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TREATMENT AND PREVENTION OF EMOTIONAL BURNOUT AMONG SPECIAL SERVICES AND MILITARY PERSONNEL: BEST PRACTICES AND PROSPECTS FOR THEIR IMPLEMENTATION

Original article

Liliia Semenenko, Uzef Dobrovolskyi, Stanislav Petrenko, Maria Yarmolchyk, Oleksii Ishchenko

MMSL 2025, 94(3):95-106 | DOI: 10.31482/mmsl.2024.010

Objectives: The purpose of this research is to identify effective treatments and promote prevention of emotional burnout among special services and military personnel. It also aims to highlight best practices and potential implementation strategies by specialists from Ukraine, Kazakhstan, Poland, UK, USA, Canada, and South Korea.Methods: The primary method utilized in this research is experimentation, employing practical psychology techniques to enhance the personal competencies of special services and military personnel. Psychological observation, conversations, questionnaires, diagnostics, and statistical analysis were auxiliary methods used to tailor emotional burnout prevention strategies specific to this group.Results: As a result, the research identifies features and specifics of the work of employees of special services and military structures, presents the main ways, and methods of treatment and prevention of emotional burnout and reveals the most effective of them for employees of special services and military personnel depending on their individual and personal characteristics. The application of emotional burnout training as a preventive measure is substantiated by the best practices and prospects of its implementation.Conclusions: The authors conclude that emotional burnout is one of the main problems of the 21st century, which concerns not only those whose activity is communication with people, but also any person who cannot regulate their emotional state. The specifics of the activities of employees of special services and military units require special professional and personal qualities, the absence of which can contribute to the formation of emotional burnout.

BEST OF ECO FORUM, ISTANBUL

Letter to the editor

Vladimír Pavlík

MMSL 2020, 89(1):52-54

The Best of ECO 2019, a scientific forum, was held under the patronage of the European Association for the Study of Obesity (EASO) in Istanbul on 19 - 20 October, 2019. The European Congress on Obesity (ECO) took place on the turn of April and May 2019 in Glasgow and there were delivered a lot of interesting presentations. The most interesting of them were then presented at the scientific forum in Istanbul. The best European obesity specialists discoursed on obesity problems there. More than 80 specialists mostly from Europe but also from India or Lebanon participated in this forum. The Czech Republic was represented by 4 obesity specialists. Within two days, there were delivered about 20 oral presentations including presentations of pharmaceutical companies....

DUAL BINDING SITE INHIBITORS OF ACETYLCHOLINESTERASE
AS THERAPEUTIC TREATMENTS FOR ALZHEIMER’S DISEASE: ANY NEED FOR AN UPDATE?

Meeting abstracts

K. Petrov, I. Zueva, J. Dias, S. Lushchekina, V. Semenov, F. Nachon, E. Nikolsky, P. Masson

MMSL 2018, 87(88):125

Alzheimer’s disease (AD) is a broadly spread neurodegenerative disorder of ageing population manifesting itself in progressing loss of cognitive functions down to total demolition of intellect and disability. Profound synaptic dysfunction contributes to early loss of short-term memory in Alzheimer’s disease. Here we show the protective effects against amyloid-induced synaptic toxicity of C-35, a potent reversible inhibitor of acetylcholinesterase (AChE). Crystal structure of the complex between human AChE and C-35 revealed tight contacts of ligand along the enzyme active site gorge. Molecular dynamics simulations indicated that the external flexible part of the ligand establishes multiple transient interactions with the enzyme peripheral anionic site. Thus, C-35 is a dual binding site inhibitor of AChE. In amyloid-transgenic mice, C-35, when administered after disease onset, reversed synapse loss, decreased the number of amyloid plaques and restored learning and memory. When administration of C-35 and the clinically relevant AChE dual inhibitor donepezil was terminated three weeks after the trial started, animals, that were receiving C-35 showed a much better ability to learn than those who received physiological saline or donepezil. Our results provide evidence that C-35 has a more pronounced Alzheimer’s disease-modifying action than donepezil.

FROM DUAL BINDING SITE AChE INHIBITORS TO CHAMELEON MOLECULES: DISCOVERY OF POTENT BuChE INHIBITORS

Meeting abstracts

Carlos Roca, Talita P.C. Chierrito, Concepción Perez, Loreto Martinez, Nuria Campillo, Ana Martinez

MMSL 2018, 87(88):62

Current pharmacotherapy for Alzheimer's disease (AD) involves compounds aimed at increasing the levels of acetylcholine in the brain through inhibition of AChE. These drugs, known as acetylcholinesterase inhibitors, have been shown to improve cognition and global functions but have little impact on improving the eventual progression of the disease. However, there are evidences that other cholinesterases such as butyrylcholinesterase (BuChE) can play an important role in cholinergic function in the brain, and the long-suspected non-cholinergic actions of acetylcholinesterase, mainly the interference with the beta-amyloid protein cascade, have recently driven a profound revolution in cholinesterase drug research [1-2]. We will present our journey from dual binding site AChE inhibitors as potent beta-amyloid modulators to the more recent serie of indolylpiperidines hybrids with an unexpected and very potent hBuChE inhibition. Experimental and computational studies have revealed the chameleon behavior of these molecules able to change their bioactive conformation depending on the cholinesterase binding site. Based on the potent activity of these compounds targeting BuChE, the low cellular toxicity and the in vivo target engagement, we can propose these indolylpiperidine derivatives as valuable tools for the study of the role of BuChE in AD and probably as potential drugs candidates for its future pharmacotherapy.

ENHANCEMENT IN PYRIDINIUM OXIME-ASSISTED REACTIVATION OF TABUN-INHIBITED ACETYLCHOLINESTERASE ACHIEVED BY ACTIVE SITE MUTATIONS

Meeting abstracts

Zrinka Kovarik, Maja Katalinić, Nikolina Maček Hrvat, Goran Šinko, Tamara Zorbaz, Anita Bosak

MMSL 2018, 87(88):14

Tabun represents a phosphoramide class of organophosphosphates that are covalent inhibitors of acetylcholinesterase (AChE), an essential enzyme in neurotransmission. The currently used therapy in excessive cholinergic stimulation consists of the muscarinic antagonist of acetylcholine stimulation, an anti-seizure drug when indicated and an oxime as the reactivator of inhibited AChE. Since common oximes are particularly ineffective in tabun exposure, we probed the reactivation of phosphoramidate conjugates in more depth by using mutants of AChE and pyridinium oximes to reveal the structural subtleties and yield more information on the architecture of the active centre gorge needed for the reactivation of phosphoramidate agents used in terrorism and as pesticides. Our results indicated that the replacement of aromatic residues with aliphatic ones at the acyl pocket and choline binding site mostly interfered with the stabilization of the oxime’s pyridinium ring(s) in the proper orientation of the oxime group toward the phosphorylated active site serine. The peripheral binding site mutation resulted in a 2-5 fold increase in the reactivation rates by bis-pyridinium oximes when compared to the AChE wild type. In the case of mono-pyridinium oximes, we reported a 150-fold enhancement of the maximal reactivation rate for the choline binding site mutation, while the molecular recognition seemed to remain preserved. Therefore, our results emphasized the positive effect of several mutations on oxime embedding and orientation into a position for productive interactions with the tabun-phosphorylated active site serine indicating a future potential for further development of pseudo-catalytic bioscavengers based on AChE mutants.

CONSIDERING THE IMPORTANCE OF MEDICINAL PLANTS AND NATURAL PRODUCTS AND THEIR MECHANISMS OF ACTION FOR TREATMENT OF GASTROINTESTINAL DISORDERS

Review article

Mohamad Hesam Shahrajabian, Wenli Sun

[Ahead of Print]MMSL X:X | DOI: 10.31482/mmsl.2025.007

Background and Purpose: The application of medicinal plants and herbs to cure diverse animal and human ailments predates recorded history. Gastrointestinal disorders have a high prevalence in human societies.Methods: This research examined the scientific literature from 1990 to June 2025 by conducting a bibliometric analysis of the literature published on the Web of Science database, including more than one thousand articles. The information provided was obtained from randomized control experiments, analytical observations, review articles, and studies which were gathered from different literature sources such as Google Scholar, Scopus, Science Direct, and PubMed.Results: The gastrointestinal tract is one of the most important organs in the human body, and it is vulnerable to great diversity of diseases such as infectious and parasitic disorders, constipation, gastroenteritis, reflux, diarrhea, and bloating. Some of the most important medicinal plants which have been used in different traditional medicinal sciences for the treatment of dyspepsia symptoms are chamomile (Matricaria recutita), cinnamon (Cinnamomum verum), ginger (Zingiber officinalis), licorice (Glycyrrhiza glabra), peppermint (Mentha piperita), and guava (Psidium guajaba). The most notable herbs used to treat bloating are aniseed (Pimpinella anisum), cassia (Cinnamomum aromaticum), celery (Apium graveolens), cinnamon (Cinnamomum verum), dill (Anethum graveolens), fennel (Foeniculum vulgare), ginger (Zingiber officinalis), parsley (Petrosilenum crispus), pennyroyal (Mentha pulegium), peppermint (Mentha spicata), star anise (Illicium verum), and thyme (Thymus vulgaris). Phytochemicals such as seaweed-derived polysaccharide, phytohemagglutinin, and allicin have been reported as important components to induce precocious gut maturation. Phytochemicals can also change the composition of gut microbiota, digest normally indigestible molecules into bioavailable molecules, and enhance nutrient availability. Ganoderma lucidum, Gegen Qinlian decoction, Huang-qin decoction, and Glycyrrhiza uralensis Fisch. are important traditional Chinese medicine with significant effects on intestinal flora and different microbial communities.Conclusions: The review article aims to study and survey the importance of medicinal plants and herbs while considering their mechanisms of action for treatment of gastrointestinal disorders.

DESIGN, CHEMICAL SYNTHESIS, AND IN VITRO  EVALUATION OF NOVEL UNCHARGED CHOLINESTERASE REACTIVATOR

Original article

Vendula Hepnarova, Martina Hrabinova, Jakub Opravil, Mojmir Vanek, Eva Mezeiova, Lukas Gorecki, Tomas Kucera, Daniel Jun, Ondrej Soukup, Lubica Muckova, Jan Korabecny

MMSL 2025, 94(4):135-145 | DOI: 10.31482/mmsl.2024.015

The primary toxicological mechanism of organophosphorus compounds (OPCs) is the irreversible inhibition of acetylcholinesterase (AChE), leading to the accumulation of acetylcholine and subsequent cholinergic crisis, which can result in fatal respiratory failure. Conventional oxime reactivators, such as pralidoxime and obidoxime, are limited by their inability to permeate the blood-brain barrier (BBB) and inconsistent efficacy across different OPC types. To address these limitations, we designed a novel non-quaternary oxime reactivator codenamed K1396, with enhanced lipophilicity for improved BBB penetration and dual-binding capability at both the peripheral anionic site (PAS) and the catalytic active site (CAS) of AChE. This study compares the in vitro reactivation potency, cytotoxicity, and BBB penetration potential of K1396 with standard oximes. K1396 demonstrated comparable or superior reactivation potency, particularly against VX-inhibited AChE, and showed lower cytotoxicity in specific cell lines. Furthermore, K1396 exhibited favorable permeability across the lipid layer, suggesting potential CNS availability. The findings support the therapeutic potential of K1396 as an effective and broad-spectrum reactivator for OPC poisoning.

ON THE INVOLVEMENT OF CBRN AND MEDICAL SPECIALISTS IN THE EXPLOITATION OF FACILITIES SUSPECTED FOR THE PRESENCE OF BIOLOGICAL MATERIAL

Original article

Radim Zahradníček, Tomáš Rozsypal, Hynek Schvach

MMSL 2023, 92(3):235-246 | DOI: 10.31482/mmsl.2022.045

The existence of chemical, biological, radiological, and nuclear (CBRN) weapons poses a significant problem in terms of possible proliferation of technologies and materials, despite international agreements and regulations. The role of military forces in operations can be to support counter-proliferation initiatives to prevent their acquisition, deployment, or employment. The article analyzes the current situation in the field of site exploitation under CBRN environments, with a specific focus on biological threats. It describes a current state and a research question, which is addressed on the basis of scenario analysis methodology. The result is a scenario for the activities of troops in CBRN environments, which illustrates the possible operational reality during the localization of biological sites, their characterization and exploitation. The following application part presents proposals for the division of phases of the exploitation process and a proposal for the determination of CBRN and medical specialists of the Czech Armed Forces as the implementation elements.

HISTOLOGICAL AND HISTOMORPHOMETRIC EVALUATION OF THE SYSTEMIC METFORMIN ADMINISTRATION ON BONE HEALING IN RABBITS

Original article

Raad M. Hussein, Ghada A. Taqa

MMSL 2024, 93(1):100-111 | DOI: 10.31482/mmsl.2023.011

Background: After injuries, infections, or tumor removal, endogenous healing depends on bone repair. Disorders of bone healing are difficult to treat in clinical settings. There are numerous induced methods for correcting bone abnormalities, such as the induced membrane technique, allogenic bone grafting, synthetic bone grafting, artificial joint replacement, and autologous bone grafting. However, the delivery of the bone graft and bone filling materials necessitates surgical implantation at the fracture site, which could cause edema, infection, and the development of heterotopic bone locally. Therefore, systemically administered osteogenic drugs will provide an excellent method for bone lesion healing. Aim of the study: to evaluate the systemic effect of metformin on bone healing after surgical induction of bony defect and to determine the amount of newly formed bone using histological, histomorphometric analysis, and the surface area measurement of newly formed bone. Also to study the safety of metformin administration at the administered dose for this purpose. Materials and methods: Twenty mature male New Zealand rabbits were separated into two groups, each including ten rabbits for the study. The same surgical procedure was performed on all rabbits. Two holes were made at the femur (3 mm in diameter and 3 mm in depth) and left empty. Metformin tablets were ground into a fine powder and the resultant powder was dissolved in 10ml of water to prepare a liquid dosage containing 50 mg /1ml of metformin. Metformin is administered orally to the rabbits through a feeding tube at a dose of 50 mg/kg body weight. Animals were euthanized at two-time intervals, 14 and 28 days. The femur was separated, sectioned preserved, and sent for histological analysis and histomor-phometry. Results: The results revealed that there is an increase in new bone formation and bone-forming cells in the metformin-treated group. Conclusion: Metformin increases bone healing by increasing the number of bone-forming cells and the surface area of newly formed bone tissues and causes less inflammatory response at the site of a bone lesion. So it possesses an osteogenic effect.

AUTOLOGOUS FAT REINJECTION AFTER PRESERVATION AT −2 TO −18°C: A CLINICAL STUDY OF 973 PATIENTS

Original article

Mohammad Salman Saeed, Qasim S. Al Chalabi, Husam Ali Salman

MMSL 2024, 93(3):288-296 | DOI: 10.31482/mmsl.2023.035

Objective: To study the efficacy of autologous fat transplantation after preservation at −2 to −18°C in a domestic refrigerator.Patients and methods: This study was conducted in a private clinic from December 2017 to December 2021. A total of 973 female patients were included. Under a full aseptic technique, fat was harvested using a 4 mm suction blunt cannula with three longitudinal slits. Three 50 mL syringes of fat were obtained before transferring it to 10 mL syringes; then, the fat was centrifuged at 3500 rpm for 1 min and injected through an 18 gauge blunt cannula. In addition, 50 mL of fat without centrifugation was stored in a domestic refrigerator for 3 weeks to be reinjected after fast thawing for 20 min, and then centrifuged to be ready for the second session. All participants had follow-up visits at 3 weeks, 6 months, and 1 year.Results: Participants ranged in age from 18 to 65 years. The abdomen was the fat donor site in 63.3% of the patients, while round-face style augmentation was performed in 48.3% of the patients. An assessment at 3 weeks revealed that 84.1% of patients required a second session. After 6 months, on an assessment using a 10-point scale, patients who received a single session and a second session scored 6.05 and 7.46, respectively. At 1 year, the assessment scores were 5.65 and 7.12 for those with a single and second session, respectively, and 60% of patients were fully satisfied.Conclusion: Autologous fat preserved in a domestic refrigerator for 3 weeks is a safe, cheap, and tolerated filler for facial augmentation.

RESISTIN IN RHEUMATOID ARTHRITIS

Review article

Fatimah Haitham Fathi, Ammar A.Y. Almulathanon, Jehan A. Mohammad

MMSL 2024, 93(2):218-223 | DOI: 10.31482/mmsl.2023.021

Rheumatoid arthritis (RA) is a chronic multisystem illness that affects millions of individuals. The primary goal of RA therapy is to improve patients' quality of life by reducing pain severity, preserving or improving functional capability, and decreasing disability. The significance of resistin in the pathophysiology of RA has been explored in recent years, although its role is unclear as it is largely produced by macrophages. In this review, we have analyzed 10 studies from the PubMed site that demonstrate a relationship between resistin levels and the severity of RA.

7-METHOXYDERIVATIVE OF TACRINE IS A ‘FOOT-IN-THEDOOR’ BLOCKER OF GluN1/GluN2 AND GluN1/GluN3 NMDA RECEPTORS

Meeting abstracts

Martina Kaniakova, Lenka Kleteckova, Katarina Lichnerova, Kristina Holubova, Kristyna Skrenkova, Miloslav Korinek, Jan Krusek, Tereza Smejkalova, Jan Korabecny, Karel Vales, Ondrej Soukup, Martin Horak

MMSL 2018, 87(88):77

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the mammalian central nervous system (CNS), but their dysregulation results in the aetiology of many human CNS disorders. Several NMDAR modulators including memantine have been used successfully in clinical trials. Indeed, 1,2,3,4-tetrahydro-9-aminoacridine (tacrine; THA) was the first approved drug for Alzheimer’s disease (AD) treatment. 7-methoxyderivative of THA (7-MEOTA) is less toxic and showed promising results in patients with tardive dyskinesia. Here, we employed electrophysiological recordings in HEK293 cells and rat neurones to examine the mechanism of action of THA and 7-MEOTA at the NMDAR. We showed that both THA and 7-MEOTA are “foot-in-the-door” open-channel blockers of GluN1/GluN2 and GluN1/GluN3 NMDARs and that 7-MEOTA is a more potent but slower blocker than THA. Furthermore, the inhibitory potency of 7-MEOTA at synaptic and extrasynaptic hippocampal NMDARs was similar, and 7-MEOTA exhibited better neuroprotective activity in rats exposed NMDA-induced lesions in hippocampus when compared with THA and memantine. Finally, intraperitoneal administration of 7-MEOTA attenuated MK-801-induced hyperlocomotion in rats. We conclude that 7-MEOTA is a promising candidate for the treatment of diseases associated with the dysfunction of NMDARs.

EFFECT OF MONTELUKAST ON HEALING OF INDUCED ORAL ULCER IN RATS

Original article

Mohammed I. Majeed, Jawnaa K. Mammdoh, Luma I. Al-Allaf

MMSL 2023, 92(4):348-355 | DOI: 10.31482/mmsl.2022.054

Background: Oral ulcers are among the common recurrent oral diseases which seek medical help; the underlying pathology is yet obscure, making medical intervention difficult.Aims: The purpose of this study was to investigate if montelukast could help mouth ulcer model in Albino rats.Methods: The rats were divided into two groups of 24, the control group of 12 rats with induced ulcer and no therapy, and the treatment group with induced ulcer and treated orally with Montelukast 20 mg/kg. Each group had six rats sacrificed after 3 and 7 days of treatment. The lingual ulcer was produced with cotton soaked in 70% acetic acid solution and rubbed against the tongue for 2 minutes. Discolouration of tongue tissue has been noticed. Animals in all groups were weighed on days 1, 3, and 7 following mucosal ulcerations were confirmed.Results: On days 1, 3, and 7, the body weight of the treatment group rats improved as compared to the control group. On days 3 and 7, the tongue histological section of the control group revealed a wide gap of the site of ulcer in the lingual mucosa, inflammatory exudate, and severe infiltration of inflammatory cells (score 3) without re-epithelialization (score 0). Lingual sections of MTK treated group after ulcer induction on day 3 showed the same lesions as the control group whereas after 7 days demonstrated improvement in inflammatory indicators as inflammatory exudate and infiltration of inflammatory cells (score 1), formation of granulation tissue composed of fibrous tissue and angiogenesis and Re-epithelialization (score 1) comparing with the control group.Conclusion: The present study found Montelukast's anti-inflammatory potential characteristics to treat generated lingual ulcers in rats.

MOLECULAR MODELING STUDIES ON THE INTERACTIONS OF AFLATOXIN B1 AND ITS METABOLITES WITH PHERIPHERAL AND CATALYTIC ANIONIC SITES OF HUMAN ACETYLCHOLINESTERASE

Meeting abstracts

Joyce S. F. D. de Almeida, Rafael Dolezal, Samir F. de A. Cavalcante, Kamil Kuca, Kamil Musilek, Daniel Jun, Tanos C. C. França

MMSL 2018, 87(88):93

Aflatoxins are secondary metabolites of the fungi Aspergillus flavus and A. parasiticus. Among them Aflatoxin B1 (AFB1) is the most frequent type in nature and the most carcinogenic and hepatotoxic for mammals. AFB1 is also inhibitor of the enzyme acetylcholinesterase (AChE) and, therefore, a potential chemical and biological warfare agent, as well as its metabolites. In order to investigate this, we performed inedited theoretical studies on the interactions of AFB1 and its metabolites inside the catalytic and the peripheral anionic sites (CAS and PAS) of human acetylcholinesterase (HssAChE), to verify their stability, suggest the preferential ways of inhibition, and compare their behavior to each other. Molecular docking, molecular dynamics and MM-PBSA calculations for the systems HssAChE/AFB1-metabolites, on both sites were performed. All the metabolites presented negative values of interaction energies in comparison to AFB1. This suggests that they can be better inhibitors of HssAChE. Also, the energy values obtained for the CAS were lower than for the PAS for all metabolites, suggesting that they may preferentially bind in the CAS and come closer to the active site. This behavior is different from the experimentally observed for AFB1, pointing to a different way of inhibition for its metabolites.

THE BOON AND BANE OF PARTHENIUM HYSTEROPHORUS FOR HUMAN HEALTH

Review article

Mohd Ubed Noor, Sadique Hussain, Sunvej Choudhary, Swati Tyagi, Mudita Mishra

MMSL 2024, 93(3):297-311 | DOI: 10.31482/mmsl.2023.033

The annual or ephemeral plant Parthenium hysterophorus L. is an upright and heavily branched member of the Asteraceae family. The herb is used to treat heart issues, fever, anemia, wounds, and ulcerated sores. It is applied topically to treat skin issues, while the plant’s decoction is frequently taken orally to address a wide range of ailments. Psoriasis, rheumatoid arthritis, diarrhea, urinary tract infections, dysentery, malaria, psoriasis, allergies, asthma, tinnitus, nausea, vomiting, and neuralgia are just a few of the health benefits that P. hysterophorus L. can provide. Asthma, bronchitis, dermatitis, and hay fever are some of the major problems caused by this weed, which is harmful to all living things because it also depletes nutrient levels and competes with the cultivation of major crops and vegetation. This review discusses the potential health benefits as well as the origin, distribution, morphology, and harmful effects of the plant on human health.

TARGETING TACRINE HEPATOTOXICITY ASSOCIATED WITH THE CYP BIOTRANSFORMATION

Meeting abstracts

Ondrej Soukup, Martin Novak, Lukas Prchal, Jan Korabecny, Martin Horak, Karel Vales

MMSL 2022, 91(88):75

Current symptomatic pharmacotherapy for Alzheimer’s disease is primarily focused on acetylcholinesterase inhibitors and blocking of the NMDA receptor (N-methyl-D-aspartate). Tacrine, a molecule with both of the mechanisms of action, was withdrawn from the market in 2013 after 20 years of use due to the hepatotoxicity probably caused by its 7-hydroxytacrine metabolite. A rationale substitution of the tacrine molecule can potentially hinder the formation of a toxic species. The introduction of the methoxy or phenoxy group to position 7 led to 7-phenoxytacrine (7-PhO-THA) which we hypothesize to bypass the toxic metabolization via 7-OH tacrine and quinon methid. Furthermore, 7-PhO-THA was confirmed being of dual potency, i.e. potent and balanced inhibition of both AChE and NMDARs. We discovered that it selectively inhibits the GluN1/GluN2B subtype of NMDARs via an ifenprodil-binding site, in addition to its voltage-dependent inhibitory effect at both GluN1/GluN2A and GluN1/GluN2B subtypes of NMDARs. Furthermore, whereas NMDA-induced lesion of the dorsal hippocampus confirmed potent anti-excitotoxic and neuroprotective efficacy, behavioral observations showed that 7-PhO-THA manages to avoid side effects, symptoms of schizophrenia typical for NMDA antagonists.

REACTIVATION OF ACETYLCHOLINESTERASE INHIBITED BY NOVICHOK AGENTS – A COMPUTATIONAL STUDY

Meeting abstracts

Tomas Kucera, Zbynek Vecera, Jakub Fibigar

MMSL 2022, 91(88):47

Novichoks are a set of militarily abused substances from the group of nerve agents. The mechanism of their action is the covalent binding to Ser203 of acetylcholinesterase and inhibition of acetylcholine degradation. Any in vitro or in vivo experimental studies of novice-inhibited acetylcholinesterase reactivation have not been published yet (1). However, the possibilities of reactivation can also be investigated computationally. For this study, we used the methods of molecular docking in combination with molecular dynamics.
We hypothesized that reactivation of novichok-inhibited acetylcholinesterase is not possible for steric reasons. In the molecular modeling study, we investigated whether the oxime group of reactivators can get close enough to the active site to make the nucleophilic attack. Calculations were performed for commercial oximes (HI6, obidoxime, pralidoxime etc.) and also for new experimental ones, in total 60 reactivators.
We have found out that some of the reactivators can adopt a position close to the active site and the nucleophilic attack is possible. Our original hypothesis was refuted.

CHOLINESTERASES INHIBITED BY NOVICHOK AGENTS – IN SILICO  STUDY OF REACTIVATION POSSIBILITIES

Meeting abstracts

Tomas Kucera, Zbynek Vecera

MMSL 2022, 91(88):48

Both molecular docking and molecular dynamics was used to visualise the active or blocked site of AChE, and to determine affinity values in silico modelling. Selection of 60 ligands (including commercially available reactivators, e.g. trimedoxime, asoxime) from peer-reviewed articles (2) were docked into into proximity of AChE-A230 complex bond using software AutoDock Vina (v. 1.1.2). The most promising 32 ligands docked in AChE were evaluated by molecular dynamics (GROMACS 2020.4 software).
Evaluation of specified simulations using Visual Molecular Dynamics (VMD) software has shown that the closest distance between the oxime group of the Z03-labeled ligand and the phosphorus of A230 was 3.14Å proposing theoretical successful reactivation regarding the near–attack conformation (NAC) criterion. The results of this study provide a rational basis for the synthesis of proposed reactivators and their consecutive in vitro evaluation.

PREDICTION OF DRUGS’ SIDE EFFECTS IN SILICO

Meeting abstracts

Jakub Fibigar, Tomáš Kučera

MMSL 2022, 91(88):25

The goal of this project is to create algorithm and software solution for prediction of drugs’ side effects. The algorithm is based on calculations of interactions between active substances and known macromolecules.
Methods of molecular docking and reverse molecular docking are used there. Each exanimated drug substance is docked into binding site of each macromolecule of sc-PDB database while the interaction between them is calculated. A set of decoys is selected from the ZINC database based on chemical properties. Decoys are docked into binding site of each macromolecule as well as exanimated drug substances. The docking results of exanimated substances and decoys are compared to determine the specificity of interactions. These methods are implemented using AutoDock Vina. All of docking interactions are analyzed by R software and the list of resulting macromolecules are released. The active drugs substances can be a substrate, inhibitor, or inducer of resulting macromolecules and they are suitable for in vitro testing.
The software solution is designed as a public service accessible by a web browser.

CORRELATION OF COMORBIDITIES AND OUTCOME IN CAD PATIENTS: A NOVEL TANGENTS SCORE STUDY

Original article

Mohammed Abdul Hannan Hazari, Kailas Laxman Rao, Bachi Tazneem, Sana Rafeeq, Syeda Rahmath Fatima, Summaya Jabeen, Kankan Kavya

MMSL 2025, 94(3):107-114 | DOI: 10.31482/mmsl.2024.009

Background: Cardiovascular diseases (CVD) are influenced by various established risk factors, including the ratio of neutrophils to lymphocytes and platelets, which has been shown to be an independent risk factor for acute coronary syndrome (ACS). This study aims to create a new scoring system called TANGENTS that utilizes discrete parameters of risk factors and diagnostic parameters to analyze the outcome of coronary artery disease (CAD) patients with comorbidities, particularly Type 2 diabetes mellitus (T2DM).Methods: We included 151 subjects (mean age 57.92 ± 23.86) who presented with ST-elevation and ST-depression on admission and were treated with heparin, clopidogrel, aspirin, and atorvastatin while undergoing all the necessary diagnostic tests. We obtained ECG and complete blood picture (CBP) results on admission, day 3, and day of discharge.Results: ST-depression on ECG on day-1 was 0.35 and decreased to 0.30 on the day of discharge. ST-elevation on ECG on day-1 was -0.89 and decreased to -0.16 on the day of discharge. The average neutrophil-to-lymphocyte ratio (NPR) was 0.49, which was high in 144 patients. The mean NLR value was 5.52, indicating a correlation between high NLR values and the magnitude of current injury on admission.Conclusion: The TANGENTS scoring system can be used as an early evaluation tool for CAD patients with comorbidities to manage and prevent further complications. It allows for progressive differentiation in the severity of clinical outcomes using all the parameters of the score, and the parameters creating the TANGENTS score scale were found to be reliable.

BEE VENOM – FRIEND OR ENEMY

Review article

Ludovit Pudelka, Sylva Janovska, Jiri Malis, Radek Sleha, Pavel Bostik

MMSL 2025, 94(2):79-93 | DOI: 10.31482/mmsl.2024.006

Increasing resistance to antibiotics, adverse effects of standard anti-cancer or anti-inflammatory treatments, or tumour types resistant to these treatments are leading to a search for alternatives. One of these is the use of natural products, such as bee venom, which have the same or better effect than these standard products. Bee venom has been used to treat a number of diseases for thousands of years. However, a significant obstacle remains the risk of severe allergic reactions, which can be caused by some of the more than 100 substances contained in the venom. Therefore, intensive research is currently underway to investigate not only the actual use of bee venom or its components in the above areas, but also ways to prevent these adverse effects.

USABILITY OF MILITARY HEALTH SERVICE TO SUPPORT AN INTEGRATED RESCUE SYSTEM

Review article

Vojtěch Humlíček, Josef Fusek

MMSL 2025, 94(4):153-161 | DOI: 10.31482/mmsl.2024.014

The Military Health Service of the Czech Army can support the Integrated Rescue System in the Czech Republic in dealing with emergency and crisis in cases where the basic components cannot ensure the execution of rescue work and clean-up operation by their own forces. The aim of the article is to evaluate the real possibilities of deploying the forces and resources of the Military Health Service to support the integrated rescue system from the point of view of valid legal and internal regulations and to analyze their availability. It was found that the fundamental conditions for the support of the Integrated Rescue System are regulated in the current legal regulations, mainly for the forces and resources of the military health service, which have the character of the other components of the Integrated Rescue System. Dedicated forces and resources of the Military Health Service have a set time of preparation for deployment of 5 - 72 hours. For the use of forces and means within the framework of other assistance, the essential prerequisites for their deployment are established, but no requirements are determined for the capabilities or availability of these forces.

NOVEL GEMINI-TYPE OF QUATERNARY AMMONIUM COMPOUNDS WITH STRONG ANTIMICROBIAL EFFECT

Meeting abstracts

Natalie Zivna, Michaela Hympanova, Hana Strakova, Lenka Pulkrabkova, Jan Marek

MMSL 2022, 91(88):88

Since the discovery of penicillin, antibiotic use and misuse lead to the development of bacterial strains resistant to not only antibiotics, but to common disinfecting agents as well. Monomeric quaternary ammonium compounds (QACs) – common disinfecting agents – are already rendered inefficient due to the acquired resistance. The development of novel agents is now a major component in the fight against the spread of diseases. New designs should enhance the advantages of existing substances (high efficacy, low price), while embracing biodegradability, improved solubility and lower cytotoxicity.
In recent years new, yet related class of disinfectants is on the rice. Diammonium quaternary salts – or so-called ‘Gemini’ QACs, which contain in contrast to their monomeric cousin two polar heads. In total, the molecule contains two positively charged nitrogen atoms and two alkyl chains. From this group; octenidine emerged. Despite its promising results against a broad range of resistant microorganisms, it has many shortcomings: low solubility and mild cytotoxicity. These properties need to be overcome.
In this report, we prepared novel series of octenidine derivates, which have been tested against common nosocomial bacterial strains and against biofilms, which possess unique properties in comparison to single cells. The antimicrobial activity has been evaluated against Gram-positive and Gram-negative bacterial strains. Furthermore, the substances have been tested for cytotoxicity on a mammalian cell line to evaluate one of the key safety parameters.

IN SILICO LIBRARY SCREENING TO FIND NOVEL ANTICANCER AGENT WITH CHEMOSENSITIZING PROPERTIES: FOCUS ON TARGETING ATAXIA TELANGIECTASIA AND Rad3 RELATED KINASE

Original article

Darina Muthna, Tomas Kucera, Zbynek Vecera, Lukas Gorecki, Martin Andrs, Martina Rezacova, Jan Korabecny

MMSL 2024, 93(1):68-83 | DOI: 10.31482/mmsl.2023.009

To bypass the resistance to conventional chemotherapy, attention is paid to the inhibition of alternative targets such as members of the DNA damage response pathway. In the present study, we performed a three-step virtual screening of potential ATR inhibitors followed by evaluation of antiproliferative and chemosensitizing properties of selected compounds in vitro on a panel of cancer cell lines. According to pharmacophore resemblance to standard ATR inhibitor VX-970, a total of 17 compounds were purchased and tested. Among those 17 compounds, two proved antiproliferative efficacy in monotherapy, whereas ten compounds were effective in cisplatin co-treatment on the panel of ten different human cell lines.

THE ROLE OF SERUM MIDKINE IN THE DIAGNOSIS AND PROGNOSIS OF THE COLORECTAL CARCINOMA

Original article

Ali H. Abd-Allah, Haider A. Jabbar, Mazen J. Ibrahim

MMSL 2024, 93(3):274-287 | DOI: 10.31482/mmsl.2023.034

Background: The second-leading source of neoplasm-related death and a primary factor in gastrointestinal cancer, colorectal cancer (CCR) affects both genders globally. Poor eating behaviours, tobacco, an intestinal inflammatory disorder, swellings, inherited characteristics, and the elderly all increase the threat of acquiring this malignancy. The illness is more hostile in patients detected at earlier ages, although 90% of patients with colorectal tumours are older than 50, with a median oldness of 64 years. American Cancer Association estimates that it caused more than 49,700 fatalities in 2015.Objectives: Study the correlation of midkine with carcinoembryonic antigen (CEA), liver function tests, and white blood cell count in patients with colorectal carcinoma.Methods: The serum midkine and CEA of all subjects were measured by the ELISA technique, Liver enzymes were measured by colourimetric methods and neutrophils, and lymphocytes were measured by an Electrical Impedance Cell Counting method (automated machine).Conclusion: The study results of the correlation between serum midkine and other parameters in colorectal carcinoma patients show a significant positive correlation of midkine with CEA, liver enzyme, neutrophils, and lymphocytes.

ALTERNATIVE COMMUNICATION TOOLS FOR THE ELDERLY IN TIMES OF RESTRICTED SOCIAL CONTACTS

Original article

Irena Tušer, Jana Pupíková, Eliška Polcarová, Rudolf Urban, Tomáš Zeman, Renata Havránková, Ludmila Čírtková, Tibor Brečka, Hana Kličková, Leoš Navrátil

MMSL 2024, 93(2):176-187 | DOI: 10.31482/mmsl.2023.025

Background and objective: Nursing homes are threatened by external and internal threats, effect of which may result in a crisis situation (state of emergency). While managing an already existing emergency, it is necessary to create conditions allowing the elderly to maintain their fundamental human and civil rights. Any interference with human and civil rights is acceptable only in a state of emergency when crisis measures are applied. Social isolation was one of the emergency measures within the Covid-19 pandemics and involuntary social isolation may result in one´s state of depression. To eliminate this prediction, it is necessary to create such conditions that enable the elderly to maintain their basic human needs as well as civil rights. The authors therefore aim to identify and evaluate the effectiveness of possible alternative communication tools and strategies in the nursing homes along with the ways of a potential reduction of negative effects of social contacts restrictions.Methods: On the basis of an online questionnaire, a community of experts evaluated alternative communication tools on a scale from 1 to 5, considering three factors: 1. benefit for the elderly; 2. financial requirements for purchasing/provision for a nursing home; 3. organization requirements for a nursing home. A cost-benefit evaluation was performed to determine a ranking of individual alternative tools.Results: The acquired results of questionnaire survey served as a tool to determine the ranking of importance of individual alternative communication tools that are feasible depending on specific conditions of a nursing home.Conclusion: The research identified useful tools that may help in the nursing homes to mitigate the impacts resulting from restrictions applied in the state of emergency and associated initiatives in the field of mental health.

THE IMPACT OF ADHD ON THE PERFORMANCE OF THE PROFESSION OF A PROFESSIONAL SOLDIER AND OTHER RISK FACTORS INFLUENCING THE USE OF ADDICTIVE SUBSTANCES IN ADOLESCENCE

Original article

Simona Sedláčková, Lidmila Hamplová, Vladimír Pavlík

MMSL 2024, 93(2):199-205 | DOI: 10.31482/mmsl.2023.028

Background: ADHD syndrome is still at the forefront of discussed diagnoses in children, and is a continuing phenomenon even into adulthood. At the same time, the development of substance and non-substance addictions at an early age is a constant problem. The phenomenon of behavioral disorders, hyperactivity, impulsivity, and inattention, resulting from the immature development of brain centers in children, often brings with it persecution from pedagogues and educators. For both children and adults, there is no suggested therapeutic procedure, except for medication, although it is possible to work with the given disorder with an appropriate bio-psycho-social approach. Subsequently, the developmental deficit persists into adulthood.Objective: The main objective of the work was to reduce the stigmatization of addicted persons and to point out all developmental factors leading to addictive behavior, one of which is ADHD and its manifestations. One of the other goals is to draw attention to the importance of therapy for people with ADHD and to reduce medication to a minimum, if this can be achieved, and at the same time to emphasize this developmental deficit in the recruitment of professional soldiers.Methods: It was a retrospective collection and analysis of anamnestic data from medical records, and further data was obtained through a questionnaire survey. The data was evaluated based on established scales. The method of surveying the analyzed data by the coefficient in the maximum value. The resulting values were obtained by summing the points within the individual risk factors.Results: The highest score in the evaluation of the answers, and therefore the highest influence on the later use of addictive substances, had a psychiatric illness in childhood (point evaluation 351), in second place with a number of 295 points was a serious illness in childhood as a significant risk factor, followed by learning disabilities (277 points) and a low level of sports skills.Conclusion: The information obtained should initiate an increase in attention in the framework of preventive examinations in children, to the expansion of screening in the framework of gross motor skills, movement skills, and the implementation of therapeutic methods through frequent training in connection with the development of brain centers. At the same time, attention should be focused on the treatment of children with ADHD by amphetamine-containing substances, which should have a decreasing tendency and expand efforts to implement therapeutic methods and knowledge of preventive medicine, such as sufficient exercise, healthy diet, and calm family background, which will lead to improved relationships in families to achieve a reduction in anxiety states in children.

EVALUATION OF CYTOKERATIN-19 EXPRESSION AND OXIDATIVE STRESS STATUS ON GINGIVAL WOUND HEALING OF RABBITS TREATED WITH OMEGA-3

Original article

O. Kh. Mahmoud, J. K. Mammdoh, M. G. Saeed

MMSL 2024, 93(1):131-139 | DOI: 10.31482/mmsl.2023.012

Background: Gingiva is a delicate tissue that protects alveolar bone against external stimuli. Gingival breaks expose alveolar bone, and the fast wounds heal the betterment of the teeth frame. We aimed to compare the influence of omega-3 on the gingival healing period after trauma and the potential involvement of cytokeratin-19 protein expression.Methods: A total of 18 rabbits were used, after trauma-induced, these rabbits were subdivided into three groups of 6 each. Group 1 is the control group that received normal saline only, the second group received omega 3 for 10 days before the trauma, while the third group received omega 3 supplements for 10 days before the gingival injury and continued receiving them for an additional 10 days afterwards. For each time point (third and seventh day of healing), 3 rabbits were sacrificed, and tissue was collected for total antioxidant capacity and malondialdehyde measurement. Tissue fixed for histopathology and immunohistochemistry analysis.Results: Omega 3 has shown improvement in the healing process regarding the period of healing, antioxidant parameters, and intensity of cytokeratin-19 expression compared to the control group. Moreover, rabbit groups exposed to omega 3 before trauma has shown better healing response compared to those initiated therapy with trauma.Conclusion: Omega 3 is notably beneficial when used for both prevention and treatment since it reduces oxidative stress and improves healing processes measured by increased expression of cytokeratin-19 in epithelial tissue. Omega 3 can therefore be thought of as a possible choice for the treatment of gingival wounds and gingivitis.

PREVENTIVE MEASURES OF RESPIRATORY DISEASES AND IMPACT ON EMPLOYEE MORBIDITY - POSSIBILITIES OF USING ELECTRONIC PLATFORMS

Review article

Klára Václavíková, Kristýna Šoukalová, Marcela Kožená, Zdeněk Brodský, Michaela Mandysová, Hana Ochtinská, Karel Šatera, Kateřina Horáčková

MMSL 2024, 93(2):206-217 | DOI: 10.31482/mmsl.2023.019

Aims: Prevention is one of the most effective methods in the fight against respiratory infections. Electronic platforms can streamline care and have positive applications in the case of infectious diseases. This study was conducted to search for and describe the current scientific knowledge on prevention and the use of electronic platforms and their impact on the application of prevention strategies.Methods: A scoping review was conducted. In January 2022, a search was performed in selected licensed and free databases (EBSCOhost, Ovid, Scopus, Web of Science) based on PCC keywords using Boolean operators.Results: A total of 1927 sources were retrieved, of which 21 were subjected to critical analysis. 8 sources were included in the final review. Vaccination, social isolation, hygienic hand disinfection and respiratory protection are described as the most common and effective preventive measures. The platforms described had a positive effect on prevention and improving the quality of care.Conclusion: The effectiveness of the use of electronic platforms in prevention has been confirmed. Future research should be directed towards the development of these platforms to enable better diagnosis and treatment. Prevention-focused platforms can facilitate, simplify and improve care and access in the prevention of respiratory diseases.

VYŠETŘENÍ UCHA NA DÁLKU A DOPORUČENÍ OCHRANY SLUCHU

Meeting abstracts

Barbora Patočková, Vlastimil Němec, Jiří Néma, Kristýna Néma

MMSL 2024, 93(88):25

Cílem práce bylo ověřit, zda je nelékařský zdravotnický pracovník schopen provést videootoskopické vyšetření pomocí vzdáleného připojení s takovou kvalitou, aby mohl lékař vyšetřit pacienta na dálku. Abychom předcházeli poškození sluchu, bylo cílem také otestovat ochranné pomůcky sluchu společně s kombinací dalších osobních ochranných pomůcek a zjistit, zda mají vliv na jejich účinnost. ....

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