BH: lauric acid molar ratio, 1:1) considerably increased BH penetration to a relatively large penetration rate. The plasma levels of BH after in vivo application of the DK-ester formulation with Azone or lauric acid (0.6 g/3.8 cm2) were also higher than those after the formulation without an enhancer, and a constant plasma level (20-50 ng/ml) was obtained during the application for 48 h. However, the bioavailability was low, 2.5 and 2.7% respectively. When the amount of BH remaining in DK-ester ointment and the skin after an 18-h application was measured, the BH content in the ointment was 88.6 +/- 8.0% for the formulation without Azone and 93.7 +/- 6.9% for that with Azone. The low penetration and low bioavailability observed will thus be due to the high drug retention of the base.

Animals↗

PubMed1991

Enhancement effect of lauric acid on the rectal absorption of propranolol from suppository in rats.

In a previous paper, we have demonstrated that medium chain fatty acids significantly enhance the in vitro rectal absorption of propranolol (PL) and that the enhancement may be partly due to the formation of a complex with a fatty acid at a 1:1 molar ratio. To confirm in vivo the enhancement effect of lauric acid on PL absorption, PL suppositories with lauric acid at various molar ratios were administered to rat rectum. PL absorption from Witepsol and macrogol suppositories with lauric acid at a 1:1 molar ratio was much larger than that after PL alone and the 1:2 or 1:3 molar ratio ones. The bioavailability (BA) after administration of the 1:1 molar ratio suppository (PL, 4 mg/kg) was 1.6- and 2.1-fold for the Witepsol and macrogol formulations respectively, compared with that after PL alone. A similar result was obtained with the PL solid dispersion suppository with lauric acid at a 1:1 molar ratio, showing a 1.7-fold higher BA compared with PL alone. The release of PL from the macrogol suppository was significantly faster at a 1:1 molar ratio than that of other preparations, but not so in the solid dispersion suppository. There was not good agreement between the release rates of PL from the suppositories and the plasma levels after dosing. These results supported the concept that a portion of PL, by forming a 1:1 complex with lauric acid, would penetrate across the rectal mucosa more easily than PL alone.

Administration, Rectal↗

PubMed1991

Percutaneous absorption of elcatonin and hypocalcemic effect in rat.

The percutaneous absorption of elcatonin (EC), a hypocalcemic peptide, was investigated. A transdermal dosage form of EC was produced using a gel base, absorption enhancer and protease inhibitor, and applied to rats for 24 h. The combination of bile salt such as taurocholate and glycocholate, and n-octyl-beta-D-glucoside or n-octyl-beta-D-thioglucoside (OTG) exerted the potent enhancing effect on the absorption of EC, and a potent hypocalcemic effect was shown for 24 h or longer. The least level of plasma calcium was obtained 6 h or longer after application, suggesting the relatively rapid absorption of EC. The apparent bioavailability of EC in system 5 was 4.6%, this value being noteworthy in the percutaneous absorption of peptides. When the enhancing effect of taurocholate and OTG was separately measured, both agents acted additively on the absorption of EC. An EC ointment maintained the hypocalcemin effect after storage for 15 d at 40 degrees C. The transdermal dosage form has the potential to be an efficient drug delivery system for Paget's disease and osteoporosis.

Animals↗

PubMed1991

[The effect of trabeculotomy on the day-time variation of intraocular pressure of the primary open-angle glaucoma].

We selected 34 eyes with primary open-angle glaucoma cases having glaucomatous visual field loss, but with relatively low base-line intraocular pressure (average intraocular pressure at normal office hour, below 20mmHg) and with one or more episodes of intraocular pressure over 21mmHg in a diurnal fluctuation estimated at 8:30, 9:30, 11:30, 13:30, 15:00 and 17:00. They were treated with trabeculotomy ab externo and we compared the pre- and postoperative diurnal fluctuation pattern of the intraocular pressure. The mean of the base-line intraocular pressure decreased from 18.4 to 16.3mmHg. The mean values of the maximal pressure of the diurnal estimation and of the diurnal difference (maximum minus minimum) also decreased, from 23.4 to 17.9 and from 7.4 to 3.9mmHg, respectively. In 31 eyes (91%) the individual maximal value did not exceed 20mmHg postoperatively. From these findings, it was speculated that trabeculotomy can be effective on primary open-angle glaucoma with relatively low intraocular pressure.

Circadian Rhythm↗

PubMed1991

[Placental transfer and pharmacokinetic parameters of flomoxef during the perinatal period].

Flomoxef (FMOX), a new oxacephem with low MIC values against not only Gram-negative bacilli (GNB) but also against Gram-positive cocci (GPC), was evaluated for its transfer into fetus, amniotic fluid, maternal milk, spinal fluid and urine during the perinatal period following a single intravenous drip infusion at a dose of 1 g for 30 minutes. The results obtained are summarized below. 1. High concentrations of FMOX were demonstrated in maternal serum, umbilical arterial serum and amniotic fluid with Cmax values of 48.0, 10.99 and 10.20 micrograms/ml, respectively. 2. Maternal urinary excretion rate was 65.4% in the first 6 hours after administration. 3. In contrast, maternal milk and spinal fluid levels were lower than 3 and 0.20 micrograms/ml, respectively. These results showed a good placental transfer of FMOX, which is very useful for various perinatal infections. No adverse effects were observed in mothers and neonates during the course of this study.

Adult↗

PubMed1991

[Clinical studies on flomoxef in pregnant women with infections during the perinatal period].

Clinical efficacies of flomoxef (FMOX), which is a newly developed oxacephem antibiotic, were evaluated in 14 cases of obstetric and gynecologic infections during the perinatal period. The results were excellent in 6 cases (42.9%) and good in 8 cases (57.1%). No side effects nor abnormal clinical laboratory test results were observed in mothers or neonates. Thus, FMOX appears to be a useful antibiotic for perinatal infections.

Adult↗

PubMed1990

Cytotoxic effects of aflatoxin B1 and its association with cellular components in chicken embryo primary cultured cells.

We have examined the cytotoxicity and cellular incorporation of aflatoxin B1 (AFB1) in several types of established and primary cultured cells. The inhibition of DNA synthesis by AFB1 at 1 microgram/ml was about 0-30% in the established cell lines, including human hepatic cells. In chicken primary hepatocytes, however, DNA synthesis as well as RNA and protein syntheses were strongly inhibited by much lower concentrations of AFB1, e.g., 0.1 microgram/ml. In contrast, chicken primary fibroblasts showed almost no significant response to the toxin. Microsomal cytochrome P-450 activities in hepatic tissues were 10-20-fold higher than those in fibroblastic tissues. The amount of [3H]AFB1 incorporated into acid-insoluble materials in the primary hepatocytes was also 10-100-fold more than that in the primary fibroblasts. However, a significant amount of AFB1, which was enough to induce cytotoxic effects on the primary hepatocytes, could be incorporated into the primary fibroblasts when the concentrations of AFB1 were increased. Characterization of the AFB1-associated cellular components showed that most of them were DNA, RNA, and proteins in the primary hepatocytes, while in the primary fibroblasts a large portion of the incorporated AFB1 was recovered from lipid fractions. In addition, the selective binding of [3H]AFB1 to several proteins was observed only in the primary hepatocytes. The possible role of the AFB1-binding proteins are also discussed.

Aflatoxin B1↗

PubMed1990

Surface hydrophobicity, adherence, and aggregation of cell surface protein antigen mutants of Streptococcus mutans serotype c.

The pac gene of the serotype c strain Streptococcus mutans MT8148 encodes a cell surface protein antigen (PAc) of approximate 190 kilodaltons. The serotype c strain S. mutans GS-5 does not produce the 190-kilodalton PAc but produces a lower-molecular-weight protein that reacts with anti-PAc serum. The SphI-BamHI fragment of the pac gene was ligated with the S. mutans-Escherichia coli shuttle vector pSA3. The chimeric shuttle vector was transformed into strain GS-5, and two transformants (TK15 and TK18) were isolated. These transformants produced a large amount of cell-free and cell-bound PAc of 190 kilodaltons. No plasmid was isolated from these transformants, and the EcoRI fragments of their chromosomal DNA hybridized with the erythromycin resistance gene in the shuttle vector DNA, indicating insertion of the chimeric shuttle vector DNA into the chromosomal DNA. The cell hydrophobicity of strains TK15 and TK18 as well as PAc-defective mutants constructed by inserting an erythromycin resistance gene into the pac gene of strain MT8148 was analyzed. Strains MT8148, TK15, and TK18 were hydrophobic. On the other hand, strain GS-5 and PAc-defective MT8148 transformants were hydrophilic. Resting cells of the hydrophobic strains attached in larger numbers to saliva-coated hydroxyapatite than did the hydrophilic strains. Human whole saliva induced the aggregation of cells of the hydrophobic strains but not that of cells of the hydrophilic strains. These results suggest that cell surface PAc of S. mutans serotype c participates in attachment of the streptococcal cell to experimental pellicles.

Antigens, Bacterial↗