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Biomedical subjects

C Niederau

Publications and source records attributed to C Niederau.

At least 145 records · Page 8Linked to original sources
PubMed1991

Effects of cholecystokinin-receptor blockade on pancreatic and biliary function in healthy volunteers.

This study used the specific cholecystokinin (CCK)-receptor antagonist loxiglumide to evaluate whether endogenous CCK, which is released after a meal, regulates pancreatic and biliary functions. Eight healthy volunteers were studied twice on separate days. The subjects received a continuous intraduodenal infusion of a 750-kcal liquid test meal for 2 hours either with or without IV infusion of 5 mg.kg-1.h-1 of loxiglumide. Loxiglumide at this dose abolishes the actions of CCK at various target organs including gallbladder and pancreas, when given at doses that mimic postprandial plasma concentrations of CCK. Loxiglumide markedly decreased the meal-stimulated outputs of amylase, trypsin, and chymotrypsin by 55%-70% of control values but only slightly decreased duodenal volume (25% inhibition of mean integrated secretion). Loxiglumide abolished gallbladder emptying induced by infusion of nutrients and even increased gallbladder volumes when compared with prior fasting values. Correspondingly, loxiglumide almost abolished the output of bilirubin after infusion of nutrients. However, loxiglumide failed to alter the increase in circulating concentrations of glucose, insulin, and C peptide after infusion of nutrients. The present results show that CCK is one of several factors that regulate pancreatic protein secretion after absorption of nutrients. However, CCK is probably not involved in regulation of pancreatic secretion of fluid. In contrast, gallbladder function is mainly regulated by CCK, both in terms of its emptying after intestinal absorption of nutrients and in terms of maintenance of its fasting volume. Cholecystokinin does not play a major physiological role as an insulinotropic factor.

Adult↗
PubMed1991

Effects of the seleno-organic substance Ebselen in two different models of acute pancreatitis.

This study evaluated the effects of the seleno-organic substance Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] in two models of acute hemorrhagic and acute edematous pancreatitis. Ebselen is known to catalyze glutathione peroxidase-like reactions and to inhibit lipid peroxidation. Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet to mice for 66 h. Edematous pancreatitis was induced by 7-h subcutaneous injections of 50 micrograms/kg of cerulein in mice. Ebselen was given from the beginning of the CDE diet either as a subcutaneous injection of 100 mg/kg at 6-h intervals or was mixed in with the CDE diet to yield a daily dose of 100 mg/kg of Ebselen. In further experiments, Ebselen was given at various time intervals after the beginning of the CDE diet as subcutaneous injections of 100 mg/kg at 6-h intervals. In the cerulein model, Ebselen was given 5 min prior to each cerulein injection at doses from 10-500 mg/kg. Prophylactic administration of Ebselen given orally or subcutaneously significantly improved survival from 38.5% in the control group of saline-injected CDE-fed mice to 61.9 and 65.0%, respectively. Ebselen also reduced increases in serum amylase and pancreatic weight in the diet model. Therapeutic administration of Ebselen significantly increased survival only when injections were started 20 h after the beginning of the CDE diet (64%), but not when started after 40 h (44%). Similarly, increases in serum amylase and pancreatic weight due to the CDE diet were significantly reduced by Ebselen only when injections were started after 20 h but not when started after 40 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Effects of CCK receptor blockade on intestinal motor activity in conscious dogs.

This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the small intestine. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by six strain-gauge transducers implanted along the small intestine. The effects of the CCK analogue caerulein and the CCK antagonist loxiglumide were studied in fasted and fed states. Computer analysis determined contractile frequency and area under contractions. Caerulein given as an intravenous bolus 30 min after phase III dose dependently caused a burst of phasic contractions preceded by a retrograde giant contraction. Continuous intravenous infusion of 10 mg.kg-1.h-1 loxiglumide completely abolished the effects of 10 ng/kg caerulein, which increases plasma CCK immunoreactivity to postprandial levels. Loxiglumide, at 10 mg.kg-1.h-1, markedly reduced the increase in phasic contractions due to a supraphysiological dose of 50 ng/kg caerulein to 14 +/- 6(SD)% of the control without loxiglumide (P less than 0.01). The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 micrograms/kg) was not altered by loxiglumide. Loxiglumide given in the fasted state decreased contractile frequency from 9.5 +/- 0.7 to 8.1 +/- 0.6/min and reduced the area under contractions during phase II to 81 +/- 5% of the control without loxiglumide (P less than 0.05). Loxiglumide also decreased contractile frequency during the fed state from 9.7 +/- 0.6 to 8.3 +/- 0.5/min and reduced the area under contractions to 78 +/- 6% of the control without loxiglumide (P less than 0.05). Thus loxiglumide acts as a specific antagonist of the actions of CCK on small intestinal motor activity in the dog. Loxiglumide, at a dose that abolishes actions of endogenous CCK, significantly decreased fasting motor activity during phase II. Loxiglumide also significantly reduced motor responses to feeding but did not prevent interruption of migrating motor complex cycle by a meal. CCK plays a physiological role in regulation of fasting and fed motor activity of small intestine, although other factors in addition to CCK mediate meal-induced motor activity.

Animals↗
PubMed1991

Epidemiology, clinical course and treatment of chronic viral hepatitis.

Chronic hepatitis may take the form of a hepatitis B infection, a delta virus infection, or a non-A, non-B hepatitis including hepatitis C. All the viruses involved are transmitted predominantly by parenteral or sexual routes. New insights into the structure of the hepatitis B virus (HBV) and the immune response mechanisms of the organism permit a clear definition of the replicative state of the virus, and allow predictions to be made about the outcome of the disease. Development of cirrhosis and hepatocellular carcinoma are the major complications associated with impaired life expectancy. Recently, the hepatitis C virus (HCV) was identified as the agent responsible for most cases of chronic non-A, non-B hepatitis. The development of an assay for the detection of HCV-antibodies facilitated the diagnosis of this type of hepatitis. Moreover, the use of screening tests for hepatitis B and hepatitis C in blood donors will decrease the risk of acquiring hepatitis via contaminated blood products. Treatment of chronic hepatitis B and C with alpha-interferon has shown promising results. However, the dosage schedule, the period of treatment, and the selection of patients needs to be evaluated in further studies.

Hepacivirus↗
PubMed1990

Pancreatic exocrine secretion in acute experimental pancreatitis.

Little is known about exocrine pancreatic secretory function in patients with acute pancreatitis, in particular during the early phase of the disease. Therefore, this study evaluates basal and stimulated pancreatic secretion in vivo and in vitro in four different models of acute pancreatitis which reflect its clinical spectrum of severity: (a) edematous pancreatitis induced in the rat by seven IP injections of 50 micrograms/kg cerulein at hourly intervals; (b) edematous pancreatitis with cellular necrosis induced in the mouse by seven IP injections of 50 micrograms/kg cerulein at hourly intervals; (c) hemorrhagic pancreatitis induced in the mouse by feeding an ethionine-supplemented, choline-deficient diet for 66 hours; and (d) hemorrhagic pancreatitis induced in the rat by retrograde infusion of 0.6 mL 5% sodium taurocholate into the pancreatic duct. Secretory studies were performed in vivo and in vitro at various times after onset of pancreatitis. The results show that the exocrine pancreas gradually became resistant to cholecystokinin stimulation after the onset of acute pancreatitis in all four animal models. Cholecystokinin-stimulated secretion was almost abolished in vivo and in vitro at the time of maximal histological damage. In vivo basal secretion was also reduced. In vitro there was an increase in basal release of amylase from isolated acini that was not caused by an increase in luminal secretion but by enzyme release from damaged cells. The time course of improvement of secretory function after acute experimental pancreatitis depended on the severity of the pancreatitis. Recovery of secretory capacity took longer after severe necrotizing pancreatitis than after edematous pancreatitis. However, the ultimate resolution of secretory function was remarkable, in particular after severe hemorrhagic pancreatitis. In all four models, secretory capacity became indistinguishable from normal before the morphological alterations had completely resolved. The present experimental data suggest that pancreatic secretion, and particularly pancreatic secretory response to cholecystokinin, may also be reduced in patients early after the onset of acute pancreatitis.

Acute Disease↗
PubMed1990

Does acute consumption of large alcohol amounts lead to pancreatic injury? A prospective study of serum pancreatic enzymes in 300 drunken drivers.

Blood samples of 300 consecutive subjects suspected for drunken driving were prospectively analyzed for concentrations of pancreatic and hepatic enzymes. Mean alcohol concentration was 1.5 +/- 0.8 0/00 (+/- SD; range 0-3.7 0/00). Increased enzyme concentrations were found in 25/300 subjects for amylase, in 43/300 for trypsin, in 49/300 for gamma-glutamyl transferase and in 82/300 for glutamic oxaloacetic transaminase. Subjects with alcohol concentrations greater than 1 0/00 had abnormal pancreatic and hepatic enzymes more frequently than subjects with alcohol concentrations smaller than 1 0/00. However, pancreatic enzyme levels were higher than twice the upper normal limit only in 3/300 subjects, whereas hepatic enzyme levels exceeded twice the upper normal limit in 31/300 subjects. Therefore, other factors in addition to alcohol are necessary to initiate acute pancreatitis. The liver is more susceptible to acute injury by alcohol than the pancreas.

Acute Disease↗
PubMed1990

Effects of long-term CCK stimulation and CCK blockade on pancreatic and intestinal growth, morphology, and function.

This study evaluated the effects of long-term cholecystokinin (CCK) stimulation and blockade on pancreatic and intestinal growth, function, and morphology. CCK release was induced by feeding of the protease inhibitor camostate and CCK blockade by feeding of the CCK antagonist CR 1409. Four groups of NMRI-mice received the following diets for 9 months (each group consisting of 36 mice): (1) chow (control); (2) chow + 100 mg/kg/day camostate; (3) chow + 50 mg/kg/day CR 1409; (4) chow + 100 mg/kg/day camostate + 50 mg/kg/day CR 1409. Long-term feeding of camostate greatly increased pancreatic weight by induction of marked hypertrophy (increase in protein content) and moderate hyperplasia (increase in DNA content). Camostate feeding also increased secretory capacity of the exocrine pancreas. Despite camostate-induced growth neither hyperplastic nor neoplastic nodules developed. The CCK-antagonist CR 1409 markedly inhibited the effects of camostate which are therefore mainly mediated by CCK. Neither long-term CCK stimulation nor CCK blockade altered morphology or composition of duodenal mucosa. Feeding of CR 1409 alone (i.e., without camostate) slightly but significantly decreased pancreatic content of protein and secretory capacity of enzymes when compared to the chow-fed control; pancreatic weight and DNA content remained unchanged after long-term administration of CR 1409. Thus, long-term, continuous and effective blockade of the CCK-receptor only slightly inhibited pancreatic growth and secretory capacity. CCK is, therefore, not an essential growth factor for the pancreas, although increases of endogenous CCK stimulate pancreatic growth and secretory capacity.

Animals↗
PubMed1990

[Pathophysiology of acute pancreatitis].

Recent experiments in different animal models of acute pancreatitis have improved our understanding of the pathophysiology of this disease. The present review discusses the individual steps and mechanisms and puts them into a pathophysiologic concept for the two most important forms of acute pancreatitis (alcoholic and biliary form). In biliary acute pancreatitis a temporary occlusion of the common channel by impacted stones may be followed by a reflux into the pancreatic duct. This reflux results in an increase of ductal permeability and extravasation of cytotoxic agents into the surrounding tissue. As consequences, disturbances of compartimentation and faulty activation of enzymes occur in pancreatic cells. Long-term cellular damage, obstruction of pancreatic ducts and increase of ductal permeability with leakage of noxious agents play a substantial role in pathophysiology of alcoholic pancreatitis. Sustained abuse of alcohol usually leads to chronic pancreatitis. Additional, as yet unknown factors are necessary to induce acute alcoholic pancreatitis. Following its initiation by different etiological sources, pathophysiology of acute pancreatitis may take a similar course. Digestive enzymes are activated and set free into intracellular, intraductal and interstitial spaces. Trypsin as the trigger-enzyme of activation cascade is thought to play a major role. In addition, lipolytic enzymes may be involved in the pathophysiologic process. Phospholipase A is known to release lysolecithin which causes membrane damage. Recent studies indicate that the release of fatty acids by lipase causes acinar cell necrosis. New insights into the pathophysiology may lead to a rational and more successful therapy of acute pancreatitis.

Acute Disease↗
PubMed1990

Prevalence of lactose malabsorption among patients with functional bowel disorders.

To investigate the prevalence of lactose malabsorption among patients with functional gastrointestinal disturbances we prospectively evaluated all patients referred to a gastrointestinal outpatient clinic over a period of 18 months. All patients had a breath hydrogen test following oral lactose in addition to the standard diagnostic procedures. In 37 of the total of 64 patients no organic cause of the gastrointestinal complaints was found. In 9 of these 37 patients (24%) the breath hydrogen test indicated lactose malabsorption. Three to 6 month later most of the patients with lactose malabsorption showed a significant reduction of gastrointestinal complaints after they had maintained a lactose-poor diet. In comparison, patients with functional disturbances but without lactose malabsorption reported nor or only minor improvement of symptoms; most of these patients had consulted another physician since the last visit in the clinic.

Breath Tests↗
PubMed1989

[Virus-associated hemorrhagic colitis in the differential diagnosis of peracute rectal bleeding].

Severe anal bleeding together with increasing abdominal discomfort occurred in an 81-year-old woman previously hospitalized numerous times because of decompensated type II B diabetes. A suspected rectal cancer was excluded by biopsy from the lower to middle rectum, but the biopsy revealed histologically indurated and bleeding ulcerations. Typical nuclear inclusion bodies provided the diagnosis of virus-associated proctocolitis. Serological tests supported the diagnosis of infection with herpes simplex and cytomegalic virus. Laser coagulation stopped the bleeding. At the same time a Guillain-Barré syndrome was noted which improved after administration of cortisone and high parenteral doses of acyclovir.

Acute Disease↗
PubMed1989

Effects of loxiglumide on gallbladder emptying in healthy volunteers.

This study evaluates the effects of the specific cholecystokinin receptor antagonist loxiglumide on gall-bladder emptying after a meal or after intravenous infusion of caerulein in humans. Ten healthy male volunteers were studied five times on separate days. The following five studies were performed in randomized order: (a) caerulein was intravenously infused at doses increasing from 7.5 to 120 ng/kg.h without the antagonist; (b) in addition to increasing doses of caerulein, loxiglumide was given intravenously at doses of 0.2, 1.0, or 5.0 mg/kg.h; (c) a solid-liquid 800-kcal meal was given without loxiglumide; (d) the 800-kcal meal was given with simultaneous infusion of 1 or 5 mg/kg.h loxiglumide; and (e) loxiglumide (5 mg/kg.h) was given. without caerulein or the test meal. Gallbladder volume was measured by ultrasound. Loxiglumide dose-dependently inhibited gallbladder emptying induced by caerulein or the meal. High doses of the antagonist did not only abolish meal-induced gallbladder emptying but increased gallbladder volume after administration of caerulein or the meal when compared with prior fasting values. The antagonist given alone markedly increased gallbladder volumes compared with prior fasting values. In conclusion, given alone markedly increased gallbladder volumes compared with prior fasting values. In conclusion, cholecystokinin is the hormone primarily and mainly responsible for mediation of gallbladder emptying after a regular meal. Cholecystokinin might also play a physiologic role in the regulation of the fasting tone of the gallbladder.

Adult↗
PubMed1989

Comparative effects of CCK receptor antagonists on rat pancreatic secretion in vivo.

The present experiments evaluate in vivo effects of recently described cholecystokinin (CCK) receptor antagonists on rat pancreatic secretion. Pancreaticobiliary secretion was studied after bile duct cannulation in anesthetized rats. After two basal 10-min fractions were selected, secretion was stimulated by intravenous caerulein (0.1-30.0 micrograms/kg) or secretin, and collected for seven further 10-min fractions. Peptide antagonists (CR 1409, CR 1392, and CR 1505) and nonpeptide antagonists (asperlicin and L364,718) were given intravenously 10 min before agonists. Increasing doses of antagonists gradually reduced secretion of protein and enzymes stimulated by submaximal and maximal doses of caerulein. The antagonists did not alter nonstimulated or secretin-stimulated secretion, indicating their specificity for the CCK receptor. Except for proglumide and asperlicin, all antagonists were able to abolish caerulein-stimulated pancreatic secretion, as evaluated by the mean integrated 1-h response to a near-maximal dose of caerulein. The caerulein dose-response curve was gradually shifted to the right by increasing doses of CR 1409, indicating competitive-like kinetics. Inhibition of secretion due to supramaximal doses of caerulein, however, could be reversed by doses of CR 1409 smaller than expected from extrapolating truely competitive kinetics from an in vitro situation to the in vivo situation. The rank order of potency of the compounds to antagonize caerulein-stimulated secretion in vivo agreed with their relative potencies to antagonize caerulein-stimulated amylase secretion from pancreatic acini in vitro as well as with their affinity to bind to peripheral CCK receptors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗