[Hormonal changes during administration of dietary fibers in patients with decreased glucose tolerance]. / Az élelmi rostok adását kísérö hormonális változások csökkent glukóz toleranciás egyénekben.

The authors carried out a self-controlled study using 11, non-obese patients with impaired glucose tolerance. The first day an oral glucose tolerance test was performed as a control. This was repeated the next day with a simultaneous intake of 20 g natural wheat bran. On both days blood samples were taken at 30 minute intervals (for three hours period) after glucose or glucose plus bran ingestion to measure the plasma sugar, insulin, C-peptid, gastrin and glucagon levels. It has been found that: 1. With simultaneous bran intake the blood glucose levels were decreased as compared to the control values. 2. The serum insulin, and C-peptid levels were similar in both tests. 3. The glucagon response curve fell below that of the control. 4. The serum gastrin levels did not show any change following either glucose or glucose plus bran intake. It has been concluded, that the dietary fibres are able to decrease of glucagon release, beside their direct inhibitory effect on the level of sugar absorption from gastrointestinal tract.

Efficacy testing of beta-galactosidase with H2 breath test in patients with carbohydrate malabsorption.

The clinical efficacy and the potential side-effects of beta-galactosidase were studied in adult lactose intolerance. Various randomized oral tolerance tests were performed using lactose solution (35 g), glucose + galactose solution (17.5 + 17.5 g), native, skimmed milk and milk pretreated with beta-galactosidase. In each case, simultaneous examinations were made of the glucose concentration of capillary blood by an instrument constructed by the authors, of the H2 content of expired air as also of the subjective complaints and of the number of stools and their pH. It was established that pretreatment of milk with beta-galactosidase has a beneficial effect in adult lactose maldigestion, since it stops dyspeptic complaints and diarrhoea due to milk, it reduces the H2 content of expired air increases blood glucose concentration. Measuring the H2 content of the breath by using and instrument constructed by the authors, exact data can be obtained noninvasively, and rapidly on the degree of carbohydrate malabsorption in patients with lactose-intolerance.

Effect of indomethacin on glucose absorption and insulin release in patients with impaired glucose tolerance.

Determinations of the levels of blood glucose and of serum insulin-like activity were made in 12 patients with impaired glucose absorption treated with indomethacin 4 x 25 mg for a day. By comparing the results with untreated control patients, it was found that the peak blood level of glucose, and the serum level of insulin-like activity, could be significantly decreased by this oral administration of indomethacin. The decrease of blood level of glucose appeared 0.5 h before the decrease of insulin-like activity in these patients with impaired glucose tolerance.

Minor modifications of the fluorimetric determination of glycosylated haemoglobin.

The fluorimetric method of Gallop et al [3] for the detection of the glycosylated haemoglobin was tested. Some minor modifications of the method are described and results of measurements performed in healthy subject are presented. The fluorimetric technique is compared to a colorimetric method and a chromatographic assay.

Evidence of the gastric cytoprotective effects of vitamin A, atropine and cimetidine on the development of gastric mucosal damage produced by administration of indomethacin in healthy subjects.

Certain compounds such as prostaglandins, atropine, cimetidine and carotenes are able to prevent the development of gastric mucosal damage produced in experimental animals or in man by intragastric administration of necrotizing agents such as indomethacin without significantly inhibiting gastric acid secretion. The clinical background of this gastric cytoprotection and its importance for man is not yet known, although the beneficial effects of these compounds have been demonstrated in human therapy. In the present study, carried out in 66 healthy human subjects, it was found that vitamin A at a dose of 100,000 IU i.m., atropine at 0.125 mg i.m., and cimetidine at 12.5 mg i.m., which doses do not inhibit the gastric basal secretion nor the maximal secretory response to pentagastrin stimulation, each prevented the gastric microbleeding produced by the oral application of indomethacin. It is concluded that this gastric cytoprotection, characteristic of prostaglandins but extending to atropine, cimetidine and vitamin A, holds good in man as well as experimental animals. Thus the potential clinical significance of gastric cytoprotection induced by these compounds may be considerable.

Gastric microbleeding measurements during one day treatment with indomethacin and indomethacin plus sodium salicylate (1 : 10) in patients.

A double-blind, prospective, randomized clinical study was carried out. Gastric microbleeding was provoked in informed patients without gastrointestinal disorders by the administration of indomethacin (4 X 25 mg, orally), sodium salicylate (4 X 250 mg, orally) or indomethacin (25 mg) plus sodium salicylate (250 mg) (Pelsonin, 4 X 1 capsules). The rate of gastric bleeding was estimated on the basis of haemoglobin losses into the gastric juice according to a rapid and sensitive chemical method (Fisher and Hunt, 1976). The observations were done before and after the day of treatment. The basic gastric bleeding was practically the same in the three groups (indomethacin, 0.91 +/- 0.12 ml/day: sodium salicylate, 0.72 +/- 0.20 ml/day: Pelsonin, 0.99 +/- +/- 0.18 ml/day: p less than 0.05). Contrary to this, the increases of gastric bleeding were found to be considerably different after a one-day application of these drugs (indomethacin, 7.3 +/- 1.2 ml/day: sodium salicylate, 1.92 +/- 0.45 ml/day, Pelsonin, 2.1 +/- 0.8 ml/day). It has been concluded that sodium salicylate can reduce the indomethacin-induced gastric microbleeding in patients.

Some metabolic and biochemical alterations during the development of stress ulcers in rats forced to swim.

Swimming of the rats in the water below body temperature (23 degrees C) for a period of 5 hours resulted in a number of acute haemorrhagic lesions, principally erosions, in the glandular part of the stomach. The objective of this study was to establish the possible roles of some hormonal, biochemical and metabolic factors in the pathogenesis of stress ulcer produced in rats forced to swim. It was found that (i) prior ligation of the pylorus caused a considerable decrease of both the incidence and the severity of the ulcers resulting from the swim-stress, (ii) a significant decrease of the gastric secretion and rectal temperature resulted during the swim-stress condition, (iii) metabolic acidosis developed during the forced swimming period, (iv) considerable increases of the plasma corticosterone and blood glucose concentration also developed, (v) the gastric mucosal level of cAMP also increased, and (vi) a prior period of starvation increased the incidence and severity of the acute ulcers resulting from the swim-stress. It was concluded that various humoral, biochemical and metabolic factors play important roles in the development of stress ulceration in rats forced to swim.

Lactose-poor milk in adult lactose intolerance.

The frequency of lactose intolerance was studied in patients with chronic gastrointestinal disease, mainly peptic ulcer to explore the possibilities of the use of lactose-poor milk. It was found that whole milk caused dyspeptic symptoms in 45% of patients with peptic ulcer; lactose-intolerance was present in 82% of the patients with milk intolerance; lactose poor powdered milk resulted in complete freedom from symptoms. Use of milk with reduced lactose contents is recommended in the diet of adult patients with lactase deficiency.

Effects of drugs on the production of stress ulcer in the rat.

The authors studied the effect of drugs with different mechanisms of action on the prevention of stress ulcer production in the rat. Stress ulcer was induced by a method developed by the authors: intact, starved rats were swum in water at 23 degrees C for 5 hours. Atropine (0.1-0.5 and 1.0 mg/kg i.m.), cimetidine (1.0-5.0 and 25 mg/kg i.p.), prostacyclin (PGI2) (5.0-25.0 and 100 micrograms/kg i.p.) and phentolamine (0.35-1.75-3.5 and 7.0 mg/kg i.m.) were shown to decrease the production of stress ulcers significantly, in a dose-dependent fashion. Propranolol (0.35-1.75-3.5 and 7.0 mg/kg i.m.) did not influence the production of stress ulcers. The finding that drugs with different actions could considerably reduce or prevent the production of stress ulcer appears to indicate the complexity of the neural, hormonal and biochemical processes involved in the pathogenesis. On the basis of the present results the authors suggest the use of a preventive therapeutic regimen in clinical practice with an appropriate combination of drugs.

Enzyme-inductive effect of a hypolipidemic compound N-bis-(p-chlorophenoxy)-acetyl-urea in man and rat.

Besides its antilipidaemic effect, the new clofibric acid derivative (N-bis-(p-chlorohenoxy)-acetyl-urea) has an enzyme-inductive effect. The drug was administered (100 mg/kg orally) to male, Wistar rats for three days. The treatment raised the weight of the liver, the content of liver microsomal protein and cytochrome p-450 and shortened the hexobarbital sleeping time. The increase of cytochrome p-450 dependent biotransformation was found by in vitro methods in 9000-g supernatant of liver homogenate. There was a growth in biotransformation of substrates of type I (ethylmorphine, aminopyrine) and an extreme increase in reduction of nitrobenzene. We did not find any change in biotransformation of the type-II substrate aniline. In 16 patients suffering from Gilbert's syndrome, there was a decrease in the level of serum bilirubin, and increase of D-glucuric-acid output in urine and bromsulphophthalein transport maximum following the treatment of this drug given in 150 mg/day orally for three weeks. After this treatment, the level of gamma-glutamyl-transpeptides did not change. The authors highly recommend the serious consideration of metabolic interaction during the clinical application.

Influence of phenobarbital pretreatment on biliary rose bengal excretion in rats.

Plasma concentration, hepatic uptake and biliary excretion of intravenously administered rose bengal was determined in rats pretreated with phenobarbital (50 mg/kg) daily, for four days). After an initial (0--16 min) rapid fall in plasma rose bengal concentration caused by hepatic uptake of the dye, the curves in control and pretreated rats did not differ from each other either after administration of a small (5 mg/kg) or a large (50 mg/kg) dose. Hepatic rose bengal concentration was significantly lower in pretreated animals than in the control group. Since liver weight was higher in the phenobarbital pretreated animals than in the controls, the total amount of rose bengal taken up by the liver did not differ in the two groups. The biliary excretion of low dose (5 mg/kg) rose bengal was significantly higher in phenobarbital pretreated than in the control rats but with doses of 50 mg/kg and 100 mg/kg no difference was observed. These doses of rose bengal diminished the increased bile flow caused by phenobarbital.

Drug-induced manifestation of hereditary hepatopathy.

PIP: Drug treatment appears to have induced the manifestation of undetected enzymopathy in 4 case studies. 2 patients had acute intermittent porphyria and 2 had Gilbert's syndrome. In acute intermittent porphyria, the effects of enzyme inducers may overproduce DALA-synthetase which may lead to an acute porphyria attack. In Gilbert's syndrome, enzyme activity is hormone-dependent and studies have shown that synthetic estrogens are inhibitory to conjugation with glucuronide. Therefore, drug use may result in the manifestation of hereditary or genetic defects.^ieng