[Prevention of the invasion of malignant cells of gynecologic tumors during surgery]. / Prevence invaze maligních bunek pri gynekologických operacích nádoru.

OBJECTIVE: In experiments performed on Vistar rats with Walker tumors, F. Luksch observed transfer of malignant cells during different manipulations into the blood circulation of the animals. During gynecologic surgery of a choriocarcinoma and of an ovarian carcinoma Luksch and Cernoch prooved trace of malignant cells within the blood circulation related to the manipulation of tumors during surgery. Therefore, as prevention of the metastazing of tumor cells, they proposed to ligate ampular portions of oviducts and hypogastric vessels as the first step of the radical surgeries. METHODS: Our observation is based on radical surgeries of 42 patients with cervical uterine carcinomas at the stage II.a (T2, N0, M0). In the first group 13 cases the ligature of oviducts and hypogastric vessels was performed at the start of the surgery. In the second group of 29 patients were operated without ligatures. RESULTS: After five years in the group of 13 ligated patients 10 patients (77%) survived. In the group of 29 unligated patients only 7 (24%) were alive. The results proove substantial differences. CONCLUSION: Although the members are small, there is doubt, that the ligation of oviducts and hypogastric vessels prior radical surgeries in patients affected by malignant gynecologic tumors substantially reduces metastazing of malignant cells nad improve the five years survival of surgically treated patients with gynecologic malignant tumors.

Exposure of postnatal rats to a static magnetic field of 0.14 T influences functional laterality of the hippocampal high-affinity choline uptake system in adulthood; in vitro test with magnetic nanoparticles.

Our previous experiments indicated an age- and sex-dependent functional lateralization of a high-affinity choline uptake system in hippocampi of Wistar rats. The system is connected with acetylcholine synthesis and also plays a role in spatial navigation. The current study demonstrates that a single in vivo exposure of 7- or 14-day-old males to a static magnetic field of 0.14 T for 60-120 min evokes asymmetric alterations in the activity of carriers in adulthood. Namely, the negative field (antiparallel orientation with a vertical component of the geomagnetic field) mediated a more marked decrease in the right hippocampus. The positive field (parallel orientation) was ineffective. Moreover, differences between the carriers from the right and the left hippocampi were observed on synaptosomes pretreated with superparamagnetic nanoparticles and exposed for 30 min in vitro. The positive field enhanced more markedly the activity of carriers from the right hippocampus, the negative that from the left hippocampus, on the contrary. Our results demonstrate functionally teratogenic risks of the alterations in the orientation of the strong static magnetic field for postnatal brain development and suggest functional specialization of both hippocampi in rats. Choline carriers could be involved as secondary receptors in magnetoreception through direct effects of geomagnetic field on intracellular magnetite crystals and nanoparticles applied in vivo should be a useful tool to evaluate magnetoreception in future research.

Antibodies against beta 2-glycoprotein I (beta 2-GP I) and their relationship to fetoplacental antigens.

Binding of beta 2-GP I to anionic phospholipids is thought to be the major antigen required in the reaction of anticardiolipin antibodies to phospholipids. The aim of this study was to investigate the changes of anti-beta 2-GP I IgG during the first and second trimester of pregnancy and the relationship between the levels of anti-beta 2-GP I and fetoplacental antigens and the correlation between anti-beta 2-GP I IgG and antibodies against oxidized low-density lipoprotein IgG (oLAb) in serum of pregnant women. We determined anticardiolipin antibodies (ACA) IgG and maternal serum levels of alpha 1-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and trophoblast-specific beta 1-glycoprotein (SP1) in 204 pregnant women in the first and second trimester. From this group we selected 52 serum samples positive for ACA IgG and 16 samples negative for ACA IgG. In the samples of selected patients, the levels of anti-beta 2-GP I IgG and oLAb IgG were determined. Anti-beta 2-GP I IgG levels significantly decreased in the second trimester (6.2+/-9.3 U/ml, mean +/- S.D.) in comparison with the first trimester (8.3+/-10.4 U/ml) (p=0.05). Multiple of median (MoM) AFP correlated negatively but not significantly in the first trimester with anti-beta 2-GP I (r = -0.261, p = 0.12). In the second trimester this correlation was significantly negative (r = -0.278, p = 0.04). The Spearman correlation coefficients for MoM HCG and anti-beta 2-GP I were 0.158 for the first trimester and 0.174 for the second trimester. MoM SP1 also did not correlate significantly with anti-beta 2-GP I in both trimesters. The correlation between anti-beta 2-GP I IgG and oLAb IgG was not significant (r = -0.06). In the first trimester 40 % serum samples were positive for anti-beta 2-GP I IgG and negative for oLAb IgG or vice versa, while 60 % samples in the second trimester were positive only for one determined autoantibody. We can conclude that the levels of anti-beta 2-GP I IgG decrease during the second trimester probably as the result of the effects of some immunosuppressive agents associated with pregnancy. The finding of negative correlation between AFP and anti-beta 2-GP I suggests that anti-beta 2-GP I has an influence on fetus development.

Antibodies against oxidized low density lipoproteins in pregnant women.

Oxidized low density lipoproteins (oxLDL) formed in vivo induce a humoral immune response. Oxidative modification of LDL renders it immunogenic and a heterogeneous population of specific anti-oxLDL antibodies is produced. These antibodies could represent a biological marker of oxidative stress and serve as markers of atherosclerosis. Autoantibodies against oxLDL (oLAb) have been detected in human subjects practically of every age. oLAb also appear in the blood of pregnant women. Some studies have shown that the levels of antibodies to oxLDL were elevated in women with established preeclampsia. The present study was aimed to estimate the oLAb IgG levels in the first and second trimester of pregnancy. Furthermore, we estimated the correlation between maternal serum (MS) levels of oLAb and alpha-1-fetoprotein (MS AFP), human chorionic gonadotrophin (MS HCG) and trophoblast-specific-beta-1-glycoprotein (MS SP1), because these proteins are determined as a part of prenatal biochemical screening for fetal congenital abnormalities. Our study deals with the oLAb changes in women with pregnancy-induced hypertension. We also investigated the correlation between oLAb IgG and anticardiolipin antibodies IgG (ACA) in the serum of pregnant women. We examined 40 pregnant women attending Institute for Mother and Child Care for their antenatal care as outpatients. Routine blood samplings between the 9-13th week of pregnancy and 16-18th week of pregnancy were performed as a part of biochemical prenatal screening for fetal congenital abnormalities (Group 1). Their mean age was 27 +/- 4.1 years. Furthermore, we examined 26 women in the second or third trimester with pregnancy-induced hypertension (Group 2). Group 2 was compared with 49 pregnant women in the second or third trimester who were normotensive (Group 3). We used commercial standardized ELISA kits for determination of oLAb IgG, ACA IgG, MS AFP and MS HCG, MS SP1 was analyzed by single radial immunodiffusion. We did not find any differences in the levels of oLAb IgG in the first and second trimester in the women of Group 1. The correlation between oLAb and ACA IgG was not statistically significant (Spearman coefficient r=0.22, p=0.1). The correlation between oLAb IgG with MS AFP, MS HCG and MS SP1 was not statistically significant. Weak negative correlation for AFP and HCG was suggested both in the first and in the second trimester. The levels of oLAb IgG in the group of women with pregnancy-induced hypertension were significantly lower than in the group of normotensive women (348 +/- 388 U/ml v.s. 579 +/- 400 mU/ml, p<0.01). We can conclude that the levels of oLAb do not differ in the first and second trimester of gravidity. However, we cannot exclude the possible influence of an inverse relationship between oLAb IgG titers and the synthesis of fetoplacental antigens. This finding is important especially in the context of the results of prenatal biochemical screening. Pregnancy-induced hypertension is associated with lower levels of oLAb. Weak cross-reactivity between oLAb and anticardiolipin antibodies may exist but there is a possibility that there are two different populations of antibodies reacting with various antigens.

Brain maldevelopment and neurobehavioural deviations in adult rats treated neonatally with indomethacin.

The risk of neurodevelopmental toxicity was studied in indomethacin (INDO), an inhibitor of prostaglandin synthesis, which is used in at-risk neonates to prevent the consequences of brain intraventricular haemorrhage or to accelerate the closure of patent ductus arteriosus. Model experiments were carried out in rats of the Wistar strain and Konárovice breed. The drug dose (2 mg/kg, s.c.) was applied to rat pups either once or twice in the following way: (1) on postnatal day 4 (PD:4) or postnatal days 4 and 5 (PD:4-5), i.e. model of brain ontogenic developmental stage in human fetus/preterm neonate of 7-month-gestational age; (2) on postnatal day 9 (PD:9) or postnatal days 9-10 (PD:9-10), i.e. model of brain ontogenic stage in full-term human newborn. The rats were followed up during development (body weight, maturation) until adulthood (age 3-9 months) using tests of behaviour (open field, social memory), nociception (tail flick, plantar test), reproduction and brain neurobiological analysis. The results were evaluated by comparison of litter-mates: treated vs control. No differences between INDO and controls were found in developmental landmarks, adult social memory or reproduction. The pattern of behavioural and neuroendocrine deviations in adult animals was dependent on the ontogenic stage exposed to drug insult. INDO rats of the groups PD:4 and PD:4-5 revealed depression of open field motor activity and emotional reactivity, and higher pituitary weight with lower TSH content. On the other hand, deviations in adult INDO groups PD:9 and PD:9-10 were characterized by pain hypersensitivity, lower pituitary weight with unchanged TSH content and deficit of monoamine transmission in the hypothalamus.

[PAPP-A in the first trimester of pregnancy]. / PAPP-A v prvním trimestru tehotenství.

OBJECTIVE: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. The aim of this study was to determine preliminary the medians of pregnancy-associated plasma protein A (PAPP-A) in the first trimester of pregnancy and to compare PAPP-A with other biochemical markers used for biochemical prenatal screening. DESIGN: Retrospective study. SETTING: First Institute of Medical Chemistry and Biochemistry and Institute for Clinical Biochemistry, First Medical Faculty, Charles University. Institute for Care of Mother and Child, Prague. PATIENTS: One hundred forty one pregnant women, who undergo biochemical prenatal screening for chromosomal disorders between 7th and 13th week were studied. In addition six women in the second trimester and five women with twin pregnancies, two cases of trisomy 21 and one case of trisomy 18 in second trimester were available for study. METHODS: Maternal serum levels of PAPP-A, human chorionic gonadotropin (hCG) and alfa-1-feto-protein (AFP) were measured using ELISA methods. A single radial immunodiffusion was used to determine trophoblast-specific-beta-1-glycoprotein (SP1). RESULTS: PAPP-A levels increased throughout the first trimester with median 1.8 mg/l in the 7th week to 23.0 mg/l in the 13th week of pregnancy. PAPP-A serum levels from 3 women with twin pregnancies were higher than in women with singleton pregnancies. Serum levels of PAPP A in two women with fetus affected by chromosomal disorders did not differ from normal pregnancies. Correlation coefficients between PAPP-A and AFP and between PAPP-A and SP1 were statistically significant (r = 0.42, P < 0.001, respectively r = 0.54, P < 0.001). The levels of PAPP-A and HCG did not correlate significantly (r = 0.019, P = 0.82). CONCLUSION: We established first trimester medians for PAPP-A, which are necessary for evaluation of the pathological values. We found statistically significant correlation between PAPP-A and SP1 and PAPP-A and AFP.

Prevalence of various antiphospholipid antibodies in pregnant women.

Antiphospholipid antibodies (APAs) are characterized as a heterogeneous population of autoantibodies directed against different target antigens, predominantly anionic phospholipids or phospholipid-containing structures. The presence of APAs has been strongly associated with a variety of clinical disorders including adverse pregnancy complications such as spontaneous abortions, pregnancy-induced hypertension, preeclampsia and intrauterine growth retardation. The purpose of this study was to compare the prevalence of anticardiolipin antibodies (ACAs), which are routinely examined, with APAs directed against phosphatidylserine (APS), phosphatidylinositol (API), phosphatidylethanolamine (APE) and phosphatidylcholine (APC) in the sera of pregnant women. We examined 410 serum samples of pregnant women hospitalized in the department for pathological pregnancies. They underwent prenatal biochemical screening of fetal congenital abnormalities in the first and the second trimester of gravidity. Anticardiolipin IgG and IgM were measured using commercial ELISA kits (ImmuLisa Anti-Cardiolipin Antibody), whereas APS, APE, API and APC were determined by our modified ELISA kit. Among 410 pregnant women we found 21 patients (5.1%) positive for ACA IgG (>20 GPL) and 30 patients (7.3%) positive for ACA IgM (>10 MPL). It was found that 7.8% of pregnant women had at least one high-titer APA IgG and 9.8% high-titer APA IgM. One third of ACA IgG or IgM positive sera contained polyspecific autoantibodies reactive to at least two various phospholipids. In the group of IgG ACA positive women, 28.6% patients were positive for APS, 28.6% were positive or moderately positive for API, 23.8% for APC and 19% for APE. In the group of IgM ACA positive women, 33.3% were also positive for APS, 26.7% for APE, 26.7% for API and 23.3% for APC were present. IgG and IgM ACA negative patients exhibited a significantly lower incidence of other APA than the group of ACA positive pregnant women. It still remains to clarify if the routine examination of APA reacting with other anionic and zwitterionic antigens other than cardiolipin would improve the probability of identifying women liable to adverse pregnancy complications.

[Comparative study of the occurrence of beta-2-glycoprotein I antibodies (anti-beta-2-GPI) and anticardiolipin antibodies (ACA) in the blood of pregnant women]. / Srovnávací studie výskytu protilátek proti beta-2-glykoproteinu I (anti-beta-2-GPI) a antikardiolipinových protilátek (ACA) v séru tehotných zen.

OBJECTIVE: It is accepted now that most antiphospholipid antibodies (APA) are not directed against phospholipids alone but complexes of phospholipid-binding proteins and phospholipids. One of the phospholipid-binding proteins is beta 2-glycoprotein I (beta 2-GPI), a normal plasma glycoprotein, which under physiological conditions binds with negative charged phospholipids. Measurement of anti-beta 2-GPI antibodies requires specific tests, since ELISA for determination of anticardiolipin antibodies (ACA) may detect both antibodies directly binding cardiolipin and antibodies against cardiolipin-binding proteins. In this study a comparison of APAs against cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylethanolamine (PE) v.s. anti-beta 2-GPI were compared. SETTING: First Institute of Medical Chemistry and Biochemistry, First Medical Faculty, Charles University and Institute for Care of Mother and Child. DESIGN: Retrospective clinical study using stored sera for determination of APA. METHODS: One hundred twenty four women in the first and the second trimester, who undergo biochemical prenatal screening for chromosomal disorders by maternal serum alpha-fetoprotein (MS AFP), human chorionic gonadotrophin (MS HCG) and trophoblast-specific beta 1-glycoprotein (MS SP1) were studied. In serum samples antibodies against CL, PS, PE, PI (isotype IgG and IgM) were examined by solid ELISA. 19 women who were positive at least for one type of APAs were selected and in the serum samples the levels of anti-beta 2-GPI were measured. RESULTS: No pregnant woman with anti-beta 2-GPI had positive antibodies against other phospholipids except CL. There was no significant correlation between levels of ACA IgG and IgM v.s. anti-beta 2-GPI IgG and IgM. Eight percent of serum samples were positive for both anti-beta 2-GPI IgG and ACA IgG. In the second trimester a statistically significant decrease of ACA IgG was found (p = 0.014). The difference of ACA IgM and anti-beta 2-GPI IgG and IgM was not statistically significant. Levels of foetoplacental antigens in anti-beta 2-GPI positive pregnant women were normal. CONCLUSION: A correlation between anti-beta 2-GPI antibodies and ACA was not found in our study. Anti-beta 2-GPI antibodies and ACA may be two different subpopulations of APA.

Neuro-immuno-teratogenicity of drugs used in neonatal pharmacotherapy in relation to the ontogenic stage at the time of their administration.

The risk of functional teratogenicity of two drugs used in neonatal pharmacotherapy was studied: indomethacin (INDO) and dexamethasone (DEX). Model experiments were carried out in Wistar strain rats, breed Konárovice, which received single subcutaneous drug injection (INDO 2 mg/kg, DEX 1 mg/kg) on postnatal day 4 (PD:4; model of human fetus/preterm newborn of 6-7-month-gestational age) or on postnatal day 9 (PD:9; model of full-term human neonate). The rats were followed up during development (body weight, maturation) till late adulthood (age 6-8 months) using tests of cognition, immune reactivity and biochemical brain analysis. The results evaluated by comparing treated and control litter-mates indicated that the functional teratogenic risk was significantly higher in DEX than in INDO. DEX-rats revealed disorganization of developmental processes: retardation of body growth, but acceleration of sensory development (pinna and eye opening), retarded male sexual maturation. Adult DEX-rats (age 6 months) of both series (PD:4, PD:9) had deficit of short-term memory (social recognition test). Disturbances of immune reactivity (decrease of humoral and rise of cell-mediated immune response) appeared both in adult INDO and DEX-rats (age 7 months), but only in the PD:9 series i.e. when the drugs were administered at a higher stage of the ontogenic development simulating neonatal period in humans. This finding may be warning from the clinical point of view for the neonatological practice.

[Intravenous administration of Augmentin in the prevention of infectious complications in abdominal hysterectomy]. / Intravenózní aplikace Augmentinu v profylaxi infekcních komplikací u abdominální hysterektomie.

Amoxycillin-clavulanate was used in prophylaxis of infectious complications after abdominal hysterectomy. A group of 29 patients was treated routinely with metronidazol introduced vaginally 2-3 days before surgery. This group was compared with 40 patients who received two perioperative doses of Augmentin intravenously. The incidence of febrile morbidity, urinary tract infection, following antibiotic treatment and pelvic infection were followed in both groups. Patients in the amoxycillin-clavulanic acid group had significantly less infectious morbidity than those in the metronidazol group. The results suggest that antibiotic prophylaxis for abdominal hysterectomy is effective. The prophylactic agent should be bactericide against aerobic and anaerobic bacteria and non-toxic. Amoxycillin-clavulanate (Augmentin) meets all these criteria.

[Anti-phosphatidylserine antibodies in women with reproductive disorders]. / Antifosfatidylserinové protilátky u zen s poruchami reprodukce.

Antiphosphatidylserine antibodies (APSA) belong to the heterogeneous population of antiphospholipid antibodies (APA) which are oriented above all against negatively charged phospholipids. The presence of APA in women is closely associated with repeated miscarriages and other complications during pregnancy. The most frequently detected specific antibodies in these patients are autoantibodies against cardiolipin and phosphatidylserine (PS). In a group of 84 pregnant women where within the framework of biochemical prenatal screening of inborn developmental defects serum levels of alpha-1-fetoprotein, choriogonadotropin and trophoblast specific beta-1-glycoprotein were examined as well as in 22 women treated for primary sterility and 22 blood donors the authors assessed, using the ELISA method, antiphosphatidylserine and cardiolipin antibodies (ACA). They found an increased prevalence of APSA in all examined groups as compared with the control group of blood donors. In pregnant women the prevalence of APSA and ACA did not differ and at least one type of antibodies was detected in 20.1%. In pregnant women with positive APSA in the case-records spontaneous abortions were recorded, or imminent abortions during the present gestation or treatment on account of sterility, and in some instances also changes of foetoplacental antigen serum levels were found. It is therefore likely that the presence of APA in women may be one of the factors participating in reproductive disorders and that assessment of APSA together with APA may extend the spectrum of immunological examinations, in particular in sterile and infertile women.

Immune response of adult rats is altered by administration of diazepam in the first postnatal week.

The potential immunotoxic risk of perinatal treatment with diazepam was investigated using early postnatal administration of the drug to the rat and monitoring the immune response until the age of 24 months. Rats given a single dose of diazepam 10 mg/kg SC on the seventh postnatal day revealed at the age of 6 months a depression of cell-mediated immune response, and at the age of 12 months significant decrease of humoral immune response. The latter persisted until senescence (age 24 months). Also, a repeated dosage of diazepam (3 x 5 mg/kg/day SC on postnatal days 5 to 7) induced a significant depression of humoral immune response in 7-month-old rats. The results demonstrate that both the humoral and cell-mediated immune response of adult rats can be altered by administering diazepam in early postnatal life.

[Perinatal pharmacotherapy and the risk of functional teratogenic defects]. / Perinatální farmakoterapie a riziko funkcne teratogenních defektu.

Perinatal period, which is characterized by intensive histogenesis and cytodifferentiation of the already shaped organs, is a highly vulnerable phase for fetal/neonatal brain and immune system-organs with high similarity in receptor equipment. Even fine deviations in the programmed developmental processes induced by drugs initiate disorders in the formation of neural network, cytoarchitectonics and receptor-transmitter communication systems. This pathology is not evident at birth, but forms the basis for various functional defects of neuro-psycho-immunocompetence which become apparent gradually during further maturation or even in adulthood. Clinical recognition of such functional teratogenic action of drugs is hampered by the long time interval (upto decades) between the drug administration and its consequences, making the identification of causal relations very difficult. Consequently, experimental research is necessary under the precondition of adequate animal models with sufficient validity for the extrapolation on human level. The authors suggest the principles of such approach using drug application in neonatal rats with lifelong follow-up of behaviour, immune reactivity and brain biochemical analysis. The evaluation of functional teratogenic risk in three drugs used in the treatment of risk pregnancies and risk neonates (dexamethazone, fenoterol, diazepam) is presented.

[Nooptropic agents and their action mechanisms in relation to neuropathology in senile dementia. II. Disorders of membrane integrity and neuron metabolism]. / Nootropní látky a jejich mechanismus úcinku ve vztahu k neuropatobiologii senilní demence. II. Poruchy membránové integrity a metabolismu neuronu.

The author discusses several newer aspects concerning neurodegenerative processes in nerve cells of aging brain on the level of membrane integrity and neuronal metabolism disturbances: aggressive impact of free radicals and excitatory amino acids, loss of calcium homeostasis, deposition of amyloid proteins. Perspective nootropic agents are presented which were synthetized with the aim to regulate these deficits and first clinical experience with their administration in senile dementia patients is evaluated.

[Nootropic drugs and their action mechanisms in relation to the neuropathobiology of senile dementia. I. Neurotransmission disorders in the brain]. / Nootropní látky a jejich mechanismus úcinku ve vztahu k neuropatobiologii senilní demence. I. Poruchy neurotransmise v mozku.

The author presents a review of agents which are presently included in the category of nootropic drugs and comments the relations between the pharmaceutical research of new nootropic and progressing knowledge of the neuropathobiology of Alzheimer's disease, senile dementia and degenerative processes of aging brain in general. In Part I., several hypotheses are discussed which explain the biological substrate of senile cognitive decline by disturbed brain synaptic neurotransmission (cholinergic, monoaminergic, petidergic) and, at the same time, drugs are suggested which may exert regulatory action on these dysfunctions.

Early postnatal diazepam treatment of rats and neuroimmunocompetence in adulthood and senescence.

Functional teratogenic risk of perinatal diazepam (D) treatment was studied in animal model experiments using early postnatal D administration in rats (single dose of 10 mg/kg sc in 7-day-old pups) and long-term follow-up till the age of 18 months with monitoring of behavior, reproductive functions, brain biochemical variables, and immune system reactivity. Behavioral tests carried out at the age of 6, 12, and 18 months indicated higher emotionality and deviations of novelty reaction in D rats in comparison with controls, and these differences decreased with aging. However, no deficits were found in memory testing. D rats revealed some transitional alterations of monoamine neurotransmission in the hypothalamus (5-HT) and striatum (DA) and minor defects in reproductive functions (irregular estrous cycles in females). Significant depression of immune response in D rats persisting for the whole life may be considered as a serious risk of neonatal D treatment.

Neuropathobiology of senile dementia and mechanism of action of nootropic drugs.

Recent advances in neuroscience and molecular neurochemistry have substantially increased the knowledge of the neuropathobiology of senile dementia and Alzheimer's disease. On the basis of various hypotheses concerning degenerative processes in aging brains, new therapeutic strategies have been developed, including nootropic drugs with different mechanisms of action and heterogenous chemical structures. Mutual relationships exist between neuroscientific research and nootropic drug development. To date, such areas of research and drug development have involved deficits of brain neurotransmission (cholinergic, monoaminergic, peptidergic), free radical-induced damage, disturbances of calcium homeostasis and excitatory amino acid function, and deposition of amyloid protein.

[Perinatal drug administration and risks of functional teratogenic defects]. / Perinatální podávání léku a riziko funkcne teratogenních defektu.

The success of perinatal medicine in saving the risk pregnancies and the lives of very immature and injured newborns is connected with a growing use of drugs which may disturb perinatal ontogenetic processes characterized by intensive histogenesis and cytodifferentiation of already formed organs, predominantly the brain. The administered drugs can change the program of the formation of neural nets, synapses, receptors and neurotransmitters and induce permanent deviations of brain cytoarchitectonics and neurobiochemical equipment. This pathology is not evident at birth, but forms the basis for functional defects of the brain which become apparent gradually during maturation or even in adulthood as neuro-psychological deviations e.g. minimal brain dysfunction or mental retardation in school children, sensori-motor deficits, epilepsy, psychic lability and maladjustment which may represent a predisposition to psychoses. Clinical recognition of this functional teratogenic action of the drug is hampered by the long time interval (upto decades) between the drug administration and its consequences what makes the identification of causal relations very difficult. Consequently, experimental research is necessary concerning functional teratogenicity of all drugs given in perinatal period, however under the precondition of adequate animal models with sufficient validity for the extrapolation on human level. The synopsis of current knowledge in this field reveals great numbers of urgent problems which are to be studied.

Comparison of the effects of aging in vivo and of oxygen free radicals in vitro on high-affinity choline uptake and hemicholinium-3 binding in the rat brain.

The effects of aging in vivo (Wistar rats aged 3-26 months) and of an oxygen free-radical generating system in vitro (Fe(2+)/ascorbic acid) on high-affinity choline uptake in the hippocampus and on (3H)hemicholinium-3 binding sites in the cortex and hippocampus are compared. The high-affinity choline transport system was found to be more damaged than the low-affinity system during aging (Na(+)-dependent part of the uptake drops to 76%: Na(+)-independent part increases to 120%). The decrease in high-affinity choline uptake values is probably more influenced by the impairment of correct function of carriers (the fall in the turnover rate of each carrier) than by a decrease in the number of transport sites (no change of the density of the carriers in the hippocampus and cortex). The causes of the defect in high-affinity choline transport during aging are discussed.