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Physiological significance of secretin in the pancreatic bicarbonate secretion. I. Responsiveness of the secretin-releasing system in the upper duodenum.

In nine normal subjects intraduodenal pH was measured by means of a glass electrode placed in the passage from the first to the second part of the duodenum. The physiological variations in pH were simulated by intraduodenal injection of 2.5, 5, or 10 ml of 0.1 mol x 1(-1) HCl and subsequent neutralization by injection of bicarbonate. A total of 26 injections of acid was followed by a pH spike from a median pH of 7.0 to a median of pH 2.1 Median spike duration was 45 sec. The concentration of secretin in plasma increased from a median of 1.2 pmol x 1(-1) to a peak value of 2.2 pmol x 1(-1) after 4 min. It is concluded that the secretin response to a brief acidification of the first 4--6 cm of the duodenum is sufficient to explain the physiological variations in the concentration of secretin in human plasma.

Bicarbonates↗

A model for simultaneous study of pressure and electric events in the rabbit sphincter of Oddi and duodenum.

An animal experimental model featuring simultaneous recordings of electromyography and pressure from the sphincter of Oddi (SO) and duodenum is demonstrated. On the basis of data from 10 rabbits, pressure recordings from the SO were shown to have phasic activity with an average basic pressure peak interval of 2.6 to 3.5 sec. Histographic analysis of SO pressure recordings showed a multimodal appearance, suggesting that the activity is paced. A substantial amount of overlap between SO and duodenal contractions was observed. As many as 30% of the pressure peaks recorded from the SO could not be assigned to a spike complex in the corresponding EMG tracings. It is suggested that combined recordings of EMG and pressure activity are needed to characterize fully the motility of the SO and duodenum.

Ampulla of Vater↗

Rabbit sphincter of Oddi and duodenum are regulated by slow waves with a common basic-mode activity.

Simultaneous recordings of pressure and slow-wave activity were obtained from the sphincter of Oddi (SO) and the duodenum in anesthetized rabbits. Histographic analysis of the recordings was performed when the following criteria were fulfilled: 1) slow waves must be present in the EMG recordings from both compartments; and 2) only pressure recordings with sufficient pressure activity (greater than 50 peaks in 10 min) would be considered. Of 12 animals fulfilling the criteria for histographic analysis of 4 channels, a common basic-mode activity was found in all channels in 9 animals (75%). Of three animals fulfilling the criteria for histographic analysis of three channels, a common basic-mode activity was seen in all channels in all animals (100%). A correlation between the amplitude of the slow waves and the amplitude of the elicited pressure peaks in the SO was significant at a 5% level or better in 12 animals (80%). In some of the animals episodes of low-amplitude pressure activity was observed in the SO, occurring synchronously with slow waves devoid of spike activity. It is concluded that rabbit SO and duodenum are paced by slow waves with a common basic-mode activity in most animals. Slow waves may not only be the chief determinant of the contractile rhythm but may also have a certain influence on the force of the individual SO contractions. It is suggested that slow waves per se may be able to mediate contractile activity.

Ampulla of Vater↗

Pancreatic, hepatic, and duodenal mucosal bicarbonate secretion during infusion of secretin and cholecystokinin. Evidence of the importance of hepatic bicarbonate in the neutralization of acid in the duodenum of anaesthetized pigs.

The effect of infusion of secretin alone or in combination with cholecystokinin (CCK) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion was studied in anaesthetized pigs. After laparotomy, catheters were inserted into the common bile duct, the pancreatic duct, and both ends of the duodenum. Pancreatic, hepatic, and duodenal mucosal secretions were collected during intraportal infusion of increasing doses of secretin, either alone or in combination with CCK. During infusion of secretin in doses that caused physiologic increases in plasma secretin concentrations the liver produced significantly more bicarbonate than the pancreas. A physiologic dose of CCK augmented the effect of secretin on both hepatic and pancreatic bicarbonate secretion, but the hepatic production of bicarbonate was still larger than the pancreatic production. Neither secretin alone nor secretin combined with CCK caused any changes in duodenal mucosal bicarbonate secretion. These results suggest that the liver plays an important role in the neutralization of acid in the duodenum.

Animals↗

Exposure of the duodenum to high concentrations of hydrochloric acid. Effects on mucosal permeability, alkaline secretion, and blood flow.

Proximal duodenum was perfused with HCl for 5 min and the effects on blood-to-lumen clearance of 51Cr-EDTA (ED-Cl), morphology, luminal alkalinization, and blood flow determined in anesthetized rats. The rate of alkalinization was determined by back titration and blood flow assessed by laser Doppler flowmetry or by ultrasonic transit time flowmetry. Perfusion of duodenum with 30, 50 or 100 mM HCl for 5 min increased ED-Cl in a concentration-dependent manner and induced a small increase in alkalinization but had no effect on blood flow. At 55 min after cessation of perfusion with 100 mM HCl ED-Cl was 2.2-fold higher than control whereas the ED-Cl values in animals perfused with 30 or 50 mM HCl were not different from pre-acid control values. 100 mM HCl also induced an increase in 14C-mannitol and 14C-polyethylene glycol 4000 clearance, suggesting that HCl does indeed increase mucosal permeability. The 100 mM HCl-induced rise in mucosal permeability most probably reflects disturbance of mucosal integrity because three of five animals exhibited villous tip damage. The increases in ED-Cl in response to 100 mM HCl were the same in control rats as in rats with the renal pedicles ligated, indicating that the acid susceptibility is not affected by acute functional nephrectomy.

Alkalies↗

[Effects of precursors and metabolites of catecholamines on motricity of isolated rat duodenum. Particular reference to dopamine].

Studying the effects, on the isolated rat duodenum motricity, of ten compounds precursors or metabolites of catecholamines, the following results were obtained: The direct metabolites of epinephrine and norepinephrine (metanephrine, normetanephrine), are either ineffective at concentrations below 5 X 10(-6) M, or weakly inhibitory at higher concentrations. Such inhibitory effects are prevented by alpha- and beta-blockers. 3-methoxy, 4-hydroxyphenylglycol and vanylmandelic acid have no significant effect. The catecholamine precursor, dopamine, the related compounds DOPA, 3 methoxytyramine, and to a lesser extent, 3-O methyl DOPA and homovanillic acid, have excito-motor effects at concentrations ranging mainly from 10(-7) M to 10(-5) M. At higher concentrations, the same compounds frequently exhibit inhibitory effects. The excito-motor effects might be due to a serotoninergic mechanism, since they are suppressed by the serotoninergic blocking agents methysergide and cyproheptadine. Furthermore, in the case of DOPA, we were able to establish a relationship between the excito-motor effects and duodenal serotonin stores. As for the inhibitory effects, they may be prevented by using alpha and beta blocking agents. Dihydroxyphenylacetic acid has no effect on the isolated rat duodenum motricity. The fact that dopamine and related compounds may have excitomotor effects at some concentrations, correlated with some physiopathological observations in man and animal allows some considerations about the eventual role of dopamine on intestinal motricity.

Animals↗

Spontaneous electromechanical activity in the rat duodenum in vitro.

Isolated rat duodenum shows spontaneous mechanical and electrical activities. Mechanical activity consists in changes both in endoluminal pressure and in isometric tension. Electrical activity is characterized by slow waves with superimposed bursts. This spontaneous activity is tetrodotoxin (TTX) resistant and therefore it is myogenic in origin. Indeed, TTX pretreatment, even in the presence of atropine and guanethidine, caused an increase in amplitude and in frequency of the electrical and mechanical activities. This finding indicates the presence of tonically active inhibitory intramural non adrenergic, non cholinergic (NANC) nerves. Duodenal longitudinal strips showed a spontaneous mechanical activity resembling that one recorded from isolated segment. Instead, circular strips are quiescent under resting condition and a contractile activity can be detected only after TTX pretreatment suggesting that: i) the circular smooth muscle layer is tonically inhibited by intramural NANC nerves and, ii) the contractions observed in the rat duodenum are due to the activity of the longitudinal one.

Animals↗

On the purinergic system in rat duodenum: existence of P1 and P2 receptors on the smooth muscle.

In rat duodenum, in vitro, in the presence of atropine and guanethidine, ATP administration caused a tetrodotoxin-insensitive relaxation followed by a rebound contraction. A similar response was obtained also after electrical field stimulation (EFS) of non-adrenergic, non-cholinergic (NANC) nerves. alpha, beta-methylene-TP and theophylline antagonized the response to ATP, but they failed to affect the noradrenaline- and EFS-induced relaxation. These results suggest that P1 and P2 receptors are present in rat duodenum, but their activation is not responsible for the inhibitor effects due to the NANC nerves.

Adenosine Triphosphate↗

Changes in graft blood flow early after syngeneic rat pancreas-duodenum transplantation.

Organ transplantation is associated with changes in graft blood flow, both acutely caused by reperfusion associated phenomena, and chronically due to e.g. denervation. The aim of the study was to investigate regional blood flow early after implantation of a syngeneic pancreas-duodenum transplant in rats, i.e. during reperfusion. Warm ischemia time was 1-2 min and cold ischemia 90 min. Blood flow values were measured with coloured microspheres both 10 and 30 min after implantation in transplanted rats, and at one time point in control rats. A marked decrease in the blood perfusion of the transplanted duodenum compared to the endogenous intestine was seen at both 10 and 30 min. Total graft pancreatic blood flow was increased both 10 and 30 min after implantation, whilst islet blood flow remained unchanged compared to the endogenous gland. We conclude that the blood perfusion of the graft is markedly changed in the immediate post-transplantation period, presumably due to reperfusion. However, islet blood perfusion remains constant, suggesting that islet vasculature is less sensitive to changes induced by the implantation.

Animals↗

Prediction of crude protein and amino acid passage to the duodenum of lactating cows by models compared with in vivo data.

To determine whether statistical inferences obtained from predictions by models were similar to those of measured data from individual cows, data from six research trials published between 1989 and 1997 were simulated using the 1989 National Research Council Model, the Mepron Dairy Ration Evaluator (version 1.1), The University of Pennsylvania release of the Net Carbohydrate and Protein System (version 2.12p), The Cornell Net Carbohydrate and Protein System (version 3), and the CPM Dairy (version 1.0). Both predicted and measured protein fractions were analyzed by ANOVA and compared to determine whether statistical inferences among treatments from predictions by the models were similar to those from the measured data. The interpretations and statistical inferences of measured data did not always agree with those for predicted data. All models responded to changes in diet composition and often predicted that dietary changes would result in statistically different amounts of protein and amino acids passing to the duodenum than were observed in the measured data. The direction of predicted change among treatments for passage of nitrogen fractions to the duodenum also did not agree with the measured data a large percentage of the time. Discrepancies in ANOVA and interpretations between predicted and measured data may be due to the reduction in variation associated with modeling biological systems, associative effects of feeds not accounted for by models, inadequate equations in the models, inadequate description of feeds, or experimental error in measured data. Before model simulations of duodenal flow of crude protein and amino acids can be substituted for experimental measurements, better descriptors of main dietary effects, microbial protein production, ruminal protein degradation, and interactions among dietary factors must be developed.

Amino Acids↗

Reassessment of biases in predicted nitrogen flows to the duodenum by NRC 2001.

The appearance of numerous plots in recent literature from which the residuals are plotted against observed values (Y) to assess a model's potential bias raises this question: should residuals be regressed against Y or against predicted values (Y)? The answer requires knowing the expected relationship under the assumption of an unbiased model. The objectives of this paper are: 1) to derive the expected relationship between residuals, Y, and Y; 2) to determine whether Y or Y should be used for the assessment of bias; and 3) to reassess the extent of mean and linear bias in the prediction of N flows to the duodenum by the NRC (2001). In the simplest case, we can assume a true model of the form Y = Xbeta + epsilon. This model is estimated by Y = Xb + e, and Y = Xb. The correlation between the residual vector e and the vector of observations Y can easily be derived. The numerator of the correlation coefficient is shown to be equal to e'e, the residual sum of squares. The denominator of this correlation is equal to the square root of e'e multiplied by the total sum of squares. Algebraic simplifications show that the correlation between e and Y is equal to the square root of (1-R2). That is, under the assumption of an unbiased model, the residuals are correlated with the observed values and the slope of e regressed on Y is equal to (1-R2). Thus, a graph of e versus Y will show a positive slope between e and Y unless the model is a perfect predictor (i.e., R2 is equal to 1.0). Significant slopes linking e to Y have been erroneously interpreted as evidence of biased models in the NRC (2001). Conversely, the slope of e regressed on Y is expected to be zero under the assumption of an unbiased model. Therefore, residuals should be regressed against Y and not Y. When Y, as opposed to Y, was used to assess biases in the prediction of flows to the duodenum of microbial N, nonammonia-nonmicrobial N and nonammonia N in NRC (2001), mean biases became nonsignificant and linear biases over the range of predicted values are of the same magnitude or smaller than the standard errors of measurements reported in literature. Thus, although N flow predictions from NRC (2001) may not be precise, they appear to have insignificant and inconsequential biases.

Ammonia↗

Effects of dietary fat and protein on fatty acid flow to the duodenum and in milk produced by dairy cows.

Four Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square with treatments in a 2 x 2 factorial arrangement. Treatments were 1) soybean meal, no fat; 2) fish meal, no fat; 3) soybean meal, fat; and 4) fish meal, fat. Cows were fed for ad libitum intake a diet of alfalfa haylage, corn silage, and concentrate (30:20:50) on a DM basis. Intake of gross energy (105 Mcal/d) was not altered by treatment comparisons. However, feeding fat decreased energy digested in the rumen (15 vs. 24%) and increased energy digested postruminally (55 vs. 43%) but resulted in similar amounts of energy (72 Mcal/d) digested in the total tract. The flow of C14:0, C16:0, C18:0, C18:1, C18:2, C18:3, and total fatty acids to the duodenum was increased by feeding fat. The average flow of C14:0, total C18, and total fatty acids to the duodenum was greater than their intake for all treatments, suggesting de novo synthesis of fatty acids by ruminal microbes. Biohydrogenation of unsaturated C18 was decreased 70, 67, 59, and 51% for treatments 1 to 4, respectively, by feeding fat and fish meal. Digestibility of total fatty acids entering the small intestine (78%) was not altered by treatment comparisons; however, feeding fat altered digestibility of individual fatty acids. The proportion of C16:0 and C18:1 was increased, and the proportion of C6:0, C8:0, C10:0, C12:0, and C14:0 was decreased in milk fat produced by cows fed fat.

Animal Feed↗

Effect of isocaloric infusion of glucose in the rumen or propionate in the duodenum.

This study was undertaken to understand better the mechanisms causing increased milk protein. Cows fed steam-flaked sorghum have increased milk protein compared with that of cows fed dry-rolled sorghum because of a large shift of starch digestion from the intestine to the rumen. Five cannulated lactating cows were infused with glucose in the rumen or with propionate in the duodenum in two trials. The experimental design was a 2 x 2 Latin square with 7 d of adjustment and 7 d of infusion. During the experiment, cows received a TMR containing 19.3% CP and 1.56 Mcal/kg of NEL (on a DM basis); alfalfa hay and dry-rolled sorghum grain were the principal ingredients. Similar concentrations in feces of cows among propionate treatments suggested complete absorption of infused propionate. Milk yield did not differ, but protein percentage of milk was higher (2.88 versus 2.72%) for cows infused ruminally with glucose than for those infused in the duodenum with propionate. For the respective treatments, duodenal flows were 2.11 and 1.76 kg/d for microbial protein and 3.44 and 2.73 kg/d for total CP (or 85 and 74% of CP intake). These data demonstrate that increased propionate availability for gluconeogenesis and a possible sparing of essential AA did not result in increased milk protein content, but ruminal infusion of glucose, which tended to increase microbial protein synthesis, did increase the protein percentage of milk.

Adenosine Triphosphate↗

Ruminal fermentation and passage of nutrients to the duodenum of lactating cows fed mixtures of corn and barley.

Five Holstein cows were used in a 5 x 5 Latin square design and fed diets containing five different ratios of starch from ground shelled corn and steam-rolled barley. The DMI decreased and both the proportions of OM and starch digested in the rumen increased as barley starch increased in the diet. Corn and barley starches fed in a ratio of 75:25 maximized the proportions of ADF and NDF digested in the rumen. Replacement of 25% of the corn starch with barley starch resulted in the largest increase in the molar percentage of propionate and the largest decrease in the molar percentage of acetate in ruminal fluid. Passage of NAN to the duodenum was not affected by treatment; however, the percentage of nonammonia nonmicrobial N in NAN decreased as barley starch increased. Passage of AA to the duodenum was largest when corn and barley starches were fed in ratios of 100: 0 and 0:100 because of the influence of DMI and microbial protein synthesis. Production of Milk, CP, and SNF was similar when cows were fed diets containing corn and barley starches in ratios of 100:0, 75:25, and 50:50 but was decreased when the ratios were 25:75 and 0:100. Increased production responses of cows when diets contained larger amounts of starch from ground shelled corn were probably due to increased DMI.

Amino Acids↗

Modeling ruminal digestibility of carbohydrates and microbial protein flow to the duodenum.

Carbohydrates are the major source of energy for dairy cows and for microbial protein synthesis in the rumen. The prediction of ruminal carbohydrate digestibility and of the flow of microbial protein to the small intestine is difficult because of the variability among various feeds in the kinetics of digestion and passage of neutral detergent fiber and starch. Disappearance of fiber and starch in vitro or in situ and gas production in vitro have been extensively evaluated, improved, and reviewed. Similarly, markers and models to measure ruminal passage rate have been extensively researched and improved. Sources of variation and decreased accuracy for these techniques are discussed. Variation and potential errors also remain for the prediction of microbial protein flow to the duodenum using in vivo procedures. However, when in vivo results were accumulated into a database, microbial N flow to the duodenum over a wide range of conditions could be predicted accurately by intake of net energy for lactation or by dry matter intake and percentage of neutral detergent fiber in the diet. Although evaluation of feeding interactions and specific dietary limitations for microbial protein production in the rumen are possible with some models but not with this regression approach, mechanistic models need further validation and more accurate rate constants for improved accuracy over a wide range of conditions.

Animals↗

Prostaglandin-mediated trophic effects on the rat duodenum: the role of polyamines.

Ornithine decarboxylase (ODC) is the initial rate-limiting enzyme in polyamine biosynthesis. The relationship between ODC and polyamines and the trophic effect of prostaglandin in the rat gastrointestinal tract are unknown. In these studies we determined whether inhibition of ODC activity and subsequent polyamine biosynthesis with the specific enzyme inhibitor difluoromethyornithine (DFMO) would attenuate prostaglandin-mediated trophic effects in the rat duodenum. Significant increases in duodenal mucosal wet weight, RNA, DNA, and protein were found following treatment with 16,16-dimethyl-PGE2 (1 mg/kg) for 1 week. This trophic response was significantly reduced (P less than 0.01) in the duodenum of rats treated concomitantly with DFMO. In addition, this prostenoid significantly increased (4X) duodenal ODC levels, 2 hr following acute administration. These results suggest that polyamines are required for the prostaglandin-stimulated growth of the rat duodenal mucosa.

16,16-Dimethylprostaglandin E2↗

Hematemesis as the initial complication of pancreatic adenocarcinoma directly invading the duodenum: a case report.

Pancreatic carcinoma is a debilitating disease and carries a poor prognosis. It is a rare cause of upper gastrointestinal bleeding, even though pancreas, stomach, duodenum and jejunum are adjacent organs. The incidence of pancreatic adenocarcinoma directly invading the gastrointestinal tract leading to gastrointestinal hemorrhage is very low, and most of them present with melena and hematochezia. Here, we describe one unique case manifesting characteristically severe and unremitting hematemesis as an initial presentation of pancreatic adenocarcinoma. This tumor directly invaded the duodenal mucosa as a bleeding protruding tumor mass. Our MEDLINE search has confirmed that this is the first reported case with an initial manifestation of hematemesis from pancreatic adenocarcinoma in Asians. Pancreatic adenocarcinoma directly invading duodenum complicated by hemorrhage can be a rare cause of hematemesis, and clinicians should be reminded of it while they are making differential diagnosis.

Adenocarcinoma↗

Characteristics of human IgA and IgM genes used by plasma cells in the salivary gland resemble those used in duodenum but not those used in the spleen.

Immunologically, the parotid salivary gland is an effector site that secretes large quantities of polyspecific Abs into the saliva, mainly of the IgA isotype. It is considered to be part of the common mucosal immune system but the inductive site for the Ab-producing cells of the salivary gland has not yet been clearly identified. The origin and diversity of cells of B lineage can be investigated by analyzing their Ig heavy chain genes (IgH). We have obtained sequences of IgM and IgA VH4-34 genes from plasma cells in human salivary gland, duodenal lamina propria, and splenic red pulp. Related sequences were found in different areas sampled within each tissue studied, indicating that the plasma cells carrying these genes are widespread with limited diversity. Examples of related IgH genes that are isotype switched were also seen in the salivary gland. The genes from plasma cells of the salivary gland were highly mutated, as were duodenal plasma cell sequences. The level of mutation was significantly higher than that seen in splenic plasma cell sequences. Analysis of CDR3 regions showed that the sequences from salivary gland had significantly smaller CDR3 regions than sequences from spleen, due to differences in number and type of DH regions used. Sequences from duodenum also had smaller CDR3 regions. Therefore, plasma cells from human duodenum and salivary gland showed characteristics that differed from those of human splenic plasma cells.

Base Sequence↗