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Biomedical subjects

R Forster

Publications and source records attributed to R Forster.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effect of iron succinyl-protein complexes on gastrointestinal motility in the fasting dog.

Studying the gastrointestinal motor effects of iron compounds may help to elucidate the mechanism originating the gastrointestinal side effects of frequently reported during martial therapy. The aims of the present study were: (1) to examine the gastrointestinal motor effects of ferrous sulfate (reference compound) and (2) to compare its effects with those of two iron succinyl-protein complexes (ITF 1096 and ITF 282, an iron-albumin and iron-casein complex, respectively). In 6 fasting, conscious dogs, fitted with 8 bipolar electrodes and 3 strain-gauge force transducers along the gastrointestinal tract, gastrointestinal motor activity was recorded. Ferrous sulfate and iron succinyl-protein complexes were administered by an orogastric tube at two dose levels: the lower and higher dose levels were approximately equivalent to 10 and 30 mg/kg as Fe, respectively. In control experiments, 154 mM NaCl, ITF 211 (succinylated albumin) and ITF 297 (succinylated casein) were used. Administration of 154 mM NaCl did not affect gastrointestinal motility nor did it disrupt migrating motor complex (MMC) cycling. ITF 1096 and ITF 282, only at the higher dose, lengthened the MMC period and increased intestinal, but not gastric spike activity. The effects of ITF 211 and ITF 297 were similar to those of ITF 1096 and ITF 282. Ferrous sulfate, at the lower dose, lengthened the MMC period; the higher dose disrupted MMC cycling and induced intense, irregular spike bursts in the stomach and in the small bowel, accompanied, in 3 out of 6 dogs, by a prolonged tonic contraction of the upper small bowel. Four out of 6 dogs vomited after the higher dose of ferrous sulfate. No vomiting was observed with any of the other treatments. We conclude that ITF 1096 and ITF 282 have a markedly better gastrointestinal tolerability than ferrous sulfate.

Animals↗
PubMed1991

Patient advocacy in Austria.

A presentation and discussion of a model of patient advocacy that can be viewed as the first comprehensive project of its kind in Austria. This service is in existence as a pilot project in only two psychiatric hospitals where some components of patient advocacy are being tested; the project refers to a concept of advocacy which is part of a draft bill on involuntary commitment that will possibly be passed this year.

Austria↗
PubMed1990

Lonidamine: a non-mutagenic antitumor agent.

Lonidiamine is a novel indazole-carboxylic acid with antitumour properties; it has been studied for potential mutagenicity in a comprehensive battery of tests. In assays for the induction of gene mutations in prokaryotes (Ames test) and eukaryotes (induction of HPRT mutations in CHO cells), negative results were obtained. There was no evidence of the induction of chromosomal damage in cultured mammalian cells in vitro. No mutagenic activity was observed in tests for chromosomal damage in vivo, in somatic cells (micronucleus test) or in germinal cells (dominant lethal test). These negative results are consistent with observations indicating that lonidamine affects cellular energy processes, rather than the mechanisms of cell division. The lack of mutagenic properties suggests that lonidamine may present significant advantages in treatment of some tumours, offering a reduced risk of resistant clones, secondary cancer and heritable genetic damage.

Animals↗
PubMed1989

Spinal opioids and the treatment of the obstetric patient with cardiac disease.

The administration of narcotics into the spinal or epidural space has proven to be efficacious in the relief of mild to moderate pain. Unlike local anesthetics, intraspinal opioids are not associated with a decrease in systemic vascular resistance. Recent research has shown that opioids alone, or combined with local anesthetics, offer distinct advantages over the use of local anesthetics, alone when providing analgesia for the pregnant patient with cardiac disease.

Analgesia↗
PubMed1988

High-dose-level effects in mutagenicity assays utilizing mammalian cells in culture.

We report here results obtained using sodium chloride and potassium chloride as model compounds to investigate the effects of high dose levels and osmolarity-mediated artefacts in mutagenicity assays using cultured mammalian cells. Three assay systems were used with different genetic end-points: (i) mutation to 6-thioguanine resistance in Chinese hamster V79 cells; (ii) induction of chromosome aberrations in Chinese hamster ovary cells; and (iii) induction of unscheduled DNA synthesis in HeLa S3 cells. In V79 cells we observed sporadic increases in mutation frequency after treatment with sodium chloride. Potassium chloride increased the mutation frequency in a narrow interval of dose levels. Chromosome aberrations were induced by both compounds at the highest concentrations tested, confirming previously published data; the effects of potassium chloride were more marked. The chromosome aberrations observed included both deletions and exchange figures. Neither compound induced UDS in our experiments. We performed the Ames test as a check for mutagenic contaminants and both compounds gave entirely negative results. Although the osmolarities of sodium chloride and potassium chloride solutions were similar, the effects of potassium chloride were always greater at equivalent concentrations; the nature of the solute, and not only the observed osmolarity, appears to influence the results obtained. Similarly, we have observed that dimethylsulphoxide causes a marked increase in the osmolarity of the culture medium without any obvious induction of chromosome aberrations. Although the presence of S9 had little effect on the osmolarity of the medium, differences in response were observed after treatments with or without S9. For the two model compounds it appears that an osmotic mechanism alone does not provide a sufficient explanation of the findings.

Animals↗
PubMed1987

Evaluation of the genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO), a broad-spectrum pesticide, in multiple in vivo and in vitro short-term tests.

The genetic and embryotoxic effects of bis(tri-n-butyltin)oxide (TBTO) were evaluated in multiple in vivo and in vitro short-term tests preparatory to its potential wide use as a molluscicide in control of schistosomiasis. When tested in the rec assay in Bacillus subtilis, TBTO was not mutagenic and it did not induce reverse mutations in Klebsiella pneumoniae. Neither in the presence nor in the absecne of rat liver activation system did TBTO produce point mutations in Salmonella typhimurium strains TA1530, TA1535, TA1538, TA97, TA98 or TA100. TBTO was matagenic in strain TA100 in a fluctuation test, but only in the presence of rat liver S9 (Aroclor-induced). TBTO did not induce gene mutations in the yeast Schizosaccharomyces pombe, mitotic gene conversions in the yeast Saccharomyces cerevisiae, nor sister-chromatid exchange in Chinese hamster ovary cells in the presence or absence of rat or mouse liver S9. In the latter cells, structural chromosomal aberrations, endoreduplicated and polyploid cells were induced. TBTO did not induce gene mutations in V79 Chinese hamster cells (to 8-azaguanine-, ouabain- or 6-thioguanine-resistance) in the presence of a rat liver postmitochondrial fraction or in cell (hamster embryo cells and human and mouse epidermal keratinocyte)-mediated assays. In mouse lymphoma cells, TBTO did not induce 6-thioguanine- or BUdR-resistant mutations. As many tumour promoters inhibit metabolic cooperation between V79 Chinese hamster 6-thioguanine-resistant/-sensitive cells, TBTO was tested but showed no such activity. TBTO was examined for the induction of recessive lethal mutations in adult Berlin K male Drosophila melanogaster, either by feeding or by injection. Doses of 0.37 or 0.74 mM did not increase the number of X-linked recessive lethal mutations. An increased number of micronuclei was observed in the polychromatic erythrocytes of male BALB/c mice 48 h after a single oral dose of TBTO (60 mg/kg bw), while a lower dose (30 mg/kg bw) was ineffective. Neither of the two doses had induced micronuclei 30 h after treatment. The reproductive toxicity of TBTO was studied in NMRI mice. In a 10-day toxicity study, the LD50 and LD10 were 74 and 34 mg/kg bw, respectively. An increased frequency of cleft palates was seen in the fetuses of mice (compared with controls, 0.7%) treated orally during pregnancy with 11.7 mg/kg TBTO (7%), 23.4 mg/kg (24%) or 35 mg/kg (48%).(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗
PubMed1982

The pathogenesis of "hot" and "cold" follicles in multinodular goiters.

The prominent characteristics of euthyroid and hyperthyroid human nodular goiters are the regional variability of iodine metabolism and the appearance of "hot" autonomous follicles. No explanation for the pathogenesis of the interfollicular heterogeneity of iodine turnover has yet been offered. We have investigated whether the recently demonstrated polyclonality of normal follicular epithelia could possibly be related to goiter heterogeneity. The present work demonstrates, by means of autoradiographic and histological techniques, that single cells or tiny cell families with widely differing metabolic properties are normally present within single mouse, rat, and human thyroid follicles. In animals, intercellular heterogeneity is demonstrated in respect to 1) iodinating capacity, 2) peroxidase content, 3) endocytotic response to TSH, and 4) proneness to replicate. Moreover, [3H] thymidine labeling of stimulated mice thyroids reveals that mitotic cells are not randomly distributed; some follicles contain large colonies of rapidly replicating cells, and these clonogenic cells give rise to new follicles. Since simple goiter formation invariably implies replication of normal thyroid follicles, we conclude that the large differences in iodine turnover among the follicles of simple goiters are a consequence of the generation of new, metabolically heterogeneous follicles from genetically distinct cell clusters existing with the epithelia of all normal mother follicles.

Animals↗
PubMed1981

Apparent activation of 2-acetylaminofluorene and some aromatic amines by cytosolic preparations.

The results presented here confirm that 2-acetylaminofluorene (AAF) can be activated to a mutagen by S105 rat liver post-microsomal fraction. The activity is Aroclor-inducible. It appears partly NADPH-independent, but on repeated centrifugation the NADPH independence is lost though the NADPH-dependent activation is retained. S105 activation is obtained whether the fraction is prepared with 0.15 M KCl or 0.25 M sucrose. Increasing amounts of S105 give increasing activation, with no evidence of an optimum. Activation by S105 is reduced in the presence of excess S9 and is inhibited by norharman. Under the same conditions, S105 produces mutagenic metabolites of 2-aminofluorene and 2-aminoanthracene but not ethidium bromide, dimethylaminoazobenzene or benzo(alpha)pyrene.

2-Acetylaminofluorene↗
PubMed1981

Enhancement of S9 activation by S105 cytosolic fraction.

The addition of supplementary cytosolic fraction greatly enhances the activation of 2-acetylaminofluorene (AAF) by uninduced 9,000 x g supernatant fractions (S9) in the Ames test. Uninduced S9 is poor at activating AAF in the Ames test (although it is effective in the liquid based fluctuation test) probably because cytosolic material diffuses into the bottom agar. An enhancing effect of cytosol supplementation was also observed with 2-aminoanthracene (AA) and 2-aminofluorene (AF) with uninduced S9. Using Aroclor-induced preparations, supplementation with cytosol enhanced the activation of benzo[a]pyrene and ethidium bromide. With AAF and Aroclor-induced preparations, supplementation with cytosol produces a slight but significant increase in activation, but interpretation is complicated by the fact that Aroclor 105,000 x g supernatant fraction (S105) alone efficiently activates AAF, AF and AA. Norharman potentiated the enhancing effect of Aroclor S105 on Aroclor-S9 activation of AAF but inhibited the activation of AAF by S105 fraction alone. The enhancing effect of S105 fraction may explain some, but not all, of the differences between liquid-based and agar overlay based activation.

2-Acetylaminofluorene↗
PubMed1980

Optimal levels of S9 fraction in the Ames and fluctuation tests: apparent importance of diffusion of metabolites from top agar.

For activation of 2-acetylaminofluorene (AAF) there is an optimal level of rat liver S9 fraction which is considerably lower in the fluctuation test than in the Ames test. The optimal level of S9 is not markedly affected by the dose of AAF used, nor by the ratio of S9 to bacteria, nor by the presence of soft agar. The difference between Ames and fluctuation tests appears to be due to diffusion of some substance or substances from the top agar layer in the Ames test. Diffusion of the co-factors NADP and glucose-6-phosphate is not responsible for the difference in S9 optima, nor is diffusion of soluble S9 constituents although this may considerably affect the performance of the S9 mix. We present evidence that diffusion of non-mutagenic metabolites of AAF from the Ames test top agar may be responsible for the difference in S9 optima. Our results are consistent with a model whereby lipophilic non-mutagenic metabolites accumulate in the microsomes and inhibit further activation. When the metabolites are able to diffuse away, a higher level of S9 will be optimal. The model is consistent with some other phenomena of S9 activation.

2-Acetylaminofluorene↗
PubMed1978

Transformation of normal follicles into thyrotropin-refractory "cold" follicles in the aging mouse thyroid gland.

Autoradiographs of thyroid glands of aging mice demonstrate the gradual appearance of "cold" follicles which fail to iodinate the intraluminar iodoproteins even after intense exogeneous or endogeneous TSH stimulation. "Cold" follicles first appear at the age of 5 months. They may account for 80% of all thyroid follicles in 13-month-old mice. Morphologically, the "cold" follicles are characterized by a larger than normal colloid volume and a comparatively flat epithelium for any given follicle size. Old thyroids are twice as large as young ones. They contain twice as much normally iodinated thyroglobulin/mg wet weight. The total number of cells per gland remains constant throughout the life time. This is probably also true for the total number of follicles. The iodide pump, as judged by the tissue to serum ratio, remains normal and TSH-responsive. Yet, it is not established whether this is due to a higher activity of the pump in normal follicles or to preservation of inorganic iodide transport in "cold" follicles. Pinocytosis is defective in "cold" follicles and is poorly responsive to TSH stimulation. Furthermore, diffusion of iodocompounds is severely impaired in the colloid of "cold" follicles. It is suggested that the primary defect in the pathogenesis of "cold" follicles in old mice is the gradual failure of endocytosis to respond to normal TSH stimulation. Because exocytosis and iodination would first proceed normally, the follicular lumina would become overdistended up to a point where the apical membrane is functionally impaired. With this sequence of events, "cold" follicles would have impaired iodination while being metabolically as active as hot ones. Thus, several puzzling reports on high metabolic activity of "cold" tissue could possibly be interpreted.

Aging↗