Comparison of human jejunal and ileal fat absorption by electron microscopy

Morphologic and physiologic experiments in rodents have demonstrated differences between jejunal and ileal fat absorption. Compared with the rat jejunum, absorbed lipid particles within rat ileal absorptive cells are larger and exit at a slower rate. To evaluate the relevance of these observations to humans, we studied jejunal and ileal ultrastructure in 3 volunteers, each of whom had an intact small intestine and an ileostomy postcolectomy for ulcerative colitis. Proximal jejunal biopsy specimens were obtained via a hydraulic tube after an overnight fast and again after a 20-min intrajejunal lipid infusion. On a separate day, terminal ileal biopsy specimens were taken via the stoma with a small steerable suction biopsy tube after an overnight fast and again after a 20-min intraileal infusion of the same lipid mixture. One volunteer underwent biopsy after a 60-min ileal infusion of a digested meal of higher lipid content. Electron microscopy of fasting human jejunal absorptive cells revealed obvious smooth endoplasmic reticulum in the extreme apical region beneath the terminal web; very low density lipoprotein particles were observed within smooth endoplasmic reticulum and Golgi cisternae. In contrast, fasting human ileal absorptive cells contained less apical smooth endoplasmic reticulum and fewer or no very low density lipoprotein particles. After the 20-min infusion of lower-lipid content, human jejunal and ileal absorptive cells were indistinguishable because they contained fat particles of the same size and number within smooth endoplasmic reticulum, Golgi cisternae, and extracellular spaces. After the 60-min ileal infusion of higher-lipid content, human ileal absorptive cells appeared to be the same as those of the human jejunum after similar lipid infusions. Our observations of the ultrastructural similarity in human jejunal and ileal absorptive cells after lipid infusions contrasts with those in rodents and may reflect species-specific differences in mechanisms of fat absorption.     

Intravenous infusions of fat emulsions containing medium and long-chain triglycerides have no effect on basal and secretin stimulated pancreatic secretion in man

The effect of an intravenous infusion of a 10% fat solution containing 50 g/l medium chain triglycerides (MCT) and 50 g/l long chain triglycerides (LCT) on exocrine pancreatic secretion was studied in 18 healthy volunteers. Each subject was studied twice on separate days. In period I 0.9% NaCl was given intravenously on both days. In the following period II either a 10% solution of MCT-fat or 0.9% NaCl were given intravenously in a randomized order at a rate of 100 ml/h. Periods I and II lasted 150 minutes each. Throughout the experiment pancreatic secretion was stimulated by saline, 0.1 U/kg/h secretin, or 0.25 U/kg/h secretin in 6 subjects each. In period II, MCT/LCT infusions did not influence pancreatic outputs of volume, bicarbonate and enzymes when compared to the NaCl infusion in the control experiment irrespective of the type of stimulation. Therefore, intravenous infusions of MCT may be used in clinical situations where the pancreas should be kept at full rest.     

Effect of repeated boluses of intravenous omeprazole and primed infusions of ranitidine on 24-hour intragastric pH in healthy human subjects

The aim of this study was to identify dosage regimens using intravenous omeprazole and ranitidine that would elevate and consistently maintain intragastric pH>6 in the first 24 hr of therapy. In 19 healthy, fasting human subjects using continuous 24-hr gastric pH-metry, we studied two dosages of primed infusions of ranitidine (50 mg bolus followed by infusion of either 3 or 6 mg/kg body wt/24 hr) and six regimens of intravenous omeprazole (80–200 mg in 24 hr in two to five boluses). Only the two ranitidine infusions and high doses of omeprazole (≥160 mg/day as four or five boluses) raised the intragastric median pH above 5.4. There was no significant difference in the median intragastric pH after high dose ranitidine and high doses of omeprazole. Considerable interindividual variation in intragastric pH was observed after omeprazole therapy. The percentage of intragastric pH>6.0 during the 24-hr study was lower after omeprazole (35–42%) than after high-dose ranitidine (58%). We conclude that it is possible to raise intragastric pH>6.0 by use of either primed ranitidine infusion or by repeated boluses of omeprazole. However, maintenance of this high pH in the first 24 hr is difficult with both, more so with omeprazole.     

The effect of sham feeding on neurocardiac regulation in healthy human volunteers.

BACKGROUND: Distension and electrical stimuli in the esophagus alter heart rate variability (HRV) consistent with activation of vagal afferent and efferent pathways. Sham feeding stimulates gastric acid secretion by means of vagal efferent pathways. It is not known, however, whether activation of vagal efferent pathways is organ- or stimulus-specific. OBJECTIVE: To test the hypothesis that sham feeding increases the high frequency (HF) component of HRV, indicating increased neurocardiac vagal activity in association with the known, vagally mediated, increase in gastric acid secretion. METHODS: Continuous electrocardiography recordings were obtained in 12 healthy, semirecumbent subjects during consecutive 45 min baseline, 20 min sham feeding (standard hamburger meal) and 45 min recovery periods. The R-R intervals and beat-to-beat heart rate signal were determined from digitized electrocardiography recordings; power spectra were computed from the heart rate signal to determine sympathetic (low frequency [LF]) and vagal (HF) components of HRV. RESULTS: Heart rate increased during sham feeding (median 70.8 beats/min, 95% CI 66.0 to 77.6; P<0.001), compared with baseline (63.6, 95% CI 60.8 to 70.0) and returned to baseline levels within 45 min. Sham feeding increased the LF to HF area ratio (median: 1.55, 95% C.I 1.28 to 1.77; P<0.021, compared with baseline (1.29, 95% CI 1.05 to 1.46); this increase in LF to HF area ratio was associated with a decrease in the HF component of HRV. CONCLUSIONS: Sham feeding produces a reversible increase in heart rate that is attributable to a decrease in neurocardiac parasympathetic activity despite its known ability to increase vagally mediated gastric acid secretion. These findings suggest that concurrent changes in cardiac and gastric function are modulated independently by vagal efferent fibres and that vagally mediated changes in organ function are stimulus- and organ-specific.     

Effect of intravenous infusions on laboratory results in blood specimens drawn proximal to the insertion site of an intravenous canula

Background: Blood sampling contralateral to the insertion site of an intravenous line is always first choice. When blood must be drawn proximal to an i.v. insertion site, dilution and contamination by the infused substance can occur.To study the effects of obtaining blood specimens proximal to a discontinued intravenous line a clinical trial in a small community hospital was designed.Methods: Ten patients received an intravenous infusion with sodium chloride 0.45%/dextrose 2.5%. Bloodsamples were taken simultaneously from the iv-arm and the control-arm with the infusion running and 1, 3, and 5 min after shutting off the infusion.Results: Between-arm differences are significant for all analytes while the infusion is running, but not after the infusion is discontinued. Wide ranges in differences in terms of percentage exist for many analytes 1 min after shutting off the infusion, and for glucose also 3 min after shutting off the infusion.Conclusions: A three minute interval is recommended when drawing blood proximal to a shut-off infusion. Longer intervals may be advisable for analytes present in the infused substance.     

长期脂肪含量较高饲料喂养对大鼠胰岛素抵抗的影响

目的探讨脂肪含量较高饲料长期喂养对大鼠胰岛素抵抗的影响。方法大鼠随机分为两组,对照组以普通饲料喂养16 w,高脂组以脂肪热量比38.5%的饲料喂养12 w,再以脂肪热量比51.3%的饲料喂养4 w。实验结束时,测定空腹血糖(FBG)、空腹血浆胰岛素(FINS)并计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(HOMA-IR);另外进行口服葡萄糖耐量试验(OGTT),计算血糖曲线下面积(AUC)。结果两组大鼠能量摄取相似,体重差别不大。高脂组大鼠FINS显著高于对照组(P<0.01),但FBG无显著差别。高脂组大鼠ISI显著下降(P<0.01),HOMA-IR显著上升(P<0.01),血糖AUC显著升高(P<0.01)。结论脂肪含量较高的饲料喂养大鼠16 w后引起了胰岛素抵抗和糖耐量异常。     

The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.     

Gastrointestinal adaptation to diets of differing fat composition in human volunteers.

The effect of a low fat diet (9 MJ) v a high fat diet (19.26 MJ), each consumed separately for four and 14 days, on gastric emptying and mouth to caecum transit time of a high fat test meal and body weight and satiety were examined in groups of 10 and six normal male volunteers. The half time for gastric emptying (t1/2) and the mouth to caecum transit time of a high fat test meal was significantly faster after the high fat diet than the low fat diet when consumed for 14 days (t1/2=98 (80-116) v 147 (88-206) minutes (median (range)), p less than 0.05; mouth to caecum transit time 240 (130-350) v 360 (200-520) minutes, p less than 0.05), but not when consumed for only four days. The mean (SEM) body weight of all subjects significantly increased during the 14 day high fat diet (74.7 (1.3) v 72.7 (1.6) kg, p less than 0.05) but was not influenced during the consumption of the low fat diet. When subjects were given an appetising meal to consume on the day that they had consumed the transit test meal, they ate similar amounts irrespective of their recent dietary history, though the eating rate was significantly slower after the high fat diet (mean (SEM)) 46.7 (1.9) v 71.3 (14.8)/min, p less than 0.05). Maintaining normal subjects on a high or low fat diet for two weeks resulted in a desensitisation or sensitisation respectively of the mechanisms by which nutrients regulate gastrointestinal transit. These findings emphasise the importance of the recent dietary history in the interpretation of gastric emptying and small bowel transit time data.     

GH responses to intravenous bolus infusions of GH releasing hormone and GH releasing peptide 2 separately and in combination in adult volunteers

OBJECTIVE Synthetic growth hormone releasing peptides (GHRP) have potent GH-releasing activity in vivo and in vitro. The nature of the Interaction of GHRP and naturally occurring GH releasing hormone (GHRH) is still far from clear. We investigated GH release in response to individual peptide doses or combined doses of GHRH1–29NH₂ and GHRP-2, a novel GH-releasing peptide, in normal adults. DESIGN Subjects underwent three tests in a randomized order: (1) i.v. bolus of GHRH1-29NH₂ (1 μg/kg BW), (2) i.v. bolus of GHRP-2 (1 μg/kg BW), (3) i.v. bolus of GHRH1-29NH ₂ combined with GHRP-2 (same dosages). SUBJECTS Eight healthy non-obese male volunteers, aged 25–34 years. MEASUREMENTS Serum GH concentrations were measured by IRMA at ?15,0, + 10, 20,30,45,60,75,90 and120 minutes after the boluses. RESULTS Peak GH levels in response to GHRH1-29NH ₂, GHRP-2 and the combined GHRH1-29NH ₂ and GHRP-2 administrations were observed between 20 and 45 minutes. Peak GH levels at30 minutes were 32.8 ± 27.3 (mean ± SD), 109.7 ± 56.1 and 140.9 ± 80.6mU/l, respectively. The area under the curve for GH levels (GH AUC) calculated for the first 90 minutes after the GHRH1-29NH ₂ test (2061.2 ± 1601.9mU/1 min) was significantly lower than those after GHRP-2 (6205.1 ± 3216.9mU/l min) and the combined GHRH1-29NH ₂ and GHRP-2 challenge (9788.3 ± 5530.4mU/l min) (P = 0.0003 and P = 0.00005, respectively; palred Student's t-test for log transformed data). Although the GH AUC of the GHRP-2 test and the combined GHRHl-29NH ₂ and GHRP-2 test differed significantly (P = 0.016, t-test), the latter was not signlflcantly dlfferent from the sum of the GH AUCs of each subject after the separate tests. CONCLUSION Although the GH releasing potency of GHRP-2 significantly exceeded that of GHRH1-29NH ₂, we were not able to demonstrate synergy between the two substances. It is possible that GHRP-2 given in our study in higher molar quantities than GHRH1-29NH ₂ masked the effect of the latter.     

高脂喂养对载脂蛋白O基因敲除小鼠表型的影响

目的 探究载脂蛋白O(ApoO)基因敲除促进高脂饮食诱导的肥胖及代谢紊乱表现.方法 将ApoO基因敲除杂合小鼠进行配种繁殖,提取子代小鼠的组织DNA,用PCR技术检测小鼠的基因型.实时荧光定量PCR和Western blot检测ApoO基因敲除mRNA和蛋白表达水平.饲喂高脂饮食后,通过小鼠体型、摄食量、肝脏脂质组学等...     

Effect of incorporating fat into a liquid test meal on the relation between intragastric distribution and gastric emptying in human volunteers.

The relation between gastric emptying and the intragastric distribution of 300 ml radiolabelled beef consommé with and without 60 g margarine was investigated by performing randomised, paired gammacamera studies in seven healthy male volunteers (aged 20-22 years). The low calorie bland meal emptied rapidly from both the proximal and distal stomach after a short lag period (4-6 min), during which 24-50% of the liquid passed into the distal stomach. Addition of margarine to the liquid test meal increased the lag period (median 32 min, range 7-60 min; p less than 0.01) and decreased the slope of emptying (T1/2 lag period 88 min, 49-146 min v 15 min, 10-57 min; p less than 0.01). During the lag period there was an initial filling of the distal stomach, similar to that with the bland liquid, followed by a redistribution of between 19% and 61% (median 46%) of the distal stomach contents back into the proximal stomach. At the onset of emptying, the distal stomach filled (median 30%, range 16-34%) and during this time the proximal stomach emptied twice as fast as the whole stomach (p less than 0.05). Thereafter, the distal stomach capacity remained relatively constant while both the proximal and whole stomach emptied at similar rates. This study shows that the delay in gastric emptying of a liquid that has a high fat content is due in part to a redistribution of distal stomach contents back into the proximal stomach.     

Effect of vertebral, carotid and intravenous infusions of lysine vasopressin on plasma vasopressin and cardiovascular function

The cardiovascular and vasopressin-releasing effects of vertebral artery, carotid artery and intravenous (i.v.) infusions of lysine vasopressin (150 microU/kg X min) were studied in anesthetized dogs. Vertebral and carotid artery infusions of lysine vasopressin led to similar decreases in cardiac output as i.v. infusions. Heart rate, however, decreased to a greater extent with vertebral and carotid artery infusions of lysine vasopressin than i.v. infusions. There were no changes in either mean arterial blood pressure or the plasma vasopressin concentration. The results indicate that peripheral vasopressin: has a central effect to reduce heart rate; has a peripheral effect on the heart to reduce cardiac output, and probably does not feed back to inhibit its own release.     

Influence of intravenous infusions of hydroxyethylstarch (HES) (MW 40,000 and 450,000) on the blood flow properties of healthy volunteers

Infusions of hydroxyethylstarch (HES) solutions as plasma substitutes and flow improvers play an increasing role in the treatment of various diseases. Little is known about the effect of HES solutions of different molecular weights on the flow properties of blood i.e. blood viscosity, plasma viscosity, erythrocyte aggregation and erythrocyte deformability (filtrability). In the present study the influence of 500 ml-infusions of a 6% solution of HES (MW 450,000) has been compared to that of 6% solutions of HES 40,000. Infusions of 500 ml of HES 450,000 into healthy persons induced a hemodilution with a subsequent decrease in whole blood viscosity whereas the plasma viscosity increased. Red cell aggregation increased as well, red cell deformability was slightly impaired. Infusions of 500 ml of HES 40,000 into healthy persons were followed by a hemodilution with a decrease in blood and plasma viscosity, a decrease in erythrocyte aggregation and a slight improvement of red cell deformability. The reason for this difference in behaviour and its therapeutical consequences are discussed.     

Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers

A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose-related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.     

Effect of intraduodenal and intravenous triglyceride infusions on plasma gastric inhibitory polypeptide and insulin in fetal and neonatal pigs

Summary The responses of gastric inhibitory polypeptide (GIP) and insulin to intraduodenal and IV triglyceride infusions were measured in 11 late fetal and 10 neonatal pigs. Basal plasma glucose, insulin, and GIP concentrations were lower in fetal than in neonatal pigs. In the fetal pigs, plasma glucose increased slightly during intraduodenal and IV triglyceride infusions, whereas plasma insulin remained unchanged during the tests. No significant changes were observed in plasma GIP concentration following intraduodenal triglyceride infusion in the fetal pigs, but plasma GIP fell during the IV infusion of triglyceride in these pigs (p<0.01). In the neonatal pigs, plasma glucose and insulin remained unaffected by intraduodenal and triglyceride infusions. Plasma GIP did not change during the IV triglyceride infusion, but exhibited a paradoxical decline after the intraduodenal triglyceride infusion (p<0.05). It is concluded that the GIP-cell response to an oral triglyceride load is suppressed in late fetal and neonatal pigs. The abolished GIP response to oral triglycerides could play a causal role in the inactivity of the enteroinsular axis which is seen in both human and animal neonates.