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Biomedical subjects

K Ikegami

Publications and source records attributed to K Ikegami.

At least 55 records · Page 3Linked to original sources

[Effects of quinapril on the development of hypertension, cardiac hypertrophy and stroke in salt-sensitive Dahl rats and stroke-prone spontaneously hypertensive rats].

The effects of repeated administration of quinapril (10 mg/kg/day) on the development of hypertension, cardiac hypertrophy and survival rate were examined, and compared with those of enalapril (10 mg/kg) in salt-sensitive Dahl (Dahl S) rats and 1% saline-loaded stroke-prone spontaneously hypertensive rats (SHRSP). The Dahl S rats were treated with the drugs at 10 to 20 weeks of age and the SHRSP, at 8-19 weeks of age. (1) In the Dahl S rats, salt loading rapidly raised systolic blood pressure, which was around 220 mmHg at 10 weeks of age. Both quinapril and enalapril significantly prevented the development of hypertension (below 160 mmHg) and cardiac hypertrophy. Age-associated histopathological alterations in the kidney and mesenteric artery in Dahl S rats were suppressed by the drug treatment. (2) Salt-loaded SHRSP rapidly developed severe hypertension (270 mmHg at 12 weeks of age) accompanied with stroke signs, and 19 animals out of 20 died by the end of the experiment. Both quinapril and enalapril significantly inhibited the age-associated development of hypertension and markedly improved the survival rate (only two animals out of 16 died in both groups). These results suggest that quinapril has protective actions against age-associated development of hypertension and cardiac hypertrophy, and as a result, it prolongs the life span.

Animals↗

Pulmonary edema: pathophysiology, methods of measurement, and clinical importance in acute respiratory failure.

Pulmonary edema is a common component of adult respiratory failure. The edema process is much more complex than simply excess water and/or protein crossing the microvascular membrane. The interstitial space itself is an active component of pulmonary edema, as are the alveolar type I and type II cells. Changes in the interstitium are particularly important in increased permeability edema. The clinical measurement of lung water can be performed by a number of methods, each with its own specific advantages and disadvantages. The role of edema itself in lung failure is variable. Depending on the disease, water content correlates well with impaired oxygenation in cardiogenic edema and relatively poorly in increased permeability edema, especially established adult respiratory distress syndrome. Recognition of the mechanisms, measurements, and relevance of lung edema is of considerable importance in the critical care setting.

Acute Disease↗

Trace analysis of quinapril and its active metabolite, quinaprilat, in human plasma and urine by gas chromatography-negative-ion chemical ionization mass spectrometry.

A highly specific and sensitive method for the simultaneous determination of quinapril and its active metabolite, quinaprilat, in human plasma and urine by gas chromatography-negative-ion chemical ionization mass spectrometry is described. Quinapril and quinaprilat were extracted from human plasma and urine by using a Bond-Elut C18 cartridge. The plasma or urine extract was treated with pentafluorobenzyl bromide followed by trifluoroacetic anhydride to convert quinapril and quinaprilat into their pentafluorobenzyl-trifluoroacetyl derivatives, which were analysed by a selected-ion monitoring method using deuterium-labelled internal standards. The limits of quantitation for both quinapril and quinaprilat were 0.05 ng/ml in plasma and 0.5 ng/ml in urine. The proposed method is applicable to pharmacokinetic and clinical pharmacological studies with satisfactory reliability.

Angiotensin-Converting Enzyme Inhibitors↗

Determination of dioxopiperazine metabolites of quinapril in biological fluids by gas chromatography-mass spectrometry.

The dioxopiperazine metabolites of quinapril in plasma and urine were extracted with hexane-dichloroethane (1:1) under acidic conditions. Following derivatization with pentafluorobenzyl bromide and purification of the desired reaction products using a column packed with silica gel, the metabolites were analysed separately by capillary column gas chromatography-electron-impact mass spectrometry with selected-ion monitoring. The limits of quantitation for the metabolites were 0.2 ng/ml in plasma and 1 ng/ml in urine. The limits of detection were 0.1 ng/ml in plasma and 0.5 ng/ml in urine, at a single-to-noise ratio of greater than 3 and greater than 5, respectively. The proposed method is applicable to pharmacokinetic studies.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of Y-20811, a thromboxane A2 synthetase inhibitor, on experimentally induced coronary thrombosis in anesthetized dogs.

The effects of Y-20811, a selective inhibitor of thromboxane A2 (TXA2) synthetase, on blood flow and local levels of immunoreactive thromboxane B2 (i-TXB2) and 6-keto prostaglandin F1 alpha (i-6-keto PGF1 alpha) in the coronary artery were investigated in the canine model of coronary thrombosis. Thrombosis was induced by applying an electric current to the intraluminal surface of the coronary artery. The plasma levels of i-TXB2 and i-6-keto PGF1 alpha were measured distal to the electrode. In the control group, coronary blood flow decreased and finally stopped 207 +/- 53 min (mean +/- S.E.M., n = 5) after the start of current application. The level of i-TXB2 rose before the coronary occlusion. Coronary blood flow did not change significantly in the Y-20811-treated group (1 mg/kg i.v.). The level of i-TXB2 decreased and remained significantly lower than that in the control group. The level of i-6-keto PGF1 alpha tended to increase slightly in the Y-20811-treated, but not in the control group. The weight of the thrombus in the Y-20811-treated group was significantly less than that in the control group (P less than 0.01). These results suggest that Y-20811 prevents coronary thrombosis by the inhibition of TXA2 production around the electrically injured lumen of the coronary artery.

6-Ketoprostaglandin F1 alpha↗

Inhibitory effect of 2-hydroxypropyl-beta-cyclodextrin on crystal-growth of nifedipine during storage: superior dissolution and oral bioavailability compared with polyvinylpyrrolidone K-30.

To prevent the crystal-growth of nifedipine during storage, 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was employed as a hydrophilic drug carrier and compared with polyvinylpyrrolidone K-30 (PVP). Amorphous nifedipine powders were prepared by spray-drying with HP-beta-CyD or PVP, and their crystal-growing behaviour at accelerated storage conditions were examined by X-ray diffraction analysis and microscopy. Although PVP initially retarded the crystallization of nifedipine, it failed to control the increase of crystal size after prolonged storage at 60 degrees C, 75% r.h., resulting in a remarkable decrease in dissolution rate in water. In sharp contrast, a relatively fine and uniform size of nifedipine crystals was maintained in the HP-beta-CyD system even after accelerated storage conditions. The enhanced dissolution observed for all the HP-beta-CyD systems in a dissolution medium containing 0.1% non-ionic surfactant HCO-60 were clearly reflected in the in-vivo absorption of nifedipine following oral administration to dogs. These results suggest that HP-beta-CyD is particularly useful in solving problems encountered on storage of amorphous nifedipine in solid dosage forms.

2-Hydroxypropyl-beta-cyclodextrin↗

Structural and functional role of the amino-terminal region of porcine cytosolic aspartate aminotransferase. Catalytic and structural properties of enzyme derivatives truncated on the amino-terminal side.

In porcine cytosolic aspartate aminotransferase, a dimeric enzyme, the amino-terminal region anchoring onto the neighboring subunit is linked to the adjoining floppy peptide segment (residues 12-47), an integral part of the small domain whose facile movement upon substrate binding is a striking "induced fit" feature of this enzyme. To assess the contribution by the amino-terminal region to small domain movement and protein stability, a series of enzyme derivatives truncated on the amino-terminal side (residues 1-9) was prepared by using oligonucleotide-directed in vitro mutagenesis. Deletion of residues 1-3 showed no effect on catalytic activity and heat stability. Del 1-5 mutant enzyme with an extra methionine at position 5 showed only 43% of the kappa cat value (in the overall transamination) of the wild-type enzyme. Further deletion up to residue 9 resulted in a slight decrease in kappa cat values. Del 1-9 mutant enzyme still retained a kappa cat value of 33% that of wild-type enzyme. Km values for aspartate and 2-oxoglutarate increased sharply upon deletion of residues 1-9. Accordingly, Del 1-9 mutant enzyme showed a striking decrease in the kappa cat/Km value, to only 2% of that for the wild-type enzyme. Deletion of amino-terminal residues 1-9 resulted also in a large decrease in thermostability and in an enhanced susceptibility to limited proteolysis by protease 401, which is known to cleave at Leu20 of the wild-type enzyme. These findings indicate that an increase in the conformational freedom of the floppy segment (residues 12-47) would occur upon the loss of most of the anchorage region, thereby presenting an entropic barrier to conformational changes that facilitate substrate binding with high affinity.

Amino Acid Sequence↗

A miniature Clark-type oxygen electrode using a polyelectrolyte and its application as a glucose sensor.

A miniature Clark-type oxygen electrode was fabricated by anisotropically etching silicon. A two-gold-electrode configuration was used and a double-layered gas-permeable membrane was formed directly on the electrolyte, poly(vinyl-4-ethylpyridinium bromide) in the sensitive area. These materials improved the electrode's stability in long-term storage and sterilization tolerance to a practical level. The 90% response time averaged 80 s and residual current 10%, with a good linear calibration curve. The oxygen electrode was also used to make an integrated sensor for the simultaneous determination of glucose and oxygen. The glucose sensor's response time was 50-110 s, with good linearity in glucose concentrations between 56 microM and 1.1 mM at 37 degrees C, pH 7.0.

Biosensing Techniques↗

[Coagula tamponade as a complication of open heart surgery: the clinical significance and diagnostic value of transesophageal echocardiography].

The pathogenesis of low cardiac output failure (LOF) immediately after open heart surgery was studied in 41 patients with LOF and 15 control patients without LOF using echocardiography. In 35 patients, transesophageal echocardiography was also performed. Left ventricular (LV) contraction was impaired in 28 of the 41 LOF patients, in whom LV fractional shortening was less than 25%. In the other 13 LOF patients, however, it was greater than 25%. In 12 of these 13 patients, transesophageal echocardiography revealed that accumulating pericardial coagula were localized in the right side of the heart, deforming the right atrial and ventricular chambers. The LV end-diastolic diameter was significantly less than the control, indicating that the pericardial coagula disrupted the distension of the heart. Emergent coagulotomy was performed in 5 patients, and hemodynamic conditions were improved. In spite of "cardiac tamponade", the wall motion and pressure tracings of the right atrium and right ventricle in these patients differed from those in fluid tamponade. Therefore, this condition should be designated "coagula tamponade." In the other 22 patients in whom transesophageal echocardiography was employed, no coagula were observed. Since pericardial coagula can hardly be detected by transthoracic echocardiography, transesophageal echocardiography is indispensable for diagnosing pericardial coagula noted immediately after open heart surgery.

Adult↗

[Efficacy of transesophageal echocardiography immediately after open heart surgery: diagnosis of coagula tamponade].

Massive pericardial coagula were detected by transesophageal echocardiography in some patients with low cardiac output failure immediately after open heart surgery. Characteristically, the coagula were localized anterior to the right atrium and right ventricle in all patients. The coagula could not be detected by transthoracic echocardiography. Despite of low output, absence of wall motion abnormality of the left ventricle, tachycardia, elevated atrial pressure and small left ventricular cavity lead to diagnose cardiac tamponade by pericardial coagula. Neither the right atrial nor the right ventricular wall showed collapsing motion except the area with pericardial effusion. Massive coagula in the anterior mediastinum produced similar clinical manifestation, but could be differentiated from pericardial coagula by echographic identification of the anterior pericardium. Pericardial coagula were also observed in patients with superior vena cava syndrome, but low right atrial pressure differentiated it from coagula tamponade. In all of the present patients, usual transthoracic echocardiography did not offer any sufficient images for diagnosing pericardial coagula. Transesophageal echocardiography was indispensable for detecting pericardial coagula soon after open heart surgery.

Adult↗

[The second report on Japanese abroad with psychiatric problems: air transportation of Japanese with mental disorders in western Europe].

This is to report on airline travel processes experienced with two Japanese psychotics (schizophrenic) abroad who were treated by the local consulates of Japan, and escorted by Japanese psychiatrists from April to May in 1989. A comparative analysis was made of the two cases from the following six points of view: psychopathology concerning travel, psychiatric evaluation at the time of travel, access to local psychiatric medical services, trust between the patient and escorting physician, method of administering drugs, and cooperation in strategy with the airline company. Results indicate that the following three points are crucial in the air transportation of Japanese psychotics: 1) Establishment of patient-escorting physician trust relationship, 2) Adequate sedation through sufficient administration of tranquilizers, 3) Establishment of communication and close cooperation with the airline company.

Adult↗

[Renovascular hypertension. Changes and prognosis of the surgical treatment].

We investigated 663 patients with renovascular hypertension (349 males and 314 females), who were surgically treated at 73 institutions of Urology or Surgery in Japan from 1963 to 1988. There were 294 cases with fibromuscular dysplasia (FMD), 178 with atherosclerosis (SC), 104 with aortitis syndrome (AO) and 87 with other causes. The mean age was 27 years old for FMD, 52 years for SC and 29 years for AO. Thirteen % of FMD, 19% of SC and 38% of AO had stenoses in both renal arteries. Since percutaneous transluminal angioplasty (PTA) has begun in early 1980's, the number of operative cases has been decreased, especially in the case of FMD due to a good result by PTA. Nephrectomy was done in 38% of 704 operations. Aortorenal bypass and autotransplantation were performed in 49% and 26% of the rest, respectively. Recently, autotransplantation has increasingly been applied for complicated vascular lesions. As regards prognosis of the surgical treatment, 77% of FMD, 59% of SC and 50% of AO presented normal blood pressure with or without antihypertensive drugs at least for 10 years after an operation. However, among the patients with normal blood pressure who were observed for more than 5 years, 30% of FMD, 56% of SC and 44% of AO had taken antihypertensive drugs. Eleven patients (1.7% of all) died within one month after the operation, 5 patient of whom had bilateral stenoses. In conclusion, PTA is the first choice for renovascular hypertension and surgery has been done for more difficult and complicated cases in which PTA is ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Mental disorders of Japanese people in western Europe].

As the number of Japanese going abroad has increased in recent years, so has there been an increase in the number of Japanese who seek for help at the Consulate of Japan due to problems relating to mental disorders. Three Consulates in Europe (London, Madrid, Paris), that had experience dealing with mental disorder cases, which had been brought for various reasons, were visited in order to investigate the state of the situation among Japanese with mental disorders in Europe. The following findings were obtained: 1. The number of mental disorder cases treated by the Consulates of Japan in Europe from April 1988 to March 1989 was 37 out of the total 147 in the whole world or 25%. 2. Among them were 7 cases in Great Britain (London), 5 cases in Spain (Madrid), and 11 cases in France (Paris), all of which required tremendous effort to resolve. 3. Among possible additional measures that are needed are support by local Japanese Organizations, development of a system of medical care manned by Japanese physicians on a rotation basis, a medical escort system for returning patients to Japan, overseas insurance and telephone counseling as well as measures to prevent manifestation of mental disorders overseas.

Adult↗

[Venous return and collapse of the right heart in cardiac tamponade].

To elucidate the characteristics of venous inflow into the heart in cardiac tamponade, transmitral (TMF), transtricuspid (TTF) and superior vena cava (SVC) flows were examined using pulsed Doppler echocardiography in nine mongrel open-chest dogs. Cardiac tamponade was produced by the slow infusion of warmed normal saline into the pericardial sac. With increment of pericardial infusion, right atrial collapse (RAC) developed followed by right ventricular collapse (RVC). The systemic blood pressure became depressed and the left ventricular end-diastolic diameter decreased, even in the RAC state, indicating that RVC is not of the primary significance for cardiac tamponade. Characteristically, peak velocities of TMF and TTF in early diastole decreased concomitantly with RAC and RVC. Neither early diastolic filling time nor its acceleration time was altered during tamponade. These changes in blood flow were accompanied by decrements of transmural filling pressure and abnormal motion of the right ventricle. In SVC flow, the diastolic wave characteristically disappeared. This change seemed to be a reflection of the decrease in peak velocity of early diastolic filling flow into the right ventricle. That is, impairment of cardiac relaxation during cardiac tamponade is represented as decreased filling flow velocity in early diastole.

Animals↗

A study on limulus amebocyte lysate (LAL) reactive material derived from dialyzers.

The amebocytes of horseshoe crab (Limulus) hemolymph contain a coagulation system highly sensitive to bacterial endotoxins. Limulus amebocyte lysate (LAL) reactive material derived from cuproammonium rayon membranes, however, is not an endotoxin and acts upon the alternative pathway in the coagulation cascade found in Limulus amebocyte lysate. This study confirmed these facts by using the coagulation system of Limulus without factor G, which is a substrate of the alternative pathway. LAL reactive material lingered in the circulation for a relatively long time. In acute hemodialysis, its plasma concentration increased by an average of 100 pg/ml with each dialysis and eventually reached a plateau of approximately 300 pg/ml. In patients with chronic renal failure under regular hemodialysis, the mean level of LAL reactive material was 330.0 +/- 8.0 pg/ml before hemodialysis which increased by 70.6 +/- 20.7 pg/ml after four hours of hemodialysis.

Acute Kidney Injury↗

False-positive result in Limulus test caused by Limulus amebocyte lysate-reactive material in immunoglobulin products.

Limulus amebocyte lysate (LAL)-reactive material other than endotoxin was detected in the plasma and urine of patients after intravenous immunoglobulin therapy. Thirty-seven vials of six different immunoglobulin products were analyzed for the LAL-reactive material by combined use of a conventional chromogenic Limulus test and a chromogenic endotoxin-specific test. The amount of LAL-reactive material in reconstituted immunoglobulin solutions ranged from a mean (standard deviation) of 10.2 (2.1) to 2,448.1 (988.9) pg/ml, and there were statistically significant differences among the six brands. The levels of LAL-reactive material in plasma increased in proportion to the amounts contained in the immunoglobulin products administered. The material accumulated in the blood with repeated administration. Urinary excretion of the material was less than 5% of the total amount administered. Such material seems to be derived from the cellulose-based membranes used during preparation of the blood products. Thus, interpretation of Limulus test results of patients receiving immunoglobulin therapy requires special consideration.

Adult↗

Effects of caffeine on the vascular smooth muscles isolated from two-kidney, one-clip renovascular hypertension in rabbits.

To examine the intracellular calcium content of the vascular smooth muscle in the chronic phase of renovascular hypertension, the effects of caffeine on isolated aortic, renal and iliac arterial strips were evaluated in two-kidney, one-clip renovascular hypertension in rabbits. 10 weeks after left renal artery constriction in the constricted group, systemic blood pressure (BP) was significantly higher than in the control group, but plasma renin activity was similar to the control value. The amplitude of caffeine-induced contraction of various vascular strips in the constricted group gradually increased and, at 10 weeks, this was higher in the constricted group than in the control group. In the constricted group, sodium loading produced BP elevation and increased the amplitude of caffeine-induced contraction, whereas sodium constriction decreased BP and the amplitude. In the control group, altered sodium intake did not affect BP and the amplitude of caffeine-induced contraction. These results suggest that in the chronic phase of renovascular hypertension, the increased caffeine-sensitive intracellular calcium store on vascular smooth muscle, which is increased by sodium loading and is decreased by sodium restriction, may contribute to the maintenance of hypertension.

Animals↗