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T Goda

Publications and source records attributed to T Goda.

At least 91 records · Page 5Linked to original sources

Effects of medium-chain triglycerides on brush border membrane-bound enzyme activity in rat small intestine.

The effects of various types of dietary fat on brush border membrane-bound enzymes in rat intestinal mucosa were examined. Four groups of five rats were pair-fed defined diets for 10 d. The control group was fed a diet containing 57% sucrose and 2% corn oil as a fixed carbohydrate reference; the three experimental groups received diets containing 57% sucrose and 2% corn oil plus 13% fat in the form of medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) (either lard as a highly saturated fat or corn oil as a highly unsaturated fat). Feeding LCT compared to the control diet, decreased sucrase activity in mucosal brush borders of the duodenum and jejunum. In these segments of MCT-fed rats, sucrase activity was similar to that in the control animals. In another experiment, measuring immunoreactive sucrase-isomaltase in jejunal brush border membranes revealed that feeding a high corn oil diet, but not a high MCT diet, led to a reduction in the sucrase catalytic activity per unit weight of enzyme protein, suggesting that the degradation status of sucrase-isomaltase might be altered by the different types of dietary fats. With MCT feeding, jejunal alkaline phosphatase activity was enhanced to a large extent compared to the activity in other groups. Feeding MCT, compared to lard or corn oil, also increased microvillus phospholipids of the jejunal mucosa. These results suggest that MCT, unlike LCT, do not suppress the activity of mucosal microvillus membrane enzymes in rat small intestine.

Alkaline Phosphatase↗

Gastric acidity-dependent bioavailability of commercial sustained release preparations of indomethacin, evaluated by gastric acidity-controlled beagle dogs.

The relationship between gastric acidity and the bioavailability of two kinds of sustained-release indomethacin (IM) formulations was investigated in gastric acidity-controlled beagle dogs, and compared with that of rapid-release IM formulations. All test dosage forms were more rapidly dissolved in simulated intestinal fluid than in simulated gastric fluid. Gastric acidity did not affect the bioavailability of IM from the rapid-release formulation. However, the bioavailability of IM from the two kinds of sustained-release formulations were markedly influenced by gastric acidity. The rates of IM bioavailability from both of the sustained-release formulations were faster under low acidity conditions than under high acidity conditions (p less than 0.01). In addition, Tmax and mean residence time (MRT) were approximately the same for the rapid-release and sustained-release formulations under low acidity conditions. These results suggest that the IM sustained-release formulations showed a rapid-release profile under low acidity conditions.

Animals↗

[Application of gastric acidity-controlled beagle dog to bioavailability study of cinnarizine].

The relationship between gastric acidity and bioavailability of a weakly basic drug, cinnarizine (CN) was investigated in the gastric acidity-controlled beagle dogs. The dissolution of CN from capsules was very fast at pH 1.2 but it decreased with an increase in pH. The capsules containing CN were orally administered to the beagle dogs of the following three groups: 1) the dogs whose gastric acidity were not controlled; 2) the dogs whose gastric acidity were controlled to high levels (less than pH 2) with pentagastrin; 3) the dogs whose gastric acidity were controlled to low levels (more than pH 6) with omeprazole. The peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-8h) of CN were most variable in the first group. On the other hand, the variations of these parameters were small in the second and third groups. The Cmax and AUC0-8h of CN in the high acidity group were about 20 times larger than those in the low acidity group (p less than 0.01). The bioavailability of CN was markedly influenced by the gastric acidity. This finding was similar to that in human subjects. The gastric acidity-controlled beagle dogs are useful animal models to evaluate the bioavailability of weakly basic drugs such as CN, exhibiting pH-dependent dissolution behavior.

Animals↗

Gastric pH profile and its control in fasting beagle dogs.

The gastric pH of fasting beagle dogs was measured by using an ion-selective field effect transistor pH sensor. In addition, a novel procedure to control the gastric pH in fasting beagle dogs was investigated. Inter- and intra-day variations in the gastric pH of the dogs were observed. The gastric pH of the dogs could be controlled by a single intravenous administration of omeprazole, an H+, K+-adenosine triphosphatase (ATPase) inhibitor (1 mg/0.25 ml/kg). The pH in the stomach was 6.6 +/- 0.2 (mean +/- S.D., n = 6) at 1 h after the omeprazole treatment, and this level of pH was maintained for a period of at least 3 h. Beagle dogs in which the gastric pH has been controlled by omeprazole are considered to be useful as an animal model to be used for the pharmaceutical evaluation of drugs in subjects with a low acidity level.

Animals↗

Effect of gastric acidity on bioavailability of N,N-dimethylcarbamoylmethylalpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate, a new prodrug-type anti-inflammatory agent.

The effect of gastric acidity on the bioavailability of N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b] pyridine-7-acetate (1), a new anti-inflammatory agent, was investigated in gastric acidity-controlled beagle dogs. The dissolution rates of this compound in media of pH 1.2 and 3.0 were greater than those in media of pH 5.0 and 6.8. Reflecting these dissolution characteristics, the peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-12h) were reduced by shifting the gastric acidity to low levels (more than pH 6) with omeprazole treatment. In designing dosage forms of 1, it is necessary to develop pharmaceutical preparations whose bioavailability is not affected by the gastric acidity.

Animals↗

Purification, properties, and developmental changes of cellular retinol-binding protein, type II, in chicken intestine.

Two distinct cellular retinol-binding proteins were detected in chicken small intestine. A predominant form was purified to homogeneity. The apparent molecular weight of this protein was estimated to be 17,200. This form was larger than a second minor form partially purified (molecular weight of 15,000). The absorption and fluorescence spectra of the bound retinol to the purified proteins were typical for the known cellular retinol-binding proteins. The results suggest that the purified binding protein corresponds to CRBP(II), previously identified in small intestine of rats and humans. To gain an insight into the possible role of CRBP(II) in chicken small intestine, the CRBP(II) contents in cytosols of small intestine of embryonic and post-hatch chicks were determined by enzyme-linked immunosorbent assay. The amount of CRBP(II) per unit DNA in small intestine was low at 15- and 17-day embryonic stage, but rapidly increased around the period of hatching. The increased level was still maintained in 6-week-old chicks, which accounted for 0.9% of total proteins in duodenum. The developmental pattern and the presence of abundant amount of CRBP(II) in chicken small intestine supports the hypothesis that CRBP(II) might play some role in the intestinal absorption of retinoids. Thus the involvement of a tissue-specific cellular retinol-binding protein in the intestinal absorption of retinoids appears to be common in mammalian and avian species.

Animals↗

[Surgical treatment of the thoracoabdominal aortic aneurysms with Marfan's syndrome].

We experienced two cases of the thoracoabdominal aortic aneurysms with Marfan's syndrome. Case 1; The 31 year-old-woman was operated upon by Crawford's procedure, which includes reconstruction of renal arteries, superior mesenteric artery, and celiac artery using temporary shunt. Although she had been well for three years after the operation before she developed acute aortic dissection, she could not tolerate the Bentall's procedure on it. Case 2; The 37 year-old woman was operated upon for dissecting aneurysm (DeBakey IIIb). The procedure included replacement of the descending and abdominal aorta by Dacron graft. Four years after the operation, enlargement of residual false lumen had been observed, which caused its dehiscence just proximal to the abdominal aortic anastomosis. The Crawford's procedure, which includes reconstruction of renal arteries, superior mesenteric artery, and celiac artery using temporary shunt was employed for repair of the remaining thoracoabdominal aortic aneurysm. She is well now 5 months after surgery. We conclude that cardiovascular changes in patients with Marfan's syndrome must be observed carefully because of its high recurrent rate after initial surgery. The operation at proper time and a careful observation of cardiovascular changes will improve the prognosis.

Adult↗

Characterization of degradation process of sucrase-isomaltase in rat jejunum with monoclonal-antibody-based enzyme-linked immunosorbent assay.

As shown previously, during degradation of sucrase-isomaltase in rat jejunum, degradation of the sucrase active site occurs before that of isomaltase active site [Goda & Koldovský (1985) Biochem. J. 229, 751-758]. To characterize further the process of sucrase-isomaltase degradation in jejunum, we determined the amounts of immunoreactive sucrase-isomaltase in rat jejunum by using a monoclonal-antibody-based enzyme-linked immunosorbent assay. By employing two alternative monoclonal antibodies (one reacting with the sucrase subunit and the other reacting with the isomaltase subunit), the amount of antigen-containing sucrase subunit and the amount of antigen-containing isomaltase subunit were separately quantified. In both upper and lower jejunum of rats, the amount of antigen-containing isomaltase subunit was always higher than the amount of antigen-containing sucrase subunit. This difference was attributable mainly to a degradation product of sucrase-isomaltase, which was identified as isomaltase monomer. Occlusion of pancreatic ducts for 18 h eliminated the difference between the amount of antigen-containing sucrase subunit and the amount of antigen-containing isomaltase subunit in both upper and lower jejunum. In jejunum of control animals, the molar ratio of sucrase subunit to isomaltase subunit was estimated to be 0.32-0.52, indicating that quite a large proportion of sucrase-isomaltase (48-68%) is present as degradation products (e.g. isomaltase monomer). These results support the model of degradation process of sucrase-isomaltase in brush-border membranes of rat jejunum, whereby degradation of sucrase subunit by the action of pancreatic proteinase(s) precedes degradation of isomaltase subunit.

Animals↗

Effects of a high-protein, low-carbohydrate diet on degradation of sucrase-isomaltase in rat jejunoileum.

During the degradation of intestinal sucrase-isomaltase by pancreatic proteinases, degradation of sucrase-active site precedes that of the isomaltase-active site in rats. In the present paper, we demonstrate that the extent of degradation of sucrase-isomaltase is altered by dietary manipulation in vivo. Adult rats were starved for 24 h and received either a standard diet (20 cal% protein, 55% carbohydrate) or an isocaloric high-protein, low-carbohydrate diet (70 cal% protein, 5% carbohydrate). Animals were killed 15 h after the refeeding. In rats fed a high-protein, low-carbohydrate diet, luminal trypsin activity was three times higher than controls, and sucrase activity in proximal ileum was significantly lower (P less than 0.001) than controls, whereas isomaltase activity was similar in both groups. In proximal jejunum, luminal trypsin activity was remarkably lower (P less than 0.01) than in proximal ileum in both groups; sucrase and isomaltase activity was similar in both groups. Crossed immunoelectrophoresis demonstrated that a degradation product of sucrase-isomaltase, i.e., isomaltase monomer, was present in a larger amount in rats fed a high-protein, low-carbohydrate diet. In rats with bypassed pancreatic ducts, the amount of this degradation product was decreased and effect of a high-protein, low-carbohydrate diet was abolished. Experiments with a sequential isolation of epithelial cells of proximal ileum revealed that sucrase activity was decreased along the entire height of the villus in animals fed a high-protein, low-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hydrolysis of alpha-D-glucopyranosyl-1,6-sorbitol and alpha-D-glucopyranosyl-1,6-mannitol by rat intestinal disaccharidases.

The hydrolyzing activities in rat small intestine for newly developed sugar substitutes, alpha-D-glucopyranosyl-1,6-sorbitol (GPS) and alpha-D-glucopyranosyl-1,6-mannitol (GPM), both of which are produced by hydrogenation of palatinose, were characterized. GPS and GPM were hydrolyzed in mucosal homogenate as well as in brush border membranes of rat small intestine at a slower rate than the rate of hydrolysis of palatinose (30%) and sucrose (6-7%). Gel filtration column chromatography of disaccharidases solubilized from brush border membranes revealed that GPS and GPM were hydrolyzed mainly by sucrase-isomaltase complex and its degradation product, i.e. isomaltase monomer. The isomaltase monomer, purified from small intestine of rats, possessed similar Km values for GPS (2.47 mM) and GPM (5.38 mM) as compared to those of purified sucrase-isomaltase complex. The Vmax values of isomaltase monomer for GPS and GPM were twice as high as those of sucrase-isomaltase, suggesting that GPS and GPM are hydrolyzed by the active site of isomaltase. On the other hand, a small amount (up to 17%) of GPS- and GPM-hydrolyzing activities was ascribed to glucoamylase, which possessed relatively high Km values for GPS (18.7 mM) and GPM (32.9 mM). To examine a physiological significance of GPS- and GPM-hydrolyzing activities, the transmural potential difference (delta PD) evoked by Na+-dependent active transport of glucose, produced by the hydrolysis of these disaccharide alcohols, was measured in everted segments of rat jejunum. The relative rates of absorption of glucose produced by the hydrolysis of GPS and GPM were 36% and 27% of that of palatinose, directly reflecting the hydrolyzing activities determined in jejunal homogenate. These results suggest that the process of hydrolysis is the rate limiting step in digestion-absorption process of palatinose, GPS and GPM in small intestine.

Animals↗

Short-term effect of a high-protein/low-carbohydrate diet on aminopeptidase in adult rat jejunoileum. Site of aminopeptidase response.

The short-term effects of high-protein/low-carbohydrate diet on aminopeptidase N activity were studied in the brush-border membranes of proximal jejunum and proximal ileum of adult rats. The animals were starved overnight and re-fed for 15 h either with a standard diet (20% protein, 55% carbohydrate, in terms of energy content) or with a high-protein/low-carbohydrate diet of equal energy content (70% protein, 5% carbohydrate). All rats consumed similar amounts of diet, and measurements were made 15 h after initiation of re-feeding. In the proximal jejunum a slight increase in aminopeptidase activity was observed after the high-protein intake. In contrast, considerable stimulation (52%) of the enzyme specific activity was obtained in the proximal ileum. This increase in ileal aminopeptidase activity was more prominent in the mature cells of the upper villus. To determine if the increase of aminopeptidase activity was due to an increased amount of enzyme protein, rocket immunoelectrophoresis was performed with detergent-solubilized brush-border protein from ileum on agarose gels containing anti-(rat brush-border) antiserum. When the same amount of enzyme activity was loaded on the gels, the peaks of immunoprecipitate for aminopeptidase were similar for animals fed on a standard or a high-protein diet. When the same amount of protein was loaded, the peak of immunoprecipitate for aminopeptidase was higher (81%) after a high-protein diet. These results showed that the high protein intake evoked an increase in aminopeptidase activity, with a concomitant increase in the amount of immunoreactive protein.

Aminopeptidases↗

Effects of enterally fed epidermal growth factor on the small and large intestine of the suckling rat.

Epidermal growth factor (EGF) has been shown to be present in the milk of several species, including the rat, and to have gastrointestinal effects when given parenterally or orally in pharmacologic doses. We investigated the effect of enteral EGF in physiologic doses on the small intestine and colon of suckling rats. Serum thyroxine (T4) levels were also measured. Rats were gavage-fed by hand with an artificial formula with or without added EGF every 3 h from 11 to 14 days of age. Intake was adjusted to deliver 30 kcal/100 g b.wt./day of formula and 16 micrograms/kg/day of EGF approximating the daily caloric intake, and about twice the estimated daily EGF intake for suckling rats. Weight gain did not differ between groups (fed EGF: 3.8 + 0.2 g; not fed EGF: 3.7 + 0.1 g). The protein content of the whole colon of rats fed an EGF-containing formula was significantly lower and the DNA content significantly higher, than in rats fed formula without added EGF. The protein/DNA ratio was therefore markedly higher in the animals fed formula without added EGF; these effects were most evident in the distal colon. In contrast, there was no effect of EGF on small intestinal protein and DNA content; lactase, sucrase, and maltase activities were likewise unaffected, as was serum T4. These data suggest a physiologic role for breast milk EGF in the development of the suckling rat colon.

Animals↗

Response of activity of jejunal disaccharidases and pancreatic amylase in young and middle-aged rats to a high carbohydrate diet.

Sprague-Dawley rats fed a nonpurified diet from weaning to 3 mo (young) or 12 mo (middle aged) of age were fed a low (5 cal%) starch (LST) purified diet for 2 wk. They were then fed a high (70 cal%) starch (HST) purified diet for up to 4 wk. Body weights of both age groups were greater in rats fed the LST than in those fed nonpurified diet throughout. The young, but not the middle-aged, group continued this gain while consuming HST. The levels of activity of intestinal disaccharidases of upper (proximal one-third) and lower (middle one-third) jejunum, and pancreatic alpha-amylase were lower in rats fed LST diet in both age groups than in rats fed HST. Similar increases of specific (per protein or DNA) activity were observed in both age groups throughout the first three (disaccharidase) to four (pancreatic alpha-amylase) days of feeding HST. Values of specific activity of the middle-aged group returned to initial levels with continued feeding of HST. In contrast, values in the young group tended to plateau (disaccharidases) or continued to increase (alpha-amylase). Differences in adaptability over 1 mo were most dramatic for alpha-amylase and sucrase, but negligible for lactase.

Aging↗

Dependency of lactose absorption on lactase activity in starved rats.

The effects of starvation on intestinal disaccharidase activities and disaccharide absorption were studied in rats. Adult male rats were starved for either 16 or 72 h and the specific activity of lactase and sucrase was determined together with the absorption of lactose, sucrose, and glucose in vitro by the everted sac technique. The specific activity of lactase was significantly higher and the specific activity of sucrase was lower in the 72-h starved animals when compared with the 16-h starved group. The higher specific lactase activity in the 72-h starved animals was reflected in enhanced absorption of lactose as determined by the transfer of the constituent monosaccharides into the serosal fluid. The transfer of glucose into the serosal fluid by the glucose sac was also higher in the 72-h starved rats but not to the same extent as that of lactose. The absorption of sucrose was not significantly different between the two groups of animals. This study shows that the increase of intestinal lactase activity induced by starvation of adult rats correlates with in vitro increased lactose absorption.

Animals↗

Myocardial revascularization by CO2 laser.

An original method of myocardial revascularization using CO2 laser has been studied in a pig model with acute myocardial infarction. Transparietal channels were created by myocardial vaporization, using a CO2 laser beam. A comparative evaluation was made against a control group using as parameters survival rate, ECG changes, anatomopathologic findings, and angiographic studies. With the exception of favorable changes in the ECG there was no other evidence of improved regional perfusion. No evidence of long-term patency of the transmyocardial channels could be demonstrated by angiographic and histologic studies.

Animals↗

Inhibitory mechanism of acarbose and 1-deoxynojirimycin derivatives on carbohydrases in rat small intestine.

The inhibitory action and mechanism of inhibition of two types of alpha-glucosidase inhibitors, acarbose (Bay-g-5421) and 1-deoxynojirimycin derivatives (Bay-m-1099 and Bay-o-1248), on small intestinal carbohydrases (sucrase, isomaltase, glucoamylase, trehalase and lactase) and pancreatic alpha-amylase were compared in vitro using small intestinal brush border membranes and pancreatic homogenates from adult Sprague-Dawley rats. Acarbose at a low (4 microM) concentration strongly inhibited the activities of glucoamylase, alpha-amylase and sucrase (98, 68, and 63%, respectively). At a high (200 microM) concentration, isomaltase activity was also inhibited (28%); effects on trehalase and lactase activities were negligible. Both the 1-deoxynojirimycin derivatives were even more potent inhibitors of sucrase (Ki = 8.6 x 10(-8) M for Bay-m-1099;Ki = 5.0 X 10(-8) M for Bay-o-1248) than acarbose (Ki = 9.9 x 10(-7) M). Whereas glucoamylase activity was strongly inhibited by the 1-deoxynojirimycin derivatives, alpha-amylase activity was not. In contrast to acarbose, the 1-deoxynojirimycin derivatives at high concentrations (20-200 microM) inhibited considerably trehalase and lactase (a beta-galactosidase) activities. The inhibition of lactase activity was stronger by Bay-m-1099 (Ki = 4.9 X 10(-6) M) than by Bay-o-1248 (Ki = 6.7 X 10(-5) M). Where inhibition was seen, kinetic analysis showed fully competitive inhibition of sucrase, isomaltase, trehalase, glucoamylase and lactase by all three inhibitors.

1-Deoxynojirimycin↗