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Biomedical subjects

M A Korsten

Publications and source records attributed to M A Korsten.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Alcohol-induced pancreatic injury (Part I). Unexplained features and ductular theories of pathogenesis.

The pathogenesis of alcoholic pancreatitis continues to be a puzzle. Classical theories of pathogenesis tend to overlook the dual nature of the disease, i.e., symptomatic acute attacks and chronic progressive parenchymal destruction. Furthermore, it is unknown why only a small minority of alcoholics develop clinical pancreatic injury. In addition, there is a lack of basic data concerning the natural history of the condition after cessation of alcohol consumption. The most widely accepted theory of pathogenesis postulates the deposition of protein plugs in peripheral pancreatic ducts as the initial lesion. However, it has not been established that these plugs are the cause rather than a result of pancreatic injury. The so-called "Big Duct" theories of pathogenesis (biliary-pancreatic reflux, duodeno-pancreatic reflux, and obstruction-hypersecretion) are confounded by a lack of agreement concerning the effect of alcohol on the sphincter of Oddi. Nutritional factors and heredity may be responsible for the selectivity of alcohol in this condition; in this regard, a number of dietary and HLA studies have been performed, but these have generally been inadequately controlled. Subcellular pancreatic injury (fat droplets, autophagic vacuoles, and mitochondrial lesions) has been observed in alcoholics without pancreatitis and in animals fed alcohol. In addition, ethanol feeding in animals has been shown to affect pancreatic cholesterol, phospholipid, and fatty acid metabolism as well as pancreatic content of digestive enzymes. Research is hampered by the lack of a suitable animal model of the disease.

Alcohol Drinking↗
PubMed1988

Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue.

Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis.

Acetates↗
PubMed1988

Alterations in synaptic membrane molecular order associated with alcoholization and protein deficiency in rats.

The effects of chronic alcoholization and protein deficiency on synaptic membrane characteristics were studied in rats fed the following four liquid diets for 4 weeks: a protein-deficient diet containing alcohol, a protein-deficient diet containing no alcohol, a non-protein-deficient diet containing alcohol and a non-protein-deficient diet containing no alcohol. A fluorescent probe, diphenylhexatriene (DPH), was used to estimate the fluidity of synaptic membranes and their sensitivity to the fluidizing effect of ethanol added in vitro, in concentrations ranging from 50 mM to 800 mM. Prior to in vitro addition of ethanol, the difference between the fluidity of synaptic membranes of alcoholized and non-alcoholized animals was significant for the two groups of protein-deficient animals but not for the two groups of non-protein-deficient animals. After in vitro addition of ethanol, the differences between the fluidity of synaptic membranes of the alcoholized and non-alcoholized animals were larger and more frequently significant for the protein-deficient animals than for the non-protein-deficient animals. In view of previous observations that rats fed a protein-deficient diet experience more severe withdrawal symptoms following alcoholization than rats fed a nutritionally adequate diet, the results of the present experiment lend additional support to the hypothesis that tolerance and dependence may be mediated by alterations in biomembrane characteristics.

Alcoholism↗
PubMed1988

Combined effects of protein deficiency and chronic ethanol consumption on rat pancreas.

This study was performed in order to delineate the combined effects of protein deficiency and chronic ethanol ingestion on the rat pancreas. Rats fed ethanol in combination with protein-deficient diets developed marked steatosis, whereas alcohol ingestion with nutritionally adequate diets and protein deficiency alone each were associated with a more moderate degree of pancreatic lipid accumulation. On biochemical analysis, it was found that protein deficiency decreased pancreatic phospholipid content. Furthermore, both protein deficiency and chronic ethanol consumption increased pancreatic cholesteryl ester content, and their effects were additive. Functional changes were studied using isolated pancreative acini. Protein deficiency depressed the tissue content of lipase and the ability of pancreatic acini to secrete lipase. Chronic ethanol feeding increased lipase levels in the acini and also their secretory capacity. Thus, to the extent that enzyme accumulation in the pancreas plays a role in the pathogenesis of alcoholic pancreatitis, these results may explain the higher incidence of pancreatitis in well-nourished alcoholics that has been documented in dietary surveys.

Alcoholism↗
PubMed1987

Use of the triolein breath test in alcoholics with liver damage.

The triolein breath test (TBT) is a simple, noninvasive technique for the evaluation of steatorrhea. However, because it depends on intermediary hepatic processes, and because both liver damage and pancreatic dysfunction often co-exist in the alcoholic, the overall usefulness of the test in patients with liver injury was reassessed. We found that even in the absence of steatorrhea, a majority of patients with advanced liver injury (alcoholic hepatitis, cirrhosis, or both) had abnormal TBT results that failed to correct with pancreatic extract. In contrast, patients with less severe lesions (steatosis) had results that were not significantly different from those in normal controls. Inasmuch as the abnormal TBT results in patients with advanced alcohol-induced lesions did not correct with pancreatic extract, the test may not accurately differentiate pancreatic from nonpancreatic steatorrhea in some alcoholics.

Breath Tests↗
PubMed1986

Decrease in lipogenesis and glucose oxidation of rat adipose tissue after chronic ethanol feeding.

This investigation was performed to determine whether chronic ethanol feeding affects adipose tissue lipogenesis and glucose metabolism. Female Wistar rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 3 weeks. Chronic ethanol feeding resulted in a depression of adipose tissue lipogenesis as assessed by labeled glucose incorporation into glyceride glycerol and glyceride fatty acids. Glucose oxidation was also impaired after chronic ethanol feeding. Such changes may contribute to the postprandial hypertriacyglyceridemia observed in alcoholics.

Adipose Tissue↗
PubMed1986

Protein deficiency alters rat pancreatic lipid composition.

Pancreatic lipid composition was found to be altered in rats fed a protein-deficient diet for 4 wk. Increases in triglycerides and cholesteryl ester content were found in association with a decrease in phospholipids. Alterations in these lipids may adversely affect membrane function and predispose to pancreatic injury.

Animals↗
PubMed1986

New technique for the isolation of functional rat pancreatic mitochondria and its application to models of pancreatic injury.

The role of mitochondria in the initiation or promotion of pancreatic pathologic conditions has not been clearly delineated. In this context, it has recently been suggested that abnormal mitochondrial function may account for the fat accumulation observed in pancreatic acinar cells in alcoholism. To study these issues, we developed a method for the isolation of functional mitochondria from the rat pancreas. The resultant mitochondrial pellet possessed oligomycin-insensitive Mg2+-adenosine triphosphatase (ATPase) activity, and coupled respiration could be demonstrated in the presence of EDTA only after Mg2+ had been excluded from the incubation medium. Albumin was also a requirement for the demonstration of coupled respiration in vitro. When this new technique was applied to a rat model of alcohol-induced pancreatic steatosis, no mitochondrial dysfunction was demonstrated, suggesting that some other mechanism is responsible for fat accumulation in pancreatic acinar cells after long-term ethanol consumption. In contrast, DL-ethionine administration to rats produced partial or total uncoupling of mitochondrial respiration in the absence of morphologic evidence of mitochondrial injury.

Adenosine Diphosphate↗