21 results on '"Martin, Valis"'
Search Results
2. Binocular video head impulse test: Normative data study
- Author
-
Maja Striteska, Martin Chovanec, Tobias Steinmetzer, Viktor Chrobok, Oliver Profant, Erich Schneider, Jan Kremlacek, and Martin Valis
- Subjects
binocular video head impulse test ,conjugate gaze ,adduction ,abduction ,ductional VOR asymmetry index ,dysconjugacy ratio ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
IntroductionThe video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It’s usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR.Purpose (Aim)To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT.MethodsWe enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test–retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane.ResultsPooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test–retest repeatability coefficient was 0.06.ConclusionOur study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes.
- Published
- 2023
- Full Text
- View/download PDF
3. Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach
- Author
-
Shopnil Akash, Arafat Hossain, Md. Sarowar Hossain, Md. Mominur Rahman, Mohammad Z. Ahmed, Nemat Ali, Martin Valis, Kamil Kuca, and Rohit Sharma
- Subjects
curcumin ,monkeypox ,smallpox virus ,molecular docking ,DFT ,admet ,Microbiology ,QR1-502 - Abstract
BackgroundIn the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox.Material and methodPreliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc.ResultsThe mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system.ConclusionIn conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.
- Published
- 2023
- Full Text
- View/download PDF
4. RETRACTED: Designing of SiO2 mesoporous nanoparticles loaded with mometasone furoate for potential nasal drug delivery: Ex vivo evaluation and determination of pro-inflammatory interferon and interleukin mRNA expression
- Author
-
Yasir Mehmood, Hira Shahid, Kashif Barkat, Muhammad Ibraheem, Humayun Riaz, Syed Faisal Badshah, Hitesh Chopra, Rohit Sharma, Eugenie Nepovimova, Kamil Kuca, Martin Valis, and Talha Bin Emran
- Subjects
drug delivery ,nasal spray ,controlled release ,ex vivo study ,mesoporous silica nanoparticles ,Biology (General) ,QH301-705.5 - Abstract
The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol–gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The in vitro dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect.
- Published
- 2023
- Full Text
- View/download PDF
5. Discovery of small molecule mechanistic target of rapamycin inhibitors as anti-aging and anti-cancer therapeutics
- Author
-
Zofia Chrienova, David Rysanek, Patrik Oleksak, Dorota Stary, Marek Bajda, Milan Reinis, Romana Mikyskova, Ondrej Novotny, Rudolf Andrys, Adam Skarka, Pavla Vasicova, Josef Novak, Martin Valis, Kamil Kuca, Zdenek Hodny, and Eugenie Nepovimova
- Subjects
aging ,cancer ,mTOR ,anti-aging therapy ,SASP phenotype ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
To date, the most studied drug in anti-aging research is the mTOR inhibitor – rapamycin. Despite its almost perfect anti-aging profile, rapamycin exerts one significant limitation – inappropriate physicochemical properties. Therefore, we have decided to utilize virtual high-throughput screening and fragment-based design in search of novel mTOR inhibiting scaffolds with suitable physicochemical parameters. Seven lead compounds were selected from the list of obtained hits that were commercially available (4, 5, and 7) or their synthesis was feasible (1, 2, 3, and 6) and evaluated in vitro and subsequently in vivo. Of all these substances, only compound 3 demonstrated a significant cytotoxic, senolytic, and senomorphic effect on normal and cancerous cells. Further, it has been confirmed that compound 3 is a direct mTORC1 inhibitor. Last but not least, compound 3 was found to exhibit anti-SASP activity concurrently being relatively safe within the test of in vivo tolerability. All these outstanding results highlight compound 3 as a scaffold worthy of further investigation.
- Published
- 2022
- Full Text
- View/download PDF
6. Metformin: Activation of 5′ AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action
- Author
-
Sanjay Goel, Ravinder Singh, Varinder Singh, Harmanjit Singh, Pratima Kumari, Hitesh Chopra, Rohit Sharma, Eugenie Nepovimova, Martin Valis, Kamil Kuca, and Talha Bin Emran
- Subjects
hyperglycemia ,oxidative stress ,cardioprotective ,anticancer ,metformin ,Genetics ,QH426-470 - Abstract
Metformin is a plant-based drug belonging to the class of biguanides and is known to treat type-2 diabetes mellitus (T2DM). The drug, combined with controlling blood glucose levels, improves the body’s response to insulin. In addition, trials have identified the cardioprotective potential of metformin in the diabetic population receiving the drug. Activation of 5′ AMP-activated protein kinase (AMPK) is the major pathway for these potential beneficial effects of metformin. Historically, much emphasis has been placed on the potential indications of metformin beyond its anti-diabetic use. This review aims to appraise other potential uses of metformin primarily mediated by the activation of AMPK. We also discuss various mechanisms, other than AMPK activation, by which metformin could produce beneficial effects for different conditions. Databases including PubMed/MEDLINE and Embase were searched for literature relevant to the review’s objective. Reports from both research and review articles were considered. We found that metformin has diverse effects on the human body systems. It has been shown to exert anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer, and antimicrobial effects and has now even been identified as effective against SARS-CoV-2. Above all, the AMPK pathway has been recognized as responsible for metformin’s efficiency and effectiveness. Owing to its extensive potential, it has the capability to become a part of treatment regimens for diseases apart from T2DM.
- Published
- 2022
- Full Text
- View/download PDF
7. Exploring the role of nanomedicines for the therapeutic approach of central nervous system dysfunction: At a glance
- Author
-
Md. Mominur Rhaman, Md. Rezaul Islam, Shopnil Akash, Mobasharah Mim, Md. Noor alam, Eugenie Nepovimova, Martin Valis, Kamil Kuca, and Rohit Sharma
- Subjects
neurodegenerative diseases ,blood-brain barrier ,drug delivery ,nanotechnology ,nanomedicine and nanocarrier ,Biology (General) ,QH301-705.5 - Abstract
In recent decades, research scientists, molecular biologists, and pharmacologists have placed a strong emphasis on cutting-edge nanostructured materials technologies to increase medicine delivery to the central nervous system (CNS). The application of nanoscience for the treatment of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), Huntington’s disease (HD), brain cancer, and hemorrhage has the potential to transform care. Multiple studies have indicated that nanomaterials can be used to successfully treat CNS disorders in the case of neurodegeneration. Nanomedicine development for the cure of degenerative and inflammatory diseases of the nervous system is critical. Nanoparticles may act as a drug transporter that can precisely target sick brain sub-regions, boosting therapy success. It is important to develop strategies that can penetrate the blood–brain barrier (BBB) and improve the effectiveness of medications. One of the probable tactics is the use of different nanoscale materials. These nano-based pharmaceuticals offer low toxicity, tailored delivery, high stability, and drug loading capacity. They may also increase therapeutic effectiveness. A few examples of the many different kinds and forms of nanomaterials that have been widely employed to treat neurological diseases include quantum dots, dendrimers, metallic nanoparticles, polymeric nanoparticles, carbon nanotubes, liposomes, and micelles. These unique qualities, including sensitivity, selectivity, and ability to traverse the BBB when employed in nano-sized particles, make these nanoparticles useful for imaging studies and treatment of NDs. Multifunctional nanoparticles carrying pharmacological medications serve two purposes: they improve medication distribution while also enabling cell dynamics imaging and pharmacokinetic study. However, because of the potential for wide-ranging clinical implications, safety concerns persist, limiting any potential for translation. The evidence for using nanotechnology to create drug delivery systems that could pass across the BBB and deliver therapeutic chemicals to CNS was examined in this study.
- Published
- 2022
- Full Text
- View/download PDF
8. Head-shaking-induced nystagmus reflects dynamic vestibular compensation: A 2-year follow-up study
- Author
-
Maja Striteska, Martin Valis, Viktor Chrobok, Oliver Profant, Luigi Califano, Jaroslav Syba, Katerina Trnkova, Jan Kremlacek, and Martin Chovanec
- Subjects
head-shaking nystagmus ,head-shaking test ,head-shaking-induced nystagmus ,vestibular compensation ,follow-up study ,velocity storage ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
PurposeWe aimed to assess the ability of a head-shaking test (HST) to reflect vestibular compensation in patients after unilateral peripheral vestibular loss and to provide missing evidence and new insights into the features of head-shaking-induced nystagmus (HSN) over a 2-year follow-up.BackgroundHSN may occur after a prolonged sinusoidal oscillation of the head. HSN is frequently observed in subjects with vestibular function asymmetry; it usually beats toward the functionally intact or “stronger” ear and can be followed by a reversal of its direction.Study designA prospective observational case-control study.SettingsA tertiary academic referral center.MethodsA total of 38 patients after acute unilateral vestibular loss (22 patients with vestibular neuronitis and 16 patients after vestibular neurectomy) and 28 healthy controls were followed for four consecutive visits over a 2-year period. A complex vestibular assessment was performed on all participants, which included spontaneous nystagmus (SPN), the caloric test, the head-shaking test (HST), the video head impulse test (vHIT), the Timed Up and Go (TUG) test, and the Dizziness Handicap Inventory (DHI) questionnaire. We established the criteria for the poorly compensated group to assess different compensatory behaviors and results.ResultsWe found a time-related decrease in HSN (ρ < −0.84, p < 0.001) after unilateral vestibular loss. After 2 years of follow-up, HSN intensity in compensated patients reached the level of the control group; TUG and DHI also improved to normal; however, the caloric and vHIT tests remained abnormal throughout all follow-ups, indicating a chronic vestibular deficit. Besides, poorly compensated patients had a well-detectable HSN throughout all follow-ups; TUG remained abnormal, and DHI showed at least a moderate deficit.ConclusionsOur study showed that, after a unilateral peripheral vestibular loss, the intensity of HSN decreased exponentially over time, reflecting an improvement in dynamic ability and self-perceived deficit. HSN tended to decline to the value of the control group once vestibular compensation was satisfactory and sufficient for a patient's everyday life. In contrast, well-detectable HSN in poorly compensated patients with insufficient clinical recovery confirmed the potential of HSN to reflect and distinguish between adequate and insufficient dynamic compensation. HSN could serve as an objective indicator of stable unilateral vestibular loss.
- Published
- 2022
- Full Text
- View/download PDF
9. Bacillus velezensis A2 Inhibited the Cecal Inflammation Induced by Zearalenone by Regulating Intestinal Flora and Short-Chain Fatty Acids
- Author
-
Jing Cai, Nan Wang, Jia Chen, Aibo Wu, Eugenie Nepovimova, Martin Valis, Miao Long, Wenda Wu, and Kamil Kuca
- Subjects
zearalenone ,Bacillus velezensis A2 ,intestinal flora ,inflammatory ,short-chain fatty acid ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Zearalenone (ZEA) as an estrogen-like mycotoxin can cause the inflammatory injury of the cecum. How to reduce the harm that ZEA causes to humans and animals is a current concern for researchers. In this study, we aimed to ascertain whether Bacillus velezensis A2 (A2) could alleviate injury caused by ZEA by regulating the intestinal flora and the content of short chain fatty acids in the cecum among mice. Our results showed that Bacillus velezensis A2 improved the fold height, myometrial thickness, and crypt depth of the cecum induced by ZEA. Enzyme-linked immunosorbent assay and Western blotting results showed that A2 could decrease the ZEA-induced increase in expression levels of IL-2, IL-6, IFN-γ, TNF-α, and FC. Studies also showed that A2 increased the content of SCFA in the cecum which was decreased by ZEA. The microbial communities in the cecum were changed when given ZEA or A2. A2 was found to greatly reduce the ZEN-induced increase in the relative abundance of p_Actinobacteria, p_Protebacteria, o_Coriobacteriales, g_Anaerotruncus, g_Pseudoflavonifractor, g_Lachnoclostridium, g_Enterorhabdus, and f_Oscillospiraceae, and increase the ZEN-induced decrease in the relative abundance of f_Coriobacteriales. Results indicated that Bacillus velezensis A2 can largely ameliorate the intestinal inflammatory injury induced by ZEA in mice by regulating the microflora and short chain fatty acids content.
- Published
- 2022
- Full Text
- View/download PDF
10. Marine Invertebrate Peptides: Antimicrobial Peptides
- Author
-
Ran Wu, Jiri Patocka, Eugenie Nepovimova, Patrik Oleksak, Martin Valis, Wenda Wu, and Kamil Kuca
- Subjects
antimicrobial peptides ,marine invertebrate ,activity ,mechanism ,marine ,Microbiology ,QR1-502 - Abstract
Antimicrobial peptides are an important component of many organisms’ innate immune system, with a good inhibitory or killing effect against the invading pathogens. As a type of biological polypeptide with natural immune activities, antimicrobial peptides have a broad spectrum of antibacterial, antiviral, and antitumor activities. Nevertheless, these peptides cause no harm to the organisms themselves. Compared with traditional antibiotics, antimicrobial peptides have the advantage of not producing drug resistance and have a unique antibacterial mechanism, which has attracted widespread attention. In this study, marine invertebrates were classified into arthropods, annelids, mollusks, cnidarians, and tunicata. We then analyzed the types, sources and antimicrobial activities of the antimicrobial peptides in each group. We also reviewed the immune mechanism from three aspects: membrane-targeted direct killing effects, non-membrane targeting effects and immunomodulatory effects. Finally, we discussed their applications and the existing problems facing antimicrobial peptides in actual production. The results are expected to provide theoretical support for future research and applications of antimicrobial peptides in marine invertebrates.
- Published
- 2021
- Full Text
- View/download PDF
11. Neural Differentiation of Mouse Embryonic Stem Cells—An in vitro Approach to Profile DNA Methylation of Reprogramming Factor Sox2-SRR2
- Author
-
Sajida Batool, Mahmood Akhtar Kayani, Martin Valis, and Kamil Kuca
- Subjects
embryonic stem cells ,SOX2 ,SRR2 ,neural differentiation ,DNA methylation ,epigenetic regulation ,Genetics ,QH426-470 - Abstract
Sox2 is one of the core transcription factors maintaining the embryonic stem cells (ES) pluripotency and, also indispensable for cellular reprogramming. However, limited data is available about the DNA methylation of pluripotency genes during lineage-specific differentiations. This study investigated the DNA methylation of Sox2 regulatory region 2 (SRR2) during directed differentiation of mouse ES into neural lineage. ES cells were first grown to form embryoid bodies in suspension which were then dissociated, and cultured in defined medium to promote neural differentiation. Typical neuronal morphology together with the up-regulation of Pax6, neuroepithelial stem cell intermediate filament and β-tubulin III and, down-regulation of pluripotency genes Oct4, Nanog and Sox2 showed the existence of neural phenotype in cells undergoing differentiation. Three CpGs in the core enhancer region of neural-specific SRR2 were individually investigated by direct DNA sequencing post-bisulfite treatment and, found to be unmethylated in differentiated cells at time-points chosen for analysis. This analysis does not limit the possibility of methylation at other CpG sites than those profiled here and/or transient methylation. Hence, similar analyses exploring the DNA methylation at other regions of the Sox2 gene could unravel the onset and transitions of epigenetic signatures influencing the outcome of differentiation pathways and neural development. The data presented here shows that in vitro neural differentiation of embryonic stem cells can be employed to study and characterize molecular regulatory mechanisms governing neurogenesis by applying diverse pharmacological and toxicological agents.
- Published
- 2021
- Full Text
- View/download PDF
12. Impairment of Executive Functions Associated With Lower D-Serine Serum Levels in Patients With Schizophrenia
- Author
-
Jaromir Hons, Rastislav Zirko, Martina Vasatova, Pavel Doubek, Blanka Klimova, Jiri Masopust, Martin Valis, and Kamil Kuca
- Subjects
executive functions ,D-serine ,schizophrenia ,excitatory amino acids ,dysregulation of glutamatergic neurotransmission ,Psychiatry ,RC435-571 - Abstract
A core symptom that is frequently linked with dysregulation of glutamatergic neurotransmission in regard to schizophrenia is impairment or damage of executive functioning as a component of cognitive deficiency. The amino acid D-serine plays the role of an endogenous coagonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor glycine modulatory site. Considerably reduced serum levels of D-serine were found in patients suffering from schizophrenia compared with healthy control participants. An increase in D-serine led to augmented cognitive functionality in patients suffering from schizophrenia who were undergoing clinical trials and given the treatment of first- and second-generation antipsychotics. The study proposed the hypothesis that the D-serine blood serum levels may be linked with the extent of executive functionality in those suffering from the mental illness in question. For the purpose of examining executive function in such patients, the Rey–Osterrieth Complex Figure, Trail Making, and Wisconsin Card Sorting tests were applied (n = 50). High-performance liquid chromatography was used to gauge the total serine and D-serine levels. The extent of damage was examined through neuropsychological tests and was found to be considerably linked to D-serine serum level and the D-serine/total serine ratio (p < 0.05) in the sample being considered. A lower average serum level of D-serine and lower D-serine/total serine ratio were observed in participants with the worst performance compared with those displaying the best performance—this was true when the patients were split into quartile groups based on their results (p < 0.05). The findings of modified D-serine serum levels and the D-serine/total serine ratio linked to the extent of damage in executive functioning indicate that serine metabolism that is coresponsible for NMDA receptor dysfunction has been changed.
- Published
- 2021
- Full Text
- View/download PDF
13. Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis
- Author
-
Raed Alroughani, Peter Huppke, Maria Mazurkiewicz-Beldzinska, Astrid Blaschek, Martin Valis, Gregory Aaen, Joe Pultz, Xiaomei Peng, and Vanessa Beynon
- Subjects
relapsing-remitting multiple sclerosis ,dimethyl fumarate ,safety ,efficacy ,pediatric ,pharmacokinetics ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS.Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13–17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR).Results: Twenty participants [median (range) age, 17 (14–18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16–24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0–6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.
- Published
- 2021
- Full Text
- View/download PDF
14. The Concentration of Memantine in the Cerebrospinal Fluid of Alzheimer’s Disease Patients and Its Consequence to Oxidative Stress Biomarkers
- Author
-
Martin Valis, David Herman, Nela Vanova, Jiri Masopust, Oldrich Vysata, Jakub Hort, Zbysek Pavelek, Blanka Klimova, Kamil Kuca, Jan Misik, and Jana Zdarova Karasova
- Subjects
memantine ,Alzheimer’s disease ,clinical study ,cerebrospinal fluid concentrations ,oxidative stress ,biomarkers ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Memantine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist utilized as a palliative cure for Alzheimer’s disease. This is the second study examining the memantine concentrations in cerebrospinal fluid. The previously published study enrolled six patients, and three of them were theoretically in a steady state. In our study, we enrolled 22 patients who regularly used a standard therapeutic dose of memantine (20 mg/day, oral administration) before the sample collection. Patients were divided into four groups, according to the time of plasma and cerebrospinal fluid collection: 6, 12, 18, and 24 h after memantine administration. The cerebrospinal fluid samples were also assessed for selected oxidative stress parameters (malondialdehyde, 3-nitrotyrosine, glutathione, non-protein thiols, and non-protein disulfides). The plasma/cerebrospinal fluid (CSF) ratio for all time intervals were within the range of 45.89% (6 h) to 55.60% (18 h), which corresponds with previously published findings in most patients. The other aim of our study was to deduce whether the achieved “real” memantine concentration in the central compartment was sufficient to block NMDA receptors. The IC50 value of memantine as an NMDA antagonist is in micromolar range; the lowest limit is 112 ng/ml (GluN2C), and this value was achieved only in three cases. The memantine cerebrospinal fluid concentration did not reach one quarter of the IC50 value in five cases (one patient was excluded for noncompliance); therefore, the potency of memantine as a therapeutic effect in patients may be questionable. However, it appears that memantine therapy positively affected the levels of some oxidative stress parameters, especially non-protein thiols and 3-nitrotyrosine.
- Published
- 2019
- Full Text
- View/download PDF
15. Microbiome and Cognitive Impairment: Can Any Diets Influence Learning Processes in a Positive Way?
- Author
-
Michal Novotný, Blanka Klimova, and Martin Valis
- Subjects
microbiome ,diet ,cognition ,learning ,SCFA ,antibiotics ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The aim of this review is to summarize the effect of human intestinal microbiome on cognitive impairments and to focus primarily on the impact of diet and eating habits on learning processes. Better understanding of the microbiome could revolutionize the possibilities of therapy for many diseases. The authors performed a literature review of available studies on the research topic describing the influence of human microbiome and diet on cognitive impairment or learning processes found in the world’s acknowledged databases Web of Science, PubMed, Springer, and Scopus. The digestive tube is populated by billions of living microorganisms including viruses, bacteria, protozoa, helminths, and microscopic fungi. In adulthood, under physiological conditions, the intestinal microbiome appears to be relatively steady. However, it is not true that it would not be influenced, both in the positive sense of the word and in the negative one. The basic pillars that maintain a steady microbiome are genetics, lifestyle, diet and eating habits, geography, and age. It is reported that the gastrointestinal tract and the brain communicate with each other through several pathways and one can speak about gut-brain axis. New evidence is published every year about the association of intestinal dysbiosis and neurological/psychiatric diseases. On the other hand, specific diets and eating habits can have a positive effect on a balanced microbiota composition and thus contribute to the enhancement of cognitive functions, which are important for any learning process.
- Published
- 2019
- Full Text
- View/download PDF
16. MicroRNAs in Alzheimer’s Disease: Diagnostic Markers or Therapeutic Agents?
- Author
-
Francesco Angelucci, Katerina Cechova, Martin Valis, Kamil Kuca, Bing Zhang, and Jakub Hort
- Subjects
microRNAs ,Alzheimer’s disease ,biomarker ,diagnosis ,therapy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
MicroRNAs (miRNAs) are small non-coding nucleic acids able to post-transcriptionally regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been estimated that at least 1% of the human genome encodes miRNA and every miRNA can regulate up to 200 mRNAs. These findings suggest that dysregulation of miRNA expression could be associated with several human pathological conditions including central neurological disorders. Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. The characteristic symptoms are a progressive loss of memory and other cognitive functions due to the impairment of particular types of neurons and synapses, leading to neuronal death. At present, the available symptomatic treatments can only slow down disease progression without stopping it. miRNAs are widely found within the nervous system where they are key regulators of functions such as neurite outgrowth, dendritic spine morphology, neuronal differentiation, and synaptic plasticity. This has been the clue for considering miRNAs crucial molecules to be studied in AD, and nowadays, dysfunction of miRNAs in AD is increasingly recognized. In this review, we summarized existing evidence about miRNAs as biomarkers or therapeutic agents. The field of miRNAs as biomarkers is more advanced in terms of human data, and it is likely that miRNAs will be used successfully in the near future. Given the huge number of miRNAs potentially involved in diagnostics, miRNA panels will be used for specific tasks such as the stage of the disease, the risk prediction, and disease progression. The field of miRNAs as therapeutics is rapidly developing, and it offers a huge variety of solutions. These include positive effects related to beta-amyloid or tau reduction, increased number of neurons, inhibition of apoptosis, protection of synapses, transformation of other cellular elements into missing/deficient neurons in AD, and so on. It is predictable that both areas of research will be carried forward. However, given the absence of an AD therapy able to stop or reverse the disease, it is desirable to accelerate research on miRNAs as therapeutic agents.
- Published
- 2019
- Full Text
- View/download PDF
17. Venous Thromboembolism as an Adverse Effect During Treatment With Olanzapine: A Case Series
- Author
-
Jiri Masopust, Vera Bazantova, Kamil Kuca, Blanka Klimova, and Martin Valis
- Subjects
antipsychotics ,olanzapine ,venous thromboembolism ,side effects ,risk factors ,Psychiatry ,RC435-571 - Abstract
Objective: Venous thromboembolism (VTE) is a serious multifactorial disorder. Patients with severe mental illness have a higher risk of developing the condition compared to the general population.Methods: We observed 10 cases of VTE in patients with mental illness who were treated with the antipsychotic drug olanzapine. The diagnosis of VTE was made at the University Hospital Hradec Kralove (UH HK) from 2004 to 2013. VTE was objectively determined by imaging techniques (duplex ultrasonography, CT angiography) and laboratory tests (D-dimer). The average age was 46 years. The clinical manifestation of VTE was deep vein thrombosis in nine cases, including one case of simultaneous pulmonary embolism and one case of a concurrent ischemic cerebrovascular accident (iCVA). None of our patients had a history of malignant disease, trauma, or surgery.Results: Apart from antipsychotic medication, all the patients had clinical or laboratory risk factors for VTE. The most frequent clinical risk factors were obesity (n = 7) and smoking (n = 6). The most frequent laboratory risk factors were increased levels of FVIII (n = 4), mild hyperhomocysteinemia (n = 3), and factor V Leiden mutation (n = 2). VTE developed within 3 months after antipsychotic drug initiation in three patients and within 6 months in three patients.Conclusion: Olanzapine can be considered a precipitating factor for VTE formation. When olanzapine is administered, we need to monitor for clinical signs and symptoms of VTE, especially when other risk factors are present.
- Published
- 2019
- Full Text
- View/download PDF
18. PPI Long Term Use: Risk of Neurological Adverse Events?
- Author
-
Michal Novotny, Blanka Klimova, and Martin Valis
- Subjects
dementia ,cognitive disorders ,affective disorders ,depression ,proton pump inhibitors ,omeprazole ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The purpose of this review study is to reveal a potential threat of one type of such widely used and freely distributed drugs, which are proton pump inhibitors that might be the cause of the onset of both dementia and depression. The authors performed a literature review of available studies on the research topic describing the adverse effect of proton pum inhibitors (PPIs) (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, dexrabeprazole, ilaprazole). For a long time, PPIs were considered to be completely safe drug substances for both short and long-term use. In recent years, there have been a few contradictory studis of absolute safety, especially in patients, who have long been using PPIs. At this time when depression and dementia are rising in the population, this is a very worrying fact that needs to be highlighted, and which needs to be carefully studied and evaluated, ideally trying to prevent it. The findings of most research studies described in this review indicate that there is a direct association between the onset of dementia and depression on one side and the long-term use of PPIs on the other.
- Published
- 2019
- Full Text
- View/download PDF
19. Nitrendipine and Dementia: Forgotten Positive Facts?
- Author
-
Michal Novotny, Blanka Klimova, and Martin Valis
- Subjects
dementia ,Alzheimer disease ,prevention ,calcium channel blockers ,nitrendipine ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Nowadays, there are about 50 million people suffering from dementia worldwide. In 2030, it is expected that there will be 82 million people living with dementia and in 2050, their number should reach 152 million. This increase in the number of people with dementia results in significant social and economic problems. Therefore, researchers attempt to reduce risk factors causing the development of dementia such as high blood pressure. Epidemiological studies have shown that hypertension increases the risk of dementia at an older age. It can, therefore, be assumed that hypertension therapy will reduce the risk of dementia. However, previous clinical studies have shown that the efficacy of different antihypertensive drugs differs in this respect. The drug group that appears to be the most effective in these analyses is calcium channel blockers (CCBs). The most significant preventive efficacy in terms of protection against dementia has been demonstrated with nitrendipine. Its use is, therefore, particularly advantageous in elderly patients with systolic hypertension who are at high risk of dementia. The purpose of this study is to restore the discussion on the prevention of vascular dementia and Alzheimer’s dementia with nitrendipine in indicated hypertonic patients. The authors performed a literature search of available sources describing the issue of dementia, hypertension and its treatment with nitrendipine. In addition, they made a comparison and evaluation of relevant findings. The results of the detected research studies indicate that nitrendipine is able to reduce the incidence of dementia [Alzheimer’s disease (AD), vascular and mixed] by 55%. The treatment of 1,000 patients with nitrendipine for 5 years may prevent 20 cases of dementia. However, what has not yet been explained is the temporal link between hypertension and dementia due to the long-time intervals between hypertension and the development of dementia.
- Published
- 2018
- Full Text
- View/download PDF
20. Tourette Syndrome: A Mini-Review
- Author
-
Michal Novotny, Martin Valis, and Blanka Klimova
- Subjects
Tourette syndrome ,tic disorders ,movement disorders ,pharmacotherapy ,quality of life ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
The purpose of this mini-review is to provide the latest information on epidemiology, pathophysiology, diagnosis, and treatment of Tourette syndrome (TS). The authors conducted a literature search of available sources describing the issue of tic disorders with special focus on TS and made a comparison and evaluation of relevant findings. The results of this mini-review indicate that TS is a complex disorder, which has a significant impact on the quality of life of both the patients and his/her family. Therefore, early and proper diagnosis and treatment are necessary in order to reduce or even eliminate both symptoms and social burden of the patient. This requires a multidisciplinary management approach in order to meet the patients’ special needs. Future research should focus on neuroimaging, new neurotransmitter targets, in functional neurosurgery, as well as the effect of non-pharmacological psychotherapies for these people.
- Published
- 2018
- Full Text
- View/download PDF
21. Smartphone Applications Can Serve as Effective Cognitive Training Tools in Healthy Aging
- Author
-
Blanka Klimova and Martin Valis
- Subjects
older people ,smartphone apps ,cognitive training ,effectiveness ,opinion ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.