<abstract xml:lang="en"><title style='display:none'>Effects of Elevated Body Temperature on Control of Breathing</title>Changes in body temperature can be evoked mainly by alterations in the peripheral temperature, or modified by shifts in the central body temperature. Two conditions can lead to abnormal elevation of body temperature: hyperthermia or fever. As regards respiratory system, exposure to heat stress is accompanied by marked alterations in breathing, especially by an increase in ventilation. Ventilation rises due to an increase in central output from hypothalamus or brainstem, an increase in peripheral output via skin temperature receptors, an increase in central or/and peripheral chemoreceptor output or sensitivity and can be also mediated through changes in thermoregulatory mechanisms.This review summarizes results of previous studies as well as of experiments done in our laboratory in order to elucidate the mechanisms included in respiratory changes under heat stress.</abstract>

Effects of Elevated Body Temperature on Control of Breathing

<abstract><title style='display:none'>Abstract</title> Hypotrophic newborn is a newborn with birth weight below the 5th percentile weight of corresponding gestational age. Hypotrophic infants have higher morbidity and mortality in comparison with eutrophic neonates. A higher incidence of hypoglycemia, polycythemia, hyperbilirubinemia, thrombocytopenia, perinatal asphyxia and caesarean section occurs typically in hypotrophic newborns. Both, intrauterine hemodynamic dysbalance and centralization of circulation due to hypotrophy cause decreased blood flow to the splanchnic circulation after the birth. There was observed a lower increase in blood flow through the coeliac artery and superior mesenteric artery in comparison with eutrophic newborns during the first postnatal week. These facts are likely to be associated with a higher frequency of abdominal problems and necrotizing enterocolitis.</abstract>

Clinic of Neonatology, Jessenius Faculty of Medicine, Comenius University and University Hospital in Martin, Kollarova 2, 036 01, Martin, Slovak Republic, Phone:+421043/4203 641

Clinic of Neonatology, Jessenius Faculty of Medicine, Comenius University and University Hospital in Martin, Slovakia

Splanchnic Circulation in Small for Date Newborns

<abstract><title style='display:none'>Abstract</title> The autonomic nervous system (ANS) is a principal regulatory system for maintaining homeostasis, adaptability and physiological flexibility of the organism at rest as well as in response to stress. In the aspect of autonomic regulatory inputs on the cardiovascular system, recent research is focused on the study of exaggerated/diminished cardiovascular reactivity in response to mental stress as a risk factor for health complications, e.g. hypertension. Thus, the analysis of biological signals reflecting a physiological shift in sympathovagal balance during stress in the manner of vagal withdrawal associated with sympathetic overactivity is important. The heart rate variability, i.e. “beat-to-beat” oscillations of heart rate around its mean value, reflects mainly complex neurocardiac parasympathetic control. The electrodermal activity could represent “antagonistic” sympathetic activity, the so-called “sympathetic arousal” in response to stress. The detailed study of the physiological parameters under various stressful stimuli and in recovery phase using traditional and novel mathematical analyses could reveal discrete alterations in sympathovagal balance. This article summarizes the importance of heart rate variability and electrodermal activity assessment as the potential noninvasive indices indicating autonomic nervous system activity in response to mental stress.</abstract>

Mala Hora 4, 03601 Martin, Slovak Republic. Phone/fax: +421 43 2633404

Department of Physiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic

Heart Rate Variability and Electrodermal Activity as Noninvasive Indices of Sympathovagal Balance in Response to Stress

<abstract>
<title style='display:none'>Abstract</title>
<bold>Background:</bold> Trichoepithelioma (TE) and basal cell carcinoma (BCC) of skin represent distinct tumor entities but they have a close histogenetic and phenotypic relationship.
<bold>Objective:</bold> A unique case of a BCC arising within a TE is described with an emphasis on the analysis of different and for each tumor type typical immunophenotype.
<bold>Material and Methods:</bold> A 71-year-old man presented with a subcutaneous solid tumor in the lumbar region. The resected tumor specimen was studied by immunohistochemistry.
<bold>Results:</bold> Histology revealed a coexistence of classic TE and nodular BCC. Both tumors were strongly positive for BerEP4 and negative for EMA. Neoplastic epithelium of the BCC showed a diffuse staining for Bcl-2, while the TE expressed Bcl-2 almost exclusively in the peripheral cells of tumor islands. In the BCC, neoplastic nodules exhibited a focal staining for CD10, while the peritumorous stroma did not. In contrast, the TE showed a focal immunoreactivity for CD10 in the stromal cells around the neoplastic islands which were completely negative. The TE contained intratumorous CK20-labeled Merkel cells but they were not detected in the BCC. A stromal immunore-activity for CD34 was found in both tumors. Proliferative activity (Ki-67) was slightly higher in the BCC than in the TE.
<bold>Conclusion:</bold> Although a concomitant presence of TE and BCC in the same skin lesion is a unique finding, it may be sometimes encountered in a biopsy practice. Pathologists should provide a careful histologic examination of the whole TE lesion with precise section sampling to unveil such possible association.
</abstract>

Basal Cell Carcinoma Arising within a Trichoepithelioma: An Immunohistochemical Study

<abstract><title style='display:none'>Abstract</title> Histamine is one of the most important biogenic amines and it mediates numbers of physiological processes. It is also involved in majority of inflammatory diseases via its receptors H1, H2, H3 and H4. The role of histamine had been recognized as substantial in many allergic diseases including bronchial asthma, thus the histamine receptor antagonists (H1) are frequently used in the clinical practice as potent anti-allergic and anti-inflammatory drugs. However, first generation of antihistamines have also adverse effects, predominantly sedation, changes in appetite and many more, and they are still not fully effective in all patients. Attention is now focused mainly on H3 and H4 receptor antagonists and their potential clinical applications. This review focuses basically on the H3 receptor, its expression pattern and some effects which are mediated by H3, discussing its clinical relevance</abstract>

Histamine and its Effects Mediated via H3 Receptor – Potential Clinical Applications of H3 Antagonists

<abstract>
<title style='display:none'>Abstract</title>
Direct oral anticoagulants represent a significant group of drugs used in the prevention or treatment of venous thromboembolic events and stroke in patients with atrial fibrillation. Although routine therapy monitoring is not required, there is an increasing evidence that plasma levels may vary between individuals, suggesting the benefit of plasma levels measurement in some situations. Therapeutic drug monitoring is becoming more popular and accessible to the broader population. Introducing microsampling techniques for the quantitative collection of blood samples has arisen nowadays. The volumetric absorptive microsampling approach using a commercially available device such as a Mitra stick overcomes the hematocrit effect present in the dry blood spot technique. This review discusses the possible application of the volumetric absorptive microsampling approach in monitoring direct oral anticoagulant therapy efficacy.
</abstract>

Volumetric Absorptive Microsampling Technique in the LC-MS Determination of Direct Oral Anticoagulants

<abstract>
<title style='display:none'>Abstract</title>
Various types of cancer exhibit distinct sensitivities to anticancer drugs, reflecting their unique developmental pathways. Exploiting mitochondrial dysfunction in cancer cells presents novel therapeutic opportunities. In recent years, advancements have underscored the significance of oxidative phosphorylation, fatty acid oxidation, and glutamine addiction in cancer cells, shifting attention towards mitochondrial metabolism. The foundation of mitochondrial medicine lies in comprehending targeted mitochondrial therapy and the development of specific mitochondrial drugs. Certain alterations within mitochondrial metabolism lead to the accumulation of oncometabolites, serving as epigenetic regulators, or an increase in reactive oxygen species production, both of which contribute to tumorigenesis. Importantly, the substantial involvement of mitochondrial metabolism in tumorigenesis offers potential avenues for exploiting as strategies for cancer therapy. Integrated pharmacological approaches targeting mitochondrial metabolic pathways are imperative for an effective eradication of tumor masses and a concurrent elimination of small subpopulations of mitochondria. The significance of mitochondria in cancer is undeniable, offering numerous appealing targets for both tailored and personalized cancer therapy.
</abstract>

Metabolic Flexibility: Targeting Mitochondrial Dynamics in Cancer Therapy

<abstract>
<title style='display:none'>Abstract</title>
The progression of tumor formation is a multifactorial process that involves changes at different levels. Within this intricate molecular and cellular landscape of tumorigenesis, specific enzymes, namely matrix metalloproteinases (MMPs), emerge as pivotal contributors. They may influence this process at the level of tissue remodelling, angiogenesis, changes in cell signalling, invasion and metastasis, but may also serve as prognostic markers or therapeutic targets. Although the function of MMPs has been known for a long time, their specific role in the pathogenesis of brain tumors has only begun to be investigated in the last three decades. Deregulation of MMPs expression, frequently observed in brain tumor tissue, is associated with malignant phenotype, dependent on the grade of malignancy and associated with a worse prognosis. They participate in tissue remodelling under physiological and pathological conditions, which predetermines their action especially in the process of invasion and migration of tumor cells into the surrounding tissue. Related to their potential in tumor progression, they are also being investigated as possible targets in anticancer therapy. It would be very difficult to characterize in detail the role of all known MMPs in the context of brain tumor pathogenesis, so we have selected those that have an essential effect in this issue.
</abstract>

The Role of Selected Matrix Metalloproteinases in the Pathogenesis of Gliomas

<abstract>
<title style='display:none'>Abstract</title>
Cancer development and progression are characterized by intricate genetic and epigenetic alternations, with DNA methylation playing a crucial role in this transformative process. Recent advancements in DNA methylation mapping technologies have significantly contributed to the identification of novel cancer biomarkers. We provide a short overview of Conformité Européenne-marked in vitro diagnostic tests designed to detect DNA methylation changes in oncology practice.
</abstract>

DNA Methylation Biomarkers in Cancer Diagnostics

<abstract>
<title style='display:none'>Abstract</title>
<sec>
<title style='display:none'>Introduction</title>
Colorectal cancer (CRC) is one of the leading oncogenic disorders, both in terms of incidence and mortality. The etiology of the disease is certainly multifactorial. Various risk factors like alcohol consumption, smoking, CRC family history, inflammatory bowel disease, hormone therapy, aspirin/nonsteroidal anti-inflammatory drugs use, higher body mass index, consumption of red and/or processed meat, insufficient physical activity, and decreased intake of fruit and vegetables have been pointed out; however, there is not enough support evidence for a single particular causative mechanism. Recently, gut bacterial microbiota has been shown to influence significantly the pathogenesis of CRC. However, little attention is paid to the putative impact of plasmids in gut flora.
</sec>
<sec>
<title style='display:none'>Material and methods</title>
We have designed and tested the workflow for semi-selective isolation and amplification of random circular sequences. The exploitation of rolling circle amplification (RCA) with a random hexamers protocol is crucial for the outcome.
</sec>
<sec>
<title style='display:none'>Results</title>
Our results suggest that it is possible to isolate and amplify plasmid DNA from gut flora and further process, sequence, and identify them.
</sec>
<sec>
<title style='display:none'>Discussion</title>
Little is known about the interactions between bacterial plasmids and human cells. The collection of plasmid sequencing data and the comparison of CRC patients and healthy control sequences can be the first step to elucidating this phenomenon.
</sec>
</abstract>

Characterization of Plasmids Isolated from Bacterial Flora of CRC Patients – Proof of Concept

<abstract>
<title style='display:none'>Abstract</title>
Hematological malignancies represent a heterogeneous group of diseases that may have overlapping clinical manifestations. Successful and optimal management depends on early and accurate diagnosis of the disease. Differential diagnosis therefore requires methods of morphology, immunohistochemistry, flow cytometry, and also molecular and cytogenetic examinations. Molecular diagnostic techniques are becoming more accurate and sophisticated, which is why nowadays hematopathological diagnosis relies heavily on molecular and cytogenetic analyses. They are beneficial not only for diagnosis, but also for evaluating prognostic and risk markers, as well as treatment monitoring. This article presents an overview of selected hematological malignancies – mature lymphoid neoplasms, multiple myelomas, myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemias; their molecular pathology, risk and prognostic markers. Understanding of the biologic basis leds to a targeted therapy development for the treatment of these diseases.
</abstract>

Molecular Pathology of Hematologic Malignancies

<abstract>
<title style='display:none'>Abstract</title>
DNA methylation is characterized as a gene regulatory mechanism that involves the methylation of the 5-carbon (C5) position of cytosine, resulting in the formation of 5-methylcytosine. The analysis of aberrantly methylated cytosine-phosphate-guanine (CpG) dinucleotides, primarily in the promoter regions of tumor suppressor genes, can serve as promising prognostic and predictive markers of cancer development. Meis homeobox 1 (<italic>MEIS1</italic>) gene, crucial for cell growth and differentiation, exhibits dysregulation linked to various cancer types, acting as both a positive and negative regulator. The selection of an appropriate method for the evaluation of gene promoter methylation status is important for clinical implementation without biases regarding false positive and false negative outcomes. The study focuses on the optimization of a novel droplet digital PCR (ddPCR) assay for identifying the methylation status of <italic>MEIS1</italic>. Compared to traditional methods, ddPCR offers an increased sensitivity and specificity, presenting a promising tool for precise DNA methylation assessment with potential implications for cancer diagnostics and prognostics.
</abstract>

Optimizing Droplet Digital PCR Assay for Precise Assessment of MEIS1 Gene Promoter Methylation

<abstract><title style='display:none'>Abstract</title> Background: Rotational thrombelastometry (ROTEM) is a real-time clotting test that provides insight into clotting factors, the fibrinolytic system and platelet function. We obtained the longitudinal values on ROTEM in normal pregnancy and in puerperium.Material and Methods: After ethics committee approval and subject informed consent, citrated blood was sampled from healthy pregnants four times during pregnancy and one time postpartum. As controls we used nonpregnant women undergoing voluntary blood donation. Extem and Intem tests and basic coagulation test were carried out.Results: We included 112 women in our study, 55 non-pregnant women (controls) and 57 healthy pregnants with 5 samplings. The values of maximum clot firmness (MCF - in EXTEM and INTEM) were significantly higher up to 34th-36th week of pregnancy than those in non-pregnant subjects. MCF in 6th-7th week after delivery was significantly higher in both tests. Clotting time (CT) in pregnant women was significantly shorter (EXTEM) compared to non-pregnant subjects. We also found a very strong correlation between MCF and platelet count in all gestational weeks.'Conclusions: Rotation thromboelastometry clearly demonstrates the hypercoagulability in pregnancy and can reflect the higher risk of venous thromboembolism in both pregnancy and puerperium. Strong correlation between MCF and platelet count can suggest role of platelets in hypercoagulability in pregnant women. This study provides a better knowledge about physiological changes in ROTEM measurement during pregnancy and postpartum.</abstract>

National Center of Thrombosis and Haemostasis, Clinic of Haematology and Transfusiology, Jessenius Faculty of Medicine, Comenius University and University Hospital in Martin, Martin, Slovakia

Clinic of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University and University Hospital in Martin, Martin, Slovakia

Department of Haematology and Blood Transfusion, KNsP Cadca, Cadca, Slovakia

Monitoring of Hemostasis by Rotational Thrombelastometry During Normal Pregnancy and Postpartum

<abstract><title style='display:none'>Abstract</title> Skin aging has become an area of increasing research interest in dermatovenerology. Changes in the skin associated with aging can be detected by high - frequency 20 MHz ultrasonography, which is a useful diagnostic technique allowing reliable imaging of cutaneous and superficial subcutaneous structures.Skin thickness is considered an objective parameter providing assessment of the influence of endogenous or exogenous factors, such as ultraviolet (UV) or infrared (IR) rays. Except for the changes in the skin thickness, there are also specific structural changes in the dermis of older subjects - subepidermal low echogenic band (SLEB) - that is a manifestation of photoaging severity. The main aim of this study was to identify and characterize the specific ultrasonographic changes of the cutaneous structure related to age and degree of photo exposure (the presence and measurement of SLEB).</abstract>

Identification of the Age Related Skin Changes Using High-Frequency Ultrasound

<abstract xml:lang="en"><title style='display:none'>Determinants of Heart Rate in Newborns</title>This paper presents an overview of cardiac chronotropic regulation determinants in newborns, which are reflected in mean heart rate (HR) and heart rate variability (HRV). Heart rate and heart rate variability in newborns are determined by many factors. Heritability and maturation play major role. Factor of the maturation can be seen in HR and HRV differences between healthy full term and preterm newborns as well as in changes over early postnatal time. These parameters in newborns are influenced also by many other factors as gender, nutrition, sleep, breathing pattern/ventilation, etc.Autoregulation and extrinsic regulation of cardiac activity has its own specificities in newborns. Homeometric mechanism (depended on HR) is dominant and baroreflex sensitivity is reduced, mainly in premature newborns. Complex cardiac regulation can be studied and evaluated by cardiac reflexes. Examination of the reflexes in newborns is limited. Therefore, new approaches for the study of maturation cardiac control are developed taking into consideration all cardiac activity in newborns determinants.</abstract>

Determinants of Heart Rate in Newborns

<abstract xml:lang="en"><title style='display:none'>Selective Inhibition of Phosphodiesterase 7 (PDE7) by BRL50481 in Healthy and Ovalbumin-Sensitized Guinea Pigs</title>Phosphodiesterase (PDE) inhibitors may have significant clinical benefit in respiratory diseases associated with inflammation. The aim was to evaluate effects of selective PDE7 inhibitor (BRL50481) on citric acid induced cough, <italic>in vivo</italic> and <italic>in vitro</italic> airway smooth muscle reactivity in both healthy and ovalbumin sensitized guinea pigs, as well as its effectiveness in changes of blood cells count.Tested drugs were administered intraperitoneally to male guinea pigs once daily for 7 days either vehicle 10% DMSO (dimethyl sulfoxide) 3 ml/kg (as control) or BRL50481 1 mg/kg. Double chamber whole body plethysmograph was used for evaluation of citric acid (0.6 M) induced cough and specific airway resistance. Organ bath method was used for measurement of tracheal and lung tissue strips contractions evoked by cumulative doses (10-8 - 10-3 mol/L) of acetylcholine (ACH) and histamine (HIS).In healthy guinea pigs we did not observe significant effect of tested drug BRL50481 on <italic>in vitro</italic> contractions (similarly to <italic>in vivo</italic> conditions). The effect on cough was in healthy animals negligible. In ovalbumin-sensitized animals, more pronounced <italic>in vitro</italic> relaxing effect of BRL50481 in HIS induced contractions was observed with similar results <italic>in vivo</italic> and no significant change in number of cough efforts.Our results suggest that PDE7 inhibitors have stronger anti-inflammatory effect compared to its direct effect on smooth muscle and cough.</abstract>

Department of Pharmacology Jessenius Faculty of Medicine, Comenius University, Martin

Selective Inhibition of Phosphodiesterase 7 (PDE7) by BRL50481 in Healthy and Ovalbumin-Sensitized Guinea Pigs

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Acta Medica Martiniana

The Journal of Comenius University in Bratislava

 Acta Medica Martiniana is a medical scientific journal, first published in print form in December 2001. It is a continuation of the journal / almanac Folia Medica...

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 Acta Medica Martiniana is a medical scientific journal, first published in print form in December 2001. It is a continuation of...

Acta Medica Martiniana

The Journal of Comenius University in Bratislava

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