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Biomedical subjects

M Bickel

Publications and source records attributed to M Bickel.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats.

The effects of 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) on various experimentally induced ulcers and gastric acid secretion were investigated in rats. HWA 285 (10-50 mg/kg, p.o.) inhibited restraint and water-immersion-induced stress, ulcers, indometacin- and absolute ethanol-induced gastric ulcers and mepirizole-induced duodenal ulcers in rats in a dose-dependent manner. HWA 285 (10-25 mg/kg i.d.) had inhibitory effects on acetylsalicylic acid-induced ulcers. The healing of acetic acid-induced chronic ulcers was significantly accelerated by HWA 285 (25 mg/kg p.o.) when it was given twice daily for 7 consecutive days. When given orally (twice a day, 11 doses in total) before the induction of gastric ulcers by stress, cimetidine at 100 mg/kg aggravated the ulcers, whereas, HWA 285 at 25 mg/kg had not such an effect. In conscious pylorus-ligated rats, HWA 285 (10-100 mg/kg i.p.) showed a dose-dependent inhibition on basal and desglugastrin- and 2-deoxy-D-glucose (2-DG)-stimulated gastric acid secretion. In stomach-lumen perfused rats, HWA 285 (30 mg/kg i.v.) inhibited 2-DG-stimulated gastric acid secretion but not carbachol-stimulated gastric acid secretion. These results suggest that the anti-ulcer effects of HWA 285 are produced by cytoprotective and central anti-secretory activity without peripheral anti-cholinergic properties. Whether the central anti-secretory effects of HWA 285 play thereby the key role, have to be clarified in further investigation.

Acetates↗
PubMed1988

A substituted thieno[3.4-d]imidazole versus substituted benzimidazoles as H+, K+-ATPase inhibitors.

S 3337, 2-(2-ethylaminobenzylsulfinyl)-5,6-dimethoxybenzimidazole, and S 1924, 2-(5-methyl-2-picolylsulfinyl)-1H-thieno[3.4-d]imidazole, are members of new classes of H+, K+-ATPase inhibitors. Their effects on H+, K+-ATPase and 14C-aminopyrine uptake in gastric glands were studied as well as in vivo in pylorus-ligated rats, stomach-lumen-perfused rats and Heidenhain pouch dogs. Their inhibitory effects were compared with the effect of omeprazole. In pylorus-ligated rats the two compounds showed a similar effectiveness as omeprazole. In stomach-lumen-perfused rats and in particular in Heidenhain pouch dogs, S 3337 was clearly less effective than omeprazole, while S 1924 was similarly effective in all in vivo models and in the H+, K+-ATPase assay as omeprazole. The difference in potency between S 1924 and omeprazole on 14C-aminopyrine uptake in gastric glands can be explained by the lower pKa value of S 1924 (3.4) than that of omeprazole (4.0). Additionally, this study shows that there was no correlation between the effects in rats, particularly in pylorus-ligated rats, and in dogs for the H+, K+-ATPase inhibitors tested. It is concluded from this study that substituted thieno[3.4-d]imidazoles represent a new class of potent gastric acid inhibitors.

Adenosine Triphosphatases↗
PubMed1988

A review of the animal pharmacology of roxatidine acetate.

Roxatidine acetate (TZU 0460/HOE 760) [N-(3-[3-(1-piperidinylmethyl)-phenoxy]-propyl)acetoxyacetamide hydrochloride] is a specific and competitive H2-receptor antagonist with a chemical structure different from those of cimetidine, ranitidine and famotidine. Roxatidine acetate and its main metabolite roxatidine inhibit histamine-induced gastric acid secretion in vitro with a potency greater than that of cimetidine, and in the range of that produced by ranitidine. Gastric acid secretion following stimulation with dibutyryl cyclic adenosine monophosphate remains unaffected by roxatidine acetate. In vivo experiments in rats and dogs confirm these in vitro findings. Thus, in rats roxatidine acetate inhibits gastric acid secretion with similar values following intraduodenal or intraperitoneal injection, indicating excellent absorption of the drug from the gastrointestinal tract. In all studies it was shown that roxatidine acetate was more potent than cimetidine. In rats single or repeated dosing with roxatidine acetate did not influence drug metabolising enzymes in the liver nor did the drug show antiandrogenic activity in long term animal studies. Extensive general pharmacological studies with roxatidine acetate demonstrate the lack of effects on the central nervous system, on gastrointestinal motility, the autonomic nervous system and the cardiovascular and urogenital systems. Studies on the pharmacokinetics and metabolism of roxatidine acetate demonstrate that there is a presystemic deacetylation producing the main metabolite roxatidine, which is responsible for the in vivo effects of the drug.

Animals↗
PubMed1988

Chemical and biologic characteristics of roxatidine acetate.

Roxatidine acetate is a specific and competitive H2-receptor antagonist, as shown in isolated rabbit gastric glands or guinea pig atria preparations. The antisecretory effect of roxatidine acetate is mediated by its main metabolite, roxatidine. In the rat, roxatidine acetate was equipotent after intraduodenal and intraperitoneal administration, indicating excellent bioavailability. Roxatidine acetate and roxatidine were equipotent in the rat after intravenous administration. In the Heidenhain-pouch dog stimulated by food ingestion or maximal histamine dosing, roxatidine acetate and roxatidine proved to be 3-6 times more potent than cimetidine in inhibiting gastric acid secretion. From in vitro experiments it can be concluded that roxatidine acetate and ranitidine are equipotent. Roxatidine acetate has no antiandrogenic effects and does not influence drug-metabolizing enzymes in the liver.

Animals↗
PubMed1988

Granulocyte-macrophage colony-stimulating factor regulation in murine T cells and its relation to cyclosporin A.

The coordinated expression of the hematopoietic growth factors, interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in activated T cells suggests common synthetic pathways. However, cyclosporin A (CsA) appears to differentially effect the synthesis of these two lymphokines. When the supernatants from the concanavalin A-stimulated thymoma EL-4 or the T-cell hybrid 2B4 were assayed on the GM-CSF/IL3-dependent PT-18 and on the IL3-dependent DA-1 cell lines, IL3 activity could not be detected following CsA treatment, but substantial growth activity, which was identified as GM-CSF, was observed on the PT-18 cell line. CsA did not affect the kinetics of GM-CSF release, but inhibited the release of IL3 over a period of 40 h after the cells were stimulated and treated with CsA. In addition, CsA could be added up to 1 h after stimulation of the cells without affecting GM-CSF activity but inhibiting completely the IL3 activity. To substantiate the inability of CsA to inhibit GM-CSF activity, GM-CSF gene expression was evaluated. By Northern analysis GM-CSF mRNA was not inhibited by doses of CsA up to 1 microgram/ml. The data reveal that CsA can dissociate between the production of IL3 and GM-CSF, suggesting that these two CSFs are regulated by different mechanisms.

Animals↗
PubMed1987

Induction of granulocyte-macrophage colony-stimulating factor by lipopolysaccharide and anti-immunoglobulin M-stimulated murine B cell lines.

The present study was undertaken to elucidate whether B cell lymphoma and hybridoma cell lines can be stimulated by lipopolysaccharides (LPS) or by antibodies against immunoglobulin M (IgM) to produce granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF activity was assayed on the basophil/mast cell line PT-18 which is GM-CSF- and interleukin 3-dependent. Antibodies against murine recombinant GM-CSF were used to identify the colony-stimulating factor activity present in the supernatants of the stimulated B cell lines. When these cell lines were stimulated with LPS, two of five lymphoma and five of six hybridoma lines produced GM-CSF. Two cell lines, the B cell lymphoma M12.4.1 and the hybridoma TH2.2, were analyzed more extensively under serum-free conditions. In these two cell lines, the production of GM-CSF was dependent on the dose of LPS used and time of exposure. Antibodies against IgM stimulated the TH2.2 (IgM+) but not the M12.4.1 (IgM-) cells to produce GM-CSF. Northern blot analysis of the M12.4.1 and TH2.2 cells showed that mRNA of GM-CSF can be detected in LPS-stimulated but not in unstimulated cells. Our data show that transformed B cells can be stimulated to produce GM-CSF. The present data and previous studies on GM-CSF production by normal bone marrow-derived B cells suggest a possible participation of B cells in granulopoiesis.

Animals↗
PubMed1987

[Comparative studies of hexosaminidase P in the serum of pregnant females and hexosaminidase I2 in the serum of children with leukemia].

Hexosaminidase isoenzymes P from serum of pregnant women and I2 from serum of leukemic children were compared using various biochemical methods, namely, ion exchange chromatography, isoelectric focusing, and molecular weight determination by gel filtration. Isoenzyme I2 is activated by calcium, magnesium, and manganese. The molecular weight of isoenzyme I2 was 110,000 compared to 130,000 of isoenzyme P. The widely differing molecular weights exclude the so far suggested identity of both enzymes. Both isoenzyme P and isoenzyme I2 possess beta-chains, however, they differ in chain structure and glycosylation. This different structure of isoenzyme P may be one of the reasons for its increase during pregnancy due to the resulting impaired clearance by liver sinusoidal cells.

Child↗
PubMed1987

Inhibition of 14C-aminopyrine accumulation in isolated rabbit gastric glands by the H2-receptor antagonist HOE 760 (TZU-0460).

Acid secretion in isolated rabbit gastric glands was measured by means of the 14C-aminopyrine accumulation technique. Hoe 760 (TZU-0460) and Hoe 062, the desacetylated compound of Hoe 760, caused a concentration-dependent reduction of histamine (100 microM) induced aminopyrine-accumulation. The IC50-values were 3.16 +/- 0.84 microM (n = 5) and 1.58 +/- 0.6 microM (n = 6) for Hoe 760 and Hoe 062, respectively. In comparison an IC50 of 9.0 +/- 0.72 microM (n = 6) was obtained for cimetidine and 3.3 +/- 1.4 microM (n = 5) for ranitidine. The IC50-values of ranitidine, Hoe 760 and Hoe 062 were significantly different (p less than 0.05) from cimetidine. The addition of increasing concentrations of Hoe 760 to the histamine concentration-response curve caused a parallel rightward shift. The transformation of these concentration-response curves according to Arunlakshana and Schild indicated that this inhibition was caused by a competitive antagonism of the histamine receptor on the parietal cell. In agreement with these findings the dbc-AMP stimulated aminopyrine accumulation remained unaffected by the H2-receptor antagonists.

Aminopyrine↗
PubMed1987

Differential regulation of colony-stimulating factors and interleukin 2 production by cyclosporin A.

Stimulation of T lymphocytes with mitogens or antigens is followed by proliferation and lymphokine production. Although cyclosporin A (CsA), an immunosuppressive drug, has been shown to inhibit the production of certain lymphokines, including interleukin 2 (IL-2), interleukin 3 (IL-3), and gamma-interferon, its effect on the production of granulocyte/macrophage colony-stimulating factor (GM-CSF) has not been evaluated. In the current study, concanavalin A (Con A)-stimulated murine spleen cells secreted GM-CSF, IL-3, and IL-2, and in the presence of CsA (0.1-1.0 micrograms/ml), IL-2 and IL-3 activities were inhibited. In contrast, significant activity was detected when the CsA-treated culture supernatants were assayed on a cell line that is dependent on GM-CSF and/or IL-3. Similar CsA-resistant activity was observed when the EL-4 thymoma cells were stimulated with a phorbol ester [phorbol 12-myristate 13-acetate (PMA)] in the presence of CsA. The activity resistant to CsA was identified as GM-CSF by the ability of specific antibodies against murine recombinant GM-CSF to neutralize its activity. These findings indicate that GM-CSF, in contrast to IL-2 and IL-3, was not inhibited by CsA. In additional experiments, transfer blot of poly(A)+ RNA isolated from PMA-induced EL-4 cells in the presence or the absence of CsA was hybridized with GM-CSF and IL-2 cDNA probes. Expression of the GM-CSF gene in EL-4 cells was detected independent of CsA, whereas CsA inhibited the expression of the IL-2 gene. The present data show that production of IL-2 and IL-3, but not that of GM-CSF, is inhibited by CsA and suggest a differential control mechanism for lymphokine synthesis in T lymphocytes.

Animals↗
PubMed1987

The effect of supragingival plaque control on the composition of the subgingival microflora in human periodontitis.

The aim of this study was to evaluate the effect of supragingival plaque control on the composition of the subgingival microflora. 8 subjects with moderate to severe periodontitis were chosen for the study. Sites with periodontal destruction (GI greater than 2; probing depth greater than 6.5 mm; vertical alveolar bone loss on radiographs) were submitted to professional plaque control 3 X a week for 3 weeks. Contralateral sites received no prophylaxis and served as controls. Patients maintained usual oral hygiene during the observation period: it consisted exclusively of tooth brushing once or twice a day with no use of interdental cleaning aids. Clinical examination and bacterial sampling were performed every week. At the end of the study, PlI scores for the experimental sites showed a marked diminution compared with the control sites. No variations were observed in GI or probing depth in test or control sites during the study. The composition of subgingival plaque in both groups showed no significant variations during that period.

Adult↗
PubMed1987

Densitometric analysis of lower molar interradicular areas in superposable radiographs.

Superposable radiographs of lower molar areas were obtained by means of a specially designed film holder and a gnathostat maintained in a constant position with respect to long-cone radiological equipement. A quantitative evaluation of the bone mass in the interradicular area was obtained by scanning the area under a photodensitometer. A photodensitometric scan of the image of an aluminium wedge adapted to each radiograph was also performed. This allowed the transformation, with the aid of a computer, of the photodensitometric recording of bone into a tracing of mm of aluminium equivalents. The reproducibility and precision of the method were verified by comparing magnifications of repeated radiographs, by photodensitometric readings of radiographs developed in different batches and by repeated quantitative readings of the same film. The method allowed one, for instance, to follow quantitatively the healing of a radiographically visible periapical lesion. It was also used to evaluate quantitatively, in the interradicular area, bone changes which could not be seen with the marked eye.

Densitometry↗
PubMed1987

Longitudinal quantitative radiodensitometric study of treated and untreated lower molar furcation involvements.

38 first or second lower molars from 16 patients showing furcation involvements of degrees 1 and 2 were treated after motivation and hygiene instruction, either by subgingival curettage, or by the modified Widman surgical procedure or by furcation plasty. The plaque index, the gingival index of inflammation and the depth of interproximal and interradicular pockets were recorded before and up to 1 year after the 3 therapeutical procedures. The above clinical indices were also followed for 2 years in 15 lower molars from 7 untreated patients. A quantitative radiographical analysis of the interradicular bone was performed in all patients, by using superposable identical radiographs and a computer-assisted photodensitometric technique. In the 3 groups of treated patients, the clinical scores were, in general, improved by the 3 therapeutic modalities. In the furcation areas, the plaque index was always higher on the lingual side, whereas the depth of "horizontal" pockets was always greater on the buccal side. Except for the lesions treated by furcation plasty, no change could be noticed clinically in the depths of vertical or horizontal penetration of a periodontal probe in the furcation areas. The quantitative radiographic analysis, however, clearly showed a loss in the first 2 mm of superficial bone during the 2 months following the 3 therapeutical procedures: this loss was followed by a statistically significant recovery and, for the group treated by curettage, even by a net gain during the 6 to 12 months following therapy. The radiographical density of the deeper layer of bone did not change in the group treated by curettage only. It showed a loss in the first 2 months following the 2 surgical procedures but a statistically significant recovery in the months thereafter. As for the group of untreated patients, at the examinations performed initially, 6 months, 1 and 2 years later, the number of plaque-free and non-bleeding sites in the furcation areas was lower on the lingual as compared to the buccal side, whereas the frequency distribution of furcation involvements was similar on both aspects. No significant changes were found in the various clinical parameters throughout the 2 years of the study. On the contrary, a significant loss of average density of the superficial layer of interradicular bone was already measured on the superposable radiographs 6 months after the initial examination and was found to increase thereafter. No changes of radiodensity could be measured for the deeper layer of bone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

The effect of plaque control after scaling and root planing on the subgingival microflora in human periodontitis.

The aim of the present study was to evaluate the effect of a strict supragingival plaque control regimen on bacterial repopulation following scaling and root planing. 7 patients with moderate to severe inflammatory periodontal disease received a full-mouth scaling and subgingival curettage. Using a split-mouth design, 2 sites of opposite quadrants were submitted to professional supragingival plaque control 3 X a week while the contralateral sites served as controls. Clinical and bacterial examination were performed on days 7, 14, 28, 49, 56, 63 and 70 following therapy. All clinical parameters (P1I, GI, probing depth, attachment levels) showed significant improvement after scaling and root planing. Shifts in the subgingival bacterial population observed by dark field were also noticed following curettage: there was a decrease in the proportions of spirochetes and motile rods and an increase in that of coccoid cells. However, bacterial distribution tended to return to base line values towards the end of the observation period. No difference in the pattern of bacterial recolonization of the subgingival area could be detected between the sites under strict supragingival plaque control and the control sites.

Adult↗
PubMed1987

Type IV collagen antigens in serum of rats with experimental fibrosis of the liver.

Specific and sensitive radioimmunoassays for the N-terminal (7S-collagen) and C-terminal (NC 1) crosslinking domains of type IV collagen were used to study the effects of prolonged treatment of rats with CCl4 on the concentrations of these antigens in serum. After four to six weeks of CCl4 treatment a highly significant increase of type IV collagen antigen levels in serum was to be seen. These elevated levels exhibited a significant correlation to the increased amounts of hydroxyproline in liver samples, when the samples were taken during CCl4 treatment. Analysis of the molecular weight distribution of serum antigens by gelfiltration revealed for 7S-collagen a bimodal distribution, whereas NC 1 eluted mainly as one peak. This peak coeluted with the high molecular weight peak of 7S-collagen, suggesting that this peak might represent intact type IV collagen. The lower molecular weight peak of 7S-collagen antigen eluted at a position which was comparable to standard 7S-collagen. Determination of type IV collagen antigens in serum might be of diagnostic usefulness for the follow up and treatment control of hepatic fibrosis.

Animals↗
PubMed1987

Relationship between tuberculous scar and carcinomas of the lung.

Results of a transversal case-control study are reported which shows that there is a statistically significant association between tuberculous scars and carcinoma of the lung. Accordingly the possibility of malignancy has to be kept in mind when radiological or scintigraphic scanning reveal the presence of lung scars.

Cicatrix↗
PubMed1986

The stimulatory effect of forskolin on gastric acid secretion in rats.

Adenylate cyclase is involved in the histamine pathway of the parietal cell. We therefore studied the effect of forskolin, a direct activator of the membrane-bound adenylate cyclase, on gastric acid secretion in anaesthetized rats. Forskolin in the range of 0.1-1 mg/kg i.v. caused a dose-dependent stimulation of acid secretion. Higher doses were not tolerated. The duration of action of the forskolin-induced acid secretion was also dose-related. The combined infusion of forskolin (0.3 mg/kg per h i.v.) and histamine at a low rate (0.5 mg/kg per h i.v.) produced a maximal stimulation of acid secretion which was comparable to that with a histamine infusion of 10 mg/kg per h i.v. without forskolin. Administration of desglugastrin at a low rate (10 micrograms/kg per h i.v.) plus forskolin by i.v. infusion produced similar results. In contrast, infusion of carbachol (3 micrograms/kg per h i.v.) together with forskolin caused only an additive effect on acid secretion. Including an isobutyl-methyl-xanthine (IBMX) i.v. injection of 3 mg/kg at the beginning of the forskolin infusion (0.3 mg/kg per h i.v.) produced an acid output after 60 min which was approximately 50% of the maximal stimulation during a histamine (10 mg/kg per h i.v.) infusion. The IBMX/forskolin-induced stimulation was completely inhibited by 0.5 mg/kg omeprazole i.v. while the equipotent antisecretory dose (during histamine stimulation) of cimetidine caused only a weak decrease in acid output.

1-Methyl-3-isobutylxanthine↗