Relationship between COVID-19 and orofacial clefts.

The work presents the connection between the infection of COVID-19 during pregnancy and non-syndromic orofacial clefts (NSOFC). Aim of the study was to compare the incidence of COVID-19 disease during mother´s pregnancy between a group of the children with NSOFC and a control group of the children without NSOFC. COVID-19 was confirmed by polymerase chain reaction (PCR) test. The study showed significantly higher incidence of COVID-19 disease in the group of mothers who gave birth to a child with NSOFC in comparison to the group of mothers who gave birth to a child without NSOFC. Our results indicate the possible participation of the infection of COVID-19 in the formation of NSOFCs.

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).

Effect of handling on ATP utilization of cerebral Na,K-ATPase in rats with trimethyltin-induced neurodegeneration.

Previously it was shown that for reduction of anxiety and stress of experimental animals, preventive handling seems to be one of the most effective methods. The present study was oriented on Na,K-ATPase, a key enzyme for maintaining proper concentrations of intracellular sodium and potassium ions. Malfunction of this enzyme has an essential role in the development of neurodegenerative diseases. It is known that this enzyme requires approximately 50% of the energy available to the brain. Therefore in the present study utilization of the energy source ATP by Na,K-ATPase in the frontal cerebral cortex, using the method of enzyme kinetics was investigated. As a model of neurodegeneration treatment with trimethyltin (TMT) was applied. Daily handling (10 min/day) of healthy rats and rats suffering neurodegeneration induced by administration of TMT in a dose of (7.5 mg/kg), at postnatal days 60-102 altered the expression of catalytic subunits of Na,K-ATPase as well as kinetic properties of this enzyme in the frontal cerebral cortex of adult male Wistar rats. In addition to the previously published beneficial effect on spatial memory, daily treatment of rats was accompanied by improved maintenance of sodium homeostasis in the frontal cortex. The key system responsible for this process, Na,K-ATPase, was able to utilize better the energy substrate ATP. In rats, manipulation of TMT-induced neurodegeneration promoted the expression of the α2 isoform of the enzyme, which is typical for glial cells. In healthy rats, manipulation was followed by increased expression of the α3 subunit, which is typical of neurons.

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.

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.

Foetal asphyxia as a strong stimulator of the sympathetic nervous system in the brain. Case Report.

The aim of the study was to analyse case report of prenatally unknown asphyxia of the foetus (a preterm newborn from the second pregnancy delivered by urgent caesarean section in 31st gestational week; birth weight 850 grams, birth length 41 cm, value of Apgar score 7/8) with signs of respiratory insufficiency immediately after birth with hypotonicity. The authors present the case of postnatal at the 1st day of life assessed cystic malformation in the brain of premature newborn. They emphasize the importance of detailed prenatal investigation as most important in preventing prenatal asphyxia and consequent complications. Central nervous system and especially white matter of the brain of the newborn is most vulnerable area of the brain. Together with oxidative stress after exceeding of antioxidant capacity belong among main factors that play an important role in the pathogenesis of hypoxic-ischemic encephalopathy.

Neonatal brain injury as a consequence of insufficient cerebral oxygenation.

Neonatal brain hypoxic-ischemic injury represents a serious health care and socio-economical problem since it is one of the most common causes of mortality and morbidity of newborns. Neonatal hypoxic-ischemic encephalopathy is often associated with signs of perinatal asphyxia, with an incidence of about 2-4 per 1,000 live births and mortality rate up to 20%. In about one half of survivors, cerebral hypoxic-ischemic insult may result in more or less pronounced neuro-psychological sequelae of immediate or delayed nature, such as seizures, cerebral palsy or behavioural and learning disabilities, including attention-deficit hyperactivity disorder. Hypoxic-ischemic injury develops as a consequence of transient or permanent restriction of blood supply to the brain. Severity of hypoxic-ischemic encephalopathy varies depending on the intensity and duration of hypoxia-ischemia, on the type and size of the brain region affected, and on the maturity of the foetal/neonatal brain. Though a primary cause of hypoxic-ischemic injury is lack of oxygen in the neonatal brain, underlying mechanisms of subsequent events that are critical for developing hypoxic-ischemic encephalopathy are less understood. Their understanding is however necessary for elaborating effective management for newborns that underwent cerebral hypoxic-ischemic insult and thus are at risk of a negative outcome. The present paper summarizes current knowledge on cerebral hypoxic-ischemic injury of the neonate, fundamental processes involved in etiopathogenesis, with a special focus on cellular and molecular mechanisms and particular attention on certain controversial aspects of oxidative stress involvement.

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.

Progressive increase of lysosomal enzyme activities in hippocampus associated with reduction of population spike in a rat model of neurodegeneration.

OBJECTIVES: Extensive effort has been made to identify early markers of neurodegeneration as late stages have no chance of treatment. Recently, many experimental models have been used to study hallmarks of neuronal injury. One of them is the model of trimethyltin (TMT)-induced damage associated with cognitive decline, thus called a model of Alzheimer-like disease. OBJECTIVE AND METHODS: Our aim was to study neuronal transmission in hippocampal slices of male Wistar rats affected with a single dose of TMT (7.5 mg/kg, i.p.) during the first three weeks of its action. The monitored time periods after TMT administration were days 1-3; 8-10 and 15-17. At the same time periods, right hippocampi were collected for determination of changes in specific activities of two lysosomal enzymes. Electrophysiological measurements were based on stimulation of Schäffer collaterals and registration of evoked responses in the stratum pyramidale and the stratum radiatum at the CA3-CA1 synapse. Specific activities of N-acetyl-ß-D-glucosaminidase (NAGA) and cathepsin D (Cat D) were determined spectrophotometrically. RESULTS: During three weeks after i.p. TMT administration to rats, we found a time-dependent reduction of postsynaptic neuronal firing, expressed by diminished population spike (PoS) amplitude recorded in the stratum pyramidale accompanied with marked increase in specific activity of NAGA to respective 111%, 163% and 252% in the 1st, 2nd and 3rd week compared to unaffected rats. In the stratum radiatum, reduction of the slope of excitatory postsynaptic potential was not time-dependent but almost constantly reduced from the 1st to 3rd week after TMT administration (55-60%) compared to control rats. Specific activity of lysosomal enzyme Cat D was significantly increased in the 3rd week after TMT administration. CONCLUSION: This work demonstrates a time-dependent reduction of somatic response in the hippocampus of TMT affected rats during the first three weeks. This reduction of neuronal firing was later accompanied with increase of specific activity of NAGA and Cat D, supporting evidence that lysosomal dysfunction may be one of the primary contributors to TMT-induced neurodegeneration.

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.

Asphyxia in newborn--risk, prevention and identification of a hypoxic event.

The aim of this review is to present the summarisation of the knowledge about biochemical and clinical changes that occur under the influence of asphyxia as well as about the treatment. Results of experimental works in animal models bring us the explanation about many postasphyxiated changes and help us to understand the pathophysiological changes and consequences of asphyxia. The authors present the most prominent consequences of neonatal asphyxia in clinical and experimental conditions. Asphyxia significantly contributes to neonatal morbidity and mortality and determines the prognosis of future development. New insights into the pathophysiology of birth asphyxia provide the opportunity how to prevent permanent damage by the activation of the fundamental molecular processes. Care of newborn asphyxia requires teamwork. Prognosis of the asphyxiated newborn is still dependent on developmental stage (gestational age), the length and intensity of asphyxia, on the level of medical care.

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.

Early and late stage of neurodegeneration induced by trimethyltin in hippocampus and cortex of male Wistar rats.

BACKGROUND: Trimethyltin (TMT), a potent neurotoxicant, elicits neuronal death in the limbic system and causes damage particularly in the hippocampus. Current interest relates to the opportunity to use TMT as an experimental model of neurodegeneration in the study of Alzheimer-like diseases. OBJECTIVE: In light of recently found species-specific and strain-specific differences in TMT intoxication, the aim of this study was to characterise the model of TMT-induced neurodegeneration in the brain of Wistar rats during early (days 1-3) and late (days 22-24) stage of neuronal damage. RESULTS: Reduced neurotransmission at the CA3-CA1 synapse and reduced number of cells accompanied with reduced width of CA1 pyramidal cell layer were observed at the late stage of TMT intoxication (7 mg/kg, i.p.). Long-term potentiation of excitatory postsynaptic potential, elicited by train stimulation (100 Hz, 1s), was not impaired by the dose of TMT tested. Activation of pro-apoptotic caspase-3 suggests involvement of apoptosis in neuronal cell death in the hippocampus at the late stage of TMT intoxication. Increased protein carbonyl formation was proved in the cortex at the early stage of TMT intoxication compared both to controls in the early and late stage and to the late stage of TMT action. CONCLUSIONS: TMT-induced neurodegeneration was proved in the brain of Wistar rats. Changes found in the parameters examined may be reliable indicators of neurodegeneration. The increased level of carbonyls in the cortex at the early stage indicates that particularly at the onset of progressive neurodegeneration compounds with antioxidative properties may be effective in slowing down brain injury.