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Biomedical subjects

S Sandor

Publications and source records attributed to S Sandor.

At least 19 recordsLinked to original sources

Experimental alcohol blastopathy.

Experimental data are presented with respect to "experimental alcohol blastopathy" performed in our laboratory. As in our interpretation the notion of blastopathy involves both pathological changes during preimplantation development due to previous, preconceptional or preimplantation influences and later, pre- or postnatal effects induced by factors active during the preimplantation period, up to now the following experimental models were applied (on rats and mice): chronic and acute maternal, biparental or paternal ethanol alcoholization; preimplantation treatment with acetaldehyde or disulfiram followed by ethanol administration; acute ethanol intoxication before implantation on the background of chronic maternal ethanol intake; chronic maternal intake of various beverages. The main components of experimental alcohol blastopathy detected (by using a complex control methodology) were: pathological changes during the preimplantation developmental stages (lower mean number of embryos/animal, retardation of development, lowered migration rate of the embryos from the oviduct to the uterus, higher number of pathological morphological features), delayed implantation, disturbances of the early postimplantation development, retarded late foetal and placental growth. The effect of ethanol may be direct (ethanol being detectable in the oviductal and uterine fluid after both acute and chronic alcoholization) or indirect, via changes of the maternal macro- or microenvironment. The increase of the maternal blood acetaldehyde level may contribute to the appearance of alcohol blastopathy. Chronic beer and wine intake and acute intoxication with cognac suggest - up to now - the enhancing effect of beverage congeners. The noxious effect of acute ethanol intoxication superposed to chronic alcoholization is more marked that the separate effect of the two kinds of treatment. The chronic ethanol intake of fertilizing males (in mice) leads, both in the case of treated or untreated females, to lowered fertilization efficiency, to retardation of development (not occurring in the experimental model with chronic alcoholization of females) and to an enhanced increase of the number of pathological features. The cytogenetic control of preimplantation embryos (after chronic, acute or combined treatment with ethanol) does not reveal significant chromosomal changes. A possible alcohol blastopathy in humans must be taken into account (i.e. a noxious effect during the very early period of pregnancy when it is ignored).

Animals

Dyes as teratogens.

The main fats and problems of the role of dyes in prenatal pathology are reviewed. The first section deals with the practical aspects related to teratological screening of industrial dyes (including also the results obtained in this laboratory). In the second section, various aspects of azo-dye teratogenesis are largely discussed, including also the experimental contributions of this laboratory. Concluding remarks are made with respect to the importance and to the perspectives of this field of research.

Animals

A new experimental model of overgrowth and consecutive exencephaly.

By intraamniotic injection of a.d. diluted rat or rabbit blood plasma in 3-day chick embryos overgrowth and consecutive cranioschisis and exencephaly may be induced. Control experiments exclude colloid-osmotic mechanism. Morphological changes suggest an early general disturbance of brain wall morphogenesis and differentiation.

Animals

Contributions to the study of bisazo dye(s) induced eye anomalies in rats.

Eye anomalies were studied in embryos and foetuses of pregnant Wistar albino rats injected i.p. on day 9 of pregnancy with trypan blue (8-15 mg/100 g) and Niagara sky blue 6B (10-15 mg/100 g). Specimens were obtained by killing or by repeated surgical interventions between the 12th and 20th day of pregnancy. Microscopical changes were recorded in 170 embryos and foetuses of the experimental series and in 50 control specimens. Anophthalmia nad microthalmia (of various degrees) were the main anomalies induced by both dyes used. Other anomalies, less frequent, involved the whole eye or one or more eye components. No degenerative and necrotic changes the whole eye or one or more eye components. No degenerative and necrotic changes were recorded and no features attesting the vascular origin of malformations could be found. The persistence of eye appendages even in the total absence of any eye rudiment was constantly observed. Control specimens showed no microscopical changes of the developing eye. Some problems concerning possible pathogenic pathways are discussed.

Abnormalities, Drug-Induced

Researches on the formation of axial organs in the chick embryo. IX. On the development of somites in axial-paraaxial segments explanted to the zona pellucida.

Axial-paraaxial segments (neural tube, chorda, unilateral meso- and endoderm) excized from explanted 36--40-hour-incubated chick embryos at the level of unsegmented mesoderm, after removal of the ectoderm, were grafted onto subectodermal pockets of the zona pellucida. Under these conditions somites develop and differentiate normally. Paraaxial segments (unilateral meso- and endoderm) grafted under the same conditions show (retarded) somitogenesis only in 15% of the cases. Pure paraaxial unsegmented mesoderm grafted under the same conditions develops somites in 14% of the cases. Since in situ, the removal of the axial organs and of the endo- and ectoderm does not inhibit somitogenesis, the above-mentioned results prove that under conditions of grafting, some additionary "factors of realization" necessary for normal somitogenesis are lacking.

Animals

Contributions to the transfer of preimplantation molse embryos into "foster-mothers".

A new method for the transfer of preimplantation stages in mice has been developed by using as recipient the "pregnant empty uterus" obtained by ligature at the utero-oviductal junction. Results obtained with several combinations between Wh, CBAT6T6, C57Bl6 strains varied according to transfer media and strain combination, the best percentage of taking being under the level of those reported by other authors. By using transfer within the RAP strain, taking (controlled at 14 days of pregnancy) was similar to the best results generally obtained by the surgical transfer method. The advantages offered by the transfer method are briefly discussed.

Animals

6-Aminonicotinamide-induced eye defects in rats.

The pathological changes and structural anomalies induced by 6-aminonicotinamide (6-AN) in the developing eye were studied in rats (Wistar and hooded randombred strain). The substance was administered in aqueous solution intraperitoneally (4 mg/kg on day 9--10 of pregnancy: 5 mg/kg on day 11 of pregnancy; 8 mg/kg on day 13--17 of pregnancy) and in physiological saline intraamniotically (0.01 ml of a 1% solution in physiological saline on day 15 of pregnancy). Embryos and foetuses from experimental series and from untreated control series were macro- and microscopically examined on day 10--20 of pregnancy. Control foetuses from mothers injected with distilled water on day 9--17 of pregnancy were examined on day 20 of pregnancy. The pathological changes and structural anomalies detected at successive developmental stages are presented. They reveal an obvious phase specificity and attest that the same substance may act through both of the main teratogenic pathways hypothetically put forward by Menkes et al. (1970). Based upon the present findings (and some previous results obtained in experiments with bisazo dyes) a working hypothesis is tentatively presented, as to the possible determination of the uni- or/and bilateral distribution of chemically induced developmental defects. In connection with some reversible or transitory pathological changes the role of recovery in teratogenesis is pointed out.

6-Aminonicotinamide

On the prenatal noxious effects of trypan blue and of a related azo dye.

Since 1948 trypan blue has been a well-known and extensively used experimental teratogen, belonging to the group of azo dyes. Chemically, trypan blue consists of a biphenyl molecule (0-tolidine or benzidine) combined by means of azo linkages with two molecules of a substituted naphthalene. Between 1987-89 the effect of the replacement of the biphenyl molecule by a molecule of p,p'-diaminobenzanilide upon the prenatal noxious action of trypan blue has been controlled. Investigations were carried out on three species: chick embryos, albino rats and albino mice. In the species used, the replacement annihilates the teratogenic properties of the dye, with the persistence of some embryotoxic effects. On the other hand, the control of o-tolidine and of p,p'-diaminobenzanilide revealed that no one had teratogenic properties (only some embryotoxic effect, more marked in the case of o-tolidine). It results that the teratogenic action of trypan blue cannot be attributed to the o-tolidine molecule proper but to an effect which results (in a for the moment unknown manner) from its combination with the other parts of the dye molecule.

Abnormalities, Drug-Induced

Homeostasis changes induced by the action of ethanol on the materno-fetal complex in rats. V. Late fetal effects of acute intoxication during the preimplantation period.

The late fetal effect of ethanol administered during the preimplantation period (in acute experiment) was investigated. Ethanol was injected i.v. (33.16% v/v in a.d., 4.80 ml/kg b.w.) to pregnant female rats on day 2 and 4 of pregnancy. Some effects concerning biochemical and morphological homeostasis on at-term fetuses (day 20 of pregnancy) were studied. Data obtained were compared with those of the control group. Biochemical investigation performed on hepatic DNA and on some serum metabolites revealed the following statistically non-significant changes: the increase of fetal hepatic DNA; the increase of total protein determined from pooled fetal serum of the whole litters; hypoalbuminemy and hyperglobulinemy; hypo-alpha 1-globulinemy and hyper-alpha 2-, beta-, gamma-globulinemy; the increase of total lipids, decrease of cholesterol; increase of uric acid and urea. In the amniotic fluid the following statistically non-significant values were found: increase of proteins, lipids, uric acid and urea content and decrease of cholesterol. Ponderal somatometry evidenced a statistically significant decrease of fetal and placental wet weight. The changes found show that--in our experimental conditions--the i.v. administration of ethanol during the preimplantation period does not significantly influence the late, fetal biochemical values and induces a significant lowering of fetal and placental wet weight and a significant increase of late fetal mortality.

Animals

In vitro studies on normal and pathological preimplantation development. I. Events of normal mouse preimplantation development as revealed by microcinematography.

After briefly presenting the main historical data of in vitro culture of preimplantation mouse embryos and their filming, the first own observations on normal preimplantation development made by using microcinematography are presented: development from two-cell to eight-cell embryos; compaction and cavitation. The timing and the duration of various developmental events were recorded. Own observations were compared with previous cinematographic data reported by other authors. Some processes needing further investigations are evidenced: rotation within the zona pellucida, penetration of cytoplasmic emissions through the zona, contraction and reexpansion.

Animals

Sulphonated phthalocyanine induced caudal malformative syndrome in the chick embryo.

Sulphonated phthalocyanine (Pht.) has been tested for its possible noxious effect on the developing chick embryo. When injected into the subembryonic cavity of 40-45 hours incubated chick embryos (mainly 10-20 somite pairs), Pht. induces a highly reproducible caudal malformative syndrome (trunk and taillessness, various anomalies of the limbs). The main effect is--in about 15% of the malformed specimens--associated with unilateral microphthalmy and, less frequently, with coelosomy. Microscopically developmental disturbances of the caudal axial organs, of the mesonephros and of the limbs are observed. The initial pathological changes, at microscopic level, are necrosis and hemorrhages in the caudal axial and paraxial area. The allantois is poorly developed or even absent. Skeletal changes involve anomalies of the ribs and of the vertebral column and total or partial absence of the pelvic girdle bones. The high mortality, mainly during the first week, is due--first of all--to the developmental disturbances including the poor development or absence of the allantois. Control experiments with CuCl2 suggest the ethiological role of Cu. Pathogenetic aspects are discussed.

Abnormalities, Drug-Induced

The effect of ethanol upon early development in mice and rats. VIII. The effect of chronic consumption of some beverages upon preimplantation development in rats.

The effects of chronic consumption of some beverages (plum-brandy 24% and cognac 20%) upon preimplantation development in rats were studied. The control of possible effects was performed on day 5 by usual flushing, examination and photographying of oviductal and uterine embryos. In order to evaluate the effect of the beverage applied, the following criteria were used: mean litter size, migration of the embryos from the oviduct to the uterus, the developmental stage attained by the pre-implantation embryos and the appearance of pathological embryos. The main results were the following: both beverages applied influenced the preimplantation development; with respect to the developmental rate and to the induction of pathological changes, the effect of both beverages was similar (retardation and an increased, number of pathological morulae and blastocysts); a different action could be detected as to the mean litter size and to the migration of preimplantation embryos: plum-brandy reduced more substantially the mean litter size, whereas cognac had a more marked retarding effect upon the migration of embryos from the oviduct to the uterus: all the changes detected show a more or less marked "litter-effect". The present data were compared with the corresponding effects of chronic ethanol administration observed previously in our laboratory. No obvious potentiating effect of beverage congeners could be established. The findings are discussed in connection with other experimental models of alcohol embryo and fetopathy.

Alcohol Drinking