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Biomedical subjects

H Hara

Publications and source records attributed to H Hara.

At least 181 records · Page 10Linked to original sources
PubMed1999

A case study for wintertime observation of atmospheric particulates by an eye-safe laser radar.

Atmospheric particulates were monitored on a typical high concentration day in early winter in Osaka, Japan, using a compact and portable eye-safe laser radar system. The height of mixing layer was about 0.4 km at 8:00 and gradually increased to 0.8 km at 14:00. The development of the layer was in inverse proportion to the decrease of particulates near the ground surface. Analysis of particulates collected with high-volume air samplers showed that concentrations of elemental carbon (EC), lead and ammonium ion near the surface decreased significantly from morning to midday, while concentrations of sulfate, nitrate, sodium and calcium ions were almost constant. The results obtained in the preliminary study suggest that anthropogenic particulates such as EC and lead are on the rise with development of mixing layer from morning to midday.

Journal Article↗
PubMed1999

Selective effects of lomerizine, a novel diphenylmethylpiperazine Ca2+ channel blocker, on cerebral blood flow in rats and dogs.

1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter). 2. Lomerizine (1.25-10 mg/kg, p.o.) dose-dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR). 3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., time at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 x 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks. 4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30-120 min after its administration. 5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose-dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min. 6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in conditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca2+ channel blockers.

Animals↗
PubMed1999

A cephalometric study of the stability of the base of the pharyngeal flap following a modified 'unified velopharyngoplasty procedure'.

A cephalometric study was conducted on 12 patients with repaired cleft palate to evaluate the stability in level and length of the base attachment of the velopharyngeal complex following pharyngeal flap surgery by a modified velopharyngoplasty. Complete velopharyngeal closure and normal articulation with a speech appliance were confirmed in all patients prior to pharyngeal flap surgery, which was performed on patients 10 years of age and above. Cephalometric radiographs were taken immediately, 1 year, 2 years and 3 years postoperatively. Cephalometric analysis revealed that although the level and length of the base of the velopharyngeal complex showed changes during the first postoperative year, they remained stable when compared with the palatal plane during the last two years. This indicated therefore that the base of a velopharyngoplasty should be attached at the same level of the palatal plane, namely the level of velopharyngeal closure, and that the procedure appeared useful in producing a stable velopharyngeal complex.

Adolescent↗
PubMed1999

Ingestion of sugar beet fiber enhances irradiation-induced aberrant crypt foci in the rat colon under an apoptosis-suppressed condition.

The induction of aberrant crypt foci (ACF) by irradiation of gamma-rays (60Co), and the effect of dietary sugar beet fiber (SBF) on irradiation-induced ACF were examined. We found that abdominal irradiation of gamma-rays could induce ACF in the rat colon. The irradiation was performed once a week at a dose rate of 2 or 3 Gy per irradiation. Irradiation-induced ACF were observed in the colon at 10 weeks after the first irradiation at dose of 2 Gy for six times or 3 Gy for four times. Dietary SBF had no effect on the number of ACF, aberrant crypts (AC) or AC/focus induced by abdominal gamma-irradiation. However, an ingestion of SBF resulted in an increase in the number of these parameters in apoptosis-suppressed rats by cycloheximide (CHX). An injection of CHX suppressed irradiation-induced apoptosis of the colonic epithelial cells for at least 6 h after the irradiation. In CHX-injected rats, an ingestion of SBF significantly increased the number of ACF, AC and AC/focus compared with fiber-free fed rats at 9 weeks after the first irradiation. On the other hand, in saline-injected rats, no significant difference was found between SBF and fiber-free diets in the number of ACF, AC and AC/focus through the experimental period. These results suggest that dietary SBF may be involved in the elimination of abnormal cells from an irradiated colon through the apoptosis of colonic epithelial cells. In this study, we have shown a new method for inducing ACF by using gamma-rays which were not influenced by luminal contents such as bacterial enzyme, at least in the initiation stage.

Animals↗
PubMed1999

Ingestion of guar gum hydrolysate, a soluble fiber, increases calcium absorption in totally gastrectomized rats.

Gastrectomy induces osteopenia. We examined the effects of feeding a diet containing soluble dietary fiber, guar gum hydrolysate (GGH, 50 g/kg diet), on intestinal calcium absorption and bone mineralization in totally gastrectomized (Roux-en-Y esophagojejunostomy) rats by comparing them with those in two control groups (laparotomized and bypassed rats). In the bypassed rats, chyme bypassed the duodenum and upper jejunum without gastrectomy. In a second separate experiment, we compared calcium absorption and bone mineralization in the gastrectomized rats fed diets containing soluble and insoluble calcium salts and in bypassed rats fed insoluble calcium. In Experiment 1, apparent absorption of calcium supplied as a water-insoluble salt was more than 50% lower in gastrectomized rats than in the intact (laparotomized) or bypassed rats 3 wk after the start of feeding the test diets (P < 0.05). Calcium absorption was higher (P < 0.05) in gastrectomized rats fed the GGH diet than in those rats fed the GGH-free diet. In Experiment 2, absorption of soluble calcium in the gastrectomized rats did not differ from the absorption of calcium from calcium carbonate by bypassed rats. The soluble calcium pool in the cecal contents was significantly lower in gastrectomized rats (Experiment 1) than in intact or bypassed control rats, and was higher (P < 0.05) in the GGH-fed gastrectomized rats than in those fed the GGH-free diet. However, calcium absorption correlated most closely (r = 0.787, P < 0.01) with cecal propionic acid concentration. The femur calcium content was significantly lower in gastrectomized rats fed insoluble calcium than in bypassed rats fed the same diet, but was partially restored in the rats fed soluble calcium (Experiment 2). Bone calcium was not increased by feeding GGH in gastrectomized rats (Experiment 1). We conclude that the severely diminished calcium absorption following total gastrectomy is totally due to a decrease in calcium solubilization, and feeding GGH partially restores calcium absorption. The decrease in bone calcium that occurs as a result of gastrectomy is mainly due to diminished intestinal calcium absorption.

Administration, Oral↗
PubMed1999

Short-chain fatty acids suppress cholesterol synthesis in rat liver and intestine.

We previously showed that plasma cholesterol levels decreased following ingestion of a short-chain fatty acid (SCFA) mixture composed of sodium salts of acetic, propionic, and butyric acids simulating cecal fermentation products of sugar-beet fiber (SBF). In the present study, we investigated whether hepatic and small intestinal cholesterol synthesis is involved in the cholesterol-lowering effects of SCFA and SBF. In vitro (expt. 1) and in vivo (expt. 2) cholesterol synthesis rates and the diurnal pattern of SCFA concentrations in portal plasma (expt. 3) were studied in three separate experiments in rats fed diets containing the SCFA mixture, SBF (100 g/kg diet), or the fiber-free control diet. Cholesterol synthesis was measured using 3H2O as a tracer. The in vitro rate of cholesterol synthesis, measured using liver slices, was greater in the SBF group, but not in the SCFA group, than in the fiber-free control group. In contrast, the hepatic cholesterol synthesis rate in vivo was lower in the SCFA group, but not in the SBF group, than in the control group. The mucosal cholesterol synthesis rate for the whole small intestine was <50% of the hepatic rate. The rate in the proximal region was slightly but significantly lower in the SCFA group, and was significantly higher in the SBF group than in the fiber-free group. The rate in the distal small intestines was also significantly greater in the SBF group than in the fiber-free group. Plasma total cholesterol concentrations were lower in the SCFA and SBF groups than in the fiber-free group in both experiments 2 and 3. Diurnal changes in portal SCFA and cholesterol levels were studied in the experiment 3. SCFA concentrations increased rapidly after the start of feeding the SCFA diet, and changes in plasma cholesterol were the reciprocal of those observed in SCFA. These results show that a decrease in hepatic cholesterol synthesis rate mainly contributes to the lowering of plasma cholesterol in rats fed the SCFA mixture diet. Changes in portal SCFA and cholesterol concentrations support this conclusion. In SBF-fed rats, SCFA produced by cecal fermentation are possibly involved in lowering plasma cholesterol levels by negating the counteractive induction of hepatic cholesterol synthesis caused by an increase in bile acid excretion.

Acetic Acid↗
PubMed1999

Guanidino group is involved in the stimulation of exocrine pancreatic secretion by protamine in normal and chronic bile-pancreatic juice-diverted rats.

We previously demonstrated that the feeding of guanidinated casein, whose lysine residues are converted to homoarginine, stimulates pancreatic secretion much higher than that of intact casein in chronic bile-pancreatic juice (BPJ)-diverted rats, which suggests that the guanidino group is involved in BPJ-independent enhancement of pancreatic secretion. However, the role of the guanidino group in the protein for the enhancement of pancreatic secretion has not been clarified. In this study, we examined the stimulation of pancreatic secretion by a arginine rich dietary protein, protamine (25, 50 mg/ml), and then determined whether the guanidino group in protamine was responsible for the secretory responses in normal and BPJ-diverted rat by comparison with pancreatic secretion between intact and deguanidinated protamine. The deguanidinated protamine was prepared by converting arginine residues of salmon protamine to ornithine using heated hydrazine (conversion rate of arginine residue was 87%). In normal rats, pancreatic protein and chymotrypsin secretion were stimulated in dose-response fashion after a duodenal instillation of native protamine solution (25, 50 mg in 1 ml). In chronic BPJ-diverted rats, native protamine (25 mg) maximally stimulated pancreatic protein and protease secretion. In contrast, deguanidinated protamine (50 mg in 1 ml) did not stimulate pancreatic secretion in both normal and BPJ-diverted rats. In addition, the duodenal administration of arginine, which is equal to the amount contained in 50 mg of native protamine, had no effect on pancreatic secretion in both rats. These results suggest that a naturally occurring protein, protamine, stimulates pancreatic secretion by a luminal BPJ-independent mechanism and that the guanidino group in this protein is responsible for stimulating pancreatic secretion in BPJ-diverted rats.

Amino Acids↗
PubMed1999

[Evaluation of a rapid enzyme immunoassay for detection of influenza A virus among adult and elderly patients].

Directigen Flu A, an enzyme immunoassay membrane test for the detection of influenza A virus, was compared with serum hemagglutinine inhibition assay in adult and elderly patients. Throat specimens were collected by vigorous swabbing from febrile patients who were suspect for influenza by clinical symptoms and tested with Directigen Flu A. Serum samples were collected from the patients at onset of illness and two to eleven weeks later and tested for antibody titer to influenza A/H1N1, A/H3N2, and B. A total of 57 patients were involved in this study; 32 under 59 years of age and 25 over 60 years of age. Influenza was diagnosed in 42 patients by HI titer elevation (73.7%). Directigen Flu A was positive in 25 patients. Results of Directigen Flu A and HI test agreed in 40 patients. Sensitivity and specificity of Directigen Flu A were 59.5% (25/42) and 100% (15/15), respectively. There was no significant difference in sensitivity between the two age groups. These results indicate the potential usefulness of Directigen Flu A in the surveillance of influenza A infection in the geriatric population. Directigen Flu A gives results within 15 minutes without expensive equipment. Use of Directigen Flu permits the timely administration of antiviral therapy and infection control among hospitalized and institutionalized geriatric patients.

Adult↗
PubMed1999

Genetic and biochemical characterization of a 2-pyrone-4, 6-dicarboxylic acid hydrolase involved in the protocatechuate 4, 5-cleavage pathway of Sphingomonas paucimobilis SYK-6.

Sphingomonas paucimobilis SYK-6 is able to grow on a wide variety of dimeric lignin compounds with guaiacyl moieties, which are converted into protocatechuate by the actions of lignin degradation enzymes in this strain. Protocatechuate is a key metabolite in the SYK-6 degradation of lignin compounds with guaiacyl moieties, and it is thought that it degrades to pyruvate and oxaloacetate via the protocatechuate 4,5-cleavage pathway. In a 10.5-kb EcoRI fragment carrying the protocatechuate 4,5-dioxygenase gene (ligAB) (Y. Noda, S. Nishikawa, K. Shiozuka, H. Kadokura, H. Nakajima, K. Yoda, Y. Katayama, N. Morohoshi, T. Haraguchi, and M. Yamasaki. J. Bacteriol. 172:2704-2709, 1990), we found the ligI gene encoding 2-pyrone-4, 6-dicarboxylic acid (PDC) hydrolase. PDC hydrolase is a member of this pathway and catalyzes the interconversion between PDC and 4-carboxy-2-hydroxymuconic acid (CHM). The ligI gene is thought to be transcribed divergently from ligAB and consists of an 879-bp open reading frame encoding a polypeptide with a molecular mass of 32,737 Da. The ligI gene product (LigI), expressed in Escherichia coli, was purified to near-homogeneity and was estimated to be a monomer (31.6 kDa) by gel filtration chromatography. The isoelectric point was determined to be 4.9. The optimum pH for hydrolysis of PDC is 8.5, the optimum pH for synthesis of PDC is 6.0 to 7.5, and the Km values for PDC and CHM are 74 and 49 microM, respectively. LigI activity was inhibited by the addition of thiol reagents, suggesting that the cysteine residue is a catalytic site. LigI is more resistant to metal ion inhibition than the PDC hydrolases of Pseudomonas ochraceae (K. Maruyama, J. Biochem. 93:557-565, 1983) and Comamonas testosteroni (P. J. Kersten, S. Dagley, J. W. Whittaker, D. M. Arciero, and J. D. Lipscomb, J. Bacteriol. 152:1154-1162, 1982). The insertional inactivation of the ligI gene in S. paucimobilis SYK-6 led to the complete loss of PDC hydrolase activity and to a growth defect on vanillic acid; it did not affect growth on syringic acid. These results indicate that the ligI gene is essential for the growth of SYK-6 on vanillic acid but is not responsible for the growth of SYK-6 on syringic acid.

Carboxylic Ester Hydrolases↗
PubMed1999

Interstitial lung disease in association with polymyositis-dermatomyositis: long-term follow-up CT evaluation in seven patients.

PURPOSE: To determine the long-term follow-up computed tomographic (CT) findings of interstitial lung disease associated with polymyositis-dermatomyositis. MATERIALS AND METHODS: CT scans in seven patients with interstitial lung disease and associated polymyositis-dermatomyositis were evaluated retrospectively. Six patients underwent sequential CT (follow-up range, 2-8 years; mean, 4.3 years). Histologic confirmation of pulmonary involvement was available in five patients. RESULTS: The predominant finding on the initial CT scans in four patients was subpleural consolidation, which corresponded to bronchiolitis obliterans organizing pneumonia with or without coexistent chronic eosinophilic pneumonia. In most cases, consolidation improved with use of corticosteroid and/or immunosuppressive therapy; in two patients, however, consolidation evolved into honeycombing. In one patient, diffuse areas of ground-glass opacity and consolidation appeared rapidly during illness; this patient died of sudden, rapid deterioration. In one patient with subpleural linear opacities, parenchymal abnormalities slowly progressed, and linear opacities had evolved into honeycombing at 8-year follow-up. In one patient with histologically proved organizing diffuse alveolar damage, bilateral patchy areas of ground-glass opacity and consolidation were seen. In one patient, subpleural bands changed to subpleural lines on sequential CT scans. CONCLUSION: CT provides an excellent demonstration of the lung changes in patients with interstitial lung disease and associated polymyositis-dermatomyositis.

Dermatomyositis↗
PubMed1999

Microvascular responses to hemodilution with Hb vesicles as red blood cell substitutes: influence of O2 affinity.

Phospholipid vesicles encapsulating purified hemoglobin (HbV) were developed to provide O2-carrying capacity to plasma expanders. Microvascular perfusion was determined for HbV with different O2 affinity (P50 = 9, 16, and 30 mmHg) prepared by coencapsulating pyridoxal 5'-phosphate (PLP) at the molar ratios of [PLP]/[Hb] = 0, 0.5, and 3, respectively (cf. hamster blood, P50: 28 mmHg), and suspended in 8 g/dl human serum albumin (HSA). Eighty percent of the red blood cell (RBC) mass of conscious Syrian golden hamsters fitted with dorsal skinfold windows was substituted with either of the HbV-HSA suspensions, washed hamster RBC suspended in HSA (RBC-HSA), and HSA alone. All three HbV-HSA groups and RBC-HSA groups showed stable blood pressure and heart rate, which could not be sustained with HSA alone. Only the HbV (P50 = 9)-HSA group showed an increase in arterial O2 tension (89.8 +/- 14.7 mmHg, baseline 58.4 +/- 4.0 mmHg) because of hyperventilation, and microvascular perfusion was decreased, indicating that facilitated O2 unloading of HbV by decreasing the O2 affinity (increasing P50) with PLP as an allosteric effector is important. Microvascular perfusion and microvascular and interstitial O2 tensions in the HbV (P50 = 16 and 30)-HSA groups were significantly higher than those in the HSA group. The O2 release rate from the HbV was 18-32 s-1 vs. 4.4 s-1 for RBC. Functional capillary density was improved from 17 to 41% on average by decreasing P50 from 30 to 16 mmHg, which appears to be an optimal value for the P50 in this system.

Animals↗
PubMed1999

Changes in resistance vessels during hemorrhagic shock and resuscitation in conscious hamster model.

The unanesthetized hamster dorsal skinfold preparation was used to monitor diameters and blood flow rates in resistance arteries (small arteries, A0: diameter, 156 +/- 23 micrometers) and capacitance vessels (small veins, V0: 365 +/- 64 micrometers), during 45 min of hemorrhagic shock at 40 mmHg mean arterial pressure (MAP) and resuscitation. A0 and V0 vessels constricted significantly to 52 and 70% of the basal values, respectively, whereas precapillary arterioles (A1-A4, 8-60 micrometers) and collecting venules (VC-VL, 26-80 micrometers) did not change or tended to dilate. Blood flow rates in the microvessels declined to <20% of the basal values. Resuscitation with shed autologous blood (SAB) showed incomplete recovery of A0 and V0 diameters even 2 h after resuscitation (71 +/- 14% and 81 +/- 18%, respectively, of basal value), whereas other vessels did not change significantly. The behavior of A0 diameter coincided with the incomplete recovery of blood flow rates in all the vessels (ca. 50%) according to Poiseuille's law, and the incomplete recovery of functional capillary density (ca. 75%). Resuscitation with 8% human serum albumin in saline (HSA) tended to show higher levels of A0 constriction and A4 dilation and lowered blood flow rates. Resuscitation with SAB restored tissue PO2 27 +/- 10 mmHg after 2 h, which was near control levels (28 +/- 5 mmHg), whereas resuscitation with HSA caused tissue PO2 to remain significantly depressed (6 +/- 2 mmHg), and flow rates were significantly lower than resuscitation with SAB. These results indicate that response of the A0 vessels is the crucial determinant of blood flow in the observed area. The constriction of A0 may help sustain MAP, and constriction of V0 may enhance blood redistribution from the skin to the vital organs under the hypotensive condition.

Animals↗
PubMed1999

A novel class of inhibitors for human steroid 5 alpha-reductase: phenoxybenzoic acid derivatives. I.

In a search for novel nonsteroidal inhibitors of human prostatic 5 alpha-reductase, we found a new series of phenoxybenzoic acid derivatives to be potent human prostatic 5 alpha-reductase inhibitors. Among them, 4-(biphenyl-4-yloxy)benzoic acid derivatives (2n, YM-31758), 2o and 2s showed more potent inhibitory activities than finasteride with IC50 values of 0.87, 0.67 and 0.56 nM, respectively. The optimized structures for the phenoxybenzoic acid derivatives 2d-2i were calculated by molecular modeling analysis, and the favorable distance between the carbon of the carboxyl group and the centroid of the phenyl group (benzene ring C) was found to be in the 9-11 A range.

5-alpha Reductase Inhibitors↗
PubMed1999

2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. III.) Synthesis of metabolites and metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 as platelet-activating factor (PAF) receptor antagonists.

The metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 was investigated, and their metabolites were compared with separately synthesized materials by measuring 1H-NMR spectra, mass spectra, and HPLC retention times, and evaluated for platelet activating factor (PAF) antagonistic activity. YM461 was metabolized by two different metabolic pathways (cleavage of the thiazolidine ring and oxidation of the benzyl position), whereas YM264 was metabolized by three metabolic pathways. The minor metabolite M7 from YM264 possessed potent PAF antagonistic activity, as strong as YM264 and this existed as an active metabolite. From pharmacokinetics studies, YM264 was almost completely absorbed from the gastrointestinal tract, but readily metabolized in rats. In dogs, pharmacokinetic parameters of YM264 were significantly improved compared to those in rats, and YM264 tended to show better pharmacokinetics than YM461 due to an extension of the half-life period.

Administration, Oral↗
PubMed1999

[Involvement of caspase on apoptosis in ischemia-induced neuronal cell death: usefulness of caspase inhibitors for stroke therapy].

This overviews recent understanding of the mechanisms of apoptosis on ischemia-induced neuronal cell death. Apoptosis is a prominent feature of the developing nervous system. Several lines of evidence suggest that apoptosis is also an important mechanism of cell death in adult brain in acute or chronic diseases such as stroke and Alzheimer's disease. In animal models of stroke, markers of apoptosis such as cytoplasmic and nuclear condensation and DNA fragmentation appear in neurons. A variety of physiological and pathological stimuli can activate signal-transduction pathways that result in the sequential proteolytic activation of caspase family members. The activation of caspases can be inhibited by several molecules, including peptide aldehydes (caspase-1 and or caspase-3 inhibitors) and crmA that target the active-site cysteine of caspase family members, Bcl-2, IAP (inhibitor of apoptosis protein) and NAIP (neuronal apoptosis inhibitory protein). Once activated, caspase-1 protease can activate the caspase family members and hydrolyze a discrete set of cellular targets. Poly (ADP-ribose)polymerase (PARP), which appears to facilitate apoptosis, was recognized as a substrate of activated caspase-3. These results suggest that caspase family, bcl-2 family, IAP family and substrates such PARP contribute to mechanisms of cell death in ischemic brain injury. Inhibition of the caspase family, particularly by non-peptide inhibitors that cross the blood-brain barrier and easily penetrate neurons and glia, could provide novel treatments for stroke and other forms of brain and spinal cord injury in humans.

Adult↗
PubMed1999

Guanidinated casein hydrolysate stimulation of cholecystokinin release via pancreatic enzyme- and cholinergic-independent mechanisms in rats.

We had demonstrated that a peptic hydrolysate of guanidinated casein that is made from casein by the conversion of lysine to homoarginine stimulated pancreatic exocrine secretion in rats with chronic bile-pancreatic juice (BPJ) diversion from the proximal small intestine. This modified protein also stimulated cholecystokinin (CCK) release from dispersed rat intestinal cells. In this study, we found that guanidinated casein hydrolysate stimulates CCK release in chronic BPJ-diverted rats with cholinergic control blocked by atropine. Intraduodenal guanidinated casein hydrolysate increased portal plasma CCK concentration and pancreatic secretion in atropine-treated BPJ-diverted rats. In contrast, the portal plasma CCK concentration was not increased by intact casein hydrolysate. We conclude that guanidinated casein hydrolysate directly stimulates CCK release from the intestine via some cholinergic-independent mechanism, and an increase of the pancreatic exocrine secretion is regulated by CCK released by guanidinated casein hydrolysate. A guanidyl residue is likely to be involved in this control.

Animals↗
PubMed1999

Stimulative effect of a casein hydrolysate on exocrine pancreatic secretion that is independent of luminal trypsin inhibitory activity in rats.

We have previously demonstrated that proteins could stimulate pancreatic secretion independently of luminal bile-pancreatic juice (BPJ) in a BPJ-diverted rat. To determine whether luminal protease-independent pancreatic secretion occurs in normal rats with BPJ returned to the upper small intestine, we investigated the pancreatic secretory response to intraduodenal instillation of a casein hydrolysate or the synthetic trypsin inhibitor, FOY 305, at concentrations which could almost equally inhibit hydrolysis of the synthetic substrate for trypsin with the luminal content. FOY 305 at 10 micrograms/ml and casein hydrolysate solutions at both 100 and 200 mg/ml similarly inhibited approx. 80% of the tryptic activity in the luminal contents of the proximal small intestine. Intraduodenal administration of casein hydrolysate solutions (100 and 200 mg/ml) significantly increased pancreatic secretion in a dose-dependent manner. However, intraduodenal administration of FOY 305 (10 micrograms/ml) was ineffective for stimulating pancreatic secretion. These results demonstrate that dietary protein enhances pancreatic secretion independently of the masking of luminal trypsin activity in rats.

Adolescent↗