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Biomedical subjects

R Okada

Publications and source records attributed to R Okada.

At least 181 records · Page 10Linked to original sources

Unidirectional interaction between flurothyl seizures and amygdala kindling.

In this report, the interaction between flurothyl convulsions and electrical kindling of the amygdala was investigated. Three flurothyl convulsions decreased the afterdischarge threshold of the amygdala and enhanced the rate of development of electrical kindling without affecting the intensity of postictal refractoriness. On the other hand, 3 generalized kindled convulsions did not alter the flurothyl convulsive threshold. The data suggest that the influence of generalized convulsions on future seizure susceptibility may depend on the agents used to induce the convulsions.

Amygdala↗

Ventromedial thalamic lesions and seizure susceptibility.

Recent data indicate that the substantia nigra is an important site in a circuitry involved in the modification of various experimental seizures with neocortical and limbic involvement. Since there are no direct nigral projections to either area, we assumed that the nigral effects on seizures are relayed by other sites such as the thalamus. To evaluate this hypothesis we produced bilateral high-radiofrequency thermocoagulative lesions of the ventromedial (VM) thalamic nuclei which receive the nigral efferents in the rat. We determined the susceptibility of lesioned and control adult rats to the development of flurothyl seizures 2 and 4 weeks later. The latency to the onset of a generalized seizure was considered as the convulsive threshold. There were no differences in the mean latencies between the groups. The results suggest that bilateral destruction of the VM thalamic nuclei does not modify the susceptibility to the development of flurothyl seizures in the rat.

Animals↗

Comparison of three semiautomatic methods for determination of left ventricular ejection fraction from gated cardiac blood pool images.

A number of computer programs exist for the determination of ejection fraction from gated blood pool images. Three commercially available algorithms were compared on the same radionuclide data from 50 catheterized patients. The methods used were: (1) simple thresholding, (2) second derivative edge determination, and (3) a combination of these two. There was good correlation with catheterization ejection fraction for all three methods using smoothed data [r = 0.781, 0.77, 0.84 respectively (P less than 0.01)]. However, interobserver variance was significantly decreased (P less than 0.01) by use of the second derivative method when compared with the other two methods and catheterization. Thus, if accuracy and low interobserver variance are required, then a combination of a second derivative and thresholding method is preferable.

Cardiac Catheterization↗

Myocarditis in autopsy.

In the Annuals of Autopsy Records for Japan from 1958 to 1977, 377,841 autopsy cases were registered; a short summary of pathologic findings was included. Of the 377,841 cases, 409 (0.11%) were registered as idiopathic, nonspecific, interstitial, or viral myocarditis and 25 cases (0.007%) as giant-cell myocarditis. The annual incidence of the myocarditis varied at 5-year intervals and a remarkable increase was observed after 1974. An analysis of 19 cases of myocarditis and 19 of postmyocarditic cardiomegaly (PMC) showed a preponderance of males. Dilatation of ventricles was found in all cases of acute, subacute, and healing myocarditis, which histologically showed interstitial mononuclear cell infiltration, necrosis, and disarray of myocytes. Hypertrophy with ventricular dilatation, ventricular dilatation without hypertrophy, endo- or epicardial involvement, and right ventricular lipomatosis were found in 70%, 20%, 30%, and 10% of cases with chronic myocarditis and PMC, respectively. In these cases, residual inflammation, fibrosis, and hypertrophy was observed histologically.

Adolescent↗

The effect of adding mannitol or albumin to a crystalloid cardioplegic solution: a prospective, randomized clinical study.

To determine if the myocardial protection afforded by a cold crystalloid potassium cardioplegic solution could be improved by the addition of either mannitol or albumin, a prospective clinical study was undertaken in which 58 patients undergoing elective aortocoronary bypass were randomized to one of three groups. Each group featured a different cardioplegic solution. The solutions were a standard potassium crystalloid solution, a solution containing mannitol sufficient to raise the osmolality by 20 to 30 mOsm, and a solution containing 5% albumin. Preoperative, intraoperative, and postoperative evaluation included serial measurements of ejection fraction, myocardial-specific isoenzyme, and hemodynamic indexes of performance. Electrocardiographic evaluation for perioperative myocardial infarction and the need for postoperative inotropic and mechanical support were also included. No differences were found among the groups. Therefore, although the use of mannitol or albumin has been shown to be beneficial in an experimental setting, superiority of either additive could not be demonstrated clinically.

Albumins↗

The synthesis and evaluation of radioiodinated 14-(iodophenyl)-3-(R,S)methyltetradecanoic acid.

Radiohalogenated fatty acids (FA) labelled with gamma-emitting isotopes have a potentially important application in studies of impaired myocardial perfusion and metabolism. Evaluation of straight-chain fatty acids radiolabelled in different positions on the FA chain has been reported by many groups. In this paper we extended our recent studies using the betamethyl branched-chain fatty acid. The synthesis, labelling and preliminary evaluation of 131I- and 123I-14-(iodophenyl)-3-(R,S)methyltetradecanoic acid (I-PBMTA) are reported. This radiolabel concentrates in the mouse myocardium with 16% injected dose g-1 and 11% injected dose g-1 at 15 and 30 min, respectively. The images of the canine heart postinjection indicate a high myocardial extraction of the label with activity retained over an hour. The rate of washout of the activity from the heart was very low. This analogue is a potential agent for myocardial imaging studies.

Animals↗

Improvement of bioavailability of poorly absorbed drugs. II. Effect of medium chain glyceride base on the intestinal absorption of cefmetazole sodium in rats and dogs.

The effect of medium chain glyceride (MCG) on the intestinal absorption of cefmetazole sodium (CMZ) was investigated in rats and dogs. In rats, MCG containing glyceryl mono-, di- and tri-caprylate enhanced the intestinal absorption of CMZ after intraduodenal administration, though the promoting effect of MCG was less than that after rectal administration. The promoting effect of MCG was found to be mainly due to glycerylmonocaprylate and dependent on the dosage of MCG. The plasma CMZ levels after intraduodenal administration as MCG solution tended to be slightly higher than those observed after administration as MCG emulsion, though the differences were found to be statistically insignificant. Moreover, the intestinal absorption of CMZ after intraduodenal administration as MCG emulsion was decreased significantly by increasing the amount of water in the emulsion. The promoting effect of MCG in dogs was more clearly demonstrated in the lower intestine than in the upper intestine. Furthermore, the oral bioavailability of pharmaceutical formulations of CMZ was also investigated in dogs. When enteric coated capsules filled with MCG solution were administered to dogs, the bioavailability of CMZ was enhanced significantly.

Animals↗

Improvement of bioavailability of poorly absorbed drugs. III. Oral acute toxicity and local irritation of medium chain glyceride.

Oral acute toxicity of medium chain glyceride (MCG) was studied in mice and rats. In mice and rats, clinical signs such as irregular respiration, laxity of movement, staggering gait and loss of righting reflex appeared after single oral administration of MCG at a relatively large dose. The LD50 values determined in male and female mice were 26.9 and 28.5 ml/kg, and in male and female rats were 27.4 and 26.7 ml/kg, respectively. In order to evaluate the biological safety of MCG suppository of cefmetazole sodium (CMZ), its local irritation on the mucous membrane was studied. Primary eye irritation of MCG suppository of CMZ was studied in rabbits. Although mild irritation was seen in conjunctivae, no remarkable changes were observed in cornea and iris. Furthermore, primary effect of MCG suppository of CMZ on the rectal mucous membrane was studied macro- and microscopically. It was observed that remarkable histological changes of rectal mucous membrane by MCG suppository of CMZ were not observed in all animals used.

Animals↗

Improvement of bioavailability of poorly absorbed drugs. IV. Mechanism of the promoting effect of medium chain glyceride on the rectal absorption of water soluble drugs.

The mechanisms of the promoting effect of medium chain glyceride (MCG) containing glyceryl mono-, di- and tri-caprylate on rectal absorption of water soluble drugs were investigated. It was found that the solubility behavior of the drugs in mucosal fluids on the surface of the membrane are critical factor for the enhanced rectal absorption. Moreover, the drugs to be readily absorbed from MCG base may be ones of low partition coefficients to MCG phase as well as high solubility in water. And it was found that MCG can't be absorbed from the rectum, different from oral administration, suggesting an interaction of MCG with absorption membrane, rather than the carrier effect of MCG itself. Furthermore, from the results in the pretreatment experiments and additional administration of MCG alone, it was suggested that the interactions of MCG with the membrane components, as well as the induction of biological or physiological changes, may be at least partly responsible for the promoting effect of MCG.

Animals↗

Improvement of bioavailability of poorly absorbed drugs. V. Effect of surfactants on the promoting effect of medium chain glyceride for the rectal absorption of beta-lactam antibiotics in rats and dogs.

The promoting effects of medium chain glyceride (MCG) on the rectal absorption of beta-lactam antibiotics were compared among various experimental animals (such as rats, rabbits and dogs). The plasma levels of cefmetazole (CMZ) after rectal administration, when MCG was used as the vehicle, significantly increased in all animals, but the bioavailability of CMZ was greatly varied among the animal species; the bioavailability of CMZ in dogs was apparently less than those in other animals (rats = rabbits greater than dogs). However, in dogs, the promoting effect of MCG on the rectal absorption of CMZ increased by addition of nonionic surfactants such as ether-type (Brij 30 and Brij 35) and ester type (Nikkol MYL-10). And the promoting effect of surfactants in the MCG vehicle is not always correlated with blood hemolysis, suggesting contribution of other physicochemical or biological factors.

Animals↗

Magnetic resonance imaging of the interatrial septum and atrial septal defects.

Magnetic resonance images were obtained in six patients with known or suspected interatrial septal defects (ASD) and 33 subjects without congenital heart disease. Image planes were oriented to the long and short axes of the left ventricle and septum and provided reproducible display of pertinent anatomic landmarks. Of the images in 33 control subjects, three (9%) were falsely positive showing apparent ASD. ASDs were correctly identified and localized in all six patients (five secundum, one primum). Long-axis views provided excellent display of the location and diameter of defects. All were confirmed at cardiac catheterization and four at surgery with good agreement in measurement of defect size and location. All showed signs of right-sided volume overload. Five had previous echocardiography, which showed definite or suspected ASD in four.

Adult↗

[Traumatic mitral insufficiency: a case report].

A 25-year-old man was admitted to Juntendo University Hospital with chief complaints of nocturnal dyspnea and shortness of breath on Sept. 22, 1983. He had no history of rheumatic fever or bacterial endocarditis. He was violently kicked in the chest while practicing Shorinji-Kempo (Karate) in July 1977. His heart murmur was first noticed in April 1978, but he was asymptomatic for six years after the accident until transient nocturnal dyspnea developed January 1983. Physical examination on admission revealed a grade 4/6 apical holosystolic murmur, a markedly accentuated third sound, and hepatomegaly of two finger breadth in the right midclavicular line. An electrocardiogram revealed sinus tachycardia (100/min), left atrial overload and left ventricular hypertrophy. Chest radiography showed slight cardiac enlargement with a cardiothoracic ratio of 55%, and slightly increased pulmonary vascular markings. Two-dimensional echocardiography showed a markedly prolapsed posterior mitral leaflet and fluttering in diastole. Cardiac catheterization showed elevated pressure of pulmonary capillaries (a: 16, v: 30, mean: 19 mmHg), the pulmonary artery and the right ventricle. Left ventriculography revealed grade four (Sellers) mitral regurgitation. Mitral valve replacement was performed on October 13, 1983. A chorda tendinae supporting the posterior leaflet of the mitral valve was found to be ruptured just above its origin from the posterior papillary muscle. Histological examination of the resected valve showed increased spongiosa tissue which mimicked so-called myxomatous changes, but it seemed preferable to interpret this as a "secondary change due to increased hemodynamic stress" rather than the "primary change".

Adult↗

Kainic-acid-induced seizures: a developmental study.

Developmental dose-response curves for kainic-acid-induced seizures were generated in rats. Rats at 15-18 days (pups), 33-37 days ( pubescents ) and over 90 days (adults) were administered kainic acid intraperitoneally. Seizures were elicited in all 3 age groups, but some of the behavioral manifestations differed in the pups. This group also had the lowest convulsive threshold, the most severe seizures and the highest mortality. Forelimb convulsions and status epilepticus were associated with the occurrence of necrotic lesions in the adults and pubescents but not in the pups. Deoxyglucose (DG) autoradiographic studies of the convulsing rats disclosed differences in the DG uptake pattern of the substantia nigra across the 3 age groups. Increases in the DG uptake were present in the two older age groups but not in the pups. Since recent data have implicated the substantia nigra as a crucial site in a seizure modifying circuitry in adult animals, our results suggest that the lack of substantia nigra involvement in the pups may account for the early generalization and the increased severity of seizures in this age group.

Animals↗

Infantile status epilepticus and future seizure susceptibility in the rat.

The long-term effects of infantile seizures on the development of seizures in adulthood were studied in rats. Infantile seizures of varying severity were induced with intraperitoneal injections of kainic acid in 15-day-old rats. In adulthood the seizure susceptibility of the rats was determined by kindling the left amygdala and by measuring their ability to resist recurrent seizures. The results suggest that infantile status epilepticus is associated with a very high mortality; however in the surviving rats, infantile seizures even as severe as status epilepticus do not cause neuronal brain damage and do not predispose to the development of convulsions later in life.

Age Factors↗

Improvement of bioavailability of poorly absorbed drugs. I. Effect of medium chain glyceride base on the rectal absorption of cefmetazole sodium in rats.

The effect of medium chain glyceride on the rectal absorption of cefmetazole sodium is investigated using an in situ experiment in rats. Each glyceride component of medium chain glyceride was separated using a high-performance liquid chromatographic method. The promoting effect of medium chain glyceride was found to be mainly due to glycerylmonocaprylate and dependent on the concentration of glycerylmonocaprylate. When cefmetazole sodium in medium chain glyceride solution was administered into the rectal lumen of rats, rapid absorption of the drug was observed leading to a residual amount of about 45% at 15 min after administration. The promoting effect of medium chain glyceride was found to be more effective in the rectum than in the small intestine.

Animals↗