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Biomedical subjects

H Sarles

Publications and source records attributed to H Sarles.

At least 91 records · Page 5Linked to original sources

[Effect of the single intravenous injection of ethanol on exocrine pancreatic secretion in conscious rats].

The studies on the effect of an intravenous infusion of ethanol on the exocrine pancreatic secretion of the rat are contradictory: weak ethanol quantities (less than 2 g/kg) being inefficient, inhibiting or stimulating pancreatic secretion according to different authors. The purpose of this work was to explain these discrepancies. Our results show that: 1) If the secretion of the rats is greater than or equal to 200 microliters/30 min (good general conditions) ethanol inhibits the protein secretion stimulated by either exogenous secretion or endogenous release of CCK (interruption of the flow of pancreatic juice into the duodenum) but does not modify non stimulated secretion (pancreatic juice reintroduced into the duodenum). 2) The differences observed in the literature are probably due to the use of rats in bad general conditions. It is recommended to use only rats, the secretion of which is greater than or equal to 200 microliter

Animals↗

[Etiopathogenesis of chronic nutritional pancreatitis].

The most current form of chronic pancreatitis, i.e. chronic calcifying pancreatitis, is often related to nutritional causes. This disease is characterized by formation within the pancreatic ducts and the lumina of accini of precipitates and calculi composed of calcium carbonate and of a newly discovered protein, the pancreatic stone protein (PSP). The formation of precipitates depends on two mechanisms: (1) a non etiological disorder reducing the secretion of PSP. This small phosphoglycoprotein is a calcium stabilizer which prevents the crystallization of calcium carbonate in a super saturated solution such as pancreatic juice, (2) modifications of the pancreatic juice related to the cause of the disease. In Occidental countries the main etiological factor is alcohol consumption associated with protein-and-fat-rich or fat-poor diets. Like hypercalcaemia, another cause of the disease, a chronic consumption of alcohol increases the pancreatic secretion of secretory proteins (enzymes) via its action on the cholinergic nerves. In some tropical countries, chronic pancreatitis is observed in children and associated to malnutrition. However, according to recent studies neither kwashiorkor nor manioc consumption seem to be responsible for the occurrence of this disease.

Calcium-Binding Proteins↗

Partial amino acid sequence of human pancreatic stone protein, a novel pancreatic secretory protein.

Pancreatic stone protein (PSP) is the major organic component of human pancreatic stones. With the use of monoclonal antibody immunoadsorbents, five immunoreactive forms (PSP-S) with close Mr values (14,000-19,000) were isolated from normal pancreatic juice. By CM-Trisacryl M chromatography the lowest-Mr form (PSP-S1) was separated from the others and some of its molecular characteristics were investigated. The Mr of the PSP-S1 polypeptide chain calculated from the amino acid composition was about 16,100. The N-terminal sequences (40 residues) of PSP and PSP-S1 are identical, which suggests that the peptide backbone is the same for both of these polypeptides. The PSP-S1 sequence was determined up to residue 65 and was found to be different from all other known protein sequences.

Amino Acid Sequence↗

Etiopathogenesis and definition of chronic pancreatitis.

This is a critical review of papers published on definition, classification, etiology, and pathogenesis of chronic pancreatitis from 1981 to 1985. Articles published earlier will only be mentioned when they are necessary to the understanding of the present knowledge or when they are insufficiently known. The more ancient literature has been reviewed elsewhere. The etiology and pathogenesis section will be limited to calcifying pancreatitis which is the most frequent form of chronic pancreatitis. The etiology of chronic obstructive pancreatitis has been studied in another review. The simple fibrosis of the pancreas is excluded from this chapter.

Alcoholism↗

Neural pathways for the release of gastrin, cholecystokinin, and pancreatic polypeptide after a meal in dogs. Role of gastric and splanchnic nerves.

We have measured gastrin, cholecystokinin (CCK), and pancreatic polypeptide (PP) release after a meal in normal dogs under basal conditions and during atropine infusion, and after various neural sections. Denervation of the gastric antrum (antral vagotomy) abolished the early part of the gastrin response to food. Truncal vagotomy, celiac ganglionectomy, and atropine reduced the early release of CCK, which occurred before the start of gastric emptying, suggesting that a neural, cholinergic mechanism may release CCK immediately after a meal. PP release was abolished by truncal vagotomy, and also by antral vagotomy. As no direct pathways are known between the antrum and the pancreas, this suggests either that antral afferents are essential for this response or that vagally mediated hormone release from the antrum mediates PP release.

Animals↗

Exocrine pancreatic function of children from the Ivory Coast compared to French children. Effect of kwashiorkor.

One hundred nineteen children, either French or from the Ivory Coast, aged 1-8 years, were submitted to pancreatic function testing by duodenal aspiration. Trypsin, chymotrypsin, lipase, phospholipase, amylase, volume, bicarbonate, chloride, and calcium were estimated before and after an intravenous injection of 1 CU secretin + 3 CHR units pancreozymin per kilogram of body weight. Sixty-two patients were normal European children, and 11 were normal African children. Twenty-five African children presented with kwashiorkor and 10 African children had presented with kwashiorkor but had recovered at the time of the test. Three cases of recurrent kwashiorkor are also included. In the normal group of African children, phospholipase concentration, volume, and bicarbonate were significantly decreased but chymotrypsin and trypsin concentrations were not, when compared to the normal European population. In kwashiorkor patients, lipase, amylase, phospholipase, and chymotrypsin concentration were significantly decreased compared to normal Africans. Trypsin, volume, and bicarbonate were not affected. These modifications disappeared after refeeding. In cases of recurrent kwashiorkor, all enzymes, including trypsin, were decreased. Calcium was never modified. These modifications were very different from those observed in chronic alcoholic and hypercalcemic pancreatitis. In a two-year study, chronic calcifying pancreatitis (CCP) was diagnosed in 14 patients (13 males), hospitalized in Abidjan. The mean age at onset of the disease was 41 years (SD 12.71), which is very similar to European cases. The most frequent cause was alcoholism, as in Occidental countries. The nutrition of the population was low in protein, calories being provided mostly by manioc, but no apparent symptoms of malnutrition were observed in the parents of our patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Three-dimensional pattern of ductuloacinar associations in normal and pathological human pancreas.

To explain the changes that must occur to produce the characteristic lesions of chronic calcifying pancreatitis, a three-dimensional reconstruction of pancreatic ductules and acini has been undertaken in normal subjects and in patients presenting with disease. This has been done with 3-micron serial sections of tissue embedded in plastic. Two approaches were used. In the first, ductules were reconstructed along with the acini directly associated with them. Using this method, adhesions or anastomoses between acini were not evident in normal specimens, and the quantity of acini associated with the ductules seemed small. The second method involved tracing the association of acini and ductules, beginning in the periphery of lobules, with the aid of a drawing tube. It became evident that an acinus was not necessarily the termination of the glandular system, but that intercalated ducts could be formed on the other side of the acinus, extending the quantity of acinar contributions that could be made to a primary ductular system. Evidence of dilation of ducts, atrophy of acini, formation of cul-de-sacs, and localized obstruction were found by three-dimensional reconstruction of serial sections from patients with chronic pancreatitis along with anastomosis between acini. It is probable that anastomosis becomes more detectable in patients as duct lumina enlarge. Anastomoses in the ductules in chronic pancreatitis may result from loss of some lobular structures, emphasizing preexisting connections or fusions of pancreatic elements, or both, as part of the pathological process.

Adult↗

Monoclonal antibodies to pancreatic stone protein. Radioimmunoassay and immunological comparison with trypsin 1.

Monoclonal antibodies were prepared against pancreatic stone protein, a protein which inhibits calcium carbonate precipitation. Two monoclonal antibodies designated D4 and 2E7 were characterized. Immunoadsorbant columns, obtained by linkage of these monoclonal antibodies to Affigel 10, have been used to isolate immunoreactive forms of pancreatic stone protein from nonactivated human pancreatic juice. These monoclonal antibodies permitted us to test the possible immunological relationship between pancreatic stone protein and human trypsin 1. No immunological similarity was found, in agreement with our previous results, and it was established that pancreatic stone protein is a novel protein and not a degradation product of human trypsin(ogen) 1.

Animals↗

Fine structure of the organic matrix of human pancreatic stones.

Pancreatic stones that were removed from the pancreatic ducts of patients with chronic calcifying pancreatitis were decalcified so the organic matrix could be studied by scanning and transmission electron microscopy. The observations made by scanning electron microscopy were compared with those made on undecalcified stones, and the findings were correlated with light microscopic observations. After the calcium carbonate was removed, the stones consisted of multiple partitions arranged like a sponge. They were embedded in a gel-like matrix. The organic partitions frequently were composed of dense surface layers and sparse central reticular accumulations, which had surrounded and bound calcium carbonate crystals. The organic matrix was heterogeneous in texture. Some areas had dense, regular, proteinaceous fibrous material. Deposits resembling fibrin were observed. Altered cellular constituents appeared to make up minor portions of the matrix. Calcium carbonate, which was precipitated in vitro in pancreatic juice, resembled the morphology of pancreatic stones more than that of pure calcium carbonate crystals. These results are consistent with the coformation of pancreatic stones from constituents in the pancreatic juice [including pancreatic stone protein (PSP), glycosaminoglycans, and occasional cells] and precipitated calcium carbonate.

Calcium Carbonate↗

Surgical complications of the Thomas pancreatic fistula.

This report describes the surgical complications of the Thomas pancreatic fistula in 23 dogs used for experiments for up to 1 year. Twenty animals survived the operation of cannula placement. The two complications noted were subcutaneous retraction of the cannula (nine of 40 cannulas) between 2 and 6 weeks, which was easily corrected, and displacement of the cannula from the gut lumen, which occurred eight times. Complete loss of the duodenal cannula was rapidly fatal. Partial displacement was corrected four times, with one death, using a specially developed technique. One lost gastric cannula was also replaced successfully. Corrective surgery for surgical complications of the Thomas fistula is feasible and has a high success rate. The preparation has a good long-term survival and so is suitable when repeated experiments in the same animals are required over a period of several months.

Animals↗

Immunocytochemical localization of pancreatic stone protein in the human digestive tract.

Recently, in our laboratory, a protein extracted from human pancreatic stones was characterized and purified and a specific antibody was obtained. This pancreatic stone protein (PSP) was shown to have an inhibitory effect on the CaCO3 crystal growth in vitro. The cellular origin of such a protein and its repartition along the digestive tract were studied by immunolocalization (protein A-colloidal gold method) at the ultrastructural level. Surgical biopsies of pancreata from normal or chronic pancreatitis patients, needle liver biopsies, gastric mucosa, and jejunum and duodenum biopsies were minced and fixed in the Karnovsky medium or in buffered 4% paraformaldehyde. The specimens were washed in buffer, dehydrated through ethanol, and embedded in Epon 812. Ultrathin sections, collected on uncoated nickel grids, were submitted to the following reactives at room temperature: protein A 1 mg/ml, anti-PSP (1:2 to 1:100), and protein A-colloidal gold. The specificity of the localization was checked by substituting buffer or nonimmune rabbit serum to anti-PSP. The stone protein was markedly present in the zymogen granules and condensing vacuoles of the normal pancreatic acinar cells, the label was found in the acinar and ductal lumen. In chronic pancreatitis, the localization of PSP, when it occurred, was extremely weak in the acinar cells. No PSP was specifically characterized in hepatocytes, gastric mucosa, and enterocytes. However, a weak but specific reaction was found in the secretory granules of Paneth cells. These results in pancreas confirm the acinar secretory origin of the PSP and are in good agreement with its possible function in stabilizing pancreatic juice in vivo, which is normally supersaturated in calcium carbonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium-Binding Proteins↗

Multicenter pathological study of chronic pancreatitis. Morphological regional variations and differences between chronic calcifying pancreatitis and obstructive pancreatitis.

To examine previous work carried out at a single center, i.e., France, on the pathologic features of chronic pancreatitis and to examine geographic differences, 359 cases of chronic pancreatitis from five centers were studied pathologically and the results analyzed according to appropriate statistical methods. It was found that it was easy to separate chronic calcifying pancreatitis from obstructive pancreatitis occurring distal to obstruction to the pancreatic duct by pathological means. On the other hand, geographic differences between France, Italy, Brazil, and South Africa, although present, were not sufficient for identification of a specific profile for each of the countries studied, and it was found that the minor differences were probably dependent on environmental rather than racial factors.

Brazil↗

Action of dopamine on the exocrine pancreatic secretion of the intact dog.

The effects of dopamine and domperidone, a dopamine antagonist, have been studied on the exocrine secretion of the dog pancreas. The purpose of this study was to see if dopamine acted on enzyme secretion and if its action was merely 'pharmacological' or had a physiological role. Conscious Beagle dogs, fitted with Thomas cannulae were studied following infusions of dopamine 125-1000 micrograms kg-1 h-1. During dopamine infusion, a secretory peak lasting 10 min was observed. This was followed by a stable plateau which was approximately 1/3 of the peak. The pattern of water, bicarbonate and protein secretion was similar. The maximum effect was obtained with 500 micrograms kg-1 h-1 dopamine. The stimulatory action of dopamine was blocked by domperidone, without any detected effect on the central nervous system, but not by propranolol or phenoxybenzamine. Domperidone 10 micrograms kg-1 almost completely suppressed the secretory response to the maximally effective dose of dopamine. This inhibition was not competitive. Atropine decreased the secretory response to dopamine. The protein response was not observed when dopamine was infused against a background infusion of secretin. This suggests that the effect of dopamine on protein secretion could be due to a wash-out phenomenon. The maximally effective dose of domperidone, 10 micrograms kg-1, did not modify the pancreatic response to a solid meal. Thus, in the non-anaesthetized dog, the effect of dopamine on water and bicarbonate secretion has been confirmed. It is concluded that dopamine had no detectable action on protein secretion and that the physiological role of dopamine with respect to pancreatic secretion is still questionable.

Adrenergic alpha-Antagonists↗