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Biomedical subjects

N Yamazaki

Publications and source records attributed to N Yamazaki.

At least 253 records · Page 14Linked to original sources

Beneficial effect of idebenone (CV-2619) on cerebral ischemia-induced amnesia in rats.

An experimental model of amnesia induced by cerebral ischemia after one-trial passive avoidance learning was established to test the effects of a novel compound, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619), and some commonly used drugs in rats. One day after the vertebral artery was electrocauterized bilaterally, the common carotid artery was transiently occluded bilaterally to produce cerebral ischemia. The amnesia was estimated by the response latency for a rat to step from a light safety compartment to a dark compartment in which a foot-shock was given. The results of the retention test given 24 hr after the ischemia indicated that amnesia was successfully produced when the 200-600 sec ischemia was provided within 20 min after the avoidance learning. The effects of drugs on the amnesia induced by a 200-sec ischemia immediately after the avoidance learning were as follows: CV-2619 (10, 30 mg/kg, i.p. or p.o.) given before the retention test significantly increased the response latency, indicating a reversal effect on the amnesia. Physostigmine (0.1, 0.2 mg/kg, i.p.) and arginine-vasopressin (10 micrograms/kg, s.c.) were also effective, and calcium hopantenate (500 mg/kg, p.o.) showed a slight reversal action. Furthermore, CV-2619 (10 mg/kg, i.p.), given before or after the ischemia, significantly inhibited the appearance of amnesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗

Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia.

The concentrations of acetylcholine (Ach) and choline in various brain regions of rats with and without cerebral ischemia and the effects of 6-(10-hydroxy-decyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the levels of these parameters were investigated. Cerebral ischemia was induced by a 200-sec occlusion of both common carotid arteries in animals in which both vertebral arteries had been permanently cauterized. The concentrations of Ach and choline in the brain were determined by means of pyrolysis gas chromatography. In normal rats, CV-2619 (10, 30 and 100 mg/kg, i.p.) did not alter the concentrations of Ach and choline in the brain regions examined. In the ischemic rats, a significant decrease in Ach and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in the concentration of choline was also observed in the cerebellum and brain stem. Pretreatment with CV-2619 (10 mg/kg, i.p.) inhibited the decrease in Ach and the increase in choline in the forebrain regions. Moreover, the same dose of CV-2619 inhibited the increment of lactate content and tended to inhibit the decrement of ATP content in the cerebral cortex. These results indicate that CV-2619 inhibits alterations of the concentrations of Ach and choline in the brain of the ischemic rats; this inhibition may be due to the ameliorating effect of CV-2619 on the disturbance of cerebral energy metabolism under ischemic conditions.

Acetylcholine↗

Cardiac performance and coenzyme Q10 in thyroid disorders.

To investigate the relationship between serum levels of Coenzyme Q10 and cardiac performance in thyroid disorders, we studied the cardiac performance and assessed serum levels of thyroid hormones and Coenzyme Q10 in 20 patients with hyperthyroidism, 5 patients with hypothyroidism and 10 normal subjects. A significant inverse correlation between thyroid hormones and Coenzyme Q10 levels was found by performing partial correlation analysis. Because low serum levels of Coenzyme Q10 were found in thyrotoxic patients and congestive heart failure may occur as a result of severe hyperthyroidism, 120 mg of Coenzyme Q10 was administered daily for one week to 12 hyperthyroid patients and the change in cardiac performance was assessed. Further augmentation of cardiac performance was found in hyperthyroid hearts, which were already augmented, after the administration of Coenzyme Q10. It appears, therefore, that the Coenzyme Q10 dose actually has a therapeutic value for congestive heart failure induced by severe thyrotoxicosis.

Adolescent↗

Lowering effect of diphenylhydantoin on serum free thyroxine and thyroxine binding globulin (TBG).

To evaluate the effect of anticonvulsants on serum levels of free thyroxine (FT4) and thyroxine-binding globulin (TBG), 32 patients with epilepsy receiving long-term anticonvulsant treatment (mean duration 81.8 +/- 8.9 months) were employed in the present study. The serum levels of total thyroxine (TT4), total triiodothyronine (TT3), T3 resin uptake (T3U) and thyrotrophin (TSH) were also measured. Free thyroxine index (FT4I) was calculated from TT4 and T3U. Mean levels of these thyroid function tests were as follows: 5.52 +/- 1.51 micrograms/dl (TT4), 1.16 +/- 0.32 ng/dl (FT4), 101.5 +/- 16.2 ng/dl (TT3), 27.5 +/- 2.6% (T3U), 19.64 +/- 3.97 micrograms/ml (TBG), 1.50 +/- 0.36 (FT4I) and 2.21 +/- 0.18 microU/ml (TSH). These values except for T3U and TSH were significantly lower than normal values (P less than 0.01). Using correlation analysis, a significant dose-dependency (daily doses) was found between diphenylhydantoin (DPH) and TT4, FT4 and TBG. Other anticonvulsants (barbiturates, carbamazepine, primidone) or duration of treatment were not significantly correlated with thyroid function tests. Therefore serum levels of DPH were also measured in 19 out of 32 patients receiving anticonvulsant treatment. Significant negative correlation was found between serum levels of DPH and FT4 (r = -0.65) and DPH and TBG (r = -0.61).

Adult↗

Effects of L-carnitine on exercise tolerance in patients with stable angina pectoris.

The effects of L-carnitine (900 mg, p.o. daily) on exercise performance were studied in 12 patients with stable effort angina using a multistage treadmill exercise test. Exercise tests were performed at the end of the placebo period and after 4 and 12 weeks of carnitine therapy. While 12 patients experienced angina during treadmill tests in the placebo period, 2 patients were free of angina after treatment with carnitine. The mean exercise time was 11.4 +/- 0.7 min (mean +/- SE) in the placebo period. This increased significantly to 12.2 +/- 0.5 min (p less than 0.05) after 4 weeks and 12.8 +/- 0.5 min (p less than 0.01) after 12 weeks of treatment with carnitine. The time required for 1 mm ST depression to occur was 6.4 +/- 0.9 min in the placebo period. This increased significantly to 7.6 +/- 0.9 min (p less than 0.01) after 4 weeks and 8.8 +/- 1.0 min after 12 weeks of treatment with carnitine. There was significantly less ST segment depression during the same exercise load after 12 weeks of treatment as compared with that in the placebo period (p less than 0.05). The heart rate and the pressure rate product at the same work load showed no significant difference among the 3 testing periods. The results of this study suggest that L-carnitine may improve exercise tolerance in patients with effort angina.

Adult↗

Unstable angina in a patient with mucocutaneous lymph node syndrome.

An 11-year-old boy with mucocutaneous lymph node syndrome, who later developed an acute anteroseptal infarction and unstable angina, is presented. Anginal attacks were shown by 24-hour long-term ambulatory electrocardiographic recording. He was shown to have multiple coronary aneurysms with thrombi, and underwent a successful aorto-coronary bypass.

Aneurysm↗

[Tumor-specific cytotoxicity of tumor infiltrating lymphocytes (TIL) induced with TCGF in murine mammary carcinoma].

A medullary carcinoma with lymphocytic infiltration is associated with relatively good prognosis following radical mastectomy in breast cancer. This suggests that tumor infiltrating lymphocytes (TIL) play an important role in the immunological resistance of the host against cancer. The cytotoxic activities of TIL in murine mammary carcinoma SC42 and SC115 of syngeneic DS mice were assessed with 51Cr release assay in this study. The tumor masses were minced and trypsinized, and lymphoid cell rich fraction was separated with Percoll discontinuous gradient centrifugation. During 10 days culture with T cell growth factor (TCGF) obtained from Con A stimulated rat spleen cells, the tumor cells were collapsed and lymphocytes were expanded. The cultured TIL from SC42 tumor had stronger cytotoxicity against SC42 tumor cells than the cultured TIL from SC115 tumor and the cultured spleen cells of SC42 tumor bearer, and the cultured TIL from SC115 tumor showed predominant activity against SC115 tumor cells. Nonspecific cytotoxic activity and natural killer (NK) activity of these TIL were weaker than the cultured spleen cells. The culture of the spleen cells with the tumor cells and TCGF failed to induce tumor-specific cytotoxic lymphocytes. Moreover, the tumor-specific cytotoxicity was reduced by the treatment of anti thy-1, 2 and complement, and NK activity was reduced by the treatment of anti-asialo GM1 and complement. These results indicate that the tumor-specific cytotoxicity is latent in the T cell population of TIL and is induced by the culture with TCGF.

Animals↗

Diltiazem for treatment of essential hypertension: a double-blind controlled study with reserpine.

In a double-blind, parallel, 12-week trial, antihypertensive effects of diltiazem and reserpine were compared in 107 patients with essential hypertension. Diltiazem reduced blood pressure from 176/100 mmHg to 154/86 mmHg after 12 weeks, and reserpine reduced blood pressure from 171/96 mmHg to 155/85 mmHg. The difference between diltiazem and reserpine was not statistically significant. However, among a subset of patients given 180 mg/day of diltiazem, a significantly better antihypertensive effect was achieved than among a subset given 0.3 mg of reserpine. The incidence of side effects and complications in the diltiazem group was about one half that in the reserpine group (12.3% and 27.1%, respectively). Side effects of diltiazem were mild, and the drug was extremely well tolerated. These results show that diltiazem is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension.

Adult↗

Effects of L-carnitine on tissue levels of free fatty acid, acyl CoA, and acylcarnitine in ischemic heart.

In order to evaluate the protective effects of L-carnitine on ischemic myocardium, its effects on tissue levels of free fatty acid (FFA), acyl CoA, acyl carnitine, and adenosine triphosphate (ATP) were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of left anterior descending coronary artery for 15 min. L-Carnitine (100 mg/kg) was administered intravenously prior to coronary ligation. In ischemic myocardium, tissue levels of free carnitine and ATP decreased, whereas long-chain acyl carnitine, long-chain acyl CoA, and FFA increased. Pretreatment of L-carnitine prevented the decrease in free carnitine and ATP and the increase in long-chain acyl carnitine and long-chain acyl CoA. A positive correlation was observed between ATP and free carnitine. On the other hand, a negative correlation was observed not only between ATP and the ratio of long-chain acyl CoA to free carnitine but also between ATP and the ratio of long-chain acyl carnitine to free carnitine. These results suggest that L-carnitine has protective effects on ischemic myocardium, probably by preventing the accumulation of long-chain acyl carnitine and long chain acyl CoA.

Acyl Coenzyme A↗

Changes in dietary fiber intake among Japanese in the 20th century: a relationship to the prevalence of diverticular disease.

In view of the fact that Japanese dietary patterns have been undergoing rapid "Westernization," in part characterized by decrease in fiber, we assessed dietary and crude fiber content in the Japanese diet using food consumption tables for the period from 1911 to 1980, and studied the trend in the reported prevalence of diverticular disease of the colon. Fiber content declined in diphasic pattern: the first decline, which probably had started in the late 19th century, progressed until the Second World War. Although records during the war period were unavailable, the high fiber content of the Japanese diet in the period immediately after the war reflects the tendency to supplement rice with more fiber-rich cereals, and to increase the amount of rice through reduced polishing during the war time. The second decline in fiber content in the Japanese diet, which started in the 1950s and progressed throughout the period of "high economic growth," was mainly due to the decrease in cereal consumption. The changes in crude fiber content in the Japanese diet after the Second World War resemble the pattern of rapid decline noted in the United States during the 1930s to the 1950s. The prevalence of diverticular disease in both countries also shows sudden steep upward turns during the period between 1930 and 1950 in the United States and the late 1970s in Japan, suggesting the presence of threshold level(s) of fiber intake for the effective prevention of diverticular disease. The prevalence of diverticular disease is still relatively low in Japan. However, if the current dietary trend continues, it may rise to a level currently found in the "Western" countries in the coming few decades.

Dietary Fiber↗

Host-Pathogen Interactions : XXIV. Fragments Isolated from Suspension-Cultured Sycamore Cell Walls Inhibit the Ability of the Cells to Incorporate [C]Leucine into Proteins.

A bioassay to measure the incorporation of [(14)C]leucine into acid-precipitable polymers of suspension-cultured sycamore (Acer pseudoplatanus L.) cells is described. Using this assay, cell wall fragments solubilized from sycamore cell walls by partial acid hydrolysis are shown to contain components that inhibit the incorporation of [(14)C]leucine into the acid-precipitable polymers. This inhibition was not attributable to a suppression of [(14)C]leucine uptake. The effectiveness of the wall fragments in inhibiting [(14)C]leucine incorporation was substantially relieved by plasmolysis of the cells. Fragments released from starch and citrus pectin are shown not to possess such inhibitory activities.

Journal Article↗