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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

Torsion and infarction of an accessory liver lobe.

Accessory lobes of the liver (ALL) may be congenital or acquired and are usually of no clinical significance. Torsions of the ALL are exceedingly rare and most are incidental findings at laparotomy, autopsy and in the course of investigation radiological investigations. A total of 17 infant and adult cases have been described previously in the medical literature. Most cases described since 1925 have been diagnosed at laparotomy, we report the 18th case of torsion of the accessory lobe of the liver in an elderly female which, despite all radiological interventions, required laparoscopy for diagnosis. We conclude that torsion of the accessory lobes of the liver is a rare finding; radiological imaging does not reveal the diagnosis and most are found at laparotomy. Laparoscopy may aid in the diagnosis of torsion of accessory liver lobes. If pain persists, we advocate the use surgical intervention with or without cholecystectomy.

Abdominal Pain↗

Susceptibility to cerulein-induced pancreatitis in inducible nitric oxide synthase-deficient mice.

Production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been proposed as a pathogenic factor in acute pancreatitis, but its role has still not been fully examined. The present study explored the role of iNOS in cerulein-induced acute pancreatitis using iNOS-deficient mice. Twelve- to 14-week-old male mice (C57B1/6 and iNOS-deficient) were administered cerulein by intraperitoneal (i.p.) injection at hourly intervals for 7 hours and killed 24 hours later after the first dose. Pancreatic wet weight, pancreatic myeloperoxidase (MPO) activity, and levels of plasma nitrite and serum amylase were measured. In another experiment isosorbide dinitrate (an NO donor) was given by oral gavage every 6 hours for 24 hours beginning simultaneously with cerulein injections in iNOS-deficient mice. Cerulein administration dose-dependently increased pancreatic wet weight, myeloperoxidase activity, and levels of nitrite and amylase in C57B1/6 mice. These parameters (except nitrite levels) were significantly intensified in iNOS-deficient mice. At the dose employed, cerulein failed to increase nitrite levels in iNOS-deficient mice. The susceptibility to cerulein toxicity in iNOS-deficient mice was abolished by NO donor treatment. NO release from an iNOS source appears to play a protective role in cerulein-induced pancreatitis. At least in part, NO may prevent neutrophil accumulation after cerulein administration.

Acute Disease↗

Reversal of the gastric effects of nicotine by nitric oxide donor treatment.

Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric mucosal injury in rats administered nicotine. A nicotine solution or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine.

Analysis of Variance↗

Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells.

BACKGROUND & AIMS: Activated pancreatic stellate cells have recently been implicated in pancreatic fibrogenesis. This study examined the role of pancreatic stellate cells in alcoholic pancreatic fibrosis by determining whether these cells are activated by ethanol itself and, if so, whether such activation is caused by the metabolism of ethanol to acetaldehyde and/or the generation of oxidant stress within the cells. METHODS: Cultured rat pancreatic stellate cells were incubated with ethanol or acetaldehyde. Activation was assessed by cell proliferation, alpha-smooth muscle actin expression, and collagen synthesis. Alcohol dehydrogenase (ADH) activity in stellate cells and the influence of the ADH inhibitor 4-methylpyrazole (4MP) on the response of these cells to ethanol was assessed. Malondialdehyde levels were determined as an indicator of lipid peroxidation. The effect of the antioxidant vitamin E on the response of stellate cells to ethanol or acetaldehyde was also examined. RESULTS: Exposure to ethanol or acetaldehyde led to cell activation and intracellular lipid peroxidation. These changes were prevented by the antioxidant vitamin E. Stellate cells exhibited ethanol-inducible ADH activity. Inhibition of ADH by 4MP prevented ethanol-induced cell activation. CONCLUSIONS: Pancreatic stellate cells are activated on exposure to ethanol. This effect of ethanol is most likely mediated by its metabolism (via ADH) to acetaldehyde and the generation of oxidant stress within the cells.

Acetaldehyde↗

Prolonged ambulatory colonic manometric studies using endoclips.

BACKGROUND: It is difficult to study human colonic motility under physiologic conditions. An important limitation associated with prolonged colonic recording is the failure of the sensors to resist normal expulsive forces. METHOD: In this article we describe a method of endoscopically positioning a manometric catheter by using clips in conjunction with a solid-state catheter. With the use of a rotatable clip-fixing device loaded on to a colonoscope, the manometric catheter was clipped to the colonic mucosa. RESULTS: Recordings for up to 120 hours were obtained from 6 subjects without apparent migration of the catheter assembly. No complications were noted, the catheter does not interfere with defecation, and defecation does not result in its expulsion. CONCLUSION: The current technique will allow reliable ambulatory measurements over prolonged periods of time in relatively comfortable and unrestrained subjects. This technique should increase our understanding of normal and abnormal colonic motility.

Colon↗

Racial factors and the risk of chronic pancreatitis.

OBJECTIVE: It is unclear why some alcohol abusers develop alcoholic cirrhosis whereas others contract chronic pancreatitis. The aim of this study was to examine the importance of race as a risk factor for the development of chronic pancreatitis. METHODS: We compared the racial status of 1883 patients discharged with a first-listed diagnosis of two diseases strongly related to alcohol abuse: 433 patients with chronic pancreatitis (ICD 5771) and 1450 patients with alcoholic cirrhosis (ICD 5712). Information came from discharge statistics maintained by two acute care hospitals in New York City and one acute care hospital in Lisbon, Portugal. The study period included the years 1989-1996 in the US and 1989-1994 in Portugal. RESULTS: A total of 215 (50%) of the 433 chronic pancreatitis patients were black compared with 333 (23%) of the 1450 patients with alcoholic cirrhosis. When adjusted for sex and hospital site, patients with pancreatitis were significantly more likely to be black than patients with cirrhosis (odds ratio 2.5, 95% confidence interval 1.9-3.2, p < 0.001). CONCLUSIONS: In comparison with white patients, black patients are two to three times more likely to be hospitalized for chronic pancreatitis than alcoholic cirrhosis. This highly significant (p < 0.001) difference was observed in both men and women: in three different hospitals, and in two different countries. The explanation is unknown, but could be related to racial differences in diet, type or quantity of alcohol consumption, smoking, or ability to detoxify substances harmful to the liver or pancreas.

Adult↗

Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis.

BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress. AIMS: To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor beta (TGF-beta). METHODS: Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-beta. RESULTS: Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose related increase in cell counts as well as in the incorporation of 3H-thymidine into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-beta showed a dose dependent increase in alpha smooth muscle actin expression and increased collagen synthesis. In addition, TGF-beta increased the expression of PDGF receptors on stellate cells. CONCLUSIONS: Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-beta by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis.

Actins↗

Metabolism of ethanol by rat pancreatic acinar cells.

It has been postulated that ethanol-induced pancreatic injury may be mediated by the oxidation of ethanol within the pancreas with secondary toxic metabolic changes, but there is little evidence of pancreatic ethanol oxidation. The aims of this study were to determine whether pancreatic acinar cells metabolize significant amounts of ethanol and, if so, to compare their rate of ethanol oxidation to that of hepatocytes. Cultured rat pancreatic acinar cells and hepatocytes were incubated with 5 to 50 mmol/L carbon 14-labeled ethanol (25 dpm/nmol). Ethanol oxidation was calculated from the production of 14C-labeled acetate that was isolated by Dowex ion-exchange chromatography. Ethanol oxidation by pancreatic acinar cells was demonstrable at all ethanol concentrations tested. At an intoxicating ethanol concentration (50 mmol/L), 14C-labeled acetate production (227+/-20 nmol/10(6) cells/h) approached that of hepatocytes (337+/-61 nmol/10(6) cells/h). Phenanthroline (an inhibitor of classes I through III isoenzymes of alcohol dehydrogenase (ADH)) inhibited pancreatic ethanol oxidation by 90%, but 4-methylpyrazole (a class I and II ADH inhibitor), carbon monoxide (a cytochrome P450 inhibitor), and sodium azide (a catalase inhibitor) had no effect. This study has shown that pancreatic acinar cells oxidize significant amounts of ethanol. At intoxicating concentrations of ethanol, pancreatic acinar cell ethanol oxidation may have the potential to contribute to pancreatic cellular injury. The mechanism appears to involve the class III isoenzyme of ADH.

Acetates↗

Bowel care for individuals with spinal cord injury: comparison of four approaches.

The efficacies of four bowel care regimens (bisacodyl suppositories, glycerin suppositories, mineral oil enemas and docusate sodium mini-enemas) were compared in seven subjects with traumatic spinal cord injury. Efficacy was assessed in terms of colonic transit time, bowel evacuation time and subjective responses to a questionnaire. Both docusate sodium mini-enemas and mineral oil enemas decreased total and left-sided colonic transit time. However, docusate sodium mini-enemas were superior to mineral oil enemas in terms of the decrease in bowel evacuation time and symptom reduction. Results in this small group of subjects suggest that docusate sodium mini-enemas may have advantages in the management of bowel evacuation in individuals with spinal cord injury.

Adult↗

Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture.

BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells (vitamin A storing cells) play a significant role in the development of fibrosis. AIMS: To determine whether cells resembling hepatic stellate cells are present in rat pancreas, and if so, to compare their number with the number of stellate cells in the liver, and isolate and culture these cells from rat pancreas. METHODS: Liver and pancreatic sections from chow fed rats were immunostained for desmin, glial fibrillary acidic protein (GFAP), and alpha smooth muscle actin (alpha-SMA). Pancreatic stellate shaped cells were isolated using a Nycodenz gradient, cultured on plastic, and examined by phase contrast and fluorescence microscopy, and by immunostaining for desmin, GFAP, and alpha-SMA. RESULTS: In both liver and pancreatic sections, stellate shaped cells were observed; these were positive for desmin and GFAP and negative for alpha-SMA. Pancreatic stellate shaped cells had a periacinar distribution. They comprised 3.99% of all pancreatic cells; hepatic stellate cells comprised 7.94% of all hepatic cells. The stellate shaped cells from rat pancreas grew readily in culture. Cells cultured for 24 hours had an angular appearance, contained lipid droplets manifesting positive vitamin A autofluorescence, and stained positively for desmin but negatively for alpha-SMA. At 48 hours, cells were positive for alpha-SMA. CONCLUSIONS: Cells resembling hepatic stellate cells are present in rat pancreas in a number comparable with that of stellate cells in the liver. These stellate shaped pancreatic cells can be isolated and cultured in vitro.

Animals↗

Chronic ethanol administration decreases rat pancreatic GP2 content.

Postulated mechanisms of alcoholic pancreatitis include (i) zymogen granule fragility facilitating intracellular activation of digestive enzymes and (ii) ductular obstruction by protein plugs. GP2, a pancreatic glycoprotein, stabilizes zymogen granule membranes and is an important constituent of pancreatic protein plugs. Therefore, this study examined the pancreatic content and messenger RNA levels of GP2 after chronic ethanol administration. Rats were fed liquid diets with or without ethanol, for four weeks. GP2 levels in pancreatic homogenates, crude zymogen granules and zymogen granule membrane fractions were assessed by immunoblotting. Messenger RNA levels for GP2 were measured by Northern and dot blotting of pancreatic RNA. Pancreatic GP2 levels were lower in ethanol-fed rats than in controls (GP2 levels expressed as % of control: 38.75 +/- 5.8, p < 0.001 in homogenate; 31.28 +/- 3.5, p < 0.0005 in crude zymogen granules and 22.89 +/- 5.4, p < 0.0005 in zymogen granule membranes). Messenger RNA levels for GP2 were unchanged after ethanol feeding. Chronic ethanol consumption decreases GP2 content of pancreatic homogenate and zymogen granules. This decrease could (i) result from an increased release into pancreatic juice thereby favouring protein plug formation and (ii) impair zymogen granule stability. Both these mechanisms could potentiate pancreatic damage.

Animals↗

Alcohol-related pancreatic damage: mechanisms and treatment.

Pancreatitis is a potentially fatal inflammation of the pancreas often associated with long-term alcohol consumption. Symptoms may result from blockage of small pancreatic ducts as well as from destruction of pancreatic tissue by digestive enzymes. In addition, by-products of alcohol metabolism within the pancreas may damage cell membranes. Research on the causes of pancreatitis may support more effective disease management and provide hope for a potential cure.

Alcohol Drinking↗

Both ethanol and protein deficiency increase messenger RNA levels for pancreatic lithostathine.

Both ethanol abuse and protein deficiency are well known associations of chronic pancreatitis. An early event in chronic pancreatitis is the deposition of protein plugs in small pancreatic ducts, leading to ductular obstruction and acinar cell damage. Lithostathine, a pancreatic secretory protein, is a major organic component of protein plugs. The aim of this study was to determine the effect of chronic ethanol administration and dietary protein deficiency, separately and in combination, on messenger RNA (mRNA) levels for pancreatic lithostathine. Male Sprague-Dawley rats were fed in groups of four, for four weeks, protein sufficient and protein deficient diets with or without ethanol. Messenger RNA levels for pancreatic lithostathine were assessed in all four groups. Both ethanol and protein deficiency, separately and in combination, increased mRNA levels for lithostathine. Thus, both chronic ethanol consumption and dietary protein deficiency increase the capacity of the pancreatic acinar cell to synthesize lithostathine.

Alcoholism↗

Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.

OBJECTIVE: To compare ranitidine to misoprostol with respect to the prevention of gastric and duodenal ulcers in patients on chronic NSAID therapy. METHODS: A multi-center, 8-wk, randomized, double-blind study. Eligible patients were on chronic NSAID therapy and were experiencing NSAID-related upper gastrointestinal (UGI) pain without UGI endoscopic evidence of gastric or duodenal ulcers. Patients enrolled in the study were randomized to either misoprostol 200 micrograms q.i.d. or ranitidine 150 mg b.i.d.. Follow-up UGI endoscopy was performed after 4 and 8 wk of treatment. Therapeutic failure was considered the development of a gastric or duodenal ulcer > or = 0.3 cm in diameter with perceptible depth. RESULTS: Gastric ulcers were found in only 1/180 (0.56%) patient on misoprostol and in 11/194 (5.67%) patients on ranitidine, a difference that was statistically significant (p < 0.01). Duodenal ulcer rates were similar for the ranitidine (2/185 or 1.08%) and misoprostol (2/181 or 1.10%) groups. CONCLUSION: Misoprostol is significantly more effective than ranitidine in the prevention of NSAID-induced gastric ulcers. Ranitidine was as effective as misoprostol for the prevention of NSAID-induced duodenal ulcers. Misoprostol should be used for prophylaxis against both gastric and duodenal ulceration in patients on chronic NSAID therapy.

Administration, Oral↗

Gastric metabolism of ethanol in Syrian golden hamster.

First-pass metabolism (FPM) of orally ingested alcohol has been attributed to gastric alcohol dehydrogenase (ADH) activity in both humans and rats. To determine whether gastric alcohol dehydrogenase is essential for alcohol FPM, we sought a species lacking this enzyme. We found that Syrian golden hamsters have negligible gastric ADH yet alcohol FPM (265 +/- 25 mg ethanol/kg) was comparable to that of rats (251 +/- 31 mg/kg). To determine whether hamster gastric mucosal cells metabolize sufficient alcohol to account for this FPM, primary cultures were established, and these cells metabolized 1.99 +/- 0.84 mumol ethanol/10(6) cells/hr, an amount sufficient to account for the bulk of alcohol FPM. In contrast to alcohol dehydrogenase, catalase activity in hamster gastric mucosa (870 +/- 93 units/g tissue) was eightfold higher than in rat gastric mucosa (111 +/- 9 units/g tissue; P < 0.0001). FPM in hamsters treated with 3-aminotriazole was reduced from 242 +/- 24 to 130 +/- 22 mg/kg (P < 0.05) but was not reduced in rats. The results imply that catalase participates in gastric alcohol metabolism of hamsters.

Alcohol Dehydrogenase↗

The effect of chronic alcohol administration on cerulein-induced pancreatitis.

Alcohol consumption i associated with pancreatitis, but the mechanism underlying this injury remains unclear. Alcohol consumption has recently been shown to increase the fragility of both rat pancreatic lysosomes and zymogen granules in vitro, which may predispose to autodigestion via the intracellular activation of digestive enzymes by lysosomal enzymes. Cerulein-induced pancreatitis is also associated with lysosomal fragility. To determine the effect of alcohol consumption on this form of pancreatic injury, the severity of pancreatitis was compared in three groups of rats following i.v. cerulein infusion: rats fed alcohol in a liquid diet, pair-fed dextrose controls, and chow-fed controls. The histological severity of pancreatitis induced by supramaximal cerulein infusion was not found to be increased by prior alcohol consumption. Since alcohol did not appear to increase the severity of pancreatic injury induced by cerulein, we sought to define biochemical parameters that might precede obvious injury. The subcellular distribution of cathepsin B activity and markers of lysosomal fragility were compared in the same groups of experimental animals. Cerulein infusion led to a marked redistribution of cathepsin B activity from the lysosomal to the zymogen-granule-enriched fractions.For animals killed in the fed state, a redistribution of cathepsin B activity toward the zymogen-granule-enriched fraction was also demonstrated in alcohol-fed animals compared to their pair-fed controls. However, chronic alcohol administration did not influence the effect of cerulein on subcellular cathepsin B distribution or lysosomal fragility. In this rat study, administration of alcohol did not increase the effects of supramaximal doses of cerulein on the pancreas.

Amylases↗

Metabolism of ethanol in rat gastric cells and its inhibition by cimetidine.

BACKGROUND/AIMS: Several studies have shown that the stomach has sufficient alcohol dehydrogenase activity to metabolize a significant amount of alcohol and that cimetidine depresses this alcohol dehydrogenase activity. However, both gastric metabolism of ethanol and its inhibition by cimetidine remain controversial. Given the difficulty in assessing gastric metabolism of ethanol in vivo, this subject was investigated in vitro. METHODS: Cultured rat gastric epithelial cells were incubated with 200 mmol/L [1-14C]ethanol for 90 minutes with and without cimetidine (0.1-1 mmol/L) or omeprazole (1 mmol/L). The quantity of ethanol oxidized by gastric cells was measured by the amount of acetate produced using ion exchange chromatography. RESULTS: The majority of cells at confluency had typical features of mucous cells. The gastric cells metabolized significant amounts of ethanol, sufficient to account for in vivo first-pass metabolism of ethanol in rats. Cimetidine, but not omeprazole, reduced ethanol metabolism by 39.9% +/- 4.9% (P < 0.01), an inhibition comparable with that previously reported for first-pass metabolism in vivo. CONCLUSIONS: Gastric cells in tissue culture are capable of significant ethanol oxidation, the in vitro rates are sufficient to account for first-pass metabolism of ethanol in vivo, and cimetidine inhibits ethanol metabolism in tissue culture, an effect that parallels its decrease of first-pass metabolism in vivo.

Alcohol Dehydrogenase↗

The effects of cisapride on the quality and tolerance of colonic lavage: a double-blind randomized study.

Colonic lavage is a preferred preparation for colonoscopy although this type of preparation does not always result in optimal cleansing. We postulated that cisapride, a new prokinetic agent, might improve the cleansing of the colon and ameliorate patient discomfort. Of 84 patients undergoing colonoscopy, 41 were randomized (double-blind) to Golytely plus cisapride (10 mg per OS three times during the day before the procedure and one 10-mg dose on the morning of the procedure) and 43 to Golytely plus a placebo of identical appearance. The adequacy of the preparation was scored on a five-point grading scale for each anatomic segment and for the overall impression. A questionnaire was also used to assess each patient's symptoms during lavage. The mean overall preparation score in the cisapride group was 4.0, compared with 3.7 for the placebo group (p = .54). In the transverse colon, the mean preparation score was higher for the cisapride group (4.3 versus 3.8, p = .02). Differences in symptom scores between the two groups were not significant. In conclusion, the use of cisapride may improve visualization of the transverse colon, but it did not result in significant improvement in the overall preparation score. Changes in the dosage of cisapride should be further evaluated.

Aged↗