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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 199 records · Page 11Linked to original sources

Effects of urethane anesthesia and age on organ blood flow in rats measured by hydrogen gas clearance method.

Apparent blood flow rate in jejunum, kidney, liver or skeletal muscle was directly measured by the hydrogen gas clearance method in 7-week-old rats anesthetized with urethane at four dose levels (0.5, 0.8, 1.0 and 1.5 g/kg, i.p.). The apparent blood flow in each organ or tissue was reduced with the urethane dose. Jejunal blood flow was most sensitive to the dose-related decrease. Assuming that the organ (or tissue) to blood partition coefficient of hydrogen gas is unity and extrapolating the flow data to zero urethane dose for each organ, the flow rate values were almost comparable with the literature data in conscious rats. The applicability of the hydrogen gas clearance method to examine the effect of age on organ or tissue blood flow in rats was also discussed. Organs with relatively high sensitivity to aging were the stomach, jejunum and kidney.

Age Factors↗

An unclassified platelet function disorder associated with bleeding tendency.

A 7-year-old boy with a history of bleeding tendency showed a prolongation of bleeding time and a decrease in platelet adhesiveness. The platelets of the patient, however, had a normal reaction to ADP, collagen, epinephrine, arachidonic acid, bovine fibrinogen, ristocetin, A-23187 and thrombin-induced aggregation, and their shape was determined by electron microscopy to be normal. Therefore, this disorder could not be thought to belong to any known platelet dysfunction. On the other hand, an increase in clot retraction, a reversal of ATP/ADP, a decrease in beta-thromboglobulin and platelet factor 4 in the platelets, and an elevation of plasma levels of released beta-thromboglobulin from the platelets were observed in the patient. We don't know any cases with such an association of hypo- and hyperfunction of platelets.

Adenosine Diphosphate↗

Age-dependence in capacity-limited uptake kinetics of propranolol by isolated rat hepatocytes.

Overall initial uptake rates of propranolol by isolated rat hepatocytes were analyzed to give both apparently linear and saturable processes. The rate constant for the linear transport process in 7- and 24-week old rats was approximately 0.01 ml X sec-1 X (10(6) cells)-1. For the capacity-limited uptake process of propranolol, the kinetic parameters in 7-week-old rats, were estimated as Vmax = 0.609 microgram X (10(6) cells)-1 X sec-1 and Km = 8.17 micrograms/ml, whereas in 24-week-old rats, Vmax = 0.348 microgram X (10(6) cells)-1 X sec-1 and Km = 9.40 micrograms/ml. The overall uptake rate, when the hepatocytes were incubated with 20 micrograms/ml of propranolol, was reduced with age of the rats between 5 or 7 and 24 weeks and declined gradually thereafter, A higher cell to medium concentration ratio for the initially, net transported component of propranolol in relatively young (5- to 11-week-old) rats suggested an age-dependent saturable uptake process. This was supported by the direct comparison of the saturable uptake rates between 7 and 24 weeks. Therefore, the saturable sinusoidal transport (i.e. saturable uptake by the hepatocytes) may be considered one of the most important mechanisms determining the age-dependence in the intrinsic hepatic clearance of this drug noted in our previous report.

Aging↗

Age-dependent propranolol clearance in perfused rat liver.

The effect of age on the hepatic clearance of propranolol was studied by perfusing the liver isolated from 3- to 104-week-old rats. Propranolol levels in the recirculating perfusate declined biexponentially with time in all age groups. When the liver isolated from 7-week-old rats was perfused with propranolol (1 microgram/ml, 100 ml), hepatic clearance of this drug by the perfused liver (CLperf) increased from 0.589 to 1.14 ml X min-1 X (g liver)-1 with the increase of the perfusion flow rate from 1.0 to 2.0 ml X min-1 X (g liver)-1, confirming evidence of "perfusion-limited" hepatic clearance for this drug. Furthermore, there was no initial concentration(dose)-dependence in CLperf up to 2.5 micrograms/ml (i.e. 250 micrograms/organ). The effect of age on CLperf was then investigated by perfusing the isolated liver with 1.0 micrograms/ml propranolol at 2.0 ml X min-1 X (g liver)-1. Elimination of this drug from the perfusion medium was relatively rapid in 5- to 7-week-old rats, yielding the highest CLperf in these relatively young rats [approximately 1.0 to 1.1 ml X min-1 X (g liver)-1]. In contrast, CLperf values in both immature and older rats were 0.5 ml X min-1 X (g liver)-1 or less. The in vitro intrinsic hepatic clearance estimated in 5- and 7-week-old rats was about ten times as high as that in 104-week-old rats.

Aging↗

Changes of somatosensory evoked potential accompanying ischaemia and hypoxia in cats.

Changes of evoked potential accompanying haemorrhagic hypotension and hypoxia were investigated on cats to evaluate the usefulness of SEP as a monitor in an intensive care unit (ICU), and the following results were obtained. Positive-negative diphasic potential was elicited at posterior sigmoid gyrus(PSG) by contralateral superficial radial nerve stimulation. This potential was recorded at the restricted area of the posterior border of PSG and regarded as primary somatosensory evoked potential. In the initial stage of haemorrhagic hypotension, both positive and negative components of SEP occasionally increased in amplitude. In profound hypotension in which CBF fell to less than the critical level of 30 ml 100 g-1 min-1, the latency was retarded and the amplitude was decreased. At CBE less than 10 ml 100 g-1 min-1, SEP disappeared. Within the range of CBF between 10 and 30 ml 100 g-1 min, a close correlation was noted between CBF and SEP amplitude. Transient increase of SEP amplitude was also observed during hypoxia induced by inhalation of nitrogen gas. (3) In normal state SEP was decreased in amplitude by conditioning stimulation of the nucleus lateralis posterior (LP nucleus) of the thalamus. This might be explained by the fact that intracortical inhibitory interneurons were activated by stimulation of LP nucleus. After haemorrhagic hypotension and hypoxia, however, the inhibitory effect on SEP elicited by LP nucleus stimulation attenuated or disappeared. Because of the initial impairment of the inhibitory interneurons by ischaemia and hypoxia, the amplitude of SEP might increase transiently. In conclusion, the authors thought that SEP might be less useful than EEG in ICU, because of its insensible change to hypoxia and ischaemia.

Animals↗

Role of mandibular striated duct in salivary excretion of urea in dogs.

The role of mandibular striated duct in salivary excretion of endogenous urea was studied by a technique of retrograde ductal injection of HgCl2 and a stop flow analysis. (1) It was verified in this study that treatment with HgCl2 markedly inhibited Na+ reabsorption in the striated duct so that water reabsorption driven by the Na+ reabsorption would be inhibited substantially. (2) The saliva/plasma concentration ratios (S/P ratios) of urea in HgCl2-treated saliva (about 0.71) were significantly higher than those in untreated saliva (about 0.37). (3) The excretion rate of urea in HgCl2-treated saliva (about 0.02 mg/min/kg) was also significantly higher than those in untreated saliva (about 0.01 mg/min/kg) despite the same flow rate for both saliva samples. Furthermore, (4) The S/P ratios of urea in the second (0.25-0.50 ml) poststop-flow saliva (about 0.65) were significantly higher than those in prestop-flow saliva (about 0.35). These results suggest a possibility that salivary urea is reabsorbed in the dog mandibular striated duct and that the enhancement of the S/P ratio as well as the salivary level of urea by the pre-treatment with HgCl2 may be due to the inhibition of urea reabsorption.

Animals↗

Protein-coated and polysaccharide-coated liposomes as drug carriers.

Saccharides on the surface of cell membranes play an important role in cell-cell recognition, which is the most important process utilizable for targeting of drugs encapsulated in an artificial cell, liposome. To design a targetable drug carrier, hence, employing synthesized or natural glycolipids as the recognition site of the liposomal drug carrier is certainly one of useful approach. On the other hand, coating the outermost surface of liposomes with polysaccharide derivatives is also another way for liposomes to be utilized as a targetable drug carrier. In this review, from such a viewpoint, the importance and usefulness of saccharide moiety on the surface of liposomes will be discussed in conjunction with the targeting of drugs.

Animals↗

Bile salt damage of egg phosphatidylcholine liposomes.

Physiochemical damage of egg phosphatidylcholine liposomes, caused by the salts of three bile acids, chenodeoxycholic acid, ursodeoxycholic acid, and cholic acid, has been investigated. Of the three bile salts, that of chenodeoxycholic acid was the most destructive, and the effect of the damage was examined by monitoring the induced 6-carboxyfluorescein release from the liposomes. For all three of the bile salts and under the experimental conditions, the minimum (effective) concentrations causing the 6-carboxyfluorescein release were below their critical micelle concentrations. In the case of the salt of chenodeoxycholic acid, the presence of cholesterol in the liposomal bilayers did not show any significant effect on the induced 6-carboxyfluorescein release, while, for the salts of ursodeoxycholic acid and cholic acid, the presence of cholesterol tended to depress the release. Permeation of bile salts into the membranes of liposomal bilayers made these membranes more fluid, and this fluidity was monitored by measuring the change in fluorescence polarization using 1,6-diphenylhexatriene entrapped in the liposomes. Coating the liposomes with polysaccharides, to make them more hydrophobic, led to their easier lysis by the bile salts.

Bile Acids and Salts↗

Liposomal membranes. XX. Autoxidation of unsaturated fatty acids in liposomal membranes.

Autoxidation of egg phosphatidylcholines and polyunsaturated fatty acids, arachidonic and linoleic acids, has been investigated in homogeneous and liposomal membrane systems. In order to monitor the very initial stage of the radical chain mechanism of the autoxidation, an improved method using 1,1-diphenyl-2-picrylhydrazyl radical was newly implemented and used with the regular thiobarbituric acid test to determine the peroxides of polyunsaturated fatty acids. Autoxidation of polyunsaturated fatty acids or lipids was significantly enhanced in liposomal bilayers compared to that in a bulk homogeneous solution. In liposomal bilayers, the reaction could be controlled by membrane fluidity, which was confirmed by the fluorescence polarization technique using 1,6-diphenylhexatriene and dansylhexadecylamine. Even vitamin E esters such as the acetate and the pivalate could depress effectively the autoxidation of egg phosphatidylcholines in bilayer systems, which supported Lucy's proposal (Diplock, A.T. and Lucy, J.A. (1973) FEBS Lett. 29, 205-210) about the importance of the side-chain of vitamin E as an antioxidant.

Animals↗

Multicentric hemangioblastomas in the cerebellum.

An 18-year-old female patient who had been diagnosed as having von Hippel-Lindau disease was admitted to our hospital with signs of increased intracranial pressure. Computed tomographic examination and vertebral angiography revealed the presence of five multicentric cerebellar nodules, of which three had newly occurred in the opposite hemisphere, probably sometime during the 3 years before admission. This case gives us some insights into the biological multipotentiality of cerebellar hemangioblastoma. We stress that close observation is absolutely necessary for this unique group of tumors, even after total excision.

Adolescent↗