Effects of duodenal perfusion with sodium taurocholate on biliary and pancreatic secretion in man

Abstract. The effects of intraluminal sodium taurocholate (STC) on biliary and pancreatic secretion were studied in man using a duodenal perfusion technique and indocyanine green (ICG) as an exogenous biliary marker. Duodenal perfusion with 15 or 30 mmol/l STC in healthy subjects markedly suppressed caerulein and secretin stimulated biliary indocyanine green (ICG) excretion in a dose responsive manner, i.e. to 40% (17–95%, ± 2 SD, n = 5) ( P < 0.025) and 32% (26–38%, ± 2 SD, n = 3) ( P < 0.003) of i.v. ICG infusion, respectively, with a maximum suppression to 26% and 10%, respectively. In cholecystectomized subjects ( n = 5), significant changes in ICG excretion were not observed during STC (15 mmol/l) perfusion. There were no suppressive effects on pancreatic enzyme or bicarbonate secretion in any of the subjects. Our observations suggest that the bile salt STC in the duodenum in man activated a mechanism which selectively suppressed biliary excretion. This is probably due to relaxation of the gallbladder and an increase in gallbladder storage of bile.     

Effect of cholestyramine on plasma cholecystokinin and pancreatic polypeptide levels, and exocrine pancreatic secretion

The effect of acute and long-term administration of cholestyramine, a non-absorbable bile salt binding resin, on exocrine pancreatic secretion, plasma-cholecystokinin (CCK) and plasma-pancreatic polypeptide (PP) was investigated in 10 healthy volunteers. Oral ingestion of 12 g cholestyramine augmented the stimulatory effect of a liquid test meal on plasma-CCK (3.5-fold) and plasma-PP (2-fold). During prolonged treatment with 3 x 12 g cholestyramine daily for 4 weeks, the most pronounced increase in basal hormone levels was observed after 1 day, but progressively decreased during treatment and had normalized after 4 weeks. However, the stimulated plasma-CCK output was still significantly elevated after cessation of treatment, compared with pretreatment values. After acute and chronic cholestyramine administration only stimulated lipase secretion was elevated, whereas trypsin and amylase remained unchanged. It is suggested that removal of bile salts enhances CCK and thereby PP release and pancreatic lipase secretion.     

Gallbladder and Small Intestinal Regulation of Biliary Lipid Secretion during Intraduodenal Infusion of Standard Stimuli

The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.     

Does jejunal feeding activate exocrine pancreatic secretion?

BACKGROUND: The upper small bowel is of pivotal importance for the stimulation of exocrine pancreatic secretion in response to a meal. We hypothesize that more distal delivery of nutrients into the small intestine will result in less activation of pancreatic secretion. MATERIALS AND METHODS: Eight healthy subjects (3 male, 5 female; age 23 +/- 1 years) participated in two experiments, performed in random order. Subjects were intubated with a 4-lumen tube. Duodenal outputs of pancreatic enzymes and bilirubin were measured by aspiration using a recovery marker. The distal opening was used for continuous administration of a mixed liquid meal and located at either the ligament of Treitz or 60 cm further distally. Gallbladder volume was measured and blood samples were drawn for determination of gastrointestinal hormones. The duration of each experiment was 4 h; with 1 h fasting and 3 h continuous administration of nutrients. RESULTS: During proximal jejunal feeding, pancreatic enzyme output increased significantly over basal levels. No significant increase over basal levels was observed during distal jejunal feeding. Bilirubin output and gallbladder contraction were significantly (P < 0.05) reduced during distal compared to proximal jejunal feeding. No significant differences were found in plasma levels of CCK, PYY and neurotensin between proximal and distal jejunal feeding. CONCLUSION: Continuous feeding in the distal jejunum does not stimulate exocrine pancreatic secretion but maintains gallbladder contraction, although to a lesser extent. These effects are not related to hormonal changes but probably reduced activation of the enteropancreatic reflexes.     

Effect of somatostatin on postprandial gallbladder relaxation

Although the inhibitory effect of somatostatin (SST) on gallbladder contraction is well known, the influence of SST on gallbladder motility during the late postprandial or relaxation phase has not been studied. We therefore investigated the effect of SST on gallbladder relaxation and gut hormone release during the late postprandial phase. Eight healthy volunteers participated in two experiments performed in random order during continuous infusion of either SST or saline (placebo) starting 2 h after meal ingestion. At regular intervals, gallbladder volumes were measured (ultrasonography) and blood samples were taken for determination of plasma cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and neurotensin levels (radioimmunoassay). Postprandial gallbladder contraction was similar in both experiments: 68 ± 4% vs. 66 ± 4%. During SST infusion, postprandial gallbladder contraction was significantly (P<0·01) reduced (2874 ± 813% *240 min) compared with saline (9391 ± 1595% *240 min). Plasma CCK, PP, PYY and neurotensin levels were in the same range in the early postprandial phase but were significantly reduced during SST infusion compared with placebo (late postprandial phase). Plasma levels of CCK correlated with gallbladder volumes during both the contraction and relaxation phase (r=0·68, P=0·01 and r=0·61, P=0·008, respectively). SST enhances gallbladder relaxation and reduces hormone secretion in the late postprandial phase. The results point to an association between CCK and gallbladder volume not only during the postprandial contraction phase but also during the relaxation phase.     

Somatostatin does not block the effect of vasoactive intestinal peptide on bile secretion in man

The effects of intravenously administered somatostatin and vasoactive intestinal peptide (VIP) on bile secretion were studied in 10 patients with complete biliary fistulas. The two peptides were administered both separately and simultaneously. During the infusion of vasoactive intestinal peptide, bile secretion increased by 85%, whereas during somatostatin infusion it decreased by 40%. When the peptides were administered together, the VIP-induced choleretic effect was not reduced by somatostatin. Vasoactive intestinal peptide infusion increased bicarbonate concentration and output, whereas somatostatin had the opposite effect. The output of chloride also increased following vasoactive intestinal peptide infusion but decreased following somatostatin infusion. The concentration of chloride was unaffected by somatostatin whereas it was decreased by vasoactive intestinal peptide. The output of bile acids was unaffected by vasoactive intestinal peptide and decreased by somatostatin infusion, whereas total lipid concentration increased during somatostatin infusion and decreased when vasoactive intestinal peptide was added. It is concluded that, in man, somatostatin acts on the bile acid-dependent canalicular bile secretion and also, to some extent, on the ductular secretion, whereas vasoactive intestinal peptide acts strictly at the ductular level. The effects of the two peptides on bile secretion are independent of each other.     

Total denervation of the pancreas does not alter the pancreatic polypeptide-induced inhibition of pancreatic exocrine secretion in dogs

Pancreatic polypeptide (PP) is a potent inhibitor of pancreatic exocrine secretion in vivo. The mechanism of pancreatic inhibition by PP is unknown, but the absence of PP receptors on pancreatic exocrine cells makes a direct effect of this hormone on the gland unlikely. In this study, we investigated the hypothesis that PP exerts its inhibitory effect via extrinsic neural pathways. Ten dogs with gastric and pancreatic fistulas were given an intravenous infusion of 250 ng/kg⁻¹ h⁻¹ secretion and 50 ng/kg⁻¹ h⁻¹ caerulein over 3 h. One hour after starting the infusion, 400 pmol kg⁻¹ h⁻¹ porcine PP were administered over 1 h. Pancreatic bicarbonte and protein secretions were measured. Later, the pancreas was extrinsically denervated. PP infusion decreased bicarbonate secretion in the intact gland by 47% and in the denervated pancreas by 57%. Protein secretion was diminished by exogenous PP by 31% in the intact and by 44% in the denervated pancreas. Despite pancreatic denervation, PP still exerted a significant inhibitory effect. Atropine infusion completely blocked the inhibitory effect of PP on caerulein-stimulated pancreatic protein secretion both in the intact and denervated pancreas and of secretion-evoked bicarbonate output in the denervated gland. We conclude that the inhibitory action of the hormone is not mediated via extrinsic neural pathways of the pancreas, but PP may exert its effect via intrinsic atropine-sensitive mechanisms.     

Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man Feedback control of cholecystokinin and gastrin secretion

The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal-stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo-controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg-1 h-1) significantly augmented integrated incremental IR-CCK levels 7.3-fold after stimulation by a standard breakfast (504 +/- 54 vs 3.665 +/- 365 pmol-1 135 min-1, P less than 0.001), as measured by a specific CCK radioimmunoassay. Basal IR-CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high-dose substitution with pancreatic enzymes (4.2 g pancreatin) reduced elevated IR-CCK levels by only 38%. CCK-like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100-250 micrograms ml-1. Plasma gastrin concentrations in response to the breakfast were elevated 3.2-fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal-stimulated integrated incremental plasma PP concentrations were significantly suppressed (55-65% inhibition, P less than 0.01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK-like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK-induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero-insular axis in humans.     

Effects of jejunal reinfusion of aspirated duodenal fluid on biliary and pancreatic secretion in man

Summary. The standard duodenal perfusion technique was used to measure biliary and pancreatic secretion in normal subjects, with and without jejunal reinfusion of aspirated duodenal fluid. In studies carried out without reinfusion of the duodenal aspirate, and where a continuous background stimulation of caerulein and secretin was given throughout the studies to eliminate extrahepatic biliary storage, a gradual fall in bile salt and bilirubin secretion was observed. In contrast, when the experiments were carried out in these same individuals, and under exactly the same experimental conditions except that the duodenal aspirate, rich in bile and pancreatic juice, was in every successive collection period re infused into the jejunum, the bile salt secretion remained stable and the bilirubin secretion increased. In neither series of studies were there any definite changes in the secretory output of trypsin. The total secretory output of bicarbonate was, however, marginally greater in studies carried out with jejunal reinfusion of the aspirate than in the studies where the aspirate was discarded. Carried out under basal conditions, a gradual fall in both biliary and pancreatic secretion was observed in both series of studies. These results indicate that partial diversion of bile and pancreatic juice from the jejunum in man may affect hepato-biliary secretion of bile salts and bilirubin and the secretion of bicarbonate.     

Bile acid content of gallbladder bile and stones in type lib and IV hyperlipoproteinemia

We examined the bile acid composition of gallbladder bile using reversed-phase high performance liquid chromatography (HPLC), in normolipemic and hyperlipidemic (types IIb and IV) patients with cholelithiasis and compared them with normal subjects. Similarly, bile acid composition was determined in the gallstones of these patients.No free bile acids were found in any of the samples examined. We observed that gallbladder bile and gallstones of patients with type IV hyperlipidemia showed a significant increase in the percentage of glyco-conjugated bile acids and reduction in taurine conjugates.Based on this finding we postulate that in addition to biliary lipid composition bile acid composition may also play a role in the pathogenesis of cholesterol gallstone formation.     

Interactions between Intraluminal Bile Acids and Digestive Products on Pancreatic and Gallbladder Function

Interactions between bile acids (taurocholate, TC; taurochenodeoxycholate, TCDC; or taurodeoxycholate, TDC) and digestive products (essential amino acids, EAA or monoolein, MO) in the lumen of the proximal small bowel, affecting pancreatic enzyme secretion and gallbladder contraction, were studied in 77 healthy volunteers by a perfusion method. Perfusion of EAA or MO caused significant increases in pancreatic enzyme output together with gallbladder contraction; MO was more potent and induced enzyme outputs comparable to the maximal response attained with intravenous cholecystokinin-pancreozymin (CCK-PZ). Perfusion of TC alone had no effect, but addition of 10 mM of either TC, TCDC, or TDC to perfusates containing EAA, or 10 mM TC to MO, or both significantly reduced pancreatic enzyme output and prevented gallbladder contraction. A lower concentration of TC (5 mM) added to EAA also produced a significant inhibitory effect. Inhibition of the stimulatory action of digestive products occurred in the jejunum as well as in the duodenum. The inhibitory action of bile acid was considered to be intraluminal since (a) bile acid did not modify the effects of CCK-PZ given intravenously; and (b) the stimulatory effect of digestive products perfused in the duodenum on pancreatic and gallbladder function was not influenced by simultaneous perfusion of bile acid in the jejunum.It is proposed that this inhibitory effect of bile acid is mediated through inhibition of CCK-PZ secretion by high intraluminal concentrations of bile acid. Inhibition of CCK-PZ secretion by bile acid may contribute to the regulation of pancreatic and gallbladder function during digestion by reducing pancreatic enzyme secretion and permitting the gallbladder to refill after evacuation of its contents.     

Effects of obesity and caloric intake on biliary lipid metabolism in man.

The effects of obesity and caloric intake on biliary lipid metabolism were investigated in a series of related studies. The degree of saturation of gallbladder bile with cholesterol was found to be significantly higher in a group of 23 obese healthy subjects than in a group of 23 nonobese controls matched for age, sex, and race. Bile was also significantly more saturated in 11 obese subjects before than after weight reduction. To determine whether supersaturated bile in obesity is due to excessive secretion of cholesterol or to deficient secretion of bile acids and phospholipids, the hepatic outputs of these three lipids were measured during constant duodenal infusion of formula in the same 11 subjects before and after weight reduction. Weight reduction resulted in significant reduction of cholesterol output but not of bile acid or phospholipid output. Moreover, very obese subjects were found to have cholesterol secretion rates markedly higher than less obese subjects previously studied by the same method. In obese subjects, bile was supersaturated with cholesterol despite increased bile acid pool sizes and increased secretion rates of bile acids and phospholipids. Supersaturated bile in the obese could therefore be attributed to a single defect in lipid secretion, namely, an excessive output of cholesterol. To determine whether the rate of caloric intake can account for the effects of obesity on biliary lipid composition and secretion, nine obese white men were studied on a weight maintenance diet and then during weight reduction on a 1,000 cal diet. As compared to weight maintenance, chronic caloric restriction resulted in reduced outputs of cholesterol, bile acids, and phospholipids, reduced bile acid pool size, and reduced synthesis and fecal excretion of cholesterol. Saturation of bile with cholesterol did not decrease during weight reduction, evidently because of the mobilization of cholesterol from adipose stores and the marked reduction in bile acid and phospholipid output observed during chronic caloric restriction. Acute alterations in caloric infusion rates did not fully reproduce the effects of chronic administration of high and low calorie diets. Likewise, chronic intake of hypercaloric diets by nonobese subjects did not reproduce the cholesterol hypersecretion characteristic of the obese. Thus, increased cholesterol secretion in obese subjects could not be fully explained by the amount of calories they ingested to maintain stable weight. It is concluded that obesity is characterized by excessive hepatic secretion of cholesterol which results in supersaturated bile.     

Effects of chlorpromazine hydrochloride on bile salt synthesis, bile formation and biliary lipid secretion in the Rhesus monkey: a model for chlorpromazine-induced cholestasis

We studied the acute effects of intravenous infusions of chlorpromazine hydrochloride on bile salt synthesis, bile formation and biliary lipid secretion in the alert female Rhesus monkey prepared with a total biliary fistula and in a steady bile salt secretory state. In twelve studies (three animals), five doses of radiolabelled chlorpromazine hydrochloride (1-10 mg identical to 2.8-28 mumol/kg) were infused intravenously for 1 h in random order. Cholestasis was induced within minutes in all experiments. The radiolabel appeared rapidly in bile, with similar recoveries in bile and urine and a 90% total cumulative output in 4 days. Both bile flow, bile salt and other biliary lipid outputs were inhibited in a dose related and reversible manner. The apparent bile salt independent bile flow was consistently abolished, and a prompt return to basal values occurred when biliary concentration of the drug and metabolities fell below 1-2 mM. When chlorpromazine hydrochloride was infused at three doses (2.5, 5.0 and 10.0 mg identical to 7-28 mumol/kg) during constant intravenous infusion of 14C sodium taurocholate (300 mumol/h), bile flow, total bile salt output and 14C taurocholate output decreased within minutes. This was accompanied by a progressive rise in the serum 14C taurocholate concentration. After 90 min the taurocholate specific activity in bile increased significantly indicating that bile salt synthesis was inhibited. Secretion of retained bile salts and reversal of inhibition of bile salt synthesis occurred with time: the course of both events was correlated with the dose of the drug. Thus, in monkeys, chlorpromazine hydrochloride induces reversible, dose related cholestasis suppression of the bile salt dependent and independent flow, inhibition of bile salt synthesis and impairment of biliary lipid secretion. We suggest that these effects are due to both bile salt-chlorpromazine interactions and the effect of the latter on canalicular and other membranes.     

Effects of taurodihydrofusidate, a bile salt analogue, on bile formation and biliary lipid secretion in the rhesus monkey.

Bile salts play a major role in bile formation and biliary lipid secretion. Sodium taurodihydrofusidate (TDHF), a derivative of the antibiotic fusidic acid, closely resembles bile salts in terms of structure, micellar characteristics, and capacity ot solubilize otherwise insolbule lipids. We have therefore studied the biliary secretion of this bile salt analogue and its influence on bile formation and biliary lipid secretion in primates. Alert, unanesthetized female rhesus monkeys prepared with a total biliary fistula were allowed to reach a steady bile salt secretion rate before each study. In three animals (group I),[14C]TDHF was infused intravenously. Most of the compound was secreted rapidly in bile chemically unchanged. The biliary secretion of this drug produced a twofold increase in bile flow; however, the bile salt output was markedly reduced during the infusion. In spite of this reduction, the phospholipid output remained essentially unchanged whereas the cholesterol output increased almost twofold. In five other animals (group II), the effect of TDHF on the bile salt secretion was further investigated by an intravenous infusion of [14C]taurocholate followed by a combined infusion of [14C]taurocholate and TDHF. When TDHF was added to the infusate, a reduction in the [14C]taurocholate output and a progressive rise in the plasma [14C]taurocholate concentration were observed in each animal. An analysis of the data in both groups indicates that (a) the most likely explanation to account for the decreased bile salt output is that the bile salt analogue, TDHF, interfered with bile salt secretion into the biliary canaliculi; (b) TDHF induces a greater secretion of biliary water than was observed with bile salts, an effect consistent with a stimulation of the bile salt-independent canalicular flow; (c) at similar 3alpha-hydroxysteroid secretion rates TDHF caused a significant increase in cholesterol secretion compared to that induced by bile salt. This finding suggests that TDHF affects cholesterol metabolism or secretion in a way distinct from bile salts. Thus, the solubilization of biliary lipids in mixed micelles, although essential, is only one of the factors which determine their secretion into bile.     

肝叶（段）切除治疗肝内胆管结石并狭窄的体会

目的探讨肝内胆管结石并／或胆管狭窄行肝叶（段）切除治疗的疗效。方法对53例肝内胆管结石并／和胆管狭窄行肝叶（段）切除及胆管整形胆囊带蒂肝胆管修补术，其中左半肝切除3例，左肝外叶切除38例，左肝外叶下段切除7例，右肝前叶下段切除3例，右肝后叶不规则切除2例，同时行胆管整形6例，胆囊带蒂肝胆管修补2例。结果除术后切口感染5例、残余结石7例、胰漏2例、左侧胸腔积液1例、右侧胸腔积液1例外，其余37例均无异常；全组无1例手术死亡。结论对肝内胆管结石并狭窄的患者，在术前经B超、CT、逆行胰胆管造影（ERCP）等检查充分了解肝内胆管结石分布、胆管狭窄情况后，拟定周密治疗方案，可确保手术成功，并取得满意疗效。     

胆汁流变特性与结石的形成

我国胆囊胆固醇结石的发病率日益增加，形成结石的原因尚未完全阐明。一般认为，胆汁成分改变及胆汁郁滞是重要因素，前者较为复杂，将另作研究。胆汁郁滞的常见原因则为胆囊收缩功能障碍，胆道梗阻及胆汁流变特性改变。其中，胆汁流变特性与结石形成的关系方面尚未见到报道。本文通过含有胆固醇结石的胆囊胆汁与正常胆囊胆汁对照研究，观察结石胆汁流变特性改变，分析与成石的关系。     

Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man

Summary. Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin II (ANG II) step-up infusion of 0·25 and 1·00 ng kg^-1× min. During the 1·00 ng kg^-1× min infusion ANG II plasma concentrations increased from 11 ± 2 to 48 ± 6 pg ml^-1; i.e., similar to those obtained during acute hypotensive hypovolemia in man. Mean arterial pressure increased (P<0·05) from a resting value of 89±3 to 97±5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P<0·05) from 36 ± 4 to 77 ± 10 pg ml^-1 during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0·25 and 1·00 ng kg^-1× min infusion subcutaneous blood flow decreased (P= 0·06) to 67 ±20 and 66 ±26%, respectively, of control. It is concluded that: (1) ANG II in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) ANG II does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG II do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma ANG II.     

Biliary lipid composition in patients with cholesterol and pigment gallstones and gallstone-free subjects: deoxycholic acid does not contribute to formation of cholesterol gallstones

BACKGROUND: Four main disturbances have been attributed to cholesterol gallstone disease: hypersecretion of cholesterol from the liver with cholesterol supersaturation in bile; disturbed motility with defective absorption and secretion by the gallbladder; increased crystallisation of cholesterol in the gallbladder bile; and slow intestinal transit with increased amount of deoxycholic acid in the bile acid pool. We aimed to evaluate the biliary lipid composition in a large series of gallstone patients, with emphasis on the amount of deoxycholic acid and with respect to number of stones, compared to gallstone free subjects. MATERIALS AND METHODS: Bile was sampled during operations through puncture of the gallbladder from 145 cholesterol gallstone patients, 23 patients with pigment stones and 87 gallstone free patients undergoing cholecystectomy. Biliary lipid composition, cholesterol saturation, bile acid composition, nucleation time and cholesterol crystals were analysed. RESULTS: The patients with cholesterol gallstones showed higher molar percentage of cholesterol, lower total biliary lipid concentration, higher cholesterol saturation, shorter nucleation time and higher proportion of crystals in bile than the other groups. The nucleation time was significantly shorter in multiple cholesterol gallstone patients, but this was not due to higher cholesterol saturation. Male cholesterol gallstone patients showed higher cholesterol levels, lower total biliary lipid concentration, and higher cholesterol saturation in bile than female patients. There was no difference in biliary content of deoxycholic acid, but significantly lower content of cholic acid in gallstone patients compared to gallstone free patients. CONCLUSIONS: We conclude that deoxycholic acid does not contribute to gallstone formation in cholesterol gallstone patients. The short nucleation time in patients with multiple cholesterol stones is not due to higher cholesterol saturation.     

Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man

Abstract. It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min^-1≙ 14.0 kJ min ^-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min^-1 (5.5 kJ min^-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3^.3 kcal min^-1 (14.0 kJ min^-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undetined inhibitor and a feedback mechanism is postulated.     

Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man.

The present study was designed (a) to characterize the activity of loxiglumide as a peripheral cholecystokinin (CCK) antagonist in healthy human subjects, and (b) to determine whether CCK is a physiologic regulator of the intestinal phase of meal-stimulated exocrine pancreatic and biliary secretions in man. Intravenous loxiglumide (22 mumol/kg per h) was highly potent in antagonizing CCK8-induced pancreatic enzyme and bile acid secretion as well as pancreatic polypeptide release. The potency and selectivity of loxiglumide as an antagonist of CCK provides the tool for evaluating the role of CCK as a physiological mediator of meal-induced pancreatic and biliary responses in humans. Infusion of a liquid test meal into the duodenum evoked an immediate response of pancreatic enzyme and bilirubin outputs, respectively. Intravenous loxiglumide significantly inhibited the meal-induced pancreatic amylase output by 63% (P less than 0.05), lipase output by 43% (P less than 0.05), and bilirubin output by 59% (P less than 0.05). These data suggest that CCK is a physiological mediator of the intestinal phase of meal-stimulated pancreatic and biliary responses.