Yoshio Yoshino

Brain eicosanoid levels in spontaneously hypertensive rats after ischemia with reperfusion: leukotriene C4 as a possible cause of cerebral edema.

The relation of brain eicosanoids to progression of cerebral edema was studied in stroke-resistant spontaneously hypertensive rats subjected to incomplete global brain ischemia induced by bilateral occlusion of the common carotid arteries. Thromboxane B2 and 6-keto prostaglandin F1 alpha levels were significantly elevated 5 minutes after reperfusion but returned to control levels by 30 minutes. In contrast, leukotriene C4 levels increased 2 hours after bilateral common carotid artery occlusion and peaked 30 minutes after reperfusion, with higher levels persisting until 60 minutes after reperfusion. Cerebral ischemia was accompanied by cerebral edema early after reperfusion. The edema correlated with increased leukotriene C4 levels. That the increased brain water content was causally related to an increase in leukotriene C4 was supported by results obtained following administration of the 5-lipoxygenase inhibitors ONO-LP-016 and AA-861. Both inhibitors suppressed the increased leukotriene C4 and brain water contents after reperfusion. Our results indicate that leukotriene C4 is closely associated with an induction of ischemic cerebral edema.

Metabolic studies of the edematous cerebral cortex of the pyrithiamine-treated thiamine-deficient rat

The pyrithiamine-treated rats produced by our method histopathologically exhibited the edematous lesion not only around the third ventricle and at the tegmentum of pons, as expected, but also in the cerebral cortex. These animals were, therefore, used in a biochemical study of the cerebral cortex, in particular, glucose metabolism. The results indicate an accumulation of lactate and severe impairment of the lipid metabolism in the edematous lesion of the cerebral cortex among the pyrithiamine-treated rats. The fact that oxygen consumption was hardly diminished, however, strongly suggested that amino acids were selectively supplied to the tricarboxylic acid cycle from the free amino acid pool.

Plasma levels of leukotriene C4, B4 slow reacting substance of anaphylaxis in chloronological phases of cerebrovascular disease

In this study we report and compare plasma leukotriene (LT) levels in seventeen (17) patients with cerebral infarction, five (5) patients with cerebral hemorrhage and twelve (12) age-matched healthy volunteers. Plasma samples were collected at intervals of 1-7 days, 8-14 days, 15-30 days and 31 days- after cerebrovascular accident. Plasma immunoreactive LTC4, LTB4 and SRS-A (Slow Reacting Substance of Anaphylaxis or total peptido-LTs) levels were measured for each sample. Immunoreactive LTC4 (and SRS-A) levels were elevated in patients with cerebral infarction whilst LTB4 levels were raised in the patients with cerebral hemorrhage. In particular, cerebral infarcted patients exhibited significantly elevated levels in phases 1-7 days and after 15 days when compared with the age-matched healthy volunteers. In patients with cerebral hemorrhage, significant increases in LTB4 were measured in days 1-7 only. These results suggest a clinical relationship between the plasma levels of LTs and cerebrovascular disease.

Decreased mucosal iron induces an increase in intestinal iron absorption in the early stage of iron-deficiency

To investigate the contribution of non-heme iron and ferritin in the intestinal mucosa in regulating intestinal iron absorption during the early stage of iron-deficiency, we performed an in vivo study using rats fed an iron-deficient diet. Intestinal iron absorption was measured using the ligated intestine method. Rats fed the iron-deficient diet for 2 days showed no change in hematological parameter values (blood hemoglobin, plasma iron, the total iron binding capacity) and no change in the content of non-heme iron and ferritin in the liver. However, uptake of iron into the mucosa (mucosal uptake) and transfer of iron from mucosal cells to blood (serosal transfer) was significantly increased compared with the initial levels. At that time, the content of non-heme iron in the mucosa significantly decreased, however, no significant change in mucosal ferritin was observed. Extending the period of feeding the iron-deficient diet resulted in a small additional decrease in the level of mucosal non-heme iron, but led to no significant increase in mucosal uptake and serosal transfer. These findings suggest that a decrease in non-heme iron content in the intestinal mucosa may induce an increase in intestinal iron absorption during the early stage of iron-deficiency. In addition, it was evident that there is an upper limit in intestinal iron absorption. This limit in iron absorption may play a role in preventing iron-overload in the body.

Effects of vitamin A on eicosanoids production in the lung of rat treated by thermal injury.

After the treatment of thermal injury, contents of leukotriene C4 (LTC4) increased significantly at early stage and then kept the high level of LTC4 during the inflammation. Administration of vitamin A (VA) on vitamin A deficient- (AD) rats suppressed LTC4 induction in the lung and also inflammation and then gradually induced the significant decrease of LTC4 contents to the normal level 3 days after treatment of thermal injury. Synthesis of 6KPGF1α in the lung of AD rat was induced gradually until 24 hours after thermal injury. While the administration of VA to AD-rat enabled in the lung to induce the synthesis of 6-KPGF1α enough at early stage of thermal injury. After this induction, the production of 6KPGF1α gradually decreased. These results suggest that VA will suppress specifically the induction of lipoxygenase products but will not interfere the synthesis of cyclooxygenase products.