Evaluation of New Approaches to Depression Treatment Using an Animal Model of Pharmacoresistant Depression.

Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group (p < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine (p < 0.05 central zone; p ≤ 0.05 periphery zone) and SMe1EC2M3 (p < 0.05 central zone; p < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST (p < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group (p < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group (p < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD.

Effect of a New Substance with Pyridoindole Structure on Adult Neurogenesis, Shape of Neurons, and Behavioral Outcomes in a Chronic Mild Stress Model in Rats.

Despite an accumulating number of studies, treatments for depression are currently insufficient. Therefore, the search for new substances with antidepressant potential is very important. In this study, we hypothesized that treatment with a newly synthesized pyridoindole derivative compound SMe1EC2M3 would result in protective and antidepressant-like effects on behavioral outcomes and reverse the impaired adult hippocampal neurogenesis caused by chronic mild stress (CMS). We found that chronic administration of 5 mg/kg and 25 mg/kg SMe1EC2M3 to adult Sprague Dawley rats ameliorated the consequences of CMS on immobility and swimming time in a forced swim test. A slight sedative effect of the highest dose of SMe1EC2M3 in the nonstress group was observed in the open field. SMe1EC2M3 in the highest dose ameliorated CMS-induced decreases in the sucrose preference test. Administration of SMe1EC2M3 significantly increased SOX2-positive cells in the hippocampal dentate gyrus (DG) in CMS compared to control animals. A significant reduction in glial fibrillary acid protein (GFAP)-positive cells in the DG of CMS compared to control animals was observed. Administration of both 5 and 25 mg/kg SMe1EC2M3 significantly increased signal of GFAP-positive cells in the DG of CMS animals. No such effects of SMe1EC2M3 were observed in the cornu ammonis hippocampal area. Additionally, we found that incubation of primary hippocampal neurons in the presence of 1.50 µM SMe1EC2M3 significantly stimulated the length of neurites. Overall, we found that the negative effects of CMS on depression-like behavior are partially reduced by the administration of SMe1EC2M3 and are associated with changes in hippocampal neurogenesis and neuronal differentiation. SMe1EC2M3 represents a potential drug candidate with positive neuroplastic effects and neurogenesis-associated effects in therapeutic approaches to depression.

Congenital cytomegalovirus infection ‒ a problem of past, present and future.

AIM: To analyse prenatal and postnatal characteristics, clinical and laboratory findings, results of investigations in the group of 11 newborns with congenital CMV infection, who were hospitalized at Neonatal Department of Intensive Medicine between January 1st 2012 and March 31st, 2022 were included. RESULTS: Prenatal foetal sonography revealed in patients 5 and 8, positive calcifications in the brain; in patients 6, 9 and 11, isolated ventriculomegaly was found. Neurological examination was clinically negative in patients 1 and 10, changes of muscular tonicity and spontaneous activity were confirmed in the rest of the group. In patients 5 and 10, one-sided positivity of otoacoustic emissions was confirmed. Chorioretinitis with bilateral negative otoacoustic emissions was confirmed in patient 5. Clinical status of patient 11 was complicated by pneumonitis. Three patients were treated with antiviral drugs orally, and 11 newborns had a combination of intravenous and oral form of treatment. CONCLUSION: The results of analysis will contribute to a society-wide solution of prevention. Monitoring of the frequency of CMV infection in the population with education of the population can decrease the number of affected newborns (Tab. 4, Ref. 29).

Combined In Silico, Ex Vivo, and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Neuro- and Cardioprotective and Antidepressant Effects.

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.

Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay.

Indole derivatives such as isatin (a natural compound), cemtirestat, stobadine, and its derivatives (synthetic compounds) are known to have numerous positive effects on human health due to regulation of oxidative status. The aim of the study was to assess radical scavenging capacities of these compounds and explore their potential protective effects against reactive oxygen species formed during Cu(II) ions and ascorbate-induced degradation of high-molar-mass hyaluronan. Based on the IC50 values determined by the ABTS assay, the most effective compound was SM1M3EC2·HCl reaching the value ≈ 11 µmol/L. The lowest IC50 value reached in the DPPH assay was reported for cemtirestat ≈ 3 µmol/L. Great potency of inhibition of hyaluronan degradation was shown by cemtirestat, followed by isatin even at low concentration 10 µmol/L. On the other hand, stobadine·2HCl had also a protective effect on hyaluronan degradation, however at greater concentrations compared to cemtirestat or isatin. SME1i-ProC2·HCl reported to be a less effective compound and SM1M3EC2·HCl can be considered almost ineffective compared to stobadine·2HCl. In conclusion, our results showed that both isatin and cemtirestat were capable of attenuating the degradation of high-molar-mass hyaluronan due to their ability to complex/sequester cupric ions.

Alterations in myocardial connexin-43 and matrix metalloproteinase-2 signaling in response to pregnancy and oxygen deprivation of Wistar rats: a pilot study 1.

Two important aspects of cardiac adaptive response to pregnancy have been studied in normal as well as hypoxic conditions: (1) intercellular signaling mediated by myocardial connexin-43 (Cx43) that is crucial to synchronize heart function; (2) extracellular signaling mediated by matrix metalloproteinase-2 (MMP-2) that is an early marker of extracellular matrix remodeling. Myocardial Cx43 distribution and functional capillary density were determined as well. Hypoxia was induced by exposure of rats to 10.5% O2 and 89.5% N2 in a hermetically sealed chamber. Findings showed that pregnancy resulted in a significant increase of Cx43 protein expression, its functional phosphorylated forms, and enhanced capillary density while did not affect either expression of total MMP-2 or its activity. Maternal hypoxia for 12 or 16 h did not affect elevated Cx43 but enhanced its distribution on lateral sides of the cardiomyocytes. In contrast, hypoxia of nonpregnant rats resulted in upregulation of Cx43, its lateral distribution, and enhanced capillary density. Hypoxia did not affect myocardial MMP-2 either in pregnant or nonpregnant rats. Cardiac adaptive response to pregnancy is accompanied by enhanced Cx43 without changes in MMP-2 signaling. Pregnant rat heart is tolerant to short-term hypoxemia, while nonpregnant rat heart reacts by upregulation of Cx43 and increased capillary density.

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors.

SMe1EC2M3 is a pyridoindole derivative related to the neuroleptic drug carbidine. Based on the structural similarities of SMe1EC2M3 and known serotonin (5-HT), norepinephrine, and dopamine reuptake inhibitors, we hypothesized that this compound may also have triple reuptake inhibition efficacy and an antidepressant-like effect. PreADMET and Dragon software was used for in silico prediction of pharmacokinetics and pharmacodynamics of SMe1EC2M3. Forced swim test was used to evaluate its antidepressant-like effects. Extracellular in vivo electrophysiology was used to assess 5-HT, norepinephrine, and dopamine reuptake inhibition efficacy of SMe1EC2M3. PreADMET predicted reasonable intestinal absorption, plasma protein binding, and blood-brain permeability for SMe1EC2M3. Dragon forecasted its efficiency as an antidepressant. Using behavioral measurements, it was found that SMe1EC2M3 decreased immobility time and increase swimming time during the forced swim test (FST). Electrophysiological investigations showed that SMe1EC2M3 dose-dependently suppressed the excitability of 5-HT neurons of the dorsal raphe nucleus (DRN), norepinephrine neurons of the locus coeruleus (LC), and dopamine neurons of the ventral tegmental area (VTA). The SMe1EC2M3-induced suppression of 5-HT, norepinephrine, and dopamine neurons was reversed by the antagonists of serotonin-1A (5-HT1A; WAY100135), α-2 adrenergic (α2, yohimbine), and dopamine-2 receptors (D2, haloperidol), respectively. We conclude that SMe1EC2M3 is prospective triple 5-HT, norepinephrine, and dopamine reuptake inhibitor with antidepressant-like properties, however future studies should be performed to complete the pharmacological profiling of this compound.

Acute Impact of Selected Pyridoindole Derivatives on Fos Expression in Different Structures of the Rat Brain.

The impacts of three pyridoindole derivatives (PDs), designated as PD144, PD143, and PD104, which have previously been shown to have antidepressant (PD144) and anxiolytic (PD143, PD104) properties, were investigated on the Fos expressions in 11 different rat brain areas, including the medial prefrontal cortex, striatum, septum, accumbens nucleus (shell, core), bed nucleus of the stria terminalis, hypothalamic paraventricular nucleus, central amygdala, locus coeruleus, dorsal raphe nucleus, and the solitary tract nucleus. Control rats received vehicle, while the other three groups the PDs in a dose of 25 mg/kg/b.w. The animals were transcardially perfused with a fixative 90 min after the treatments. Coronal sections of 40-µm thickness were processed for Fos-immunostaining by avidin-biotin-peroxidase complex and visualized by nickel-intensified diaminobenzidine complex. Fos-labeled sections were counterstained with neuropeptides including corticoliberine (CRH), oxytocin (OXY), vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) and processed for immunofluorescence staining using Alexa Fluor 555 dye. In all the three groups of animals, the upregulation of PDs-induced Fos expression only in 2 of 11 brain areas was investigated, namely, in the hypothalamic paraventricular nucleus (PVN) and the central amygdaloid nucleus (CeA). The other brain structures studied were devoid of Fos expression. Counterstaining of the Fos-labeled CeA-containing sections with VIP antibody revealed that the Fos expression stimulated by the PDs was upregulated in all the CeA subdivisions (lateral, ventral, capsular), except the medial one. Dual immunoprocessings showed Fos/CRH-labeling in both the PVN and the amygdala and Fos/OXY in the PVN. No Fos/AVP colocalizations were seen in the PVN. The obtained data provide the first view on the intracerebral effects of three new PDs derivatives, which effects were restricted only to the PVN and CeA areas. The present data may help to improve our understanding of the impact of the selected PDs on the brain and to anticipate possible behavioral and neuroendocrine consequences.

Perinatal exposure to venlafaxine leads to lower anxiety and depression-like behavior in the adult rat offspring.

Depression during pregnancy and in the post-partum period is a growing health issue. Venlafaxine, a representative of serotonin and noradrenaline reuptake inhibitors, is used to treat a wide spectrum of mood disorders. However, the limited number of prenatal and perinatal studies raises the question about the long-term consequences of venlafaxine therapy. The aim of this study was to investigate the effect of venlafaxine exposure during pregnancy and lactation on anxiety-like and depression-like behaviors, as well as adrenocortical hormone concentrations in the adult rat offspring. For this purpose, rat dams were treated orally with venlafaxine from day 15 of gestation to postnatal day 20 at doses of 7.5, 37.5, and 75 mg/kg. Administration of venlafaxine during gestation and lactation affected anxiety-like and depression-like behaviors in adult rat offspring of both sexes. The animals exposed through their mothers to venlafaxine, particularly at the lowest and middle doses, were less anxious and less depressive in several relevant behavioral tests, which can be considered a deviation from the normal state. At clinically relevant doses, venlafaxine did not alter circulating level of corticosterone and aldosterone in the adult offspring. In general, the consequences of venlafaxine were dose dependent and more apparent in females. Together, these results suggest that prenatal and early postnatal exposure to venlafaxine may interfere with functional development of the brain, though not necessarily in a negative way.

Effects of venlafaxine and chronic unpredictable stress on behavior and hippocampal neurogenesis of rat dams.

OBJECTIVE: Epidemiological studies strongly support the theory that stressful life events play an important role in the etiology of depression. The mechanism of chronic stress induced depression involves a number of systems. Chronic stress represents a serious health issue especially during pregnancy and lactation. In this sensitive period, stress can lead to changes in emotion and cognitive behavior both of the mothers and the offspring. It is thus necessary to properly manage stress events during gestation. Venlafaxine belongs to the group of serotonin and noradrenaline re-uptake inhibitor drugs. It is used for the treatment of depression, anxiety disorders and other mood disorders. During pregnancy, however, the use of venlafaxine is questionable due to the lack of experimental and clinical studies. Therefore the aim of this study was to evaluate the effect of chronic unpredictable stress and/or venlafaxine treatment on maternal and open field behavior of dams. Moreover, hippocampal neurogenesis was investigated either. METHODS: Female Wistar rats were subjected to 2-week chronic unpredictable stress induced by random stressors and treated with venlafaxine orally at a dose of 5 mg/kg twice a day. Maternal behavior was evaluated within 5-min observations twice a day. Mothers were also tested in the open field 8 weeks after chronic unpredictable stress procedure in a single 15-min session. Hippocampal neurogenesis was investigated by immunohistochemistry essay using DCX staining. RESULTS: Results of the present study showed altered maternal and open field behavior of the dams. Stressed dams had lowered hippocampal neurogenesis, while venlafaxine treatment reversed this lowering. CONCLUSIONS: These results suggest that stress and antidepressant therapy can have significant impact on behavior and hippocampal neurogenesis in rat dams.

Twenty-Year History of the Organization of the International Interdisciplinary Toxicological Conferences TOXCON.

This is an overview and assessment of the value of the International Interdisciplinary Toxicological Conferences TOXCON, which have been organized reciprocally in Slovakia and the Czech Republic since 1996. Characterization of the individual annual conferences and the results of mutual cooperation between the Slovak Toxicology Society (SETOX) and the Toxicological Section of the Czech Society for Experimental and Clinical Pharmacology and Toxicology of the Czech Medical Association of J. E. Purkyne (TS CSEKFT CLS JEP) are presented. Moreover, cooperation and common efforts to promote toxicology as a modern interdisciplinary subject with toxicological organizations from the Visegrad Group (V4) and within the Federation of European Societies of Toxicology EUROTOX are also highlighted.

Chronic unpredictable mild stress paradigm in male Wistar rats: effect on anxiety- and depressive-like behavior.

OBJECTIVES: There are several models of depression. Chronic unpredictable mild stress (CMS) appears to have the greatest validity, although it is often being criticized for low reliability. METHODS: Male Wistar/DV rats were used in this study to assess our modified 2-week model of CMS as a combination of psychosocial, physical and metabolic stressors and to compare the effect of acute administration of venlafaxine (VFX) and diazepam (DZP), either in stress or no stress conditions. The animals were exposed to one particular stressor each day. The time of day and duration of the stressor differed across the procedure to avoid animals to adapt to the stress stimulus. After cessation of stress, the animals underwent the following behavioral tests to assess motor activity, cognition, anxiety- and depression-like behavior: Open field test, Elevated plus maze, Forced swim test, Stress-iduced hyperthermia, Light/dark test and Y maze. To assess hypothalamic-pituitary-adrenal axis (HPA) reactivity in our CMS model, plasma corticosterone levels were measured 24 h after termination of stress. RESULTS: Corticosterone levels were significantly increased compared to control values (p<0.05) in our experimental schedule of CMS. Our paradigm produced delayed anxiety-like behavior observed in Open field (decreased time spent in central zone 3 weeks after CMS, p<0.05), with anxiolytic effect of CMS shortly after its cessation. Stressed animals spent more time in the open arms of Elevated plus maze (p<0.05) and travelled longer distance in the light zone of the Light/dark box (p<0.01). CMS did not increase the behavioral despair analyzed in Forced swim test yet it disrupted the capacity of the Stress-induced hyperthermia test (CMS rats failed to react to the stress by increasing the core temperature). CONCLUSIONS: Based on our results, we can conclude that our CMS protocol leads to increased corticosterone levels as a result of HPA axis hyperactivity and produces delayed onset of anxiogenic behavior. Moreover, CMS exerted a substantial effect on the behavioral outputs, interfering with drug testing.

Neonatal withdrawal syndrome and perinatal asphyxia. How to manage the patient? Case Report.

The aim of this work is to present the pitfalls of management of newborns with neonatal withdrawal syndrome (NWS) of different forms, which were complicated with the presence of severe perinatal asphyxia. The authors present some case reports of asphyxiated newborns of different gestational age with different forms of NWS. Prenatal and perinatal asphyxia determines the prognosis of future development of newborn. The combination of the asphyxia and NWS is stressful not only for the patient, but also for the physician. The most important step in management of this group of patients is to know the detailed mother's and patient's history and to perform detailed physical investigation. The optimal prenatal, perinatal and postnatal management with good cooperation between gynecologist and neonatologist can improve the quality of newborn's life. Care of newborn requires all the time teamwork.

EDITORIAL.

This Supplement of the Journal Neuroendocrinology Letters presents papers from the 19th Interdisciplinary Toxicological Conference TOXCON 2014: Connecting for Safer Europe held in Stará Lesná, Slovakia from Septembert 24-26, 2014. This event was organized by the Slovak Toxicology Society SETOX, Bratislava, Slovakia, with the Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. The scientific program of the conference involved various subjects of experimental, clinical and industrial toxicology. The program was divided into individual sections dealing with specific topics of in vivo and in vitro studies, such as cellular and organ toxicity, genotoxicity, cytotoxicity, mutagenicity, developmental toxicology, military toxicology, ecotoxicology, methodological approaches in toxicology as well as problems of relative safety assessment of drugs and xenobiotics, alternative methods in toxicology, ethical problems and legislation. The meeting attendance exceeded 170 scientists from 8 countries. The presence of outstanding scientists giving keynote lectures provided an opportunity to familiarize with up-to-date research in various fields of toxicology and related subjects. Out of the 143 presentations given at the Conference, the outstanding 29 selected by the scientific committee, are highlighted and documented in this Supplement.

Does nasal neuroglial heterotopia represent a risk for the newborn during delivery?

Neuroglial heterotopia is a rare developmental abnormality. Most frequently the diagnosis is established at birth or in early childhood by a typical clinical presentation. Neuroglial heterotopia can be intracranial or extracranial. A typical example of extracranial heterotopia is nasal glioma, which can be isolated or can communicate directly with the intracranium. The most sensitive investigation for the confirmation of its site is magnetic resonance imaging. Histological investigation is crucial in establishing the diagnosis. The authors present the case of postnatally assessed nasal glioma. They emphasize the importance of detailed prenatal investigation as most important in preventing birth trauma and consequent complications.

Subchronic perinatal asphyxia increased anxiety-and depression-like behaviors in the rat offspring.

OBJECTIVES: Perinatal asphyxia is one of the major cause of mortality in newborns and cause of neurological disorders in adulthood. Brain damage is of the most concern due to high sensitivity of nervous system to suboptimal intrauterine oxygen condition. The aim of this study was to assess effect of subchronic prenatal asphyxia (SPA) during sensitive stages of brain maturation on behavioral changes in rats, as a method of prenatal programming of anxiety and depression-like behavior. METHODS: Pregnant Wistar/DV females were exposed to environment containing lower oxygen (10.5% O2) during sensitive stages of brain maturation (day 19-20 of gestation) for 4h a day and anxiety- and depression-like behaviors in offspring were assessed using battery of behavioral tests--Open field (OF), Elevated plus maze (EPM), Light/dark test (L/D), Forced swim test (FST), and Stress induced hyperthermia (SIH). RESULTS: OF did not induced changes of locomotor and exploration activities. The anxiety-like behavior was induced by SPA in EPM and L/D. These results were significant in males SPA group only. The higher response to the stress stimulus in SIH was recorded in both males and females SPA group. The intensity of climbing on the walls of cylinder in FST in males SPA group was significantly decreased indicating depression-like behavior in adulthood. CONCLUSIONS: In conclusion, we found out that perinatal asphyxia on 19th and 20th day of gestation caused anxiety- and depression-like behaviors in the rat offspring. Our model of SPA has proved to be useful to study the conditions of asphyxia during pregnancy, and could be suitable model for studies uncovering the mechanisms of prenatal programming of psychiatric diseases.

Pyridoindole antioxidant-induced preservation of rat hippocampal pyramidal cell number linked with reduction of oxidative stress yet without influence on cognitive deterioration in Alzheimer-like neurodegeneration.

BACKGROUND: The idea of antioxidant therapy attenuating Alzheimer disease (AD) neuropathology starts to be attractive. Animal models are often used in these studies. An AD-like model of trimethyltin (TMT)-induced neurodegeneration, targeting the hippocampus, involves neuronal cell death and cognitive impairment. OBJECTIVES: Effect of the pyridoindole SMe1EC2 (3×50 mg/kg) and vitamin C (3×50mg/kg) was analyzed in the model of TMT-induced (8 mg/kg) neurodegeneration. METHODS: The study was focused on the effect of the antioxidants tested on learning performance in the Morris water maze (MWM) on days 21-25 after TMT administration, on biochemical variables - malondyaldehyde (MDA) and lysosomal enzyme NAGA in brain cortex and blood serum, and on pyramidal cell number in the CA1 area of the hippocampus on day 31 after TMT administration in adult male Wistar rats (n=32). RESULTS: Critical deterioration of learning performance was observed due to the TMT administration in the MWM. Further, apparent reduction of pyramidal cell number to 21% in the CA1 area of the hippocampus, increased MDA and NAGA activity in serum and increased NAGA activity in the cortex were determined contrary to controls. In serum, an increase of MDA level was prevented by both antioxidants tested without any effect on NAGA activity. SMe1EC2 apparently preserved pyramidal cell viability in the CA1 area. Both substances tested failed to ameliorate the detrimental effect of TMT on spatial memory. CONCLUSION: The biochemical and morphometrical findings suggest that reduction of oxidative stress may play a role in AD-like neurodegeneration. Different doses and timing of SMe1EC2 administration might bring improvement in next learning performance.

Oxidative stress in twins.

OBJECTIVES: The aim of the study was to determine the value of the total antioxidant system (TAS) and level of malondialdehyde (MDA), and the activity of glutathione peroxidase, superoxide dismutase in the case of premature twins - identical twins, monozygotic, on the 1st and 5th day of life and to compare the values between the first-born twin A and the second-born twin B. RESULTS: We confirmed the difference between A and B twins in values of TAS and MDA, as well as the difference between the 1st and 5th day of life. CONCLUSION: The values of TAS, which show the total activity of antioxidant enzymes in a newborn's organism, reflect the ability of protection against oxidative stress before and during delivery. In the case of twin pregnancy, the value of TAS is crucial and determines the degree and severity of consequences of asphyxia. MDA values indicate the presence of lipoperoxidation.

Ideas that persist for centuries - by Erasmus of Rotterdam, the prince of humanists.

The paper highlights the personality of the founder of European student exchange program ERASMUS (EuRopean Community Action Scheme for the Mobility of University Students) Erasmus of Rotterdam. He was one of the leading European humanists and has left a literary legacy of large dimensions. His thoughts, ideas, opinions, and mainly the works have a great benefit for society even today. From 16th century to the present time they are the subject of unchanged interest.

From pediatric history. Important personalities in relation to some genetic defects - "trisomies".

The aim of this study is to present a short biography of some important physicians and describe the most prominent differences between trisomy 13, 18 and 21. The authors present the most prominent differences between trisomy 13, 18 and 21. The work of many important physicians, geneticists, has helped in the process of recognition of congenital anomalies. This group of famous persons includes Patau, Edwards and Down.