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Biomedical subjects

H Okuda

Publications and source records attributed to H Okuda.

At least 271 records · Page 15Linked to original sources

Model of electrocardiographic changes seen with subarachnoid hemorrhage in rabbits.

We developed a new method for introducing drugs into the basal cistern of rabbits. With minimal surgical invasion, we used either the opening of the craniopharyngeal duct to access the chiasmatic cistern or the suture between the basisphenoid and basioccipital bones to access the interpeduncular cistern. With our method, 0.5 ml contrast medium injected into three rabbits was determined roentgenographically to remain in the basal cistern; histologically, all the brain tissue remained intact. Intracisternal injection of 0.5 ml physiological saline into five rabbits had no effect on the cardiovascular system. In 23 rabbits, injection of 0.5 ml 0.1% prostaglandin F2 alpha led to a variety of electrocardiographic changes, including sinus bradycardia (in 43.5%), premature atrial contractions (in 17.4%), and premature ventricular contractions (in 39.1%). In 15 rabbits with severe changes, arrhythmia was followed by ST depression (in 30.4%), ST elevation (in 8.7%), T wave inversion (in 4.3%), ventricular tachycardia (in 17.4%), or ventricular fibrillation (in 4.3%). Intracisternal injection of 0.5 ml 1.0% lidocaine into the 23 rabbits was very effective in overcoming bradycardia and arrhythmias. We conclude that the clinical features of electrocardiographic changes seen in patients with subarachnoid hemorrhage are reproducible in this rabbit model.

Animals↗

Teratogenic effect of californium-252 irradiation in rats.

The teratogenicity of californium-252 (Cf-252) irradiation which generates approximately 70% 2.3 MeV fast neutron and 30% gamma rays was evaluated. A single whole body exposure of Cf-252 at various doses was given to pregnant rats on day 8 or 9 of pregnancy, followed by microscopic autopsy of the fetuses at the terminal stage of pregnancy to search for external and internal malformations. For comparison, pregnant rats were irradiated with various doses of cobalt-60 (Co-60) standard gamma rays at the same dose rate (1 rad/min.). The doses were 20-120 rad of Cf-252 and 80-220 rad of Co-60. Using frequency of radiation induced malformations observed on day 8 of pregnancy as an index, relative biological effectiveness (RBE) of 2.3-2.7 was obtained from the straight line obtained by modifying by the least squares method the frequency curves of malformed fetuses in total implants and in surviving fetuses. The types of malformations induced by Cf-252 and Co-60 irradiation were alike. Using fetal LD50 as an index, 2.4 was obtained as RBE when irradiated on day 8 of pregnancy and 3.1 as that when irradiated on day 9. The results showed that Cf-252 had stronger a teratogenic effect than Co-60 gamma rays.

Abnormalities, Radiation-Induced↗

Effects of a diphenyl ether herbicide (CNP emulsion) on mouse fetuses.

We investigated the effects of a diphenyl ether herbicide, a chlornitrophen (CNP) emulsion, on mouse fetuses. An MO emulsion was used as the experimental chemical twenty percent of this herbicide consisting of CNP. CNP and other components were extracted and evaporated (undegraded solution). The chemical was diluted 10 times by deionized water and then exposed to sunlight until the CNP concentration in the mixture became 10% of the initial CNP concentration. CNP, degradation products, and other materials were extracted from the mixture and evaporated (degraded solution). The undegraded and degraded solutions were administered subcutaneously to the backs of pregnant mice from the 6th to 15th fetal day, once daily. The mice were sacrificed on the 18th day of pregnancy. The number of fetuses and implantations, their weights, externals and skeletons were observed. Infant mice born from maternal mice treated in the same way as above were weighed once a week. Mean fetal body weights of the undegraded and degraded solution dose groups were significantly lower than those of the control (p less than 0.001). Fetal skeletal abnormalities were also higher than those of the control. The degraded solution dose group differed particularly in this regard from the control (p less than 0.05). In the degraded solution dose group, all 21 newborn infants from two maternal mice out of a total of 43 newborn infants from four maternal mice died within one week. The above results suggest that the degraded solution of CNP is no less noxious on mouse fetuses than the undegraded solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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

We have conducted pharmacokinetic and clinical trials of a new cephem derivative, cefodizime (THR-221, CDZM), and obtained the following results. 1. We administered CDZM to 4 cases with abdominal simple hysterectomy due to myoma uteri at a dose level of 1 g by drip intravenous injection and studied average levels of transfer measured at various locations in the uterine tissues and adnexa at an average of 2 hours after administration. CDZM level was highest in the oviduct, 13.7 micrograms/g (ratio with respect to the uterine arterial blood: 91.3%), followed by the ovary, portio vaginalis, cervix uteri and endometrium, and was lowest in the myometrium, 8.3 micrograms/g (55.3%). CDZM concentrations were higher than 6.04 micrograms/g in any tissues. 2. To study CDZM transfer to pelvic cavity fluid, we administered CDZM to 5 cases with total hysterectomy due to cervical cancer of uteri at a dose level of 2 g using drip intravenous injection. The drug was transferred at high levels to the pelvic cavity fluid. A level of 11.7 micrograms/ml was observed at 3 hours after injection. The drug levels in the pelvic cavity fluid were maintained continuously higher levels than those of venous blood. These concentrations in the uterine tissues and pelvic cavity fluid were higher than the MIC against many strains of Gram-positive and Gram-negative bacteria, hence we considered them to be therapeutically effective concentrations. 3. Eleven cases of gynecological infections receiving in totals of 8 to 48 g of CDZM demonstrated "excellent" results in 3 cases, "good" in 8 cases. Eight strains of organisms were isolated from 10 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Establishment of osteoblastic cell line (OR-D 3)].

To establish an osteoblastic cell line, new-born mouse calvaria was cultured in alpha MEM with 10% fetal calf serum. Four colonies with marked cell division were formed at the 3rd generation. By the limiting dilution method, eight clones (A1, B1, C1, C2, C3, D1, D2, D3) were obtained. Cells from C3 and D3 had marked alkaline phosphatase activities. After the addition of 10 mM beta-glycerophosphate to the medium, white nodules stained by Kossa's method were formed in D3 dish. Transmission electron microscopy revealed matrix vesicles, collagen fibers and needle-like crystals of hydroxyapatite in these nodules. These findings indicated that D3 clone had the ability of mineralization.

Alkaline Phosphatase↗

The effects of fenitrothion emulsion (organic phosphorous pesticide) and its degraded solution on mice.

Experiments were carried out to examine the effects of degradation products on mice. Fenitrothion (MEP) emulsion, a kind of an organic phosphorous insecticide, adjusted to pH 8, pH 10, and pH 14 were degraded by exposure to natural sunlight. Physiological saline, an untreated MEP emulsion, and the three degraded solutions were prepared as experimental chemicals and were administered subcutaneously at a dosage of 0.1 ml/10 g body weight (BW) into the backs of pregnant mice once a day, from the 3rd to the 15th fetal day. Each dose included 20, 40, or 90 mg/kgBW of MEP and several degradation products of MEP. LD50 was determined according to Behrens' method. The mean fetal body weights of 18th day of pregnancy in 40 and 90 mg/kgBW of MEP of the pH 8 degraded solution were 1.09 and 1.16 g, respectively, significantly lower than that of untreated MEP emulsion (1.27 g). Further, LD50 values of the three kinds of degraded solutions were 60-120 mg/kgBW, much lower than that of the untreated MEP emulsion (410 mg/kgBW). These results indicate that the degradation products of MEP emulsion degraded by the exposure of sunlight have an influence on both adult and fetal mice.

Animals↗

Rubidium (Rb) treatment of rats: biological effects and implications for psychiatry.

Experiments were carried out on rats in order to find out the implications for psychiatry of the basic biological effects of rubidium (Rb). The forced swimming test (FST), used to evaluate the effects on rats of treatment with Rb, was conducted after 1 or 3 mEq/kg Rb was given chronically or subacutely. The weight of rats treated with 1 or 3 mEq/kg Rb, once daily, was observed daily for two weeks. Rb levels in the blood and brain of rats treated with Rb chronically or subacutely were determined by atomic absorption spectrophotometry. The rectal temperature was observed at 30, 60, 90, 120, 180, and 240 min after injections of 1 or 3 mEq/kg Rb. The increase in the mean body weight of treated rats was almost the same as that of the control. The rectal temperature in rats treated with Rb showed a hyperthermic response. With both the 1 and 3 mEq/kg Rb treatments, Rb levels in the brains were significantly higher in the chronic experiments than in the subacute experiments. The experiments conducted to determine the effect of chronic and subacute treatment of Rb are hereafter termed 'chronic experiment' and 'subacute experiment' respectively. Almost the same significant difference was also observed in the Rb levels in the blood. In the FST, a decrease in the mean immobility time was not observed in either the subacute or the chronic experiments. Thus, antidepressant effects, as judged from the FST, were not observed although Rb did actually accumulate in both brain and blood.

Animals↗

p-nitrophenyl butyrate hydrolyzing activity of hormone-sensitive lipase from bovine adipose tissue.

The "esterase" activity of hormone-sensitive lipase (HSL) was studied using water-soluble p-nitrophenyl butyrate (PNPB) as a substrate. Bovine adipose tissue HSL was purified to near homogeneity by precipitation at pH 5.0, followed by chromatography on DEAE-cellulose, phenyl-Sepharose, and high performance ion-exchange columns on Mono Q and Mono S. The purified preparation hydrolyzed emulsified triolein and cholesteryl oleate (CO), and water-soluble PNPB. In the two last steps of purification, the elution profile of the CO-hydrolyzing activity coincided with that of PNPB-hydrolyzing activity. The HSL was adsorbed to heparin-Sepharose and the CO- and PNPB-hydrolyzing activities were eluted together in the same peak. Diisopropylfluorophosphate (DFP) strongly inhibited the HSL activities and the inhibition profiles of the triolein-; CO-, and PNPB-hydrolyzing activities were essentially identical. Only one polypeptide of Mr 84,000 in partial purified HSL fraction was labeled by affinity labeling with [3H]DFP. On digestion of the enzyme with trypsin, the triolein- and CO-hydrolyzing activities were lost more rapidly than the PNPB-hydrolyzing activity. Phosphorylation increased the triolein-hydrolyzing activity to 40% more than that of the control, but did not affect the CO- and PNPB-hydrolyzing activities.

Adipose Tissue↗

Covalent binding of 4-nitrobenzyl mercaptan S-sulfate to the sulfhydryl groups of hepatic cytosolic proteins and bovine serum albumin with mixed disulfide bond formation.

4-Nitrobenzyl [35S]mercaptan S-sulfonic acid ([35S]NBM S-sulfate), a new type of reactive metabolite of the thiol [35S]NBM in rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate, bound rapidly and covalently at pH 7.4 and 37 degrees C to the sulfhydryl groups of rat liver cytosolic proteins with formation of disulfide bonds. From the radioactive proteins was isolated and identified the sole amino acid adduct, S-([35S]NBM)cysteine, after their acid hydrolysis under the anaerobic conditions. Bovine serum albumin (BSA), a model protein with a single SH group, also reacted readily with radioactive NBM S-sulfate to form a disulfide bond in stoichiometric manner. S-([35S]NBM)-cysteine was also isolated and identified as the sole amino acid adduct from the well-washed, radioactive BSA after the same anaerobic acid hydrolysis. A normal hepatic level of GSH not only retarded the BSA-NBM adduct formation completely, but also detached the radioactivity from BSA by the reduction of the disulfide bond with formation of [35S]NBM and its disulfide. Of twenty-one amino acids examined at pH 7.4 and 37 degrees C, only cysteine reacted with NBM S-sulfate and afforded S-(NBM)cysteine with concomitant formations of S-sulfocysteine, cystine, NBM, and its disulfide.

Animals↗