[Comparison of fungal lipase and pancreatic lipase in exocrine pancreatic insufficiency in man. Study of their in vitro properties and intraduodenal bioavailability]. / Comparaison d'une lipase fungique et d'une lipase pancréatique au cours de l'insuffisance pancréatique exocrine chez l'homme. Etude de leur propriété in vitro et leur biodisponibilité intraduodénale.

Assuming that acidic degradation of lipase was the major cause of failure for the correction of steatorrhea by pancreatic extracts, we compared the in vitro and in vivo activities of a fungal lipase (FL) (Rhizopus arrhizus) with classical porcine pancreatic extract (Eurobiol). The choice of FL was determined by its two optimum pH (3.5 and 7.4). Five factors known to modify lipase activity were tested: pH, biliary acids colipase, trypsin and albumin. Bioavailability was measured by using a double intubation method in 13 patients with severe pancreatic insufficiency. Each enzymatic preparation was given during a test meal in a randomized and cross-over fashion. Results of the in vitro study showed that FL differed from pancreatic lipase by the following properties: better resistance in acidic solution, inhibition by biliary salts, absence of effect of colipase and rapid degradation by trypsin. In vivo the percentage of lipase activity recovered was 14.2 +/- 10.6 p. 100 for FL and 56 +/- 50 p. 100 for the classical pancreatic preparation. Compared with placebo significant differences in the recovery rate of lipolytic activity were observed with the pancreatic preparation only and started at the 40th min after the end of the test meal. These results showed that lack of degradation in acidic milieu is not the only valuable criterion for the choice of an efficient lipase preparation. The role of other potential factors such as gastric emptying as well as proteolytic degradation of the enzyme should be considered as well.

Immunoperoxidase localization of albumin and fibrinogen in rat liver fixed by perfusion or immersion: effect of saponin on the intracellular penetration of labeled antibodies.

Immunoperoxidase localization of albumin and fibrinogen in rat liver was tested with perfusion or immersion fixation and saponin as a membrane permeabilizing agent. The distribution of albumin- or fibrinogen-containing hepatocytes was examined by light microscopy. Labeled antibody penetration was assessed by electron microscopy on transversely cut cryostat sections. Paraformaldehyde liver fixation by perfusion, followed by incubation of the sections with labeled antibodies together with saponin, demonstrated that albumin and fibrinogen were present in all hepatocytes; mainly in the Golgi apparatus and rarely in the endoplasmic reticulum, the ultrathin sections being labeled throughout their entire thickness. A constant labeling of the endoplasmic reticulum was obtained when saponin was added from the beginning of fixation. In the absence of saponin, albumin was seen in most of the hepatocytes but only at the periphery of the transverse sections, in a few Golgi apparatus, and in some parts of the endoplasmic reticulum; under this condition, fibrinogen was not visualized in the hepatocytes. Paraformaldehyde liver fixation by immersion showed the presence of albumin or fibrinogen in a few hepatocytes only, with irregular labeled antibody penetration. The use of saponin did not improve albumin and fibrinogen localization, except when the liver was poorly fixed. These results show that liver fixation by perfusion gives a homogeneous labeling of all the hepatocytes, whereas fixation by immersion leads to a heterogeneous labeling. Satisfactory results are obtained with saponin, which must be used to improve the penetration of labeled antibodies when the liver is fixed by perfusion. Saponin does not work when immersion is employed, at least under the conditions tested.

Effect of somatostatin on diarrhea and on small intestinal water and electrolyte transport in a patient with pancreatic cholera.

The effects of somatostatin on diarrhea and on small intestinal flow of water and electrolytes (slow-marker perfusion technique) in a patient with pancreatic cholera are reported. Continuous intravenous infusion of somatostatin (8 micrograms/kg/hr) suppressed the diarrhea, but a rebound was observed after somatostatin. Infusion of somatostatin at the same dosage decreased the ileal fluid flow rate to within control values. This effect was mainly due to a sharp reduction in the rate fluid entered the jejunum, but was also due to a suppression of the abnormal water and electrolyte secretion in the proximal jejunum. Secretion in the rest of the small bowel remained unchanged. Somatostatin did not noticeably alter the high preinfusion plasma level of prostaglandin E1, but decreased the initially high plasma concentration of vasoactive intestinal peptide to normal values. These results suggest that long-acting somatostatin analogs could be of value in the symptomatic treatment of diarrhea in pancreatic cholera.

Streptozotocin treatment in pancreatic cholera (Verner-Morrison) syndrome.

A case of pancreatic cholera (Verner-Morrison syndrome) associated with a pancreatic endocrine tumor and hepatic metastases is presented. VIP and HPP plasma levels, initially elevated, were accurately followed in various conditions: during corticosteroid therapy, after pancreatic tumor excision, during and after streptozotocin therapy (1.5 g/m2) by repeated intraarterial route). Only streptozotocin therapy resulted in a reduction of the stool volume with concomitant decrease in VIP plasma levels. However, the size of the hepatic metastases was unchanged and HPP plasma levels remained elevated. It is suggested that VIP represents the tumoral secretion and HPP a marker of the residual malignant tissue.

Effects of somatostatin-14 and somatostatin-28 on bombesin-stimulated release of gastrin, insulin, and glucagon in the dog.

The effects of somatostatin-14 (S14) and somatostatin-28 (S28), a novel intestinal peptide containing somatostatin tetradecapeptide in its C-terminal position, on the bombesin-stimulated release of gastrin, insulin, and glucagon were tested. On iv infusion of bombesin, the increase in the level of glucagon was seen to be twice that of gastrin, and the insulin increase was 8 times that of gastrin. Plasma concentrations of somatostatin were not modified. S14 and S28 inhibited the release of gastrin, insulin, and glucagon; insulin release was inhibited most effectively, with glucagon release next, and gastrin release least inhibited. Based on the exogenous dose needed to produce equal effects, S28 was more potent than S14 on a molar basis, but based on the plasma concentrations needed to produce equal effects, S14 and S28 were equipotent.