Manjit Singh

Sucralfate therapy in patients with symptoms of alkaline reflux gastritis: A randomized, double-blind study

The effects of sucralfate (6 g per day) and placebo on symptoms, endoscopic findings, and gastric mucosal histology were compared in 23 patients with symptoms of alkaline reflux gastritis who had undergone Billroth I, Billroth II, or vagotomy and pyloroplasty. Patients were randomly assigned to receive sucralfate (n = 11) or placebo (n = 12) for six weeks. Then all received six weeks of open sucralfate therapy before treatment codes were revealed. Twelve gastric biopsy specimens were obtained before patients began treatment and at six and 12 weeks. The two groups did not differ significantly with respect to symptom scores or endoscopic findings at baseline, after the double-blind phase, or after open sucralfate treatment. There were also no significant differences between the treatment groups with respect to epithelial cell scores and conventional gastritis scores. However, after the six-week, double-blind phase, the inflammatory cell score of the sucralfate-treated group was significantly lower (p less than 0.05) than that of the placebo-treated group (1.3 +/- 0.3 versus 1.9 +/- 0.4). After six weeks of open sucralfate treatment, patients who had initially received placebo had a significant reduction (1.4 +/- 0.3 versus 1.9 +/- 0.4) in their inflammatory cell score. Sucralfate lowered the inflammatory cell scores of patients with symptoms of alkaline reflux gastritis. This reduction, however, was not associated with an improvement in symptoms.

Folate Deficiency and Pancreatic Acinar Cell Function

Abstract The present study was designed to determine the effect of folate deficiency on pancreatic acinar cell function. In the first series of experiments, three groups of rats were fed ad libitum regular rat feed, folate-deficient diet, or an equivalent amount of folate-sufficient diet. In the second series of experiments, rats were either fed ad libitum or rendered folate deficient by a purified folate-deficient diet; half of the folate-deficient group was replenished with oral folate. Body weight, pancreatic weight, DNA, [methyl-14C]thymidine incorporation into DNA, RNA, [8-14C]adenine incorporation into RNA, protein content, synthesis of proteins, amylase content, and basal and bethanechol-stimulated amylase secretion were determined. The parameters were the same in the rats fed a folate-sufficient diet as in those fed a regular rat feed. Feeding a folate-deficient diet resulted in impaired DNA synthesis as evidenced by diminished incorporation of [methyl-14C]thymidine into DNA. There was no change in secretion of amylase. Similar results were obtained in the second series of experiments. These studies indicate that folate deficiency (rather than antibiotic content of the diet) impaired pancreatic function. Folate deficiency may therefore contribute to pancreatic injury in malnutrition and alcoholism.

Effect of Chronic Ethanol Feeding on Factors Leading to Inappropriate Intrapancreatic Activation of Zymogens in the Rat Pancreas

In rats fed control and ethanol-containing Lieber-DeCarli diets for a period of 12 months, the bile did not contain any enterokinase, the pancreatic juice did not contain any plasmin or thrombin, but in animals fed high fat diet with ethanol, trypsinogen and chymotrypsinogen were significantly increased and trypsin inhibitor decreased. In the tissue, free trypsin and cathepsin B were increased. Composite profile of trypsinogen in gel segments obtained from the pancreatic juice and the tissue showed higher peaks of cationic and anionic variants of trypsinogen in animals fed ethanol. There was no evidence of mesotrypsinogen or of enzyme Y in the juice or the tissue. These studies show that serine proteases and cathepsin B may play a major role in the pathobiology of alcoholic pancreatitis.

Amylase secretion from isolated pure acinar cells.

Isolation of pure acinar cells of the rat pancreas was achieved employing counterflow sedimentation filtration technique (CSFT). The preparation of purified acinar cells contained an occasional red blood cell (RBC, 200:1) with total absence of endocrine and duct cells. A significant stimulation of amylase secretion from isolated pure acinar cells was produced by octapeptide of cholecystokinin (CCK8) and insulin produced potentiation of the effect of CCK8. Synthetic glucagon inhibited basal and CCK8 stimulated amylase secretion. Non-synthetic purified glucagon stimulated amylase secretion and potentiated the effect of CCK8. Vasoactive intestinal polypeptide (VIP) did not stimulate amylase secretion but potentiated the effect of CCK8. No leakage of lactic dehydrogenase (LDH) was detected from the cells in any of the secretion studies. Thus a highly purified preparation of isolated pure acinar cells of rat pancreas could be obtained with excellent morphologic and functional integrity.

An in vitro study of pancreatic ductal cells.

Summary Although pancreatic duct cells have been characterized morphologically and histochemically, information on their biochemistry and mechanism is lacking. The aim of the present work was to study selected metabolic parameters in the pancreatic duct of fed and fasted rats. The intact duct was quickly isolated by dissection and opened longitudinally. Twelve ducts were pooled for each study. Fasting for 72 hr was associated with decreases in [14C]glucose oxidation to 14CO2 and alkaline phosphatase activity. There were no changes with fasting in the following parameters: protein, RNA, or DNA content; 14Clabeled amino acid incorporation into proteins; [14C]glucose or [14C]glucosamine incorporation into g1ycoproteins; Mg2+-ATP-ase, HCO3 -ATPase, 5′-nucleotidase, or leucine aminopeptidase activities. In contrast to acinar cells, duct cells did not actively synthesize proteins. This study points out that pancreatic duct cells are metabolically active and that fasting was associated with reductions in glucose oxidation and alkaline phosphatase activity. Whether these metabolic activities are under the control of gastrointestinal hormones remains to be determined. Moreover, the significance of the reduction in alkaline phosphatase activity with fasting is not known.

Hydropneumothorax Following Peritoneoscopy

Peritoneoscopy is recognized as a safe and effective procedure, even though numerous complications have been reported. We have seen a patient in whom left hydropneumothorax developed after laparoscopy, a complication not previously reported.

Pancreatic amylase in chronic alcoholic rats.

To The Editor: In a recent study, Singh (1) observed the pancreatic amylase activity to be 37,075 5343 units/organ in rats maintained ad libitum for three months on Wayne Rodent-Blox diet. The enzyme activity was reduced by about 30% in those rats maintained for the same duration on AIN-76 formula liquidiet (26,024 -+ 4894 units/organ). The daily energy intake in either diet group was similar (246 vs 249 kJ). Both diets provided a similar proportion of energy from carbohydrate (65 vs 67%). Hence, it can be concluded that both groups of rats had a similar level of daily carbohydrate intake. It is surprising that a marked reduction in amylase activity was observed despite a similar intake of energy and carbohydrate. This reduction was termed liquid diet effect (1). Pancreatic amylase content has been known to be controlled by the level of dietary carbohydrate (2). It is logical to expect a similar level of enzyme activity in rats ingesting similar amounts of carbohydrate daily. This is also evident from the results of LaSure et al (3), which showed a similar amylase activity (37,076 vs 36,024 units/organ) in rats fed the Lab Blox diet or the AIN-76 liquid diet. The similarity in the level of enzyme activity with diets containing an average content of fat (12% of total calories) and a marked decrease in rats fed the Lieber-DeCarli control diet containing a high level of fat (35% of total calories) was suggested to be due to a high fat diet effect (3). In rats fed the ethanol diet, an alcohol effect was also suggested without ascertaining whether pancreatic tissue was exposed to high blood alcohol levels. In view of the discrepancies in the amylase levels in the pair-fed controls (AIN-76), the significance of the effects referred above and the suggested combined effects on pancreatic amylase remains unclear. Several other discrepancies also exist; for example, although many parameters in rats fed the AIN76 liquid diet plus ethanol for three months were the same as reported earlier (3), the body weight given was different (229 4 g and not 290 + 4 g) (1). Furthermore, although all the parameters in rats fed the Rodent-Blox diet were the same in the two reports (1, 3), the composition of the diet given was different. Such a discrepancy could have occurred in the reported values for amylase activity in rats fed the AIN-76 liquid diet. Since the amylase activity in rats fed the liquid diet for six months was similar to that in those fed for three months (21,503 vs 26,024 units/organ), it is likely that the activity observed in the earlier study is also 26,024 units/organ and not 36,024 units/organ. If so, when the enzyme activity of rats fed the Lieber-DeCarli control diet (15,549 units/organ) is compared to that in those fed the AIN-76 liquid diet (26,024 units/organ), a 40% decrease is observed. This decrease may not be related to the consumption of higher amounts of fat (2.3 vs 0.8 g) but rather to a 30% decrease in daily carbohydrate consumption (6.6 vs 9.4 g, and not 7.8 g as reported). It is perplexing that the anorexigenic effect of 36% alcohol diet (4) was not observed by Singh (1). The amount of alcohol diet ingested daily by rats, 69 kcal (1) or 57 kcal (3), is similar to that reported by others (5-7). However, when fed the liquid control diet ad libitum, the consumption increased markedly (90-100 kcal) (5-7). Even when fed a solid control diet, they ate about 25 g/day or about 100 kcal/day (6, 8) and not 15 g/day as reported by Singh (1). Hence it is difficult to comprehend that rats fed the Lab-Blox diet or the ethanol diet ingested the same amount of energy daily (1). It is possible that in the studies by Singh and coworkers, the ad libitum-fed controls ate considerably more than 15 g diet and hence obtained more carbohydrate compared to the pair-fed controls, causing the high levels of amylase activity reported. However, this is unlikely since, if the ad libitum-fed controls ingested more than 15 g of Lab-Blox diet, their body weight would have been considerably greater than that of the pair-fed controls and not similar as reported (295 vs 293 g) (1). Thus, many of the results reported by Singh are paradoxical and their explanation is difficult. The possible interpretation of the data in the two papers is that irrespective of whether the diet contains ethanol or not the amylase activity in rats fed these diets is directly proportional to the level of carbohydrate ingested. The liquid diet effect, high fat effect, and combined effects that have