Cucumis sativus and Cucurbita maxima extract attenuate diabetes-induced hepatic and pancreatic injury in a rat model.

Diabetes is usually associated with oxidative stress that causes hepatic and pancreatic tissue injury. This work was carried out to evaluate the effect of Cucumis sativus and Cucurbita maxima methanol extracts on the streptozotocin-induced diabetic hepatic and pancreatic injury in rats. Diabetes was induced in seven equal groups of rats by a single intraperitoneal injection of streptozotocin (40 mg/kg), in addition to the non-diabetic control group. Two diabetic groups were treated with Cucumis sativus methanol extract and two were treated with Cucurbita maxima, each at 200 and 400 mg/kg for 21 days after streptozotocin-induced diabetes. Another diabetic group was treated with both Cucumis sativus and Cucurbita maxima at 200 mg/kg of each. Another group was treated with metformin (200 mg/kg orally). The plant extracts normalized serum liver enzymes activities, oxidative stress markers, and restored serum proteins and lipid profile. They also significantly reduced blood sugar to values comparable to non-diabetic rats. The hypoglycemic effect is also confirmed by the improvement of the immunohistochemical expression of insulin in ß-cells of islets of Langerhans. Hepatic and pancreatic protection was also confirmed by the improvement of the histopathological picture as compared to STZ-diabetic rats. The GC-MS analysis revealed the presence of 35 and 34 compounds in the methanol extract of cucumber and pumpkin, respectively. Finally, the methanol extract of cucumber and pumpkin could be beneficial acting synergistically in the protection of the liver and pancreas against diabetes-induced tissue damage.

Taurine supplementation in high-fat diet fed male mice attenuates endocrine pancreatic dysfunction in their male offspring.

Obesity in fathers leads to DNA damage and epigenetic changes in sperm that may carry potential risk factors for metabolic diseases to the next generation. Taurine (TAU) supplementation has demonstrated benefits against testicular dysfunction and pancreatic islet impairments induced by obesity, but it is not known if these protective actions prevent the propagation of metabolic disruptions to the next generation; as such, we hypothesized that paternal obesity may increase the probability of endocrine pancreatic dysfunction in offspring, and that this could be prevented by TAU supplementation in male progenitors. To test this, male C57Bl/6 mice were fed on a control diet (CTL) or a high-fat diet (HFD) without or with 5% TAU in their drinking water (CTAU and HTAU) for 4 months. Subsequently, all groups of mice were mated with CTL females, and the F1 offspring were identified as: CTL-F1, CTAU-F1, HFD-F1, and HTAU-F1. HFD-fed mice were normoglycemic, but glucose intolerant and their islets hypersecreted insulin. However, at 90 days of age, HFD-F1 offspring displayed normal glucose homeostasis and adiposity, but reduced glucose-induced insulin release. HFD-F1 islets also exhibited ß- and α-cell hypotrophy, and lower δ-cell number per islet. Paternal TAU supplementation prevented the decrease in glucose-induced insulin secretion and normalized ß-cell size and δ-cell number, and increased α-cell size/islet in HTAU-F1 mice. In conclusion, HFD consumption by male founders decreases ß-cell secretion and islet-cell distribution in their offspring. TAU attenuates the deleterious effects of paternal obesity on insulin secretion and islet-cell morphology in F1 offspring.

Pancreas volume in health and disease: a systematic review and meta-analysis.

INTRODUCTION: The pancreas plays a central role in metabolism and is involved in the pathogenesis of several diseases. Pancreas volume is a holistic quantitative measure of pancreas size but the clinical relevance of pancreas volumetry is poorly understood. Areas covered: The aim was to systematically review studies in adults that used computed tomography or magnetic resonance imaging to measure pancreas volume in health and disease, to determine normal pancreas volume range, and to quantify changes in pancreas volume that are associated with disease. Expert commentary: The normal pancreas volume range in adults is 71-83 cm3, with no statistically significant difference between men and women. Type 2 diabetes and type 1 diabetes are associated with a progressively reduced pancreas volume. Overweight and obesity are associated with a progressively increased pancreas volume. There is a paucity of studies on pancreas volume in the setting of diseases of the exocrine pancreas, which should become a research priority in the future.

What the radiologist should know about postoperative MDCT evaluation of a patient treated with cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery (CRS), often associated with hyperthermic intraperitoneal chemotherapy (HIPEC), is now a well-recognised treatment for most peritoneal malignancies in selected patients. As imaging is frequently performed postoperatively, radiologists are increasingly confronted with postoperative multidetector-row computed tomography (MDCT) examinations in these cases. In this article, after briefly describing the procedures that are currently being performed for the treatment of peritoneal metastases, the normal postoperative MDCT changes that may be encountered after these procedures are described. We then highlight complications that may arise after CRS, depending on the surgery performed, and those related to HIPEC, and illustrate their MDCT features.

Pancreatic impairment and Igf2 hypermethylation induced by developmental exposure to bisphenol A can be counteracted by maternal folate supplementation.

Increasing evidence indicates that bisphenol A (BPA), a widely manufactured environmental pollutant, can induce changes in DNA methylation paatterns, which is a potential mechanism linking this environmental exposure to disease development. We investigated the influence of developmental exposure to BPA on pancreatic DNA methylation patterns and whether maternal folate supplementation can modify the epigenetic status and pancreatic impairment induced by BPA. Our results showed that maternal dietary folate supplementation in rats exposed to BPA counteracted the observed BPA-induced pancreatic impairments in the offspring, which included disrupted insulin secretion and glucose intolerance, and impaired morphology and ultrastructure of ß cells. Moreover, these pancreatic dysfunctions were shown to be associated with low expression and DNA hypermethylation of insulin-like growth factor-2 (Igf2) in islets induced by exposure to BPA during the developmental period. Importantly, maternal dietary folate supplementation was demonstrated to negate this Igf2 DNA hypermethylation in the offspring, which was consistent with the upregulation of Igf2 expression. Overall, our results suggest that early developmental exposure to BPA alters the DNA methylation of Igf2, that these altered methylation patterns are associated with impaired ß-cell function in the offspring and that these effects can be counteracted by maternal folate supplementation. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of maternal use of flaxseed oil during pregnancy and lactation on glucose metabolism and pancreas histomorphometry of male offspring from diabetic rats.

AIM: Investigate if the maternal use of flaxseed oil prevents pancreatic alterations in the offspring of diabetic mothers. METHODS: Diabetes was induced in female wistar rats (n=12) by a high-fat diet and low-dose of streptozotocin. After the confirmation of the diabetes (glucose >300 mg/dL), rats were mated and once pregnancy was confirmed, they were allocated into three groups (n=6): high-fat group (HFG); flaxseed oil group (FOG); and control group (CG) (nondiabetic rats). At weaning, male offspring (n=12/group) received a standard chow diet. The animals were euthanized in two phases: at 100 and at 180 days, (n=6/group). The pancreas was collected for histomorphometric and immunohistochemistry analysis. RESULTS: HFG showed hypertrophy of pancreatic islets at 100 and at 180 days (p<0.0001), while the FOG offspring had islets with smaller diameters compared to HFG at both phases of sacrifice (p<0.0001). HFG had a lower percentage of small islets when compared to CG and FOG, which had a higher percentage when compared to HFG (p=0.0053) at 100 days. At 180 days HFG showed higher percentage of larger islets (p=0.00137) and lower percentage of smaller islets (p=0.00112), when compared to FOG. HFG showed lower islet insulin immunodensity at 100 days (p<0.0001) and 180 days (p<0.0001), whereas FOG was similar to CG (p<0.0001) at 100 days and higher at 180 days (p<0.0001). CONCLUSIONS: Flaxseed oil reduced the damage caused by maternal hyperglycemia, promoting normal pancreas histomorphometry and ß cell mass.

Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

CONTEXT: A major role of the pancreas in zinc homeostasis has been suggested. OBJECTIVE: To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. PATIENTS: One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. MAIN OUTCOME MEASURE: Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. RESULTS: Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; P<0.001), and in tropical chronic pancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, P<0.001). Erythrocyte zinc levels were significantly lower in diabetic patients as compared to non-diabetics (P=0.036). CONCLUSIONS: This study demonstrates zinc deficiency in chronic pancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

[Severe acute liver and pancreas damage in anorexia nervosa].

Anorexia nervosa, a syndrome most commonly affecting young women, is characterized by weight less than 85% of weight that is considered normal for that persons age and height, distorted body image, and fear of becoming obese, and its mortality is up to 9%. We present a case of a 33-year-old woman with a 9-year history of anorexia nervosa. She admitted to our institution with decreased mentality, and her body mass index was 11.5 kg/m2 of the time admission. Initial aminotransferase level was severely elevated, but it was normalized solely with improved nutrition and weight gain. Five and sixteen days after the admission urinary tract infection and elevation of pancreatic enzymes occurred. They were successfully treated with antibiotics and nutritional support. Fifty seven days after the admission, she discharged. We report a case of acute hepatitis and pancreatitis treated with nutritional rehabilitation in a patient with severe anorexia nervosa for the first time in Korea.

[Ultrasound-guided percutaneous tube drainage combined with directly-viewed debridement with cholangioscopy: a mini-invasive strategy for peripancreatic necrotizing infection].

OBJECTIVE: To establish "an integrative therapy" of drainage and debridement on peripancreatic necrotizing infection (PPNI) with minimally invasive technique, and to detect its clinical effects. METHODS: There were 17 patients who accepted ultrasound-guided percutaneous tube drainage combined with directly-viewed debridement with cholangioscopy from March 2006 to January 2008. Percutaneous puncture and catheter (6 - 8 F) drainage were adopted on the patients suffering from PPNI with B-us guidance, then the drainage sinus was expanded progressively from 8 F to 24 F in diameter with Cook fascia dilator by degrees, and the 22 F or 24 F tube was easily placed into the interior of PPNI instead of the prior catheter. So a better drainage effect was achieved. One week later, the necrotizing tissue of PPNI could be observed and debrided with choledochoscope under a directly-viewed way through the enlarged new sinus. Thus, with the continuous tube drainage and repeated debridement, the focus was absorbed and covered gradually. RESULTS: Seventeen cases accepted the mini-invasive therapy, 15 cases were saved finally with cure rate of 88.2%, and 2 cases conversion to laparotomy because of some technical reasons. The mean healing time was 73 days, and the mean hospitalization time was 57 days. Bleeding was occurred in 2 cases localized in sinus and the inside of PPNI, digestive tract fistula was detected in 2 cases, and these patients with the complications were cured under nonoperative management. All the patients were still alive with following-up, neither remains nor recurrence of the PPNI was found in our group. CONCLUSIONS: Ultrasound-guided percutaneous tube drainage combined with directly-viewed debridement with cholangioscopy, as a mini-invasive therapy, could complete the goal-directed therapy of PPNI, meanwhile, realize the modern surgery ideal of damage control.

Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases.

Prion diseases are fatal neurodegenerative diseases that can induce endocrinopathies. The basis of altered endocrine function in prion diseases is not well understood, and the purpose of this study was to investigate the spatiotemporal relationship between energy homeostasis and prion infection in hamsters inoculated with either the 139H strain of scrapie agent, which induces preclinical weight gain, or the HY strain of transmissible mink encephalopathy (TME), which induces clinical weight loss. Temporal changes in body weight, feed, and water intake were measured as well as both non-fasted and fasted concentrations of serum glucose, insulin, glucagon, beta-ketones, and leptin. In 139H scrapie-infected hamsters, polydipsia, hyperphagia, non-fasted hyperinsulinemia with hyperglycemia, and fasted hyperleptinemia were found at preclinical stages and are consistent with an anabolic syndrome that has similarities to type II diabetes mellitus and/or metabolic syndrome X. In HY TME-infected hamsters, hypodipsia, hypersecretion of glucagon (in both non-fasted and fasted states), increased fasted beta-ketones, fasted hypoglycemia, and suppressed non-fasted leptin concentrations were found while feed intake was normal. These findings suggest a severe catabolic syndrome in HY TME infection mediated by chronic increases in glucagon secretion. In both models, alterations of pancreatic endocrine function were not associated with PrP(Sc) deposition in the pancreas. The results indicate that prominent endocrinopathy underlies alterations in body weight, pancreatic endocrine function, and intake of food. The prion-induced alterations of energy homeostasis in 139H scrapie- or HY TME-infected hamsters could occur within areas of the hypothalamus that control food satiety and/or within autonomic centers that provide neural outflow to the pancreas.

Protective effect of Hachimi-jio-gan against the development of pancreatic fibrosis and oxidative damage in Otsuka Long-Evans Tokushima Fatty rats.

In our previous study, the polyherbal drug Hachimi-jio-gan was reported to possess a protective effect against the progression of diabetic nephropathy by attenuating glucose toxicity and renal damage with a type 2 diabetic model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Based on these findings, this study was undertaken to reveal the effect of Hachimi-jio-gan on pancreatic damage focusing on fibrosis and oxidative stress in type 2 diabetes. OLETF rats were orally administered Hachimi-jio-gan for 32 weeks, and we assessed the changes in the serum glucose level every 8 weeks, as well as those of body weight, and food and water consumption every 4 weeks. In addition, pancreatic wet weight, insulin content, and Western blot analyses of transforming growth factor-beta(1), fibronectin, and nuclear factor-kappaB-related inflammatory enzymes, such as inducible nitric oxide synthesis and cyclooxygenase-2, were also performed in the pancreas. As a consequence, long-term treatment with Hachimi-jio-gan had a hypoglycemic effect, reducing pancreatic atrophy and fibrosis, and ameliorating the oxidative status. Therefore, this may provide evidence that Hachimi-jio-gan is a therapeutic target for preventing the development of pancreatic damage concomitant with hyperglycemia in type 2 diabetes.

Treatment of Shwachman syndrome by Japanese herbal medicine (Juzen-taiho-to): stimulatory effects of its fatty acids on hemopoiesis in patients.

Juzen-taiho-to (a Japanese herbal medicine) has been traditionally administered to patients with anemia, neutropenia, or wasting syndrome. We previously attempted to isolate and purify the hemopoiesis-stimulatory components in Juzen-taiho-to extracts using an in vitro hemopoietic stem cell (HSC) assay method in which mouse HSCs can proliferate on a stromal cell line (MS-5). We have found that fatty acids (particularly oleic acid and linolenic acid) actively promote the proliferation of HSCs, and that the effect is mediated by stromal cells, rather than by any direct action on the HSCs. In the present study, we show, using human normal bone marrow cells (BMCs) and umbilical cord blood cells, that similar stimulatory effects are due to the presence of oleic acid and linolenic acid, which stimulate the proliferation of HSCs in stroma-based culture systems. Furthermore, a marked stimulatory effect was noted on BMCs from patients with Shwachman syndrome, which shows pancreatic and bone marrow dysfunctions. We also show the data on hemopoietic recovery after the administration of Juzen-taiho-to to a patient with Shwachman syndrome. These findings suggest that decreased fatty acid levels in the blood, caused by exocrine pancreatic insufficiency, induce bone marrow dysfunction in Shwachman syndrome.

[Giant benign gastric ulcer penetrating into the liver, pancreas and mesocolon]. / Ulcera gastrica gigante benigna penetrante nel fegato, nel pancreas e nel mesocolon.

Penetration of the liver, pancreas and transverse mesocolon by a giant benign gastric ulcer is relatively uncommon, and literature contains a few reports of this complication. The preoperative histological diagnosis may be difficult or impossible. A 63-year-old female patient with a history of seven months of lack of appetite, asthenia, epigastric pain, a remarkable weight decrease, presenting at physical examination a large, smooth margins, not pulsating, quite fixed abdominal mass, is reported. Echography confirmed the presence of a mass of approximately 14 x 19 cm, with solid and liquid content. Biopsy showed inflammatory elements and cellular detriti. Barium enema showed that the mass compressed the descendent colon, which appeared dislocated. Tumor markers (CEA, CA 19-9, alpha-fetoprotein) where in the normal range. Endoscopy showed a giant angular ulcer whose bottom was represented by necrotic material (after the definitive histological examination it proved to be hepatic tissue). At TC scan of the abdomen, a remarkable thickening of the gastric wall was present. At surgery the stomach appeared increased in volume, with remarkably thickened walls, tenaciously sticking to II and III hepatic segments, to the pancreas and transverse mesocolon. A total gastrectomy was performed because of the depth of the ulcer penetration and the extension of the alteration of the gastric wall, even if the giant gastric ulcer, in the literature, is more frequently benign than malignant.

Effect of kinin inhibition in experimental acute pancreatitis.

Activation of the endogenous kinin system is a consistent observation in acute pancreatitis and has repeatedly been implicated in the pathophysiology of the disease. We have studied the effect of a potent bradykinin antagonist on the onset and development of acute pancreatitis in four unrelated animal models. Pancreatitis was induced in rats by either supramaximal stimulation with caerulein, intraductal injection of sodium taurocholate, or pancreatic duct ligation with secretin infusion, and in mice by feeding a choline-deficient, ethionine-supplemented diet. The potent, long-acting bradykinin antagonist HOE-140 was administered subcutaneously (0.1 mg/kg every 5 h). Effective kinin inhibition had no effect on pancreatitis-associated mortality, the extent of morphological damage and inflammation, or the intracellular distribution of lysosomal hydrolases. Pancreatic edema was only reduced in caerulein-induced pancreatitis, the only model in which edema formation was paralleled by increased vascular permeability. We conclude that, contrary to previous suggestions, kinins do not play a predominant role in the development of acute pancreatitis. Their participation is strictly limited to vascular events and does not involve the early cell biological alterations in pancreatic acinar cells.

Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring.

Many mutagenic nitroso compounds are also diabetogenic. Betel-nut (Areca catechu) chewing populations have an increased incidence of foregut cancers related to betel-nut nitrosamines which suggests that betel consumption could be diabetogenic. Young adult CD1 mice with a low spontaneous incidence of diabetes were fed betel nut in standard feed for 2-6 days. Single point (90 min) intra-peritoneal glucose tolerance tests were used to follow glucose tolerance up to 6 months of age. Glucose intolerance was defined as over 3 SD above mean control values. Glucose intolerance was found in 3 of 51 male and 4 of 33 female adult mice which were fed the betel diet (p < 0.01). Studies on the progeny of these mice are presented separately for animals studied in Aberdeen (Group 1) and London (Group 2). In matings of Group 1 betel-fed parents glucose intolerance was found in 4 of 25 male and 1 of 22 female F1 offspring, with significant hyperglycaemia in F1 males born to hyperglycaemic but not to normoglycaemic mothers (p < 0.01). In the F2 generation 4 of 23 males and 1 of 16 females and in the F3 generation 1 of 16 males and 0 of 20 females were glucose intolerant. In the Group 2 studies where betel-fed parents were mated to normal controls glucose intolerance was found in 10 of 35 male and 10 of 33 female F1 progeny (p < 0.005), and mean islet areas were increased in offspring of betel-fed parents (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperbaric oxygen therapy in the treatment of refractory peripancreatic abscess associated with severe acute pancreatitis.

Five patients with peripancreatic abscesses associated with severe acute pancreatitis were treated by hyperbaric oxygen therapy (HBO). In 3 patients, the course after surgical mobilization of the pancreas and drainage of the pancreas bed was complicated by peripancreatic abscesses. HBO was conducted under a pressure of 2.8 atmospheres for two hours daily. Four of the 5 patients showed a progressive improvement in their condition. In one patient who failed to respond despite seven sessions of HBO, Pseudomonas aeruginosa was isolated from the discharge, and resection of necrotic tissue and drainage were performed. The main effects of HBO were the alleviation of high spiking fever, the improvement of white blood cell count and serum amylase levels, and the reduction of the abscess size. We recognized HBO to be a successful treatment for peripancreatic abscess associated with severe acute pancreatitis and better results were obtained than in cases that did not receive HBO.

Vitamin E supplementation reduces the incidence of diabetes but not insulitis in NOD mice.

The incidence of diabetes was reduced in non-obese diabetic (NOD) mice fed a diet containing 1000 IU/kg of vitamin E. Histologic examination of the islets of these mice, however, disclosed a frequency of insulitis that approximated the frequency found in animals fed conventional diets. The vitamin E-treated mice were not immunosuppressed, as judged by normal T cell subsets in the spleen and normal T cell proliferative responses to concanavalin A. NOD mice deprived of vitamin E were also protected from diabetes. However, these mice had delayed growth, reduced T cell numbers in the spleen, and impaired proliferative responses to mitogens, which is indicative of secondary immunodeficiency. The data are consistent with the view that antioxidant treatment may limit immunologically mediated damage to islet beta cells.

Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis.

We investigated the therapeutic potential of an acid-resistant fungal lipase prepared from Aspergillus niger. We first demonstrated in vitro that it had a wide pH optimum of 2.5-5.5 and was resistant to pepsin and trypsin. We gave the enzyme or matching placebo in random order by mouth with a fatty meal to 10 adult patients with pancreatic steatorrhoea due to cystic fibrosis (CF) and sampled gastric contents for the following 2 h. Mean acid-resistant lipase activity was 330 nmol/ml/min free fatty acid released on placebo, compared with 896 nmol/ml/min on fungal lipase (p = 0.006 for area under the curve). We compared this lipase's clinical efficacy with that of two conventional pancreatin microsphere formulations in an open randomised crossover fat-balance study in 10 similar patients. Each preparation was given for 2 weeks, and a fat-balance study, using a faecal recovery marker, was performed on the final 3 days; a period without treatment was also included. The fungal lipase had no effect on faecal wet weight or on the coefficient of fat absorption (59.0% vs. 52.3%; NS) in comparison with placebo. The established enteric-coated microsphere preparation (Creon) produced a significant reduction in faecal wet weight and improvement in coefficient of fat absorption (81.4% vs. 52.3%; p less than 0.01) in comparison with placebo. The newer microsphere preparation (Pancrex M) was also effective, but perhaps less so than Creon; there were no significant differences between the two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Selected organopathies caused by experimental magnesium deficiency]. / Wybrane organopatie wywolane doswiadczalnym niedoborem magnezu.

A role of enzyme mediated metabolic processes is discussed. Unfavourable effect of magnesium deficiency on the functioning of various organs may lead to extensive and irreversible morphological changes of focal character. Basing on the results of several experiments and own experience, the author discusses an effect of low-magnesium diet on histological, histochemical, and microscopic lesions to the myocardium, skeletal musculature, liver, and pancreas. Magnesium deficiency predisposes to myocardial necrosis which simulates electrolyte-steroid-cardiomyopathy by necrosis (ESCN). Low-magnesium diet decreases resistance of the animals to various types of stress such as: cooling, immobilization, and noise. Insignificant degree of the lesions to skeletal musculature produced by magnesium deficiency and no progress in these lesions during the experiment may depend upon relatively stable magnesium reserve in the muscles. Low-magnesium diet increases the number of so-called Ito cells in the liver. It is probable that these cells together with hepatocytes contribute to the formation of collagen fibres. Magnesium deficiency may lead to the abnormal digestion of nutrients in the pancreas, interfering with exocytosis of zymogen granules. Supplementation of the diet with magnesium may prevent various organopathies.