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Biomedical subjects

E Carlsson

Publications and source records attributed to E Carlsson.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1986

Cryoultramicrotomy and immunocytochemistry in the analysis of muscle fine structure.

Cryoultramicrotomy, which avoids the use of harsh fixation procedures, deleterious dehydration and plastic embedding can be combined with immunocytochemistry to determine the ultrastructural localization of cellular proteins. Our attempts to use the cryosectioning technique in combination with immunolabelling to bridge the gap between light and electron microscopic analysis of muscle morphology have enabled us to obtain new information on fibre typing at the ultrastructural level. Furthermore, we have obtained a marked improvement in the resolution of myofibrillar structures by using semithin cryosections for fluorescence microscopy. Data are also presented on correlated light and electron microscope immunocytochemistry of myocardial intermediate filaments confirming the presence of longitudinally oriented intermediate filaments of desmin in the region of the intercalated discs of mammalian cardiac myocytes, whereas elsewhere in the myocyte the bulk of intermediate filaments of desmin is concentrated in the intermyofibrillar space at the level of the Z disc.

Animals↗
PubMed1985

Urinary tract infection in children with type I diabetes.

The prevalence and incidence of bacteriuria in 304 girls and 337 boys with type I diabetes was studied by screening for bacteriuria at their regular outpatient controls. In 90 girls and 108 boys a urine specimen was sampled every third month during a year. The prevalence of bacteriuria was 3/304 in girls and 0/337 in boys. During the one year follow-up one of the 90 girls had pyelonephritis and two cystitis while none of the boys had bacteriuria. It is concluded that the rate of urinary tract infection in young diabetic persons does not differ from that present in healthy young people.

Adolescent↗
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

Toxicological studies on omeprazole.

As part of the safety evaluation of the gastric antisecretory drug, omeprazole, toxicological studies have been performed in several species of animals. The acute toxicity after oral administration to rodents was low. The oral LD50 value was above 4 g/kg. The general toxicity after repeated administration has been studied in rats and dogs. No clinical signs of adverse reactions were seen. Some minor changes in hematology parameters were observed. In rats and mice decreases in the erythrocyte count, hematocrit and hemoglobin have occasionally been found at doses of 125 mumol/kg/day and more. Hyperplasia of oxyntic mucosal cells, concomitant with increases in stomach weight, oxyntic mucosal thickness and folding, has been observed in the species investigated, the dog, rat and mouse. In addition, slight chief cell atrophy and eosinophilia of the chief cell granules were observed in rats. The oxyntic mucosal effects were reversible upon treatment being discontinued. In the oncogenicity studies, gastric carcinoids occurred in the rat but not in the mouse. Investigations of the carcinoids showed that the vast majority of the endocrine cells could be characterised as ECL-cells. The hyperplasia of oxyntic mucosal cells, including hyperplasia of endocrine ECL-cells and development of gastric carcinoids in rats, is attributable to the pronounced hypergastrinemia produced as a secondary effect of almost complete inhibition of acid secretion by the large doses of omeprazole used in the toxicity studies. In agreement with this hypothesis, the hyperplasia of the oxyntic cells was prevented by antrectomy. The reproduction studies performed in rats and rabbits showed no sign of fetal toxicity or teratogenic effect. The results of the short-term mutagenicity tests, Ames test, the micronucleus test in mice and the mouse lymphoma test were all negative.

Administration, Oral↗
PubMed1984

[Acid secretion inhibition with new mechanisms of action: substituted benzimidazole].

Omeprazole and other substituted benzimidazoles produce a marked inhibition of gastric acid secretion with a long duration of action. Any kind of stimulated acid secretion is inhibited by the substituted benzimidazoles. The inhibitory mechanism of action is very selective. The substituted benzimidazoles inhibit the parietal cell H+, K+-ATPase, an enzyme which is the proton pump in the secretory membrane of the parietal cell. An oral daily dose of 15 mg omeprazole in humans produced about 80% acid inhibition just after dosage and about 40% 24 hours later. Preliminary results in duodenal ulcer patients show that a daily dose of 20-60 mg omeprazole produces fast ulcer healing in almost all patients.

Animals↗
PubMed1984

Effects of in vivo treatment with isoprenaline or prenalterol on beta-adrenoceptor mechanisms in the heart and soleus muscle of the cat.

The full agonist isoprenaline (5.3-6.6 nmol/kg . min) and the partial beta-adrenoceptor agonist prenalterol (10.6-13.3 nmol/kg . min) were administered to cats continuously via osmotic minipumps (i.p.). After seven days the functional and adenylate cyclase responsiveness to the agonists, as well as the beta-adrenoceptor-binding characteristics, were studied in cardiac and soleus muscle preparations in vitro. After isoprenaline pretreatment, the papillary muscles and soleus muscle strips wer 15-18 times less sensitive to isoprenaline compared with muscles from control cats. The stimulatory potency (pD2) of prenalterol in the papillary muscle was not changed significantly. The affinity of the agonists to the beta-adrenoceptors was unaffected in both tissues by the pretreatment, but the densities of beta-adrenoceptors were significantly reduced, by 36% (myocardium) and 47% (soleus) respectively. In the cat papillary muscle the intrinsic sympathomimetic activity (ISA) of prenalterol on contractile parameters was reduced from 84 (Tmax), 69 (dT/dtmax) and 71% (dT/ dtmin ) in control animals, to 33, 22 and 28%, respectively in the animals pretreated with isoprenaline. Prenalterol pretreatment did not induce any marked changes, either in the stimulatory potency or affinity of the agonists in the two tissues or in the maximal response (ISA) of prenalterol in the papillary muscle. The marked reduction in the stimulatory potency of isoprenaline and the reduced ISA of prenalterol in the myocardium after isoprenaline pretreatment can not be explained by the reduction in beta- adrenoceptor density alone. Since the affinity to the beta- adrenoceptors is unaffected, a reduced efficiency in the signal transmission must be the main cause.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1984

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs.

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Animals↗
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

Ultrastructural localization of M-band proteins in chicken breast muscle as revealed by combined immunocytochemistry and ultramicrotomy.

Cryo-ultramicrotomy and "conventional" plastic sectioning have been used in combination with extraction and immunolabeling techniques to determine the location of the two M-band proteins characterized to date, MM-creatine kinase (MM-CK: Mr, 80,000) and M-protein "myomesin" (Mr, 165,000) within the M-region of chicken pectoralis muscle. The following main results were obtained. (1) The M-band in chicken pectoralis muscle contains five major striations (M1, M4 and M4', M6 and M6' in the terminology of Sjöström & Squire, 1977a). (2) Extraction of the bulk of the electron-dense M-band with low ionic strength removes the M-striations M1, M4 and M4' while M6 and M6' are retained. Cross-sections through the M-region of such muscles lack primary M-bridges connecting the thick myosin filaments. (3) Labeling with antibodies against MM-CK enhances the M-striations M4 and M4'; sometimes the whole region between M4 and M4' is labeled. (4) Incubation with antibodies against myomesin results in the labeling of the whole M-band from M6 to M6'; no label is found in the rest of the bare zone outside M6 and M6'. (5) Incubation of low ionic strength extracted muscle fibers with antibodies against myomesin leads to an "incomplete" labeling of the M-band between M6 and M6'; lines M6 and M6' are sometimes seen to be enhanced presumably due to antibody labeling. From these results it is concluded that MM-CK is the major protein of the M4 and M4' (and possibly also of the M1) M-bridges. Myomesin is bound within the M-band along the thick filaments from M6 to M6'. Two hypothetical models for the possible location of myomesin are discussed. According to these models myomesin would either make up the M-filaments or be directly attached to and along the central bare zone of thick myosin filaments.

Animals↗
PubMed1983

Cardiovascular malformations associated with administration of prenalterol to young chick embryos.

Prenalterol (levo-1-[4-hydroxyphenoxy]-3-isopropyl-amino-2-propanol), a new stimulant of cardiac beta-adrenergic receptors in man, induces cardiovascular malformations when topically administered to 2 1/2- through 5 1/2-day chick embryos (Hamburger-Hamilton stages 17-27). Ventricular septal defects (VSD) located in the middle portion of the conal septum and classified as the simple, punched-out type VSD without septal malalignment were the predominant malformations observed throughout the developmental period tested. Arch malformations of the aortic circulation were also observed throughout the test interval, while anomalies of the pulmonary system were observed only at Hamburger-Hamilton stages 17 and 26-27. At stage 25 prenalterol demonstrated an acute toxicity significantly less than (1/50-1/20) epinephrine (P = .035 at concentrations of 8-10 mM) but was relatively equipotent with epinephrine in producing cardiovascular malformations. The effective median concentrations of the two agents were comparable (0.5-1.0 mM). The spectra of malformations induced by prenalterol and epinephrine were qualitatively similar. Malformations included absence of the right and/or left third aortic arch (innominate arteries), persistent remnant of the left fourth aortic arch, and VSD. These results support a previously proposed theory by these investigators that hyperstimulation of cardiac beta-adrenergic receptors in the chick embryo produces cardiovascular malformations.

Abnormalities, Drug-Induced↗
PubMed1983

Characterization of mechanical effects and beta-adrenoceptor binding of prenalterol in rat myocardium.

The partial beta-agonist prenalterol has been found to differ from the full agonist isoprenaline in some aspects of its cardiac action. We therefore studied in rat myocardium whether prenalterol elicited the same qualitative changes of the contraction-relaxation cycle as was previously found for isoprenaline. We also measured binding of prenalterol to beta-adrenoceptors. Prenalterol augmented relaxation more than contraction and thus evoked the same qualitative changes of the contraction-relaxation cycle as did isoprenaline. However, the response developed slower than that to isoprenaline, and the effect on relaxation followed a more protracted time course than the effect on contraction. Prenalterol bound non-selectively to beta 1- and beta 2-adrenoceptors in both heart and lung broken cell preparations. pKd for binding to beta-adrenoceptors and pD2 values for functional effects in heart were similar, i.e. prenalterol had to occupy half the amount of beta-adrenoceptors in order to evoke half-maximal functional effects. The non-selective alpha-blocker phentolamine potentiated the effects of prenalterol on contraction, but did not change the equilibrium binding of prenalterol to cardiac beta-adrenoceptors. Phentolamine did not change the potency and efficacy of isoprenaline. Thus, although prenalterol qualitatively evoked the same response as isoprenaline, it also exhibited some properties which differed.

Animals↗
PubMed1983

Lack of functional influence by prenalterol through alpha 1-adrenoceptors in rat myocardium.

Some of the cardiac properties of the partial beta-agonist prenalterol may indicate a contribution from alpha 1-adrenergic stimulation. We therefore studied whether prenalterol interacted with alpha 1-adrenoceptors in rat myocardium. Combination with propranolol did not reveal an alpha 1-adrenergic inotropic effect of prenalterol in papillary muscles. Neither did prenalterol block the alpha 1-adrenergic response to phenylephrine. In myocardial cells, prenalterol inhibited 3H-prazosin binding to alpha 1-adrenoceptors only at very high concentrations. Prenalterol thus exhibited no functionally important interactions with alpha 1-adrenoceptors in myocardium, and its properties cannot be accounted for in terms of contribution from alpha 1-adrenergic effects.

Animals↗
PubMed1983

CT attenuation ratio of myocardium and blood pool in the normal and infarcted canine heart.

The CT attenuation of the myocardium varies with the contrast medium concentration of the blood at steady state. The demonstration of myocardial infarcts depends on the differences of CT numbers within the myocardium. In order to make possible objective estimation and measurement of myocardial ischemia the normal regression between CT attenuation of the blood pool and the myocardium has been determined in 13 dogs. The relationship has been applied to 15 dogs with experimental infarcts examined with contrast enhanced CT. The results indicate that this method may be of value in identifying and sizing myocardial infarcts of different ages in patients.

Animals↗
PubMed1983

Intrinsic sympathomimetic activity of the partial agonist prenalterol in relation to beta adrenoceptor interaction in various tissues, in vitro.

The intrinsic sympathomimetic activity (ISA) of prenalterol was studied in isolated tissues from different species, including tissues containing predominantly beta-1 adrenoceptors (cardiac preparations from cat, rabbit, rat and guinea pig) and tissues characterized by beta-2 adrenoceptor predominance (cat skeletal muscle and rat uterus). The ISA of prenalterol, varying between 0 and 94% in the various tissues, was found to be positively correlated to the stimulatory potency (-log EC50) of isoproterenol and prenalterol. In the cardiac preparations from the rabbit there was an interindividual variation in the ISA of prenalterol, which was also positively correlated to the stimulatory potency of the beta agonists. The density of beta adrenoceptors in the tissues studied correlated neither to the variable ISA of prenalterol nor to the -log EC50 values of isoproterenol or prenalterol. The affinities of isoproterenol and prenalterol for the beta adrenoceptors were subject to less variation than were the stimulatory potencies of the agonists. The degree of separation between the concentration-effect curves for beta adrenoceptor occupancy and mechanical performance, expressed as the ratios Kd/EC50 for both agonists, were positively correlated to the corresponding ISA of prenalterol in various tissues. However, a considerably steeper relationship between occupancy/potency ratio and ISA was seen with prenalterol than with isoproterenol. The present data suggest that the level of ISA of the partial agonist, prenalterol, depends upon the efficiency of signal transmission from the activated receptor to the final end-organ response. The separation between the concentrations of the full agonist, isoproterenol, required for receptor occupancy and response serves as an index of the efficiency of coupling between the stimulus, elicited by activation of the receptor, and the response.

Adrenergic beta-Agonists↗
PubMed1983

[Diagnosis of myocardial infarction by CT: the study of an initial filling defect and late enhancement of the infarcted myocardium after injection of contrast material].

Several animal experimental studies have shown that the enhanced CT gives the direct evidence of acute myocardial infarction characterized by an initial filling defect and late enhancement in the site of the damaged myocardium. Therefore, we studied experimentally and clinically the diagnostic value of these CT findings in detecting and quantitating recent and remote myocardial infarctions. Sixteen mongrel dogs with anterior myocardial infarction were subjected to the present study. The cardiac infarction within one month after coronary arterial ligation was visualized as a filling defect by early CT scan after intravenous injection of contrast material. The delayed scan after the injection showed late enhancement of the infarcted area in both acute and chronic phases. Post mortem histologic studies confirmed that the area of filling defect coincided with the necrotic myocardium and late enhancement coincided with the totally infarcted myocardium including healed scar. The total infarct size measured from CT images was closely correlated with histo-pathological infarct volume (r = 0.96). In the clinical study, the enhanced CT was performed on 112 patients with myocardial infarction and 12 patients with angina pectoris. The filling defect and late enhancement of the infarcted myocardium in the antero-septal or apical wall were detected as clearly as in the animal experiment; the former was found in 85% of the patients with recent infarction, and the latter was detected in about a half of the patients with both recent and remote infarctions. However, these CT findings were not clearly recognized in the patients with infero-posterior infarction, subendocardial infarction or angina pectoris. These results indicate the usefulness of CT in the noninvasive diagnosis and a follow-up study of myocardial infarction.

Animals↗
PubMed1983

Inhibition of gastric acid secretion by omeprazole in the dog and rat.

The gastric antisecretory properties of omeprazole, a new potent substituted benzimidazole, have been evaluated in dogs and rats. Omeprazole was compared with another benzimidazole, picoprazole (H 149/94), and with the histamine H2-receptor antagonist cimetidine. The intravenous or intraduodenal administration of omeprazole in the gastric fistula dog inhibited histamine- and pentagastrin-stimulated acid secretion. The intravenous and intraduodenal, ED50 values for inhibition of histamine-stimulated secretion were 0.35 and 0.26 mumol/kg, respectively. Omeprazole was found to be approximately 5-10 times more potent than both picoprazole and cimetidine. After oral omeprazole administration in the Heidenhain pouch dog, the ED50 on histamine-stimulated acid secretion was found to be 1.2 mumol/kg, which corresponded to a potency 2 and 3.5 times greater than that of cimetidine and picoprazole, respectively. Measurement of the plasma concentration of unchanged omeprazole revealed an intraduodenal bioavailability of approximately 70% whereas the oral bioavailability was only approximately 15%. This variation is probably a result of partial degradation of omeprazole in the acid gastric juice. Single intraduodenal doses of omeprazole had a long-lasting inhibitory effect on histamine-stimulated acid secretion in the dog. After a dose of omeprazole, which produced total inhibition initially, the antisecretory effect was detectable for 3-4 days. Omeprazole inhibited basal and stimulated acid secretion in the rat. The intravenous ED50 was calculated to be 1.5 mumol/kg, whereas the oral potency was about 10 times lower. The effect in the rat was also of long duration. After a dose giving maximal inhibition, control acid secretion was restored after approximately 13 h.

2-Pyridinylmethylsulfinylbenzimidazoles↗