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Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 73 records · Page 4Linked to original sources
PubMed1999

Progressive development of diffuse liver hemangiomatosis.

Diffuse liver hemangiomatosis is extremely rare. The etiology and natural history of the disease are unknown. It is also unclear whether tumor growth is induced or modulated by drug therapy. Tumor recurrence after ablative therapy has not been described in patients with diffuse liver hemangiomatosis. Diffuse hemangiomatosis of the left hepatic lobe was suspected in a 35-year-old woman by ultrasonography, CT and hepatic arteriography, and confirmed by laparotomy and biopsies. The patient denied any drug or estrogen use. The tumor was removed by left hepatectomy. Two and six years later, the patient was again hospitalized with progressive tumor growth into the right hepatic lobe. Although diffuse liver hemangiomatosis is a rare disease, its diagnosis should be considered in patients with progressive tumor growth in one or both hepatic lobes. The absence of drug intake or estrogen use does not exclude the diagnosis.

Adult↗
PubMed1999

Evidence for different ABC-transporters in Caco-2 cells modulating drug uptake.

PURPOSE: Secretory systems contribute to drug absorption in the gastrointestinal tract. The purpose of this study was the identification of members of the ATP binding cassette superfamily of secretory transport proteins that may potentially modulate drug absorption in Caco-2 cells, which are an important cellular model predicting enteral absorption of drugs. METHODS: Kinetic studies as well as PCR- and Western blot studies with confluent epithelial layers of human Caco-2 cells. RESULTS: The study demonstrates functional expression of multidrug resistance related protein (MRP) and P-glycoprotein (P-gp) in Caco-2 cells: 1) Efflux studies with the MRP specific substrate glutathion-methylfluorescein (GS-MF) showed functional activity of MRP in Caco-2 cells preloaded with the metabolic precursor of GS-MF, chloromethylfluoresceine-diacetate, CMFDA. Excretion of GS-MF was decreased in presence of the MRP-blocker M K-571.2) Transport experiments with cyclosporin A demonstrated the functional activity of P-gp. Cellular accumulation was increased in presence of the P-gp blocking agent SDZ-PSC 833. 3) The expression of the 190 kDa protein MRP and the 170 kDa protein P-gp in Caco-2 cells was shown by Western blot analysis with specific monoclonal antibodies. 4) The expression of MRP-mRNA in Caco-2 cells was detected by RT-PCR and compared with the MRP over-expressing cell line H69AR. MRP primers recognize specifically human MRP1 (GenBank accession number L05628), but not all other published sequences of MRP (MRP2-MRP6). P-gp expression on mRNA-level was also confirmed by RT-PCR. CONCLUSIONS: The data demonstrate that besides P-gp, multidrug resistance related protein (MRP) is functionally expressed in Caco-2 cells and contributes to the active excretion of substrates in this cell line.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects.

AIMS: Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release. METHODS: Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured. RESULTS: After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment. CONCLUSIONS: The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.

Administration, Cutaneous↗
PubMed1999

Effects of spiroglumide, a gastrin receptor antagonist, on acid secretion in humans.

BACKGROUND: A gastrin receptor antagonist, CR2194 (spiroglumide), was used to explore the physiological role of gastrin in regulating gastric acid secretion in humans. MATERIALS AND METHODS: The effect of CR2194 on inhibition of gastrin-stimulated acid output was evaluated in a four-period crossover study. Each subject received intravenous doses of 1, 2.5 or 7.5 mg kg-1 h-1 CR2194 or saline (control) followed by graded increasing doses of gastrin (6.4-800 pmol kg-1 h-1). Secondly, the effect of CR2194 on meal-stimulated intragastric acidity was evaluated by infusing either saline (control) or CR2194 (7.5 mg kg-1 h-1) before and after food ingestion. RESULTS: Acid secretion was dose-dependently inhibited by CR2194. With CR2194, acidity was significantly reduced in the pre-meal and post-prandial period (P < 0.01 and 0.002 respectively), and the integrated gastrin response was augmented to 8.0 +/- 1.4 ng mL-1 240 min compared with 1.5 +/- 0.8 ng mL-1 240 min in the control experiment (P < 0.01). Finally, acid secretion in response to sham feeding was significantly reduced: 15.9 +/- 0.9 mmol 90 min-1 in the control experiment compared with 2.8 +/- 0.9 mmol 90 min-1 during CR2194 infusion (P < 0.05). CONCLUSION: Gastrin receptor blockade with CR2194 alters gastric acid secretion in response to food ingestion or to sham feeding. The results support a physiological role for gastrin in regulating acid secretion in humans.

Adult↗
PubMed1999

Glucagon-like peptide-1: a potent regulator of food intake in humans.

BACKGROUND/AIMS: Studies in animals suggest a physiological role for glucagon-like peptide-1-(7-36)-amide (GLP-1) in regulating satiety. The role of GLP-1 in regulating food intake in man has, however, not been investigated. Subjects-Sixteen healthy male subjects were examined in a double blind placebo controlled fashion. METHODS: The effect of graded intravenous doses (0, 0.375, 0.75, and 1.5 pmol/kg/min) of synthetic human GLP-1 on food intake and feelings of hunger and satiety was tested in healthy volunteers. RESULTS: Graded GLP-1 infusions resulted in a dose dependent reduction in food intake (maximal inhibition 35%, p<0.001 v control) and a similar reduction in calorie intake (32%; p<0.001). Fluid ingestion was also reduced by GLP-1 (18% reduction, p<0.01). No overt side effects were produced by GLP-1, but subjects experienced less hunger and early fullness in the period before a meal during GLP-1 infusion at the highest dose (p<0.05). CONCLUSIONS: Intravenous infusions of GLP-1 decrease spontaneous food intake even at physiological plasma concentrations, implying an important role for GLP-1 in the regulation of the early satiety response in humans.

Adult↗
PubMed1999

Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2.

Glucagon-like peptide-1-(7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis. Recent experimental evidence in animals and healthy subjects suggests that GLP-1 has a role in controlling appetite and energy intake in humans. We have therefore examined in a double-blind, placebo-controlled, crossover study in 12 patients with diabetes type 2 the effect of intravenously infused GLP-1 on appetite sensations and energy intake. On 2 days, either saline or GLP-1 (1.5 pmol. kg-1. min-1) was given throughout the experiment. Visual analog scales were used to assess appetite sensations; furthermore, food and fluid intake of a test meal were recorded, and blood was sampled for analysis of plasma glucose and hormone levels. GLP-1 infusion enhanced satiety and fullness compared with placebo (P = 0.028 for fullness and P = 0.026 for hunger feelings). Energy intake was reduced by 27% by GLP-1 (P = 0.034) compared with saline. The results demonstrate a marked effect of GLP-1 on appetite by showing enhanced satiety and reduced energy intake in patients with diabetes type 2.

Appetite↗
PubMed1999

Inhibition of food intake in response to intestinal lipid is mediated by cholecystokinin in humans.

Intraduodenal fat inhibits gastric emptying and exerts early satiation in animals and humans, but it is not clear whether the effects are mediated by cholecystokinin (CCK) in humans. Here, we tested whether CCK-A receptors mediate the inhibition of fat on food intake. Two sequential, double-blind, crossover studies were performed in 24 male subjects. First, subjects received either intraduodenal fat or saline together with a preload of either water or banana shake. Second, 12 subjects received either intraduodenal fat or saline perfusion plus a concomitant infusion of saline or loxiglumide, a specific CCK-A receptor antagonist, together with a preload of banana shake. In both studies, subjects were free to eat and drink as much as they wished. Fat induced a reduction in calorie intake (P < 0.05) compared with controls. Furthermore, a decrease in hunger feelings was observed. Infusion of loxiglumide abolished the effects of fat. Duodenal fat interacts with an appetizer to modulate energy intake in humans. This effect is mediated by CCK-A receptors.

Adult↗
PubMed1999

Potential role of cholecystokinin in the development of acute pancreatitis.

Evidence based on animal studies suggests that cholecystokinin (CCK) is involved in the induction and development of acute experimental pancreatitis. However, the results obtained with CCK or CCKA receptor antagonists in different species (rats, mice) and different models of acute pancreatitis (cerulein pancreatitis, hemorrhagic pancreatitis induced by choline-deficient, ethionine-supplemented diet, arginine-induced pancreatitis, sodium taurocholate-induced pancreatitis) produced variable results. The route of administration, the specificity and potency of compounds and the design of the study are predictive for the outcome. Based on the available information, CCK appears to play a contributory role in the development of acute experimental pancreatitis in mice and rats. No conclusions can be drawn from these results with respect to the human disease.

Acute Disease↗
PubMed1999

The role of octreotide in the treatment of gastroenteropancreatic endocrine tumors.

Gastrointestinal-endocrine pancreatic (GEP) tumors are rare, occurring in less than 1% of the population. They are usually divided into functionally active or nonfunctioning tumors. Functionally active tumors produce a variety of substances (mainly peptides or serotonin). The tumors are classified according to the dominant clinical syndrome that they cause. Surgery is the treatment of choice in patients with GEP tumors and it should always be considered, even if total tumor excision cannot be achieved. Reduction in tumor mass (debulking) may improve the patients symptoms. Medical treatment is used in patients with advanced malignant endocrine tumors. The most important compounds to control symptoms in these patients are somatostatin analogues. Natural somatostatin is produced in different molecular forms and has inhibitory effects on a number of functions. The observation of potent inhibitory effects on various hormone-secreting cells led to the use of somatostatin for symptomatic treatment of peptide-secreting tumors. Natural somatostatin is not suitable for long-term clinical application; therefore, synthetic somatostatin analogues were developed with improved pharmacokinetic characteristics. The best characterized analogue, octreotide, has been successfully applied to patients with functioning GEP tumors. Octreotide can dramatically ameliorate the debilitating symptoms of patients suffering from the clinical manifestations of endocrine tumors such as diarrhea and flushing. The success of octreotide therapy is best reflected in terms of its impact on the patient's quality of life as defined by the activity to perform normal daily activities.

Antineoplastic Agents, Hormonal↗
PubMed1999

Octreotide. Outlook.

Explore the source record for details and available documents.

Gastrointestinal Agents↗
PubMed1999

Modulation of multidrug resistance protein expression in porcine brain capillary endothelial cells in vitro.

Multidrug resistance-associated protein (MRP) is a transport system that is involved in the elimination of xenobiotics and biologically active endogenous substrates. Recently, the presence of MRP has been demonstrated in cultured brain capillary endothelial cells (BCECs). The time-dependent, functional expression of MRP in porcine BCECs was investigated to assess the value of this cell culture model for drug transport at the blood-brain barrier. Western blot analysis was used to investigate MRP expression in freshly isolated porcine BCECs and compared to MRP expression at days 8 and 10 in culture. Subcellular localization of MRP was investigated by immunocytochemistry with an MRP-specific monoclonal antibody, MRPr1. Functional activity of MRP was assessed by efflux studies with the fluorescent MRP substrate glutathione-methylfluorescein (GS-MF). No significant MRP expression was detected in freshly isolated endothelial cells. However, MRP expression is up-regulated in cell culture in a time-dependent manner. Immunostaining revealed predominantly perinuclear and, to a lesser degree, plasma membrane localization of MRP. At 10 degrees C GS-MF efflux was significantly decreased, indicating the involvement of an energy-dependent transport system. Efflux of GS-MF was apparently inhibited by MK571, a specific inhibitor for MRP. Porcine BCECs demonstrate up-regulation of functional MRP expression during culture, as observed in human tissue, and therefore might serve as a useful in vitro system for studying MRP-mediated blood-brain barrier transport.

ATP-Binding Cassette Transporters↗
PubMed1999

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group.

The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.

Antibodies, Monoclonal↗
PubMed1998

Helicobacter pylori infection in infants and children of Bangladesh.

Helicobacter pylori is an important cause of chronic gastritis and plays important roles in the etiology of peptic ulcer disease, gastric cancer and non-ulcer dyspepsia. While H. pylori infections occur worldwide, the great majority of information is from the developed countries, and little is known about the epidemiology of H. pylori in the developing countries, particularly in children.

Bangladesh↗
PubMed1998

[The role of cholecystokinin as a regulator of gastrointestinal functions].

Cholecystokinin (CCK), a peptide synthesized in the small bowel, is secreted into the blood stream after food intake. Its effects are primarily hormonal but of equal significance is that of a neurotransmitter. Its central role as a digestive peptide is illustrated by the following sequence: Mostly fat and protein of a consumed meal liberate CCK which triggers the contraction of the gallbladder and stimulates secretion of pancreatic enzymes. At the same time CCK slows down gastric emptying leading to an optimal ratio of foodstuff and digestive secreta. Via activation of afferent nerves CCK induces the sensation of saturation and thus limits food intake. Many questions remain open or undefined in this context but two conclusions may be drawn. 1. The significance of Pawlowian neural regulation of digestive functions is supported by new evidence, although hormones may support or modulate these functions. 2. It has become clear that a peptide may assume diverse regulatory functions be it as a hormone or as a neurotransmitter. Dear old concepts have therefore to be revised.

Cholecystokinin↗
PubMed1998

[Nonulcer dyspepsia].

Nonulcer dyspepsia or chronic dyspepsia (defined as upper gastrointestinal symptoms of at least 3-weeks duration) is a common problem in Western countries. Up to 30% of the general population suffer from dyspepsia and the dyspepsia-related work-load of the general practitioner is considerable. The general practitioner has to formulate a management approach: what therapy, if any, and which patient should be investigated? A considerable overlap of symptoms make a precise diagnosis without additional investigations difficult, but empirical acid inhibition is an attractive option. Disturbances of gastrointestinal motility and, perhaps, Helicobacter gastritis are additional possible pathogenetic mechanisms. At present, conclusive, controlled clinical trials are lacking and it remains controversial which strategy is most cost-effective but at the same time optimal for the patient.

Diagnosis, Differential↗