Biomedical subjects

Ryszard Miedzybrodzki

Publications and source records attributed to Ryszard Miedzybrodzki.

11 recordsLinked to original sources

PubMed2006

The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells.

During the last decade, olfactory ensheathing cells (OECs) have been successfully applied in multiple experimental approaches aimed to repair damaged mammalian spinal cord. Some of these experiments have consequently been translated into clinical trials. Finding a reliable source of human OECs that is easily accessible and can ensure a sufficient number of cells is a major prerequisite for conducting studies on OEC-mediated spinal cord regeneration. Here, we present a procedure for obtaining olfactory bulbs (OBs) and olfactory mucosa (OM) simultaneously from adult cadaver heart-beating donors for OEC isolation and analyze some of the factors that may condition successful OEC culture. We show that the results of OEC culture from OBs (10 cases) correlated significantly with warm ischemia time (WIT) as well as the initial viability of the isolated cells. Efficient OEC culture was possible when the WIT for the OB was up to 20 min. Brain damage, assessed by determination of S100B serum level, was not related to the success of OEC culture from the OB. Cadaver OM (7 cases) was shown to be a more reliable source of human OECs than the OB. In most of the examined cases the efficacy of culturing OECs from cadaver OM obtained even 180 min after cardiac arrest was comparable to that of living patients. The method of obtaining OBs and OM from cadavers enables the use of an alternative source of primary adult human OECs for further preclinical and clinical studies on their neurotrophic properties.

Adult↗

PubMed2006

Effects of bacteriophages on free radical production and phagocytic functions.

Reactive oxygen species (ROS) play a major role in mediating antibacterial functions of phagocytic cells. However, excessive ROS production may cause oxidative stress and tissue damage. Uncompensated ROS release has been implicated in a variety of disorders. Novel means of controlling elevated ROS production are urgently needed. We showed that homologous but not the heterologous phages inhibited, in a dose dependent manner, the degree of chemiluminescence in phagocytes induced by Escherichia coli. Treatment of the cells with the phages alone resulted in a small increase in ROS production. Homologous phages also facilitated phagocytosis when preincubated with bacteria. On the other hand, both homologous and heterologous phages inhibited phagocytosis following preincubation with phagocytic cells. The treatment of infected and uninfected mice with phages did not significantly alter the rate of phagocytosis by blood granulocytes and monocytes. In conclusion, we showed that bacteriophages can decrease ROS production by phagocytes. Although in some in vitro experimental models the phages tended to diminish phagocytosis, this phenomenon may be of little significance in clinical situations, since the process of eliminating bacteria in phage-treated patients is predominantly accomplished by both phages and phagocytes.

Animals↗

PubMed2006

New isothiazole derivatives: synthesis, reactivity, physicochemical properties and pharmacological activity.

The synthesis and biological investigation of the series of amide and ester derivatives 10-20 of 5-(4-chlorobenzoyl)amino-3-methyl-4-isothiazolecarboxylic acid 5 are presented. Because the amide series of 5-benzoylamino-3-methyl-4-isothiazolecarboxylic acid 2 has been studied extensively and from this series denotivir (vratizolin) 4 became the antiviral drug. The influence of exchanging the N-benzoyl for a N-(4-chlorobenzoyl) group at position 5 of the isothiazole ring on the pharmacological activity of 5-benzoylamino-3-methyl-4-isothiazolecarboxylic acid 2 derivatives is dealt with here. The effect of structure modifications in the carboxylic group of the 5-(4-chlorobenzoyl)amino-3-methyl-4-isothiazolecarboxylic acid 5 series of derivatives on their biological activity is discussed. Some of the tested 5-(4-chlorobenzoyl)amino-3-methyl-4-isothiazolecarboxylamides revealed significant anti-inflammatory activity in carrageenan induced edema and air-pouch inflammation tests. Physicochemical properties of 6-(4-chlorophenyl)-3-methylisothiazolo[5,4-d]-4H-1,3-oxazin-4-one 6 are described. Its use in the synthesis of isothiazole derivatives and its reactivity are also presented.

Animals↗

PubMed2006

Bacteriophage translocation.

The occurrence of phages in the human body, especially in the gastrointestinal tract, raises the question of their potential role in the physiology and pathology of this system. Especially important is the issue of whether phages can pass the intestinal wall and migrate to lymph, peripheral blood, and internal organs and, if so, the effects such a phenomenon could have (such passage by bacteria, known as bacterial translocation, has been shown to cause various disturbances in humans, from immune defects to sepsis). Available data from the literature support the assumption that phage translocation can take place and may have some immunomodulatory effects. In addition, phages of the gut may play a protective role by inhibiting local immune reactions to antigens derived from gut flora.

Animals↗

PubMed2006

[RANTES expression in nasal polyps fibroblasts; spontaneously and after stimulation with lipopolisaccharides (LPS) and phytohemagglutinin (PHA)].

INTRODUCTION: According to the results of research carried out by a number of authors, one of the main mechanisms of the generation of polyps is local inflammatory processes accompanied by immune system disorders. It has recently been shown that a number of differentiation factors and inflammatory mediators may be involved in the growth of nasal polyps. RANTES is a eosinophil chemoattractant factor likely could play an important role in a chronic inflammatory response in the nasal tissue that subsequently leads to the development of nasal polyps. OBJECTIVE: The objective of this study was detection of the chemokine RANTES in nasal polyps fibroblasts and researching influence of stimulation with lipopolisaccharides and phytohemagglutinin for RANTES expression in cultured nasal fibroblasts in vitro. METHODS: Nasal polyps were obtained from 17 subjects (9 atopic and 8 nonatopic) during polypectomy. RANTES was measured by immunofluorescence method. RESULTS: Intensive granular luminescence was observed in all cytoplasm of cells with the exception of nucleus. Immunoreactive RANTES was found to be present in 70% of cells. We not find increase percentage of positive RANTES fibroblasts after stimulation with lipopolisaccharides and phytohemagglutinin. RANTES expression was similar in the both: atopic and nonatopic polyps. CONCLUSIONS: This study demonstrates that cultured fibroblasts derived from both atopic and nonatopic patients release RANTES spontaneously and after stimulation with lipopolisaccharides and phytohemagglutinin. This observation and the finding that RANTES is present in nasal polyps fibroblasts suggest that this chemokine may be an important mediator of eosinophil in both atopic and nonatopic nasal polyposis. More research needs to expand on chemotactic factors such as RANTES and their interplay with other local cytokines.

Adult↗

PubMed2005

Bacterial viruses against viruses pathogenic for man?

In this review, we discuss possible models of bacteriophage-virus interactions. The first is based on the mechanism by which phages may interact indirectly with viruses. Its essence is that bacteriophage-derived nucleic acid may inhibit pathogenic virus infection. It seems that this phenomenon can be partly explained on the basis of interferon induction. We also discuss a study by Borecky's group (conducted over two decades ago) which provided some clinical data on the effectiveness of the application of native bacteriophage RNA in the treatment of viral infections. The second interaction model is based on the direct competition of bacteriophages and viruses for cellular receptors for viral cell-entry. The use of bacteriophages as inducers or displayers of antibodies with antiviral action is considered as the third model. In this part of the article, we also discuss other data and hypotheses on conceivable interactions between bacterial and animal viruses. As our current supply of antiviral drugs is quite limited, using natural agents such as bacteriophages as a weapon against pathogenic viruses could be an attractive and cost-efficient alternative, and further studies are urgently needed to test this possibility.

Animals↗

PubMed2004

[Trends in nonsteroidal anti-inflammatory drug development and application].

Since the synthesis of salicylic acid, research into the synthesis of new nonsteroidal anti-inflammatory drugs (NSAIDs) has continued in two directions: drugs with higher anti-inflammatory activity and those causing less adverse side-effects. Several very potent classic, non-selective NSAIDs were already available in the 1970's, but problems with their toxicity, especially gastro- and nephrotoxicity, have remained unsolved. The discovery of two cyclooxygenase (COX) isoforms, COX-1 and COX-2, was a breakthrough that led to obtaining the so-called coxibs, which selectively inhibit COX-2. This property makes this kind of NSAID less gastrotoxic than classic, non-selective NSAIDs. Other strategies to reduce the toxic effects of NSAIDs were their applications as prodrugs or purified enantiomers. The latest are the synthesis of classic NSAIDs combined with a chemical group that serves as a nitric oxide donor or the synthesis of double cyclooxygenase/5-lipoxygenase inhibitors. Simple inhibition of prostaglandin (PG) synthesis cannot completely stop the inflammatory process. Therefore new agents are tested for their influence on many other elements of the mechanism of inflammation, e.g. the formation of inflammatory cytokines, free radicals and biogenic amines by the stimulated inflammatory cells. Such pleiotropic activity of an NSAID might increase its anti-inflammatory action.NSAIDs are widely used not only for their anti-inflammatory, but also analgesic, antipyretic, and (as in case of aspirin) anti-coagulating activity. Results of the latest studies suggest that NSAIDs prevent colorectal cancer and may protect against the development of Alzheimer's disease as well. Precise studies of NSAIDs' mechanism of action (e.g. research on the genetic conditions of NSAID metabolism, the discovery of COX-3, studies on microsomal PGE synthase or PG receptors) will probably enable the synthesis of other more selectively acting compounds.

Alzheimer Disease↗

PubMed2003

Serological characterization of anti-endotoxin serum directed against the conjugate of oligosaccharide core of Escherichia coli type R4 with tetanus toxoid.

The covalent conjugate of oligosaccharide core of Escherichia coli type R4 with tetanus toxoid was prepared using reaction of reductive amination. The neoglycoconjugate was a good immunogen in rabbits yielding a high level of anti-lipopolysaccharide (LPS) antibodies of the IgG class. It was found that antiserum was able to react with the smooth LPS molecules of identical (R4) or related (R1) core type. The reactions were shown in the enzyme-linked immunosorbent assay and the immunoblotting test. Flow cytometry showed that anti-core antibodies reacted with LPS present on intact, live, smooth bacteria labelling more than 90% of cells. The anti-OS R4-TT serum used for in vitro studies showed high endotoxin neutralization activity. The serum inhibited endotoxin-induced tumor necrosis factor alpha and nitric oxide synthesis by the J-774A.1 cell line and attenuated pulmonary retention of YAC-1 cells.

Animals↗

PubMed2003

[Biological activity of the isothiazole derivatives].

The isothiazole ring was first synthesized in 1956 by Adams and Slack. It was known earlier in condensed structures such as benzisothiazole (saccharin for example). The first found natural origin isothiazole derivative was brassilexin--a phytoalexin from Brassica juncea. In this review diverse biological activity of isothiazole derivatives and their application has been presented.

Anti-Bacterial Agents↗

PubMed2002

[Potential use of cysteine endopeptidase inhibitors in radiodiagnostics of laryngeal and tongue neoplasms].

The methods applied up to now do not allow to define the border between the tumor and healthy tissue especially in advanced cases. Microlaryngoscopy facilitates the evaluation of the infiltration superficially, but does not allow for estimation its deeper penetration. CT and MRI often do not answer the question concerning the tumor spread as well. That is why the monoclonal antibodies marked with isotopes directed against specific antibodies of different neoplasms are applied in diagnostic. In the neoplasm development the great role play endopeptidases. They degrade the intercellular matrix and basement membrane and by this way made possible the neoplasm invasion. The high level of the endopeptidase in patients with neoplasm is a bad prognosis. The disposition of endopeptidase in neoplasm tissue is characteristic and gives opportunity to localise the border of healthy tissue thanks their inhibitors application. The inhibitor of cysteine endopeptidase obtained from hen egg and marked by J 125 was used in our study. The reaction between the cysteine endopeptidase inhibitor and malignant cells received directly from patients with tongue and laryngeal carcinoma and cells cultivated in vitro from the carcinoma.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Olfactory glial cells: hope in the treatment of spinal cord injuries].

Spinal cord injuries (SCI) have been reckoned for many years a serious clinical problem. Current strategies of SCI treatment prevent the occurrence of secondary injury in the spine (neuroprotection methods) as well as induce the anatomical and functional reorganization of intact nerve tracts in the spinal cord due to the plasticity of the central nervous system (neurorehabilitation methods). The observed functional recovery in patients treated for SCI depends on the severity of the injury and not always is satisfying. The elucidation in the last two decades of the mechanisms responsible for the induction of regeneration in the central nervous system enabled new strategies for SCI treatment to be developed. These strategies give an opportunity to obtain clinically-essential recovery of motor, sensor and vegetative functions, even in cases of total lesion of the spinal cord. The milestone in these studies was the usage of intraspinal transplants containing cells with neurotrophic properties, tested on the experimental model of rat SCI. Among the transplanted cells special attention should be paid to the olfactory ensheathing cells (OEC) on account of their unique property to stimulate the central neuroregeneration. In this paper the authors present basic characteristics of rat OEC, discuss their neurotrophic properties after transplantation into the injured animal spinal cord, as well as refer to the first attempts to use human olfactory glial cells in the treatment of SCI in humans.

Humans↗