A potential role for lysophosphatidie acid (LPA) in the regulation of malignant diseases has been widely considered. Migratory response to LPA in glioma cells was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki 16425, or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin. LPA action on migration was also suppressed, though incompletely by several specific inhibitors for intracellular signaling pathways such as Racl, p38 mitogen- activatcd protein kinase (p38 MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase. Nearly complete inhibition of the migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Racl suppressed JNK but not p38MAPK, and dominant-negative form of Cdc42 abrogated p38MAPK activity. These findings suggest that, in glioma cells, the PI3K/Cdc42/ p38MAPK and PI3K/Racl/JNK pathways arc equally important for LPA1 receptor- mediated migration.

A potential role for lysophosphatidie acid (LPA) in the regulation of malignant diseases has been widely considered. Migratory response to LPA in glioma cells was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki 16425, or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin.LPA action on migration was also suppressed, though incompletely by several specific inhibitors for intracellular signaling pathways such as Racl, p38 mitogen- activatcd protein kinase (p38 MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase.Nearly complete inhibition of the migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Racl suppressed JNK but not p38MAPK, and dominant-negative form of Cdc42 abrogated p38MAPK activity. These findings suggest that, in glioma cells, the PI3K/Cdc42/ p38MAPK and PI3K/Racl/JNK pathways arc equally important for LPA1 receptor- mediated migration.

Swelling and pain appear when blood flow is delayed in states of “oketsu.” Until now “oketsu” as a circulatory disturbance has been studied from profiles of vascular resistance characteristics and blood fluidity. Blood fluidity is influenced by blood cell function, plasma ingredients and reactive oxygen. In this study, we administered the various Chinese herbal medicines, tokishakuyakusan, saikokaryukotsuboreito, tokakujokito, keishibukuryogan and juzentaihoto to determine the effect of these medicines on “oketsu” by observing reactive oxygen dynamics and blood fluidity in rats.SPF male Wistar rats weighing 200 g were used. Each experimental group was given feed containing 3% extract of one Chinese herbal medicine for1week. Blood samples were mixed with heparin, EDTA-2K or sodium citrate to block coagulation. Blood fluidity was measured with a Micro Channel Array Flow Analyzer (MC-FAN). A PA-20 examined platelet aggregation by the reaction to ADP, which activates platelet aggregation. Reactive oxygen dynamics were measured with a Free Radical Elective Evaluator (FREE).As a result, anti-oxidative ability and blood fluidity increased in all Chinese herbal medicine-administered groups. Furthermore, an inverse correlation between the fluidity of erythrocyte suspensions and anti-oxidative ability was shown. We speculate that an anti-oxidative influence of Chinese herbal medicines affected erythroid deformability or stickiness. In addition, tokishakuyakusan, tokakujokito and keishibukuryogan decreased platelet aggregation ability.This study shows that “oketsu” improves blood properties and suggests that Chinese herbal medicine improves decrease in blood fluidity, the causes of conditions such as thrombosis or embolism.

Purpose: Autoregulation of retinal vessels is stronger than that of choroidal vessels. This study aimed to use laser speckle flowgraphy to determine the time course of changes in retinal hemodynamics of healthy eyes after a cold pressor test. Methods: This prospective study included 44 right eyes of 44 healthy volunteers (age, 21.7 ± 5.0 years). The mean blur rate, which is a quantitative index of the relative blood flow velocity in the retina, was measured using laser speckle flowgraphy. The vessel average of mean blur rate at the optic nerve head, intraocular pressure, systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and ocular perfusion pressure were evaluated at baseline, immediately after the cold pressor test, and 10, 20, and 30 minutes after the test. Results: Immediately after the test (0 minutes), systolic blood pressure, diastolic blood pressure, mean blood pressure, and ocular perfusion pressure were significantly increased compared with those at baseline; however, no changes were observed at 10, 20, and 30 minutes after the test. In contrast, intraocular pressure, heart rate, and the vascular mean blur rate values at the optic nerve head did not change throughout the course of the study. Conclusions Sympathetic hyperactivity induced by the cold pressor test increased systemic circulatory dynamics, but not retinal circulatory hemodynamics, suggesting the involvement of vascular autoregulation.