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.     

The effect of ethanol upon early development in mice and rats. XIV. The effect of acute intoxication with beer and wine upon preimplantation development in rats

The preimplantation effect of acute intoxication during the preimplantation period of pregnancy (i.p. or i.v. injection on day 4) with beer and wine has been investigated on female albino rats (Wistar strain). The following criteria were applied for checking preimplantation development: mean number of embryos/animal; topographical distribution of the embryos; developmental stage attained; occurrence of pathological embryonic forms. The control on day 5 of pregnancy revealed no significant effect upon the developmental criteria used. The data obtained are compared with our own previous results.     

The effect of ethanol upon early development in mice and rats. IV. The effect of acute ethanol intoxication of day 4 of pregnancy upon implantation and early postimplantation development in mice

Acute ethanol intoxication in albino mice (RAP) induced by intravenous administration of ethanol on day 4 of pregnancy delayed or inhibited implantation in about 25 per cent of the cases. The noxious action upon the implantation process showed a clear-cut "litter effect" and the mean litter was not affected by the experimental intervention. In very early postimplantation stage (day 6 of pregnancy) a statistically significant advance of some main morphogenetic indices was detected in treated specimens. As a possible explanation of this finding, a "selection" of more resistant and viable embryos by the acute ethanol intoxication is presumed. The data discussed in the present paper, together with authors' previous findings suggest a possible noxious action of acute ethanol intoxication during preimplantation stages upon implantation.     

The effect of ethanol upon early development in mice and rats. II. In vitro effect upon early postimplantation rat embryos

The direct effect of ethanol upon in vitro cultured 9.5 day rat embryos was investigated (2, 4, 8 and 10% ethanol added to the culture medium). The main effects recorded were as follows: 1. Significant increase of the number of "dying" embryos (beating heart without yolk sac circulation); 2. No significant increase of mortality; 3. Significant increase of the number of living embryos with deficient blood circulation; 4. Significant retardation of coiling in living embryos with a significant dose-effect relation, when the effects of 20/00 and 80/00 ethanol were compared; 5. Lowering of the mean somite number in living embryos; 6. Various macro- and macroscopical pathological changes (mainly necrotic areas in the central nervous system).     

The effect of ethanol upon early development in mice and rats. VI. In vivo effect of acetaldehyde upon preimplantation stages in rats

In completion of the previously outlined "experimental alcohol blastopathy", the role of acetaldehyde in the induction of preimplantation pathological changes in rat embryos has been controlled. Two experimental models were used: the direct administration of acetaldehyde by gavage and the blockage of acetaldehyde metabolization by ANTALCOL (an aldehyde-dehydrogenase blocking compound). The main results were as follows: The exogenous acetaldehyde in the blood of pregnant animals has an obvious effect upon the developmental rate during the late preimplantation period (retarding segmentation, blastulation), and in one of the experimental models upon the oviductal-uterine migration rate. The increase of the blood acetaldehyde level by blockage of its further metabolization has a more marked effect as compared with the direct intravenous administration of the substance. According to our previous observations the intravenous application of ethanol on the same day (day 4) has no such effect. The direct noxious influence upon the developing preimplantation embryos (fragmentation) of the increased level of acetaldehyde obtained by ANTALCOL treatment is similar but more marked than this effect obtained previously by ethanol administration. The same effect observed after the direct administration of the substance is less marked than the effect of ANTALCOL treatment but more marked than the effect of intravenous ethanol administration. These results attest that acetaldehyde may contribute (alone or together with the effect of ethanol) to the induction of "experimental alcohol blastopathy". The less marked action of the substance proper introduced into the blood stream may be due--in our opinion--to its possible alteration during the period between distillation and application.     

The effect of ethanol upon early development in mice and rats. I. In vivo effect upon preimplantation and early postimplantation stages

The preimplantation and early postimplantation effect of chronic alcohol consumption (at least a month before mating and during pregnancy until killing) and of acute ethanol intoxication during the preimplantation period (i.v. infection of ethanol) was studied on albino rats (Wistar) and albino mice (RAP). The main results were as follows: Chronic alcoholization. Rats: significant retardation of preimplantation development and in early postimplantation stages; a tendency of lowering of the mean litter size. Mice: significant increase of the number of preimplantation pathological forms; a tendency of lowering of the mean litter size. Pathological changes show, both in rats and mice, an obvious "litter effect". Acute ethanol intoxication. Rats: significant retardation in some litters, normal or even advanced development in others. This effect differs from the previously reported effect of acute ethanol intoxication during early postimplantation stages. The results obtained attest the prenatal noxious effect of chronic ethanol consumption in both species used and of acute ethanol intoxication during preimplantation development upon early postimplantation development in rats. Within the limits of extrapolation possibilities, they represent a risk signal for other species (including human).     

The effect of chronic oral alcoholization upon late fetal development in mice

The late fetal effect of chronic alcoholization in two strains of mice (RAP and RAP female x CBAT6 male) was controlled. Unilateral ocular anomalies (retinal folding, various degrees of ocular disorganization) were detected in 16% of the alcoholized RAP female x CBAT6 male group. The findings are discussed in connection with other experimental models of alcohol embryo and fetopathy.     

The effect of ethanol upon early development in mice and rats. III. In vivo effect of acute ethanol intoxication upon implantation and early postimplantation stages in mice

Female albino mice (RAP strain) were injected intravenously with absolute alcohol diluted aa by a.d., on days 2, 3 and 4 of pregnancy respectively. Macroscopically pregnant and empty uteri were controlled by microscopic examination. The developmental rate of postimplantation embryos was controlled by a previously reported biometrical method. The acute ethanol intoxication did not influence the postimplantation developmental rate (except for the appearance and development of the allantoic bud). In some of the uteri of the treated females (mainly of those treated on day 4), free blastocysts were found in the uterine lumen on day 9 of pregnancy, supposedly due to the deleterious effect of ethanol intoxication on central and local factors of implantation. Regressive changes of the decidua and consecutive embryonic death found in two litters may be caused by the same deleterious effect or (and) by inflammatory changes present in the endometrium of some control and treated females. The acute ethanol intoxication lowered the mean litter size in all the experimental groups.     

The effect of ethanol upon early development in mice and rats. V. In vivo effect of acute preimplantation intoxication with or without previous chronic alcoholization

Albino rats (Wistar) and albino mice (RAP) were either injected intravenously with ethanol during the preimplantation period (day 4 and 3, respectively) or injected in the same way after a previous chronic alcoholization (peroral consumption of 20% ethanol for 50-60 and 32-35 days, respectively before mating, adding the days until killing). The control of possible effects was performed on day 5 (rats) and 4 (mice) by usual flushing, examination and photographing of oviductal and uterine embryos. A group of albino rats, with chronic alcoholization, was controlled for late, fetal effects (resorption rate, skeletal control, possible ocular anomalies). The main results obtained were as follows: Acute ethanol intoxication. Rats: significant increase of pathological, fragmented preimplantation embryos with a marked "litter effect". Mice: no deleterious effect upon preimplantation development. Chronic alcoholization + acute ethanol intoxication. Rats: significant retardation of the preimplantation development rate and a significant increase of the number of pathological, fragmented embryos with a marked "litter effect". Mice: demonstrable advance of preimplantation development and migration rate. Chronic alcoholization--late fetal control in rats: the increase of resorption rate; the more frequent absence of sacral vertebrae; very rare rib anomalies and the absence of ocular malformations.     

The effect of cholesterol on macrophage-foam-cell generation upon zymosan-induced inflammation in mice

It has been shown that a significant number (about 40% of the total population) of macrophage-foam cells (MFCs) are formed during the early period (24 h) of zymosan-induced peritonitis resolution. Agonists of peroxisome proliferator-activated receptors α, γ (PPAR-α, γ) exert an anti-inflammatory effect, preventing its formation (Dushkin et al., 2007). The work is devoted to the influence of cholesterol-containing liposomes (CHLs) on the dynamics of zymosan-induced peritonitis in C57Bl/6 mice. Cholesterol accumulation, cytokine production, PPAR-γ activity, and cholesterol efflux in macrophages have been assayed. Infiltration of neutrophils, mononuclears, and increased MFC number in the peritonel cavity of zymosan-induced mice enhanced the inflammation process and MFC resolution period. Macrophages obtained after zymosan injection preferentially accumulated triglycerides (TGs) incorporated into TG, whereas CHLs at zymosan-induced inflammation promoted utilization of the [1-¹⁴C]oleate pool in cholesterol ethers (maximum after 2 days) and reduction of fluorescent NBD-cholesterol efflux from macrophages during the whole inflammation period. Cholesterol efflux after zymosan exposure was inhibited for 1–2 days, restored after 3 days, and enhanced at the fifth day. CHLs stimulated TNF-α and TGF-β1 production but inhibited IL-10 production and PPAR-γ DNA-binding activity in macrophages at early stages of zymosan-induced peritonitis. Thus, accumulation of cholesterol in inflammatory macrophages and MFC generation prolong the resolution of acute inflammation changing the balance of pro- and anti-inflammatory cytokins and inhibiting PPAR-γ activity and cholesterol efflux.     

Geometrical factors influencing muscle force development. I. The effect of filament spacing upon axial forces.

The influence of geometry on the force and stiffness measured during muscle contraction at different sarcomere lengths is examined by using three specific models of muscle cross-bridge geometry which are based upon the double-hinge model of H. E. Huxley (Science [Wash. D.C.]. 1969, 164:1356-1366) extended to three dimensions. The force generated during muscle contraction depends upon the orientation of the individual cross-bridge force vectors and the distribution of the cross-bridges between various states. For the simplest models, in which filament separation has no effect upon cross-bridge distribution, it is shown that changes in force vectors accompanying changes in myofilament separation between sarcomere lengths 2.0 and 3.65 microgram in an intact frog skeletal muscle fiber have only a small effect upon axial force. The simplest models, therefore, produce a total axial force proportional to the overlap between the actin and myosin filaments and independent of filament separation. However, the analysis shows that it is possible to find assumptions that produce a cross-bridge model in which the axial force is not independent of filament spacing. It is also shown that for some modes of attachment of subfragment-1 (S1) to actin the azimuthal location of the actin site is important in determining the axial force. A mode of S1 attachment to actin similar to that deduced by Moore et al. (J. Mol. Biol., 1970, 50:279-294), however, exhibits rather constant cross-bridge behavior over a wide range of actin site location.     

The effect of Walker-256 tumour development upon Kupffer cell metabolism

The liver plays a central role in the establishment and maintenance of the cachectic state in rats bearing extra-hepatic tumours. Kupffer cells, which as macrophages, show a strong relationship between metabolism and function could be involved in the alterations observed in the disruption of many functions of the organ as a whole. To assess whether the metabolic/functional pattern of Kupffer cells was altered by cachexia we have investigated the utilization of glucose, glutamine and palmitate by the cells from tumour-bearing and control rats. We have found an enhanced utilization of the three substrates by the cells from tumour-bearing rats as compared with controls, which was related to greater energy production through the Krebs cycle and enhanced production of precursors for the synthesis of the many substances the cells secrete when activated. The use of palmitate as substrate was also augmented in these cells, in the opposition to the observation in stimulated peritoneal macrophages. The availability of palmitate however, was not associated with a reduction of glucose or glutamine consumption. The cycle of interconversion, free fatty acids/triacyglycerol in Kupffer cells from tumour-bearing rats was also found to be increased, as was hydrogen peroxide production. Taken together the results suggest an increased utilization of substrates for both energy production and for synthetic processes (e.g. NADPH for hydrogen peroxide production). © 1998 John Wiley & Sons, Ltd.     

The effect of mepyramine on the development of morphine tolerance and physical dependence in mice.

Latency relaxation (LR) as well as resting tension and twitch tension of frog toe muscles are studied in an isotonic solution (= 1 T) and in solutions made hypotonic by leaving out the appropriate amounts of NaCl and KCl (0.54 T and 0.76 T). In hypotonic solutions there is an increase in peak twitch tension as well as a decrease in the depth of the LR: the resting tension is increased at sarcomere lengths which are greater than 2.8 μm and is decreased at sarcomere lengths which are less than this value. The behaviour of twitch tension is discussed with respect to the influence of the sarcoplasmic ionic strength on the interaction between the contractile filaments. Concerning the decrease in both the LR and the resting tension, it is assumed that these effects are induced osmotically, the tension of the membranes of the longitudinal sarcoplasmic reticulum being the particular parameter which is influenced.