W służbie władzy czy społeczeństwa? Wybrane problemy kultury i nauki na Środkowym Nadodrzu w latach 1945-1989

148 s. : il. : portr.

The influence of soybean extract on the expression level of selected drug transporters, transcription factors and cytochrome P450 genes encoding phase I drug-metabolizing enzymes

Objective: Soybean phytoestrogens, such as genistein and daidzein, reduce climacteric symptoms and the risk of certain chronic diseases such as cancer and cardiovascular diseases. Despite their widespread use in functional foods and dietary supplements, there is very little data available on their safety and herb-drug interactions, especially with antineoplastic agents. Hence, the aim of our study was to assess the effects of soybean extracts on the expression level of CYP genes and their transcriptional factors. We also investigated the effect of soybean on the mRNA level of transporters, such as P-glycoprotein (MDR1) and multidrug resistance-associated proteins (MRP1, MRP2). Materials and methods: Wistar rats were fed a standardized soybean extract (100 mg/kg, p.o.). cDNA was synthesized from total RNA isolated from different tissues (liver and intestinal epithelium) using reverse transcription. Gene expression level was analyzed by RT-PCR method. Results: We demonstrated a significant increase of CYP1A1 mRNA level (by 89%, p=0.002 and 125%, p=0.004) as compared with the control group. An increase of AHR and CAR expression after 10 days was also observed (by 60%, p0.05, respectively). Additionally, an inductive effect for CYP2D1 by 22% (p=0.008), Mdr1a by 267% (

Effect of Epilobium angustifolium and Serenoa repens extracts on regulation of non-genomic signaling pathway of kinases

Objectives: Changes of kinase activity of non-genomic cellular signaling pathway may influence the effectiveness of pharmacotherapy in case of hormone-dependent tumors. Our study investigated a possible interaction at the molecular level between an aqueous herbal extract of Epilobium angustifolium as well as a lipid-sterolic fruit extract of Serenoa repens and synthetic drugs used in the treatment of hormone-dependent cancers. Material and methods: E. angustifolium and Serenoa repens extracts were orally administered to testosteroneinduced rats for 21 days. Changes of RafA/Mapk3/Mapk1 mRNA levels were analyzed by real-time quantitative PCR using target specific primers. Results: The level of RafA mRNA slightly increased in rats receiving Epilobium angustifolium (p=0.076) and Serenoa repens (p=0.016) extracts. Administration of these extracts resulted in significantly elevated Mapk1 and Mapk3 transcripts in the investigated animals (

Znaczenie polimorfizmu CYP1A1 i regulacji jego transkrypcji w podatności na raka jajnika i endometrium

Abstract Human cytochrome P450 1A1 is one of the most important enzymes participating in human carcinogenesis because it metabolites several procarcinogens to active carcinogenic metabolites. Additionally, enzymes of CYP450 family play an important role in estrogenes catabolization (17-β-estradiol and estron) to intermediate products (2-, 4-hydroxyestradiol and 2-, 4-hydroxyestrone) including CYP1A1 that catalyses hydroxylation to 2-hydroxyestrogens in the endometrium. Derivates of these compounds (4-hydroxyestrogens) are carcinogenic and could induce DNA damage leading to tumour transformation. The presence of CYP1A1 enzyme in genital tract tissues could induce chemical carcinogenesis initiating cancer development. Recent studies also confirmed the role of CYP1A1 in the development of ovarian and endometrial cancer in humans. The presence of mutated CYP1A1 polymorphic variants influencing the CYP1A1 activity could be responsible for different interindividual susceptibility to genital cancers in women.Streszczenie Ludzki cytochrom CYP4501A1 jest jednym z najważniejszych enzymów uczestniczących w procesie kancerogenezy, ponieważ metabolizuje wiele pro-kancerogenów do ich aktywnych kancerogennych metabolitów. Dodatkowo, enzymy z rodziny CYP450 odgrywają ważną rolę w katabolizmie estrogenów (17-β-estradiol i estron) do produktów pośrednich (2-, 4-hydroksyestradiol oraz 2-, 4-hydroksyestron) uwzględniając CYP1A1, który katalizuje hydroksylację do 2-hydroksyestrogenu w endometrium. Pochodne tych związków (4-hydroksyestrogeny) są kancerogenne i mogą indukować uszkodzenia DNA prowadząc do transformacji nowotworowej komórki. Obecność enzymu CYP1A1 w tkankach narządów płciowych może indukować chemiczną kancerogenezę inicjując rozwój nowotworu. Najnowsze badania potwierdziły rolę CYP1A1 w rozwoju raka jajnika i endometrium. Obecność zmutowanych wariantów polimorficznych genu CYP1A1 wpływających na aktywność CYP1A1 może być związana ze zróżnicowaniem osobniczym w podatności na nowotwory narządów płciowych u kobiet

Znaczenie polimorfizmów rs1021737 i rs482843 gamma-liazy cystationinowej w etiologii stanu przedrzucawkowego w populacji kaukaskiej

Introduction: Recently, an increasing number of reports indicate the participation of genetic factors in the pathogenesis of preeclampsia (PE). The genes involved in the synthesis of nitric oxide that participates in the vasolidation, may play an important role in the development of this disorder. Hydrogen sulfide (H2S) which is produced by cystathionine gamma-lyase exhibits a similar effect to nitric oxide. It is suggested that certain polymorphisms of the CTH gene may participate in the development of chronic hypertension and preeclampsia. Aim of the study: To evaluate the frequency of genotypes and alleles of rs1021737 and rs482843 polymorphisms of CTH gene in women with preeclampsia from Wielkopolska region. Material and methods: The study group consisted of 60 patients with diagnosed preeclampsia, into the control group 120 healthy pregnant women were enrolled. The examined rs1021737 and rs482843 polymorphisms of CTH gene were determined using PCR-RFLP method. Results: Analysis of rs482843 polymorphism in the CTH gene showed a statistically significant difference in the prevalence of mutated GG genotype (pWstęp: W ostatnim czasie coraz więcej doniesień wskazuje na udział czynników genetycznych w etiopatogenezie stanu przedrzucawkowego (PE – preeclampsia). Istotną rolę mogą odgrywać geny uczestniczące w syntezie tlenku azotu, głównego wazodylatora naczyń. Podobne działanie wazodyletacyjne pełni także siarkowodór (H2S) syntetyzowany przy udziale gamma-liazy cystationinowej. Sugeruje się, że określone polimorfizmy genu CTH mogą mieć znaczenie w rozwoju nadciśnienia przewlekłego i stanu przedrzucawkowego. Cel pracy: Określenie częstości występowania genotypów i alleli polimorfizmów rs1021737 i rs482843 genu CTH w grupie kobiet ze stanem przedrzucawkowym z regionu Wielkopolski. Materiał i metody: Grupa badana obejmowała 60 pacjentek ze zdiagnozowanym stanem przedrzucawkowym, natomiast grupa kontrolna stanowiła 120 zdrowych kobiet ciężarnych. Analizowane polimorfizmy rs1021737 i rs482843 genu CTH oznaczono przy pomocy metody PCR-RFLP. Wyniki: Analiza polimorfizmu rs482843 genu CTH wykazała różnicę istotną statystycznie w częstości występowania genotypu zmutowanego GG (

Analysis of Ignition Capability of Flammable Gases from Small Arms Propellant Gases

The article presents the results of tests on the temperature of propellant gases shortly after the bullet leaves the barrel. The temperature and movement of these gases were recorded with thermal cameras and a high-speed camera. Weapons with and without muzzle devices (flash suppressor, silencer) were used. The aim of the research was to check the capability to ignite flammable gases located in the vicinity of the propellant gases produced during firing. Comparison of the maximum temperature of the propellant gases and the ignition temperature of the flammable gases makes it possible to determine the probability of fire. The lowest temperature of propellant gases was in the case of shooting with 9 19 mm bullets with the lowest kinetic energy (518 J), and the highest temperature of these gases was during shooting with 5.56 45 mm HC (SS109) bullets with the highest kinetic energy (1,785 J)

Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women

Objective: Preeclampsia (PE) belongs to main causes of mortality rates of mothers, fetuses and new born children. Polymorphism of MDR1 gene is connected with reduction of P-glycoprotein expression in placenta and increased fetal exposure to xenobiotics. The aim of the study was to determine the frequency of C3435T and G2677T/A polymorphisms of MDR1 gene in pregnant women with preeclampsia. Materials and methods: The study consisted of 180 Polish women including 60 women with PE and 120 healthy pregnant women. Determination of C3435T and G2677T/A polymorphisms of MDR1 gene was performed using PCR-RFLP method. Results: No significant association between genotypes of the examined polymorphisms and the clinical parameters of pregnant women with PE was observed. However the interesting tendency to higher prevalence of mutated 2677A allele of G2677T/A MDR1 polymorphism in PE group has been shown (2,50 vs. 0,83% in controls, OR=3,05, ns). Conclusions: The results of this study suggest no significant effect of examined C3435T and G2677T/A MDR1 polymorphisms in PE pathogenesis. However given the noteworthy results related to mutated 2677A allele of G2677T/A MDR1 polymorphism in preeclamptic women further studies seem to be needed. Nevertheless, the frequency of investigated polymorphisms was consistent with the distribution in other Caucasian populations

The importance of 8993C>T (Thr399Ile) TLR4 polymorphism in etiology of osteoporosis in postmenopausal women

Introduction: Toll-like receptors (TLR) may play a key role in initiating cellular signaling pathways by increasing the levels of inflammatory cytokines which, cooperating with osteoclasts, influence bone turnover. Numerous research articles focused on the genetic background of this condition, among others on polymorphic variants in TLR genes. The aim of the study was to examine the role of 20877G>A (Arg753Gln) in TLR2 gene and 8993C>T (Thr399Ile) in TLR4 gene in the etiopathogenesis of postmenopausal osteoporosis in Polish women. Material and methods: This study included 180 postmenopausal women (t-score ≤ -2.5), 153 postmenopausal women with osteopenia (t-score between -2.5 and -1), and 91 postmenopausal healthy women with correct t-score (t-score >-1). The 20877G>A TLR2 and 8993C>T TLR4 polymorphisms were determined by PCR/RFLP analysis. Results: The analysis did not reveal statistically significant differences in the distribution of genetic variants of 20877G>A TLR2 polymorphism between the investigated groups of women. The most interesting results were connected with 8993C>T TLR4 polymorphism. Comparison of the group with osteoporosis and controls revealed overrepresentation of heterozygous 8993CT genotype (13.3 vs. 5.5%, OR=2.65, p=0.03). Also, mutated 8993T allele was overrepresented in the group with osteoporosis (6.7 vs. 2.7%, OR=2.52, p=0.04). Higher frequency of heterozygous 8993CT genotype (13.3 vs. 4.6%, OR=3.21, p=0.004) and mutated 8993T allele (6.7 vs. 2.3%, OR=3.05, p=0.005) was noted in osteoporotic women as compared to the group with osteopenia. Higher frequency of heterozygous 8993CT genotype (13.3% vs. 5.3%, OR=2.73, p=0.003) and mutated 8993T allele (6.7 vs. 2.7%, OR=2.61, p=0.004) was observed in the group with osteoporosis as compared to women with osteopenia and with correct t-score. Conclusions: Results of our study suggest an important role of mutated 8993T allele of 8993C>T TLR4 polymorphisms in the etiology of postmenopausal osteoporosis. Nevertheless, this observation requires further investigation with larger sample size comprised of Polish women

The influence of a standardized soybean extract (Glycine max) on the expression level of CYP3A enzymes and pregnane X receptor in in vivo model

Abstract Objective: Soybean phytoestrogens, such as genistein and daidzein, have become a popular alternative for women undergoing the treatment of menopause symptoms. These isoflavones are also commonly used in traditional medicine in the prevention and treatment of osteoporosis, cardiovascular diseases and cancer. Despite the widespread use of soybean preparations as functional foods and dietary supplements, data regarding the safety as well as interactions between herbal medicines and synthetic drugs, especially with antineoplastic agents, remain scarce. Therefore, the aim of the present study was to determine the influence of soybean extract on the expression levels of CYP3A and PXR genes using real-time PCR (RT-PCR). Materials and methods: Male Wistar rats were given a standardized soybean extract (100mg/kg p.o.) for 3 and 10 days. Total RNA isolated from the liver tissue was transcribed into cDNA. The level of CYP3A1/2 and PXR mRNAs expression was analyzed by real-time quantitative PCR using SYBR Green I dye. Results: Our findings showed that soybean extract containing 37% isoflavones resulted in a significant decrease of CYP3A1 expression level by almost 35% (

Rocznik Lubuski (t.31, cz.2): Pogranicze Lubusko-Brandenburskie po II wojnie światowej

Pogranicze Lubusko-Brandenburskie po II wojnie światowejPod redakcją:<br> Czesława Osękowskiego<br>i RobertaSkobelskieg