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K Kitani

Publications and source records attributed to K Kitani.

At least 163 records · Page 9Linked to original sources
PubMed1987

Increasing anticonvulsant effect of AD-810 (zonisamide) in aging BDF1 mice.

The anticonvulsant efficacy of a newly developed anticonvulsant, AD-810 (zonisamide, 3-sulfamoylmethyl-1,2-benzisoxazole) was examined in relation to mouse age in three different age groups of female BDF1 mice (7-, 25- and 29-month-old). The minimal effective concentration (MEC) of AD-810 in both plasma and brain for abolishing the electroshock-induced maximal seizure steadily decreased with age, the 25- and 29-month values being 50 and 30% of respective 7-month values. The observation in the present study was almost identical to previous observations by the authors on phenytoin, phenobarbital and oxazepam. The present results support our previous contention that the dose and plasma concentration of anticonvulsants can (and probably should) be reduced in the elderly regardless of the drug. Since the anticonvulsant mechanism of AD-810 has been reported to differ from those of previously examined drugs (phenobarbital and oxazepam), the results also suggest that the apparent increase in the pharmacological effect of these anticonvulsants may be due to old animals' lowered response capability for seizures rather than a specific age effect on the pharmacological reaction sites for individual anticonvulsants.

Aging↗
PubMed1987

The mobility of concanavalin A receptors and surface immunoglobulins on rat hepatocyte plasma membranes.

Lateral mobilities of lectin receptors and surface immunoglobulins were measured in plasma membranes of hepatocytes prepared by smearing small pieces of rat liver tissue and then using the fluorescence recovery after photobleaching (FRAP) technique. Smears were treated with various doses of fluorescein isothiocyanate (FITC) conjugated concanavalin A (ConA), succinylated ConA (SConA), wheat germ agglutinin (WGA), and soybean agglutinin (SBA), as well as with rabbit anti-rat IgG (RARa/IgG) and goat anti-rat IgM(Fc) (GARa/IgM(Fc] antisera. 10 micrograms/ml ConA and SConA concentrations and a 55 X dilution of the GARa/IgM(Fc) antiserum were found to be suitable for measuring the lateral mobilities dependent on age. Diffusion constant and mobile fractions of receptor complexes were measured in different age groups of female Fisher rats (from 1 to 26 month-old). The FRAP measurements revealed that at least two major receptor sites can be distinguished in cell membranes of compact tissue (similar to the cultured and isolated cells), forming a mobile and an immobile fraction. The mobile fractions of both the lectin receptors and the surface immunoglobulins tended to decrease with age, while the age differences of the diffusion constants were not statistically significant. The observed alterations could be due to the covalent crosslinking of the mobile receptors to immobile patches and/or to the retardation of free diffusion by the cytoskeleton, dependent on age.

Aging↗
PubMed1987

Biliary excretion of ouabain in aging male and female F-344 rats.

The biliary excretion of ouabain was examined in Fischer-344 rats of both sexes and of different ages. The biliary recoveries for the first 10-min period after the intravenous injection of ouabain (0.1 mg/100 g body weight) were nearly 2-fold higher in female than in male rats for all age groups compared (4, 6, 12, 24, 28 months). In both sexes, the biliary recovery showed a gradual decrease with age, and the first 10-min value in 24-months old rats was about one third of those in the youngest rats. The 60-min total recovery values also significantly decreased with age. Some very old (males, 28 months; females, 31 months) rats, however, showed higher 60-min total recovery values than younger rats comparable to the youngest animal values. It was concluded that the biliary excretion of ouabain in rats decreases with age in both sexes which suggests that this is a general phenomenon in this animal species.

Aging↗
PubMed1987

Aging and pancreatic exocrine function: studies in conscious male rats.

Changes in pancreatic exocrine function in young (6- and 12-month-old) and old (24- to 27-month-old) male Fischer (F-344) rats were examined. Rats were prepared with cannulae draining bile and pancreatic juice separately and with duodenal and right jugular vein cannulae. Experiments were conducted between the third and the seventh postoperative day in conscious rats. Bile and pancreatic juice were returned to the intestine during both the recovery period and between experiments. Pancreatic responses to endogenous [bile-pancreatic juice (BPJ) diversion from the intestine] and exogenous stimulation [0.086, 0.432, and 1.728 nmol/kg secretin and 0.033, 0.167, and 0.667 nmol/kg cholecystokinin-octapeptide (CCK-8)] were determined. Basal secretions of fluid, bicarbonate, and protein were not affected by aging. The pancreatic responses of fluid and bicarbonate secretion to BPJ diversion or secretin were unaffected by aging. However, the increment of protein secretion in response to BPJ diversion and the largest dose of CCK-8 was attenuated in old rats. It appears the duct cell function is hardly affected by aging, but that the reserve capacity for protein secretion in response to stimulation may decrease in old rats.

Aging↗
PubMed1987

Proglumide stimulates basal pancreatic secretion in the conscious rat.

The effect of proglumide, a glutaramic acid derivative, on pancreatic secretion was examined in vivo in the conscious rat with and without the return of bile-pancreatic juice (BPJ) to the intestine. Intravenous infusion of both 300 and 60 mg/kg proglumide significantly decreased protein output in a dose-related manner during BPJ diversion, but did not completely abolish the pancreatic hypersecretory response to BPJ diversion. Conversely, during basal secretion with BPJ being returned to the intestine, 300 mg/kg/h of proglumide increased the protein output. Dibutyryl cyclic GMP infused simultaneously with proglumide did not abolish the stimulatory effect of proglumide on basal secretion. It was concluded that proglumide inhibits pancreatic protein output during stimulated secretion by means of the luminal feedback mechanism but increases protein output during basal (BPJ returned) secretion in the conscious rat.

Animals↗
PubMed1986

The effect of age on the adaptation of the brain to the anticonvulsant effect of phenobarbital in mice.

The anticonvulsant effect of phenobarbital was examined in young (6 month old) and old (24 month old) BDF1 female mice consisting of three groups each (one control and two chronically dosed phenobarbital groups), using the abolition of the tonic hindlimb extensor component of maximal electroshock seizure as the index. The minimal effective concentrations (MEC) of phenobarbital in plasma and brain in old control mice that were given a vehicle (tragacanth) for one week were significantly lower in comparison to the respective values in young adult control mice with the same treatment, confirming our previous findings. In young mice chronically treated with phenobarbital for one week (20 mg/kg daily for two days followed by daily dose of 50 mg/kg for 5 days), the MECs in both plasma and brain were significantly higher compared with respective control values. The 3 week treatment also produced an increase in MEc comparable to the one-week treatment. The same one-week treatment with phenobarbital in old mice similarly caused significantly higher plasma and brain MEC values but 3-week-treatment values were not significantly different from corresponding control values. It is concluded that the development of brain adaptation to phenobarbital is almost equal for young and old mice, so that the reduction in MEC with age indicates the need for lowered dosages for the aged, even when the age effect on brain adaptation developed to chronic dosing is taken into consideration.

Adaptation, Physiological↗
PubMed1986

Age-dependent increase in the threshold for pentylenetetrazole induced maximal seizure in mice.

The thresholds for inducing the maximal seizure by pentylenetetrazole (PTZ) were compared for BDF1 mice of both sexes with varying ages after intraperitoneal administration of various doses of PTZ. The minimal effective PTZ concentrations (MECs) in the brain for inducing the maximal seizure were significantly higher in 24-month or older mice than in 6-month-old animals of both sexes. Some mice of 30 months did not demonstrate the maximal seizure but died within the 15-min observation period, a phenomenon never observed in mice of 24 months or younger. The relationship between plasma and brain concentrations of PTZ changed little during aging. It was concluded that the brain becomes less sensitive to PTZ with age in regard to its convulsant activity, as was previously shown for electroshock by the authors. This observation, coupled with our earlier observations on anticonvulsants, appears to support the classical hypothesis that age has a dual effect on drug sensitivity i.e. a decrease for stimulants but an increase for sedative (or depressant) drugs.

Aging↗
PubMed1986

Effects of bile salts on bile formation in rabbits.

The effects of different species of bile salts: deoxycholate, taurochenodeoxycholate, ursodeoxycholate, glycodeoxycholate, tauroursodeoxycholate, chenodeoxycholate and cholate (DCA, TCDC, UDCA, GDCA, TUDC, CDCA, CA) on bile secretion were examined in anesthetized rabbits using two different infusion routes. When bile salts were infused intravenously, all bile salts (except for TCDC) significantly increased the volume of bile and bile salt excretion, but their respective efficiency for bile formation was different. The concentration of bicarbonate ion in the bile significantly increased during the choleretic periods induced by DCA, UDCA, GDCA and CDCA but remained unchanged with the other bile salts (CA, TCDC, TUDC). In rabbits, where a bile salt solution was infused in the duodenum and then drained from the intestine through an incision in the distal part of duodenum, none of these bile salts affected bile secretion. The effects of intravenously administered bile salts on rabbit bile secretion are different in terms of their choleretic potency and bicarbonate excretion depending on the species of bile salts used. Furthermore, it was concluded that the intraduodenal infusion of UDCA, which was found to stimulate the pancreatic exocrine function, did not affect bile secretion.

Animals↗
PubMed1986

A difference in stimulatory effects on pancreatic exocrine secretion between ursodeoxycholate and trypsin inhibitor in the rat.

We previously reported that intraduodenally infused ursodeoxycholate produced hypersecretion of pancreas in bicarbonate and fluid secretion in the rabbit (Digestive Diseases and Sciences, 28:942, 1983). Since trypsin inhibitor stimulates pancreatic secretion in the rat whose pancreatic exocrine secretion is regulated by a luminal feedback mechanism, in the present study we examined the stimulatory effect of ursodeoxycholate in comparison to Trasylol in unanesthetized rats with both the presence and the absence of returning bile-pancreatic juice. Under the condition in which bile-pancreatic juice were continuously returned to the intestine, the intraduodenally infused ursodeoxycholate produced significant increases in juice flow and bicarbonate and protein outputs, while Trasylol significantly increased protein output only. After an 8- to 10-hr period of bile-pancreatic juice diversion, Trasylol no longer affected pancreatic secretion, whereas ursodeoxycholate still stimulated the bicarbonate output significantly. Trypsin activities in the proximal half of the small intestine were not decreased by the infusion of UDCA. The mechanism of stimulatory effect of ursodeoxycholate on pancreatic secretion is independent of luminal feedback regulation and appears to differ from that of trypsin inhibitor.

Animals↗
PubMed1986

Age-dependent decrease of the lateral diffusion constant of proteins in the plasma membrane of hepatocytes as revealed by fluorescence recovery after photobleaching in tissue smears.

When fresh liver is smeared on slides and incubated in Krebs-Henseleit Ringer solution containing 1 mM H2O2 at 37 degrees C, a yellowish-green autofluorescence develops in the hepatocyte plasma membrane. Indirect evidence shows that this peroxide-induced autofluorescence (PIAF) is due most probably to chemical reactions between proteins and the malondialdehyde produced by the membrane lipid peroxidation. Although the chemical nature of the PIAF has not been clarified yet, it is suitable under certain conditions for the measurement of the average lateral diffusion constant of the membrane proteins by means of the fluorescence recovery after photobleaching (FRAP) technique without the addition of any external fluorescent label. Analysis of four age groups for both sexes of Fischer 344 rats (3-5 rats per group, total 32) from 2 to 31 months of age revealed a significant negative linear correlation of the lateral diffusion constant of proteins with age in both sexes, with the slope of the females being somewhat smaller. Young males showed a diffusion constant about 2.8 X 10(-10) decreasing to 1.7 X 10(-10) cm2 X s-1 by 31 months of age at 37 degrees C, whereas the respective values in females were 2.7 X 10(-10) and 1.9 X 10(-10). The results are consistent with the predictions of the membrane hypothesis of aging, according to which an age-dependent loss of the passive permeability of the cell membrane for potassium (and probably for water) is the crucial point of the cellular aging.

Aging↗
PubMed1986

Plasma neuroleptic levels in the elderly patients on propericiazine therapy--possible role of morbidity.

Plasma neuroleptic levels of 31 elderly psychiatric patients (8 males and 23 females, age 80.1 +/- 8.95 years) on chronic propericiazine therapy and with multimorbidity were measured by means of radioreceptor assay. There was no significant correlation between the daily dose and the plasma neuroleptic level. Nor was there any significant correlation between the patients' age and the ratio of plasma neuroleptic level to the daily dose. On the other hand, the immobility score of patients (GBS scale) had a high correlation with the ratio of the plasma neuroleptic level to the daily dose. Furthermore, patients with positive C-reactive protein (CRP) had an average ratio value 3-fold higher than the CRP negative group. The results suggest that the plasma neuroleptic level of propericiazine in elderly patients is raised by morbidity and immobility rather than chronological age per se.

Aged↗
PubMed1986

Age-estimations of rats based on the average lateral diffusion constant of hepatocyte membrane proteins as revealed by fluorescence recovery after photobleaching.

A method has been developed recently for measuring the average lateral diffusion constant of the proteins (D) in the cell membrane of hepatocytes in liver smears by fluorescence recovery after photobleaching (FRAP). A peroxide-induced autofluorescence (PIAF) of the membrane proteins was used as a fluorescent label. It has been established that D displays a significant negative linear correlation with age. The present paper describes age-estimations carried out on 12 male Fischer 344 rats (7-29 months of age) in so-called "blind experiments": the operator knew only the sex of the rat, determined D from a small piece of the freshly removed liver, and estimated the age of the rat from the age-dependent regression line for D established previously on 16 other Fischer 344 male rats of various ages. There was a strong correlation of the estimated age with the actual one (r = 0.92), the slope of the regression line was 0.98 and its intercept differed from 0 by only 0.5 months. These results indicate that D may play a decisive role in the determination of membrane functions as predicted by the membrane hypothesis of aging.

Aging↗
PubMed1986

Effects of bile salts on pancreatic secretion in rabbits: ursodeoxycholate infused into the duodenum stimulates pancreas.

The effects of six species of bile salts, deoxycholate, ursodeoxycholate, glycodeoxycholate, tauroursodeoxycholate, chenodeoxycholate, and cholate (DCA, UDCA, GDC, TUDC, CDCA, CA), on pancreatic secretion were examined in anesthetized rabbits. When bile salts were infused intraduodenally, only UDCA significantly increased the pancreatic juice flow and bicarbonate output, whereas the increase in protein output was only transient. In contrast, UDCA infused intravenously did not affect the pancreatic secretion. Furthermore, none of the other bile salts, either intraduodenally or intravenously administered, had any significant effect on pancreatic exocrine function. Pancreatic responses to the intraduodenally administered UDCA in terms of fluid, bicarbonate, and protein secretion were similar to those of secretin infused intravenously. Thus, it was suggested that UDCA infused intraduodenally stimulates pancreatic secretion, possibly via the release of a secretin-like substance(s) from the duodenal wall.

Animals↗
PubMed1986

The sequential changes in pancreatic exocrine function after abdominal surgery in the rat.

The sequential changes in pancreatic secretion in the conscious rat after pancreatic and intestinal surgery were examined. Rats were prepared with two duodenal cannulae and one cannula each for the pancreas, bile, and jugular vein. Pancreatic responses to Trasylol infused intraduodenally, bile-pancreatic juice (BPJ) diversion, and exogenous secretin and cerulein administrations were determined every 24 h after the operation. The body weight significantly decreased during the first 24 h after the operation but remained constant thereafter. The basal protein output was significantly lower on the first and second postoperative days compared with values on the third through seventh days, although the fluid output was almost constant throughout the observation period. Intraduodenal infusion of Trasylol failed to stimulate pancreatic secretion on the first and second postoperative days. Pancreatic feedback responses to BPJ diversion were observed during the entire experimental period, but were attenuated during the first 3 days. Responses to exogenous secretin and cerulein were relatively unaffected by postoperative recovery time. Results suggest that the pancreas itself may recover sufficiently within 24 h after the operation to respond consistently to direct stimulation. However, considering the effects on basal secretion and the responses to intestinally mediated secretion, it appears best to wait at least 3 days after the operation before using these rats in experiments on pancreatic exocrine functions.

Animals↗
PubMed1986

Differing transport maxima values for taurine-conjugated bile salts in rats and hamsters.

It was recently suggested that the apparent biliary transport maximum (Tm, secretory maximum) for bile salts is primarily determined by their degree of cytotoxicity (the cytotoxicity hypothesis), based on experiments on male rats [Hardison, W. G., D. E. Hatoff, K. Miyai, and R. G. Weiner. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G337-G343, 1981]. To confirm this hypothesis, we determined the Tm of three different bile salts, taurocholate (TC), taurochenodeoxycholate (TCDC), and tauroursodeoxycholate (TUDC) in female rats and hamsters. The order of Tm values in female rats was the same as that reported for male rats (TUDC greater than TC greater than TCDC), whereas in female hamsters it was TC greater than TCDC greater than TUDC. On the other hand, in hamsters, the order of cytotoxicity, evaluated in vivo by the biliary excretion of hepatocyte enzymes such as lactate dehydrogenase and alkaline-phosphatase and an increase in plasma lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase levels under a fixed rate infusion (0.6 and 1.2 mumol X min-1 X 100 g body wt-1) of bile salts, was inverse to the order of Tm values (TCDC greater than TC greater than TUDC) in rats, but in hamsters, too, TCDC was most cytotoxic. The order of Tm value in hamsters thus does not correspond to the order of cytotoxicity of these bile salts, suggesting that the cytotoxicity of bile salts may not be the sole determinant of bile salt Tm.

Animals↗
PubMed1986

Effect of tauroursodeoxycholate on the biliary transport maximum of sulfobromophthalein in the rat.

The effect of tauroursodeoxycholate (TU) infusion on the plasma level and biliary transport maximum (Tm) of sulfobromophthalein (BSP) was examined in male rats during a continuous intravenous infusion of BSP with different TU infusion rates. The infusion rate of 0.6 mumol/min/100 gm body weight of TU caused significantly higher bile flow and BSP Tm values compared with the respective control values in rats with only a BSP infusion. These values, however, were significantly lower than values obtained by an equimolar infusion of taurocholate (TC). The higher infusion rates of TU (1.2 and 1.8 mumol/min/100 gm) tended to cause higher bile flow rates, but the BSP Tm value did not increase beyond the value obtained at the lower infusion rate (0.6 mumol/min/100 gm). In the highest TU infusion rate study (1.8 mumol/min/100 gm), plasma BSP concentrations were significantly higher than corresponding control values or values at a lower TU or TC infusion rate. It was concluded that in rats TU can significantly increase the BSP Tm, but to a lesser extent than TC. Furthermore, it was suggested that TU infusion at a higher rate significantly interferes with the hepatic uptake (or storage) of BSP.

Animals↗