IMPACT OF GENISTEIN AND PHYTIC ACID ON THE VIABILITY AND PROLIFERATION ACTIVITY OF NASAL POLYPS' CELLS IN AN IN VITRO MODEL.

In developed countries, chronic rhinosinusitis with nasal polyps is one of the diseases that diminish patients' quality of life most significantly. Treatment of that often incurable disease is based on the steroids and surgery in patients who had failed thorough conservative management. It appears that the introduction of new treatment agents suppressing inflammation process and inhibiting cells' proliferation would be a valuable therapeutic option. The aim of the present study was to evaluate the in vitro effect of genistein and phytic acid on the viability and growth rate of fibroblasts derived from nasal polyps. Cells were incubated with various concentrations of genistein (5-500 µM) and phytic acid (100-20,000 µM). After 72 h incubation, cells survivability and cells' growth rate were estimated by combination of WST-1 and LDH methods. QRT-PCR technique was used to determine the expression of histone H3, BCL-2, BAX and P53 genes. Caspase-8 and -9 expressions were evaluated by ELISA assay. Genistein and phytic acid significantly and in dose-specific manner decreased nasal polyps fibroblasts survivability and growth rate. Both agents in similar way decreased cell proliferation as measured by the expression of histone H3. They induce apoptotic machinery by modulating the expression of BCL-2, BAX and caspase-8 activity. Genistein and phytic acid have significant potential for a therapeutic role in the treatment of chronic rhinosinusitis.

ANTIPROLIFERATIVE AND CYTOTOXIC EFFECT OF SELECTED VITAMIN D ANALOGS ON NASAL POLYPS FIBROBLASTS AND OTHER CELLS WITH HIGHER PROLIFERATIVE POTENTIAL.

Besides well-known effect on bone and mineral metabolism vitamin D is involved in essential non-calcemic regulatory mechanisms, such as cellular proliferation, differentiation and apoptosis in various cell types. Major limitation for therapeutic use of calcitriol, a hormonally active form of vitamin D, is its calcemic and phosphatemic action. Recently, more selective vitamin D analogs which retain clinically useful activities with reduced toxicity have been designed. The aim of the present study was to evaluate the in vitro effect of vitamin D analogs on proliferation rate and survivability of cells with increased proliferative activity. The effect of calcitriol, PRI-2191, PRI-1890, PRI-1906 and PRI-2205 was examined. The experiments were performed on cultures derived from nasal polyps and cancer cells lines (SNB-19, C32 and SH-4). Cultures were incubated 72 h with tested compounds, each at the concentration of 0.025, 0.25, 2.5 and 25 µg/mL. The cytotoxic effect of vitamin D analogs and their influence on growth rate were determined using WST-1 assay. RT-QPCR technique was used to evaluate the expression of anti-apoptotic BCL-2 and pro-apoptotic BAX gene. Each of the tested compounds presented significant effect at the concentrations above 0.25 µg/mL. The strongest inhibition of the growth rate and decrease in cell survivability was observed after treatment with PRI-1890 and PRI-2191. Stimulation with calcitriol and other vitamin D analogs led to decrease BCL-2/BAX mRNA ratio in each cell lines. The apparent pro-apoptotic action revealed PRI-2191 followed by PRI-1890. It might be hypothesized that vitamin D analogs supplementation may provide therapeutic benefits not only in oncological patients but also in chronic rhinosinusitis.

[Damage of mitochondrial DNA in selected pathologies]. / Uszkodzenia mitochondrialnego DNA w wybranych patologiach.

The presence of separate genetic information in the mitochondria let consider them as semiautonomous structures. Changes of mitochondrial genetic material were detected in many pathologies; they have a number of common traits, but they also differ in terms of frequency of occurrence. This paper presents data concerning mtDNA and a review of most commonly encountered mutations and the associated pathologies.

[ Mutation of mtDNA and genetic background of hypertrophic cardiomyopathy]. / Mutacje w obrebie mtDNA a genetyczne podloze kardiomiopatii przerostowej.

The operation of the structural and functional units of the myocardial contractile apparatus relies on mutual myofilament movement, totally ATP dependent. As a consequence, cardiac action is integrally connected with the production of high energy ATP molecules, which are mainly synthesised in cellular mitochondrial structures. Mitochondrial dysfunction can lead to a reduced level of ATP, which is necessary to generate movement in the actino-myosin system. ATP insufficiencies may be a result of the genetic mitochondrial material (mtDNA) mutation, poorer expression of mitochondrial genes (at the transcription and/or translation stage), distorted import of proteins from the cytoplasm to the mitochondria or erroneous composition of mitochondrial breathing complexes. It has been proved that the efficacy of oxidative phosphorylation (mitochondrial ATP synthesis) is reduced with accumulated mutation of mitochondrial and/or nuclear DNA. The paper is a review of findings on the mutation of mitochondrial DNA discovered in patients with hypertrophy of the cardiac muscle. In many cases these changes accompany the mutations of the nuclear genes, but they may also be the only change discovered in the patient's genetic material.