Papers by Slawomir Michalak
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease... more As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respirat...
Folia Neuropathologica, 2010
Cerebellar degeneration belongs to indirect effects of malignancy on the nervous system. Although... more Cerebellar degeneration belongs to indirect effects of malignancy on the nervous system. Although the involvement of immune system is accepted as a hypothesis of its pathology, the clinical observations of ineffective immunomodulatory therapy suggest complex pathomechanisms, which await elucidation. The aim of this study was to prove the blood-brain barrier integrity, its relation to cerebellar degeneration and the role of circulating Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) and Cytokine-Induced Neutrophil Chemoattractant-2alpha (CINC-alpha) in indirect effects of experimental malignancy. Two transplantable neoplasms: breast cancer (BC) and Morris hepatoma (MH) in rats were used in the study. The blood-brain barrier breakdown was clearly proved in the course of both malignancies. We observed also morphological signs of cerebellar degeneration in both models, with linear loss of Purkinje cells and homogenization changes more pronounced in breast cancer bearing rats. We ...
Purpose The aim of our study was the evaluation of HE4 usefulness as a test in assessment of ovar... more Purpose The aim of our study was the evaluation of HE4 usefulness as a test in assessment of ovarian tumors which are suspicious and difficult to classify correctly via sub-jective ultrasound examination. Methods In this retrospective cohort study 253 women diagnosed with adnexal masses were examined preopera-tively. Suspicious tumors (n = 145) were divided into groups of: ‘‘probably benign’ ’ (n = 70), ‘‘uncertain’’ (n = 34), and ‘‘probably malignant’ ’ (n = 41). ‘‘Uncer-tain’ ’ tumors were also assessed as ‘‘benign’ ’ (n = 11) or ‘‘malignant’ ’ (n = 23). The logistic regression model was performed to analyze if the serum marker improves the prediction of a malignant finding and net reclassification improvement (NRI) was calculated to measure diagnostic improvement. Results Within the analyzed group 85 (58.6 %) benign and 60 (41.4 %) malignant tumors were confirmed hist-opathologically. The comparison of HE4 with subjective ultrasound assessment showed lowered NRI in the entire ana...
Cardiovascular Research, 2018
antagonist SR59203A (100nM). The role of the adipokine, adiponectin, was examined using exogenous... more antagonist SR59203A (100nM). The role of the adipokine, adiponectin, was examined using exogenous adiponectin (5mg/ml) and a blocking peptide for adiponectin receptor 1 (5mg/ml). Immunohistochemistry was used to examine b3-adrenoceptor expression. Results: During EFS PVAT elicited a reproducible anti-contractile effect, which was lost in obesity. Solution transfer from stimulated exogenous PVAT to a -PVAT vessel significantly reduced contraction, confirming that stimulated healthy PVAT releases a transferable anti-contractile factor. Pharmacological denervation using 6-hydroxydopamine abolished the anti-contractile effect. In health, the b3-adrenoceptor antagonist SR59203A reduced the anti-contractile effect; however b3-adrenoceptor agonist CL-316,243 could not restore function in obesity. Using immunohistochemistry, expression of b3-adrenoceptors was reduced in obesity. Exogenous application of adiponectin induced vasodilation of healthy vessels, and a blocking peptide for adiponectin receptor-1 significantly reduced the anti-contractile effect of PVAT in health. However, in obese vessels exogenous adiponectin no longer exerted a vasodilator effect. In obese exercised mice, the PVAT anticontractile was restored, and the development of hypertension and type-II diabetes was reversed, although the mice remained obese. Exercise increased b3-adrenoceptor expression, and restored the vasodilator effects of adiponectin. Conclusions: In conclusion, sympathetic nerve stimulation elicits an anti-contractile effect via activation b3-adrenoreceptors and release of adiponectin. This effect was lost in obesity, which may contribute to development of hypertension and type-II diabetes. Exercise restored PVAT dysfunction in obesity, and normalised glucose, insulin, and blood pressure independent of weight loss.
Neurology, 2015
OBJECTIVE: In this study we wanted to evaluate the association between brain atrophy markers and ... more OBJECTIVE: In this study we wanted to evaluate the association between brain atrophy markers and neurotrophic factors secreted by peripheral blood mononuclear cells (PBMCs) in relapsing-remitting multiple sclerosis (RRMS) patients. BACKGROUND: In MS autoimmune response may lead to both, destruction and neuroprotection. Potentially destructive immunological cells, namely PBMCs, can produce neurotrophins, release them into the periplaque area, salvaging tissues and thus delaying neurodegeneration in the central nervous system (CNS). DESIGN/METHODS: Thirty-four relapsing-remitting MS patients (21 females, 13 males, median age 39 years, median disease duration 2.25 years, median EDSS 1.5), were included in the study. Neurotrophin-3 (NT-3) and beta-nerve growth factor (beta-NGF) levels were measured with ELISA in PBMCs isolated from patients, using Ficoll-Paque gradient. Diffeomorphic registration algorithm (SyN) was applied to volumetric T1-weighted 1.5T-MRI images, to obtain log-jacobi...
Folia Neuropathologica, 2010
Cerebellar degeneration belongs to indirect effects of malignancy on the nervous system. Although... more Cerebellar degeneration belongs to indirect effects of malignancy on the nervous system. Although the involvement of immune system is accepted as a hypothesis of its pathology, the clinical observations of ineffective immunomodulatory therapy suggest complex pathomechanisms, which await elucidation. The aim of this study was to prove the blood-brain barrier integrity, its relation to cerebellar degeneration and the role of circulating Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) and Cytokine-Induced Neutrophil Chemoattractant-2α (CINC-2α) in indirect effects of experimental malignancy. Two transplantable neoplasms: breast cancer (BC) and Morris hepatoma (MH) in rats were used in the study. The blood-brain barrier breakdown was clearly proved in the course of both malignancies. We observed also morphological signs of cerebellar degeneration in both models, with linear loss of Purkinje cells and homogenization changes more pronounced in breast cancer bearing rats. We have fo...
Acta Neurobiologiae Experimentalis, 2009
Kemajuan pesat di bidang industri kendaraan harus diimbangi oleh kemajuan ilmu pengetahuan bidang... more Kemajuan pesat di bidang industri kendaraan harus diimbangi oleh kemajuan ilmu pengetahuan bidang otomotif, khususnya pada bidang simulasi dinamika kendaraan. Hasil simulasi dari pemodelan dinamika kendaraan dapat digunakan untuk mengetahui respon dan karakteristik kendaraan terhadap perintah pengendara maupun gangguan jalan. Untuk melakukan simulasi tersebut, dibutuhkan sebuah model dinamis yang dapat merepresentasikan sebuah kendaraan, dimana model tersebut tersusun dari persamaan-persamaan matematis yang bersesuaian. Pada tugas akhir ini dilakukan pemodelan gerak belok kendaraan empat roda, dengan menggunakan jenis pemodelan kendaraan single-track. Gerak belok kendaraan dianalisa pada dua kondisi, yaitu kondisi steady-state dan transient. Input dari model dinamis yang dibuat adalah nilai dari parameter kendaraan (meliputi massa, inersia, letak pusat massa, dan kekakuan belok ban), kecepatan kendaraan konstan, dan sudut kemudi roda depan. Model dinamis gerak belok kendaraan yang telah dibuat dapat menampilkan karakteristik kemudi kendaraan (understeer, neutralsteer, dan oversteer), grafik respon variabel gerak belok kendaraan (radius belok, yaw rate, dan sudut slip), besarnya kecepatan kritis kendaraan, serta visualisasi lintasan belok kendaraan. Hasil simulasi model dinamis kendaraan telah sesuai bila merujuk dari penelitian model single-track dan mempunyai ketidaksesuaian 30-60% jika dibandingkan dengan penelitian model twin-track. Kata Kunci-gerak belok, model dinamis, single-track, steady state, transient.
Acta Neurobiologiae Experimentalis, 2009
Advances in Experimental Medicine and Biology, 2016
Journal of Clinical Oncology, 2018
e22081Background: Neurological symptoms in the course as well as after completed chemotherapy are... more e22081Background: Neurological symptoms in the course as well as after completed chemotherapy are one of the most frequently reported complications affecting the quality of life of patients. Method...
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2018
The role of matricellular proteins like secreted protein acidic and rich in cysteine-like 1 (SC1)... more The role of matricellular proteins like secreted protein acidic and rich in cysteine-like 1 (SC1) has been shown in important functions in the central nervous system, including the regulation of synaptic stability with upregulation throughout axonal regeneration. The aim of this study was to determine whether SC1 is related to ischemic stroke severity. A total of 132 consecutively recruited patients admitted for acute ischemic stroke were included in this observational prospective study. Stroke severity was evaluated in the National Institutes of Health (NIHSS) scale on hospital admission. There was a positive correlation between SC1 levels and NIHSS score (r = .22, P = .009). Compared with patients with NIHSS scores lower than 5 at admission, patients with moderate and severe stroke (NIHSS ≥ 6) had significantly higher SC1 levels: 4.84 (2.53-11.58) ng/mL versus 3.31 (1.67-8.95) ng/mL (P = .01). SC1 was an independent predictor of stroke severity at admission (adjusted odds ratio =1...
Neurologia i neurochirurgia polska, 2018
The role of the thyroid gland in ischemic stroke pathology is not well understood. As thyroid hor... more The role of the thyroid gland in ischemic stroke pathology is not well understood. As thyroid hormones modulate the extracellular matrix, we explored the possible link between them and secreted protein acidic and rich in cysteine like 1 (SC1) - one of the extracellular matrix molecules. In the 81 patients with acute ischemic stroke, serum SC1 levels were much higher compared with 30 control subjects: 4.47 vs 2.43ng/mL (p<0.001). Serum levels of free thyroxine (fT4) were higher in stroke subjects compared to those of controls (p=0.03). In stroke patients, TSH concentration was lower than in the control group (p=0.03). SC1 levels positively correlated with fT4 levels (p=0.02) and negatively with TSH (p=0.03) in stroke patients. Our results confirmed the association between thyroid hormones and SC1 - extracellular matrix protein.
Reviews in the neurosciences, Sep 25, 2018
Paraneoplastic movement disorders are rare, autoimmune-mediated, nonmetastatic complications of m... more Paraneoplastic movement disorders are rare, autoimmune-mediated, nonmetastatic complications of malignant neoplasms. Common paraneoplastic movement disorders include paraneoplastic chorea, dystonia, cerebellar degeneration, different types of encephalitis, opsoclonus-myoclonus syndrome, stiff person syndrome, and neuromyotonia. Syndromes usually develop before tumor diagnosis, have subacute onset, and are associated with serum or cerebrospinal fluid antibodies. Two types of antibodies can be distinguished: antibodies against nuclear and cytoplasmic neuronal antigens (anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-CV2/CRMP5, anti-Gephrin, and anti-GABATRAP) and antibodies recently identified against cell surface and synaptic proteins (anti-NMDAR, anti-LGI1, and anti-Caspr2). These two types differ from each other in a few important aspects. Antibodies against cell surface and synaptic protein disrupt cell-surface antigens. Clinical symptoms are related to the disruption of antigens and pot...
Journal of neural transmission (Vienna, Austria : 1996), Jan 29, 2018
The blood-brain barrier (BBB) disruption is a critical step in paraneoplastic neurological syndro... more The blood-brain barrier (BBB) disruption is a critical step in paraneoplastic neurological syndrome (PNS) development. Several cytokines have been implicated in BBB breakdown. However, the exact step-by-step mechanism in which PNS develops is unknown, and the relationship between a systemic neoplasm and BBB is multilevel. The aim of the present study was to examine serum markers of BBB breakdown (S100B protein, neuron-specific enolase, NSE) and concentrations of proinflammatory (TNF-alpha, VEGF) and anti-inflammatory/immunosuppressive cytokines (IL-4), and to establish their interrelationship in patients with PNS. We analyzed 84 patients seropositive for onconeural antibodies that originated from a cohort of 250 cases with suspected PNS. Onconeural antibodies were estimated with indirect immunofluorescence and confirmed with Western blotting. Serum S-100B was estimated using electrochemiluminescence immunoassay. NSE, VEGF, TNF-alpha and IL-4 were analyzed with ELISA. We found that S...
Neuroimmunomodulation, 2017
Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly und... more Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE. Selected neurotrophins (BDNF, NGF, NT-3, and NT-4/5) were measured with ELISA within peripheral blood mononuclear cells (PBMCs) isolated from 38 NPSLE patients matched with 39 healthy controls. Subcortical and cortical structure volumes were segmented with the Freesurfer 5.3 pipeline on T1-weighted isotropic images acquired on a 1.5-T MRI scanner. BDNF and NGF levels in PBMCs were reduced in NPSLE compared to the healthy population. The PBMC BDNF level was associated with reduc...
Advances in experimental medicine and biology, Jan 22, 2018
Obstructive sleep apnea (OSA) is a condition of breathing pathology occurring during sleep, chara... more Obstructive sleep apnea (OSA) is a condition of breathing pathology occurring during sleep, characterized by repeated episodes of upper airway obstruction. The aim of the study was to determine the occurrence of airway obstruction in smoking males with OSA in whom lung function tests had not been performed before. One hundred and four current smokers selected from 1241 patients were enrolled for the research. The subjects included in the study smoked minimum 20 cigarettes a day for at least 10 years. The diagnosis of OSA was confirmed by polysomnography (PSG) in the Sleep Laboratory and subjects were assigned to one of three groups, depending on the severity of OSA. The control group consisted of 30 age-matched male smokers in whom OSA was not confirmed in PSG. Patients from the study and control group scored ≥ 11points in the Epworth Sleepiness Scale. Spirometry, impulse oscillometry, and body plethysmography were used to assess pulmonary function. Airflow limitation in subjects of...
PLOS ONE, 2017
Introduction The impact of choroid plexus with its blood-cerebrospinal fluid barrier in the ische... more Introduction The impact of choroid plexus with its blood-cerebrospinal fluid barrier in the ischemic stroke pathology is poorly explored. Transthyretin (TTR) is a protein synthesized in liver and just in choroid plexus. Objectives The current study was designed to assess the prognostic value of serum TTR for functional outcome (at the time of hospital discharge) and long-term (one-year) overall mortality in ischemic stroke patients.
Journal of Clinical and Laboratory Investigation Updates, 2013
ABSTRACT Paraneoplastic neurological syndromes (PNS), indirectly caused by systemic malignancy, a... more ABSTRACT Paraneoplastic neurological syndromes (PNS), indirectly caused by systemic malignancy, are traditionally diagnosed by the presence of onconeural antibodies in the blood. Extracellular vesicles (EV) are membrane-bound structures that shed from cells and can migrate in body fluids to reach distant tissues, which may implicate their involvement in PNS. Na+/K+-ATPase activity is considered to be a plasma membrane marker and can, therefore, also be present in EV. The aim of this study was to analyze two methods of EV isolation with reference to Na+/K+-ATPase activity and to discover correlations between the humoral immune response and Na+/K+-ATPase activity in EV fractions obtained from patients with suspected PNS. Thus, neurological examination was performed on 11 cancer patients suspected to have PNS, and their sera were tested for the presence of onconeural antibodies. Two methods of EV isolation were compared: one utilizing Sepharose column chromatography and the other using 0.22-μm filters. The protein concentration obtained with the use of microfilters was significantly higher than that obtained for the Sepharose fractions. The activity of Na+/K+-ATPase was highest in the Sepharose fraction with highest protein content, but higher levels were again observed in the EV aliquots obtained with the use of microfilters, although this difference was not significant. Furthermore, ouabain caused significant inhibition of this activity in both the Sepharose and microfilter EV fractions. Importantly, Na+/K+-ATPase activity appears to be increased in patients expressing onconeural and other autoantibodies, as well as in individuals diagnosed with definite PNS. We conclude that the use of microfilters in the preultracentrifugation step for the isolation of EV seems to be the superior method. Furthermore, the activity of Na+/K+- ATPase is a useful marker of EV and, moreover, it is upregulated in patients with a humoral response during the course of PNS.
International Journal of Molecular Sciences, 2017
The aim of the present study was to investigate the levels of circulating CD14 in relation to the... more The aim of the present study was to investigate the levels of circulating CD14 in relation to the expression of tumor necrosis factor alpha (TNF-α) in monocytes, and serum levels of TNF-α and macrophage inflammatory protein-1 (MIP-1) in migraine patients. Numerous studies revealed controversial changes in the components of the immune system during attacks and the interictal period in migraine patients. Our study included 40 migraineurs and 39 controls. The levels of TNF-α, MIP-1 and CD14 were measured in peripheral monocytes and in sera with the Enzyme-Linked Immunosorbent Assay (ELISA) method, and the monocyte expression of TNF-α was also analysed by immunostaining. Serum CD14 concentrations were higher and the expression of TNF-α in monocytes was decreased in migraineurs. The serum MIP-1 level correlated with Verbal Rating Scale (VRS); the MIP-1:CD14 ratio in monocytes correlated with Visual Analogue Scale (VAS); the MIP-1:CD14 ratio correlated with Migraine Severity (MIGSEV)-Pain scores; and serum CD14 concentration correlated with migraine duration in years. Increased serum CD14 and depletion of TNF-α in monocytes can orchestrate other components of the immune system during the interictal period.
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Papers by Slawomir Michalak