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Biomedical subjects

T Takaya

Publications and source records attributed to T Takaya.

At least 37 records · Page 2Linked to original sources
PubMed1996

Use of epidural anesthesia in non-cardiac surgery in two cases complicated by hypertrophic cardiomyopathy.

Two patients with hypertrophic cardiomyopathy (HCM) who underwent non-cardiac surgery were managed successfully using epidural anesthesia as the principal intraoperative anesthesia. Epidural block was induced by inserting an epidural catheter from the lumbar vertebrae toward the caudal side. Epidural anesthesia is usually avoided in HCM patients because of the risk of a decreased preload or afterload causing stenosis in the left ventricular outflow tract. However, in surgery that requires an anesthesia level at L1 or below, which has little effect on sympathetic nerves, epidural anesthesia that maintains a stabilized hemodynamic state appears to be an excellent option.

Adult↗
PubMed1995

Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs.

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.

Animals↗
PubMed1995

Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs.

A novel ethylcellulose (EC) capsule which releases drug with a time-controlled fashion has been prepared. This capsule is composed of four parts, drug container, swellable substance, capsule body and cap. At the bottom of the body, micropores are made. As water penetrates through these micropores, the swellable substance such as low substituted hydroxypropyl cellulose (L-HPC) swells. When the cap made of water-insoluble macromolecular substance such as EC cannot persist the swelling pressure, the EC cap disintegrates and the drug in the container is released from the capsule. The lag-time is utilized for the delivery of drug to the colon. The release time of the drug from the capsule was measured both in vitro and in vivo experiments. In the case of an in vitro experiment, after 12mg of fluorescein as a model drug and 238mg of starch were filled into the container, caps having different thickness were attached to the capsule body and release study was performed. The release time of the drug was mainly dependent on the thickness of the cap. Using test capsules of which mean cap thickness were 39.1 +/- 2.3 (SE)microns, 63.1 +/- 5.0 microns and 75.6 +/- 4.1 microns, the in vivo release time was estimated after administration to beagle dogs. As a parameter, the peak time (tmax) when plasma fluorescein concentration reached to its maximum level was determined for the estimation of the release time of the drug from the capsule in the gastrointestinal tract. The in vivo tmax was well correlated with the cap thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[A case of status asthmatics relieved by long-term inhalation of isoflurane].

A 58 year old man in status asthmatics refractory to drug therapy, was relieved by long-term isoflurane inhalation. In status asthmatics, it takes long time to recover from airway-damage, and inhalation-time will be prolonged in many cases. It is appropriate to use isoflurane because it is devoid of significant adverse effects compared with halothane and enflurane. Especially, isoflurane did not cause an increase in the serum fluoride revel, and will not lead to renal insufficiency in spite of its inhalation for 120 hours. It seems that isoflurane is suitable for long-term inhalation.

Administration, Inhalation↗
PubMed1994

Studies on a novel, potent and orally effective cholecystokinin A antagonist, FK-480. Synthesis and structure-activity relationships of FK-480 and related compounds.

We prepared various novel tricyclic 1,4-benzodiazepine derivatives as cholecystokinin (CCK) A antagonists, which were evaluated preliminarily for inhibition of 125I-CCK-8 binding to rat pancreatic membranes in vitro and inhibiting effect on CCK-8-induced inhibition of charcoal meal gastric emptying in mice. On the basis of structure-activity relationship (SAR) studies, as well as the stability and availability of the starting materials of those compounds, (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo- pyrrolo[3,2,1-jk][1,4]benzodiazepin-3-yl]- 1H-indole-2-carboxamide (9f, FK-480) was selected as a candidate compound for further evaluation. The absolute configuration of the precursor of FK-480, (3S)-amino-1,4-benzodiazepine derivative ((S)-8a, R1 = F) was determined by an X-ray crystallographic study of its ureido derivative with (S)-alpha-methylbenzyl isocyanate. FK-480 is now undergoing clinical studies for the treatment of chronic pancreatitis.

Animals↗
PubMed1994

Potentiation of neuromuscular blockade by calcium channel blockers.

A significant reduction was noticed in the amount of vecuronium needed to maintain steady neuromuscular blockade at 20% twitch height (T1) in patients given nicardipine intraoperatively. Bolus injection of either nicardipine or diltiazem during constant infusion of vecuronium produced transient depression of T1 and the train-of-four ratio (TOFR). Reversal of neuromuscular blockade with a choline esterase inhibitor (neo-stigmine) was not retarded by previous administration of Ca-channel blockers but concurrent administration of anticholine-esterase agent and Ca-channel blockers caused a delay in recovery from motor blockade. Monitoring of neuromuscular junction activity is strongly recommended whenever a large cumulative dose of Ca-channel blockers is used.

Adult↗
PubMed1994

[Effect of preoperative liver function on serum lidocaine level during continuous epidural block].

To determine whether the blood lidocaine level during the continuous epidural block correlates with the preoperative liver function, i.e. serum albumin level, serum cholinesterase (ChE) activity, glutamic pyruvic transaminase (GPT) and indocyanine green retention rate (ICG R15), we measured the arterial serum lidocaine level in 45 abdominal surgical patients. The epidural catheter was advanced cephalad from Th10-L2 interspace, for a distance of 4 to 5 cm. Anesthesia was induced with thiopental, and maintained with continuous epidural block plus N2O, O2 and low concentration of isoflurane inhalation. We started epidural block with 0.3 ml.kg-1 body weight of 1.5% lidocaine and added half of the initial dose every 30 minutes for 2 hours. Serum lidocaine concentration was measured every 15 minutes after the lidocaine injection into epidural space. The result revealed that the lower the serum albumin level and ChE activity were, the higher the serum lidocaine level was and, that it had no significant correlation with GPT and ICG R15. We conclude that any patient with hypoalbuminemia and low serum ChE activity might have higher blood lidocaine levels during the continuous epidural block.

Adult↗
PubMed1993

Right atrial contractile performance in patients with myocardial infarction.

To evaluate right atrial (RA) contractile performance in patients with myocardial infarction, we validated a cineangiographic method of RA volume measurement, and investigated RA volume change in 'normal' individuals and patients with a previous myocardial infarction. Sixteen silicone rubber RA casts made from human cadavers were filmed in the postero-anterior and left lateral projections. The cast volumes calculated following Simpson's rule were in good agreement with those measured by water replacement (r = 0.992, P < 0.01). At cardiac catheterization, biplane RA cineangiography was performed in 19 'normal' individuals (N group), in 14 patients with a previous antero-septal infarction (AMI group) and in seven patients with a previous inferior infarction (IMI group). The RA volume-time curve was constructed at 20-40 ms intervals for one cardiac cycle. RA volume at the beginning of the atrial contraction (RAVd), which was defined as the 'preload' of the RA, tended to be larger in both the AMI and IMI groups compared with 'normal' individuals. The RA ejection volume was significantly larger in both the AMI (18.4 +/- 2.1 ml.m-2, P < 0.01) and IMI groups (19.4 +/- 2.8, P < 0.01) than in the N group (14.5 +/- 1.9), even for a comparable level of RAVd (range from 26 to 36 ml.m-2) (18.6 +/- 2.1, P < 0.01, 18.2 +/- 2.0, P < 0.01, 14.7 +/- 1.9, respectively). These results suggest that RA contraction increases in patients with myocardial infarction by increasing both the 'preload' and 'contractility' of the RA.

Adult↗
PubMed1993

Possible involvement of hypersecretion of ADH in hyponatremia in a diabetic patient complicated with severe neuropathy.

The present case was a 44-year-old man who had been diagnosed as having noninsulin-dependent diabetes mellitus 2 years before admission. He gradually showed severe neuropathy and emaciation because of poor control of his blood glucose levels. He was admitted to our hospital because of disturbance of consciousness with hyponatremia. The endocrinological findings including thyroid and adrenal functions revealed no abnormalities. Insufficiency of water diuresis was noted in the water loading test. Severe orthostatic hypotension was noted during the standing up test, and an excessive response in the plasma ADH level was also noted. These findings demonstrated that excessive ADH secretion occurred to compensate for the fall in blood pressure because of the breakdown of homeostatic regulation in blood pressure due to diabetic neuropathy. It is suggested that hyponatremia seemed to be subsequently induced by hypersecretion of ADH.

Adult↗
PubMed1993

[Research and development of new oral cephems, cefixime and cefdinir].

This article reviews the structure-activity relationships, biological properties and synthesis of two new oral cephalosporin antibiotics, cefixime (CFIX) and cefdinir (CFDN). Our research into new oral cephalosporin antibiotics began in the late 1970's. The first goal of our research was to discover a new oral cephem possessing similar antibacterial activity and resistance to beta-lactamase as the 3rd generation injectable cephalosporins. We focused our attention on searching for a non-prodrug type cephem, that is, a new parent structure with high intrinsic absorption. We selected ceftizoxime (CZX) as a seed compound due to its relatively high excretion rate (8.5%) in the urine after oral administration to rats. We concentrated our research on the chemical modification of the oxime moiety in CZX based on our hypothesis for oral absorption, and discovered a lead compound with a carboxymethoxyimino group which displayed better urinary excretion (41.0%). Optimization studies led to a new oral cephem, CFIX. However, CFIX shows only low to moderate antibacterial activity against gram-positive bacteria such as S. aureus. Hence, the second goal of our research was to discover a new oral cephem with enhanced activity against gram-positive bacteria. From a consideration of structure-absorption relationships, we studied the activity and absorbability of cephems bearing other acidic functional groups at the oxime moiety of CFIX. As a result, we found a new oral cephem, CFDN with a hydroxyimino group at the 7-position. CFIX has excellent biological properties, displaying potent antibacterial activity against a wide range of gram-positive bacteria except S. aureus and gram-negative bacteria including opportunistic pathogens, high stability towards beta-lactamases and long acting efficacy. CFDN exhibits excellent and well balanced antibacterial activities against gram-positive and gram-negative bacteria. The pharmacokinetic of CFDN in healthy volunteers showed that serum levels were high enough to make CFDN as an effective antibacterial agent. The proposed mechanisms of intestinal absorption of CFIX and CFDN are briefly described. The efficient synthetic methods to CFIX and CFDN were achieved via a common intermediate, 7-amino-3-vinylcephalosporanic acid diphenylmethyl ester from 7-ACA.

Administration, Oral↗
PubMed1993

[The genetic application for Japanese patients with coronary artery diseases using restriction fragment length polymorphisms (RFLPs) of apolipoprotein gene].

We applied restriction fragment length polymorphisms (RFLPs) for apolipoprotein (apoAI, apoCIII, apoAIV, apoCI, and apoB) genes to analyze differences between Japanese and Caucasian in allele frequencies as well as those between normal Japanese subjects and patients with coronary artery disease confirmed with coronary arteriography. Although the allelic fragment sizes in the two racial groups showed complete correspondence, the allelic frequencies of these markers detected by the combination of probes and restriction enzymes showed 60% difference in Japanese and Caucasian. There was a significant (p < 0.01) difference between the normal subjects (with arteriographically-confirmed absence of stenosis in all coronary branches) and those with severe coronary artery disease (50 to 100% stenosis in at least one branch) in plasma levels of apoAI, apoB, total cholesterol, HDL-cholesterol, and LDL-cholesterol. RFLP analysis for 13 markers, however, revealed no significant difference between these groups when analyzed in subjects of all ages (range, 12 to 82 years; N = 306). However, when analysis was restricted to data for 12-to 50-year-olds, a significant (p < 0.02) difference between the normal control group and the severe coronary artery disease group in 3' apoB probe and EcoRI enzyme test results. An acquired and environmental factors were assumed to be involved in this disease because the correlation between allelic frequencies and coronary artery disease status showed dilution when the subject age distribution included older subjects.

Adolescent↗
PubMed1992

[A new oral cephem, cefdinir: its structure-activity relationships and biological profile].

This article reviews structure-activity relationships and biological properties of a new oral cephem, cefidinir (CFDN). It also describes a hypothesis concerning the absorption mechanism from the intestine. Antibacterial activities and the oral absorption efficiencies were studied with regard to 3-vinyl cephalosporins with various 7-acyl side chains. From the study, 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetyl group was selected and various 3-substituents were screened. As a result, it was found that the vinyl compound, CFDN, showed excellent antibacterial activity and good oral absorption in rats. In vitro and in vivo antibacterial activities, the affinity for PBPs and the stability to beta-lactamases revealed that CFDN had well balanced antimicrobial activities against Gram-positive and Gram-negative bacteria and good biological properties. The pharmacokinetics of CFDN in healthy volunteers showed that serum concentration and half life were good enough to make CFDN an effective therapeutic agent. The mechanism of intestinal absorption of CFDN and related oral cephems are discussed and a hypothesis for molecular recognition by the carrier protein in the intestine is proposed.

Animals↗
PubMed1991

Studies on beta-lactam antibiotics. XIX. Structure-activity relationships of cephalosporins having a thiadiazolylthiomethyl group at the C-3 side chain.

The synthesis and antibacterial activity of 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-(hydroxy or alkoxy)iminoacetamido]cephalosporins with various thiadiazolylthiomethyl moieties at the 3-position are discussed. Of the compounds (1a-1e, 7a-7d), 7 beta-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxyiminoacetamido]-3-[(1,2 ,4- thiadiazol-5-yl)thiomethyl]cephalosporin (1d: FK312) exhibited the highest activity against Gram-positive and Gram-negative bacteria, especially, against methicillin-resistant Staphylococcus aureus. Furthermore, the pharmacokinetic profiles of the compound 1d showed longer serum levels than that of ceftriaxone in rats.

Anti-Bacterial Agents↗
PubMed1990

[Studies on FK482 (Cefdinir). IV. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]- 3-substituted cephalosporin derivatives].

The synthesis of 7 beta-[(Z)-2-(aminothiazol-4-yl)-2-hydroxyiminoacetamido] cephalosporins (Ia-i) modified at the C-3 position of a cephem nucleus and the effect of the C-3 substituents on the antibacterial activity and oral absorbability are discussed. The cephems (Ie, h and i) having a C-3 substituent such as 1-propenyl, ethylthio and vinylthio group as well as FK482 (cefdinir) exhibited excellent antibacterial activities against both gram-positive and gram-negative bacteria. However, those compounds showed poor absorption rate after oral administration in rats. It is concluded that the vinyl moiety at the 3-position is necessary to display fairly oral absorptivity in a series of 7 beta-[(Z)-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]c eph ems.

Animals↗
PubMed1990

[Studies on FK482. II. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives].

Various 7 beta-[2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives (Ia--e, IIa--g) were synthesized in order to find a new orally active cephalosporin improving the antibacterial activity of cefixime (CFIX) against Staphylococcus aureus. These derivatives include three types of alpha-substituted 2-(2-aminothiazol-4-yl)acetyl side chain; i) mono or non substituted acetyl moiety, ii) carboxyalkoxyimino acetyl moiety, iii) phosphonomethoxyimino and hydroxyimino acetyl moiety. Their structure-activity relationships and urinary recoveries in rats were studied. As a result, the compound with a hydroxyimino acetyl side chain (IIg, FK482) showed good oral absorption and excellent antibacterial activity against both gram-positive and gram-negative bacteria and was selected as a candidate for clinical trial.

Animals↗
PubMed1990

[Studies on FK482 (Cefdinir). III. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinyl-3- cephem-4-carboxylic acid derivatives].

The synthesis, antibacterial activity and oral absorption of the 7 beta-[(Z)-2-aryl-2-hydroxyiminoacetamido]-3-vinylcephalosporins (Ia--e) are described. All of these compounds exhibited excellent activity against Staphylococcus aureus. Against Gram-negative bacteria FK482 exhibited more excellent activity than the other compounds (Ia--e). These compounds except Ie showed good oral absorption. The relationship between the oral absorption rates and the lipophilicity of these cephalosporins is discussed.

Animals↗