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Biomedical subjects

M Tsukamoto

Publications and source records attributed to M Tsukamoto.

At least 145 records · Page 8Linked to original sources

Angiotensin-converting enzyme inhibitors: synthesis and biological activity of N-substituted tripeptide inhibitors.

A new series of highly potent angiotensin-converting enzyme (ACE) inhibitors, 1-(N2-substituted L-lysyl-gamma-D-glutamyl)octahydro-1H-indole-2-carboxylic acids, was synthesized; various acyl groups were introduced at the alpha-amino group of the N-terminal P1 Lys. The effect of the N2-acyl groups on in vitro inhibitory activity and oral antihypertensive effect was examined. All of the synthesized N-acyl tripeptides were found to have in vitro inhibitory activity at an approximately nanomolar level, and showed antihypertensive potency in renal hypertensive rats at a dose of 10 mg/kg, when administered orally. Among them, compounds 7e, g and 9f, i, m showed potent and long-lasting antihypertensive effects compared with enalapril (2a). Their structure-activity relationships are also discussed.

Angiotensin-Converting Enzyme Inhibitors↗

A new mutant, White larva, of the mosquito Toxorhynchites splendens: genetics and cannibalism.

A strain of a new body-color mutant, white larva (wl), was established from a field-collected wild-type strain of Toxorhynchites splendens. The mutant can be distinguished from the wild type in both the larval and pupal stages, but not in the adult. Crossing experiments confirmed its mode of inheritance to be a single recessive system. This is the first visible mutant found in Tx. splendens. Larvae of the wl phenotype seem to be recognized as prey by other individuals in mass larvae rearing.

Animals↗

[Long-term results of mitral valve replacement using glutaraldehyde-treated porcine bioprostheses--comparison of the Hancock and the Liotta valves].

Long-term results of mitral valve replacement using glutaraldehyde-treated porcine bioprostheses were evaluated. The subjects were 77 patients with the Hancock valve (Hancock group) and 60 with the Liotta valve (Liotta group) who survived operation. The maximum follow-up was 14 years and 8 years, and the cumulative follow-up was 631 patient-year (p-y) and 301 p-y in the Hancock and Liotta groups. The actuarial survival rate at 8 years was 80.1 +/- 4.6% for the Hancock group and 88.1 +/- 4.2% for the Liotta group, and there was no significant difference in survival rate between the both groups. The actuarial survival rate at 14 years was 74.3 +/- 5.9% for the Hancock group. The valve-related complications in the Hancock and the Liotta groups were as follow; thromboembolism 1.9%/p-y vs 1.3%/p-y, bleeding 0 vs 0.7%/p-y, perivalvular leak 0.3% vs 0, infection 0.3%/p-y vs 0.7%/p-y, primary tissue failure (PTF) 3.3%/p-y and all valve-related complications 5.9%/p-y vs 6.0%/p-y. There was no significant difference in valve-related complications between the both groups. However, the actuarial event free rate of PTF was significantly lower in the Liotta group than the Hancock group between 4 and 7 years after operation (100% vs 88.8 +/- 4.3% in the 4th year p less than 0.01, 87.7 +/- 4.4% vs 73.5 +/- 8.0% in the 7th year, p less than 0.05). Although the both anti-thrombogenicity and anti-inflammation were acceptable in the porcine bioprostheses, this prosthesis is now used only in the selected patients because of the limited long term durability of this valve.

Adult↗

[Report of a case successfully weaned from long left ventricular assist with complete recovery after coronary artery bypass grafting].

A 45-year-old female underwent coronary artery bypass grafting (CABG) due to medically uncontrollable unstable angina. After completion of CABG, left ventricular contraction was remarkably diminished to maintain systemic circulation. Because intraaortic balloon pumping and veno-arterial bypass with large amount of catecholamines could not improve left ventricular wall function, we decided to use left ventricular assist device (LVAD). After application of LVAD, the patient could easily be weaned from cardio-pulmonary bypass. LVAD was used for 25 days and the patient was successfully weaned from LVAD too, and are now living 6 months postoperatively. As far as we know, this case is the first survival patient after the longest cardiac assist in our country.

Acute Disease↗

[Plasma and tumor gastrin in patients with primary hyperparathyroidism].

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.

Calcium↗

Enhancement of arterial thrombolysis with native tissue type plasminogen activator by pretreatment with heparin or batroxobin: an angioscopic study.

The enhancement of canine arterial thrombolysis with native tissue type plasminogen activator (nt-PA) obtained from human-derived normal cells by pretreatment with heparin or the defibrinogenating agent, batroxobin, was evaluated with angioscopy. The nt-PA, 0.25 mg/kg, was infused intravenously to lyse 1-hour-old thrombus (eight thrombosed arteries without medication, seven with nt-PA alone, seven with nt-PA and heparin, and seven with nt-PA plus batroxobin). Angioscopy provided a cross-sectional view of the vessel lumen with clear visualization of the thrombus. Thirty minutes after nt-PA infusion, the percent luminal obstruction decreased from 74 to 61 in nt-PA alone (p less than .025), from 77 to 37 in nt-PA plus heparin (p less than .005), and from 79 to 25 in nt-PA plus batroxobin (p less than .005). Fifteen minutes after drug infusion, plasma fibrinogen levels decreased to 89% of preinfusion value in nt-PA alone, to 84% in nt-PA plus heparin, and to less than 5% in nt-PA plus batroxobin. Thus rapid infusion of nt-PA alone provided slight thrombolytic effects. However, heparin and batroxobin showed marked enhancement of thrombolytic effects of nt-PA.

Angiography↗

The thrombolytic effects of native tissue-type plasminogen activator (AK-124) on experimental canine coronary thrombosis.

To evaluate the thrombolytic effects of the native tissue-type plasminogen activator (t-PA), the authors used a thrombus model simulating clinical situations. The native t-PA (AK-124) was obtained from human-derived normal cells. Experimental canine coronary thrombosis was produced by partial constriction and endothelial denudation of the vessel. In 19 dogs, coronary occlusive thrombus was produced. Three hours after total occlusion of the coronary artery with thrombus, the authors attempted the thrombolytic therapy in 16 dogs. Histologically, three-hour thrombus was composed of a mixture of platelet aggregates, fibrin, and blood cells. They infused 0.375 mg/kg t-PA intravenously in 7 dogs and 20,000 IU/kg urokinase (UK) in 9. Coronary recanalization was achieved in 5 (71%) with t-PA infusion and 6 (67%) with UK infusion. Plasma fibrinogen levels decreased to 76% of preinfusion value in the dogs with t-PA infusion and to 34% in those with UK infusion. Coronary reocclusion occurred in 2 dogs with t-PA and 3 with UK. Thus, the native t-PA (AK-124) can provide coronary thrombolysis without severe depletion of plasma fibrinogen levels.

Animals↗

Angiotensin-converting enzyme inhibitors: synthesis and structure-activity relationships of potent N-benzyloxycarbonyl tripeptide inhibitors.

A new series of gamma-D-Glu-containing N-benzyloxycarbonyl (Z) tripeptide inhibitors of angiotensin-converting enzyme (ACE) was synthesized. The effect of varying the antepenultimate amino acid residue in this series on the biological activity was studied. Introduction of Lys and Orn residues at the P1 position provided the most potent inhibitors, 25a and 25b (IC50: 3.5 and 4.9 x 10(-9) M, respectively), which exhibited an oral antihypertensive activity. This result suggests that basic amino acid residues at the P1 position play an important role in binding with the S1 subsite of ACE in this series. Oral antihypertensive activity of selected compounds was evaluated.

Angiotensin-Converting Enzyme Inhibitors↗

Pathogenesis of water-immersion stress-induced gastric ulcers in rats with renal failure.

Rats with or without renal failure, produced by uranyl acetate, were subjected to water-immersion stress for 6 h. The severity of stress-induced gastric ulcers in the renal failure group was significantly higher than that in the control group. The intragastric pH did not significantly differ between the two groups. Transmucosal electrical potential difference, gastric mucosal blood flow, and gastric mucosal hexosamine content in the renal failure group were significantly lower than in the control group. These results suggest that decreases in defensive factors, rather than an increase in an aggressive factor, may be more closely involved in the development of acute gastric ulcers in rats with renal failure.

Acute Kidney Injury↗

[Evaluation of color pattern VECP in deutan].

Using an Equi-Energy-Color Pattern Generator, color vision experiments were performed on nine normal subjects, six cases of deuteranomalies, and six cases of deuteranopias with the use of Visually-evoked cortical potentials (VECPs). Checkerboard patterns, consisting of the pairing of any chosen one of three colors with its complementary color in terms of equal energy, were used. The pairing of a neutral color with its complementary color of protan, deutan and tritan were displayed on a color TV monitor. We measured the amplitude and latency of P100 component of VECPs. Cases of deuteranopia showed significantly smaller amplitude and longer latency of P100 component in protan and deutan responses than did normal subjects. Cases of deuteramomaly showed significantly smaller amplitude and longer latency of P100 component in only protan response compared to those of normal subjects. It was possible to objectively detect the deutan in color pattern VECPs.

Adolescent↗

[An immunohistochemical study of endogenous estradiol and testosterone in human colo-rectal cancer tissues].

An immunohistochemical method (peroxidase antiperoxidase method) was carried out to examine the distribution of endogenous estradiol (E2) and testosterone (Te). One hundred and twenty four (48.2%) of 257 colo-rectal cancer cases, and 36.7% of male cases and 58.4% of female cases revealed E2-immunostain. This immunohistochemical reaction for E2 was found more frequently in female patients than in male patients, while Te-immunostain was found in 15 (17.6%) of 85 colo-rectal cancer cases. E2 and Te were demonstrated mainly in the cytoplasms and occasionally in the nuclei of cancer cells. Since E2 or Te-positive cancer cells were mainly distributed in the deeper or invasive portion of tissue sections, it might deserve further investigation to elucidate a certain relationship between cancer growth and endogenous sex-hormones.

Colorectal Neoplasms↗

Experimental studies on the pharmacokinetics and therapeutic effect of cefbuperazone in biliary infection.

A study was carried out using an experimental biliary infection model to investigate the pharmacokinetic characteristics and therapeutic effect of cefbuperazone in the rabbit. Thirty rabbits were divided into three equal groups; a control group of normal animals, a group of infected animals receiving no cefbuperazone, and a group of infected animals receiving 50 mg cefbuperazone/kg intramuscularly. The experimental infection was made by direct inoculation of a suspension of E. coli into the common bile duct after ligation. The results showed that extremely high levels of cefbuperazone were achieved in bile and tissues of the biliary tract and were higher than those in the blood. Moreover, the levels were maintained at effective concentrations even after 6 hours. Viable bacterial cells from bile and the gall-bladder were barely detectable 24 and 48 hours after infection in the cefbuperazone-treated group, whilst counts remained high in the other infected group. White blood cell counts were increased at 24 hours after infection but were significantly lower in the cefbuperazone-treated group. Histological examination revealed marked inflammatory changes in the gall-bladder and bile duct of infected, untreated animals but few, mild changes only were seen in cefbuperazone-treated animals. Similarly, total bilirubin and liver enzymes were markedly increased in infected animals, but transaminases and alkaline phosphatase were significantly lower in the treated compared to the untreated group. The findings indicate, therefore, that cefbuperazone can be a useful antibiotic in biliary infection.

Animals↗

[Surgical management of acquired tricuspid valve disease--the effects and comparison of tricuspid annuloplasty (De Vega) and tricuspid valve replacement].

A total of 92 patients with tricuspid valvular disease (TR) had surgical repair of DeVega's annuloplasty in 80 patients (87%) and of valve replacement in 12 patients (13%) from January, 1978, to March, 1988. All of those patients were diagnosed by cardiac catheterization and angiogram, clinical findings and in recent cases, pulsed and color Doppler echocardiography were applied. Eighty-nine of 92 patients (97%) were in NYHA class III or IV before operation. There were 7 early death (8.5%) with DeVega procedure and one death (8.3%) in TVR and late deaths were noted in 3 patients (3.6%) (DeVega's procedure) and one (8.3%) in TVR. Two patients after DeVega procedure at 5 and 6 years were required re-operation of TVR because of recurrent mitral valvular disease. Seventy-seven of 80 survivors were in NYHA class I or II postoperatively. Twenty-seven randomized selected patients after DeVega's annuloplasty were investigated by pulsed and color Doppler echocardiography, 17 of them (63%) had no regurgitation and the remaining 10 patient had mild to moderate regurgitation. This study suggests that DeVega's annuloplasty has a simple and reliable procedure in patients with functional TR and results in excellent hemodynamic and functional effects postoperatively.

Adolescent↗