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Biomedical subjects

H Hashizume

Publications and source records attributed to H Hashizume.

At least 145 records · Page 8Linked to original sources
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a meta-substituent on the benzene ring in the side chain.

Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activities towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphenyl)ethyl]-3-hydroxy-methyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.

Animals↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a side chain mimicking the extended structure of 1233A.

Structural analogs of 1233A, a microbial metabolite inhibiting 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) synthase, were designed and synthesized. The 2-oxetanone moiety was left intact. All analogs prepared were tested for inhibition of HMG-CoA synthase activity and sterol synthesis in mouse liver and for effect on serum triglyceride levels. Of these analogs, trans-4-[2-[3-(7-carboxy-2- naphthyl)phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (4a) showed the highest inhibitory activity in vitro, and also had in vivo inhibitory activity without causing any increase in triglyceride level.

Animals↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitors: 2-oxetanones with a side chain mimicking the folded structure of 1233A.

To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-1-naphthyl)ethyl]-2-oxe tanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.

Animals↗
PubMed1994

Collagen framework of the volar plate of human proximal interphalangeal joint.

The functional roles of the three-dimensional fibrillar ultrastructure of the proximal interphalangeal joint volar plates of human fingers were studied by light microscopy and scanning electron microscopy. The results revealed that the volar plate consists of three layers of fibers. The first layer forms an intracavity wall with two parts, the proximal "membranous portion", and the distal "meniscoid protrusion" that is separated from the middle phalangeal base by a "recess". The second layer contains the "check ligament", which lies parallel to the fibers of the tendon, anchors tightly into the middle phalangeal base, and protects the joint from hyperextension. The third layer connects to the fibers from the accessory ligament and ligamentous tendon sheath of the A3 pulley, perpendicularly crosses the fibers of the tendon, becomes the periosteum of the middle phalangeal base, and functions as a hanging support for the volar plate and as a gliding floor for the flexor tendon.

Adult↗
PubMed1994

Computer simulation analysis of fracture dislocation of the proximal interphalangeal joint using the finite element method.

Stress is a proximal interphalangeal (PIP) joint model was analyzed by the two-dimensional and three-dimensional finite element methods (FEM) to study the onset mechanisms of the middle phalangeal base fracture. The structural shapes were obtained from sagittally sectioned specimens of the PIP joint for making FEM models. In those models, four different material properties were given corresponding to cortical bone, subchondral bone, cancellous bone and cartilage. Loading conditions were determined by estimating the amount and position of axial pressure added to the middle phalanx. A general finite element program (MARC) was used for computer simulation analysis. The results of the fracture experiments compared with the clinical manifestation of the fractures justify the applicability of the computer simulation models using FEM analysis. The stress distribution changed as the angle of the PIP joint changed. Concentrated stress was found on the volar side of the middle phalangeal base in the hyperextension position, and was found on the dorsal side in the flexion position. In the neutral position, the stress was found on both sides. Axial stress on the middle phalanx causes three different types of fractures (volar, dorsal and both) depending upon the angle of the PIP joint. These results demonstrate that the type of PIP joint fracture dislocation depends on the angle of the joint at the time of injury. The finite element method is one of the most useful methods for analyzing the onset mechanism of fractures.

Aged↗
PubMed1994

Clinicopathological analysis of de Quervain's disease.

Excised extensor retinacula of the first compartment and tenosynovium from 35 patients (6 men and 29 women) with de Quervain's disease were examined by light and electron microscopy to investigate the pathogenic mechanism. The patients, aged from 22-78 years, averaging 50 years, comprised the study group. Two hundred and thirty-two specimens from cadavers of 95 men and 75 women were macroscopically examined as the control. In the study group, the extensor retinaculum and tenosynovium were macroscopically thickened, and were histologically classified into 4 groups based on presence or absence of septum, and the location of retinacular thickening. Morphologically, the thickening of the tenosynovium and retinaculum was due to fibrosis in every layer, although fibroses were seen mainly in the middle layer. The ratios of proliferation of fibroblasts, myxoid changes and/or hyaline degeneration, and vascular proliferation were varied between layers. Minimal round cell infiltration was found in the retinaculum as well as in the tenosynovium. The results also indicate that the Iwahara-Nozue test can be used to accurately predict relatively greater thickening of the retinaculum on the extensor pollicis brevis side. Based on clinicopathological analyses, it appears that de Quervain's disease is induced not only by extrinsic factors such as superficial friction but also by intrinsic factors.

Adult↗
PubMed1993

Superoxide radical scavenging activity of phenolic compounds.

1. Superoxide radicals (O2-.) were generated from a hypoxanthin-xanthin oxidase (HPX-XOD) reaction system and detected by the electron spin resonance (ESR) spin-trapping technique. 2. The inhibitory effect on O2-. generation occurred in the order: superoxide dismutase (SOD) > L-ascorbic acid > eugenol > guaiacol > phenol. 3. And the second-order rate constants between O2-. and samples were: SOD 1.7 x 10(9)/M/S, L-ascorbic acid 3.4 x 10(5)/M/S, eugenol 8.3 x 10(3)/M/S, guaiacol 2.5 x 10(3)/M/S and phenol 5.8 x 10(2)/M/S. 4. It was clarified that the phenolic compounds have O2-. scavenging activity.

Ascorbic Acid↗
PubMed1993

Posterior interosseous nerve paralysis related to focal radial nerve constriction secondary to vasculitis.

A case of posterior interosseous nerve paralysis is reported with discussion of some characteristics that appear to distinguish it from entrapment neuropathy and neuralgic amyotrophy. The surgical implications are also discussed. More than ten similar cases have been reported, but the pathogenesis of this condition is still controversial. The patient presented with posterior interosseous nerve paralysis related to focal radial nerve constriction secondary to vasculitis in the perineurium. The constriction site was resected and the radial nerve was sutured. The patient recovered completely after 8 months.

Adult↗
PubMed1993

Epidermal antigens and complement-binding anti-intercellular antibodies in pemphigus vegetans, Hallopeau type.

The serum of a 34-year-old woman with the Hallopeau type of pemphigus vegetans (PVg) contained antibodies against a 130-kDa polypeptide in human epidermal lysates, as revealed by Western blot analysis. The serum strongly fixed complement in vitro, and the PVg lesional skin contained a predominance of complement-fixing IgG2 and IgG4. Although the antigens reactive with sera from PVg and pemphigus vulgaris were the same, strong fixation of complement by PVg antibodies, due to the presence of complement-dependent IgG subclasses, and subsequent in situ activation of complement, might explain the marked infiltration of neutrophils and eosinophils in PVg.

Adult↗
PubMed1993

Absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy )propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate.

To clarify the absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy+ ++)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate (DSCG), a study was made using rats. N-556 gave the highest plasma level of DSCG following its injection into the loop at the upper part of the small intestine. N-556 was stable in acidic washings of gastric contents, but rapidly hydrolyzed to M1 with twin ethyl residues on DSCG in the washings of the small intestinal contents. N-556 and M1 were hydrolyzed to DSCG via M2 having a mono ethyl residue in the homogenate of the small intestinal mucosa. The oral absorption of M1 following its administration in 50% (v/v) propylene glycol solution was essentially the same as that of N-556. That of M1 administered in aqueous suspension was low. After the oral administration of N-556, a small amount of M2 and a trace of M3 having L-lysyl residue were detected in the portal plasma, but no hydrolytic intermediate except DSCG could be found in the general plasma. The major absorption mechanism of N-556 may thus be concluded as follows: N-556 given orally is transferred to the small intestine in essentially intact form. N-556 is then rapidly diffused to an aqueous layer on the surface of the mucosal membrane and hydrolyzed to M1. The resultant M1 is transported to the mucosal membrane and hydrolyzed to DSCG via M2. DSCG generated in the mucosal membrane is used for general circulation through the portal blood and liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Protective effect of crataegus extract on the cardiac mechanical dysfunction in isolated perfused working rat heart.

The effect of the water-soluble fraction of Crataegus (Crataegus extract) on the cardiac mechanical and metabolic function was studied in the isolated, perfused working rat heart during ischemia and reperfusion. Ischemia (15 min) was produced by removing afterload pressure, and reperfusion (20 min) was produced by returning it to the original pressure. In the control (no drug) heart, ischemia decreased mechanical function to the lowest level, which did not recover even after the end of reperfusion. Crataegus extract (0.01 or 0.05%) was applied to the heart from 5 min before ischemia through the first 10 min after reperfusion. With the high concentration of Crataegus extract (0.05%) the mechanical function recovered during reperfusion incompletely without increasing coronary flow, but the low concentration of Crataegus extract (0.01%) did not. In the heart treated with the high concentration of Crataegus extract, the reperfusion-induced recovery of the energy metabolism was accelerated, and the level of lactate during ischemia was lower than that in the control heart, although the myocardial levels of free fatty acids during ischemia and reperfusion were not greatly affected. These results demonstrate that Crataegus extract (0.05%) has a cardioprotective effect on the ischemic-reperfused heart, and that the cardioprotective effect is not accompanied by an increase in coronary flow.

Adenine Nucleotides↗
PubMed1992

[A comparative study of cefepime for bacterial pneumonia].

The efficacy, safety and usefulness of cefepime (CFPM), a new cephem antibiotic, in bacterial pneumonia, were evaluated in a comparative study against ceftazidime (CAZ). Each drug was administered by intravenous drip infusion at a dose of 1.0 g (nominal potency) twice daily for 14 days, and the following results were obtained. 1. A total of 183 cases were enrolled in this study. Efficacy rates ("good" or better responses) as evaluated by the subcommittee were 90.3% (65/72) in the CFPM group and 94.0% (63/67) in the CAZ group, with no significant difference between the 2 groups. 2. Efficacy rates ("good" or better responses), as evaluated by attending physicians, (in the same bacterial pneumonia cases which were subjected to evaluation by the subcommittee) were 87.5% (63/72) in the CFPM group and 89.6% (60/67) in the CAZ group, with no significant difference between the 2 groups. 3. Bacteriologically, eradication rates were 96.9% (31/32) in the CFPM group and 96.7% (29/30) in the CAZ group with no significant difference between the 2 groups. 4. The incidence of side effects was 5.9% (5/85) in the CFPM group and 4.8% (4/84) in the CAZ group, with no significant difference between the 2 groups. No significant difference was also found between the 2 groups in the incidence of abnormal laboratory findings; 28.4% (23/81) of the case in the CFPM group and 34.1% (28/82) in the CAZ group. 5. As for overall usefulness of the drug in bacterial pneumonia cases, utility rates ("useful" or better evaluations) as evaluated by the subcommittee were 88.9% (64/72) in the CFPM group and 92.5% (62/67) in the CAZ group. The rates as evaluated by investigators (in cases judged as evaluable by the subcommittee) were 87.5% (63/72) and 85.1% (57/67), respectively. There were no significant differences between the 2 groups. These results indicated that CFPM is very useful for the treatment of bacterial pneumonia.

Adolescent↗
PubMed1992

Importance of hydrolysis of amino acid moiety in water-soluble prodrugs of disodium cromoglycate for increased oral bioavailability.

The relationship between physicochemical properties and oral absorption was investigated in prodrugs for the oral delivery of disodium cromoglycate (DSCG). To improve the lipophilicity of DSCG, various lipophilic moieties were introduced into the twin carboxyl groups. However, this did not lead to improved oral absorption in rabbits because of loss of water solubility, in spite of improved lipophilicity. Water-soluble prodrugs, in which an amino acid was introduced into a hydroxy group by ester linkage in addition to ethyl residues at twin carboxyl groups of DSCG, were synthesized and examined for oral absorption in rabbits and rats. The oral absorption of these prodrugs was affected by the species of amino acids introduced as a water-soluble moiety. Therefore, we examined the relation between the oral absorption of water-soluble prodrugs and the hydrolysis rate of the amino acid moiety. A good linear correlation was obtained between the oral absorption and the hydrolysis rate constant catalyzed by digestive enzymes, trypsin or alpha-chymotrypsin. It was thus concluded that the amino acid moiety of water-soluble prodrugs must be rapidly hydrolyzed to a permeable lipophilic prodrug still possessing the ethyl moiety at twin carboxyl groups in the small intestinal tract for good oral absorption.

Administration, Oral↗
PubMed1992

Characteristics of 1,3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2-((S)- lysyloxy)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate, in absorption and excretion in rats and rabbits.

The absorption and excretion of 1,3-bis-(2-ethoxycarbonylchromon-5-yloxy)-2- ((S)-lysyloxy)propane dihydrochloride (N-556), which is a prodrug for the oral delivery of disodium cromoglycate (DSCG), were studied in rats and rabbits. In both animal species, the plasma concentration of DSCG after oral administration of N-556 peaked within 1.0 h, and thereafter declined with a half-life of about 1.2 h in rats and rabbits. The area under the plasma DSCG level versus time curve (AUC) increased in proportion to the dose of N-556 in both animals. The bioavailability of N-556 as calculated from AUC was about 6% in rats and 40% in rabbits, whereas that of DSCG was only 0.1% in rats and 2.5% in rabbits. About 2% and 15% of the dose were respectively excreted as DSCG in the urine and bile after the oral administration of N-556 in rats. The ratio of biliary excretion to urinary excretion (B/U) after the oral administration of N-556 was about twice that after the intravenous injection of DSCG. In rabbits, the urinary and biliary excretions of DSCG after oral administration of N-556 were about 25% and 5%, respectively. The B/U ratio after the oral administration of N-556 in rabbits was similar to that after intravenous administration of DSCG. The difference in the systemic bioavailability of N-556 between rats and rabbits thus appears to be due to a first-pass effect, in addition to a difference in the absorption rate.

Absorption↗
PubMed1992

Effects of phenylalaninol on centrally induced gastric acid secretion.

The effects of phenylalaninol (D-isomer) on gastric acid secretion and gastric ulcer were studied in rats. The compound reduced the gastric acid secretion stimulated by intracisternal thyrotropin releasing hormone and intravenous 2-deoxy-D-glucose, but not that stimulated by subcutaneous carbachol or histamine. Phenylalaninol prevented stress- and indomethacin-induced gastric ulcers. We conclude that phenylalaninol inhibits ulcer formation mainly by central inhibition of gastric acid secretion.

Animals↗