Search PubMed⌕ Search

Biomedical subjects

M A Korsten

Publications and source records attributed to M A Korsten.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of ethanol and protein deficiency on pancreatic digestive and lysosomal enzymes.

The pathogenesis of alcoholic pancreatitis is not fully understood. An increase in pancreatic digestive and lysosomal enzyme synthesis because of ethanol consumption could contribute to the development of pancreatic injury in alcoholics. This study aimed, firstly, to determine the effect of ethanol on the content and messenger RNA levels of pancreatic digestive enzymes and on the messenger RNA level of the lysosomal enzyme cathepsin B, and secondly, to examine the influence of concomitant protein deficiency (a known association of alcoholism and pancreatic injury) on these effects. A rat model of chronic ethanol administration was used in which rats were fed in groups of four, and for four weeks, protein sufficient and protein deficient diets with or without ethanol. Ethanol increased the pancreatic content of lipase but did not influence chymotrypsinogen or trypsinogen values. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in rats fed ethanol. Protein deficiency resulted in reduced tissue levels of lipase, chymotrypsinogen, and amylase but did not influence trypsinogen values. mRNA levels for proteases were increased in protein deficient rats, while those for lipase remained unaltered. Both ethanol and protein deficiency increased mRNA levels for cathepsin B. It is concluded that chronic ethanol consumption, in both protein sufficient and protein deficient states, increases the capacity of the pancreatic acinar cell to synthesise digestive and lysosomal enzymes.

Amylases↗
PubMed1995

Ethanol-induced alterations in messenger RNA levels correlate with glandular content of pancreatic enzymes.

Ethanol abuse is a well-known association of pancreatitis. The effects of chronic ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an important role in the development of pancreatic injury. The aims of this study were to determine the effects of ethanol on gene expression and glandular content of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen). Pancreatic content and mRNA levels for lipase, trypsinogen, and chymotrypsinogen were determined in rats that were pair-fed a nutritionally adequate liquid diet with or without ethanol for 4 weeks. mRNA levels for the lysosomal enzyme cathepsin B were also assessed in this model. Ethanol significantly increased the content of lipase in the pancreas. There was a trend toward an increase in trypsinogen and chymotrypsinogen levels; however, these differences were not statistically significant. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in ethanol-fed rats. Ethanol feeding also increased mRNA levels for the lysosomal enzyme cathepsin B. Furthermore, there was a close, statistically significant correlation between changes in mRNA levels and tissue activities of pancreatic digestive and lysosomal enzymes after ethanol consumption. These results suggest that ethanol increases the capacity of the pancreatic acinar cell to synthesize digestive and lysosomal enzymes, thereby increasing the susceptibility of the gland to enzyme-related injury.

Acetaldehyde↗
PubMed1995

The effect of cisapride on segmental colonic transit time in patients with spinal cord injury.

OBJECTIVES: The pathophysiological consequences of spinal cord injury (SCI) on function of the colon are complex and poorly understood. Regardless of the mechanism, many patients with SCI have deficient bowel control, which is frustrating and difficult to treat. We designed a study to assess whether a new prokinetic medication, cisapride, might be useful in this setting. METHODS: Total and segmental colonic transit time were measured using the radiopaque marker technique in nine subjects with spinal cord injury and seven control subjects after the double-blind administration of cisapride (10 mg q.i.d.) or placebo. RESULTS: In five quadriplegic subjects with prolonged colonic transit time, administration of cisapride was found to reduce left-sided colonic transit time from 24.2 to 13.8 h. In three of these five subjects, cisapride administration resulted in subjective improvement. No effect of cisapride on right-sided, rectosigmoid, or total colonic transit time was observed. CONCLUSION: The data suggest that cisapride might be a useful adjunctive measure in treating a subset of SCI patients with colonic inertia, but a larger study is needed before this can be routinely recommended.

Adult↗
PubMed1994

Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules.

Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases is thought to be an early event in the pathogenesis of pancreatic injury. As ethanol excess is an important association of pancreatitis, experimental work has been directed towards exploring possible mechanisms whereby ethanol may facilitate contact between inactive digestive enzyme precursors and lysosomal enzymes. The aim of this study was to find out if chronic ethanol administration increases the fragility of rat pancreatic zymogen granules. Sixteen male Sprague-Dawley rats were pair fed ethanol and control liquid diets for four weeks. Zymogen granule fragility was then assessed in pancreatic homogenate by determination of (a) latency and (b) per cent supernatant enzyme after sedimentation of zymogen granules. Amylase was used as a zymogen granule marker enzyme. Latency was significantly reduced in pancreatic homogenates of ethanol fed animals suggesting increased zymogen granule fragility. In support of this finding, there was a trend towards increased supernatant enzyme after ethanol feeding. In conclusion, administration of ethanol increases the fragility of pancreatic zymogen granules in the absence of morphological evidence of pancreatic injury. It is proposed that zymogen granule fragility may play an early part in the pathogenesis of alcoholic pancreatitis by permitting contact between digestive and lysosomal enzymes.

Amylases↗
PubMed1994

Gastric emptying rates to liquid or solid meals appear to be unaffected by spinal cord injury.

OBJECTIVES: There is controversy with regard to the effect of spinal cord injury (SCI) on gastric emptying times of liquids. The emptying rates of solids in subjects with SCI have not yet been addressed. Thus, the gastric emptying rates for both liquids and solids were studied by radionuclide imaging in subjects with chronic SCI. METHODS: After an overnight fast, subjects with SCI were evaluated for gastric emptying rates for iso-osmolar (normal saline) and hyperosmolar (glucose) liquids and a mixed meal of liquids and solids. Twenty-five subjects received normal saline (500 ml). Of these 25 subjects, 16 and 4 others (a total of 20 subjects) received 75 g glucose dissolved in 225 ml water. Each of the liquid meals was labeled with 300 microCi technetium-99-m-diethylenetriaminepentaacetic acid (99mTc-DPTA). The mixed meal consisted of egg white labeled with 300 microCi technetium-99m-sulfur colloid (99mTc-SC) between two slices of toast with water (110 ml). Each test meal was followed by anterior radionuclide imaging of the stomach with the subject seated. The results were compared with those of matched healthy nonSCI subjects from the literature. RESULTS: Compared with gastric emptying times reported in the literature in healthy subjects without SCI, no significant differences were noted in those with SCI with regard to rates of gastric emptying for liquids (whether iso- or hyperosmolar) and for solids. CONCLUSIONS: Our findings do not support the previously reported results of a delay in gastric emptying for liquids in subjects with SCI. We have extended our findings of essentially normal rates of gastric emptying of liquids to that of solids.

Adult↗
PubMed1994

Sequelae after esophageal variceal ligation and sclerotherapy: a prospective randomized study.

OBJECTIVES: Esophageal variceal ligation is a new approach to the treatment of esophageal varices that does not result in transmural tissue injury and inflammation, and therefore might produce fewer sequelae and symptoms than sclerotherapy. We conducted a prospective, randomized comparison of sclerotherapy with ligation to study the relative short-term risks of these two procedures with respect to bacteremia, pulmonary and coagulation function, esophageal motility, and gastroesophageal reflux. METHODS: Patients with previously documented high grade esophageal varices were randomized to receive sclerotherapy or ligation. Blood was drawn for culture and coagulation profiles, and patients underwent pulmonary function tests, esophageal manometry, and intraesophageal pH monitoring before and after treatment. RESULTS: Six patients with Childs class B cirrhosis and one patient with pre-sinusoidal portal hypertension underwent 20 courses of therapy. Neither sclerotherapy nor ligation produced significant clinical changes in pulmonary or coagulation parameters, or bacteremia requiring treatment. The majority of ligation treatments were without worsening of motility or reflux scores, and none were associated with symptoms. Sclerotherapy was followed by significantly greater esophageal dysmotility and worsening reflux patterns. CONCLUSIONS: Patient acceptance of ligation was much greater than that for sclerotherapy. Our data define the advantages of ligation over sclerotherapy.

Bacteremia↗
PubMed1994

An overview of extrapancreatic factors in the pathogenesis of alcoholic pancreatitis.

Although alcohol is likely to have direct effects on the subcellular integrity of the pancreas, other factors arising outside the pancreas may modulate or potentiate alcohol-induced damage. Among these factors are the hepatic metabolism of ethanol to acetaldehyde (via isoenzymes of ADH), the hepatic production of free radicals, the release of G.I. hormones, pancreatic ischemia (and reperfusion injury), hyperlipemia, diet and smoking. This article summarises what is known about these extrapancreatic factors. It is suggested that the pathogenesis of alcoholic pancreatitis is multifactorial but that many studies in this field are difficult to interpret because of methodological problems, particularly with regard to inadequate controls.

Acetaldehyde↗
PubMed1993

Cathepsin B inhibition in two models of acute pancreatitis.

The possible role of cathepsin B in the pathogenesis of two forms of acute pancreatitis was studied using the cathepsin B inhibitor known as E-64. In an edematous, nonfatal pancreatitis induced by supramaximal doses of cerulein, increases in the serum amylase and lipase levels were less pronounced in rats pretreated with E-64. Other parameters of pancreatic injury were unaffected by inhibition of cathepsin B. In a necrohemorrhagic type of pancreatic injury induced by retrograde infusion of bile salts into the pancreatic duct, E-64 partially attenuated increases in serum levels of amylase and lipase, and in addition, reduced the activation of trypsinogen. However, the high mortality in this model of pancreatitis was not modified.

Acute Disease↗
PubMed1992

Gastrointestinal transit after spinal cord injury: effect of cisapride.

Heartburn, bloating, and abdominal discomfort are common problems in patients with spinal cord injury but, despite its clinical significance, little is known about the gastrointestinal effects of spinal transections. To address the potential gastrointestinal pathophysiology of spinal cord injury, we measured mouth-to-cecum transit time (MCTT) in seven subjects with paraplegia and seven with quadriplegia. Gastric emptying was studied in six subjects with quadriplegia. MCTT was significantly prolonged in patients with quadriplegia, an abnormality corrected by the administration of cisapride. Patients with paraplegia, in contrast to those with quadriplegia, have normal mouth-to-cecum transit time. In addition, patients with quadriplegia had neither a prolonged gastric emptying time nor a change in gastric emptying time, with cisapride. Changes in gastrointestinal transit after spinal cord injury and the improvement of mouth-to-cecum transit time in subjects with quadriplegia, but not in those with paraplegia, may be explained by an imbalance between parasympathetic and sympathetic outflows to the gastrointestinal tract in this group of subjects.

Adult↗
PubMed1991

Chronic alcoholic gastritis. Roles of alcohol and Helicobacter pylori.

We assessed the relative roles of alcohol and infection with Helicobacter pylori in the pathogenesis of chronic gastritis in alcoholic patients. Helicobacter pylori was found in 14 of 18 alcoholics with dyspepsia and was associated with chronic antral gastritis. Gastric biopsy specimens were normal in four H pylori-negative alcoholics. Studies were repeated 3 to 4 weeks after controlled abstinence. There was no change in histologic findings during this period, indicating that alcohol itself was not the major causative agent. We then eliminated H pylori in 10 subjects by giving triple therapy (bismuth subsalicylate, amoxicillin, and metronidazole). Treatment for H pylori was associated with almost complete normalization of histologic findings. Four control subjects who received antacids alone showed no improvement. Dyspeptic symptoms in H pylori-positive patients significantly improved after elimination of this organism, whereas there was no change with antacid treatment.

Adult↗
PubMed1991

Severity of Helicobacter-induced gastric injury correlates with gastric juice ammonia.

We postulated that ammonia produced by Helicobacter pylori may contribute to gastric mucosal injury. This hypothesis was evaluated in Helicobacter-positive patients with chronic renal failure in whom a high urea concentration might amplify this phenomenon. Gastric urea and ammonia were measured, and the severity of gastritis was evaluated by counting mononuclear and polymorphonuclear cells. High gastric ammonia and low urea in Helicobacter-positive patients, and the converse in Helicobacter-negative subjects, were observed. There was a significant correlation between gastric ammonia and interstitial polymorphonuclear leukocytes infiltration (P less than 0.05), suggesting a causal link. Eradication of Helicobacter pylori was associated with a decrease of ammonia and an increase of urea (P less than 0.01). The significant correlation between the severity of gastric inflammation and the gastric juice ammonia concentration suggests that ammonia may play a pathogenic role in Helicobacter-associated gastric injury.

Ammonia↗
PubMed1991

The effect of the prostaglandin analogue-misoprostol on rat liver mitochondria after chronic alcohol feeding.

Rats fed ethanol (36% of total calories in a nutritionally adequate liquid diet) for 5 weeks develop functional alterations of hepatic mitochondria and steatosis of the liver. At the fatty liver stage, ADP-stimulated respiration of mitochondria was depressed in ethanol fed rats by 30% (p less than 0.001) with glutamate + malate and by 23% (p less than 0.001) with succinate as substrates. A similar decrease was noted in the respiratory control ratio (RCR) (34% and 29%, respectively). The total lipid content of the liver increased 2.6 fold (p less than 0.001). Mitochondrial dysfunction could be prevented, in part, by the treatment with a synthetic derivative of prostaglandin E1, misoprostol, at a mean daily dose of 80 micrograms/kg of body weight. The RCR with glutamate + malate as substrates was improved by 36% (p less than 0.05). We conclude that misoprostol attenuates several functional alterations in liver mitochondria during alcohol feeding.

Alprostadil↗
PubMed1991

Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury.

OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency.

Chronic Disease↗
PubMed1990

Interactive effects of dietary protein and ethanol on rat pancreas. Protein synthesis and enzyme secretion.

Nutritional factors, especially the protein and fat content of the diet, may alter the likelihood of pancreatic injury after a number of insults, including chronic ethanol intake. This issue was studied experimentally by match-feeding rats liquid diets of varying protein content with and without ethanol. Protein synthesis and enzyme secretion were investigated, because these parameters are believed to increase the capacity for pancreatic autodigestion. Protein synthesis was assessed by determining the incorporation of tritiated phenylalanine into trichloroacetic acid precipitated protein 10 minutes after IP injection and then corrected for the size of the precursor pool. Enzyme secretion was studied using pancreatic acini, which were prepared using clostripain-poor collagenase. Chronic ethanol feeding stimulated protein synthesis and lipase secretion and content in rats receiving adequate amounts of protein. These stimulatory effects of ethanol were markedly attenuated in rats administered protein poor diets. Protein deficiency per se significantly decreased the weight, protein, and enzyme content of the rat pancreas as well as increased the percentage release of lipase from acini. Although extrapolation from animal studies may be tenuous, the present findings may explain the link between nutrition and the occurrence of alcoholic pancreatitis.

Animals↗
PubMed1990

Effects of arachidonic acid on hepatic lipids in ethanol-fed rats.

The effects of arachidonic acid supplementation on rats fed ethanol employing an ad libitum schedule have been reported to be different from those observed when rats are fed in more limiting, matched fashion. To reexamine this issue, rats were fed unrestricted amounts of a diet in which 36% of the energy was provided by either ethanol or isocaloric amounts of carbohydrate. In half the animals, 7% of fat consisted of arachidonic acid. Despite earlier reports to the contrary, arachidonic acid had no effect on weight gain and did not attenuate the ethanol-induced fatty liver. Arachidonate supplementation tended to increase hepatic total lipids and triacylglycerols, and to potentiate the ethanol-induced elevation of cholesterol esters. Our present results are consistent with those previously reported using pair-feeding techniques in which dietary intakes are somewhat limited. Thus, regardless of the feeding technique employed, relative arachidonic deficiency cannot be involved to explain the lipid accumulation observed after chronic ethanol consumption.

Animals↗
PubMed1990

Both ethanol consumption and protein deficiency increase the fragility of pancreatic lysosomes.

Both ethanol abuse and protein deficiency result in pancreatic injury. Moreover, these two variables frequently coexist. As lysosomal enzymes may play a role in the initiation of pancreatic injury, the aim of this study was to determine the effects of ethanol consumption and protein deficiency on pancreatic lysosomal stability. For 3 weeks, male Sprague-Dawley rats were match-fed (in groups of four) isocaloric amounts of one of the following liquid diets: (1) protein-sufficient diet, (2) protein-sufficient diet containing ethanol as 36% of the total energy, (3) protein-deficient diet, and (4) protein-deficient diet containing ethanol as 36% of energy. Pancreatic lysosomal stability was assessed by determining (a) latency, as indicated by the percentage increase in lysosomal enzyme activity in pancreatic homogenate induced by Triton X-100, and (b) by the percentage of lysosomal enzyme remaining in the supernatant after sedimentation of the lysosomal pellet from the pancreatic homogenate. Protein deficiency was associated with a decrease in latency and an increase in supernatant enzyme. Ethanol administration was associated with a decreased latency. Both protein-deficient and ethanol-fed animals exhibited higher pancreatic activities of cathepsin B, a lysosomal protease capable of activating trypsinogen. In addition, protein-deficient animals exhibited higher pancreatic activities of acid phosphatase, N-acetyl-glucosaminidase, and beta-glucuronidase. As lysosomal enzymes are postulated to play a role in the initiation of pancreatitis, these results suggest that ethanol consumption and protein deficiency may at least partly exert their toxic effects on the pancreas by altering pancreatic lysosomal stability and increasing the glandular content of cathepsin B.

Acetylglucosaminidase↗
PubMed1989

Gastric origin of the first-pass metabolism of ethanol in humans: effect of gastrectomy.

The areas under the curve (AUCs) of blood ethanol concentrations are much smaller after oral than after intravenous administration of a small dose of ethanol. To study whether this difference is due to ethanol oxidation in the stomach, in the small intestine, or during first pass through the liver, we compared the AUCs after random administration of the same ethanol dose by the intravenous, oral, and intraduodenal routes to 5 abstaining alcoholics and via the two former routes to 10 subjects with Billroth II subtotal gastrectomy. In the nonoperated subjects, the AUCs after an ethanol dose (0.15 g/kg) given orally were 17% (p less than 0.01) of those achieved intravenously, in spite of the fact that greater than 99% of the dose had disappeared from the stomach at the completion of the AUC. By contrast, the AUCs after intraduodenal administration did not differ from those produced intravenously, indicating that neither the intestine nor the liver make a detectable contribution to this first-pass metabolism. Moreover, gastrectomy completely abolished the first-pass metabolism of ethanol. Gastric metabolism decreases the bioavailability of the ingested alcohol and thus attenuates its systemic toxicity. The abolition of this "protective barrier" in gastrectomized patients may increase their vulnerability to ethanol.

Ethanol↗