Biomedical subjects

H Larsson

Publications and source records attributed to H Larsson.

At least 145 records · Page 8Linked to original sources

PubMed1986

Evaluation of visual pathways in multiple sclerosis. I. After-images compared to visual evoked potentials.

The value of flight of colours (FOC), i.e. the succession of coloured afterimages following light stimulation, in diagnosing and following visual impairment was evaluated in 65 patients with multiple sclerosis (MS). Previous optimistic reports of the use of a pocket flashlight (PFL) method could not be confirmed, and are ascribed to inadequate methods. An electronic flashlight (EFL) method developed by us, proved a significantly better diagnostic tool (61% abnormal versus 18% abnormal). The EFL method was diagnostically less sensitive than pattern reversal visual evoked potential (PR-VEP) (80% abnormal). It did, however, add to PR-VEP by diagnosing 16 eyes with normal PR-VEP latency. The EFL method reflected the degree of degenerative changes in the central visual pathways and may be of value in following the disease activity in MS. The potential of the EFL method may be further improved by proposed modifications.

Afterimage↗

PubMed1986

Evaluation of the visual system in multiple sclerosis. II. Colour vision.

A study of colour vision (CV) in 65 patients with multiple sclerosis (MS), (30 patients had had previous optic neuritis) and 51 controls was carried out with Ishihara's pseudoisochromatic plates (I-test), Farnsworth's panel D-15 test (F-test), and Lanthony's desaturated 15-hue test (L-test). CV defects were classified as to type and severity. Error scorings were calculated by Bowman's computerized method and our own simple proposal for scoring, which was found of equal value. Results were compared with pattern-reversal (black/white) visual evoked potentials (PR-VEP) (80% of eyes abnormal). The I-test (56% of eyes abnormal) was a more sensitive indicator of demyelination than the L-test (47%) and F-test (26%). In 14 eyes CV defects (10 blue-yellow, 4 red-green) were only revealed with the L-test. Abnormal CV, mostly blue-yellow defects, occurred in 16 patients (19 eyes) having normal VEP latencies; 29 patients were re-tested within one week. It is proposed that the performance of the I-test, which showed the highest reproducibility, could be improved by adding more cards, particularly blue-yellow, to the test.

Color Perception↗

PubMed1986

Hypergastrinemia after blockade of acid secretion in the rat: trophic effects.

The availability of potent and long-acting blockers of acid secretion, such as omeprazole, has paved the way for experimental studies on the long-term effects of permanently raised levels of circulating gastrin without the complication of surgical intervention. We have examined rats given high doses of the antisecretagogues omeprazole and ranitidine during 10 or 20 weeks for general trophic effects on the gastrointestinal tract and pancreas and for the effects on endocrine cells such as the somatostatin cells and the enterochromaffin-like (ECL) cells, which are present in the oxyntic mucosa. The ECL cells, which in the rat produce and store histamine (in addition to an as yet unidentified peptide hormone), are known to be activated by gastrin. In rats given high doses of omeprazole, the serum gastrin levels rose about 10-fold. General trophic effects were restricted to the stomach; the weight was increased, as was the thickness of the oxyntic mucosa. Omeprazole treatment resulted in a 3- to 5-fold increase in the ECL cell density. A close correlation was found between plasma gastrin levels and the ECL cell density as well as the levels of histidine decarboxylase and histamine in the oxyntic mucosa. The somatostatin cell density was unaffected by the hypergastrinemia. During a 10-week recovery period after discontinuation of the omeprazole treatment, the ECL cell density diminished, but was still significantly higher than in age-matched control rats. Plasma gastrin levels and gastric histidine decarboxylase activity rapidly returned to control values. The results suggest that the observed general trophic effects on the oxyntic mucosa and on the ECL cells are related to the plasma gastrin levels and not to an action of the antisecretagogues per se.

Animals↗

PubMed1986

Gastric regulatory peptides in rats with reduced acid secretion.

Gastric acid secretion is known to be controlled by a complex system of interacting factors. Amongst these, regulatory peptides make a significant contribution. In the present study, immunocytochemistry and radioimmunoassay were used to investigate gastric regulatory peptides in animals with pharmacologically reduced gastric acid secretion. Increased numbers of densely immunostained antral gastrin-immunoreactive (G) cells were seen in rats which had been rendered virtually achlorhydric by administration of high-dose (400 mumol/kg daily) omeprazole over a 10-week period. These morphological changes were accompanied by increases in the plasma, antral and fundic concentrations of gastrin, as measured by radioimmunoassay. In contrast, antral somatostatin-containing cells were reduced, and there was a corresponding fall in the tissue content of the peptide. Ten weeks after treatment had ceased, the peptide profiles had returned to normal. No other regulatory peptide, whether endocrine or neural, appeared to alter during treatment with high-dose omeprazole. Treatment with high-dose (700 mumol/kg daily) ranitidine also caused an elevation in the G cell population and the antral and plasma content of gastrin, but to a lesser extent than that observed during omeprazole treatment. Somatostatin cells and tissue levels did not alter in these animals, and no other morphological changes could be detected. Radioimmunoassay, however, measured reduced quantities of vasoactive intestinal peptide, peptide histidine isoleucine and calcitonin gene-related peptide. Achlorhydria, induced by omeprazole at a dosage of 250-500 times that required for effective acid inhibition in man and animals, therefore resulted in reciprocal changes in gastrin and somatostatin cells. These changes are support for the postulated roles of these peptides in the control of gastric acid secretion.

Achlorhydria↗

PubMed1986

Pharmacology and toxicology of omeprazole--with special reference to the effects on the gastric mucosa.

Omeprazole is a long acting inhibitor of gastric acid secretion in different species including rat and dog. Due to the long duration of action, steady state inhibition at repeated once daily administration is reaches within 4-5 days in dogs and in about 3 days in rats. Daily dosing at high dose levels results in virtually complete 24-hour inhibition of acid secretion in experimental animals. The elimination of the inhibitory feedback effect of acid on gastrin secretion leads to hypergastrinaemia. Because gastrin has a trophic effect on the oxyntic mucosa, the hypergastrinaemia results in a reversible hypertrophy of the oxyntic mucosa and an increased capacity to produce acid following maximal stimulation with exogenous secretagogues after discontinuing treatment. Despite the increased capacity to produce acid, basal acid secretion seems to be unchanged. The pronounced hypergastrinaemia which occurs during long-term treatment with high doses rapidly normalizes after discontinuing treatment. The hyperplasia of the oxyntic endocrine ECL cells, and the eventual development of gastric ECL cell carcinoids after lifelong treatment of rats with high doses, can also be attributed to the hypergastrinaemia developing after almost complete elimination of gastric acid secretion in these animals.

Animals↗

PubMed1986

Inhibition of gastric acid secretion by omeprazole and ranitidine. Effects on plasma gastrin and gastric histamine, histidine decarboxylase activity and ECL cell density in normal and antrectomized rats.

Female rats were subjected to various treatments for 10 weeks to study effects on plasma gastrin levels. Intact rats were treated orally with omeprazole, 10 or 400 mumol/kg, ranitidine, 175 + 175 + 350 mumol/kg, or vehicle; antrectomized rats were treated with omeprazole, 400 mumol/kg, or vehicle. In addition to plasma gastrin levels, histidine decarboxylase (HDC) activity, histamine levels and ECL cell density in the oxyntic mucosa were determined. Gastrin levels were increased in unoperated rats treated with the high omeprazole dose and with ranitidine, whereas they were lowered in antrectomized controls. A small increase in plasma gastrin was seen in the low-dose omeprazole group. In antrectomized rats treated with omeprazole, the plasma gastrin level was the same as in intact control rats. The ECL cell density, the activity of HDC and the concentration of histamine in the oxyntic mucosa were found to reflect the plasma gastrin concentration. The results suggest that the changes in ECL cell density are secondary to the changes in plasma gastrin, induced by inhibition of acid secretion or antrectomy. It is concluded that neither omeprazole nor ranitidine per se is likely to induce proliferation of ECL cells.

Animals↗

PubMed1985

The relationship between gastric acid secretion and gastric H+,K+-ATPase activity.

The H+,K+-ATPase has been postulated to be the enzyme responsible for H+ secretion by the parietal cell. Omeprazole has been shown to be an inhibitor of acid secretion in vivo, but also in in vitro test models for acid secretion, including partly purified H+,K+-ATPase, the inhibitory action of omeprazole has been demonstrated (Wallmark, B., Jaresten, B. M., Larsson, H., Ryberg, B., Brändström, A., and Fellenius, E. (1983) Am. J. Physiol. 245, G64-G71). It was thus possible to use this compound to demonstrate a correlation between H+,K+-ATPase activity in rat oxyntic mucosa and in vivo H+ secretion. Two results were found. (a) Increasing oral doses of omeprazole progressively inhibited acid secretion, H+,K+-ATPase activity, and phosphoenzyme formation of a microsomal fraction isolated from the inhibited rat mucosa. Furthermore, a Mg2+-stimulated ATPase activity, associated with the H+,K+-ATPase membrane fraction, was not affected by the omeprazole treatment. (b) Recovery of H+,K+-ATPase activity following complete omeprazole inhibition was correlated with the appearance of acid secretion. The results indicate a strict relationship between the activity of the gastric H+,K+-ATPase in the microsomal fraction and gastric acid secretion.

Adenosine Triphosphatases↗

PubMed1985

Reversal of increased whole blood and plasma viscosity after treatment of hypothyroidism in man.

Blood and plasma viscosity was measured in 13 patients with hypothyroidism before and during replacement therapy with l-thyroxine. Blood viscosity was measured at natural hematocrit and after adjustment to 40%. The values were compared to those of 12 healthy subjects. Both blood viscosity at hematocrit 40% and plasma viscosity were increased in the hypothyroid state and decreased to the levels of the reference group after treatment. The therapy-induced changes in blood and plasma viscosity were intercorrelated at low but not at high shear rates. The changes in viscosity were not correlated to the reductions in lipoprotein concentrations resulting from therapy. The institution of l-thyroxine replacement therapy was also followed by reductions in erythrocyte sedimentation rate and diastolic blood pressure, both with significant correlations to the decrease in blood viscosity. It is concluded that in hypothyroidism there are changes in both plasma and erythrocytes that increase blood viscosity, with normalization upon treatment with l-thyroxine to euthyroidism.

Adult↗

PubMed1985

Pulmonary blood flow determination with selective rebreathing of CO2.

A new CO2-based non-invasive method for pulmonary blood flow has been developed. Selective rebreathing of CO2 was obtained in an open-circuit system by measuring the expired instantaneous CO2 flux in the expired air and by mixing pure CO2 into the inspired air. The time course of the inspired PCO2 was altered so that end-tidal PCO2 changed as a linear function of time (ramp). Pulmonary blood flow was computed as the ratio between the rate of change in net CO2 elimination (or uptake) and the concomitant rate of change of estimated arterial CO2 content. In comparison to simultaneously determined cardiac output by means of the O2 Fick method, the proposed CO2 ramp method underestimated cardiac output by some 20 per cent in 22 supine sedated patients with valvular heart disease. Differences in PCO2 between end-tidal gas and the gas in perfused alveoli are thought to be the main cause of this underestimation.

Adult↗

PubMed1985

Animal pharmacodynamics of omeprazole. A survey of its pharmacological properties in vivo.

In the present paper, a collection of experimental data is presented describing the pharmacological profile of omeprazole mainly in dogs and rats. Omeprazole potently inhibited gastric acid secretion in different experimental models. In the dog, for instance, omeprazole was 2-7 times more potent than cimetidine, depending on the route of administration, and in the rat the difference was even greater. Omeprazole was equally potent against different types of stimulation, whereas cimetidine was not, indicating differences in their mechanisms of action. In the dog, the duration of the antisecretory effect was long and lasted for 3-4 days after a single maximal dose of omeprazole. The inhibitory effect after repeated, daily administration of submaximal doses therefore gradually increased and attained a steady-state level after five doses. Treatment up to one year with very high oral doses did not affect the duration of effect. During long-term treatment with high doses of omeprazole a 10-fold increase in meal-stimulated plasma gastrin levels was recorded. This was probably due to a nearly complete inhibition of acid secretion over 24 hours during the study. The gastrin values returned to control levels within eight days after the end of the treatment. Omeprazole was rapidly absorbed (peak plasma levels were reached within one hour) and the elimination half-life was approximately one hour. In the dog, the gastric antisecretory effect was related to the total dose and the area under the plasma concentration curve, whereas the peak level or the shape of the curve was of minor importance. Omeprazole, given orally to rats, dose-dependently prevented experimentally induced gastric lesions. Neither inhibition of acid secretion, stimulation of gastric bicarbonate secretion nor interference with the synthesis of endogenous prostaglandins seems to be of any great importance for the gastric protective effect of omeprazole. Omeprazole seems to be very specific in its gastric acid antisecretory and gastric protective actions since, apart from a decrease in the rate of gastric emptying found after very high oral doses in the rat, no other general pharmacological effects of omeprazole have been observed. Thus, omeprazole was devoid of histamine H2-receptor blocking properties, did not affect the intestinal transport rate, pancreatic secretion, autonomic control of the cardiovascular system or kidney excretion of hydrogen ions.

Administration, Oral↗

PubMed1985

The mechanism of action of omeprazole--a survey of its inhibitory actions in vitro.

In order to study the mechanism of inhibition of gastric acid secretion by omeprazole, its action was investigated in several different in vitro preparations. In preparations from isolated gastric mucosa, isolated rabbit gastric glands and isolated parietal cells, omeprazole was found to inhibit both basal and stimulated acid secretion. These effects were seen irrespective of whether acid formation was stimulated by histamine or by db-cAMP. The inhibitory pattern of omeprazole was found to be of a non-competitive nature against db-cAMP stimulation. Furthermore, in isolated glands, omeprazole was found to inhibit stimulation induced by high medium K+ and low Na+ concentrations. The basal membrane of the intact gland preparation was made permeable to molecules of large size by the use of digitonin, and acid secretion was subsequently initiated by the addition of exogenous ATP. Even under these conditions, omeprazole was found to be inhibitory, with an IC50-value comparable to that of intact glands. SCN- was found to mimic the action of omeprazole in that it counteracted both basal and stimulated acid secretion in the test models described above. In contrast, cimetidine was found to inhibit only histamine stimulation, consonant with its H2-receptor-blocking properties. In the gastric gland preparation, changes in oxygen consumption is closely related to changes in acid formation. When oxygen consumption and acid formation were measured in parallel under histamine stimulation, another benzimidazole, timoprazole (H 83/69) (structurally related to omeprazole), was found to inhibit both parameters. However, under non-stimulated conditions, timoprazole was found to have only a minor effect on the oxygen consumption. The isolated H+K+ATPase preparation was used in order to investigate the effects of omeprazole at the "proton pump level". This enzyme was found to be inhibited by omeprazole in a pH-dependent manner. Under neutral or slightly alkaline conditions, slight inhibition occurred. When the pH of the incubation media was progressively decreased, the inhibitory activity of omeprazole was augmented. Several reactions of the H+K+ATPase enzyme cycle were investigated, i.e., K+-stimulated ATPase- and pNPPase- activities and formation of phosphoenzyme. All three of these reactions were inhibited. The results presented are in agreement with the hypothesis that omeprazole inhibits gastric acid secretion by blocking the gastric H+K+ATPase.

Aminopyrine↗

PubMed1984

Evidence for acid-induced transformation of omeprazole into an active inhibitor of (H+ + K+)-ATPase within the parietal cell.

The chemical reactions of omeprazole, leading to inhibition of gastric acid secretion, were investigated. In acid buffer solutions, omeprazole was found to be labile, whereas at physiological pH it was stable (t1/2 greater than 17 h at pH 7.4). The stability of omeprazole was also studied in isolated, acid producing, gastric glands under conditions where acid formation was either stimulated or inhibited. The rate of transformation of omeprazole was high (t1/2 approximately 3 min) under stimulation. Inhibition of acid formation in the gland greatly retarded the decomposition of omeprazole (t1/2 approximately 73 min). The time-course for inhibition of acid formation by omeprazole was parallel to that for decomposition. The major product formed from omeprazole was the reduced form, H 168/22. The inhibitory action of omeprazole was shown to depend on acid-induced transformation, since no inhibition was obtained when omeprazole was incubated under neutral conditions, both in the isolated gastric mucosal- and the (H+ + K+)-ATPase preparations. Despite the fact that H 168/22 was the major product formed in the glandular preparation, it was found to be virtually inactive in both the glandular- and (H+ + K+)-ATPase preparations. Therefore, a model is proposed in which the inhibition of acid formation by omeprazole is mediated by a compound formed during the reduction of omeprazole to H 168/22 within the acid compartments of the parietal cell. Furthermore, mercaptanes, such as beta-mercaptoethanol, were found to prevent as well as reverse inhibition by omeprazole in both the glandular- and (H+ + K+)-ATPase preparations. This indicates that -SH groups are most likely involved in the chemical reactions leading to inhibition of acid secretion.

Adenosine Triphosphatases↗

PubMed1984

Effect of omeprazole on gastric secretion in H+,K+-ATPase and in pepsinogen-rich cell fractions from rabbit gastric mucosa.

In order to study the effects of the substituted benzimidazole omeprazole on gastric secretory functions, parietal cells and chief cells from rabbit gastric mucosa were separated and enriched by density gradient centrifugation in Percoll. H+,K+-ATPase activity, as well as a 100,000 dalton protein, was found to copurify with a cell fraction morphologically characterized as mainly parietal cells (purity approximately 65%), while pepsinogen copurified with a cell fraction morphologically characterized as chief cells (purity approximately 90%). A spontaneous pepsinogen release (9.9 micrograms/mg cell dry wt X 2 hr), unaffected by both atropine and omeprazole, was found in the chief cell fraction. The release was approximately doubled by both carbacholine (4 X 10(-5)M) and dibutyryl cAMP (db-cAMP, 10(-3)M). The cholinergic stimulation was selectively blocked by atropine, while omeprazole had no effect on pepsinogen release induced by either of the secretagogues. On the other hand, omeprazole inhibited both db-cAMP- and histamine-stimulated acid secretion quantified as [14C]aminopyrine (AP) accumulation in the parietal cell fraction. Cimetidine counteracted only acid secretion induced by histamine. These findings indicate that omeprazole has a specific effect on acid secretion, and are consonant with the hypothesis that the effect is due to H+,K+-ATPase inhibition.

Adenosine Triphosphatases↗

PubMed1984

Behçet's disease and close contact with pigs.

Six male patients out of seven with Behçet's disease were found to have a very similar and close contact with pigs and pork. These six cases are reported and we ask the question whether the contacts with pigs are just coincidental findings or whether an external agent, e.g. a virus, could be forwarded to man from pigs and pork. Immune complex associated vasculitis is described e.g. in patients with hepatitis B and the same mechanisms might be operating in patients with Behçet's disease.

Abattoirs↗

PubMed1984

Effects of omeprazole and cimetidine on gastric acid secretion and right atrial beating frequency in isolated organ preparations from the guinea pig.

The effects of omeprazole , a substituted benzimidazole, on gastric acid secretion and on right atrial beating frequency have been investigated in guinea pig preparations in vitro. Cimetidine was used as a reference compound. Omeprazole , at 10(-6) mol/l, inhibited basal acid secretion, whereas cimetidine, at 10(-5) mol/l, did not. There were also differences in the effects on stimulated secretion. Cimetidine (10(-5) mol/l) competitively inhibited histamine-stimulated acid secretion without affecting the maximal histamine response. In contrast, omeprazole concentration dependently depressed (EC50 approximately 5 X 10(-7) mol/l) the maximal histamine response without any effect on the histamine sensitivity. Furthermore, dibutyryl-cAMP-stimulated acid secretion was inhibited by omeprazole but not by cimetidine. The inhibitory effect of omeprazole (2 X 10(-6) mol/l) on histamine-stimulated acid secretion was reversed by repeated washing of the serosal side of the mucosa. Omeprazole was devoid of histamine H2 receptor antagonistic activity, since it had no effect on the chronotropic response to histamine in the guinea pig right atrium. It is concluded that omeprazole inhibits gastric acid secretion by a non-histaminergic, reversible mechanism and that the site of action is beyond the cAMP step within the parietal cell.

Animals↗

PubMed1983

Omeprazole provides protection against experimentally induced gastric mucosal lesions.

Omeprazole, given orally to rats, protects the gastric mucosa against various necrotizing agents, in doses (ED50 values 12-40 mumol/kg) which inhibit acid secretion. However, the protection is due to reduced acid secretion since omeprazole given intravenously in doses which completely inhibit acid secretion is not protective. The mechanism of the protective effect of omeprazole is unknown, but does not seem to be due to stimulation of the endogenous synthesis of prostaglandins since the effect was not blocked by indomethacin.

Animals↗

PubMed1983

The profilin--actin complex: further characterization of profilin and studies on the stability of the complex.

Two forms of profilin can be isolated from calf spleen profilactin by chromatography on phosphocellulose. They can be distinguished by C-terminal analysis, which suggests that one of them lacks the C-terminal tyrosine and the penultimate glutamine residue. This is confirmed by treatment of profilin (+Tyr) with carboxypeptidase A, which removes the C-terminal tyrosine (rapidly) and the penultimate glutamine residue (slowly), and thereby converts it to the other form as judged by chromatography on phosphocellulose. The two forms of profilin differ also in solubility and in mobility during so-called 'charge shift' electrophoresis, indicating differences in their ability to bind detergents. Recombination studies using profilin with or without a modified C-terminus demonstrated that this part of profilin is relatively unimportant for the interaction with actin. On the other hand, experiments with native and modified actin revealed that the C-terminus of actin is of the utmost importance for the stability of the profilactin complex. Analysis of the u.v. absorbance and far-u.v. circular dichroism spectra of profilin and actin did not reveal any major changes in the conformation of the proteins accompanying the modifications at the C-terminal ends. Finally, it is reported that purified profilactin contains variable amounts of a protein factor which causes an apparent stabilization of profilactin in solution.

Actins↗

PubMed1983

Differentiation among inhibitory actions of omeprazole, cimetidine, and SCN- on gastric acid secretion.

The action of the substituted benzimidazole omeprazole (H 168/68) was studied in three different in vitro preparations: the isolated guinea pig gastric mucosa, isolated intact and permeable rabbit gastric glands, and hog fundic microsomal membrane vesicles containing H+-K+-ATPase. The effects of omeprazole were compared with those of cimetidine and thiocyanate (SCN-). Under all the conditions studied, cimetidine only counteracted histamine-induced acid secretion, consonant with its H2-receptor antagonism. In contrast, omeprazole and SCN- were found not only to inhibit histamine-induced secretion but also basal acid formation and acid formation induced by dibutyryl cAMP and a high cell medium concentration of K+. Moreover, acid production induced by ATP in permeable gastric glands was antagonized by omeprazole and SCN-, whereas cimetidine was without effect. The interaction pattern of omeprazole and SCN- was differentiated by studies using the weak base antipyrine in the isolated mucosal preparation, where it was found that antipyrine could reverse the inhibition induced by SCN- but not that of omeprazole. Furthermore, omeprazole was found to inhibit the isolated H+-K+-ATPase, whereas cimetidine or SCN- was without effect. In the isolated mucosal preparation omeprazole caused an increase in K+ secretion rates in parallel with the inhibition of acid formation. This was in contrast to what was observed for cimetidine and SCN-, which exhibited no such increased K+ secretion. The results obtained from intact mucosa and isolated glands are in agreement with the ability of omeprazole to inhibit the isolated H+-K+-ATPase and thus provide evidence of a novel mechanism of action for this inhibitor.

Adenosine Triphosphatases↗