Sławomir Maśliński

Morphology and immuno-distribution of the histamine H4 receptor and histamine - releasing factor in choroid plexus of patients with paraneoplastic cerebellar degeneration

Histamine acts in the brain as a neurotransmitter produced by particular neurons or as amonoamine produced by mast cells, glial cells and vascular endothelial cells. Several studies suggest that deranged function of histamine may contribute to the brain neurodegenerative processes. One of such processes is paraneoplastic cerebellar degeneration (PCD), which is a nonmetastatic remote effect of cancers located in some peripheral organs [1]. PCD represents an enigmatic autoimmune phenomenon with serum autoantibodies that react with CNS extracts. The pathological hallmark of PCD is loss of Purkinje cells of the cerebellum [2, 3]. Thus, PCD pathogenesis has to involve functions of the brain barriers and one of these barriers is blood-cerebrospinal fluid barrier (CSF) located in the choroids plexus. The choroid plexus (CP) plays pivotal roles in an extraordinary range of processes that establish, survey and maintain the biochemical and cellular status of the central nervous system (CNS) under both normal and pathological conditions. Alterations in CPmorphology and effects of histamine on its function that may contribute to PCD pathogenesis are not known, therefore the aim of the present study was to examine inPCDpatients the ultrastructure ofCP, number of mast cells that may infiltrate the CP, and immunodistribution in CP of histamine receptors H4 and histamine-releasing factor (HRF). Material and methods

Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

Objectives Esculetin (6,7-dihydroxycoumarin) is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX) and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9). Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose) and experimental (treated with esculetin – 10 mg/kg ip.). The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4) in plasma was determined by a competitive enzyme immunoassay. Results The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively). Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01). Conclusions LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834). Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive drug candidate for patients with rheumatoid arthritis.

The human body as an energetic hybrid? New perspectives for chronic disease treatment?

Inflammatory response is accompanied by changes in cellular energy metabolism. Proinflammatory mediators like plasma C-reactive protein, IL-6, plasminogen activator inhibitor-1, TNF-α or monocyte chemoattractant protein-1 released in the site of inflammation activates immune cells and increase energy consumption. Increased demand for energy creates local hypoxia and lead in consequence to mitochondrial dysfunction. Metabolism of cells is switched to anaerobic glycolysis. Mitochondria continuously generate free radicals that what result in imbalance that causes oxidative stress, which results in oxidative damage. Chronic energy imbalance promotes oxidative stress, aging, and neurodegeneration and is associated with numerous disorders like Alzheimer’s disease, multiple sclerosis, Parkinson’s disease or Huntington’s disease. It is also believed that oxidative stress and the formation of free radicals play an important role in the pathogenesis of rheumatoid diseases including especially rheumatoid arthritis. Pharmacological control of energy metabolism disturbances may be valuable therapeutic strategy of treatment of this disorders. In recent review we sum up knowledge related to energy disturbances and discuss phenomena such as zombies or hibernation which may indicate the potential targets for regulation of energy metabolism.

Commitment of protein p53 and amyloid-beta peptide (Aβ) in aging of human cerebellum

Protein p53 is known to induce the cell cycle arrest and apoptosis in response to a variety of cellular distress signals and DNA damage. A recent study has demonstrated that in blood cells of aging subjects, p53 may induce early pathological changes that precede the amyloidogenic cascade. However, it is not clear whether p53 participates in the local deposition of amyloid-beta peptide (Aβ) in the nerve tissue of normal aging subjects. Therefore, in the present study, we analyse the distribution of both (Aβ and p53) proteins in the cerebellum of individuals without any history of dementia or other neurological illness who died suddenly in traffic accidents. We found that in the subjects at the beginning of their aging process (60-65 years of age) Aβ deposits were localized in subependymal areas of the cerebellar cortex and such deposits were not linked to the presence of p53 in the nerve tissue. In groups of subjects over 65 years of age, numerous Aβ diffuse plaques were scattered throughout the cerebellar cortex. In these subjects, p53 protein was detected in the cytoplasm or in the nucleus of the cerebellar nerve cells. All the results lead to the conclusion that in nerve tissue p53 participates in the process of neurodegeneration and then it is involved in the deposition of A in the nerve tissue.

The role of physiological elements in future therapies of rheumatoid arthritis. III. The role of the electromagnetic field in regulation of redox potential and life cycle of inflammatory cells

Each material consisting of charged particles can be influenced by a magnetic field. Polarized particles play an essential role in almost all physiological processes. Locally generated electromagnetic fields several physiological processes within the human body, for example: stimulation of nerves, muscles, and cardiac electrical activity. This phenomenon is used today in many medical applications. In this article, we discuss ways in which electromagnetic field affects the physiological and pathological processes in cells and tissues. This knowledge will help to better understand the electrophysiological phenomenon in connective tissue diseases and can bring new therapeutic strategies (in the form of “invisible drugs”) for the treatment of rheumatic diseases?

Role of physiologic issues in future therapy of rheumatoid arthritis I. Chronic inflammation toward action of parasympathetic system

Odkrycie wspólnego biochemicznego języka, jakim komunikują się między sobą układ nerwowy i odpornościowy, uznawane jest za jedno z największych odkryć współczesnej biologii. Wykazanie, że samo zakłócenie równowagi w poziomie cytokin, wydzielanych przez komórki biorące udział w zapaleniu, może spowodować wystąpienie objawów chorobowych rzuca nowe światło na genezę przewlekłych zapaleń. W niniejszej publikacji przeanalizowano wstępnie znaczenie układu autonomicznego w regulacji procesów zapalnych oraz możliwą rolę nerwu błędnego w rozwoju reumatoidalnego zapalenia stawów. S u m m a r y

Role of endothelial progenitor cells and redox potential in synovium neovascularisation

Zwiększona neowaskularyzacja błony maziowej jest jednym z istotnych elementów patomechanizmu rozwoju reumatoidalnego zapalenia stawów (RZS). Jednym z czynników mających znaczenie w przebiegu tego procesu jest produkcja wolnych rodników tlenowych, które wpływają zarówno na proces neowaskularyzacji, jak i na metabolizm endotelialnych komórek progenitorowych. Zaburzenia związane z produkcją wolnych rodników tlenowych w przebiegu zapalenia mogą być więc nie tylko bezpośrednią przyczyną uszkodzeń obserwowanych w przebiegu RZS, lecz także czynnikiem wpływającym na przebieg choroby. W niniejszej publikacji przedstawiono stan aktualnej wiedzy na temat procesu neowaskularyzacji, ze szczególnym omówieniem znaczenia potencjału redoks. S u m m a r y