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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 343 records · Page 19Linked to original sources

Effects of tannins on the oxidative damage of mouse ocular lens. I. Using the oxidative damage model induced by the xanthine-xanthine oxidase system.

The protective effects of various tannins on ocular lens against the induced oxidative damage were examined. Oxidative damage on mouse lenses was induced by incubating them with xanthine-xanthine oxidase, ADP and Fe3+ (X.XOD system). X.XOD system caused an increase in lipid peroxide of lens membrane and decreases in Na,K-ATPase and GSH reductase activities in the lenses. After pretreatment of lenses with X.XOD system, the lenses were incubated with tannins in the medium containing no X.XOD system and the effects of tannins on biochemical parameters in the lenses were determined. Higher molecular tannins (penta-O-galloyl-beta-D-glucopyranose and geraniin) decreased the lipid peroxide in the lens and restored GSH content, Na,K-ATPase and GSH reductase activities in the lens to the level comparable to control. However, all of tannins tested restored much insufficiently the cation level (ratio of Na+/K+) in the lens regardless of extents of restoration of Na,K-ATPase level by them. Because it was supposed that tannins might act primarily on the plasma membrane, the effect of tannins on lens plasma membrane was examined using cell free system. Lens was homogenated and separated into membrane pellet and supernatant. When the pellet was treated with X.XOD system, the lipid peroxide in the pellet increased and its Na,K-ATPase activity decreased. In addition, the treated pellet decreased the GSH level and GSH reductase activity in the supernatant, when the pellet was combined with the supernatant. Higher molecular tannins reduced lipid peroxide content in the X.XOD-treated pellet to control level and the pellet in which lipid peroxide content was reduced by tannins caused much less decreases of GSH level and GSH reductase activity in the supernatant. These results suggest that, in intact lens, higher molecular tannins act on plasma membrane to eliminate lipid peroxide produced by the X.XOD system and consequently suppress the decreases in both Na,K-ATPase and GSH reductase activities without their entering inside the cell.

Animals↗

The evaluation of therapeutic efficacy of hachimi-jio-gan (traditional Chinese medicine) to rat galactosemic cataract.

Hachimi-jio-gan (Rehmannia Eight Formula, pa-wei-ti-huang-wan or Bawei dihuang wan) is one of traditional Chinese medicines which has been used for treating various senile disease for a few hundred years. This drug was evaluated for its therapeutic efficacy to rat galactosemic cataract from the suppressive rate of variance of some biochemical parameters, whose variation with cataractogenesis or the advance of cataract have been reported already. The dose of 500mg of Hachimi-jio-gan/day/200g of rat body weight suppressed significantly the variations of hydration rate, Na/K ratios, and calcium ion level in the lens with the advance of galactosemic cataract, especially when the drug was administered by the pre- or concurrent-administration before or with 30% of galactose diet respectively. This drug also could delay the progressive rate of lens opacification. However, the drug had no effect to suppress the galactitol accumulation in the lens. From these results, we presume that a drug action of Hachimi-jio-gan may control the balance of sodium, potassium and calcium ions which are important in relation to the maintenance of lens transparency. Then, we realized, that this drug may have a prophylactic efficacy to diabetic cataract, though a more detail study should be needed to apply this drug to human cataract disease.

Animals↗

Influence of calmodulin antagonists on Ca2+ transport in the lens.

Attempts were made to elucidate the relation between lens opacification resulting from inhibition of Ca2+ transport and high calcium accumulation in the lens. Mouse lenses were incubated with naphthalenesulfonamide compounds (W-5, W-7, W-12 and W-13) which act as calmodulin antagonists. When lens Ca2+-ATPase activity was inhibited by those calmodulin antagonists, an accumulation of calcium in the lens was observed. This phenomenon depended on the chemical structure of calmodulin antagonist. In lenses treated with W-7, more than 97% of excess calcium was bound. Insoluble protein increased from 8.5 to 17% of the total protein and the degree of lens opacification increased to 85.1%. These results suggested that dysfunction of the Ca-pump system leads to calcium accumulation, thus in turn inducing protein denaturation which in turn is followed by lens opacification.

Animals↗

Changes of lens crystallins photosensitized with tryptophan metabolites.

The effect of UV irradiation on bovine lens soluble proteins (crystallins) in the presence of tryptophan metabolites was investigated in vitro. The cross-linking of crystallins by UV irradiation was accelerated by kynurenine, 3-hydroxykynurenine, anthranilic acid and 3-hydroxyanthranilic acid. On denaturation of crystallins by photooxidation, alpha-crystallin was characterized by the formation of water-soluble HMW (high molecular weight) protein, while water-insoluble HMW protein was produced from beta- and gamma-crystallin. These HMW aggregates showed cross-linking by non-disulfide covalent bonds. LMW (low molecular weight) peptides were formed by degradation of alpha- and beta-crystallin.

Animals↗

In vitro subacute cataractogenic study in rainbow trout lens.

Crystalline lens of rainbow trout can be incubated in H10 medium at 0 degrees C for 2.5 months without loss of transparency and change in cation level. Applicability of this lens incubation system to test for drug toxicity was investigated. Changes in cation and glutathione (GSH) levels and lactic acid production which occurred with opacification were examined when the lens was treated with diamide, p-chloromercuribenzoic acid (PCMB), N-ethylmaleimide (NEM), 1,2-naphthoquinone, ouabain and valinomycin. Among biochemical parameters, the increase in Na+-K+ ratio (Na+/K+) was most closely related to lens opacification, as in mammalian lenses. Lens opacification was observed macroscopically. Therefore, Na+/K+ was used as a lens toxicity parameter of the drug. Valinomycin was found to be the most effective drug as measured by the lowest concentration (1.0 X 10(-10) M) which gave an increase in Na+/K+. On the other hand, the lens treated with 2.5 X 10(-5) M NEM demonstrated neither change in Na+/K+ nor loss of transparency for 2.5 months. Lens toxicities due to diamide, PCMB, valinomycin and ouabain were detectable in the rainbow trout lens at 1000 times lower concentrations than those in the mouse lens. By using rainbow trout lenses incubated at 0 degrees C, drug toxicity can be characterized by well-defined biochemical parameters and can be observed at lower concentrations for long periods of time. The rainbow trout lens is, therefore, very useful for studying long-term drug toxicity and the lens opacification mechanism.

Alkylating Agents↗

Purification and characterization of calmodulin-dependent functional protein, phosphodiesterase, in the lens.

Calmodulin and calmodulin-dependent functional protein play an important role in the maintenance of lens transparency and homeostasis. In the present study, phosphodiesterase, one of the typical calmodulin-dependent functional proteins, was purified from bovine lens by DEAE-cellulose chromatography, calmodulin-Sepharose 4B chromatography and Superose 12 chromatography. Moreover, calmodulin-dependent phosphodiesterase, and independent phosphodiesterase were separated from crude lens extract using DEAE-cellulose column. The calmodulin-dependent phosphodiesterase was purified 4500-fold with a 0.7% yield; it was a dimer formed with two single polypeptides of 59K as the molecular weight. The enzyme had a higher affinity for cyclic GMP than for cyclic AMP, and functioned at calcium ion concentration above 10(-6) M in the incubation mixture. W-7 as calmodulin antagonist indirectly inhibited the enzyme activity and nifedipine as calmodulin-dependent phosphodiesterase antagonist directly inhibited the enzyme activity. These results suggest that an appearance of calmodulin-dependent phosphodiesterase activity depends on the interrelation between the calcium ion and calmodulin in the lens.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Comparative, controlled study on an ampicillin suppository (KS-R 1) with an oral form of ampicillin in urinary tract infections].

Subjects were in-patients with bacterial urinary tract infections, ranging in age 4 months to 11 years 4 months. As a rule, daily dose was either four 125 mg (in potency) suppositories or four 125 mg (in potency) oral form given at 6-hour intervals over a period of 5 days. The number of children subjected to this study was 105. These children were divided into 2 groups (suppository 54; oral form 51) with matched pretreatment background factors. Therapeutic effectiveness rates were 70.4% for the suppository and 66.7% for the oral form, and no significant difference was observed between the 2 groups. Rates of efficacy by severity, presence or absence of underlying and/or complication diseases, daily dose and causative microorganisms did not differ significantly between the 2 groups. There was no significant difference in time-courses of improvement of clinical signs and symptoms between the 2 groups. Eradication rates for causative microorganisms were 65.9% for the suppository and 62.5% for the oral form. Most frequently isolated causative microorganisms were Escherichia coli and Proteus mirabilis. No significant differences were recognized in the therapeutic effect and usefulness evaluated by physicians in charge. The frequency of side effects did not differ significantly between the suppository group (6 with diarrhea and 1 with anal pain: 12.1%) and the oral form group (5 with diarrhea, 1 with displeasure and 1 with vomiting: 12.7%). Abnormal laboratory findings appeared in 6 cases (2 with eosinophilia, 2 with increased GOT and 2 with increased GPT) in the suppository group and 7 cases (2 with eosinophilia, 2 with thrombocytosis, 2 with increased GOT and 1 with increased GPT) in the oral form group.

Administration, Oral↗

[Bacteriological and clinical studies on flomoxef in the pediatric field].

Bacteriological and clinical studies on flomoxef (FMOX, 6315-S) were performed and the results obtained are summarized below. 1. The MIC values of FMOX against 307 clinically isolated strains of Staphylococcus aureus were 0.024 to 100 micrograms/ml with a peak MIC of 0.39 microgram/ml, and the MIC90 value was 1.56 micrograms/ml. The MIC90 against methicillin resistant S. aureus (MRSA) was 25 micrograms/ml. 2. FMOX was administered to 15 children with pediatric bacterial infections, and the effectiveness was rated excellent or good in all cases. 3. In bacteriological evaluation, 7 of 11 strains identified prior to the treatment were eliminated (63.6%). 4. As side effects, diarrhea or soft stool was found in 3 cases and eruption in 1 case. As abnormal laboratory values, eosinophilia and thrombocytosis were found in 1 case each. 5. On the intestinal bacterial flora, FMOX had a marked influence just as did other Group 4 and 5 cephems antibiotics. 6. FMOX interfered little with the coagulation system or platelet aggregation.

Age Factors↗

Characterization of water-insoluble proteins in human lens nuclei.

Water-insoluble proteins from the nuclei of human normal and cataractous lenses were analyzed by solubilizing the lens material in various organic solvent/water mixtures. Gel permeation chromatography with TSK-3000 and TSK-4000 columns and a high performance liquid chromatography system were utilized to fractionate the water-insoluble proteins. The effective solvent systems were a) acetonitrile:tetrahydrofuran: water = 20:60:20, v/v%; b) tetrahydrofuran:water = 50:50, v/v%; and c) methanol:water = 25:75, v/v%. Different protein fractions could be selectively extracted with different solvent mixtures. The fractions obtained were partially identified using antibodies made against the soluble alpha-, beta-, and gamma-crystallins. Protein profiles obtained from cataractous nuclei differed markedly from those obtained from normal nuclei of the same age. In particular, an approximately 350K protein aggregate was found to increase with age in cataractous nuclei. This 350K aggregate is only a minor component in the nuclei of normal lenses.

Aged↗

[Report of two cases of advanced renal cell carcinoma and our experience at Mito Saiseikai General Hospital].

A tumor thrombus in the vena cava (infrahepatic) was identified in a 70-year-old male with chronic obstructive lung disease, and right nephrectomy and thrombectomy were performed successfully. Therefore, he enjoyed good health for 6 months until he developed bone metastasis in the vertebrae and upper gastrointestinal bleeding. In another case of a 51-year-old male who presented with a mass in the posterior part of the chest; the biopsy specimen of the mass was reported to at least resemble renal-cell carcinoma. Subsequently, he underwent right nephrectomy and thoracotomy to remove the mass. He has since led an uneventful life without tumor recurrence. In our hospital from 1971 to 1980, 9 cases of renal-cell carcinoma have been experienced, including the above 2 cases. Their average age was 49.4 years, with ages ranging from 34 to 70 years. Seven patients presented with gross hematuria, and 2 patients, with flank pain. All 9 cases, all of whom underwent radical nephrectomy, were diagnosed pathologically as having renal cell carcinoma. The right side was involved in 3 cases, and the left, in 6 cases. The upper pole of the kidney was involved in 2 cases the middle in 1 case, and the lower in 5 cases. The mean 5-year survival rate was 69.2% and was closely associated with the tumor stage.

Adult↗