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Biomedical subjects

M Kanao

Publications and source records attributed to M Kanao.

At least 19 recordsLinked to original sources

[Introduction and some problems of the rapid time series laboratory reporting system].

We introduced an on-line system of biochemical, hematological, serological, urinary, bacteriological, and emergency examinations and associated office work using a client server system NEC PC-LACS based on a system consisting of concentration of outpatient blood collection, concentration of outpatient reception, and outpatient examination by reservation. Using this on-line system, results of 71 items in chemical serological, hematological, and urinary examinations are rapidly reported within 1 hour. Since the ordering system at our hospital has not been completed yet, we constructed a rapid time series reporting system in which time series data obtained on 5 serial occasions are printed on 2 sheets of A4 paper at the time of the final report. In each consultation room of the medical outpatient clinic, at the neuromedical outpatient clinic, and at the kidney center where examinations are frequently performed, terminal equipment and a printer for inquiry were established for real-time output of time series reports. Results are reported by FAX to the other outpatient clinics and wards, and subsequently, time series reports are output at the clinical laboratory department. This system allowed rapid examination, especially preconsultation examination. This system was also useful for reducing office work and effectively utilize examination data.

Clinical Laboratory Information Systems↗

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↗

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↗

Syntheses and 5-HT2 antagonist activity of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives.

A series of bicyclic 1,2,4-triazol-3(2H)-one and 1,3,5-triazine-2,4(3H)-dione derivatives with a 4-[bis(4-fluoro-phenyl)methylene]piperidine or 4-(4-fluorobenzoyl)piperidine group has been prepared and tested for 5-HT2 and alpha 1 receptor antagonist activity. Among the compounds prepared, 2-[2-[4-[bis(4-fluorophenyl)methylene]-piperidin-1-yl]ethyl]- 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (7b) had the most potent 5-HT2 antagonist activity, which was greater than ritanserin (2), while 7b did not show alpha 1 antagonist activity in vivo. The central 5-HT2 receptor antagonism was approximately 1/30 that of 2 when tested for the ability to block head twitches induced by 5-hydroxytryptophan. Compound 21b, 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6,7,8,9-tetrahydro- 2H- pyrido[1,2-a]-1,3,5-triazine-2,4(3H)-dione also displayed potent 5-HT2 antagonist activity. The compound had moderate alpha 1 receptor antagonism, and the potency inhibiting head twitches was about one-third that of ketanserin (1). These results indicate that 5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrimidin-3(2H)-one and 6,7,8,9-tetrahydro-2H-pyrido-[1,2-a]-1,3,5-triazine-2,4(3H)-dione ring systems are useful components of 5-HT2 antagonists.

Animals↗

Syntheses of monocyclic and bicyclic 2,4(1H,3H)-pyrimidinediones and their serotonin 2 antagonist activities.

New serotonine 2 (5-HT2) antagonists with a monocyclic or bicyclic 2,4(1H,3H)-pyrimidinedione have been prepared and their activities evaluated. In a series of monocyclic compounds, 1-substituted 5-phenyl-2,4(1H,3H)-pyrimidinedione 14 showed potent in vitro activity, and the corresponding 3-substituted 5-phenyl and 6-phenyl derivatives 3, 8 and 20a also showed moderate activity. In the bicyclic compounds, 3-substituted 5,6,7,8-tetrahydro-2,4(1H,3H)-quinazolinedione 33 exhibited the most potent activity among the compounds prepared in this paper. The in vivo antagonist activity of 33 was comparable to that of ketanserin, a typical peripheral 5-HT2 antagonist.

Animals↗

Thromboxane A2 synthetase inhibitors. 2. Syntheses and activities of tetrahydronaphthalene and indan derivatives.

A series of 1-imidazolylalkyl-substituted or 5-thiazolylalkyl-substituted tetrahydronaphthalenecarboxylic acid and indancarboxylic acid derivatives were prepared and tested for the inhibitory activities of thromboxane A2 (TXA2) production in vitro and ex vivo. Most of the compounds showed potent TXA2 synthetase inhibitory activities in vitro and had long duration of inhibition of TXA2 production in rats when orally or intravenously administrated. The imidazole analogues had slightly less potency in vitro than the thiazole analogues, but the activities of the imidazole analogues in ex vivo models were equal or superior to the activities of the thiazole analogues. 6-(1-Imidazolyl-methyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate (47a, DP-1904) was chosen for clinical studies.

6-Ketoprostaglandin F1 alpha↗

[Clinical studies on cefodizime in the field of obstetrics and gynecology].

Clinical studies on cefodizime (THR-221, CDZM), a new injectable cephem antibiotic, were performed and the following results were obtained. Ten patients with obstetrical and gynecological infections such as intrauterine infections, pyometra, adnexitis, parametritis and lymphocystitis. The clinical results were evaluated as excellent in 1 case, good in 4 cases and poor in 5 cases. The efficacy rate was 50.0%. Bacteriologically, 10 organisms were isolated from 8 patients and the eradication rate was 44.4%. No side effects were observed in any of the cases treated with CDZM. In laboratory examinations, transient elevations of serum GOT, GPT and Al-P were noted in 1 case.

Adult↗

[Pharmacokinetic and clinical studies on ceftizoxime in the perinatal period].

Pharmacokinetic and clinical studies were carried out on the use of ceftizoxime (CZX) in the perinatal period. The results obtained are summarized below. 1. Mean maternal serum concentrations of CZX reached 57.3 micrograms/ml at about 15 minutes after a single intravenous injection of CZX 1 g and then gradually decreased to 13.1 micrograms/ml in 1 hour and 55 minutes, 3.59 micrograms/ml in 4 hours and 20 minutes and 0.11 microgram/ml in 17 hours and 51 minutes. CZX in umbilical cord serum was at detectable concentrations soon after administration and peaked to 23.5 micrograms/ml in 32 minutes. Although the concentrations in umbilical cord serum gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and more after an injection and was 0.41 microgram/ml at 17 hours and 51 minutes. The CZX in amniotic fluid became detectable a little later than CZX in umbilical cord serum. The concentration of CZX in amniotic fluid was below 1.00 microgram/ml at 30 minutes after administration. Concentrations then gradually increased to 21.3 micrograms/ml in 1 hour and 55 minutes and, even in 17 hours and 51 minutes, they were as high as 9.44 micrograms/ml. 2. In the clinical evaluation, CZX was given to a total of 7 cases, i.e., 1 of amnionitis, 2 of puerperal endometritis, 1 of puerperal fever, and 3 of pyelonephritis. The treatment showed satisfactory results, i.e. excellent result was obtained in 1 case, good in 5 and poor in 1 with an clinical efficacy rate of 85.7%. Microbiological examinations resulted in the isolation of 5 bacterial strains of 4 species and 1 fungal strain from 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical study of imipenem/cilastatin sodium in the perinatal period].

A clinical study was carried out on imipenem/cilastatin sodium (IPM/CS) in the perinatal period, and the results obtained are summarized as follows. IPM/CS was given to 5 cases with puerperal intrauterine infection and 2 with puerperal fever. The clinical efficacies were evaluated as good in 6 cases and poor in 1. The clinical efficacy rate was 85.7%. In a bacteriological examination, 9 strains were isolated from 6 cases, and 7 strains were eradicated with an eradication rate of 77.8%. No side effects were observed in any of the cases treated with IPM/CS.

Adult↗

[Pharmacokinetic and clinical studies on ceftriaxone in the perinatal period].

The pharmacokinetics of ceftriaxone (CTRX) and its clinical efficacy in perinatal infections were studied. The obtained results are summarized as follows. 1. Concentrations of CTRX in maternal serum, umbilical cord serum and amniotic fluid were determined following intravenous injection with 1 g of CTRX. Maternal serum levels were not lower than 100 micrograms/ml immediately after administration, and gradually decreased to about 10 micrograms/ml in 12 hours, and to 4 micrograms/ml in 24 hours. The half-life of CTRX in maternal serum was 5.6 hours. CTRX levels in umbilical cord serum were about 7 micrograms/ml at 10 minutes after injection, increasing to 12 to 13 micrograms/ml in 12 hours and decreasing to 5 micrograms/ml in 24 hours. CTRX levels in amniotic fluid were slightly lower than those in the umbilical cord serum, and about 2 micrograms/ml at 10 minutes after injection, and they remained at 4 to 8 micrograms/ml thereafter for 28 hours. 2. CTRX (1 g) was intravenously administered twice daily to 9 patients with perinatal infections for 3 to 7 days. Clinical efficacies of CTRX were judged excellent in 2 cases and good in 7, suggesting that CTRX was effective in all cases. No side effects or laboratory abnormalities were observed in any case. As a result of these findings, CTRX may be considered a very useful antibiotic in perinatal infections.

Amniotic Fluid↗

[Fundamental and clinical studies on cefuzonam in the field of obstetrics and gynecology].

Fundamental and clinical studies on cefuzonam (CZON, L-105), a new oxime type cephalosporin, were performed and the results obtained are summarized below: 1. Concentrations of CZON were determined in serum, internal genital organs and retroperitoneal fluid after a single intravenous administration of 1 g dose. The peripheral serum level of CZON was 74.0 micrograms/ml at 15 minutes after the administration. A sufficient transfer of CZON into internal genital organs and retroperitoneal fluid was demonstrated. 2. In clinical trial, CZON was given to 11 cases with obstetrical and gynecological infections. Efficacies were evaluated as good in 9 cases and poor in 2 cases. No side effects were observed in any of the cases treated with CZON. In laboratory examinations, transient elevation of serum GOT, GPT and alkaline phosphatase was noted in 1 case.

Adult↗

[Study on tissue transfer of ceftizoxime suppository in the field of obstetrics and gynecology].

A pharmacokinetic study on ceftizoxime suppository (CZX-S), a new rectal suppository of ceftizoxime (CZX), was carried out in the field of obstetrics and gynecology. Concentrations of CZX after single rectal administrations of a 500 mg dose in peripheral venous serum, uterine arterial serum and internal genital organs of 15 patients who received simple panhysterectomy were examined. Peak levels of CZX in peripheral venous serum were 7.26 to 8.88 micrograms/ml at 30 minutes after the administration. Concentrations of CZX in internal genital organs reached 2.12 to 8.96 micrograms/g at 30 minutes after the administration and then decreased slowly, but still remained at 0.37-3.12 micrograms/g after 4 hours.

Adult↗

[Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

Fundamental and clinical studies on imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic, were performed and the following results were obtained. Concentrations of MK-0787 and MK-0791 in serum, internal genital organs and retroperitoneal fluid were determined after a 30 minutes drip infusion of 500 mg/500 mg dose. Venous serum levels of MK-0787 and MK-0791 were 47.3 to 67.5 micrograms/ml and 44.2 to 61.4 micrograms/ml, respectively, at the end of the administration. Sufficient transfer of MK-0787 and MK-0791 to internal genital organs and retroperitoneal fluid was demonstrated. In clinical trials, MK-0787/MK-0791 was given to 18 cases with obstetrical and gynecological infections, such as endometritis, puerperal fever, pelvic peritonitis, parametritis and lymphocystitis. The clinical efficacy was evaluated as excellent in 1 case, good in 14 and poor in 3. The efficacy rate was 83.3%. In a bacteriological study, 43 strains were isolated from 16 cases and the eradication rate was 61.1%. No side effects were observed in any of the cases. In laboratory findings, a transient elevation of GOT, GPT was noted in 1 case. From the above results, it was concluded that MK-0787/MK-0791 was useful drug for infections in the field of obstetrics and gynecology.

Adult↗

[Pharmacokinetic and clinical studies of cefotiam in the perinatal period].

Pharmacokinetic and clinical studies on cefotiam (CTM) in the perinatal period were performed and results obtained are summarized below. Concentrations of CTM in maternal serum, umbilical cord serum and amniotic fluid were examined after a bolus intravenous administration at a dose of 1 g. Data were analyzed using simulation curves drawn by the two- or three-compartment open model. The peak level of CTM in maternal serum was 86.6 micrograms/ml and the half-life of the beta-phase was 0.91 hour. Peak levels of CTM in umbilical cord serum and amniotic fluid were 20.8 micrograms/ml at 0.1 hour and 9.2 micrograms/ml at 3.2 hours after the administration, respectively. The concentration of CTM in amniotic fluid decreased after reaching the peak, but it was still as high as 1.6 micrograms/ml even at 12.0 hours after the administration. These results clearly demonstrated that the transfer of CTM to umbilical cord serum and to amniotic fluid was efficient in protection of perinatal infections. In a clinical trial, CTM was given to 11 patients with perinatal infections. Clinical efficacies were evaluated as excellent in 2 patients, good in 8 patients and poor in 1 patient. No adverse effects were observed in any of the patients studied. In conclusion, CTM was useful and safe antibiotic for the treatment of infections in the perinatal period.

Amniotic Fluid↗

[Fundamental and clinical studies on ceftazidime in the perinatal period].

Fundamental and clinical studies were carried out on ceftazidime (CAZ) in the perinatal period, and the results obtained were summarized below. Following bolus intravenous injection of CAZ 2 g, maternal serum concentrations of CAZ were as high as 145.3 +/- 17.2 micrograms/ml (mean +/- S.D.) at about 10 minutes, and then gradually decreased to 46.7 micrograms/ml at 2 hours, 5.31 micrograms/ml at 5 hours and 4 minutes, and 1.54 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in umbilical cord serum immediately after the administration, and concentrations were 31.0 +/- 1.54 micrograms/ml at about 10 minutes. Although the concentrations gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and later and was 3.00 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in amniotic fluid a little later than in umbilical cord serum, and concentrations of CAZ in amniotic fluid were as low as 1.50 +/- 0.67 micrograms/ml at about 10 minutes after the administration. Concentrations then gradually increased to 12.8 micrograms/ml at 2 hours and 26.5 micrograms/ml at 5 hours and 4 minutes, and even at 11 hours and 10 minutes, they were as high as 14.2 micrograms/ml. The above results demonstrated that the transfer of CAZ through placental barrier was very rapid and satisfactory. Also, CAZ showed good transfer into amniotic fluid, as well as sufficient retention, and was considered to be an effective antibiotic for prophylaxis of both fetal infections and amniotic fluid infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A case of ruptured hepatoma followed by elastase-induced disseminated intravascular coagulation.

In the present study, the first case of ruptured hepatoma followed by disseminated intravascular coagulation is reported. An elastase-like enzyme which possessed elastolytic and caseinolytic activities was confirmed from patient plasma. On the other hand, no elastase activity was detected in the plasma of patients with hepatitis, liver cirrhosis or hepatoma without disseminated intravascular coagulation. The patient plasma did not possess H-D-Val-Leu-Lys-p-nitroanilide hydrochloride, succinyl-L-alanyl-L-alanyl-p-nitroanilide, and pyro-Glu-Pro-Val-p-nitroanilide amidolytic activities. However, when chromatographed on Sephadex G-200, the presence of low-molecular weight plasminogen was confirmed. Its molecular weight was approximately 52,000. A slight decrease of alpha 2-plasmin inhibitor was noted, but no decrease of alpha 2-macroglobulin was detected.

Aged↗

[Interaction of proteases and their inhibitors in the pathogenesis of pancreatitis].

It was confirmed that esterolytic activity was significantly elevated in plasma of patients with acute pancreatitis, which correlated better with the stage of the disease than serum amylase level. Using the several column chromatography procedures, pancreatic kallikrein, trypsin and pancreatic elastase were separated and purified from alpha 2-macroglobulin (alpha 2-M) fractions of patients plasma with acute pancreatitis. From this this result, it was confirmed that kallikrein was liberated into the blood stream from the pancreas during attacks of acute pancreatitis and the liberated kallikrein combined with alpha 2-M. Furthermore, the coexistence of trypsin is required for the complex formation of alpha 2-M and pancreatic kallikrein. It was speculated that alpha 2-M might be decomposed by the excessive amount of elastase, and consequently, might release all of its combining enzymes into the blood stream. In the present study, the activation mechanism of fibrinolytic enzyme system in plasma by human pancreatic elastase was investigated. Elastase not only converted the co-existing plasminogen to low molecular weight plasminogen which could be easily activated by the activators, but also inhibited alpha 2-M and alpha 2-plasmin inhibitor, and consequently, induced the activation of the fibrinolytic enzyme system in plasma. Furthermore, it was also confirmed that elastase could activate plasma kallikreinogen to kallikrein.

Acute Disease↗