Vladimir Nosal

Clinical correlations of proton magnetic resonance spectroscopy findings in acute phase after mild traumatic brain injury

Abstaract Introduction: Standard brain magnetic resonance imaging (MRI) is typically normal in most patients after mild traumatic brain injury (MTBI). Proton magnetic resonance spectroscopy (1H-MRS) is more sensitive to detect subtle post-traumatic changes. The aim of the study was to evaluate the clinical correlations of these changes in the acute phase (within 3 days) after MTBI. Methods: Twenty-one patients with MTBI and 22 controls were studied. Both groups underwent neuropsychological testing and single-voxel 1H-MRS examination of both frontal lobes and upper brainstem. Results: Significant decrease in NAA was found in both frontal lobes and in NAA/Cre ratio in the right frontal lobe (p < 0.05). Correlation analysis showed a correlation of NAA in the left frontal lobe with Backward Digit Span (p = 0.022) and Stroop test A (p = 0.0034) and a weak correlation with TMT B time (p = 0.046). The NAA/Cre in the right frontal lobe correlated with Stroop test A (p = 0.007) and with the total score of Digit Span (p = 0.016). Lower NAA was found in the upper brainstem (p = 0.0157) in the sub-group of patients with post-traumatic unconsciousness. Conclusions: This study found a correlation of 1H-MRS metabolite changes with cognitive decline and presence or absence of loss of consciousness in the acute phase after MTBI.

Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment

The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment.

Unique case of eleven Bell's palsy episodes

Bells palsy (BP) is a peripheral facial nerve paralysis of unknown etiology. It is not a life-threatening condition; however, incomplete recovery may leave an individual stigmatized functionally, occupationally as well as socially. Recurrent paralyses are seldom, noted in 7–8% of all BP cases. More than two BP relapses are even less frequent. Adour et al. (1977) reported only two patients with four BP episodes from 1700 patients. Only one patient with more than four BP recurrences in the group containing 2414 BP cases was reported by Yanagihara et al. (1984). The highest reported number of BP recurrences in the accessible literature has been nine. We are presenting an unusual patient who suffered a total of eleven relapses of an idiopathic facial nerve palsy. Description of the case along with review of the relevant literature are discussed.

Melatonin enhanced bexarotene efficacy in experimental mammary carcinogenesis.

The aim of this paper was to test lower, safe bexarotene dose administered alone and in combination with melatonin to improve its efficacy. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea in female Sprague-Dawley rats, administered in two doses intraperitoneally between 42.-54. postnatal days and chemoprevention was initiated 7 days prior to first N-methyl-N-nitrosourea injection and lasted 15 weeks. Bexarotene, particularly in combination with melatonin decreased mammary tumor incidence and frequency with a shift from poorly to well differentiated carcinomas. Bexarotene alleviated glycaemia and liver/heart muscle glycogen concentration decreased as well as liver/thymus malondialdehyde increased in comparison with control group. The combination of bexarotene and melatonin is therefore beneficial in preventive-curative model of experimental mammary carcinogenesis and may be applied in oncological practice as such.

Adipokines in neurovascular diseases

Adipose tissue is now described as an endocrine organ secreting a number of adipokines contributing to the development of inflammation and metabolic imbalance, but also endothelial dysfunction, vascular remodeling, atherosclerosis, and ischemic stroke. Leptin, adiponectin, and resistin are the most studied adipokines which play important roles in the regulation of cardiovascular homeostasis. Leptin and adiponectin mediate both proatherogenic and antiatherogenic responses. Leptin and adiponectin have been linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of ischemic stroke. Resistin, a pro-inflammatory cytokine, is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. The changes in serum levels of novel adipokines apelin, visfatin are also associated with acute ischemic stroke. These adipokines have been proposed as potential prognostic biomarkers of cardiovascular mortality/morbidity and therapeutic targets in patients with cardiometabolic diseases. In this article, we summarize the biologic role of the adipokines and discuss the link between dysfunctional adipose tissue and metabolic/inflammation imbalance, consequently endothelial damage, progression of atherosclerotic disease, and the occurrence of ischemic stroke.

Perspectives and challenges of antioxidant therapy for atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. There is growing evidence that oxidative stress is involved in the pathogenesis of AF. Many known triggers of oxidative stress, such as age, diabetes, smoking, and inflammation, are linked with an increased risk of arrhythmia. Numerous preclinical studies and clinical trials reported the importance of antioxidant therapy in the prevention of AF, using vitamins C and E, polyunsaturated fatty acids, statins, or nitric oxide donors. The aim of our work is to give a current overview and analysis of opportunities, challenges, and benefits of antioxidant therapy in AF.

Therapeutical strategies for anxiety and anxiety-like disorders using plant-derived natural compounds and plant extracts

Anxiety and anxiety-like disorders describe many mental disorders, yet fear is a common overwhelming symptom often leading to depression. Currently two basic strategies are discussed to treat anxiety: pharmacotherapy or psychotherapy. In the pharmacotherapeutical clinical approach, several conventional synthetic anxiolytic drugs are being used with several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being sought by researchers. The results of a plethora experimental studies demonstrated that dietary phytochemicals like alkaloids, terpenes, flavonoids, phenolic acids, lignans, cinnamates, and saponins or various plant extracts with the mixture of different phytochemicals possess anxiolytic effects in a wide range of animal models of anxiety. The involved mechanisms of anxiolytics action include interaction with γ-aminobutyric acid A receptors at benzodiazepine (BZD) and non-BZD sites with various affinity to different subunits, serotonergic 5-hydrodytryptamine receptors, noradrenergic and dopaminergic systems, glutamate receptors, and cannabinoid receptors. This review focuses on the use of both plant-derived natural compounds and plant extracts with anxiolytic effects, describing their biological effects and clinical application.

The safety and efficacy of Heparin and Nadroparin compared to placebo in acute ischemic stroke - pilot study

AIMS This study aimed to compare the efficacy and safety of heparin and nadroparin in order to provide an additional therapeutic option for patients with acute ischemic stroke in, whom systemic thrombolysis was excluded, or thrombectomy could not be performed. METHODS We describe a prospective randomized double-blind placebo-controlled pilot study in acute ischemic stroke. The therapeutic window was between 4.5 and 24 h after the onset of stroke. During the first 24 h of treatment, the patients divided into 3 groups received placebo, heparin or nadroparin (in therapeutic doses). During the following 48 h, each patient received nadroparin in the therapeutic dose. 24 h after start of treatment they began taking 100 mg aspirin daily. The primary safety indicator was incidence of complications such as intracerebral or systemic hemorrhage, or death. Efficacy was primarily monitored by the neurological modified Rankin Scale (mRS) at 90 days. RESULTS There were no signs of intracerebral or systemic bleeding in the cohort of 87 patients. Two patients died - one (3.7%) in the heparin and one (3.8%) in the placebo group due to causes not connected with the treatment. There was a statistically significant difference in mRS on the 90th day between the heparin and placebo groups (21 (80%) vs 13 (50%), P=0.0350) and between the nadroparin and placebo groups (29 (85%) vs 13 (50%), P=0.0031). CONCLUSION The results show that the treatment with heparin and nadroparin is safe and effective. TRIAL REGISTRATION Trial is registered in ClinicalTrials.gov: NCT01862978.

Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2

INTRODUCTION Episodic ataxias (EAs) are rare dominantly inherited neurological disorders characterized by recurrent episodes of ataxia lasting minutes to hours. The most common subtype is EA type 2 (EA2) caused by pathogenic variants of calcium voltage-gated channel subunit alpha1 A gene (CACNA1A) on chromosome 19p13. SUBJECTS AND METHODS We examined a Slovak three-generation family. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. CACNA1A variants were screened by Sanger sequencing. RESULTS We identified four family members with recurrent episodes of ataxia. Complex differential diagnosis was performed. Genetic analysis with direct sequencing revealed a novel heterozygous variant of CACNA1A - c.5264A>G (p.Glu1755Gly) located in the pore loop of domain IV of calcium channel alpha-1A subunit. CONCLUSION We identified a novel missense variant of a voltage-dependent P/Q-type calcium channel alpha-1A subunit in a Slovak three-generation family with recurrent episodes of ataxia. The heterozygous missense variant resulted in changing a highly conserved glutamic acid within the pore loop of domain IV.

Measurement of platelet p-selectin expression by flow cytometry in patients with acute ischemic stroke

Abstract Aims: The aim of this study was to asses the platelet activation in the acute phase of ischemic stroke and transient ischemic attack (TIA) by defining p-selectin (CD62) expression by flow cytometry in vivo – without stimulation with agonists. We also studied whether antiplatelet therapy supresses the levels of baseline p-selectin expression and verified if there is a correlation between platelet CD62 expression and the type of ischemic stroke. Methods: We determined the expression of platelet surface p-selectin using whole-blood flow cytometry within the first 48-hours after onset of cerebral symptoms in patients with atherothrombotic and lacunar ischemic stroke and in healthy volunteers. We studied the realationship between antiplatelet medication and the type of ischemic stroke to baseline p-selectin expression. Results: Patients with acute cerebral ischemia have an excess of circulating platelets that express p-selectin, compared to healthy volunteers. The difference between average p-selectin expression in the group of healthy volunteers and the group of patients with stroke was statistically significant (p-value < 0,000001). Patients with stroke without antiplatelet medication showed a higher p-selectin expression than patients with antiplatelet medication (ASA, CLP, or ASA and CLP), hovewer, the difference was not statistically significant. There is no relationship between CD62 expression and the type of stroke. Conclusions: We can conclude that p-selectin is a highly sensitive blood biomarker of increased platelet activation. Antiplatelet therapy suppresses baseline p-selectin expression only minimally, insignificantly according to our results.