[Therapy of autonomic diabetic neuropathy of the gastrointestinal tract].
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Biomedical subjects
Publications and source records attributed to W F Caspary.
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A new and versatile method for the identification and quantification of short-chain fatty acids, such as formic, acetic, propionic, butyric, isobutyric, valeric, isovaleric and mercaptoacetic acids, in biological specimens by high-performance liquid chromatography is described. After sample purification by vacuum transfer and concentration by alkaline freeze-drying, the acids were measured without any further preparative step, using a sulphonated polystyrene-divinylbenzene column as stationary phase. Ultraviolet detection of the native acids was done at 214 nm. Peak resolution and reproducibility were as good as with gas chromatography. Many examples of the application of this method to a variety of biological specimens and fluids both from the rats and humans are described.
Both putrescine and the polyamines spermidine and spermine are essential factors for growth and differentiation in all cells of higher eucaryotes. In principle, increased requirements of polyamines in mucosal cells either can be met by de novo-synthesis or by increasing the uptake from lumen (brush border membrane) or bloodstream (basolateral membrane). We therefore evaluated putrescine uptake in intestinal mucosal cells by using human brush border membrane vesicles (BBMV). Intravesicular uptake of putrescine was shown by osmoplots. This process was not saturable over a substrate range from 1 to 80 microM. Putrescine transport was also found to be independent of temperature (Q10 = 1.23). No differences in putrescine uptake rates were found in the presence or absence of Na+, and there was no evidence for any dependence of putrescine uptake from other cations. Our data indicate that putrescine uptake by human intestinal brush border membrane vesicles occurs by passive diffusion. It is concluded that a formerly described saturable and carrier mediated uptake in isolated intestinal mucosal cells from different species is probably influenced by active transport across the basolateral membranes. Therefore, further studies with isolated basolateral membranes are advocated.
Peripheral insulin resistance is suggested to play an important role in the pathogenesis of type II diabetes mellitus. In this study we investigated insulin receptor binding, D-glucose transport under equilibrium conditions for insulin and the activation kinetics of insulin stimulated D-glucose transport in isolated human adipocytes from type II diabetics and healthy controls. While the insulin receptor binding affinity was not significantly different between both groups, basal and insulin stimulated glucose transport rates were reduced in adipocytes from type II diabetics compared to normal controls. The activation of D-glucose transport was significantly delayed in the diabetics, the time to achieve maximal transport rates was 7.7 +/- 1.1 vs. 4.2 +/- 1.4 min, respectively (p < 0.05). Thus a reduced velocity of glucose transport activation by insulin appears to be a further factor contributing to peripheral insulin resistance in type II diabetics.
Anorectal motor function was evaluated in 15 female patients with Addison's disease and androgen deficiency and 15 age-matched healthy volunteers. Medical history revealed symptoms of faecal incontinence in 5 patients. The patients showed decreased maximum retention volumes (p less than 0.01) in the rectal saline infusion test. Lowered anal sphincter resting (p less than 0.01) and squeeze pressure (p less than 0.01) was demonstrated in patients with adrenocortical insufficiency. No differences between patients and controls were found in respect of perception volume, minimal distension volume for sphincter relaxation and rectal compliance by means of intrarectal balloon distension. Electromyography of the external anal sphincter was performed in 8 patients and showed no evidence for a neurogenic defect. Relevant morphological changes of the anorectum could be excluded endoscopically in 13 of the 15 patients. Therefore impaired anorectal muscular function is responsible for faecal incontinence in patients with Addison's disease and androgen deficiency. Further investigations will show, whether these findings are the consequence of lowered androgen production.
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Antacids are able to prevent acetylsalicylic acid-induced functional and morphological changes of the gastric mucosa. In order to test whether a new antacid in chewing-tablet form (Gastropulgit Tabs) might be able to protect the gastric mucosa from acetylsalicylic acid-induced functional changes similarly to liquid antacids the effect of this antacid on acetylsalicylic acid-induced changes of transmural gastric potential difference was measured in healthy volunteers. The decrease of transmural potential differences induced by 640 mg acetylsalicylic acid could be prevented by simultaneous addition of 2 tablets of Gastropulgit Tabs. Thus the antacid in tablet form is able-like liquid antacids-to protect the gastric mucosa against acetylsalicylic acid-induced functional changes.
The effect of a new complex oligosaccharide (Bay g 5421) of microbial origin on human intestinal alpha-glucosidehydrolase activity was tested in mucosal homogenate from human small bowel biopsy specimens. The alpha-glucosidehydrolase inhibitor (alpha-GHI) exerted a potent inhibitory effect on glucoamylase, sucrase, and maltase, was minimally effective on isomaltase, and did not affect trehalase and lactase activity. Kinetic analysis revealed a fully competitive type of inhibition with a Ki of 1.3 x 10(-6) M; thus the inhibitor had a 15,000-fold higher affinity to the enzyme sucrase than its natural substrate sucrose. The new compound may prove to be useful in the study of carbohydrate maldigestion and malabsorption and may possibly be of therapeutic benefit in diabetes and obesity.
The effect of a new complex oligosaccharide exhibiting potent inhibitory action on alpha-glucoside hydrolases on intestinal absorption of sucrose in man was tested by constant in vivo perfusion of the jejunum. At concentrations of 4.65 or 15.5 X 10(-6)M the alpha-glucosidehydrolase inhibitor (alpha-GHI) markedly inhibited absorption of glucose from sucrose and absorption of sodium and water. Oral administration of the alpha-GHI resulted as well in depression of solute, sodium, and water absorption. This new compound can serve as an interesting tool to induce carbohydrate malabsorption by inhibition of final digestion and may possibly be of beneficial therapeutic effect in dietary control of diabetes or obesity.
Postvagotomy-diarrhea, a troublesome complication of truncal vagotomy, seems to be caused by an increased concentration of bile acids reaching the colon due to intestinal hurry. Whether a dilatation of the gallbladder may contribute to bile acid malabsorption with its consequences of watery diarrhea cannot be decided at the moment. The beneficial therapeutic effect of cholestyramine or aluminiumhydroxide-containing antacids supports the concept that postvagotomy-diarrhea is induced by bile acids.
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Demethylation of aminopyrine was measured in 25 healthy controls and 19 epileptics on long-term treatment with anticonvulsants by the 14C-aminopyrine breath test. Compared to controls epileptics exhibited increased cumulative 14CO2-exhalation rates (88.7% at 30 min, 62.6% at 2 h and 24.8% at 8h) following ingestion of 2 mu Ci 14C-aminopyrine. The results suggest that long-term treatment with antiepileptic drugs results in increased demethylating function of the liver which can be easily detected by a simple breath analysis technique like decreased demethylation in chronic liver disease.
Oxalate-urolithiasis and hyperoxalaria have been reported to be a frequent complication in patients with small bowel disease, especially in patients with ileal resection due to Crohn's disease. Hyperabsorption of oxalate seems to be the main patholgenetic factor for "enteric" hyperoxalaria. Intestinal absorption and urinary excretion of oxalate was measured in patients with various gastrointestinal diseases after oral or rectal administration of 14C-oxalate. Kinetic data suggest that 14C-oxalate is absorbed in the small, the large bowel and the rectum as well. Oxalate absorption was decreased in patients with a colectomy and in active ulcerative colitis, but increased in patients with ileal resection, chronic liver disease, and steatorrhea due to chronic pancratitis or sprue. There existed a positive correlation between 14C-oxalate absorption and the amount of fecal fat excretion. The data suggest that hyperoxaluria and hyperabsorption of oxalate are not a specific finding in patients with bile acid malabsorption, but may occur too, in steatorrhea without alteration of bile acid metabolism.
The effect of an alpha-glucosidehydrolase inhibitor (alpha-G.H.I.) on intestinal absorption of sucrose was assessed by measuring rises in blood-glucose and intestinal hydrogen production after ingestion of 100 g sucrose. 200 mg alpha-G.H.I. given with the sucrose completely inhibited early postprandial blood-glucose rises, prevented late postprandial dips in blood-glucose, and considerably increased breath-hydrogen levels, which indicates sucrose malabsorption. Thus the inhibitor can be used to study carbohydrate malabsorption and may be useful as a method for retarding carbohydrate absorption.
The bile acid binding capacity of various liquid antacids and of colestyramin were compared. Aluminium hydroxide containing antacids showed the highest binding capacity. This seems to be of importance also in therapeutic doses for treatment of chologenic diarrhoea, vagotomy diarrhoea and gastric ulcer.
D-Galactose metabolism and demethylation of aminopyrine by healthy controls and patients with chronic active hepatitis (CAH) and cirrhosis (Ci), were assessed by a breath analysis technique measuring 14CO2 exhalation after oral ingestion of 14C-D-galactose or 14C-aminopyrine. Patients with CAH and Ci exhibited decreased 14CO2-exhalation rates following 14C-D-galactose or 14C-aminopyrine. D-Galactose oxidation capacity of the liver can be assessed by a breath analysis technique in analogy to the demethylating function for aminopyrine. The ordinary oral D-galactose tolerance test seems, however, superior in comparison to the 14C-D-galactose tolerance test, in discriminating between healthy controls and patients with chronic liver disease.
The effect of glycocholic acid (GCA) on functional changes of the gastric mucosal barrier was examined by measurement of transmural gastric potential difference (PD) in humans in the presence and absence of cholestyramine and of A1(OH)3-containing antacids possessing potent bile acid binding properties. Intagastric instillation of GCA induced reduction of PD which could be prevented by the more potent buffering Mg-A1(OH)3-containing antacid, but not by cholestyramine or the less potent A1(OH)3-containing antacid. It is concluded that for the prevention of bile acid induced damage of gastric mucosa potent antacids are superior to potent bile acid binding agents loosing the binding properties at low pH-values.