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Biomedical subjects

M Classen

Publications and source records attributed to M Classen.

At least 253 records · Page 14Linked to original sources

Effects of CCK-8 in combination with natural or synthetic secretin on amylase, lipase, trypsin, and chymotrypsin secretion in rats.

In the present study, we examined the interaction between CCK-8 and natural or synthetic secretin on pancreatic enzyme secretion. On anaesthetized rats, a proximal duodenal segment was continuously perfused with saline and amylase, lipase, trypsin, and chymotrypsin were determined in the perfusate. Neither during iv saline nor during iv secretin (natural or synthetic) at doses of 0.01, 0.05, or 0.1 CU/kg/h, any of the four enzymes changed significantly from basal values over a period of 100 min. Iv CCK-8 at stepwise increasing doses of 5, 10, and 20 pmol/kg/h elicited a significant increase of all four enzymes at the medium dose, with a further increase of amylase and trypsin, but not lipase and chymotrypsin at 20 pmol/kg/h. The addition of secretin at all 3 doses potentiated CCK-induced trypsin output. The effects of natural secretin were more pronounced than those of the synthetic peptide. Secretin significantly increased amylase secretion over basal at the lowest dose of CCK-8 (5 pmol/kg/h) that by itself had no effect on amylase release. Only the higher doses of natural but not synthetic secretin augmented lipase secretion during the lowest dose of CCK-8. Both forms of secretin had no further stimulatory effect on CCK-induced chymotrypsin secretion. The present data demonstrate that, first, in rats a potentiation of CCK-8-induced enzyme secretion by low doses of secretin is different for the four enzymes, which suggests a differential regulatory action of these two intestinal hormones on pancreatic enzyme release. Second, the different effects of natural secretin may represent those of contaminants suggesting that only synthetic secretin should be employed in future studies of this peptide on pancreatic enzyme secretion.

Amylases↗

Leukotrienes C4 and D4 potentiate acid production by isolated rat parietal cells.

The effects of leukotrienes (LTs) B4, C4, and D4 on acid production by enriched (80%-85%) rat parietal cells were investigated. Acid production was indirectly measured by [14C]aminopyrine uptake into the cells. Leukotriene B4 (10(-10)-10(-6) mol/L) had no effect on basal or prestimulated [14C]aminopyrine uptake. Leukotriene C4 and LTD4 (10(-10)-10(-6) mol/L) also did not change basal acid production but potentiated prestimulated [14C]aminopyrine uptake. Maximal effects were observed with 1 x 10(-7) mol/L LTC4 or with 3 x 10(-7) mol/L LTD4. At these concentrations LTC4 and LTD4 induced the indicated increases above the responses to the following prestimulants (= 100%): 10(-4) mol/L histamine (71% and 74%, respectively), 10(-5) mol/L forskolin (54% and 106%), 10(-4) mol/L dibutyryl cyclic adenosine monophosphate (34% and 81%), and 10(-4) mol/L carbamylcholine (160% and 116%). Yet, adenosine triphosphate (2.5-5 x 10(-3) mol/L)-induced [14C]aminopyrine uptake in digitonin-permeabilized parietal cells was not further increased by LTC4 or LTD4. At 10(-5) mol/L the selective LTD4 antagonist L-660,711 (MK-571) reduced the effect of 3 x 10(-7) mol/L LTD4 by 74% but had no effect on the potentiation by LTC4. We conclude that the sulfidopeptide LTs C4 and D4, but not LTB4, exert a direct effect on rat parietal cells, and that this effect seems to be mediated by separate specific receptors. Leukotriene C4 and LTD4 potentiate prestimulated H+ formation by interacting with an intracellular mechanism that is commonly activated upon occupation of histamine H2- as well as muscarinic receptors, and that is also activated by the postreceptor stimuli forskolin and dibutyryl cyclic adenosine monophosphate; yet, this mechanism seems to be localized proximal to the H+,K+-adenosine triphosphatase.

Animals↗

Endostomy: a new approach to small-bowel endoscopy.

A percutaneous access to the gastrointestinal hollow organs created by new endostomy tubes permits diagnostic and therapeutic endoscopy in particular of the small intestine. A case of a patient with chronic gastrointestinal bleeding of hitherto unknown origin, in whom enteroscopy and electrocoagulation of an angioma in the lower jejunum was performed, is presented.

Chronic Disease↗

Self-expanding biliary stents: preliminary clinical experience.

Nine self-expanding metallic stents were implanted in 7 patients to relieve biliary obstruction. One patient had a benign stricture and 6 patients had malignant stenoses. The stent was inserted percutaneously on a 7 F delivery catheter in 6 patients. Endoscopic transpapillary implantation was performed in one patient. After release the stent expanded to a diameter of 8-10 mm. The correct position was checked by fluoroscopy and cholangiography. In addition, percutaneous cholangioscopy was carried out in 6 patients. No complications were observed within 30 days. Clinical improvement was seen in all patients. After a mean follow-up period of 11 weeks (range: 3-17) 6 of the 7 patients are still alive with no evidence of biliary reobstruction. One patient died of disseminated malignancy. The initial results are promising. The wide-bore diameter, the macroporous configuration and the small surface area of the implanted self-expanding stents would seem to be associated with lower rates of infection, clogging and migration as compared with conventional endoprostheses. Further trials are warranted to determine the future role of self-expanding stents in biliary obstruction.

Adult↗

Role of amino acids in stimulation of postprandial insulin, glucagon, and pancreatic polypeptide in humans.

Protein-rich meals stimulate secretion of insulin, glucagon, and pancreatic polypeptide (PP) from the endocrine pancreas. On the one hand, this is due to increased levels of circulating amino acids, and, on the other, neural and/or endocrine factors can contribute to activation of islet cell function. The present study was designed to determine, first, pancreatic endocrine function and postprandial amino acid levels after a protein and a protein-carbohydrate meal and second, insulin, glucagon, and PP levels during infusion of amino acid mixtures that imitate the postprandial amino acid pattern. In healthy volunteers the ingestion of a protein-rich meal (300 g tenderloin steak) elicited within 1 h an increase of virtually all amino acids by 20-400 mumol/L above basal values. The infusion of two different amino acid solutions available for use in humans showed that Aminosteril-N-Hepa (AS) was better for the imitation of the so-called "insulinogenic" amino acids while Aminoplasmal L-10 (AP) gave more comparable plasma levels of the "glucagonogenic" amino acids. Both solutions were not able to imitate the postprandial amino acid pattern completely. With regard to insulin levels, both solutions gave a comparable increase, while AP but not AS stimulated glucagon and PP levels. This suggests that circulating amino acids may be responsible for 60% of the postprandial insulin response after a protein meal, while their contribution to glucagon release can only be roughly estimated at 30-60%. The contribution of circulating nutrients to the greater insulin response after the protein-carbohydrate meal was comparable (60%), while the attenuated glucagon response can be ascribed almost completely to the effect of circulating nutrients. In conclusion, the present data demonstrate that the composition of amino acid mixtures is as yet not ideal for a complete imitation of the postprandial amino acid pattern. The insulin, glucagon, and PP response depends on the amino acid mixtures and accordingly the respective plasma amino acid concentrations obtained during infusion studies. The adequate imitation of plasma amino acid levels is of critical importance for the evaluation of absorbed and circulating amino acid effects in the postprandial state.

Adult↗

Effect of CCK on insulin, glucagon, and pancreatic polypeptide levels in humans.

The present study was designed to determine the effect of low doses of cholecystokinin (CCK) on insulin, glucagon, and pancreatic polypeptide (PP) secretion in the basal state and during prestimulation with amino acids and glucose alone or in combination. Two different amino acid solutions available for use in humans were employed. Aminosteril-N-Hepa was better for the imitation of the so-called "insulinogenic" amino acids while Aminoplasmal L-10 gave more comparable plasma levels of the "glucagonogenic" amino acids as observed after a protein-rich meal. In healthy volunteers, low-dose CCK infusion [Thr28,Nle31-CCK 25-33 (CCK-9)] in stepwise increasing doses of 5, 10, and 20 pmol/kg/h had no effect on basal, glucose-, or amino acid-stimulated insulin release. During the combination of Aminoplasmal + glucose, there was a small and only transient increase of plasma insulin levels that did not occur during Aminosteril + glucose. CCK did not alter glucagon levels either during i.v. amino acids alone or during combination of amino acids with glucose. CCK-stimulated PP levels in the basal state in a dose-dependent manner. This effect was enhanced during i.v. Aminosteril but not i.v. Aminoplasmal infusion. During i.v. glucose, the effect of CCK on PP levels was abolished. In conclusion, the present data demonstrate that CCK is unlikely to be a stimulus of insulin and glucagon secretion in the basal state and also during prestimulation by fairly physiological quantities of amino acid mixtures. On the other hand, the present data support a physiological role of CCK in the regulation of PP secretion.

Adult↗

Effect of amino acids on H+ production by isolated rat parietal cells.

We investigated the hypothesis of a direct effect of amino acids on gastric parietal cells. [14C]aminopyrine uptake into isolated enriched rat parietal cells served as a quantitative index of H+ production. Cells were incubated in media containing 1 mM Ca2+ in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), or 3 mM Ca2+ without IBMX. Under these different conditions, L-arginine, L-phenylalanine and L-tryptophan (10(-6) M to 3 X 10(-2) M) failed to alter basal [14C]aminopyrine uptake as well as the response to submaximal stimulation by histamine, forskolin, N6O2-dibutyryladenosine-3',5'-(cyclic)-phosphate (db cAMP) or carbachol. Pentagastrin failed to elicit an appreciable response in the presence and absence of 10(-3) M of all three amino acids studied. It is concluded that in vivo the potent stimulation of gastric acid secretion by L-arginine, L-phenylalanine and L-tryptophan is mediated by other than direct mechanisms.

Amino Acids↗

Circulating amino acids and pancreatic endocrine function after ingestion of a protein-rich meal in obese subjects.

We measured plasma amino acid together with insulin, glucagon, pancreatic polypeptide (PP), and glucose concentrations after the ingestion of a protein meal in lean and obese subjects. The basal plasma amino acid levels were similar in both groups. The postprandial increase in the plasma amino acid levels in the obese subjects was only 15-50% of that in the lean subjects. The mean basal and peak postprandial plasma insulin levels were significantly higher (72 and 165 pmol/L) in the obese group than in the lean group (36 and 115 pmol/L; P less than 0.05-0.01). The postprandial rise in plasma glucagon was largely attenuated in the obese subjects, and there was no difference in plasma PP and glucose levels in the 2 groups. To further evaluate the role of circulating amino acids on pancreatic endocrine function in obese and lean subjects, an amino acid mixture consisting of 15 amino acids was infused iv. During the infusion the plasma amino acid levels were comparable in both groups. Plasma insulin rose by 36 +/- 7 (+/- SE) pmol/L (5 +/- 1 microU/mL) in the lean and 129 +/- 22 pmol/L (18 +/- 3 microU/mL) in the obese subjects, whereas plasma glucagon, PP, and glucose levels were similar in both groups. In view of the 3.6-fold greater insulin responses in the obese subjects, it is likely that circulating amino acids contribute to their hyperinsulinemia in spite of the reduced postprandial rise of amino acids in this group (50-85%). Thus, under physiological conditions amino acids have to be considered as an important regulatory component of postprandial insulin release in obese subjects.

Adult↗

Omeprazole in the acute treatment of gastric ulcer.

Antisecretory drugs are known to be valuable in the treatment of gastric ulcer. Recent studies have shown that this also holds true for omeprazole, the most effective antisecretory drugs currently available. At 30-40 mg once daily omeprazole provides cumulative healing rates of up to 100% after 4-8 weeks. In one study, omeprazole, 20 mg, and ranitidine, 150 mg b.d., produced similar healing rates in the acute treatment of gastric ulcer, though there was a tendency towards more rapid healing with omeprazole. In a more recent multicentre study including more than 600 patients, significantly more ulcers healed after 4 weeks with omeprazole, both 20 mg and 40 mg once daily, than with ranitidine, 150 mg b.d. Omeprazole was also superior to ranitidine with respect to relief of night-time pain and in gastric ulcer healing during concomitant therapy with non-steroidal anti-inflammatory drugs. After omeprazole therapy, the proportion of patients in remission during the following half-year period was higher than after ranitidine, arguing against the hypothesis that rapid ulcer healing following more effective inhibition of acid secretion might be of lower quality. During acute therapy, no drug-specific serious side-effects occurred. Omeprazole is a valuable alternative in modern treatment of gastric ulcer, being superior to histamine H2-receptor antagonists.

Cimetidine↗

Effect of gastrin-releasing peptide (GRP1-27), neuromedin-C (GRP18-27), and neuromedin-B on gastrin and somatostatin secretion from the rat stomach.

In the present study the effects of gastrin-releasing peptide (GRP1-27), its C-terminal decapeptide neuromedin-C (GRP18-27) and the related peptide neuromedin-B were examined on the secretion of gastrin and somatostatin-like immunoreactivity (SLI) from the isolated perfused rat stomach at intraluminal pH 7 or pH 2. GRP1-27 and GRP18-27 stimulated gastrin secretion equally effective at concentrations of 10(-10), 10(-9), 10(-8), 10(-7) and 10(6)M at luminal pH 7. In addition neuromedin-B was tested at 10(-11), 10(-10), 10(-8) and 10(-6)M and it increased gastrin release similar to equimolar doses of GRP18-27. At luminal pH 2 GRP1-27 stimulated gastrin secretion at 10(-9), 10(-8), 10(-7) and 10(-6)M while GRP18-27 was only effective at 10(-8) and 10(-7)M. Neuromedin-B elicited a gastrin increase at 10(-8)M similar to GRP18-27 and also at 10(-6)M. All three peptides had no significant effect on SLI release at luminal pH 7. At luminal pH 2 GRP1-27 at 10(-9)M and 10(-6)M and GRP18-27 and neuromedin-B at 10(-10)M elicited a significant stimulation of SLI secretion. These data demonstrate that all three bombesin-like peptides GRP1-27, GRP18-27 and neuromedin-B can stimulate gastrin release at either a neutral or an acidic luminal pH, while SLI release is affected only at an acidic intragastric milieu. This suggests that all three forms of bombesin-like peptides are good candidates for the peptidergic regulation of gastrin release in the rat stomach, while their role in somatostatin release seems to be more restricted.

Animals↗

[Substitution of F XIII concentrate in ulcerative colitis].

A 33 years old female with ulcerative colitis was admitted with an acute exacerbation of the disease characterised by haematochezia, diarrhoea (10 stools/die) and anaemia (haemoglobin 6.5 g/dl). Therapy with 5-ASA and corticosteroids for six weeks failed to decrease the activity of the disease. Since deficiency of coagulation factor XIII (activity 60%, subunit A 56%) was present, in addition, concentrates of factor XIII (Fibrogammin HS, Behring, F.R.G.) 1250 U/die were given for ten days. The substitution resulted in an immediate increase of reduced F XIII activity (164%) and F XIII subunit A (333%) as well as in a marked improvement of symptoms.

Adult↗

Cholinergic stimulation of isolated rat parietal cells: role of calcium, calmodulin and protein kinase C.

We studied the cholinergic stimulation of isolated and enriched rat parietal cells. H+ production was indirectly measured by the uptake of 14C-aminopyrine into the parietal cells. Stimulation by carbachol required the presence of extracellular Ca2+ not only in the initial phase but also during the sustained phase of a 100-min incubation period. The response to carbachol was prevented by the Ca2+ entry blocker lanthanum IC50: 1.5 X 10(-7) mol/l). Furthermore, the dependence on Ca2+ influx of cholinergic stimulation was demonstrated by a 269% increase in total intracellular Ca2+ in response to carbachol, as determined by optical emission spectrometry. The naphthalene sulfonamides W7 and W5 which bind calmodulin and thus block the intracellular transduction of Ca2+ effects also inhibited a carbachol-induced H+ production. In the following experiments we studied the effect of agents which activate the protein kinase C, an enzyme which is supposed to play a key role in intracellular signal transduction of Ca2+-dependent effects. Phospholipase C is supposed to activate protein kinase C via induction of the phosphoinositol breakdown. In our preparation of isolated rat parietal cells, phospholipase C (4-100 mU/ml) exerted inhibition instead of amplification of the response to 10(-4) mol/l carbachol. Similarly, the direct activation of protein kinase C by 12-O-tetradecanoylphorbol-13-acetate or by 1-oleoyl-2-acetyl-sn-glycerol (both tested at 10(-7) to 10(-5) mol/l) reduced the submaximal and maximal response to 10(-5) or 10(-4) mol/l carbachol. We conclude that the cholinergic stimulation of rat parietal cells is dependent on the influx of extracellular Ca2+. Calmodulin seems to mediate intracellular Ca2+ effects during cholinergic stimulation. The activation of protein kinase C impairs carbachol-induced H+ production instead of augmenting the response. This might be due to an already maximal activation of protein kinase C by carbachol alone or to autoregulatory down-regulation by the protein kinase C of muscarinic parietal-cell receptors.

Aminopyrine↗

Optical performance of electronic imaging systems for the colon.

Electronic (video) endoscopes are a significant new development in gastroenterology, offering the potential of enhanced teaching and permanent storage of pictorial data. The primary concern of gastroenterologists is the resolution and color performance of these instruments, as these parameters have important bearings on the ability to discern pathological changes in mucosa. We sought to determine the resolution and color capabilities of electronic colonoscopes and compare them with a conventional fiber colonoscope. Resolution was determined using a standard test chart at various distances and the number of picture elements (a measure of resolution) was calculated. The mean number of picture elements was Fujinon (219), Fiber (172), Pentax (169), Toshiba (142), Olympus (140), and Welch Allyn (133). In close focus examination (target distances less than 1 cm), the Fujinon and Toshiba endoscopes had significantly higher resolution than the other instruments. Color was measured quantitatively using a standard color chart and a color analyzer. Color polygons were plotted for each endoscope on a reference chromaticity diagram. All systems had an acceptable overall performance but color was undersaturated with some systems. The optical performance of electronic endoscopes has improved considerably since the inception of electronic endoscopy.

Colonoscopes↗

[Device for a single-operator resuscitation].

A simple type of reanimation equipment is described which - independent of energy supply - makes it possible for a single operator to perform complete mechanical cardiopulmonary resuscitation. The apparatus is placed on the distal half of the sternum of the supine patient and connected to the respiratory tract via a connecting tube. Inspiration occurs by depressing the apparatus, while the subsequent expiration is followed by cardiac massage by means of depressing the apparatus. This new method has proved itself effective in three patients with acute cardiocirculatory arrest.

Aged↗