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Biomedical subjects

R Jelínek

Publications and source records attributed to R Jelínek.

At least 19 recordsLinked to original sources
PubMed1998

[Clinico-teratologic counseling and the Teratology Information Service].

Medical records of 1179 pregnant women counselled at the Department of Medical Genetics Klimentska during the period 1990-1995 because of exposure to medicaments during the preconception period and in the first trimester were analyzed. Women exposed to antimicrobial agents prevailed (48 per cent). Most frequent was treatment with Doxycycline, Co-trimoxazole and Metronidazole. 23 per cent of women were exposed to sex hormones, most frequently to oral contraceptives and norethisterone. The average gestational age at exposure to antimicrobial agents was 21.5 days and 30 days at exposure to sex hormones. Specific features of clinical-teratological counselling and the role of the Czech Teratologic Information Service are described.

Counseling↗
PubMed1996

Interaction between quercetin and heat shock. A preliminary study on the chick embryo.

A hyperthermic shock (43 degrees C/30 min) enhances in somite stages of the chick embryo development the activity of the caudal morphogenetic system, manifested by intensive growth of the embryonic trunk. The exposure also induced the synthesis of heat shock proteins (HSP 70). A single administration of a bioflavonoid quercetin dissolved in DMSO to chick embryos in stages HH 10-11 (10-14 somites) prior to heat exposure inhibited both the growth acceleration and the HSP induction.

Animals↗
PubMed1994

Embryotoxicity in chick embryo of thalidomide hydrolysis products following metabolic activation by rat liver homogenate.

Three and four-day-old chick embryos were exposed to thalidomide as well as to its hydrolysis products before and after in vitro biotrasformation of these compounds with rat liver homogenate. Significant embryotoxic effects of 30 and 100 micrograms doses per embryo encountered only in the case when the products of alkaline hydrolysis of thalidomide were pretreated with rat liver homogenate.

Animals↗
PubMed1994

Validation of the Chick Embryotoxicity Screening Test (CHEST). A comparative study.

With the aim of investigating the predictive value of the Chick Embryotoxicity Screening Test (CHEST) with respect to regulatory rat-rabbit procedures, we compared the results of testing 50 chemicals of different pharmacological properties. Besides all being tested in the alternative technique, 27 substances were tested both in rats and rabbits, 22 only in the rat, and one only in the rabbit, respectively. The predictive value of CHEST with respect to the both official whole-animal procedures was found satisfactory, exhibiting about 80% consistent results. It is argued that the purpose of alternative testing methods is not in replacing the official routine procedures, but in contributing to the development of new predictive systems based on recent teratological knowledge.

Animals↗
PubMed1994

Teratogenic effects of bilirubin--a study using chick embryotoxicity screening test (CHEST).

Using the Chick Embrotoxicity Screening Test (CHEST), two samples of bilirubin of different commercial origin were tested on 2, 3 and 4- day old chick embryos. Water soluble Bilirubin Lachema (containing 20 mg albumin per 1 ml) had no teratogenic effect. On the opposite, Bilirubin Merck (containing 8 mg albumin per 1 ml) manifested an apparent teratogenic potential when single doses 0.2 and 0.6 micrograms were administered intraamniotically on day 4. Dose-dependent malformations of brain and eyes, cleft beak and reduction deformities of limbs were observed. No such effects could be produced by administration of Bilirubin Merck on either day 2 and 3. A tentative explanation of the difference between teratogenic properties of Merck and Lachema bilirubin preparations may be sougth in the different proportion of the free and albumin bound fractions.

Abnormalities, Drug-Induced↗
PubMed1993

Antimitotic and teratogenic effects of acyclic nucleotide analogues 1-(S)-(3-hydroxy-2-phosphonomethoxyethyl)cytosine (HPMPC) and 9-(2-phosphonomethoxyethyl) adenine (PMEA).

The acyclic nucleotide analogues, HPMPC and PMEA, differ in their in vitro effect on the genetic material of eukaryotic cells. While HPMPC exerts a cytostatic effect on eukaryotic cells in vitro, PMEA has a genotoxic activity. These results correspond with the mode of embryotoxic action of these compounds: HPMPC exhibits a general embryolethal effect, whereas PMEA is apparently teratogenic and interacts with the mutant allele producing preaxial polydactyly of the hind limbs.

Adenine↗
PubMed1992

Embryotoxicity of T-2 toxin and secalonic acid in embryonic chicks varies with the site of administration.

A crucial role of the site of administration in the sensitivity of the alternative system using chick embryo for testing embryotoxicity was demonstrated by morphological evaluation of the effects of T-2 toxin and secalonic acid D, and by incorporation of [14C]sodium acetate radioactivity. Secalonic acid D, administered to 2-, 3-, and 4-day-old embryos in doses higher than 1 microgram produced mostly malformations of the face (bilateral cleft beak, microphthalmia) while the teratogenic effects of T-2 toxin were being limited to the embryonic trunk of 2-day-old embryos (rumplessness) after administering doses higher than 0.001 microgram. In case of subgerminal and intraamniotic injections, the doses of both mycotoxins needed for producing embryotoxic effects comparable to those obtained with the more commonly used yolk sac injections appeared to be lower by one and two orders of magnitude, respectively. The results stress the need of using the shortest transport channel of test substances from the site of application to the target tissues of the embryo, when the maximum sensitivity and reproducibility of the test system are to be expected.

Age Factors↗
PubMed1992

Embryotoxicity of 25 psychotropic drugs: a study using CHEST.

Twenty five psychotropic drugs were ranked according to the embryotoxicity dose ranges estimated by the Chick Embryotoxicity Screening Test (CHEST). The chick results were compared with some data for common laboratory mammals. In 17 psychotropic drugs a deleterious dose-dependent effect upon the embryonic cardiovascular system was disclosed, terminating in immediate cardiac arrest.

Animals↗
PubMed1991

Observations on the biological activity of epitestosterone.

Epitestosterone, a 17 alpha-epimer of testosterone is a normal constituent of body fluids in many species including man. It has long been believed that it is devoid of any biological significance. However, it is now demonstrated that in in vivo experiments on castrated male mice it counteracts the action of testosterone on androgen-dependent organs. In vitro experiments show that on the overall antiandrogenicity of epitestosterone participate true antiandrogenic action due to the binding to androgen receptors, strong 5 alpha-reductase inhibiting activity as well as a weak antigonadotropic activity. Epitestosterone is devoid of any embryotoxicity as checked by chick embryo-toxicity screening test.

5-alpha Reductase Inhibitors↗
PubMed1991

Experimental models for drug teratogenicity.

Teratogenicity a specific manifestation of embryotoxicity, is explored in the course of the preclinical phase of drug testing. The official routine rat-rabbit procedures employ an integral experimental model--the whole animal with its species-specific metabolism. Although it has been widely accepted that pharmaco-kinetics of drugs represents the most important source of interspecies differences in teratology, the official procedure is still considered satisfactory. The reason why a new thalidomide affair has not occurred can be explained by the extremely low expression of teratogenic potential at the human population level--a condition inherent in the principles of teratogenesis. On the other hand, many partial experimental models have been developed that use mainly suborganismic objects (i.e. isolated morphogenetic systems, explanted tissues and cell populations). These objects possess many limitations disgracing their use as candidates for replacing the whole-animal experiments. Nevertheless, some of the partial models can be used and must be used in deeper analysis of the teratogenic potential of drugs with the aim of improving the predictive power of embryotoxicity risk assessment. (Fig. 1, Ref. 7.)

Animals↗
PubMed1990

Mutagenic and teratogenic effects of cyclophosphamide on the chick embryo: chromosomal aberrations and cell proliferation in affected and unaffected tissues.

Chromosomal aberrations and cell proliferation were analyzed in the chick embryo blood, limb bud, and facial tissues 12 and 24 hours after cyclophosphamide (CP) administration on day 3. The cytogenic findings were compared with teratogenic effects evaluated on incubation day 8. Low dose (0.3 micrograms) resulting in heart defects exclusively, increased the frequency of aberrant cells with simultaneous depression of cell proliferation in blood only. High dose of CP (6 micrograms), besides the heart defects, also induced facial clefts and limb malformations, and strong clastogenic effects associated with mitotic inhibition were observed in all tissues investigated. The results support the idea that the consequences of mutagenic action of cyclophosphamide--cell cycle delay and excessive death of cells with unstable aberrations--result in abnormal morphogenesis.

Animals↗
PubMed1989

An explanation of the stability of the incidence of inborn defects.

We propose a mathematical model for the malformation incidence in a population. The model is based on the assumption that malformations occur in a narrow range of embryotoxic doses for a given toxin and that this range varies in the population. Using this assumption, we exhibit malformation incidence curves which are in qualitative agreement with experimental data.

Abnormalities, Drug-Induced↗
PubMed1988

Orofacial clefts. A theoretical basis for their prevention and treatment.

In spite of the existing huge number of data on palate development as well as the incidence, experimental induction and clinical treatment of orofacial clefts, no unitary concept has been made available that would make possible their sorting out, further interpretation and extrapolation. The aim of this monograph has been to provide firm grounds for managing the data within categories consistent with the general principles of teratogenesis reformulated and extended upon the theory of morphogenetic systems, and, upon this basis, to evaluate the present chances of preventing the origin of orofacial clefts. Chapter 1 introduces the problem of birth defects that possess some distinct features in common with the recognised prime problems of present medicine, that is neoplastic and cardiovascular diseases. Orofacial clefts represent a substantial component of the human birth-defect spectrum that is a mere remnant of the original volume of teratogenesis estimated as affecting about 35% of human embryos. The merciful process of prenatal extinction of abnormal conceptuses, or terathanasia, reduces this eminent figure by approximately one order of magnitude. Basing upon the prevalence of clefts in embryos and infants we may say that the prenatal extinction of individuals with orofacial clefts lies somewhere between 70-90%. Chapter 2 deals with the history of recognising and formulating the general principles of teratology that go back to Isidore Geoffroy Saint-Hilaire. Estimating the contribution of the great personalities such as Dareste, Schwalbe, and J. G. Wilson, the chapter enumerates and describes the ten principles of teratogenesis as having arisen from the known rules extended and reformulated by the original theory of morphogenetic systems. In their sum, the principles constitute a deductive system defining teratogenesis at several levels of bioorganisation, capable of predicting the large-scale effects of environmental impact on animal and human reproduction. Chapter 3 presents the orofacial clefts in the light of the theory of morphogenetic systems. Palatal morphogenesis is accomplished under the conditions of extraordinary spatial complexity and extends over a relatively long period of development. Several morphogenetic subsystems may be distinguished, namely the morphogenetic subsystem (smgs) of facial outgrowths, the smgs of palatal shelves, the smgs of the glossomandibular complex and, eventually, the smgs of the axial cervical region, acting at different phases of palatal development.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Microscopic-anatomical changes in the chick embryo after administration of 9-(RS)-(2,3-dihydroxypropyl) adenine.

Microscopic-anatomical changes were followed in embryos of white leghorn fowl 1-5 days after administration of 9-(RS)-(2,3-dihydroxypropyl) adenine on day 2 of incubation. The main changes involved the spinal cord, eyes, and extremities, manifesting gross structural abnormalities. Development of the limb buds appeared to be arrested at stages corresponding to the third day of incubation, with their apical ectodermal ridges frequently absent. A conspicuous feature of all the experimental embryos was a seriously damaged spinal cord. The disturbance of spinal cord development was reflected in defective formation of vertebral anlagen. Development of eye anlagen was arrested at the optic cup stage. The lens, however, developed normally. No causal relationship between the CNS abnormalities and limb damage was determined.

Abnormalities, Drug-Induced↗