Endothelial calcium-calmodulin dependent nitric oxide synthase in the in vitro vascular hyporeactivity of portal hypertensive rats.

BACKGROUND/AIMS: Increased nitric oxide production has been implicated in impaired vascular responsiveness to vasoconstrictors in portal hypertension. However, there is no firm evidence concerning the involved nitric oxide synthase isoform. The present study investigated the possible contribution of one nitric oxide synthase isoform, the endothelial constitutive Ca2+-calmodulin dependent, in the overproduction of nitric oxide in portal hypertension. METHODS: Vascular responses to norepinephrine and acetylcholine were evaluated in isolated thoracic aortic rings from normal and portal vein stenosed rats. RESULTS: An impaired concentration-dependent contraction to norepinephrine was observed in intact rings from portal hypertensive rats compared to controls. The hyporeactivity to norepinephrine was reversed after endothelium denudation, the inhibition of nitric oxide synthase with L-NOARG or the inhibition of calmodulin with W-7, but not after pre-incubation with indomethacin. Stimulation of intact rings with norepinephrine after the inhibition of calmodulin with calmidazolium was followed by a decreased vascular response in vessels from normal rats but not in those from portal hypertensive rats. Stimulation of intact rings with norepinephrine in a Ca2+-free medium was followed by a decreased vascular response in vessels from both portal hypertensive and normal rats. No difference in vasoconstrictive responses was observed between the two groups after calmidazolium or in a Ca2+-free medium. Relaxation induced by acetylcholine in norepinephrine-precontracted rings was more marked in rings from portal hypertensive rats than in controls. No differences in the vasodilator responses were observed after relaxations had been inhibited by the removal of the endothelium, pre-incubation with L-NOARG, indomethacin, W-7 or calmidazolium and in a Ca2+-free medium. CONCLUSIONS: This study demonstrates the involvement of the endothelial constitutive Ca2+-calmodulin dependent nitric oxide synthase isoform in the overproduction of nitric oxide in portal hypertension.

Effects of lanreotide, a somatostatin analogue, on postprandial gastric functions and biliopancreatic secretions in humans.

AIMS: Lanreotide is a novel synthetic somatostatin analogue. A long-acting formulation of lanreotide has been shown to be effective for the treatment of gastroentero-pancreatic hormone-producing tumours but effects on postprandial digestive and absorptive functions remain obscure. The aim of the present study was to evaluate the effects of intravenous lanreotide on gastric and biliopancreatic secretions in man as well as the absorption of nutrients and the duodeno-caecal transit time after ingestion of an homogenized meal (500 kcal, 55% carbohydrates, 15% proteins, 30% lipids). METHODS: Eight healthy male volunteers were studied on two occasions within a 2 weeks interval, using a perfusion method. They received in single-blind and random order continuous i.v. infusion of either placebo or lanreotide (100 micrograms h-t after a bolus of 100 micrograms 15 min before the beginning of the study). RESULTS: Lanreotide significantly decreased gastric acid secretion (90%) for the initial 3 h period. Gastric emptying was not significantly modified by lanreotide infusion. Compared with placebo, lanreotide almost completely abolished both bile salts and lipase responses to the meal. It largely increased the duodeno-caecal transit time and decreased significantly the duodenal absorption of carbohydrates and triglycerides. CONCLUSIONS: Since lanreotide has powerful effects on gastrointestinal functions, it could be useful in the prevention or in the treatment of pancreatic and bowel fistulas as well as short bowel syndrome.

Could oral erythromycin optimize high energy continuous enteral nutrition?

BACKGROUND: Intravenous erythromycin has previously been reported to stimulate gastric emptying, to inhibit gastric acid secretion and to stimulate pancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers. AIM: The aim of this study was to evaluate the effects of oral erythromycin (160 mg/h) on gastrointestinal function under these conditions in seven healthy subjects. METHOD: This randomized double-blind cross-over study measured the gastric emptying rate of nutrients, gastric acid secretion, gastric pH, jejunal flow rate as well as biliopancreatic secretion and duodeno-caecal transit time during a 19.9 kJ/min continuous infusion of a nutrient solution (4.18 kJ/mL) in the antrum over a 6-h period by a perfusion method. RESULTS: The nutrition was well tolerated except by one subject with placebo perfusion. During the 6-period, total gastric volume and gastric volume of nutrient decreased during erythromycin administration by 22 +/- 8 and 22 +/- 6%, respectively. Gastric acid secretion was not modified by erythromycin. Lipase and bile salt outputs were significantly higher with erythromycin. The duodeno-caecal transit time was not statistically different with drug and placebo (169 +/- 15 and 146 +/- 19 min, respectively). CONCLUSION: During continuous gastric infusion of a liquid diet, the effect of oral erythromycin on gastric emptying could be useful to optimize cyclic enteral nutrition or to enhance the tolerance of enteral nutrition.

Effects of erythromycin on gastric emptying, duodeno-caecal transit time, gastric and biliopancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers.

OBJECTIVE: Erythromycin, a macrolide antibiotic, has been reported to increase gastric emptying. The aim of this study was to evaluate the effects of intravenous erythromycin (150 mg/h) on gastric emptying, small intestinal transit time, gastric and biliopancreatic secretions during gastric infusion of a liquid diet in healthy volunteers. DESIGN: A randomized double-blind crossover study (erythromycin versus placebo). METHODS: Gastric emptying rates of nutrients, gastric acid secretion, gastric pH, jejunal flow rates, as well as biliopancreatic secretions and duodeno-caecal transit time, were evaluated during a continuous infusion at 4.5 kcal/min of a nutrient solution (1 kcal/ml) in the antrum, over a 6 h period, by a perfusion method. RESULTS: During the 6 h period, total gastric volume and gastric acid secretion decreased during erythromycin administration of 37 and 22%, respectively (area under the curves). Lipase outputs were significantly higher with erythromycin than placebo. Bile salt output was not significantly different between erythromycin and placebo. Duodeno-caecal transit time increased significantly during erythromycin infusion compared with placebo (191 +/- 12 versus 159 +/- 17 min; P < 0.05). CONCLUSION: During continuous gastric infusion of a liquid diet, intravenous erythromycin has a powerful effect on gastrointestinal function. The motor and secretory effects may enhance the tolerance and the efficiency of enteral nutrition in humans.

[Comparative effects of ricinoleic acid and senna on orocecal and oroanal transit time in healthy subjects. Application of the salacylazosulfapyridine method]. / Effets comparés de l'acide ricinoléique et d'un sennoside sur le temps de transit oro-caecal et oro-anal chez l'homme sain. Application de la méthode de la salacylazosulphapyridine.

The appearance in plasma of sulphapyridine after oral administration of salicylazosulphapyridine (Salazopyrin) was shown to be useful for measuring the orocecal transit time in normal subjects. The purpose of this study was to use this method in diarrhea with accelerated intestinal transit time. A two-step study was performed in 12 healthy volunteers: a) under resting conditions; b) 2 weeks later with ricinoleic acid 40 ml (n = 6) or senna 19 mg (X-Prep = 1.2 g; n = 6) administration. In each step, Salazopyrin (2 g) and 20 radiopaque markers were ingested with a 200 kcal meal (Polydiet TCM = 200 ml). The following parameters were determined: a) plasmatic level of sulphapyridine (spectrophotometry) at 30 min intervals during 12 h; b) 2-day stool frequency and weight; c) oro-anal transit time (passage of the first marker and half of the markers in stools). In one subject, no sulphapyridine level was detected after administration of ricinoleic acid. With senna, 2 day stool frequency and weight increased by 80 and 131 percent respectively: orocecal transit time decreased from 6.1 +/- 1.3 to 4.8 +/- 1.2 h (m +/- SD; P less than 0.01) and oro-anal transit time (first marker) decreased from 31.8 +/- 9.6 to 20.7 +/- 8.9 (P less than 0.05). With ricinoleic acid, 2 day stool frequency and weight increased by 212 and 350 percent respectively; orocecal transit time decreased from 5.8 +/- 1.8 to 2.2 +/- 0.7 (P less than 0.01) and oroanal transit time (first marker) decreased from 25.3 +/- 7.1 to 8.0 +/- 6.8 h (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Tubulovillous adenoma of the colon with hyperdiploidy, double-minute chromosomes, and inversion of chromosome 1.

A sessile adenoma of the left flexure of the colon was studied after surgical colectomy. Specimens were obtained for complete histologic evaluation. The tumor consisted of glandular tubes with decreased mucin production and a papillary structure on the luminal aspect. The muscularis mucosa was not involved; there was no carcinomatous focus. Cytogenetic study was carried out on 56 cells; none was normal, 77% were hyperdiploid (52-87 chromosomes), 16% were hypodiploid (18-39 chromosomes), and 7% were paradiploid. The supernumerary chromosomes were chromosomes #3, #6, #13, #19, and #20; chromosome #18 was missing in 80% of the cells. A marker for chromosome #1 resulting from a q21.1-q21.2 break with inversion of the centromere-bearing segment (pter-q21) was observed in 58% of the cells. Twenty-five percent of the cells had double minute chromosomes. Despite the histologically benign nature of the tumor, all the cells showed significant cytogenetic aberrations, some of which are considered to be markers of neoplastic transformation (polyploidy, double minutes, chromosome #1 marker).

Human chromosome analysis in 24 cases of primary carcinoma of the large intestine: contribution of the G-banding technique.

As in the haemopathies, the application of cytogenetics to epithelial cancers could aid in the study of their pathogenesis evaluation. In this context we performed chromosome analyses on a series of human colo-rectal cancers. The technique was consistently reliable since the modal number of chromosomes could be determined in all 24 cases. In 22, karyotypes could also be established. Each tumour was characterized by a single cell clone in 21 cases and by a mosaic of 2 populations in 3 cases. Numerical anomalies were not due to chance: they enabled near-diploid (11 cases), near-triploid (9 cases), mosaic (3 cases) and highly polyploid (1 case) cancers to be distinguished. Supernumerary chromosomes were primarily in groups C and F. The most frequent markers before denaturation techniques were No 2q +, No F and minutes. Each time double-minutes were observed (5 cases), they were in invasive cancers (B and C Dukes classification). Cells were generally diploid in non-invasive cancers with fewer quantitative and structural anomalies. Tumour cytogenetics were related to the histological type and localization in the colon, as well as to the local and metastatic spread.

[Initial trial of a new test for the evaluation of hepatocellular function: the TMB test]. / Premiers essais d'un nouveau test d'évaluation du fonctionnement hépatocellulaire: le test au TMB.

The oral administration of 400 mg of trimethoxy 1-3-5-benzene or T.M.B. is normally followed by a high urinary excretion of dimethoxy, 1, 3, hydroxy 5 benzene and other metabolites mainly in the form of conjugates. Urinary excretion during the first 3 hours is strongly reduced in liver disease. By a simple blind test we showed that the test is positive in subclinical and laboratory-negative liver failure.