The effects of antiplatelet agents on agonist-induced cytosolic Ca2± response and lipid metabolism, phosphatidylinositol turnover (PI turnover) and arachidonic acid metabolism, in human platelets were investigated. In aequorin-loaded platelets, verapamil (Ca2+ channel blocker), TMB-8 (intracellular Ca2± antagonist) and W-7 (calmodulin inhibitor) suppressed 0.05U/ml thrombin-induced elevation of cytosolic Ca2+ concentration. They, however, had no effect on 0.25U/ml thrombin-induced Ca2± change. Their specific inhibitory effects on Ca2+ influ x from extracellular fluid or intracellular Ca2+ mobilization, on which verapamil and TMB-8are considered to have their primary actions, were not evident. Thromboxane A2 (TxA2), an arachidonate metabolite, or Inositol 1,4,5-trisphosphate (IP3) derived from PI turnover is a main mediator of Ca2± mobilization in platelets stimulated by 0.05 or 0.25U/ml thrombin, respectively. These drugs seem to affect the production of the mediator rather than the Ca2±movement itself. They significantly suppressed arachidonic acid release from 14C-AA-labeled platelets stimulated by thrombin. Therefore, these drugs are considered to reduce TxA2 production by inhibiting the release of arachidonic acid from membrane phospholipids and, thus, to prevent the increase in cytosolic Ca2+ concentration under 0.05U/ml thrombin stimulation. In contrast, these drugs did not have any effect on the PI turnover estimated by production of phosphatidic acid (PA) and the Ca2±change in platelets stimulated by 0.25U/m1 thrombin. It has been assumed that cAMPproducing agents have direct action on intracellular Ca2± sequestration, but this Ca2± pump has not been identified yet. From the result of suppression of PA production, PGE1 and Forskolin seem to influence the PI turnover and subsequent Ca2+mobilization. In conclusion, these antiplatelet agents reduce agonist-induced Ca2± response in part by effect on phospholipid metabolism which is closely associated with Ca2+ mobilization.

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One hour after an intraperitoneal injection of 32 IU of ACTH into adult male Wister rats, when serum levels of ACTH, corticosterone and aldosterone elevated, cytoplasmic lipid droplets decreased markedly in zona fasciculata cells of the adrenal cortices. Compared with control group, smaller and irregularly shaped lipid droplets were observed in the peripheral portions of the cytoplasms, whereas no prominent changes of cell organellae were detected except for the more proliferation of microvilli. Using our mixture-immersed technique, numerous blackish and minute lipid droplets,0.20-0.25 pm in diameter, were identified. Morphomerical analysis of lipid droplets was carried out on the electron micrographs prepared using this technique. Both the volume density and the diameter of lipid droplets in the ACTH-stimulated cells decreased significantly (when) compared with those of control group, while their number increased in ACTH-stimulated cells. Therefore, acute stimulation with ACTH introduced the reduction in the total volume of lipid droplets in the adrenocortical cells, accompanying with the increase in minute lipid droplets, some of which might be produced by splitting of the large lipid droplets.

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The effect of ethyl alcohol on central and peripheral nervous system activity was investigated electrophysiologically in the rabbit and the following observed. The threshold of the arousal reaction due to stimulation of the brain stem reticular formation and evoked muscular discharges of the fore and hind limbs due to stimulation of the cerebral cortex decreased with administration of a small amount of ethyl alcohol, but increased when the quantity was increased. On the other hand, the threshold of evoked muscular discharges of the fore and hind limbs due to stimulation by turns. These findings suggest that the administration of a small amount of ethyl alcohol results in activation, while that of a large quantity results in suppression of both the consciousness level and pyramidal motor activity. An inhibitory effect of ethyl alcohol on extrapyramidal motor activity is also suggested. The frequency of spontaneous unit discharges of the brain stem reticular formation increased with a small amount of ethyl alcohol, but decreased with larger quantities. This result supports the effect on arousal reaction. The amplitude of the recruiting response due to stimulation of the nucl. ventralis anterior thalami (VA) with frequency of 8Hz decreased following administration of ethyl alcohol. In the experiment on eyelid microviblation, the amplitude of photo-evoked eyelid microviblation (MV) decreased with a small amount, but increased with a large quantity of ethyl alcohol. On the other hand, the amplitude of sciatic evoked eyelid microviblation (SMV) decreased following administration of ethyl alcohol, which suggests that ethyl alcohol has an effect of suppressing pain sensation. Regarding reflex activity, ethyl alcohol increased the amplitude of M wave, H wave and the nociceptive reflex induced by stimulation of the sciatic nerve in that order. Regarding autonomic nerve activity, ethyl alcohol had almost no effect on the blood flow volume in the common carotid artery, whereas that in the femoral artery tended to decrease with the administration of a small amount of ethyl alcohol. Intestinal movement was facilitated by the administration of ethyl alcohol, but it was markedly inhibited by a large quantity of 1600mg/kg. According to EEG topography with a minicomputer system, the administration of a small amount of ethyl alcohol resulted in an increase of fast waves, while that of a large quantity resulted in an increased delta bands. These findings suggest that the administration of a small amount of ethyl alcohol results in activation, while that of a large quantity results in inhibition of central nervous system activity.

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To study the effects of ketamine hydrochloride (hereafter, ketamine) on the autonomic nervous system, experiments on intestinal movement, heart rate and mean blood pressure were conducted in rabbits.
EEG topogra phy by a minicomputer system (ATAC-3700) was performed in order to investigate the effect of ketamine on the EEG activity, too.
1) Administration of ketamine induced no significan t change in intestinal movement.
2) Ketamine tended to decrease the inhibitory effect on intestinal movemen t as a result of stimulation of the brainstem reticular formation.
3) In the rabbit, there was no sign ificant change in the heart rate or blood pressure following administration of ketamine (0.3-5.0mg/kg), but the heart rate and blood pressure decreased with administration of ketamine (10.0mg/kg), which resulted in decreases of 9.6% in the heart rate and 15.5% in the blood pressure.
4) Administration of ketam ine (0.3-0.5mg/kg) resulted in no change in either power (V) or power ratio (%) in delta and theta bands, but resulted in tendency to increase in both power (V)and power ratio (%) in betal and beta2 bands. These EEG findings support the prev ious reports which shows that administration of small doses of ketamine (0.3-0.5mg/kg) somewhat elevates the level of consciousness.
5) Administration of ketamine (0.3-10.0mg/kg) resulted in an increase in power (V) in all bands and tendency to increase in power ratio (%) in betal and beta2 bands.

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Fifty-four Parkinson disease and thirty Parkinson syndromes (P-group) were served for our experiment. For control subjects, microhemodynamics and hemorheology were measured in essential hypertensions (EH-group) without having suffered from autonomic nerve disorders. In addition, the same parameters were examined in "Oketsusho (O-group)" with having suffered from stagnation in the peripheral organs. Oketsu-sho is pathophysiological concept about the human body in traditional oriental medicine, and it means that blood and fluid in human body dose not flow smoothly and causes stagnation in the peripheral organs. An Intra-Vital Videomicroscopic System was used to observe and record the microcirculation kinetics on the human bulbar conjunctiva. A Distance Meter Method was utilized for measurement of the blood flow velocity. Diameter of erythrocytecolumes were calculated by internal diameter and blood flow velocity. Whole blood viscosities were measured by CONTRAVES Low Shear 30R. In order to know the erythrocyte deformabilities, the passage time of 40% red blood cell suspension were measured. Blood samples were withdrawn from elbow vein before and after administration of each drugs. Microcirculation was observed and measured at the same part of the same vessel. All results are expressed as mean ± standard error, the significance is assessed using the paired t-test, the level of significance being calculated at P<0.05.

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21 CRF patients undergone hemodialysis were se rved. On dialysis days, they were administered rHuEPO in does of 1,500 and/or 3,000 units. When the Ht values reached 25%,30%,35% (at posthemodialysis), whole blood viscosities at high shear rate (94.5sec-1) and at low shear rate (0.376sec-1), plasma viscosities at high shear rate were measured before and after hemodialysis. The passage time of 40% red cell suspension (for RBC deformability) was also measured. Internal diameters (ID), blood flow velocities (FVE), blood flow volumes (FVO) and intravascular erythrocyte aggregations (IEA) were analyzed in same microvenules on the human bulbar conjunctiva by using IVVMS and Distance Meter Method.

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