Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.
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PMID:The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans. 156 84

Zymosan (Z) and its major insoluble carbohydrate component beta-linked glucan activate human neutrophils (PMN) through a trypsin-sensitive recognition mechanism. This mechanism is believed to involve the PMN CR3R. Both Z and glucan generated dose and time-dependent release of the secondary lysosomal granule marker vitamin B12 binding protein, leukotriene B4 (LTB4) and superoxide from PMN and were phagocytosed with similar dose-dependent kinetics. The PMN superoxide and LTB4 responses to glucan; however, were consistently greater than those to the same doses of Z. The phagocytosis of both particles was significantly reduced after partial digestion with beta-laminarinase but not beta-glucosidase or alpha-mannosidase suggesting a recognition mechanism dependent on intact beta-1,3-glucosidic bonds in both particles. TNF-alpha (rhTNF-alpha) promoted a time- and dose-dependent increase in the expression of PMN CR3 up to 60 min. The increased expression of CR3 was paralleled by the release of the secondary lysosomal granule marker vitamin B12-binding protein. This granule contains a population of CR3R in its boundary membrane and it is the fusion of this membrane with the plasma membrane that may represent the mechanism by which CR3 expression is increased. Preincubation of PMN with 10(-9)M rhTNF-alpha augmented phagocytosis, LTB4, and superoxide generation by PMN in response to activation by Z. In contrast, none of the responses to glucan was significantly increased after incubation with rhTNF-alpha. These differences suggest a lack of absolute homology between the recognition mechanisms for zymosan and glucan and that there is a component of the recognition mechanism for zymosan that is independent of that for glucan and is up-regulated after rhTNF-alpha pretreatment.
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PMID:Differential augmentation by recombinant human tumor necrosis factor-alpha of neutrophil responses to particulate zymosan and glucan. 215 33

Factors influencing the effectivity of replacement therapy with Panpur and Creon were controlled by in vivo and in vitro investigations. Both enteric coated preparations were equally acid protected, they even seemed to be more effective in hyperacid than in anacid chronic pancreatitis patients. Thus the uneven results of Panpur treatment in pancreatic steatorrhea cannot be explained by acid inactivation of the enzymes. Creon dose-dependently ameliorated the steatorrhea as well as vitamin B12 absorption while crushed but not the intact Panpur has only some insignificant effect. Good mixing of pancreatin with the B12-intrinsic factor - R protein complex and with the protein containing meal seems to be important for digestion of protein as well as fat. Unbound, overflowing trypsin activity of Panpur resulted in fast proteolytic inactivation of lipase. This could be diminished by soybean trypsin inhibitor which increased the in vivo effectiveness of the preparate. In summary Creon fulfilled two important factors of replacement therapy more successfully than Panpur: good mixing with meals and stability of lipase against proteolytic splitting, that is why it proved to be more effective for replacement therapy of pancreatic insufficiency.
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PMID:[Requirements for successful pancreatic enzyme replacement therapy (comparative study of Kreon and Panpur)]. 230 64

A multi-channel small diameter tube was used to study the secretion of bicarbonate by 3 cm long segments of the proximal duodenum isolated between balloons. The tube had an outer diameter of 5.3 mm and two central and four smaller, peripheral channels. Measurements of infused phenol red, 14C-PEG and vitamin B12 and of trypsin activity were performed to rule out contamination of the perfusate by gastric and pancreatic secretions. Basal secretion of bicarbonate by the duodenal mucosa in healthy subjects varied between 135 and 220 mumol/cm of intestine per hour. Perfusion of the lumen with acid (100 mM HCl for five minutes) increased the secretion to greater than 400 mumol/cm/h and the alpha 2-adrenoreceptor agonist clonidine (150 micrograms iv) decreased the HCO3- secretion by 70 mumol/cm/h. Clonidine simultaneously reduced the mean arterial blood pressure and plasma noradrenaline concentration, but did not affect the plasma glucose or adrenaline concentration. Duodenal bicarbonate secretion is important in the protection of this mucosa against acid discharged from the stomach. Increased sympathetic activity may, by inhibiting the bicarbonate secretion, decrease the protection in proximal duodenum in man and facilitate ulceration.
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PMID:Duodenal mucosal bicarbonate secretion in man. Stimulation by acid and inhibition by the alpha 2-adrenoceptor agonist clonidine. 255 85

Epidermal cysts are one of the most common tumors of the skin. Although asymptomatic ordinarily, they may sometimes become severely inflamed with massive invasion of polymorphonuclear leukocytes (PMN). We studied in vitro PMN chemotactic properties of the aqueous extract prepared from the horny material of epidermal cysts obtained from three patients. A crude aqueous extract of the horny content of the cysts showed PMN chemotactic activity, which, however, was less than that of a horny layer extract prepared from normal skin. Characterization of PMN chemotactic activity using a Sephadex G-75 column showed a peak in the low molecular weight fractions eluting between the vitamin B12 and phenol red markers, which corresponds with the peak of absorbance at 280 nm. The chemotactic substances withstood boiling and trypsin or protease digestion. Although the chemotactic activity was partially ether-extractable, the presence of leukotriene B4 was not demonstrated by radioimmunoassay. In addition to their own chemotactic activity, the horny extracts of epidermal cysts showed cytotaxigenic properties in the presence of fresh serum.
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PMID:Leukocyte chemotactic properties of soluble horny contents in epidermal cysts. 343 73

Experiments were conducted to investigate a possible interference by raw soybean meal (RSM) with B12 nutriture of chickens. In Experiment 1, day-old chicks were fed B12-free isonitrogenous and equienergetic diets containing 0 or 40% RSM to determine if RSM accelerated storage losses of B12. After 42 days, RSM decreased growth (P less than .01), decreased hepatic (P less than .01) and blood (P less than .05) concentrations of glutathione (GSH), and increased (P less than .01) pancreas and liver weights. However, statistically significant differences due to treatment were not detected in hepatic B12 concentration, indicating that RSM does not enhance B12 turnover in chicks. To ascertain the effect of RSM on B12 absorption, 9 micrograms B12/kg diet was added to diets containing 0 or 40% RSM and fed to chicks to 42 days of age. Raw soybean meal depressed growth (P less than .001) and hepatic GSH (P less than .01) and increased (P less than .001) pancreas weights. The RSM had no effect on hepatic B12 concentration, suggesting that RSM trypsin inhibition does not impair B12 absorption in chicks. A third experiment was designed to test the hypothesis that vitamin B12 stimulates egg production or feed intake of hens fed a diet with 27% RSM. Vitamin B12-depleted hens were fed RSM or heat-treated soybean meal (HSM) diets containing equivalent amounts of soybean protein, oil, and hulls. Hens received either 26 micrograms B12/kg BW per os or 13 micrograms B12/kg BW intramuscularly twice within a 30-day period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin B12 nutriture of chickens fed raw soybean meal. 396 Aug 9

Bovine rotavirus infectivity for continuous green monkey kidney (BSC-1) cells was enhanced in hypertonic medium and following incorporation of cortisol, retinoic acid and vitamin B12 into the cell culture maintenance medium. The virus yields produced under these conditions were similar whether obtained in the presence or absence of trypsin. Infectivity titres were increased following the incorporation of trypsin in the maintenance medium throughout the infection cycle but remained unchanged after trypsin treatment of infected cell extracts. Bovine rotavirus infectivity was not affected by incorporation of phytohaemagglutinin, thyroid gland extracts or foetal calf serum in similar experiments. Unexpectedly, serum promoted virus growth when used with cells treated with actinomycin D. Marked differences in the stability of the newly produced infectious rotavirus were observed, suggesting that cell permissiveness to rotavirus infection may vary following the physiological state of the host cell.
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PMID:Enhanced production of infectious rotavirus in BSC-1 cell cultures by various factors in the presence of absence of trypsin. 626 38

A serum-free culture of dissociated neurons from embryonic rat hippocampus has been established as a rapid and quantitative in vitro test system for neurotrophic signals in the mammalian brain. By means of this cell culture bioassay, a novel low molecular weight neurotrophic factor (NTF) could be identified. NTF is essential for in vitro brain neuron development, promoting survival and neurite outgrowth. The diffusible factor is synthesized and secreted into serum-free defined medium by cultured astrocytes from rat cerebral hemispheres. The number of viable neurons responding to NTF by neurite outgrowth is dependent on the concentration of the factor. Fractionation of astroglial conditioned medium by gel filtration on columns of Sephadex G-10 recovered biological activity of NTF in a single sharp peak corresponding to an apparent molecular weight of approximately equal to 500. NTF is stable to heat and cold and resistant to trypsin and pronase. Unlike nerve growth factor, NTF has no apparent effect on the neurite outgrowth of peripheral neurons. NTF-like activity is present in situ in the mammalian brain, in certain other nonneural tissues, and in C6 and B12 glioma cell conditioned media.
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PMID:Neurotrophic factor for central neurons. 636

Vitamin B12 absorption was measured in 30 patients with cystic fibrosis by means of the urinary excretion method and found to be impaired, i.e. less than 10%, in 25. The mean urinary excretion amounted to 4.7 +/- 0.8%. In all patients vitamin B12 absorption improved by the addition of trypsin (18.9 +/- 2.1%). Addition of the vitamin B12 analogue cobinamide, which prevents vitamin B12-binding by R-binders, raised the vitamin B12 absorption to 15.0 +/- 2.2%. A further improvement was obtained by the simultaneous addition of cobinamide and trypsin, 18.2 +/- 2.6%, the same value as with trypsin alone. Assuming that cobinamide addition was effective in suppressing all R-binder activity, the additional effect of trypsin suggests a second, stimulatory function of trypsin on vitamin B12 absorption, separate from R-binder-inactivation. In 5 patients only marginal improvement of vitamin B12 absorption was gained by the addition of either trypsin or cobinamide. The deficient serum vitamin B12 (110 pmol/l) in one of them indicates that the normal pancreas-substitution therapy not always implies sufficient restoration of vitamin B12 absorption.
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PMID:Vitamin B12 absorption in cystic fibrosis. 646 42

Human milk contains unsaturated lactoferrin and vitamin B12 binding protein. It has been suggested that these proteins may exert antibacterial effects in the intestine of the breast fed infant, but the effect of the intestinal environment on the antibacterial effect of these proteins has not been described. In this study human milk was treated with pepsin and trypsin and the influence of digestion on iron and vitamin B12 binding capacity, bacterial uptake of iron and vitamin B12 from milk and bacteriostatic effect was studied. Pepsin digestion had no effect on vitamin B12 binding capacity, or the ability of bacteria to take up vitamin B12, or the growth inhibitory effect on a vitamin B12 dependent strain. In contrast, trypsin digestion did not affect iron binding or bacteriostatic effects attributable to lactoferrin. The. findings support an in vivo bacteriostatic role for lactoferrin in the breast fed neonate's intestine but do not support a similar role for the vitamin B12 binding protein.
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PMID:The effect of digestive enzymes on the binding and bacteriostatic properties of lactoferrin and vitamin B12 binder in human milk. 677 68


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